Document 3eJ9e4JYw2LO9OanYdrK6RDpa

260 METABOLISH OF BENZO[a]PYRENE (BP), N-NITROSOOIMETHYLAMINE (DMN) AMD N-N1TR0S0PYRR0LIDINE (NPy) AND IDENTIFICATION OF THE MAJOR CARCINOGEN-DNA ADDUCTS FORMED IN CULTURED HUMAN ESOPHAGUS. C. C. Harris, H. Autrup, B. F. Trump and A. M. Jeffrey. Human Tissue Studies Section, LEXP, NCI, Bethesda, ID 20014, Dept. Pathology, Unlv. MD., Baltimore, MO 21201 and Inst. Cancer Res., Columbia Unlv., New York, NY 10032. The 300-fold variation In the worldwide Incidence of esophageal carcinoma suggests that environmental agents. Including chemicals, cause this cancer. Since the Interac tion between chemical procarcinogens and human esophagus has not been previously studied, we examined the metabolic fate of BP, DKN and NPy In cultured non-tumorous esophagus from 2 patients with and 6 without esophageal carcinoma. Esophageal explants were cultured la a chemically-defined medium for 7 days prior to adding [3H]BP (1.5 vM), [14C]0MN (100 pN) or [J,C]NPy (100 uH) for 24 hrs. Radioactivity was found bound to protein (BP, DMN, NPy) and to DNA (BP, 10W). The major carcinogen-DNA adducts were: 1) trans addi tion of BP diol eooxide I at the 10 position to'the 2-amlno of guanine; and 2) with DMN, N-7 methyl guanine and 0-6 ethylguanlne (0-6 MeG/N-7 MeG-0.3). The Inter-individual variations In binding levels to DNA were 65-fold for BP and TO-fold for DMN.v In the 2 cases studied the variation in binding levels among the 3 major anatomical segments (proxi mal, mid, caudal) was less than 2-fold. The metabolism of BP Into water-soluble metabolites varied among the 8 patients from 1 to 681 of the total metabolism. The quali tative chromatographic patterns of water-soluble metabo lites [s*rtph*te ester (range, 21-551), glocuronlde conju gates (7-371) and glutathione conjugates (24-661)] and of organic-extractable metabolites were similar In all patients. Whether or not quantitative differences in carcinogen metabolism and in carcinogen bound to DNA will play a role In human susceptibility to environmental chemi cal carcinogens. Is not -os yet known. AACR ABSTRACTS, 1979 262 ' IN VITRO BINDING OF DIETHY LNIT ROSA MINE (DEN) AND N-NITROSOPIPERIDINE (NPiP) TO DNA. David Y. Lei. Joseph C. Arcos end Mery F. Argus. USPHSRes. Lab.. Tulane Med. Ctr., 210 State St., New Orleans, LA 70II8. Factors influencing the binding of alkylating segments from two potent carcinogenic nitrosamines to DNA were studied using an in vitro system containing rat liver microsomes. 4C-DEN and 4C-NPiP, a higher dialkyl and cyclic nitroaamine, respectively, bind to calf thymus DNA (at 37 for 1 hr). The reaction is NADPH.dependent. Pretreatment of rats with phenobarbetal (PB) enhances the binding of both DEN and NPiP; binding of DEN is decreased by 3-methylcbolantfarene pretreatment. The PB effect, as observed with DEN, La more pronounced with young (120-180 g) than with older (235-280-g) rats. Addition of cyto sol enhances the binding of DEN 3-4 fold and that of NPiP 2-3 fold. Mitochondria increase slightly the binding of DEN and over 5-fold that of NPiP. Benxylamine (I mM), a substrate of monoamine oxidase, inhibits the mitochondri al effect of NPiP binding by 39% and 45% in the control and PB-pretreated systems, respectively. The mitochondrial effect decreases with the decrease of nitrosamine molecu lar weight; mitochondria do not increase the binding of MC-dimethylnitroaamine to DNA. Supported by Grant No. 922A from The Council for To bacco Research. 261 sensitive assay tor carciroceh-ihdoced early changes ir *RNA KECTTLTRANSFERASE ACTIVITY.' Elsie Vainfan, Howard Brody, amd M. Earl Balia. Ths'Mev'Ygrl- Blood Center and' Memorial Sloea-Retterlng Cancer Cent>:, Nee York, N.Y. 10021. Liver tRKA methyltransferases from Ulster rats treated with either acetylamlnofluorene (AAT) 6r ethionlne have / been assayed using amino acid specific tRNAe from g.coll me substrates. When 0.06XAAF was added to the diet ^1 / Rale rats, which develop liver tumors after about 6 months f such treatment, selective changes in specificities of liver tKRa methyltransferases could be seen, after 7 deya. Tto.msslm methyl group transfer to certain.tMAt such * tKNAtyr, and tRHAgie, catalysed by ItVer uymes from treated animals was significantly higher then that seen with liver eccymes from male eontrol rats, while transfer to tUUUhe, eon-initiator tRNAaet, and ttBAval. were substantially the sane with entynee from Itber group. Similarly, when 0.5Z D,L--ethionlne was fed 18 female rata, which develop hepatocerclnoma after *l#ut * year of ethionlne Ingestion, selective Increases im the ability of liver encymes to catelyse methyl group transfer to several amino add specific tXNAs Including **K*Mfmst were observed after only one week of treatment with this hspatocardnogen. While additional changes in activities of these enzymes occurred when the ttaon drvtloped, most of the early changes persisted. It thus *JP**T* Rbet some characteristic prs-neoplastic altera- 1 tlNA nethylese activities can be Identified 1*^1* early in carcinogenesis. These may prove to be aful Indicators of exposure to tumorlgenic agents. "R^ortsd in pert by R1H grants HL09011 and CA08748. 263 ROLE OF TOE NUCLEAR FROTFIN MATRIX (NPH) IN CRATJLOCYTE . PYKNOSIS AND SECKERIATION. C.E. Eastoent. R.B., Scott, * K.R. Shelton, J. Hear. Departments'o' Medicine, Pathology; Biochemistry, end Jta*t"my and the Cancer Center, Medical College of Virginia, Virginia Commonwealth Universif, Richmond, Virginia 23298. The NPH 1- a network of several fibrillar proteins which remains after removal of the majority of nuclear DNAr RNA, lipid and protein.- Changes in this meshwork may be associated with muclear pyknosis and segmentation occurring during granulocyte maturation. Nuclei were ex tracted from rabbit granulocyte precursors separated into differing etagee of development in Ficoll/Hypaque density gredlentfl, and the RPM isolated by extraction with 0.5 M NeCl followed by MAase treatment In the presence of 8-merceptoethanol and the protease Inhibitors. NFH com prises only 10-151 of the total nuclear protein In both immature and mature granulocytes and electrophoresis on KPM In SDS-polyacrylamlde gels shows that most of the protein is accounted for by a limited number of major peptides. Synthesis of NPH occurs predominantly in young precursors as shown by ^S-methionine incorporation in vitro. A major difference in mature nuclei is the presence of NPM-bouod DNA which is highly resistant to removal by DNAase. Scanning electron micrographs (EM) reveal lntqct spherical or segmented "nuclear" shapes in the NPM preparations and transmission B1 show a fibrillar internal structure that Is similar in both immature and mature cell nuclei. These data lead to a model of nuclear pyknosis which Involves synthesis of NPH st early stages of cell development, followed by increasingly tight nuclease-resistant packing of DNA to the fibrillar NPM structure, and subsequent "collapse" of the NPM-DNA structure. "ARCH 1979 65 & U* S* Code) " it NOTICE: Tliis material may be protected` CARCINOGENESIS I (6202-6207) TUESDAY, AM athology L-ETR10N1NE METABOLISM IK LIVER OF RATS FED DL-ETKIONIKE AND OTHER HEPATOTOXINS. Z. Brad* and S. Bulba.* Papanicolaou Cancer Re*. Inst., Ml art1, FI. 32101. The metabolism of L-ethlonine (L-E) administered lntTaperltoneally waa Investigated In the liver of rats maintain ed for varying lengths of tine on a diet containing 0.31 OL-E ot 0.03X 2-N-Fluorenylacetamide (FAA) or 0.1X "-naphtyl liothlocyanate (NITC). Rats fasted for 16 hrs. received 100 mg/100 g body wc. (14C) L-E and A hra. later che concentration of S-adenosylethlonlne (SAE) waa determined. All hepetotoxlns ware found to decrease the accumulation of SAE In liver as follova: FAA ''Dl-E `NITC, SAE acctsaulstlon dccreaaed within one week Of feeding and thereafter Its levels retained low for the period of obser vation. Except SAE, the concentration of E mi ita Metabo lites Increased In the experimental rata. In coaparlaon with the control valuea, Che levels of E and E sulfoxide Increased approximately 2 end 1.3 fold respectively In livers of rats fed DL- for 42 days. DL--R fed rats had lower ATP concentration which did not change by L-E Injec tion. Accumulation of SAE in liver wai restored quickly after the diets containing K1TC or DL4 were replaced by basal diet. In FAA-fed rata the SAE concentration also Increased but it did not reach the levels found in controls. The role of Methionine edenoxyltrsnsfetaae In the forMation of SAE during rheee Metabolic perturbations is being Investigated. (Supported by USPHS Grant CA 23316.3 REPAIR OF ULTRAVIOLET RADIATION- AND N-ACET0JCY-.2-ACETYUMIN0FLUORENE-INDUCED DtIA DAMAGE IN PERMEABILIZED HUMAN CELLS. John D, Roberts* and Michael W. Llebernan. Washington Univer sity School of Medicine, St. Louis, Missouri 63110 We have developed a system for studying SNA repair synthe sis In permeablllsed, human diploid fibroblasts. With a syn thesis Mixture containing dATP, dGTP, BrdUTP and (3HldCTP, the Incorporation of labeled nucleotides Into parental DNA (p - 1.73 g/cml in alkaline CsCl) was stimulated 10-20 fold by the exposure Of the cells to either UV or N-acetoxy-2acetylsmlnofluorene; this daaage-dependent DNA synthesis was absent when cells deficient In excision repair (xeroderma pigmentosum, complementation group A) were used. Repair syn thesis In this system waa strongly dependent upon ATP and Mg^+, had a pH optimum in Trts/HCl of 8.0, was Inhlbltsd by NaCl, and was only partially dependent upon the addition of exogenous dNTPs. The reaction was linear for 10 Minutes and continued for St least one hour, labeled deoxycytldlne and dCMP were also Incorporated during repair synthesis but at reduced levels (38Z and 88S, respectively) when compared to dCTP. The addition of 6-HAD+ (the active form of the cofactor), a-NAD+ (a competitive inhibitor), or nicotinamide had little effect on repair synthesis in this system. This permeabllleed cell system should be useful In the further characterlistion of the molecular events Involved in eu karyotic SNA repair. (Supported In part by NIH Grant CA 20S13.) by copyright law 6204 satholocv 6205 PATHOLOGY INCREASED ACTIVATION OF PROCARCINOGENS AFTER ETHANOL.H,K, HEPATIC RHA SYNTHESIS IN RATS TREATED WITH ETHYLENE THIOUREA. 5eitr*,A.J. Garro* and C.S. Lleber.Alcohol Research Center, Gerth E. Austin and Geoffrey H. Moyer. UCLA Pathology Dept. . V.A.Hosp.,Bronx,N.Y.and Mt.Sinai Sch.of Med.(CUNY),N.Y.,N.Y. Lob Angeles, Ca. 90024. Alcoholics have an enhanced incidence of cancer of the Ethylene thiourea (ETll) Is che major degradation product of alimentary tract and the liver. Since a variety of procarcin- the ethylene-bis-dithiocarbamACe fungicides which are used oo ogens are activated through microsomal enzyme activity we egrlculturel crops. This compound has been reported to pro omdered whether alcohol (which increases these activities) may promote the activation of procarcinogens. To study this, rats were pair fed liquid diets containing 361 of total cal duce tumors of thyroid and liver after prolonged administra tion to rats or mice. However, in vitro testing has indicated that the compound Is not mutagenic, suggesting that ETU may c jt: ories as either ethanol or carbohydrates for 4 weeks. Micro- not be an initiator of carclnogtnesls. Another property we tr some from liver and small intestine were prepared. After have found to be cimamon to Most and posalbly all carcinogens alcohol feeding the activity of benzo(a)pyrene (BP) hydroxy Is the ability to Inhibit transcription. Thus, we have i: lase was significantly increased in both liver (128^_7 vs. examined the effect of ETU administration on RNA synthesis In to 90-3 pmoles 3-OHBP/mg microsomal protein/min; p<0.01) and in rat liver. The compound was administered to rate by intra- er> testine (18-3 vs. 7-1; p<0.01). he also found that the capac perltoneal Injection, by nasogastric tube or In the diet. ity of hepatic "and intestinal microsomes to activate BP to a Even doses which produced extreme clinical toxicity end Mutagen for Salmonella typhimurium TA 100 was significantly marked depression of serum thyroxin levels brought about no increased. Furthermore activation of 2-aminofluorene and reduction in the rate of nuclear or cytoplasmic RNA synthesis. tryptophan pyrolyiate to mutagens by intestinal microsomes By contrast, the structurally related weak hepacocarcinogen, was significantly enhanced. Moreover, there was an increased thioacetamide, at comparable doses, did inhibit liver RNA activity of hepatic demethylation of ditnethylnitrosaaine, a synthesis as did the potent hepatocarcinogen, N-2 acetyl- known procarcinogen (1.81^0.12 vs. 1.14*0.08 nmoles formalde aminofluorene. These results support the suggestion that hyde/mg microsomal protein/siin; p<0.01). In conclusion, ETU Is not e direct-acting carcinogen but that it Increases chronic ethanol ingestion increases the activation of pro- tumor Incidence by an indirect mechanism, possibly Involving carcinogens in liver and intestine; this may contribute to Its antithyroid properties. (Supported by a gift from Rohm the enhanced incidence of various cancers in the alcoholic. and Haas, Philadelphia, Pa.) (Supported by the VA, NIAAA and KIAM0D). 6206 PATHOLOGY CORRELATION BETWEEN IRON-INDUCED L1POPEROXIDATION AND "UN SCHEDULED" DNA SYNTHESIS IN ISOLATED NUCLEI AND CULTURED HEPATOCYTES. Thomas K. Shires and Charles Lovlg*. Department of Pharmacology, University of Iowa, Iowa City IA 52242 In freshly isolsted ret liver nuclei, the stimulation of llpoperoxldation (LPO > measured by thlobarblturlc acid assay for malondlaldehyde) by Fe^ was accompanied by Incorporation of ^H-dTTP Into DNA as demonstrated by acid precipitation or in CSCI-CB2SO4 gradients. Incorporation was dependent on the combined presence of dGTP, dATP, dTTP and dCTP but did not require ATP and was insensitive to hydroxyurea. Neither LPO dot incorporation occurred at <luMole or >2Sulioles Fe2+ per 4 0D2S, units of nuclei, while boch were maximal at 'lOuMole. Incorporation as well as LPO was inhibited by a-tocopherol. uperoxide dlsmutase, catalase, hydroxybutyltoluene, or mannitol. LPO produced by NADPH or by ascorbic acid also cor related with ^H-dTTP incorporation. As little as 1 mHole of pure malondialdehydc Incubated with 4 ODjtj nuclei also stimu lated 3H-dTTP incorporation. Preliminary studies with non proliferating rat hepatocytes cultured on collagen substrate Indicate that Fe^* stimulates ^H-dTTP incorporation into DNA at concentrations less than those that depress viability (measured by dye uptake) belov 90S. The Involvement of llpo- peroxidation In the mechanism of Iron-related carcinogenesis Is considered. (Supported In part by USPH5 NIH Grant 12675-) rATHOLOGY LONG TERM MAINTENANCE OF NORMAL HUMAN ENDOMETRIAL CELLS IN MONOLAYER CULTURE. 7.A. Adamec*, S.A. Melln*, and Q.G. Kaufman. Department of Pathology, University of North Carolina, Chapel Hill, NC 27514 In an effort to better understand the process of carcino genesis in human endometrial tissue, methods have been devel oped for the prolonged maintenance of this tissue in monolayer cultures. Endometrial tissue was obtained from hysterectomy specimens of consenting patients with no evidence of intrinsic endometrial disease. Endometrium was enzymatically dispersed into single cells and plated at high density; cultures were obtained from all specimens. Five morphologic types of cells were observed including two presumed to be immature and ma ture epithelial cells. All types except the presumed mature epithelial cells were readily subcultured. Treatment of pre sumed innature epithelial cells with 17e-estradiol followed by 17e-estrad1ol plus progesterone caused rearrangement of cells into gland-like clusters with PAS-positive cytoplasmic mate rial. This response was retained after multiple passages or storage of cells in liquid nitrogen. Fibroblasts treated similarly did not respond, nor did epithelial cells not priirtd with 17e-estrad1ol. These results show a greater rate of establishment of long-term human endometrial cell cultures and a more normal response to hormones than in previous reports. (Supported by NCI contract CP75956 and grants CAO0431 and CA17973) 44 P.229 11 j. E. ur M. t, W. `I I V' (IlM. k.)t . 1 "On wit I In w <y .'fin c-i^hl ( hr j f'-ir.ir Cnint qr< "t| with I n co ) i v, , tmd I i i 230 i C i 'li'mi I In- i n I i' use I't'ti'S <>11 c, comp ir v d i rsi i l.lr.l ,il t'l col ] ! wit h ilex.lnicl I II r.*v , | 'I I Mill , II I , , 1 .1 I I mu y "i nit... I ml'. i>., ti ... i in I i k r anil <1 I i nj> nf hist IV.I'MC r V Y> \- \ > .o o o o U t/> D r- S I & `6 oo. URL 14H7 F ATI'ase-DEFICIKNT \Hr.EN-UNCl hin a few week?-, owley females -LTase and <> close of .= i t hr, line(N-NM) (9.1 mt,, f tor 2 wei'kh with were 1 rea t ed >1 i slants were persist dorinc/ <*rgor and int heir promotiup ize twofold and ar 2 weeks aft it reafter both experimental lal treatment- n1andfi in t hr I i a ] amis w i I h IAI. CF 1,1 S : h Hn i t i t ne ct d '! r . I in i v . Namur oped in order iloRiral |inrcarcinomn. nan skin were 'ol lagcnnse prese r ved, fibroblasts om> dav (I c leosid>'s, f 11 - T)t; i t tin- ijrowi li 'ratinor y 11 s `.itniLiu . K<lie pro u ni c Inrplio log i, i l ...... yl < ami gr.inu) a i easy htrr- ''vi'ii t i.I i on . short-ierii in vivo mammalian pre-screen FOR PULMONARY CARCINOGENS P.231 I. BODAN, P. KAUY, I. ARANY, E. UZVULGYI and P. KERIAI /Dept. Hyg. tpid., Med, llniv. School, Debrecen, Hungary/ The activities of pyruvate kinase /PK/ and lactate dehyd rogenase /LDH/ as well as the isozyr-iic pattern of LDH in lungs of Cflf n;cr treated with a variety of carcinogens and non-carcinoqens were determined 28 days after the single exposure to the chemicals. In the lungs of aduJ t mice treated w.'tk the potent carci nogens urethane, dimeth ylni trosamine, ?-r'cthyichol&nthrene, berizo/a/pyrene , 7,1 Z-dime t h yl t enz/a/an t h ratune and aflatoxin B, the activities of PK and L.DH increased and the isozyme pattern of LDH shifted towards the tumorous pattern,However, exposure to the non-carrinogenic analogues phenylure thane, c t hyl f orma t e , chrysene, perylene and pyrene as well as the non-carcinogenic pulmonary toxicants Paraquat, butylated hydroxytoluene and cadmium chloride caused no alterations in the enzyme activities, Transplacental exposure to the ta rcinogens also resulted enzyme alterations very similar to those observed in adult mice. According to the results it car. be supposed that the cercinogenicity of chemicals might be predicted by the determi nation of activities of PK and LDH in mouse lung even before the macroscopic appearance of lung tumors. P.232 INDUCTION OF I IVFH Al UFMYIlF DFHYDROCKNASK ACTIVITY - AN INDICATOR OF CIIK.M1CAI. EXPOSURE? R. TiiRRoNF.N, II. NOUS [A INKN and M. MARSEI.OS (Department nf Physiology, University of Kuopio, Kuopio, Finland) The cytosolic aldehyde dehydropenase activity of rat liver is increased due to exposure to several foreign chemicals. The best-known example is the induction by phonobarbita 1. In the Wistar rat the response to phenoharbital is deter mined by genetic factors. A similar, genetically determined induction was observed also after the administration of p,p'-DDT. An other type of induction of the hepatic aldehyde dehydrogenase activity is produced by TCDD, 3,4-ben7.pyrene and 3-me thy 1 cho 1 an threne . The indiu lion by these toxic agents is not under the same genetic control as the induction by phenobarbit.il. A new isoenzyme is formed and it can be differentiated from the normal and phenohnrhita I-inducihle isoenzymes in a simple wav: it is active with hrn-zn I ilehyde .t: a substrate antf NAIJP as a i oenzyme . whereas the other enzymes lie 11" I a |0 I . 1,1 Mill III I .......I the lie-p i I i . .1 I I It 11 vde ililivl I < >> n I ,i i I i v i I v w.i 9 observed after the administration of a single dose {BO jig/kg) of ICD1). The highly Ciin i nopt'ii t e polycyclic liyd rocnr bons T,4-benzoyrene and 3-me t hy I clto lanthrene (100 mg/kg tlaily for 4 days) produced a 30-fold increase and the weakly c.m iiinp.enii 1 , .`-In n/.nit lii.ii one a 9-fold increase in the activity. On the i cut i.ii v, .elm i n i s t r a t i mi of t he ti on - r a re i tinge n i < polycyclic ft yd roc a rhons ,intlir;tii'iii1. plu'ii.ui I h 11 in .iihI ilityscnc prodined only a 2-3-foltl i mine t i on . Thus in this group of six pn 1 yi yi 1 i i hydrocarbons I lie-re seems to he a correlation between the carcinogenicity ol the compound and tile induction of the hepatic: aldehyde dehydrogenase activity. No induction, however, was observed with a si mi lar dose of ihc rai' i nei'f n i ?-acetyl ami nof I uorene nr u re thane . IcJ^^/^fyi -- >. *.*;<:;'- r*v f- r^-. ,.> S ;***? ^ 09[/7>T^ 115 can be studied in specific organs of Chinese hamsters after acute dosing with chemical carcinogens. In preliminary experiments an increase in mutation at both loci was detected in cultures derived from lung tissue of 3-week-old Chinese hamsters after intraperitoneal dosing with ethyl methanesulphonate or diethylnitrosamine. Subse quent experiments have shown the induction of mutation in cells derived from the bladder of animals dosed with diethylnitrosamine or methyl nitrosourea, and in a variety of other tissues from animals dosed with methanesulphonates, 2-acetylaminofl.uorene and urethane. URL 14138 23 *oo1, B.L., German Cancer Research Center, Institute for Toxicology and Chemotherapy, Im Neuenheimer Feld 280, 6900 Heidelberg (West-Germany) 3 Comparison of synergism in mutagenesis and carcinogenesis assays 3? Combination effects of chemical carcinogens were investigated in the Ames test system under a variety of conditions. The studies were performed in order to establish a new parameter for correlation of mutagenesis and carcinogenesis. It was also performed in order to gain knowledge on potential synergism of compounds, since man is exposed to a complex of different types of chemicals. An attempt was made to answer the following questions: 1. Are synmutagenic effects present under the described experimental conditions? 2. How do combi nation effects in the mutagenesis assay compare.to those from long-term car cinogenicity experiments? * Four pairs of test compounds were chosen for the investigations: (a) benzo- (o)pyrene and diethylnitrosamine; (b) 4-dimethylamino-azobenzone and diethylnitrosamine; (c) 4-dimethylaminostilbene and diethylnitrosamine; (d) urethane and 7,12-dimethylbenzanthracene. The first two pairs of compounds indicated the presence of additive effects whereas the latter two did not. These results would correlate to those of long-term carcinogenicity experiments in vivo, which had a similar outcome. The validity of these results and the possi bilities of using the Ames assay for studying synergistic effects of compounds will be discussed. * t. 24 Hartley-Asp, B., AB Leo, Research Laboratories, 251 00 Helsingborg (Sweden) Metronidazole: chromosome analysis in patients treated for Trichomoniasis vaginalis> and the micro-nucleus test in mice Metronidazole (Flagyl) and its analogs ffave exhibited mutagenic activity in Salmonella, Klebsiella pneumoniae and Citrobacter freundii in the plate test and the fluctuation assay. However, little information is available from higher organisms. Therefore we carried out cytogenetic studies in mammalian and Quman cells in vitro and in vivo. Human lymphocytes were exposed to doses pA^ _ Aw . ^ A*- -C MEGALOCYTE INDUCTION IN LIVERS OF RATS & treated with METHYLAZOXYMETHANOL acetate. H. S. Zedeck, S. S. Sternberg and J. McGowan. Sloan-Ketcering Institute for Cancer Research, New York, N. Y. 10021 Methylazoxymethanol acetate (MAMac), a hepatocarcinogen. induces within hours a num ber of diverse biochemical and pathological changes in rat liver. To determine whether other changes are initiated but not immediately evident rats were partially hepatectomized 1 wk after a single Injection of MAMac (35 mgAs). At 48 hr after partial hepatectomy (HEPX) more than 90% of hepatocytes were enlarged indicat ing that almost all parenchymal cells had been altered by MAMac. At 96 hr abnormal mitoses were present. By 7 days only 3S% of the cells were megalocytes. HEPX as late as 8 wk after treatment with MAMac induced megalocytosis indicating the long persistence of the latent effect. Similar treatment with the non-hepatocarcinogen actlnomycin D which like MAMac causes early changes in nucleolar structure and in RNA synthesis did not result in the for mation cf megalocytes. Preliminary experiments indicate that HEPX 1 wk after MAMac does not increase the incidence of animals with hyper plastic foci and hepatocellular carcinoma. (Supported, in part, by NCI Grant CA 08748.) ;/ ' f 26 INHIBITION OF CHEMICAL CARCINOGENESIS BY ' BUTYLATED HYDROXYANIS0LE (BHA) AND THIURAM { DISULFIDE DERIVATIVES. Lee W. Wattenberg. j Department of Pathology, University of Minne sota, Minneapolis, MN 55455. | BHA inhibits carcinogenic effects of 7,12- j dimethylbenz(*)anthracene (DMBA) and benzo(a)} pj'rene (BP) on mouse forestomach and diethyl- ! nitrosamine and 4-nitroquinoline-N-oxide on mouse lung (J. Nat. Cane. Inst. 48_, 1425, (1972); Fed. Proc. 31, 633, (1972)). Further inhibitory effects of BHA are reported now as veil as studies with thiuram disulfide antiox idants. Groups of female A/HeJ mice were placed on diets with or without BHA 5 mg/g. I They were then given BP 3 mg or DMBA 0.75 mg X 2 doses per os at 14 day intervals, uracil mus tard 0.05 mg X 4 doses per os over 14 days or urethane 10 mg i.-p.. In about 20 weeks average number of pulmonary adenomas per mouse were (groups designated by c'arclnogen and diet; control, C or BHA): BP-C 5.3 - BP-BHA, 2.5; DMBA-C 28.2 - DMBA-BHA, 12.7; uracil mustard-C 9.3 - uracil mustard - BHA, 3.8 and urethane-C 12.3 - urethane-BHA, 2.7. Female Ha/ICR mice w*re fed diets containing BP 0.3 mg/g with or vithout tetraethylthiuram disulfide (TETD) lOmg or tetrabutylthiuram disulfide (TBTD) ID mg/g for 6 weeks. 14 weeks later the average number of tumors of forestomach per mouse were: antioxidant, 3.7; TETD, 0.4; and TBTD, 0.9. HID and TBTD inhibit DMBA induced(30mg per os) adrenal necrosis in rats. Data show a cons Arable diversity of inhibitory effects of Antioxidants against chemical carcinogens. , March 1973 Abstracts, 1973 27 MALIGNANT TRANSFORMATION IN VITRO OF MOUSE FIBROBLASTS BY 7,12-DIMETKYLBENZ (A). ANTHRACENE, 7-HYDROXYMETHYLBENZ(A)ANTHRACENE AND BY THEIR 'K-REGION1 DERIVATIVES'. H.Marquardt,J.E.Sodergren,P.Sima,and P.L.Grover. Sloan-Kettering Inst., New York,N.Y.10021 and Chester Beatty Res.Institute,Loodon,UK. 'K-reglon' epoxides of benz(a)anthracene , dibens(a,h)anthracene and 3-methylcholanthrene are more active in producing malignant trans formation of cells in culture than the parent hydrocarbons and may be "proximate carcinogens". Transformation by these parent hydrocarbons is influenced by alterations in the activity of microsomal mixed-function oxidases. However , similar alterations do not modify transforma tion by 7a12-dlmethylbenz(&)anthracene. He now report on transformation experiments where fibroblasts derived from C3H mouse pros tate were treated with the K-region epoxides of 7,12-dimfthylbenz(a)anthracene and of 7-hydroxymethylbenz(a)anthracene that are known micro somal metabolites of these hydrocarbons. The epoxides were more lethal but they produced fewer transformed foci than the parent hydro carbons. Neither the toxic 'K-region1 phenols nor the corresponding non-toxic cls-dihydrodiols Induced transformation* These and other data Indicate that in 7methyl-substituted benz(a)anthracenes trans forming activity and stability of 'K-region' epoxides are decreased. The Involvement of epoxides in carcinogenesis by these hydrocar bons remains unproven.(Supported in part by Grant CA 08746 from the National Cancer Inst.) 28 ANALYSIS OF 1'" 25,I-LABELED ANTIGLIOMA ANTIBODIES ADSORBED BY INTACT MONOLAYERS OF CULTURED GLI OMA CELLS. Eugene D. Day and Darell D. Bigner. Duke University Medical Center, Durham, N. C. 27710. The sequential method of adsorption analysis (J. Irmunol. 107:1611. 1971) was applied to anti glioma radioantibodies adsorbed by Intact monolayer cultures of glioma cells. A non-centrifugal tech nique was devised to permit transfer of radioanti body solutions from one culture to the next in a sequence, and to effect removal of unbound radio globulins. When established mycoplasma-free clonal lines of the N-nitrosomethylurea-induced C6 rat astrocytoma and 2 different rat fibroblast cultures were utilized, simple primary ^binding of 125x-igc was readily measured in a particularly sensitive and reproducible manner over and above control IgG. With proportions varying from one serum to the next, all antiglioma radioantibodies from 9 different rabbit antisera, after preadsorp tion x 3 with rat liver, still retained cross- reactivity for fibrobLast cultures, and, after adsorption x 3 with fibroblasts, still retained selective reactivity for glioma cells. When ad sorbed with glioma cells first, the bulk of all binding activity remained with the glial cells. When varying amounts of unlabeled antibody IgG were mixed with fixed quantities of labeled anti body IgG and glioma cells, an equivalence point was established by competitive binding curves and, independently, by microscopic examination of the monolayer-antibody complexes after light trypsin- ization: cell clumps in excess antibody; free cells otherwise, parame rs of IgG binding could ib.e. obtain__e.1d.; e._g., tK, _* I .x. i10M a. _* n0.66, and s * 6.7 x 107 sites/cell. NINDS-NS-10237 and NCI-CA-1L898 7 00013009 BURCHFIELD PT 5 PAGE 27 99 AU TI SI SO AB 95 AU TI SI SO AB SI SO LA AB 97 AU AO TI SI SO LA AB 6RAF N Danger of carcinogenic substances In the environment. HEEP/72/019BB OEFF GESUNDHEITSWES5 33 (3). 1971 121-133 HEEP COPYRIGHT^ BIOL ABS. Despite an alarmingly large number of known chemical, physical end biological carcinogenic substances* there Is still no satisfactory explanation of the etiology of carcinoma development. Aside from this* 3/9 of all types of cancer ore attributed to exogenous environmental factors. The Druckrey summation theory Is valuable for judging the overall carcinogenic situation. Only a dosage-related study of the toxicology of these damaging substances promises any progress. With regard to the dangers of exposure for modern man, the essential distinction must be made between occupational* environmental and natural cancer hazards. Among the natural carcinogenic substances, nltrosemine* mycotoxlns (aflatoxln) and 3,9-benzpyrene and Its derivatives pley a decisive role. DI PAOLO JA i DONOVAN PJ *, NELSON RL TRANSFORMATION OF SYRIAN HAMSTER FETAL CELLS IN-VITRO BY CHEMICAL CARCINOGENS HEEP/72/00S56 PROC AMER ASS CANCER RES! 12. 1971 95 HEEP COPYRIGHTS BIOL ABS. ABSTRACT X IRRADIATION BENZO-A-PYRENE 2 ACETYL AMINO FLUORENE AFLA TOXIN B-l 01 BENZ ANTHRACENE 1 METHYL CYCLO PENTA-OL PHENATHREH-17-ONE 3 HYDROXY BENZO-A-PYREHE 7 12 DI METHYL BENZ-A ANTHRACENE URETHANE N HYDROXY URETHANE 01 ETHYL NITROSAHINE Sula UP Med. Fac. Charles Unlv.* Prague* Czech. Nature, precursor of civilization In chemical carcinogenesis CA/079/079373B Prot. Vitae; VOL 17, ISS 9, 1972,215-6 Ger CBAC COPYRIGHT: CKEM ABS A review with 30 refs, on the occurrence of carcinogens such as 3,9-benzpyrene 11), dlmethylnltrosemlne, ethionine, aflatoxln, sterlgmatocystlne, end luteoskyrine* In the environment and their potential In producing tumors. (50-32-8 3,9-Benzpyrene)(62-75-9 Dlmethylnltrosemlne>(13073-35-3 EthionineX1902-96-2 Aflatoxln) Kolesnichenko TS Inst. Exp. Clin. Oncol., Moscow, USSR Trensplaeental action of some carcinogens In organ cultures of golden hamster embryonal pulmonary tissues CA/078/106799N Vop. Onkol.; VOL 18, ISS 10, 1972,98-52 Russ CBAC COPYRIGHT: CHEH ABS Proliferation of the bronchial epithelium of hamster embryonic pulmonary tissue explants occurred when the mother animals in the last third of pregnancy 00013010 BURCHFIELD PT 5 PAGE 26 98 AU A0 TI SI 50 LA AB reeieved 20 mg 9,10-diroethyl-l,2-benzanthracene (I), 0.02 mg diethylnitrosamine, or 6 mg nitrosomethylureo. i57-97-6 9,10-D1methy1-1,2-benzanthracene)(55-18-5 Diethylnitrosamine)(689-93-5 Nitrosomethylurea) Schmeehi 0 5 Krueger C i Preisiler P Inst. Exp. Toxikol. Chemother.* Otsch, Krebsforschungszentrum Heidelberg, Heidelberg, Ger. Cancer prophylaxis by vitamin A CA/077/122056K Arzneim.-Forsch.} VOL 22, ISS 5, 1972,996-9 Ger CBAC COPYRIGHT: CHEH ABS Oral administrat1 on of vitamin A or 0001269a BURCHFIELD PAGE 11 a 25 t AU SO LA AB from a comparison between mutegenicit1es with intact hepatocytes and with S9 prepared from disrupted hepatocytes. The results support previous reeommendat1 on* that tests with Intact cell metabolism should be included In a battery for screening of carcinogens in vitro. ANON Chimneysweeps die young CIS/82/01394 Working Environment 1982, p.18-20. Illus. Eng Nearly 3 times es many chimneysweeps In Sweden die of lung cancer than would be normal? 5 times es many die of throat cancer. There were 441 deaths among the 2*495 chimneysweep* studied* compared with an expected figure of 355 (excess mortality of 24XJ} of these* 32 dfed of lung cancer* against an expected figure of 12* i.e. nearly 3 times the normal population rate. 8 chimneysweeps died of oesophageal cancer, whereas 1.6 such deaths could normally be expected (5 times the normal population rote). Liver cancer also was 5 times the normal population rate. Cardiovascular diseases killed 162 of chimneysweeps studied* against an expected figure of 152. Hazards to which chimneysweeps are exposed: polycyclic aromatic compounds (including benzo(aJpyrene)* nitrogen compounds which can convert Into nitrosamines )* arsenic* asbestos, sulfur dioxide* carbon monoxide* solvents (for cleaning ventilation channels). Mortality among chimneysweeps could be reduced by use of respirators* expansion of 5& V ..iT w->- />r>S. '.-rS . 26 AU J^arv/holm B * lavenius 8 TI A cohort study on cancer among workers exposed to an antirust ell 51 CIS/62/00601 30 50 Scandinavian Journal of Work, Environment and Health Sep. 1961, Vol.7* No.3, p.179-164. 15 ref. LA Eng AB 3 groups of a total of 96 workers who hod worked in a packing ST-V-J department between 1954 and 1957 in which an antirust oil containing N-phenyl-l-naphtylamine (PNA) and sodium nitrite tea (NaND(2)) was used* 33 workers in a different packing department end exposed only MeNOC23 * and 31 workers who had exhibited eczema as a result of exposure to PNA in the oil* were examined for excess cancer. Among women exposed to the oil containing PNA 12 cancer cases were found versus 3.9 expected. The tumours were situated in the uterus* ovaries, breast, thyroid* brain, colon KyrSts,4^1r,*V . end bladder. No known carcinogenic substance was found that could explain this increased incidence but PNA* or Its nitroso derivative* is likely to be the causative agent. *. - ,, jp?2*Kmr/; 00012739 BURCHFIELD PAGE 52 l'- * INOUE K 5 SUNAKAWA T J OKAMOTO K *, TANAKA Y MUTAGENICITY TESTS AND IN VITRO TRANSFORMATION ASSAYS ON TRIETHANOLAMINE EHIC/82/004651 MUTAT RES; 101i305-313,1962 ENG EM1C/ORNI SEE: CA 97-56796 HUH N I NEMOTO N \ UTAKOJX T METABOLIC ACTIVATION OF BENZOt AIPYRENE. AFLATOXIN Bl> AND DIMETHYLNITROSAMINE BY A HUMAN HEPATOMA CELL LINE EMIC/82/004627 MUTAT RES! 99:339-398*1982 ENG EMIC/ORNL SEE: CA 97-51017 ABE S ; SASAKI M INDUCTION OF SISTER-CHROHATID EXCHANGES BY INDIRECT MUTAGENS/CARCINOGEHS IN CULTURED RAT HEPATOMA AND ESOPHAGEAL TUMOR CELLS AND IN CHINESE HAMSTER DON CELLS CO-CULTIVATED WITH PAT CELLS EMIC/82/004253 MUTAT RES* 93:909-918,1982 ENG EMIC/ORNL 195 AU - AMACHER DE 5 TURNER GN TI - THE EFFECT OF LIVER POSTMITOCHONDRIAL FRACTION CONCENTRATION FROM AROCLOR 1259-TREATED RATS ON PROMUTAGEN ACTIVATION IN L5178Y CELLS SI - EMIC/82/009237 SO - MUTAT RES', 97:131-137,1982 LA - ENG AB - EMIC/ORNL SEE: CA 96-175811 196 AU - CHEN DJ i OKXNAKA RT 5 STRNISTE GF ; BARNHART BJ TI - INDUCTION OF 6-THIOGUANINE-RESISTANT HUTATIONS BY RAT-LIVER HOHOGEMATE tS9)-ACTIVATED PROMUTAGENS IN HUMAN EMBRYONIC SKIN FIBROBLASTS 31 - EMIC/62/009213 50 - MUTAT RES? 101:87-98,1962 LA - ENG AB - EMIC/ORNL SEE: CA 96-175918 197 AU - PAINTER RB i HOWARD R TI - THE MELA DNA-SYNTHE5IS INHIBITION TEST AS A RAPIO SCREEN FOR MUTAGENIC CARCINOGENS 51 - EHIC/62/004200 SO - MUTAT RES? 92:427-437,1982 LA - ENG AB - EMIC/ORNL SEE: CA 96-175817 00012740 BURCHFIELD PAGE 53 148 AU - PARODI S i TANINGHER M } BDERO P J SANTI L TI - QUANTITATIVE CORRELATIONS AMONGST ALKALINE DUA FRAGMENTATION, DNA COVALENT BINDING, MUTAGENICITY IN THE AMES TEST AW CARCINOGENICITY, FOR 21 COMPOUNDS SI - EM1C/62/004142 SO - MUTAT RES} 93:1-24,1982 LA - ENG AB - EMIC/ORNL SEE: CA 96-117313 149 AU - SUTEP U : JAEGER X 'e'Ti :?rm fe' S-i-it'* r.v.'!*:,- . . NAtf'?#c: S?" *1^ *N$feuM m ?j$0. .v' 1I 00012761 BURCHFIELD PAGE 74 Feron VJ * Kruysse A * Woutersen RA Institute CIVO-Toxicology end Nutrition TNO Zeist* The Netherlands. TI - Respiratory tract tumours in hamsters exposed to acetaldehyde vapour alone or simultaneously to benzole ipyrene or diethylnitrosamine. SI TOXBIB/82/210845 SO Eur J Cancer Clin Oncol; VOL 18> ISS 1> 1982* P13-31 LA Eng 249 AU Ognua K ; YoKokown K Tomoyori T Ono'e T AD Department of Pathology* Sapporo Medical College* Sapporo* Japan. TI - Induction of gamma-glutamyltranspepttdase-positive altered hepatocytie lesions by combination of transplacental-initiation and postannl-selection. SI TOXBIB/62/166490 SO Int J Cancer; VOL 29. ISS 3. 1982. P333-6 LA Eng 250 AU Pitot HC ; Goldsworthy T ; Moran S > Siriea AE * Meeks J AD McArdle Laboratory for Cancer Research* Department of Oncology Medical School. University of Wisconsin* Madison. TI - Properties of Incomplete carcinogens and promoters in hepntocarcinoaenesis. SI - TOXBIB/62/162602 SO - Coreinog Compr Surv; VOL 7* 1982* P85-98 (REF: 48) LA - Eng 251 AU TI SI SO LA AB BOGOVSKII PA THE DEVELOPMENT OF EXPERIMENTAL ONCOLOGY IN THE ESTONZAN-SSR USSR HEEP/64/04122 EKSP OHKOLJ 4 (6). 1982 (RECD. 1983). 66-67. RUS HEEP COPYRIGHT: BIOL ABS. REVIEW HUMAN BENZO A PYRENE NITROSO DI ETHYLAMINE POLY CYCLIC AROMATIC HYORO CARBON CARCINOGEN HEPATOMA OIL REFINING POLLUTION 252 AU TI SI SO LA AB POLAND A ; PALEN D ; GLOVER E TUMOR PROMOTION BY TETRA CHLORO DI BENZO-P-DIOXIN IN SKIN OF HRS-J HAIRLESS MICE HEEP/83/12949 NATURE (LOND )* 300 (5889). 1982. 271-273. ENG HEEP COPYRIGHT: BIOL ABS. 01 METHYL BENZ A ANTHRACENE N NETHYL-N'-NITRO-N-NITROSO GUANIDINE CARCINOGEN DIOXIN PAPILLOMA ENVIRONMENTAL TOXICANT II 00012762 BURCHFIELD PAGE 75 ? i 253 AU - HAUSER TR { BROMBERG SM TI - ENVIRONMENTAL PROTECTION AGENCY MONITORING PROGRAM AT LOVE CANAL NEW-YORK USA I960 SX - HEEP/83/12302 SO - ENVIRON MONIT ASSESS; 2 (3). 1982 (RECD. 1983). 249-272. LA - ENG AB - HEEP COPYRIGHT: BIOL ABS. INDUSTRIAL POLLUTION HAZARDOUS WASTE DISPOSAL 254 AU - HIR5ALIS JC *, TY5n"_ CK ; BUTTERNORTH BE 'c ------- ... ......... m iim Circmogtmcuy YesT system In rats* In vlvo-ln vitro* Is discussed In light of the validation results obtained to far. The new test lasts only 3 wk and Involves the use of peritoneal cells as target cells. Colony growth In soft agar Is considered as a criterion for eell transformation which* In turn* Is taken as evidence for a carcinogenic potential of the agent tested. There was an absence of colony growth in 96 of the cultures made from the 225 control rats tested so far. Neg. results were also obsd. with 2 known noncarclnogens* whereas pos. cultures were obsd. for 7 known carcinogens belonging to 5 different classes. These chosen target cells are sensitive enough to detect the carcinogenic effect of agents applied In vivo even if these are strictly organotrople In their action. - Li M - Inst. Cancer Res.* Chin. Acad. tied. Scl.* Peking - Studies on potential carcinogens In the diet of Individuals at high risk for esophageal cancer CA/094/186612V - Cancer Res. People's Repub. China U. S. A.* Epidemiol.* Causation New Approaches Ther.* tProc. Confl 1961*131-6 LA - ENG U R L H I44 00012835 BURCHFIELD PT 2 AB - CBAC COPYRIGHT: CHEN AB$ The formation of DHN, diethylnltrosamlne* methylbenzylnitrosamine* and N-(1-methyleeetonyl )-N-(3-methylbutyl>n1trosamlne was demonstrated (n moldy cornbread after an 6-day incubation following the addn. of NoN02. 162-75-9 DHNM55-18-5 D< ethylnltrosamlne )(937-90-6 Methylbenzylnitrosamlne M 71016-15-9 N-t1-methylecetonyl)-N-(3-methylbutyl)n1trosamine) Cornbread Inoculated with Fusarium moni11 forme and treated with NaN02 caused tumors In rats. Roussin rad He ester was isolated from pickled vegetables and this compd. Induced forestomach tumors In mice. (16071-96-8 Roussin red methyl ester) BenzoCol pyrene (I) and other polycyclic erom. hydrocarbons were Isolated from the pickled vegetables. (50-32-8 Benzo(a)pyrene> The results were discussed in relation to the diet of Individuals at high risk for esophageal cancer. 130 AU - Ckinaka RT } Barnhart BJ Chen DJ AD - Los Alamos Scl. Lab.* Univ. California* Los Alamos TI - Comparison between sister-chromatid exchange and mutagenicity following exogenous metabolic activation of promutagens SI - CA/099/059300S 50 - Mutat. Res.! VOL 91* ISS 1* 1981,57-61 LA - ENG AB - CBAC COPYRIGHT: CHEN ABS Benzo[a)pyrene (I) and dlmethyln<trosamlne (DHN) were toxic to Chinese hamster ovary (CHO) cells after being metebolically activated with S9 proteins. (50-32-8 Benzota]pyrene)(62-75-9 Dimethylnltrosamine) In contrast* neither compd. elicited a cytotoxic effect when microsomal enzymes were not present. At 1-9 mug/mL* 1 and DHN induced mutation and sister chromatid exchange (SCE) in the presence of S9 protein. The response* as a function of dose* was pos. and linear. A pos. relation apparently exists between mutation and SCE when an exogenous supply of rat liver microtomes Is used to activate the promutagens* and SCE anal, may therefore be a useful measure of genetic damage in systems utilizing metabolic activation. 131 AU - Pesch GG i Peseh CE ; Hclcolm AR AD - Environmental Research Lab.* Norragansett. RI. TI - 'Neanthes arenaceodentata* a Cytogenetic Hodel for Harine Genetic Toxicology 51 - NTIS/PB82-169202 SO - Govt Reports Announcements 4 Index (GRA4D* Issue 12* 1982 OD - NTIS/PB82-169202, 13p PR - NTIS Prices: PC AQ2/MF A01 AB - TD3: Genetic toxicants are present in polluted marine environments and may represent a long-term threat to populations of marine organisms. A cytogenetic model Is useful to study the effects of these toxicants. The polveheeta* Neanthes arenaceodentata* was chosen as si."' -odel because It has a w w *4 * V 9 4 00012836 BURCHFIELD PT 2 PAGE 50 /> [ 132 AU V. ' T1 SI SO OD PR AB 133 AU AD TI SI SO OD PR AB (SCE) analysis* a sensitive cytogenetic technique* to this marine worm. In earlier studies* N arenaceodentata exhibited a dose response to mitomycin C IMMC) at concentrations comparable to these that elicited responses In In vivo mammalian systems. Exposure to 5 times 10 to the 7th power M MMC for 46 h Increased the frequency of SCE In the worm from a baseline value of 0.14 exchanges/chromosome to 0.5 exchanges/chromosome. Positive SCE responses in the worm have also been demonstrated In this study for other known* direct-acting mutagens such as 5-bromodeoxyuridlne and methylmethanesulfonate* as well as for compounds that need metabolic activation such as benzol aJpyrene* dimethylnltrosamine and cyclophosphamide. These results Imply that N* arenaceodentata can metabolize promutagens and suggest that the worm may be sensitive to a bread spectrum of genetic toxicants. The significance of these findings* as well as directions for future research* are discussed. Journal article Baines TM Envlronmental Protection Ageney* Ann Arbor* MI. Control Technology Assessment and Characterization Branch. Nitrosamines and Other Hazardous Emissions from Engine Crankcases NTIS/FBB2-127960 Govt Reports Announcements A Index IGRAAIl* Issue 06* 1982 NTIS/PB82-127960. 15p NTI5 Prices: PC A02/MF A01 T03: The emissions from heavy duty Diesel erenkeases contain a number of hazardous compounds. Research has discovered some of them and it may be possible that there are some that have not yet been quantified. Nitrosemines (a potent carcinogen In animals and probably also in humans) are emitted from engines using fresh oil. These emissions seem to be a function of the type of oil used and some engine parameters such as crankcase flow rate of HOx compounds. Used lubricating ell has been shown to contain carcinogenic compounds such as benzo-a-pyrene. It has also been shown to be mutagenic. Therefore it can be concluded that the particulate portion of the crankcase effluent stream may start out after an oil change at a level containing few carcinogenic compounds but the level of these compounds increases with time. In conclusion* crankcases emit a variety of hazardous chemicals and evaluation of the costs and benefits of the control of these emissions should be seriously considered. Technical rept. langenbach R * Mallek L * Nesnow S Health Effects Research Lab.* Research Triangle Park* NC. Rat Bladder Cell-Mediated Mutagenesis of Chinese Hamster V79 Cells and Metabolism of Benzol aIPyrene NTIS/PB82-127362 Govt Reports Announcements A Index (GRAAD* Issue 05* 1982 NTIS/PB82-127382* 7p NTIS Price*: PC A02/MF A01 TD3: Primary rat bladder epithelial cells were cocullvated with Chinese hamster V79 cells In the presence of carcinogens* and the induction of 6-thioguanine resistance In the V79 cells was used 00012890 BURCHFIELD PT 3 PAGE 49 alkaline sucre** gradient centrifugation; unscheduled DNA synthesis (UDS) In CRFK. Syrian hamster embryo (SHE) and rat hepotocyt* cultures measured by liquid scintillation counting; and UD5 in CRFK, SHE and ret hepatoeyte cultures measured by autoradlography. DNA strand breaks were observed with 3 procerc1 nogens and 4 ultimate carcinogens. Only 2 procarcinogens and 3 ultimate carcinogens could be Identified by liquid scintillation counting. A positive autoradiographic response for UDS was observed in CRFK cells with 4 of 5 ultimate carcinogens and 1 precarcinogen. SHE cells showed a positive autoradlographlc response for UDS with all ultimate carcinogens end 3 procarcinogen*. The autoradiographic system with primary rat hepatoeyte cultures was the only one in which a positive response for DNA damage was elicited for all 20 carcinogens. 239 ; AU --< AD TI SX SO AB - ROBERTSON DJ t GROTH RH 5 BLASKO TJ - Xnstrum. Group* Pratt end Whitney Aircr. Group* Commer, Prod. Div.* East Hartford. Conn. 06108, USA. - Organic content of particulate matter In turbine engine exhaust. - HEEP/80/10674 - J AIR POLLUT CONTROL ASSOC; 30 (3). 19S0. 261-266. - HEEP COPYRIGHT: BIOL ABS. Solid particulate matter, mainly C emitted into the air from the combustion f fossil fuels contains a variety of organic species adsorbed on it. In an examination of these partieulates from the eombustton of kerosene type fuels In a gas turbine engine, attention was focused on polynuelear aromatic (PNAI compounds, phenols, nltrosamlncs and total organics. Polynuclear* were determined by HPLC (high performance liquid chromatography> GC/HS (gas chromatogrephy/mess spectrometry) and NMR examination. Phenols and nltrosamlnes were isolated and measured by GC using a flam* Ionization detector and N detector. Total organics were determined by a beekflush chromatographic procedure. The partieulates were'collected using a high capacity pumping system and 293 mm diameter teflon filters through which passed up to 43 m3 of exhaust gas. Extraction of the organie matter was done In a Soxhlct extractor usually using hexane. The engine was operated of idle, approach, climb and takeoff power settings with low S and high S (0.25)0 fuels. Host of the PAH (polyaromatic hydrocarbons ) were small 3 and 4 fused ring compounds with very feu, at low concentratIons of 5 and 6 fused ring species. No nltrosamlnes were found end except in a few eases, at low levels, no phenols. PNA and total organie levels decreased with Increase in a power setting and were higher in the exhaust from low S fuels. Less than IX of the organic matter emitted by the engine was absorbed on the particulate matter. ere important variables in assessing the potential effect of microsomal enzyme-inducing agents on the metabolism of mutagenic substances. * ;I .`T.* 00012926 BURCHFIELD PT 4 PA6E 7 14 jW AD TI SI SO LA AB 15 AU AD TI SZ SO LA AB Hetivler H 5 Masse R ; L'Hullier I ; Lafuma J Lab. Toxicol. Exp.. Inst. Prot. Surete Nucl. Montrouge Study of the combined action of Inhaled plutonium oxide and two chemical carcinogens present in the environment CA/095/019358F Biol. Implic. Radionuclides Released Nucl. Ind.* Proc. Int. Symp.J VOL 2. 1979,93-104 FRE CBAC COPYRIGHT: CHEH ABS The modifications of risk attributable to benzo(a)pyrene (II and dimethylnltrosamine (DUN) following Inhalation of Pu02 were studied in rats. (50-32-6 benzolal pyrene X62-75-9 Dimethylnitrosamine) 1 (2 .times. 5 mg) was given intratracheally in assocn. with Fe203 2 and 3 uk after inhalation of Pu02. DMN (2 or 20 ppm) was added to the animals' drinking water. For X. a strong synergistic effect occurred which manifests itself in a substantial redn. of lifetime in animals that have Inhaled a small quality of Pu02 (17 nCi) and in a greater incidence of tumors and enhanced tumor Invasiveness whatever the dose of Pu02 Inhaled. Inhalation of Pu02 assoed. with regular ingestion of DMN multiplies the metestases of liver cancer* in the lung. Addn. of X or DMN modifies the hlstol. profile of radiation-induced tumors. The synergistic effects are no longer obsd. when the pollutant concns. used produce subacute Intoxication. Carver JH J Adair GM 5 Mandres DL Lawrence Livermore Leb. California l>Mv., Livermore Mutagenicity testing in mammalian cells. Multiple drug-resistance markers CA/093/216146V Report: ISS EPA-600/7-79-173* UCXD-16599! Order Ho. PB60-183114,, 1979,79 pp. ENG CBAC COPYRIGHT: CHEM ABS Chinese hamster ovary (CH0) cell lines heterozygous at th* adenine phosphorlbosyltransferese iaprt) end thymidine kinase (tk) loci were isolated and used for single-step selection of spontaneous end Induced mutants resistant to 6-azaadenine (AAr), 6-thioguenine (TGr), 5-fluorodeoxyuridine IFUdRr), or ouabain (OUAR). Mutation date are reported for direct mutagens Et methanesulfonate (EHS), N-methyl-H'-nitro-N-nltrosoguanidine (HNNG), 4-nltroqulnoline-l-oxlde <NQ0) and for promutegens dimethylnitrosamine IDMN) and benzota)pyrene (BaP) activated by rat liver homogenates. (42-50-0 Ethyl methanesulfonate)(70-25-7 N-Methyl-N*-nitro-N-nitrosoguanidine )(56-57-5 4-N1troquinoline-l-oxide)(62-75-9 Dimethylnltrosamine )(50-32-6 Benzo(a )pyrene) Crlt, plating densities were established for AAr, TGr, end FUdRr. Optimal expression of mutant phenotypes after mutation induction with EMS DMH, or BaP were 2 to 4 d for AAr, 6 to 6 d for TGr, 3 d for OUAR, end 1 to 3 d for FUdRr. The induced mutant frequencies as a function of relative cell survival after treatment with EMS, DMH, or BaP showed TVf... W-/. h' stU > V 14* - ' I *> ' . *'>*** > \ ' .'f . ' - 'm 0 * I I $ I I Total binding mlghT indicate a mgner carcinogenic poiency (nan was actually obsd. SO AU AD TI SI SO LA AB 21 )AU C V AD r* TI SI 50 LA AB - Ounkel VC - Natl. Cencar Inst.. NIH. Bethesda - Collaborative studies on the Salmonella/alerosome mutagenicity assay - CA/091/064117H - J. Assoc. Off. Anal. Che*.; VOL 62. ISS 4, 1979.874-82 - ENG - CBAC COPYRIGHT: CHEH ABS Although the Salmonella plate test has been used extensively, a collaborative study was undertaken to det. the Interlob. reproduclbl11ty of this microbial mutagenicity assay. All chemicals 161) were tested both with and without metabolic activation in S. typhlmurium strains TA1S35, 1537, 1538. 98. and 100. The metabolic activation systems used were derived from the livers of both unindueed and Aroclor 1254-lnduced Fischer rats. B6C3F1 mice, and Syrian hamsters. Results on 23 of the ehems. tested In 3 of the participating labs, showed that 8 were neg. when tested in all labs, and 13 were pos. Two ehems. gave pos. results in 2 labs., but were neg. when tested in the 3rd lab. - Pitts JN Jr - Statewide Air Pollut. Res. Cent.. lAtlv. California. Riverside. Calif. - Photochemical and biological implications of the atmospheric reactions of amines and benzol aipyrene - CA/090/181263Q - Philos. Trans. R. Soc. London. Ser. A; VOL 290. ISS 1376. 1979,551-76 - ENG - CBAC COPYRIGHT: CHEH ABS Exposure of glass fiber filters coated with benzola)pyrene (I) to 1 part N02/106 land a trace of HN03) In air formed mutagenic nitro derive. (50-32-8 benzoCal pyrene ) Nonmutagen1c perylene (II) under similar conditions gave a moderate mutagen 3-nitroperylene. (196-55-0 PeryleneK20589-63-3 3-Nitroperylene) Older similar expts. 1-nltropyrene was formed from pyrene, another nonmutagen. (5522-43-0 1-N1tropyrene 1(129-00-0 Pyrene) The significant reactivity of I. It. and even pyrene with N02 was also obsd. in the dark at well as 1 with 03, peroxyeeetyl nitrate (PAN) and ambient photochem. smog. (2278-22-0 Peroxyaeetyl nitrate) These reactions of polycyclic arom. hydrocarbons strongly suggest the possibility of similar reactions occurring in the environment, possibly to a major degree. In a related study, diethylamine and triethylamine readily formed photochem.smog (i.e., rapid conversion of NO to N02 and the formation of 03. AcH PAN and light-scattering particles) when amine-NO-elr mixts. were solar irradiated. (109-89-7 d1ethylam1ne)(121-44-8 triethylamine) Addnl. small but 4 il % * 00012932 Bl/RCHFIELD PT 4 PAGE 11 URL 14148 significant amts, f (Et)2NN0 were formed In dark from (Et)2MH but destroyed In sunlight. (55-18-5 Diethylnltrosamine ) In contrast, (Et)2NN0 was initially formed from (Et)3N on irradn. of the gaseous mixts.. then photodecompd. Other major compds. formed included dielkylnitramines and substituted amides. Environmental implications are discussed. fi 22 AU - Rao TK ; Stoltz DR Epler JL AD - Biol. Div.t Oak Ridge Natl. Lab.. Oak Ridge TI - Lack of enhancement of chemical mutagenesis by saccharin In the Salmonella assay t V. SI - CA/09Z/089050M SO - Arch. Toxicol.S VOL 43, ISS 2, 1979,141-5 LA - ENG AB - CBAC COPYRIGHT: CHEH ABS A purified batch of saecherin (I) was assayed for mutagenicity and comutegeniclty by the Ames Salmonella assay. (81-07-2 Saccharin) I was not mutagenic and failed to enhance the mutagenic activity induced by a wide ,, S- variety of known mutagens. These results do not argue against the tumor-promoter-11ke activity of I, but only Indicate that the Ames Salmonella essay is not capable of detecting I os a promoter of mutagenesis. 1 bu - Lancer *es * vul ao* ajo /* reuua-iu LA - Eng r- AB * The metastatic capabilities of well-defined nodular hepatic S H H ia n il 00012944 f BURCHFIELD PT 4 PAGE 23 lotions Induced by benzola )pyrene ethylnltrosouree* benzldine.2HC11 end dlethylnitrosamin* were evaluated. Coded liver end lung tissues from 1264 treated C57BL/6J x C3HeB/FeJ FI mice were assessed Independently for the presence of primary nodular lesions ond metastases* respectively. Primary lesions uere classified according to their size* cell morphology* and growth patterns Into hyperplastic* adenomatous* and trabecular nodules. Hone of the 126 mice bearing hyperplastic nodules had pulmonary metastases. Four of 291 (1.42) mice with adenomatous nodular lesions showed metastases. In contrast* of the 733 mice bearing the trabecular type of nodular lesions alone or in combination with other lesions 266 (362) showed pulmonary metastases. The pulmonary metastases were first detected in mice dying between 51 end 60 weeks of age (52). This rate increased at a function of age at death* reaching an Incidence of 512 In mice surviving more than 61 weeks. It was concluded that nodules showing trabecular end the more anaplastic solid sheet type of growths represented bona fide hepatocellular carcinomas In the mouse. / 53 Xu AI SI SO LA AB Preussmann R (Envlronmenlal carcinogen*: mechanisms of action and occurrence. Some aspects (author's trensi)) T0XBIB/7B/1S3349 Zentralbl Bakterlol tOrig B1`, VOL 166* 1S3 2-3. 1976, P144-58 Ger New aspects on the mechanism of action of known environmental carcinogens are described. These compounds are not active as such* but ere bioactivated in the mammalian metabolism vie chemically reactive Intermediates to electrophilic reactants* forming with Information-bearing blopolymeres covalent bonds. This change In the genetic code Is In agreement with the mutation hypothesis of carcinogenesis. Aflatoxin Bl* N-nltroso compounds end benzol aJpyrene are taken as examples. "Threshold levels"* e.g. no-effect-levels derived from animal experiments with all their inherent limitations* are compared with data from human exposure to benzol a )pyren* aflatoxine* N-nltroso compounds end vinyl chloride. The difficulties of such risk evaluations ore discussed. 54 AU - von Nleding G AD - Bethonien Hospital* Hoars> Hast Germany. TI - Possible mutagenic properties ond carcinogenic action of the irritant gaseous pollutants N02* 03* and $02. SI - T0XBIB/76/16B876 SO - Environ Health Perspect; VOL 22* 1976* P91-2 LA - Eng AB - Carcinogenic or eoearcinogenlc effects of N02* 03* and S02 have not been proven to date with sufficient reliability. However, nltrosomine formation after exposure to N02- or 03-1ndueed decrease in benzpyrene hydroxylase ere potential hazards. A final revaluation of a possible cocarelnogenic action of S02 requires further experimental studies. u t "1 for long period Is unusual. In comparison In analogous expts.* uncharged polycyclic arom. hydrocarbons (PAH) disappeared practically completely by 5-6 h after administration. The concn. of Z after maternal administration* in contrast to PAH* was several-fold lower in the liver of the mother than that in the 0 embryo. 56 AU - Robertson DJ > Broth RH t Blasko TJ AD - Pratt and Whitney Airer. Group* East Hartford TI - Organic content of particulate matter in turbine engine exhaust SZ - CA/093/030970D SO - Proe.* Annu. Meet. - Air Pollut. Control Assoc.* VOL 71st. Vol. 2* 1975*78-26.6* 16 pp. LA - ENG AB - CBAC COPYRIGHT: CHEM ABS Particulate matter from a gas turbine engine uas collected for the detn. of org. matter. Org. matter in particles uas >1'/. of the total orgs. emitted. Nitrosamine end phenols were found in only 2 samples. (35576-91-1 Nitrosamine) Most of the polynuclear arom. hydrocarbons (PAHs) hod 3 or A fused rings and a feu had 5 or 6. The total orgs. and PAHs decreased with Increase In engine power. PAHs were high in the exhaust from low-S fuels. 0 " Jtl *** si SO LA AB - Div. Chem. Card nog.* Inst. Cancer Res.* Peking - Further study on the etiology of esophageal cancer - CA/093/020427T - Chung-hua X Hsueh Tsa Chlh (Peking); VOL 5B* XSS 10* 1978*593-7 - CHI - CBAC COPYRIGHT: CHEM ABS Environmental factors responsible for a high Incidence of esophageal cancer in Lin country (in northern China) were investigated. High concns. of nitrates* nitrites* secondary amines* nitresamines and a low level of ho were found in the environment (drinking water, food, etc.). Some mycobacteria found In food reduced nitrates to nitrites* and hydrolyzed proteins to secondary amines, which promoted the formation of earelnogenic nitresamines. DMN* dlethylnitrosemlne* 0 0/ URL H I 50 00012946 BURCHFIELD PT A % PAGE 25 ft % methylbenzylnitrosamine* and N-3-methylbutyl-N-l-methylacetonylnitrosamine were found in contaminated food. (62-75-9 Dimethylnltrosamine>(55-18-S D1ethylnltrosamine )(937-AO-6 Methylbenzylnltrosamine)(71016-I5-A N-3-methylbutyl-N-l-methylacetonylnitrosamine) In In vitro expts.* inoculation of Fusarlum moniliforme on corn in the presence of nitrites resulted in the formation of these carcinogenic substances. The atm. content of benzo(a)pyrene (X) * during winter was .ltoreq.17.36 mug/100 m3. (50-32-6 Benzoto)pyrene) Thus* multiple factors may be responsible for the high incidence of esophageal cancer. * 58 AU - Tanaka T * Keno-Taneka K AD - Lab. Cell Biol.* Aichi Cancer Cent. Res. Inst.* Nagoya TI - The effect of cocarcinogen on transplacental carcinogenesis SI - CA/092/08906AU SO - Proc. Perugia Quadrenn. Int. Conf. Cancer? VOL 6th* XSS Tumours % Early Life Man Anlm.* 1978,963-71 LA - ENG \ AB - CBAC COPYRIGHT: CHEM ABS Rets transpleeentally exposed to 5 mg 0 f dlmethylnitrosamlne/kg on the 17th* 18th and 19th days of gestation developed tumors* while animals receiving the dose only on the 17th day produced no tumors. (62-75-9 Dimethylnitrosamine) Nitrosomethylurethane at 10 mg/kg qlven on e the 17th day of gestation did not cause tumors in the offspring while Me methanesulfonate at 8 mg/kg provoked few tumors in the offspring. (615-53-2 Nitrosomethylurethane)(66-27-3 Methyl l methanesulfonate ) Prenatal exposure to 3 mg benzo la)pyrene m (I)/kg and postnatal treatment with 20 mg diethylnitrosamlne/kg and 5 mg Me methonesulfonate/kg caused no tumors. (50-32-8 Benzo(a)pyrene) Combined exposure to 2 carcinogens in prenatal then postnatal life caused a dramatic Increase In tumors. Dodecane and phenyldodecane applied topically to progeny of animals treated with I* chrysene* or benzotb)triphenylene on the 17th day of gestation produced tumors in the offspring. 1 - 'v'*C Sr s& 00012977 BURCHFIELD PT 4 PAGE 56 - Semegyt A J Maliek LE * Langenbach R Sallaeh K - (Contemporary animal nutrition and 1t potential hazards to human health (author1* trensl)) - TOXBIB/77/107592 - Zentralbl Bakterlol tOrig BJ ! VOL 163* ISS 1-4* 1976 P153-72 - Ger - The growing challenge to secure wholesome food of animal origin in quantities sufficient to feed the ever Increasing world . population leads to the compelling need of search for new means to enhance animal production. Such an endeavor often Involves the use of pharmacologically active agents. As new substances are continuously introduced into agriculture* the necessity clearly arises to reassess the requirements for the approval of compounds ltkely to appear in the food of man via the edible tissues of animals. Since a number of animal drugs and feed additives have been recently found to show carcinogenic potency* using examples from their own research* the authors discuss problems encountered while planning animal studies for the safety evaluation of chemicals. Among the most important factors to be reckoned with is the metabolism of the test substance. Most carcinogens require metabolie transformation in order to react with macromolecules and* thus* exert their biological aetion. Similarly* residues of many drugs in animal tissues appear to be various metabolites rather than the parent compounds themselves. At present* it is not known whether many chemical residues are simply stored in different compartments of the carcass as a result of their physico-chemical properties or whether they are covalently bound to vital macromolecules (e.g.* nucleic acids). Hence* their biological significance is not quite clear. The enzyme system which metabolizes numerous drugs* pesticides* as well as other endogenous and exogenous substrates is responsible for both the activation end detoxification of carcinogenic chemicals. The delicate balance between these two processes of opposing toxicological consequence is determined by genetic end environmental factors. Depending upon the metabolie profile of ehemieals* certain compounds are carcinogenic in one animal species while not in others. The manipulation of their metabolism by physiological te.g. stress) or pharmacological (e.g.* Inducers or Inhibitors of microsomal enzymes) means can result In a profound change of various biological actions of chemicals le.g.* cytotoxicity* eercinogenieity mutagenicity). To ascertain that potential toxicological hazards to human health by animal drugs and feed additives will be recognized during the phase of testing* appropriate test animals have to be selected with great care. It is indispensible that the metabolic break-down of the investigational substance proceeds via similar pathways in both test animals and the target species. This will assure that the same metabolites which* in the form of residues in food* man might be exposed to will have ample opportunity to exert their possible adverse effects to the experimental animals during a life-long feeding of the test substance. Therefore* it can* with a reasonable certainty* be assumed that* in experiments performed 4 6* -- , 00012976 BURCHFIELD PT 4 PAGE 57 under such preceut1onary measures* toxico-pharmecologlcal properties relevant to human safety evaluation will not remain undetected. 137 AU - Thust R TI - Screening of potential chemical carcinogens by means of mammollan cells in vitro. * SI - TOXBIB/77/0B6605 SO - Arch Geschwuls1forsch* VOL 46, ISS 7, 1976* P536-48 mi LA - Eng 136 AU - Hard GC I Gresso P TI - Nephroblastoma in the rat: histology of a spontaneous tumor* idantltv with resoeel to rona) mosi*rirhmal . r>.iJ *. Q 45. MORTALITY PATTERNS IN EIGHT U. K. OIL REFINERIES. Aldersou M, Rusbtou L last. Cancer Res., Suttoa, Surrey, England Ann NY Acad Sci; 381:139-145 1982 The patterns of mortality are described for 33,000 male em ployees, with a minimum of I year's continuous service, who worked at 8 refineries in the UK. in the period 1 January 195131 December 1973. The trace rate of those involved was 99.8%. Overall the ratio of observed to expected deaths was 0.84 (O = 4,406, E = 5,239.9 p less than 0.00001). The num bers of deaths for many of the chronic degenerative diseases were lower than `expected'. The number of observed deaths from all cancers were appreciably less than expected (O = 1,147, E = 1,286.4, O/E -- 0.89, p = 0.00006). Lung cancer was particularly reduced (O 416, E *= 532.7, O/E = 0.78, p 0.00001); there was no excess of leukemia (in workers includ ing some exposed to benzene). Other comparable studies have suggested an excess of gastrointestinal cancer. In the present study deaths from esophageal, stomach, intestinal, and rectal cancer were slightly raised for all workers (O = 346, E = 328.6, O/E s 1.05, p less than 0.4); this was particularly true for those joining before 1950 with long service and increased latent interval. There were also excesses based on small num bers of deaths from nasal cancer (O = 7, E = 3.1, O/E -- 2.24, p less than 0.05), and melanoma (O -- 14, E = 6.5, O/E = 2.16, p less than 0.01). There was no evidence of an excess of brain tumors (O = 36, E = 44.8, O/E = 0.80, p less than 0.2). (Author abstract) (18 Refs) 46. BRAIN CANCER: ISSUES AND DILEMMAS. Hauls NM, Holmes TM, Newill VA, Smith FR, Smith LG Exxon Corporation, East Millstone, NJ, 08873 Ana NY Acad Sci; 381:83-90 1982 A cohort study covering the 8 yr period, 1970-1977, identi fied eight deaths attributed to brain cancer among employees at a refinery/chemical plant. Five of the cases were primary brain cancers and three were either metastatic from another site or the site was undetermined. A ninth case of brain tumor unspecified was identified. Five primary brain cancers would have been expected, based on national statistics. Some issues and dilemmas related to such a cohort study were discussed. (Author abstract) (4 Refs) 47. CORRELATION OF OCCUPATION AND KARYOTYPE IN ADULTS WITH ACUTE NONLYMPHOCYTIC LEUKEMIA. Gotomb HM, Altmans G, Rowley JD, Vardiaia JW, Testa JR, Sorik C Box 420, 950 East 59th Sl, Chicago, IL, 60637 Blood; 60(21:404-411 1982 Seventy-four adult patients with acute nonlymphocytic leu kemia (ANLL) were classified retrospectively as to whether or not they had had occupational exposure to insecticides, chemi cals and solvents, or petroleum products. Fifty-eight patients were considered nonexposed and 16 were considered exposed. The chromosome banding pattern was abnormal in 37 of the 74 patients (50%). Twenty-five of the 58 (43%) nonexposed pa tients had a clonal chromosome abnormality, compared with 12 of the 16 (75%) exposed patients (p = 0.02). Only 2 of 23 (8.7%) females with an abnormal karyotype were exposed, whereas 10 of 14 (71%) males with an abnormal karyotype were exposed. Either a-5/5q- or a-7/7q- was present in 67% of the exposed patients with a chromosome abnormality, com- F* d - W&iSZCc ?r pared to 28% of the aneumoid fonexposed patients. The-7/7qabnormality was present m 7 Jf the 12 (58.3%) exposed pa tients, vs 5 of the 25 (20%f) nonexposed patients with abnormal karyotypes (p less than 0,65). TJne-5/5q- anomaly was observed in 4 of the 12 (33%) expelledpatients and in 4 of the 25 (16%) nonexposed abnormal patiefttff Our study supports the observa tion that a subset of patients with ANLL de novo have a histo ry of occupational exposure and a unique pattern of chromo some abnormalities. (Author abstract) (18 Refs) 48. CANCER MORTALITY AMONG THREE SWEDISH MALE ACADEMIC COHORTS: CHEMISTS, ARCHITECTS, AND MINING ENGINEERS/METALLURGISTS. Olia GR, Ahlboa A Preventive Occupational Medicine Unit, Royal last. Technology, S- 100 44 Stockholm, Sweden Aaa NY Acad Sci; 381:197-201 1982 Cancer mortalities were investigated in three cohorts of pro fessionals graduating from the same academic institution during the same period of time (1930-59). The study included 820 chemists, 581 mining engineers, and 657 architects, of which 83, 49, and 59, respectively, were deceased. Standard mortality ratios comparing the three groups to the overall Swedish male population showed that all of them had ratios well below 100. Relative risk rates were not significantly different among the three groups. The neoplasm rate differed among the cohorts, with the relative risk for chemists being 2.5 x that of architects and for mining engineers 1.8 x. The difference in neoplastic mortality between the architects and chemists seems to be due to different rates of death among two neoplastic code-groups: leukemia/lymphoma (including 3 cases of Hodgkin's disease), and glioma. Of 32 neoplastic deaths among the chemists, 5 were attributed to gliomas. Methylnitrosourea was used rou tinely without special precautions for diazosynthesis in Swed ish educational laboratories up until the middle 1960's, but the significance of this fact to the present results has not bees de termined. (8 Refs) 49yBRAIN AND CENTRAL NERVOUS SYSTEM CANCER -Mortality in u. s. rubber workers. Symoas MJ, Andjelkovich DA Spirtas R, Hernua DR Occupational Health Studies Group, Sch. Public Health, Uaiv. North Carolina, Chapel Hill, NC, 27514 Ann NY Acad Sci; 381:146-159 1982 Since 1963 the observed mortality experience of BCNS can cers among rubber workers appears to be very comparable to that expected. A possible exception to this statement is the ex perience of one plant in Akron, Ohio, reported by Monson and Nakano. Excesses in earlier yean may also be localized to one or two companies. The results of a case-control study did not support a hypothesized association of elevated BCNS cancer risk with exposures in the tire building/tire assembly segments of the rubber tire manufacturing process. The direction of future epidemiologic studies would benefit by the assembly of as large a number of cases as possible and should focus on cal endar periods of exposure, make allowance for a latent period, and include retrospective industrial hygiene assessments of the specific exposures. (Author abstract) (28 Refs) URL 14152 12 ENVIRONMENTAL ANO OCCUPATIONAL CARCINOGENESIS , Scknitter AR kraiology, Uaion Carbide Corporation, Old Ridaebury Rond, y, CT, 06817 paring the numbers of pulmonary and non-pulmonary malig nancies) are elevated among foundry workers, miners, workers in ceramic and miscellaneous industries. Only the stone/slate industry has not yielded a significant excess of lung cancers. (Author abstract) (In GER) The relationship between chemical exposures and deaths at tributable to primary brain tumors among employees of a Texas petrochemical plant was investigated. Cases consisted of 21 deaths in which the underlying cause was confirmed as a primary brain tumor. Two control groups of 80 employees each were randomly selected from 430 decedents known to the company in June, 1979. Potential exposures while employed were compared between cases and controls for five known or suspect carcinogens. Exposure potentials were also compared for an additional 37 chemicals to which at least four cases were potentially exposed. Overall and 15-yr latency analyses were performed. The proportion of cases exposed to the five poten tially carcinogenic chemicals (including vinyl chloride) were lower than or consistent with the proportion of exposed con trols. No statistically significant differences between the pro portions of cases and controls exposed to the 37 other chemi cals were found. (Author abstract) (10 Refs) 55. POSSIBILITIES FOR IDENTIFYING CENOTOXIC RISKS IN THE RUBBER INDUSTRY: USE OF THE URINARY MUTAGENICITY ASSAY AND SISTER CHROMATID EXCHANGE. Viinto H, Fakit K. Maki-Paakkuea J, Sorsa M Departnent of Industrial Hygiene and Toxicology, Institute of Occu- potions! Health, Helsinki, Finland. IARC Sci Publ; (321:571-7 1982 Two approaches have been used for biological monitoring of exposure to genotoxins in the rubber industry: (1) assay of mu tagenic activity in urine with the bacterial fluctuation test; and (2) analysis of sister chromatid exchange frequencies in periph eral blood lymphocytes. Workers in the rubber industry have significantly more mutagenic activity in their urine than nonexposed controls. Mutagenic activity was tested with Escherichia coli WP2 uvrA as indicator bacteria was significantly higher in urine of workers after a normal work week than in urine sam ples from the same individuals after a holiday. The mean freQuency of sister chromatid exchange in rubber workers who smoked was significantly higher (p less than 0.01) than that in unexposed smokers. The only job categories in which workers who smoked had statistically significantly higher mean fre quencies than others were mixing and weighing. People in these jobs generally also had high mutagenic activity in their urine. (Author abstract) 57. ORGANIC SOLVENTS-AN INCREASING PROBLEM IN THE OCCUPATIONAL ENVIRONMENT Huaen L Frederiksberg hospital, DK, Kbcnbevn. Nord Med; 97<12fc299-301 1982 Keywords (MeSH): Abnormalities, Drug-induced/etiology; Brain/drug effects; Female; Human; Male; Neoplasms/chemi cally induced; Occupational Diseases/*chemically induced; Pregnancy; Solvents/*adverse effects. 58. A CASE-REFERENT STUDY ON NASAL CANCER AND EXPOSURE TO WOOD DUST IN THE PROVINCE OF SIENA, ITALY. Battista G, Cavallucci F, Combe P, Qaerda A, Viadigni C, Sartorelli E Iitituto di Medicine del Lavoro, Via dal Tufi 1, Siena, Italy Scam! J Work Environ Health; 9(lk25-29 1983 The aim of the present study was to assess the risk of nasal cancer associated with exposure to dust in the wood and furni ture industry in the province of Siena, Italy. Four to seven per cent of the active male population is employed in this sector. A case-referent approach was used. The cases included male sub jects seen at the Ear, Nose and Throat Clinic and the Radio therapy Unit of Siena and diagnosed as having cancer of the nasal cavities or paranasal sinuses between 1963 and 1981. The referents were male patients admitted to the Medical Clinic of Siena for all causes except nasal neoplasia; they were matched 5;1 to the cancer patients for age and time of admission. Infor mation was gathered (by postal questionnaires) on the occupa tional histories of all 36 of the cancer patients and 164 of the 180 referents. The odds ratio associated with exposure to wood dust was 5.4 (1.7-17.2) for all carcinomas, and 89.7 (19.8-407.3) for mucinous adenocarcinoma. The woods used by the exposed cancer patients were mainly oak, chestnut, poplar, and fir. The median duration of exposure was 40 years; no exposed cancer patient reported the presence of exhaust systems in their work environment. (Author abstract) (13 Refs) 56. INCIDENCE OF LUNG CANCER AND AGE AT DEATH IN SILICOSIS DEATHS OF THE SWISS NATIONAL ACCIDENT INSURANCE FUND, 1960-1978 Schuler G, Welch! P, Ruttner JR, Delmore M, Taylor M, Schnieper R Zurcber Arbeitssemeinscbaft air Erforechung und Bckampfang der Staublungea in der Schweiz, Soz Praveatinaed; 27(5)^18-9 1982 The frequency of lung carcinoma among the deaths of silicotics registered by the Swiss National Accident Insurance Fund from 1960 to 1978 has been compared with the causes of death of all Swiss males during the same period- The PMR, while underestimating the true risk, is significantly raised among foundry workers. SMR's for lung cancer (estimated by com- 59. LEUKEMIA IN HOSPITAL PATIENTS WITH OCCUPATIONAL EXPOSURE TO THE SAWMILL INDUSTRY [LETTER] Burkart JA West J Med; 137(5):440-1 1982 Keywords (MeSH): Adult; Aged; Human; Leukemia/*etiology; Male; Middle Age; Occupational Di$eases/*etiology; Wood. 12 ENVIRONMENTAL ANO OCCUPATIONAL CARCINOGENESIS URL 14154 REVIEWS INCLUDING NITROSO COMPOUNDS t/ S3. FORMATION OF METHYLAMINES FROM INGESTED CHOLINE AND LECITHIN. Zfttad SH, Wisbaok JS, Blwxtaja JK Department of Pathology, Bonton Uilrmhjf School of Madldae, Massachusetts. 4 Pharmacol Exp Thar; 239(2)^30-* 19*3 Humans ingest.substantial amounts of cholurcand Iecithin_as part of common foods. Physicians have recently begun admin istering large doses of these compounds to individuals with neurological diseases. A significant fraction of ingested choline is destroyed by enzymes within gut bacteria, forming trimethylamine (TMA), dimethylamine (DMA) and monomethylamine (MMA). Some of these methylamines are eventually excreted into the urine, presumably after being absorbed and carried to the kidneys via the bloodstream. The methylamines formed after choline is eaten could be substrates for the formation of aitrosamines, which have marked carcinogenic activity. Twenty-seven millimoles, of choline chloride, choline stearate or lecithin were administered to healthy human subjects. It was found that these treatments markedly increased the urinary ex cretion of TMA, DMA and MMA, with choline chloride having the greatest effect. Rats were treated with 2 mmol/kg b wt. of choline chloride or lecithin, and it was found that these treatments significantly increased urinary TMA excretion and did not alter DMA or MMA excretion. Our choline chlo ride preparation contained no MMA, DMA or TMA; howev er, it was found that our choline stearate and all the commer cially available lecithins tested were contaminated with methy lamines. Prior removal of methylamines from our lecithin prep aration minimized the effect of oral administration of this com pound on roethylamine excretion in urine of rats and humans. (Author abstract) 3d. THE URINARY BACTERIAL FLORA IN PATIENTS WITH THREE TYPES OF URINARY TRACT DIVERSION. HU1 MJ. Hafeoo MJ, Stewart M ^ . . u. Bacterial Metabolism Rmarch Laboratory, PHLS Centre for Applied Microbiology aad Research, Wilts, London. J Mxl 1A2H221-6 1983 There is known to be a high risk of malignancy at uretero- colic anastomoses and it has been postulated that bacteria cata lyse both the local formation and the activation of carcinogens such ax N-nitrosamines. If this theory is correct, then the risk of malignancy should be greatest when the prevalence of mixed urinary tract infection is greatest. Bacterial culture was performed on samples of urine obtained from 56 patients with three forms of urinary tract diversion: ureterosigmoidostomy, isolated ileal and colon conduits. As expected, the rectal urine of all patients with a ureterosigmoidostomy had a rich bacterial flora. However, 11 of the 15 patients with ileal conduits (73%) had significant growths of bacteria in the loop urine, whereas only six out of 16 colon loop urines (37.5%) were in fected, all being monobacterial infections. The implications of these bacteriological findings for carcinogenesis associated with urinary diversion are discussed. (Author abstract) 35. CANCER AND SECONDARY LEUKEMIA. Rasner F Qweni Hospital Center Affiliation of (be Long Island Jewiab-Hillside Medical Center, Jamaica, New York. Bull Cancer (Peris); TOUfcSS-tfO 1983 Acute myeloid leukemia or one of its variants is being re ported with increasing frequency as a second neoplasm in pa tients being treated for multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma and a variety of other primary neo plasms and non-neoplastic diseases. Although many of these patients were treated with both chemotherapy and radiothera py, many received no radiotherapy at all. Drugs most frequent ly implicated in the causation of acute leukemia and other second neoplasms are the alkylating agents, procarbazine and the nitrosoureas. The frequency of this syndrome varies from less than 1 per cent to 7 per cent in many reported series of patients. There could develop a reluctance to use cytotoxic agents to treat malignant neoplasms for fear of inducing acute leukemia. Although one has to consider this complication, one should not, however, withhold these drugs from a patient with a neoplasm or other potentially fatal disease in whom such therapy is the treatment of choice. We seem to be faced with the paradox that patients benefiting most from chemotherapy may be at highest risk of suffering its undesirable conse quences. Although the risk ofleukemogenesis or carcinogenesis in man may be smalt, these drugs should be used with caution in patients with indolent non-neoplastic diseases such as rheu matoid arthritis. (Author abstract) I CHEMICAL CARCINOGENESIS; Nltroso Compounds "V / y i'/U 17. INHIBITION BY ALCOHOLS OF THE LOCALIZATION OF RADIOACTIVE NITROSONORNICOTINE IN SITES OF TUMOR FORMATION. 1 j I 1 1 1 1 \ . INFLUENCE OF ETHYL-ALCOHOL ON CARCINOGENESIS INDUCED WITH NNITROSOD1ETHYLAMINE (MEETING ABSTRACT). Gridnte L, Castegnaro M, Bereziat JC Waddell WJ, Marlowe C Oncological Rrwwcfc tatttarte of Litkiniu SSR, Vitalaa, nwlx Dtpufft of Pkaraaeology um) Toxicology. Uaiverxity of Loaicrille, Kcotocky. Sdcocc; 221<405)^l-3 1983 SynpociiiB oa Role of Cocardaogem aad Promoters ia Hamaa aad Experimental Cardaogenctii, May 16-18, 1983, Budapest, Haagary Haagariaa Cancer Society, 1983. Oral administration of ethanol, n-butanol, or t-butanol to mice 20 minutes before injection of carbon- 14-labeled nitroson* omicotme inhibited the localization of radioactivity in bronchi al and salivary duct epithelium and in the liver. Localization of radioactivity in the nasal epithelium and esophagus was not significantly reduced. These alcohols therefore may selectively inhibit tumor formation in three of the five sites where this car cinogen typically acts. (Author abstract) 8*. MECHANISM OF CO-CARCINOCENIC ACTION OF ETHANOL ON NITROSAMINE CARCINOGENESIS IN RAT LIVER (MEETING ABSTRACT). Scfewarx M, Baehnaaa A, Kni W laatliaii of Biochemistry, German Cnscer Research Center, D-6900 Heidelberg, W. Germany Symposium oa Role of Carcinogens and Promoter* la Human and Ex- pcrimestal Carcinogenesis, Msy 16-18, 1983, Budapest, Hungary Haagariaa Cancer Society, 1983. Chronic consumption of alcohol containing beverages is as sociated with an increased risk in cancer of various organs in cluding the liver. Ethanol by itself appears to show no carcino genic potential but may possess co-carcinogenic or tumor-pro moting activity. In contrast to the results of in vitro studies ethanol does not interfere with the activation metabolism of the model carcinogen dimethylnitrosamine in vivo. However, simultaneous treatment of rats with ethanol and carcinogen leads to an increase in number and especially in size of ATPase-deficient preneoplastic foci in liver induced by either diethylnitrosamine or nitrosomorpholine. The alcohol levels used in these experiments were found to markedly increase DNA synthesis in liver. Enhancement of prenoplastic response, which seems to be limited to ethanol doses associated with such an increase in DNA synthesis, may be referred to by defi nition as co-carcinogenic action. At this dose level however, ethanol does not show any promoting activity in liver. When given after cessation of carcinogen treatment following a tumor-promotion feeding protocol the extent of enzyme-defi cient areas was found to be rather decreased. Ethanol treat ment does not lead to any enhancement in the total amount of liver DNA with concomittant liver growth. The observed in crease in DNA synthesis might therefore be due to an accel eration of cell turnover as a consequence of the known hepatotoxic action of alcohol. The significance of this stimulus of re generative DNA synthesis induced by ethanol seems to differ from that of known tumor-promoting drugs (eq phenobarbital) which result in an increase in the total amount of liver DNA. Chronic liver regeneration induced by ethanol therefore only leads to an increase in risk when the alcohol acts in the pres ence of a liver carcinogen. (1 Ref) Small quantities of N-nitrosodiethylamine (NDEA) are being commonly detected in strong colored beverages. Some of these are believed to increase the morbidity of mouth and esophagus cancer in humans. The aim of our experiment was to establish whether ethyl alcohol, used as a solvent, influences the car cinogenic activity of NDEA. Two hundred twelve mice C57 Bl, male or female have been divided into 3 groups: I gr intragastric instillations of 0.03 mg of NDEA in 40 degree ethanol was administered twice a week for SO weeks; II gr the same dose of NDEA in tap water has been administered at the same time; III gr control 40 degree ethanol was given. A lot of benign and malignant tumors have been detected in groups I and II, but only several in group III. The forestomach tumor was the main tumor attributable to NDEA. This cancer devel oped in about 40 per cent of animals in the I ethanol group and about 10 per cent in the II water-group. Apart from this a big part of forestomach cancers in the I group, but none in the II group, metastasized ltT lungs, liver* and other sides. There were no forestomach cancers in control group. In conclusions: eth anol used as a solvent enhanced both cancerogenic activity of NDEA and progression of tumors. The mechanism of this phe nomenon is being studied, (no Refs) 90. DIETARY LIPID EFFECTS ON THE GROWTH, MEMBRANE COMPOSITION, AND PROLACTIN BINDING CAPACITY OF RAT MAMMARY TUMORS (MEETING ABSTRACT). Cave WT, Jurkowiki JJ Ualv. of Rockeitcr Medical Center, Rochester, NY, 14611 Proc Am Axcoc Cancer Res; 24:685 1983 The purpose of this study was to evaluate the effects of qualitative as well as quantitative differences in dietary lipid on mammary tumor growth and to examine some of the mecha nisms that might be involved. Female F-344 rats were divided into 3 dietary groups: (a) 0.5% corn oil, (b) 3% corn oil, (c) 3% com oil + 17% lard, (d) 20% com oil, (e) regular lab chow (approx 6% lipid). All animals were simultaneously ad ministered the carcinogen nitrosomethylurea and those devel oping tumors were killed when their tumors exceeded 2 cm in diameter. Specific prolactin (PRL) binding measurements were then performed on the microsome membrane fractions of these tumors and their fatty acid profiles were determined by gas chromatography. We conclude that (I) once the dietary poly unsaturated fat content of the diet exceeds 3%, it is the total amount of lipid in the diet rather than the type that determines the ultimate mammary tumor growth rate (2) reductions in di etary polyunsaturated fat below 3% are associated with reduc tions in mammary tumor growth (3) alterations in the specific binding of prolactin to mammary tumor membranes seem most closely related to this latter process and less so with variations in tumor growth caused by diets containing more than 3% polyunsaturated fatty acid, (no Refs) URL 14155 CHEMICAL CMCtNUSMEM* HttroM taapaaadi 23 <3 J, did not cause a change in diet (eg, fj tui s) was almost identi- cal to that among population corn 1s. hese results suggest that, in hospital-based case-control tud rs of the effects of coffee consumption, it would be p nt 3 restrict the referent group to those patients hospitals for conditions that prob- ably did not cause a change in diet, agnitude of bias re- suiting from failure to exclude controffliospiulized for diet-al tering conditions will depend on two factors that may vary be tween studies: (1) the distribution of diet-altering conditions among the hospital controls, and (2) the relationship of these diseases to coffee consumption. (Author abstract) 177. THE LOUISIANA CANCER CONTROVERSY: SOME SCIENTIFIC PERSPECTIVES. Carlo GL, Currier MF, Flanagan KJ United States Area Medical, 1*03 Building, Dow Chemical D5.A., Midland, Ml, 48640 J La State Med Soc; 135<3>:*-9,11-13,16 1983 Possible misconceptions regarding the cancer death rate in Louisiana are discussed. Information sources on the cancer rates in Louisiana include cancer mortality maps, data gathered through the Surveillance, Epidemiology, and End Result Pro gram and the epidemiological studies. It is suggested that errors could occur through differences between the numerators or denominators of rates from different geographic areas which result in differential rates, differences in age distribution of the population, differences in survivorship, and differences in inci dence of disease. (8 Refs) colm Grow). In the Montefiore population, the answer was `yes'; 67% of the node-positive patients, but only 31% of the node-negative patients were obese (20% or more above ideal weight) (p less than 0.03). In the Malcolm Grow population, the answer was *no`; 20% of the node-positive and 20% of the node-negative patients were obese. The different answers, we believe, are due to the biological differences between (he popu lations; the Montefiore population was shorter (by an average of 1.7 inches), heavier (by an average of 20 lbs), and more obese. The incidence of obesity was about three times as high in the Montefiore population (52% versus 20%; p less than 0.02) and it contained a statistically distinct subpopulation of obese patients, while the few obese patients in the Malcolm Grow population constituted merely the upper tail of a unimodal log-normal distribution of weight in that population. We propose that it is possible to demonstrate a relationship of obe sity to node-positivity in the Montefiore population but not in the Malcolm Grow population because obesity was highly prevalent in the former and almost nonexistent in the latter. It seems self-evident that it is not possible to demonstrate an effect of obesity in a population if that population manifests no significant obesity, statistically speaking, but disregarding this principle, we believe, may account for the controversy in the literature about whether obesity is a risk factor in breast cancer. (Author abstract) 180. ISOLATION OF A GROUP AT RISK FOR STOMACH CANCER BASED ON GENETIC AND EPIDEMIOLOGICAL STUDY DATA 178. HETEROGENEITY IN HISTORICAL COHORT STUDIES: A SOURCE OF BIAS IN ASSESSING LUNG CANCER RISK. Altshuler BA, Glazkova TG, Koabcheev VA, Vapuik VN, Prytkov AN Vopr Onkoi; 29(2)4-13 1983 WitoW Dlv. Occupational Medicine, Hahnemann UbIt. Scb. Medicine, 230 N. Broad St, Philadelphia. PA, 19102 JOM; 2544k290-294 1983 Historical cohorts that are heterogeneous with respect to era in which exposure to a hazard began are subject to chronology bias. Those historical cohorts assembled some time after onset of exposure are also subject to selection bias through attrition of the original populations prior to the time of registration. Such cohorts may be called multiserial cross-sectional. The two forms of bias in such cohorts may account for some of the elevated risk of lung cancer reported in occupational studies of .this type. Historical cohorts comprising all workers who began exposure in a relatively limited era can be called inception co horts. Three occupational investigations are reviewed in which both multiserial cross-sectional cohorts and inception cohorts were studied. In all three investigations the inception cohorts showed lower risks of lung cancer than the multiserial crosssectional cohorts. (Author abstract) (7 Refs) The predictive value of risk factors of stomach cancer was studied on the basis of the results of a complex genetico-epideraiologic survey conducted with a view to identifying the group at risk. An optimal combination of these factors and the multifactor method of mathematical statistics were used in working out a decision instruction. Application of the latter offers an 80% credibility in selecting persons at high risk for stomach cancer development. The paper deals with the find ings on a significant relationship between stomach cancer de velopment and genetic and familial factors as well as on indica tions at certain changes in gastrointestinal function observed before clinical manifestation of the disease. The results point to the efficacy of complex clinical, genetic and epidemiologic studies conducted for prediction of neoplasms caused by a set of factors. (Author abstract) (In RUS) EPIDEMIOLOGIC APPROACHES TO CANCER ETIOLOGY. (76 REFS) / q c .U A 'M fl 179. RELATIONSHIP BETWEEN BODY WEIGHT AND THE INCIDENCE OF POSITIVE AXILLARY NODES AT MASTECTOMY FOR BREAST CANCER. Zumoff B, Daagupu I Clinical Research Center, Montefiore Hospital and Medical Center, Bronx, New York. J Sum Oncol; 22(4)417-20 1983 The question, whether obesity is associated with an in creased incidence of positive axillary nodes at mastectomy for breast cancer, was studied in two quite different hospital popu lations; one from a large urban teaching hospital (Montefiore) and one from i medium-sized Air Force medical center (Mai- Fraomeni JF Jr Eartraamcatal Epidemiology Branch, National Cancer Institute, Na tional Institute* of Health, Betheada, Maryland. Annu Rev Public Health; 3A5-100 1982 Keywords (MeSH): Alcohol Drinking; Environmental Pol lutants/adverse effects; Epidemiologic Methods; Epstein-Barr Virus/immunology; Estrogens/adverse effects; Human; Im munosuppressive Agents/adverse effects; Neoplasms/chemical ly induced/*etiology/familiai and genetic/occuirence; Neo plasms, Radiation-induced/etiology; Nutrition; Occupational Diseases/chemically induced; Review; Smoking; Sunlight/ad verse effects. ENVIRONMENTAL AND OCCUPATIONAL CARCINOGENESIS 35 109. CANCER REPORTING IN PAPUA NEW G 1958-70 AND 1971-78. Atkinson L, Purohit R, Reay-Youag P, Scott GC Institute of Oncology and Radiotherapy, Prince of Wales, Wales, Australia. Natl Cancer last Moaocn <62fc45-71 1983 In 1958, a cancer registry was established in Papua New Guinea for a population of 2 million who had remained in near isolation for millenia until recently. This report includes cancer data for 1970 through 1978. During those years, the registra tions increased from 200 to 600. The reasons for this increase and the patterns of reporting over the entire 21-year period are examined. The data offered us opportunities to examine changes in case findings according to geography, time, and sex. Genuine differences in cancer incidence and pattern within this diverse country, mainly between the highland and lowland re gions, were studied, particularly concerning oral, skin, liver, and penile cancers, and Burkitt's lymphoma. The controversy remains over the relationship of oral cancer and chewing of substances other than tobacco; but in this country, at least, a chew consisting only of areca nut mixed with lime must be held suspect. With the emergence from isolation, profound so cioeconomic changes are occurring in this country; the pat terns of cancer must change also, and we may be seeing the beginning of this already. Possible fruitful areas for further de tailed studies are indicated. (Author abstract) 110. CANCER INCIDENCE IN SINGAPORE: 1975-77. lee HP, Shanmagaratnain K Department of Pathology, National University of Singapore, Singapore General Hospital. Nad Cancer Inst Monogr, (621:57-60 1982 The Singapore Cancer Registry started operations on Janu ary 1, 1968. It is a population-based registry that seeks to obtain basic epidemiological and clinical data on all cases of cancer diagnosed in Singapore. The results presented pertain only to Singapore citizens and permanent residents and cover the period from 1973 to 1977. Of special interest are the cancer patterns of the main ethnic groups in Singapore. Generally, the Chinese (76% of total population) have significantly higher risks for cancer; the most prevalent sites are the nasopharynx, esophagus, stomach, liver, and lung. Within the Chinese group are also dialect group differences. The Malays (15% of popula tion) have the lowest rates for most sites, whereas among the Indians (7% of population), mouth cancer is an important site for both sexes. All these variations provide useful clues in the search for etiological factors. (Author abstract) 111. CANCER PATIENT SURVIVAL: SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS PROGRAM, 197579. Rks LG, Pollack ES, Youag JL Jr Division of Cancer cause and Prevention, National Cancer Institute, Betbesda, Md. JNC1; 70(4)^93*707 1983 Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used in the evaluation of cancer patient survival experience for almost 10% of the U.S. population. This first report contains actuarial (life table) survival analysis on 368,263 patients with first pri mary cancer diagnosed in 1973-79 from nine SEER areas: the entire States of Connecticut, Iowa, New Mexico, Utah, and Hawaii and the metropolitan areas of Atlanta, Detroit, San Francisco, and Seattle. Both observed and relative survival rates were shown for whites and blacks, sex, age, primary site, and time period (each yr, 1973-78). The largest racial differ ence in survival was for cancer of the corpus uteri: 87% 5-year relative survival rate for white females versus only 54% for black females. Survival rates varied considerably by primary site. For most sites, as age increased the relative and observed survival rates decreased. Analysis of relative survival rates by each year of diagnosis, 1973-76, and for each year following di agnosis suggested increasing rates for cancers of the colon, lung, and prostate gland, whereas there were no definite in creases for cancers of the female breast and corpus uteri. A dramatic increase in survival from acute lymphocytic leukemia was found for children under IS years of age, with the 4-year relative survival rate increasing from 51% among those diag nosed in 1973-75 to 65% for those diagnosed in 1976-78. (Author abstract) / 112. CANCER AND LIFESTYLE IN LOUISIANA. Correa P, Johnson WD Dept. Pathology and Biometry, Louisians State Uni*. Medical Center, New Orleans, LA J La State Med Soc; 135(3)4-6 1983 A cancer survey of men in southern Louisiana is reported. Respiratory cancer rates among these men are among the high est in the United Slates. Results of the survey indicated that one-third of the white labor force works in oil and shipbuilding industries and that more river water is used for drinking water in the south. Cigarette smoking is also more prevalent in the south. (5 Refs)......... OTHER EPIDEMIOLOGICAL FINDINGS 113. POPULATION STUDIES OF POLYMORPHISM IN DRUG OXIDATION AND ITS RELEVANCE TO CARCINOGENESIS. Ritchie JC, Idle JR Department of Pharmacology, St Mary's Hospital Medical School, London, UK. 1ARC Sci Pub); (32)481-94 1982 Metabolic oxidation plays a centra) role in both the detoxica tion and chemical activation of many environmental procarcin ogens. A plethora of in vitro data suggests that metabolic acti vation and subsequent DNA covalent binding of such sub stances vary widely between individuals. The need for a simple test in vivo of human variability in metabolic oxidation is ap parent, not only to help understand the variation in disposition of many drugs and other chemicals, but also as an aid to pre dicting individual cancer risk from metabolically activated pro carcinogens. Current methodology has failed to provide such information for a number of reasons, which are discussed. A genetic polymorphism affecting the metabolic disposition and biological effects of a number of drugs is described. Persons can be phenotyped as either extensive or poor metabolizers, using the drug debrisoquine. The measured variable, urinary `metabolic ratio', which is distributed across these two pheno types with values of 0.1 to 200, gives a clear indication of the metabolic behaviour of many drugs and, possibly therefore, of certain procarcinogens. Accordingly, two groups of cancer pa tients were investigated with debrisoquine, namely Nigerians with hepatocellular and related tumours and white smokers with bronchia] carcinoma in the United Kingdom. These pre liminary studies are suggestive of a phenotype component in relative cancer risk, poor metabolizers appearing to be less vul- 22 ENVIRONMENTAL AND OCCUPATIONAL CARCINOGENESIS 8 :P .> un rtion or >or cell NAL SOF loadoa. thylhyonce a four to KleDum : hemaasuring ze, the ions of sed by ntative lysis of sells at of the ng the Crypt lowing ] mini. vfitotic te per?x) re* al nni* * from 8 +A razine 12 eq reach* icleoli Jeolar n con* * main e four some *e at* sr ab* dara J Sidacr if dis ine in e speghout le sustruc* Furth a, or . We izine* :h as sociated epithelMim i/ these animals. In addition, we defined the normal disributipn of colonic lymphoid patches in both DMH-treated aid c&trol rats. Patches were found macrosco* pically and cyifimifd by histologic examination at five con stant sites: lower pae of cecum, proximal ascending colon, the major colonic wasere, mid descending colon, and the rectosig moid. There are also the predominant sites of DMH induced carcinomas in W/Fu rats. In 120 DMH-treated animals, 109 colon carcinomas were found. Eight percent were in the lower pole of the cecum, 56% in the proximal ascending colon, 16% at the major flexure, 15% in the mid descending colon, and 5% in the rectosigmoid. Lymphoid patches could often be de tected histologically in association with DMH-induced tumors. The depth of tumor invasion was found to correlate inversely with our ability to identify tumor-associated lymphoid patches suggesting that tumors arising at the anatomical sites were lymphoid patches occur progressively destroyed them. Of colon tumors confirmed histologically to be ttawiatwl with lymphoid patches, 88% were superficial lesions confined to the submucosa and 12% were more extensive but confined to the bowel wall. No lymphoid patches could be found with tumors that extended through the bowel wall. Thus, DMH-induced colon carcinomas in W/Fu rats arise at sites containing preexisting LP-GALT with associated specialized epithelium. (Author abstract) 4. EFFECT OF 13-CIS-RETINOIC ACID ON EARLY PRECANCEROUS ANTIGENIC GOBLET-CELL MODIFICATIONS AND INDUCTION OF CANCER DURING 14-DIMETHYLHYDRAZINE CARCINOGENESIS IN RATS. Diems C, Ross B, Ban 3, Daber N, Butin P Laborttoire dlauBaaochiaile, IRSC, VlUcjuif, France. CardBogeaesis; 4<9):117M 1983 The possible effect of oral 13-cis-retinoic acid (13-cis-RA) on the carcinogenic process induced by 28 weekly s.c. injections of 1,2-dimethylhydrazine (DMH) in 34 Wistar rats was investi gated. Using immunohistology, precancerous and cancerous stages were compared with the same stages induced by DMH without additional 13-cis-RA in 33 rats. Ml antigens, which characterize modifications in goblet-cell differentiation occur ring early in rat colonic carcinogenesis, were used to investi gate the possible effect of retinoids on differentiation during precancerous stages. From 3-20 weeks after the start of the ex periment, no significant differences were observed in the timing of M1 antigens in the 2 groups of rats. It was also ob served that 13-cis-RA had no effect on histological lesions as sociated with precancerous mucosa, nor on the occurrence of intestinal adenocarcinomas. Thus, under these conditions, oral administration of 13-cis-RA did not significantly inhibit precancerous or cancerous stages of intestinal carcinoma develop ment (Author abstract) 5. TUMORJGENIC ACTION OF REPEATED f SUBCUTANEOUS ADMINISTRATION OF N-METHYL-NFORMYLHYDRAZINE IN MICE, Toth B, Path K Eppley Institute for Research in Cancer and Allied Disease*, Ualverni- ty of Nebraika, Medical Center, Omaha. Neoplasma; 30(4):37-41 1983 N-Methyl-N-formylhydrazine (MFH), an ingredient of the edible false morel mushroom, was administered to Swiss mice as 40 weekly subcutaneous injections at 20 micrograms/g body weight for females and 10 micrograms/g body weight for CHEMICAL CARCINOGENESIS; Miscellaneous Agents males. The treatments gave rise to statistically significant dences of lung turnon: 56% in females and 40% in males administration of the chemical resulted in no detectable cinogenic effect 4n other organs. The findings are discusst light of the results from earlier studies with this compc (Author abstract) 3D HETEROCYCLIC COMPOUNDS - cn CD 6. MUTAGENICITIES OF GLYCIDYL ETHERS FOR SALMONELLA TYPHIMURIUM: RELATIONSHIP BETWEEN MUTAGENIC POTENCIES AND CHEMICA REACTIVITY. Saglm* K, Goto M lamtnte of Eeotoxkology, Gekncbiia University, Toehima-kn, T Japan. Cham Blot Interact; 4H3):i53-C9 1983 The lethal and mutagenic effects of ethyl, benzyl, 1-nai ylmethyl, 2-naphthylmethyl, 1-naphthylethyl, 2-napbthyl< and 9-anthrylmethy! glycidyl ethers on Salmonella typhi turn (TA100, TA1535, TA98 and TA1538) were investig LD30-value became smaller with an increase in compounc drophobicity. The mutagenicities of these compound TA100 increased in the order: 1-naphthylethyl glycidyl < less than 2-naphthylethyl glycidyl ether less than benzyl g dyl ether less than 2-naphthylmethy] glycidyl ether less th naphthylmethyl glycidyl ether less than 9-anthrylmethyl g dyl ether. 1-Naphthylmethyl and 2-naphthylmethyl gly> ethers were mutagenic toward TA1535. In TA98, 1-naph methyl and 9-anthrylmethy] glycidyl ethers showed mutat activity and 9-anthrylmethyl glycidyl ether was more t genic than 1-naphthylmethy! glycidyl ether. 9-Anthrylmt glycidyl ether was also active in TA1538. In the reactic glycidyl ethers with deoxyguanosine and related eompo> glycidyl ethers attacked at only N-7 of guanine. The alky] rates of glycidyl ethers toward guanine residues in DNA determined and the exciplex-formation ability of 7-substi' guanines was studied. The reactivity of glycidyl ethers guanine residues in DNA has not provided a sufficient exp tion for the variation in mutagenic potencies of glycidyl el (Author abstract) 7. EFFECTS OF P-METHOXYPHENOL AND DIET ON CARCINOGEN-INDUCED NEOPLASIA OF THE MOU.* FORESTOMACH. Wattenberc LW, Borebert P, Deetafoey CM, Coeds JB Department of Laboratory Medicine and Pathology, UaJversi Minnesota, Minneapolis. Cancer Res; 43(10)^747-51 1983 Previously, p-methoxyphenol fed in the diet was found > the most potent inhibitor of benzo(a)pyrene-induced neop of the mouse forestomach of 18 phenols investigated. It present study, the effects of p-methoxyphenol on the di acting carcinogen, beta-propiolactone (BPL), were determ p-Methoxyphenol administered at 1 or 4 hr prior to BP fed in the diet markedly inhibited BPL-induced neoplas the mouse forestomach. Of 10 phenols tested by p.o. in' tion, it was the only one that exerted a significant inhib activity. Thus far, p-methoxyphenol appears to be an effe inhibitor only when given prior to carcinogen administm During these studies, it was found that the nature of the markedly altered the neoplastic response of the mouse stomach to BPL but not to benzo(a)pyrene. (Author abst CHEMICAL CARCINOGENESIS-, Miscellaneous Agents 0.004/the relative risk estimated for truck drivers employed at least^O yr/rs was 5.5 (Cl = 1.8-17.3). Truck drivers with a history o/operating vehicles with diesel engines experienced a si.jjriifscant elevated risk compared to non-truck drivers (rela tive rir/ = 11.9; Cl = 2.3-61.1). but whether the increased risk oosor^ed among truck drivers was attributable to diesel expo sure could not be evaluated. Nonsignificant excess risks were also seen for tool and die makers as well as for workers in sev eral other industries and occupations. Employment in the motor vehicle manufacturing industry was associated with no significant excess risk of lower urinary tract cancer (relative risk = 1.1; Cl 0.8-1.5). (Author abstract) S 65. SMOKING, OCCUPATION, AND HISTOPATHOEbGS^ OF LUNG CANCER: A CASE-CONTROL STUDY WITH - THE USE OF THE THIRD NATIONAL CANCER SURVEY. Stayner LT, Wegman DH Industrywide Studies Branch, National Institute for Occupational Safety' and Health. Cincinnati, Ohio. JNCI; 70(3):421-6 1983 The relationships between occupation, smoking, and the three most common histologic types of lung cancer (squamous cell carcinoma, small-cell carcinoma, and adenocarcinoma) were explored in a case-control study with the use of data col lected during the Third National Cancer Survey. The largest histologic group was squamous cell carcinoma (152 cases), fol lowed by adenocarcinoma (50 cases), and small-cell carcinoma (45 cases). The control series was comprised of cancers at all anatomic sites except those believed to be associated with either smoking or occupational exposures. Cigarette smoking was significantly associated with all three histologic types of lung cancer. Overall, the relationship with small-cell carcinoma was strongest (odds ratio = 5.1), whereas those with squamous and adenocarcinoma were approximately equivalent (odds ratio 3.1). Dose-response relationships were evident for all three histologic types: however, the linear relationship was found to be statistically significant (P less than 0.05) only for squamous and small-cell carcinomas. Squamous cell carcinoma was the type most frequently associated with occupational categories. It was significantly associated (P less than 0.05) with 'blue collar' professions (odds ratio = 2.1). No occupational catego ries were significantly associated with adenocarcinoma. In ad dition, no occupational categories were associated with all his tologic types of lung cancer combined. This last observation suggested that the sensitivity of epidemiologic studies might not only be increased by use of improved occupational histor ies but more specifically by consideration of histology in exam ination of associations between occupation and respiratory cancer. (Author abstract) 66. RESPIRATORY CANCER AND PROFESSIONAL ENVIRONMENT. Curte* JP No ftfniiatioR given Arch Mai Prof; X):669-70 1982 dust which is responsible for cancer of the upper airways. In dustrial carcinogenesis should be studied in an urgent manner to determine the nature of carcinogens to which workers are exposed and to determine the relationship of carcinoger the number of workers exposed to different carcinoger Refs) (In FRE) 67. BRONCHIAL PULMONARY CANCERS A PROFESSIONAL FACTORS. Cbailteux E Travail de Service de pneumopbtuiologie, Hopital Laenaec, CHU dc Nantes. 44035 Nantes, France Arch Mai Prof; 43<8k6S7-69 1982 It is estimated that 80-85% of lung cancers are caused by to bacco, however, work related factors are also responsible for a large percentage of lung cancers. Latency time depends on the particular carcinogen (8-16 yr for chloromethylethers or ioniz ing radiation and 40 yr for arsenic). Latency is a factor of the cumulative dose, the host response and the type of target cells. Metaltic carcinogens which have been extensively studied in clude nickel, chromium, arsenic, iron, beryllium and asbestos. Asbestos exposure and cigarette smoking are synergistic, and individuals who encompass both factors are 53-24x more likely to develop lung cancer than nonexposed, nonsmoking individ uals. Chemical carcinogens include polycyclic hydrocarbons, chloromethylethers. vinyl chloride, and mustard gas. The only causes of pulmonary bronchial cancer officially recognized in France are ionizing radiation, asbestos, and Fe exposure, (no Refs) (In FRE) 68. EXPERIENCE IN ACTIVE DETECTION OF ONCOLOGICAL DISEASES AT INDUSTRIAL ENTERPRISES IN THE ARMENIAN SSR Mkrtchiaa LN, Ambartsumian AM. Magakian AG Vopr Onkok 290)47-90 1983 A questionnaire-based mass screening was conducted at a number of industrial enterprises in the Armenian SSR. The re sults were evaluated on the basis of 11,035 comprehensive questionnaires. It was found that instrumental, laboratory, Xray and morphological examination had to be carried out in 1,116 persons (10,1%). Neoplasms of the most frequent local izations were detected in 19 cases (0.17%). The advantages of premedication with seduxen during mass screening are dis cussed. (Author abstract) (In RUS) 69. ENVIRONMENTAL AND OCCUPATIONAL FACTORS IN SKIN CARCINOGENESIS. INDICATIONS FOR THERAPY AND PREVENTION Montemsri G. Sturia M, Seccia A Universita Cattolica 4d Sacro Caore, Roma. Facolta di Mediciaa e Oururiw. Miaarra Mod; ?4O3):735-40 1983 Certain studies have shown that 80% of human cancers are linked to environmental factors. For respiratory cancer, it is certain that the most important causal factor is cigarette smoke followed by industrial pollution. Industrial carcinogens include mineral agents and organic agents. Mineral agents which have been seriously implicated in carcinogenesis are As, Be, Cr, Fe, and Ni. Gas and radioactive particles are responsible for pul monary cancers, and in South Africa, Rn has been responsible for increased rates of pulmonary cancer among miners. Car cinogenic agents include aromatic hydrocarbons and wood The authors review the environmental and occupational fac tors in cutaneous cancerogenesis, group them according to their characteristics, and in particular distinguish between fac tors of physical and chemical nature. The authors also discuss the influence of predisposing factors related to the somatic makeup (xeroderma pigmentosum) and to work environment. Particular emphasis is given to precancerous skin and therefore to the importance of a mass screening and an effective health education. The authors illustrate the disorder with their clinical pictures- (Author abstract) (In ITA) 14 ir v, -- 1/ ^ QmtOttttCWm AND OCCUPATIONAL CARCINOGENESIS I 6S IH la n i sponses were checked for significant differences and a factor analysis was performed. Three factorts were extracted for each group. Now is was possible to observe that the smoking and nonsmoking cancer patients displayed very similar results in factor analysis. In the group of smokers we find some more differences between patients and control persons, also in the group of nonsmokers, (no Refs) 99. FUR APPAR HORM' R STUDIES ON SKIN MELANOMAS Y DEPENDENT ON FEMALE SEX Lae JA, Stum BE Sch. PubUe Health aad Community Medicine, Dept. Epidemiology SC 36, Ualv. Washington, Seattle, WA, 99195 Iat J Epidemiol; 11(2):127.U1 1992 95. EPIDEMIOLOGY AND EARLY DETECTION OF CANCER OF THE ESOPHAGUS. Soroori P 900 Hillside Road. WUmiagtoa, DE, 19*07 Gastrointestinal Cancer 1. Decoik Aland Sherlock P, ed. The Hague, Martinus Nijhoff Publishers, Caacar Treatment and Research, VoL 3. 452 19S1. The extraordinarily high incidence of esophageal cancer in Iran provides the data base for a review of the epidemiology and early detection of cancer of the esophagus. Cancer of the esophagus is discussed in relation to incidence, sex, age, and racial factors; etiology; and prevention. (153 Refs) 96. EPIDEMIOLOGY OF GASTRIC CANCER AND ITS PRECURSOR LESIONS. In the British Isles the incidences and mortality rates from malignant melanoma of the skin have been shown to be higher in females than in males in the later years of reproductive life. In populations with higher rates for malignant melanoma of skin (Scandinavia, Australasia, etc), and also in Japan, where the rates are low, the ratio of female to male deaths is lower than in the British Isles. However, a similar pattern of age-spe cific sex ratios (risks for females compared with males peaking at some age in the latter half of reproductive life, and relative ly low in middle age) is found in these populations. This `gyne cologic* factor is not an artifact of interactions between age and year of birth effects, and appears to act multiplicatively with other etiologic factors. These findings have implications for studies of the etiology and pathogenesis of malignant mela noma, as well as for the descriptive mathematical modelling of the rates for purposes of environmental legislation. (Author ab stract) (22 Refs) Correa P State Uoiv. Medical Center, New Orleaas, LA, 70112 Gastrointestinal Cancer 1. Decoass JJaad Sherlock P, ed. The Hague, Martinas Nijhoff Publishers, Cancer Treatment and Research, VoL 3, 452 1961. Epidemiology of gastric cancer is reviewed with respect to etiology. Topics include geographic distribution, sex ratio, time trends, migrant studies, histopathology, blood groups, socio economic class, geochemistry, diet, and pernicious anemia. His toric aspects, histologic characteristics, distribution by sex and age, diet, and nitrate intake are considered in relation to pre cursor lesions of gastric cancer. (40 Refs) METABOLIC EPIDEMIOLOGY OF LARGE BOWEL CANCER. Hill MJ Central Public Health Ltb,, CoUndata Ava, London NW9, Gaatroiataati&al Cancer 1. Decoaae JJaad Sherlock P, ad. The Hagna, Martians Nijhoff Publishers, Caacer Tnatmant and Research, VoL 3, 452 p*, 1961. The epidemiology of large bowel cancer and predisposing and associated diseases are reviewed. Possible causative agents, evidence for the role of bile acids as co-carcinogens, and meta- lie epidemiology vis results of studies of the histopathology large bowel cancer and the adenoma-carcinoma sequence e considered. Variables examined in relation to the develop ment of large bowel cancer include geography, sex, socioeco nomic group, race, religion, population density, time and cul tural environment. Predisposing rlhrartei include adenomatosis coli, cancer family syndrome, and colorectal adenoma. Associ ated diseases include associated cancers, diseases of fiber deple tion, and others. Possible causative agents are stress and physi cal factors, radiation, immunological factors, virologies! fac tors, environmental agents, endogenous agents (cholesterol, bile acids, steroid estrogens, tryptophan metabolites, tyrosine me tabolism, and N-nitroso compounds), nutrition, and genetic fac tors. (I54jefs) 20 X ^ 99. SOCIO-ECONOMIC CLASS DIFFERENCES IN CANCER INCIDENCE IN CAU, COLOMBIA. Gaulle C, Coma P, Hseam! W Dm. Pathology, Faculty Medicine, Uaiveraidad del Valk Galt, rn, Colombia Iat J Cancer, 29(6h637-43 1992 Based on census tract information, cancer incidence rates for three socioeconomic strata of the city of Cali, Colombia, were calculated. Strong negative associations with socioeconomic status were found for cancers of the cervix and stomach. Colon cancer and endocrine-related cancers were positively associat ed with socioeconomic status, while no such association was found for rectal cancer. Contrary to data from developed countries, all smoking-related cancers were positively associat ed with socioeconomic class. The role of socio-economic gra dients in developing countries is stressed as a basis for etiologi cal research. (Author abstract) (30 Refs) 100. TUBERCULOSIS AND LUNG CANCER RISK IN NONSMOKING WOMEN. Hiada MW, Cohea HI, Kokwel LN Epidemiology Propaa, Confer Center of Hawaii, Ualv. Hawaii, Salta 407B, 1236 Iauhala SU Hooolulu, HI. 96813 Am Rev Reaplr DM; 125(6):776-77S 1992 We ascertained prior pulmonary tuberculosis infection in 211 non-Caucasian female lung cancer patients and 419 sex, race, age, smoking history and birthplace-matched control subjects by searching the Hawaii State Tuberculosis Branch patient re cords. Among never-smokers we found a significant increase in risk associated with prior tuberculous infection (odds ratio, 8.2; 95% confidence limits = 1.3 to 54.4). No such association was found among smokers. Prior tuberculous infection was identi fied in only 5-3% of never-smoking lung cancer patients, how ever, suggesting that this factor is a relatively unimportant con tributor to the etiologic aspects of lung cancer in persons who have never smoked. (Author abstract) (26 Refs) ENVIRONMENTAL AND OCCUPATIONAL CARCINOGENESIS template Jbr formation of new complementary strands. The timiig o*he replication process is controlled by a biologicalclo** mJbhanism that operates within the nucleus. The bonds bet^eeq/components of the DNA molecule are very sensitive to/chaes in temperature, to chemicals, and to radiation of vKKUjykinds. Any of these agents may change the patterns of bonding in the DNA, resulting in a loss of genetic information coded by the DNA base pairs. Loss of information results in a reduction of the cell's capacity to reproduce itself properly. Cross-linking in the DNA molecule contributes to the process of aging and leads to cell death and ultimately to death of the organism. Cellular repair mechanisms exist to correct errors in replication and alterations produced by agents to which DNA is sensitive. Damage to the DNA can result in carcinogenesis, which involves a loss of control over cellular replication. Ex amples of carcinogenesis include skin cancer induced by expo sure to sunlight, lung cancer induced by asbestos dust, and can cers induced by radiation that penetrates the body. Cocarcino genesis is essentially a process of chemical catalysis. An under standing of the chemical mechanisms of carcinogenesis pro vides a basis for prevention and treatment of cancer. (43 Refs) (In GER) 187. ETIOLOGY OF ORAL SQUAMOUS CELL CARCINOMA. Bionic WH. Rankin KV, Mackenzie IC Department of Pathology, Baylor College of Dentistry, Dalles, Texas. J Oral Pathol; 12(l}:11-29 1983 The traditional list of etiological factors related to oral squa mous cell carcinoma namely, tobacco, alcohol, syphilis, and oral sepsis has been expanded to include iron deficiency, chronic candidosis, and herpes simplex virus. The development of current concepts in these areas is discussed. In evaluating the need for future research, special emphasis is given to the concepts of muhifactorial etiology and the role of mutagens. Suggestions for future research are discussed. (Author abstract) (95 Refs) W8. ENVIRONMENTAL CAUSES OF CANCER DEATH. Greenberg ER, Meier FA Department of Community and Family Medicine, Dnrtmouth-HHcb* cock Medical Center. Hanover, New Hampehire. Am J Forensic Med Pathol; 3(*):309-13 1982 People increasingly look to the forensic autopsy as a way of determining whether a particular cancer death was environ mentally caused. The forensic pathologist must be diligent pur suing evidence that links potential environmental causes to cancer but must also educate the public providing reassurance that most cancers are not due to industrial pollution. Cigarette smoking and various life-style factors appeai.ia account, for more cancers than do man-made environmental contaminants. Assessing the possibility that a cancer death is due to a specific environmental agent requires extensive information. First, one must obtain an accurate history of lifetime occupational and environmental exposures. Second, one must analyze this infor mation in view of epidemiologic data on the cancer risks asso ciated with each exposure. Finally, one should seek to docu ment through the autopsy that exposure to a potentially harm ful agent actually occurred. The carefully done forensic autop sy can alert the public to dangerous conditions and can pro vide individuals a basis for recovery in court for damages due to harmful exposures. (Author abstract) 189. ENVIRONMENTAL ASPECTS OF RESPIRATORY CANCER: MEDICAL LEGAL UPDATE. Cordawe EM, Morgat EH, Beervl F, Ptworiel M, Murphy F Med Trial Tech Q; 29(2*229-37 1982 Keywords (MeSH): Carcinogens, Environmental/`adverse effects; Environmental Exposure; Human; Occupational Dis eases/chemically induced; Respiratory Tract Neoplasms/ chemically induced; United States Occupational Safety and Health Administration. 190. THE CLINICAL ILLNESS PROMOTION FACTOR: A THIRD INGREDIENT. Evaaa AS WHO Serum Reference Laboratory, Department of Epidemiology tad Public Health, Yale University School of Medicine, New Haven, Connecticut. Yale J Biol Mod; S5<3-4>:193-9 1982 The interactions between a causative agent and a susceptible host involve a series of responses most of which are subclinical or asymptomatic but a few of which are manifested by clinical illness. The factor(s) which tip the balance are poorly under stood in both acute and chronic diseases. It is designated here as the clinical illness promoting factor (CIPF), a third ingredi ent. Among infected persons some leads have been found as to why clinical illness develops: in tuberculosis genetic suscepti bility plays a key role, as shown in twin studies; in EBV infec tions age at the time of infection, genetic, and psychosocial fac tors determine both the expression and the severity of illness; in poliomyelitis age, exercise in the incubation period, and ge netic background are related to the development of paralysis. In the relationship between viruses and cancer, viruses and chronic diseases, or inanimate pathogens like tobacco and lung cancer, we know very little as to the factors that result in clini cal disease among the many who are presumably susceptible and fully exposed. Epidemiologic study is urged to identify this CIPF or `third ingredient. (Author abstract) 191. RATES OF MUTANT STRUCTURAL CHROMOSOME REARRANGEMENTS IN HUMAN FETUSES: DATA FROM PRENATAL CYTOGENETIC STUDIES AND ASSOCIATIONS WITH MATERNAL AGE AND PARENTAL MUTAGEN EXPOSURE. Hook EB, Schreinemacben DM, Willey AM, Croat PK Bureau of Maternal aad CUM Health, New York State Department of Health, Albaay. Am J Hum Genet; 35<lh96-109 1983 In 27,225 prenatal cytogenetic studies of amniotic fluid re ported to the New York State Chromosome Registry and the United States Interregional Chromosome Register System, there were 61 cases with a structural chromosomal abnormality not known inherited, a rate per 1,000 of 2.24. Of these 33, 1.21 per 1,000 were known de novo and nonmosaic; consequently, the rate of events resulting from germinal mutation is highly likely to be between these two limits. The rates per 1,000 of unbalanced abnormalities were 0.59-1.29; of balanced abnor malities, 0.62-0,96; of balanced Robertsonian translocations, 0.22-0.29; and of unbalanced Robertsonian translocations, 0.070.11. The rates of fetuses with supernumerary markers and fragments were unexpectedly high: 0.26-0.70 per 1,000. These abnormalities were associated with increased maternal age (38.0 +/ 5.4 to 38.4 +/- 3.6 compared to 35.6 +/- 4.3 in con trols), but even after adjustment for the bias to preferential study of older women, the observed rates of these supemumer- URL 14161 ENVWOMIEJfTAL AW OCCUPATIONAL CAftCINOOENESiS 37 cytolytic activity directed against an antigen that was specific for the original tumor cell line. (Author abstract) 14*. PRODUCTION OF VACCINE TO DEN-INDUCED CARCINOMAS BY IN VITRO ATTENUATION (MEETING ABSTRACT). larynx, and respiratory tract. Interim dietary guidelines to reduce the nsk of cancer were proposed in accordance with these conclusions. No definitive conclusions were reached for other dietary factors, including total calories, cholesterol, fiber, and selenium, nor could the quantitative contribution of diet to overall cancer risk be estimated. (Author abstract) Jamasbi RJ, Perkin EH Bowliag Greea State Uaittnity, Bowling Green. OH Proc An Amoc Cancer Ran 24:939 1983 148. NITRATE AND NITRITE CONTENTS IN CUBAN CHEESE OF THE GOUDA TYPE. The degree of immunogenicity of individual diethylnitrosamrne (DEM-induced forestomach carcinomas in female BALB/c mice was investigated following m vivo and in vitro Garda Rocae MO, del Poro E, Izqnienlo L, Foataiae M Caban National lastitute of Hygiene, Havaaaa. Nahnug; Z7(Z):125-8 1983 cultivation. Of five transplantable tumor lines studied (DENI, The nitrate and nitrite contents in cheese of the Gouda type, DEN3, DEN6, DENS and DEN9), DENI. DEN3, and DEN9 produced by the Milk Complex of Havanna, were investigated were highly tumorigenic, and exhibited very little immunogeni and compared with those found in 5 types of imported cheese city as judged by the tumor transplantation assay. WINN neu consumed in Cuba. No significant differences were found in tralization and antibody-binding tests. Two lines (DEN6 and the mean value (mean) of NaN03, whereas in the mean value DENS) showed significantly higher immunogenicity by the (mean) of NaN02 differences were found when comparing all same assays. Cultured cell lines established from DENI, cheeses against each other. From these results it is inferred that DEN3. DEN6 and DEN9 produced squamous cell carcinomas the consumption of Gouda type cheese does not represent an following in vivo inoculation. DEN6 and DEN9 cell lines lost important contribution to the daily intake of nitrates and ni their tumorigenicity at P5 and P40 in culture. In contrast, triles, precursors in the synthesis of cancerogenic N-nitroso DENI and DEN3 did not lose tumorigenicity through 30-50 compounds. (Author abstract) passages. However, the number of cells required to produce tumors increased substantially and their ability to metastasize was lost with increase in in vitro passage. Tumor transplanta 149. INHIBITORY EFFECT OF BETEL NUT EXTRACTS tion studies in normal and in immunosuppressed recipients sug ON ENDOGENOUS NITROSATION IN HUMANS. gested that the decreased tumorigenicity was immunological. When mice were immunized with cells from an in vitro line, strong immunity resulted against both the in vitro and in vivo parental lines suggesting the presence of same or similar anti Stick HF, Ohshima H, Pignteili B, Micbelon J, Banach H Enriroamentai Carcinogenesis Unit, British rvUfmhiq Cancer Re search Centre, Vaacoarer, Canada. JNCI: 70(6):lM7-50 1913 genic determinants. The antigen(s) involved were not related to retrovirus antigens, since the cell lines did not show viral protein expression To exclude other in vitro contaminants, such as heterologous serum antigens, tumor cells used for im munization were passaged in vivo at least once, (no Refs) Extracts of betel nut (Areca catechu) were tested for their capacity to inhibit the endogenous formation of nitrosamines by measurement of the amount of urinary N-nitroso-L-proline (NPRO) following ingestion of sodium nitrate (300 mg) and Lproline (300 mg) by 2 volunteers. A water extract of the dried nuts, an ether extract containing mainly (+)-catechin and (-)- epicatechin, and a caffeine-precipitated n-butyl alcohol extract containing primarily proanthocyanidins (tannins) strongly re EPIDEMIOLOGICAL STUDIES AND PUBLIC HEALTH ISSUES INVOLVING NITROSO duced the endogenous formation of NPRO. An average of 14.7 and 10.9 micrograms NPRO (8 expts per individual) was ex creted in the urine of the 2 volunteers over a 24-hour period COMPOUNDS following the intake of sodium nitrate and L-proline. The water extract and the proanthocyanidin (tannin)-containing ex 147. DIET, NUTRITION, AND CANCER: INTERIM tract, both of which contain the dose equivalent of one-quarter of a nut, reduced the excreted NPRO to background levels, DIETARY GUIDELINES. which varied from 0.5 to 3.6 micrograms and from 0.6 to 2.1 Palmer S, Bakshi K National Academy or Scieacea, Washington, D.C. JNCI; 70(61:1151-70 1983 micrograms (6 expts) in 24-hour urine samples from the 2 vol unteers. These results may exemplify the way in which natural ly occurring phenolics, which are ingested daily in relatively The Committee on Diet, Nutrition, and Cancer of the Na tional Academy of Sciences recently evaluated the role of diet large quantities, could affect the endogenous formation of carcinogemc nitrosamines. (Author abstract) in carcinogenesis. Both epidemiological and laboratory evi dence suggests that a high intake of total fat increases suscepti !bSoJOT* THE ENDOGENOUS FORMATION OF N- bility to cancer of different sites, particularly the breast and \NlirROSAMINES IN CIGARETTE SMOKERS (MEETING colon. In epidemiological studies frequent consumption of cer ABSTRACT). tain fruits and vegetables and in laboratory experiments some components of fruits and vegetables, especially cruciferous Hoftaaan D, Haley NJ, Hmnnrinsnn KD, Wya4er EL vegetables, appear to decrease the incidence of cancers at var ious sites. In contrast, frequent consumption of salt-cured, salt- American Health Foaadation, Valhalla. NY Proc Aa Amoc Caacer Rea; 24J41 1983 pickled, or smoked foods, possibly because they may contain Age adjusted groups of five cigarette smokers and five non- nitrosamines or polycyclic aromatic hydrocarbons, appears to smokers were placed on a standardized and controlled diet for increase the risk of esophageal or stomach cancer. Excessive 12 days. Daily supplements of 300 mg proline were given on alcohol consumption among smokers appears to be associated days 4, 5 and 6. Supplements of 300 mg proline and 1,000 mg with an elevated risk of cancers of the oral cavity, esophagus, ascorbic acid were given on days 7, 8 and 9. Finally, on days URL 1416 ro CHEMICAL CAICINMENESIS; Nitroso Compeonis 37 10, 11 and 12, only 1,000 mg ascorbic acid were given in addi 152. AGRICULTURALLY RELATED CARCINOGENIC tion to the standardized diet. Twenty-four hour urine samples were collected in stopping solution on days 3, 6, 9, and 12. Ali quots of these were analyzed for nicotine and cotinine by RIA (radioimmunoassay) and for pH, creatinine, PRO, nitrite and nitrate. For the analysis of N-nitrosoproline (NPRO), an indi cator for in vivo N-nitrosation of amines, we modified the RISK (MEETING ABSTRACT). M, Torek C, Piatar A. Sarjaa A Natioaal laalllale of Hygiene, 1966 Battpeet, Haagary Sympodam oa Rok of Cocardaogeas aad Promoters la Hbmu ett Experimental Cardaogeaeris, May 16-10, 19*3, Battpael. Ha^my Haageriaa Caacar Society, 1963. method of Ohshima and Bartsch. The results suggest that ciga rette smokers can form higher amounts of NPRO in vivo than Carcinogenesis is a multistage process where etiological fac nonsmokers. This observation cannot be explained only by the depth of inhalation of smoke which is determined by blood tors can be regarded as complete carcinogens, initiators or pro moters. Despite the rather ii*nit*H number of definitive human analysis for nicotine, continine, and COHb. The presentation carcinogens, the increasing amount of environmental pollutants will include data as to the in vitro formation of nitrosamines might fall in one or other categories of carcinogens. Develop from PRO and nicotine in the blood of these smokers. The in ment in chemical industry resulted in chemiaation of agricul creased formation of NPRO in cigarette smoke inhalers is in ture which along with the spread of industrial methods might hibited by the addition of ascorbic acid to the diet. These find represent real danger for human being. In this paper we give ings and data on the in vivo formation of tobacco-specific N- an account about agricultural chemicals which could play a i nitrosamines and on the transnitrosation from NPRO will be role in the carcinogenic process. The use of the herbicide 1- i presented and discussed. (1 Ref) naphthyiamine may be dangerous because of the prerence of bladder carcinogen 2-naphthylamine. Important group of agri cultural chemicals have alkylating properties like halogenated 151. INHIBITION OF N-NITROSAMINE FORMATION IN BACON BY ALPHA-TOCOPHEROL-COATED SALT SYSTEMS. hydrocarbons (alkanoles, ary] derivatives, alkan halides etc), which are mutagenic and carcinogenic in animals. Some organ- ophosphate pesticides are also widely used and proved to be genotoxic Pesticides containing secondary, tertiary and quater Ratty SK Michigan State Uaivereity, Eaet Laaeiag. MI nary amino groups could be converted to N-nitroso com pounds in vitro and in vivo. We were able to demonstrate in Dim Abetr lat [B]; 4*9)-.2S46-B 19*3 vivo nitrosation of carbamate, morpholine, urea, piperazine and The effects of alpha-tocopherol-coated salt systems on the inhibition of N-nitrosamine formation were investigated in both dry cured and brine cured bacon. In dry cured bacon, approxi mately a 95% reduction in N-nitrosopyrrolidine (NPYR) levels in the fried bacon was achieved with an ingoing alpha-toco pherol level cf 500 mg/kg. NPYR levels in the cook-out fat were reduced approximately 92% using the same level of alpha-tocopherol. Bacon prepared by a small scale commercial operation also contained reduced levels of NPYR when proc essed with alpha-tocopherol-coated salt, despite the high levels (greater than 100 mg/kg) of residual sodium nitrite in the fin guanidine pesticides, of which N-nitroso derivatives caused tumors in experimental animals. This points to the importance of nitrite and nitrate, present in the environment. The above discussed compounds, having definitive effect in short term genotoxicity tests might endanger human population as initu tors or complete carcinogens. Non-genotoxic agricultural chemicals include some highly stable, eventually cumulating compounds which either do not induce tumors or increase only the frequency of spontaneous neoplasms. Such group of chemi cals is represented mainly by polychlorinated biphenyl pesti cides and the TCDD as pesticide contaminant, (no Refs) ished bacon alpha-Tocopherol also appeared to be more effec tive as a blocking agent (91% versus 73% inhibition of NPYR) 153. N-NTTROSODIETHANOLAMINE IN ANTIFREEZE. compared to the mixed tocopherols. Brine cured bacon was also manufactured using brines containing alpha-tocopherolcoated salts. In order to achieve greater stability in the brine system, lecithin was also coated on the surface of the salt. Re sults of the N-nitrosamine analyses indicate a very high degree of inhibition of NPYR formation in both fried bacon (approxi Dam P, Main C, 1 lusn JC, Gattla S lastitM Nation! de Betttrcbt et de Secarite, Naaey, France. Eariroe Rea; 31(lh9S-9 1903 Carcinogenic N-nitrosodiethanolamine has been found at concentrations varying from 15 to 5700 mg/liter in several mately 90%) and the cook-out fat (97-100%) with an ingoing leading French brands of antifreeze. Moreover, mixtures of an alpha-tocopherol level of 500 mg/kg. Alpha-Tocopherol was tifreezes which, separately, are innocuous, can form this nitrosalso effective in minimizing N-nitrosodimethylamine (NDMA) amine which appears to arise from interaction of triethanola formation in fried bacon. However, there was a wider vari mine derivatives with sodium nitrite. It is recommended that ation (76-92%) in the percent inhibition obtained for NDMA. sodium nitrite be abandoned as an anticorrosion additive. Less inhibition of NDMA formation in the cook-out fat was (Author abstract) also observed- The possible relationship of unsaturated fatty acids to the formation of N-nitrosamines in bacon was evaluat ed by swine feeding trials in which pigs were fed regular, alpha-tocopherol-enriched and corn oil-supplemented diets. Fatty acid analyses of the bacon indicated an approximate two fold increase in linoleic acid in bacon made from pigs fed the 154. LONG-TERM RISK OF NEOPLASMS AFTER BILLROTH I AND BILLROTH II RESECTION OF THE STOMACH FOR DUODENAL ULCER (MEETING ABSTRACT). com oil-supplemented diet. No obvious effects on the forma tion of NPYR were observed in bacon manufactured from the pigs. However, bacon made from swine fed the com oil-sup plemented diets contained much higher levels of NDMA (an approximate six-fold increase) than the control bacon. These results may indicate that the high levels of unsaturated fatty Caadagri S, Bcraardtaia G, Pitta MA, Amicacd G, Taaeaae D, Maad C, AfaiflU A Negro P fUaka Chtrwifea, L'Aqaila, Italy 1 Ceres latenuukmale tt Agofeirmaamato ia Diagaoetk* e CUrargia Eadcmmpia, December 2-4, 1902, rwk Sicily. Sodeta Italiaa 4i Eadoacopla IMgMtire 304 pp- 1903. acids in bacon adipose tissue may enhance the formation of Billroth 11 resections of the stomach seem to have a higher NDMA in fried bacon, (no Refs) incidence of carcinoma of the gastric stump than Billroth I op- 38 BBNCAL CARCMMENESIS; Nttresa Cwpttt URL 14164 cytolytic activity directed ag. for the original tumor cell line. 146. PRODUCTION OF VA N CARCINOMAS BY IN VTTR ABSTRACT). antigen that was specific r abstract) O DEN-INDUCED UATION (MEETING larynx, and respiratory tract. Interim dietary guidelines to reduce the risk of cancer were proposed in accordance with these conclusions. No definitive conclusions were reached for other dietary factors, including total calories, cholesterol, fiber, and selenium, nor could the quantitative contribution of diet to overall cancer risk be estimated. (Author abstract) Jomaobi RJ, Perkias EH Bowliag Green State Uaiveraity, Bowling Green. OH Proc Ab Aoaoc Cancer Rea; 24:939 1983 The degree of immunogenicity of individual diethylnitrosamine (DEN)-induced forestomach carcinomas in female BALB/c mice was investigated following in vivo and in vitro cultivation. Of five transplantable tumor lines studied (DENI, DEN3, DEN6, DEN8 and DEN9), DENI, DEN3, and DEN9 were highly tumorigenic, and exhibited very little immunogenicity as judged by the tumor transplantation assay, WINN neu tralization and antibody-binding tests. Two lines (DEN6 and DEN8) showed significantly higher immunogenicity by the same assays. Cultured cell lines established from DENI, DEN3, DEN6 and DEN9 produced squamous cell carcinomas following in vivo inoculation. DEN6 and DEN9 cell lines lost their tumorigenicity at PS and P40 in culture. In contrast, DENI and DEN3 did not lose tumorigenicity through 30-50 passages. However, the number of cells required to produce tumors increased substantially and their ability to metastasize was lost with increase in in vitro passage. Tumor transplanta tion studies m normal and in immunosuppressed recipients sug gested that the decreased tumorigenicity was immunological. When mice were immunized with cells from an in vitro line, strong immunity resulted against both the in vitro and in vivo parental lines suggesting the presence of same or similar anti genic determinants. The antigen(s) involved were not related to retrovirus antigens, since the ceil lines did not show viral protein expression. To exclude other in vitro contaminants, such as heterologous serum antigens, tumor cells used for im munization were passaged in vivo at least once, (no Refs) EPIDEMIOLOGICAL STUDIES AND PUBLIC HEALTH ISSUES INVOLVING NITROSO COMPOUNDS 1*7. DIET, NUTRITION, AND CANCER: INTERIM DIETARY GUIDELINES. Palmer S, Bakaki K National Academy of Sciences, Waakiagtoa, D.C. JNC1; 70<6):ll5l-70 1983 The Committee on Diei, Nutrition, and Cancer of the Na tional Academy of Sciences recently evaluated the role of diet in carcinogenesis. Both epidemiological and laboratory evi dence suggests that a high intake_of total Fat increases suscepti bility to cancer of different sites, particularly the breast and colon. In epidemiological studies frequent consumption of cer tain fruits and vegetables and in laboratory experiments some components of fruits and vegetables, especially cruciferous vegetables, appear to decrease the incidence of cancers at var ious sites. In contrast, frequent consumption of salt-cured, saltpickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, 148. NITRATE AND NITRITE CONTENTS IN CUBAN CHEESE OF THE GOUDA TYPE. Garda Rook MO, del Pom E, Izaaierdo L, Foetaiae M Cubaa National Iaatitute of Hygiene, Haeanna. Nahrug; 27<2>:12$-8 1983 The nitrate and nitrite contents in cheese of the Gouda type, produced by the Milk Complex of Havanna, were investigated and compared with those found in 5 types of imported cheese consumed in Cuba. No significant differences were found in the mean value (mean) of NaN03, whereas in the mean value (mean) of NaN02 differences were found when comparing all cheeses against each other. From these results it is inferred that the consumption of Gouda type cheese does not represent an important contribution to the daily intake of nitrates and ni trites, precursors in the synthesis of cancerogenic N-nitroso compounds. (Author abstract) 149. INHIBITORY EFFECT OF BETEL NUT EXTRACTS ON ENDOGENOUS NITROSATION IN HUMANS. Stich HF, Ohikima H, PignateUI B, Micbeloa J, Bartsch H Eariroamental Carcinogenem* Uait, British Coliabli Cancer Re search Centre, Vancouver, Canada JNCI; 70(0:1047*50 1983 Extracts of betel nut (Areca catechu) were tested for their capacity to inhibit the endogenous formation of nitrosamines by measurement of the amount of urinary N-nitroso-L-proline (NPRO) following ingestion of sodium nitrate (300 mg) and Lproline (300 mg) by 2 volunteers. A water extract of the dried nuts, an ether extract containing mainly ( + >-catechin and (-)epicatechin, and a caffeine-precipitated n-butyl alcohol extract containing primarily proanthocyanidins (tannins) strongly re duced the endogenous formation of NPRO. An average of 14.7 and 10.9 micrograms NPRO (6 expts per individual) was ex creted in the urine of the 2 volunteers over a 24-hour period following the intake of sodium nitrate and L-proline. The water extract and the proanthocyanidin (lanninj-contaming ex tract, both of which contain the dose equivalent of one-quarter of a nut, reduced the excreted NPRO to background levels, which varied from 0.5 to 3.6 micrograms and from 0.6 to 2.1 microgratns (6 expts) in 24-hour urine samples from the 2 vol unteers. These results may exemplify the way in which natural ly occurring phenolics, which are ingested daily in relatively large quantities, could affect the endogenous formation of car cinogenic nitrosamines. (Author abstract) iWoN THE ENDOGENOUS FORMATION OF N- .MTROSAMINES IN CIGARETTE SMOKERS (MEETING ABSTRACT). Hoffmann D, Haley NJ, Bruanemaaa KD, Wynder EL American Health Foundation, Valhalla, NY Proc Am Amoc Cancer Rea; 24:241 1983 Age adjusted groups of five cigarette smokers and five nonsmokers were placed on a standardized and controlled diet for 12 days. Daily supplements of 300 mg proline were given on days 4, 5 and 6. Supplements of 300 mg proline and 1,000 mg ascorbic acid were given on days 7, 8 and 9. Finally, on days CHEMICAL CARCINOGENESIS; Nitroso Compounds 37 />. ANALYTICAL AND METHODOLOGICAL / , 56. GROUPING OCCUPATIONS ACCORDING TO ASPECTS OF CANCER EPIDEMIOLOGY / / CARCINOGENIC POTENTIAL: OCCUPATION CLUSTERS FROM AN EXPOSURE LINKAGE SYSTEM. 54. SUSCEPTIBILITY TO CANCER AND SPONTANEOUS INCIDENCE. Hsleh CC, Walker AM, Hoar SK Deportment of Epidemiology, Harvard School of Poblic Health, Am J Epidemiol; 117(5*575-89 1983 Rdf AE laboratory of Experimental Cancer Immoaotberapy, Boetoa Uairod* ty School of MaUdae, Booton City Hospital, Mam. Oncology; 400*210-7 1983 Susceptibility to cancer implies being easily affected by car cinogen, as well as having an overt spontaneous incidence of cancer. The susceptibility of a population to the development of fatal cancer of a given organ can be represented by a fre quency distribution. This distribution depends both upon the genetic susceptibility of the population and upon all environ mental carcinogens that have impinged on that population. The method for construction of such a susceptibility distribution has been simplified and applied to experimental data on bone tumor induction with 90Sr in mice, and to bone tumor mortal ity and prostate cancer mortality in man. The relative suscepti bilities of different human organs to the development of fatal tumors can be defined in terms of the spontaneous tumor mor talities. (Author abstract) An occupational clustering scheme has been developed from an occupation and exposure linkage system. In this scheme, oc cupational titles are grouped together hierarchically according to the numbers and degrees of their shared exposures. The use of the clusters obtained from this hierarchy is demonstrated in the analysis of the data from a case-control study of bladder cancer. (Author abstract) 57. EPIDEMIOLOGIC INVESTIGATIONS. CARE IN CONDUCT, CARE IN ANALYSIS, AND CARE IN REPORTING. MaateIN Dept of Mathematics, Statistics aad Computer Science, Americas OaJvenJty, Betbeada, MD. i Cancer Res Clin Oncol; 105(2>:113- 1983 Keywords (MeSH): Adult; Age Factors; 'Epidemiologic Methods; Female; Human; Lung Neoplasms/mortality; Male; Middle Age; Prospective Studies; Research Design; Smoking; Statistics; ; . 55. REPRODUCIBILITY OF A DIET HISTORY QUESTIONNAIRE IN A CASE-CONTROL STUDY OF BREAST CANCER. Hankin JH, Nomara AM, Lee J, Hirobiu T, Kolooei LN Epidemiology Program, Ualvenlty of Hawaii, Hoaolniu. Am J Clia Netr, 37(5*981-5 1983 The reproducibility of a diet history questionnaire was as sessed as part of a case-control breast cancer study in Cauca sian and Japanese women in Hawaii. The method was designed to estimate the intakes of total and saturated fat, cholesterol, and animal protein during a usual week before symptoms or di agnosis of disease in cases, and during a usual recent week in controls. Except for the time period of reference, the dietary technique was identical for all cases and controls. A subsample of 61 Japanese women (19 cases and 42 controls) and 56 Cau casian women (23 cases and 33 controls) participated in the di etary reinterview conducted within 3 months of the first inter view. The mean difference in intake between the two inter views was small and not statistically significant (p greater than 0.05) for all four nutrient items among Japanese cases and con trols and Caucasian cases, whereas the mean difference for all four nutrients was substantial and statistically significant (p less than 0.05) among the Caucasian controls. The intraclass corre lation and the product-moment correlation were moderately high for all four nutrient items among Japanese cases and con trols and Caucasian cases, but not among Caucasian controls. These findings indicate that the diet history method is reason ably reproducible in three of the four groups of studied sub jects. Possible reasons for the poor reproducibility among Cau casian controls are discussed. (Author abstract) 56. IS THERE A CANCER-PRONE PERSONALITY? (44 REFS) Welliscb DK, Yager 3 Nearweychiatric Institute, Uaiversity of California, Los Angelas. CA; lJ(3H45-33 1983 Keywords (MeSH): Disease Susceptibility; Epidemiologic Methods; Hormones/physiology; Human; Neoplasms/immunology/occurrencc/'psychology; 'Personality; Research Design; Review. GENERAL AND MISCELLANEOUS FACTORS 59. ROLE OF EXOGENOUS AND ENDOGENOUS FACTORS IN THE ETIOLOGY OF HUMAN TUMORS Tarasov VS Arkh Patol; 45(2*3-13 1983 The factors of major importance in the development of human tumors: exogenous chemical carcinogens, endogenous carcinogens, hormones, radiation, immunity disorders, heredity, nutrition, harmful habits are analysed on the basis of epidemi ological and experimental evidence. Close interaction of exoge nous and endogenous factors in the process of tumor develop ment is demonstrated. Occupational carcinogens affecting at high doses small human contingents are frequently the major etiological cause of tumor development. In the general popula tion exposed to the effect of quite low doses of carcinogens the latter are probably only initiators of neoplastic process com pleted by specific and nonspecific stimulators of carcinogenesis (cocarcinogens, promoters). The mechanisms of action of modifying factors on carcinogenesis (the effect of carcinogens on endogenous synthesis and metabolism, their interaction with cell macromolecules, tumor growth) are discussed. (Author ab stract) (67 Refs) Gn RUS) URL 14165 DM80IMENTAI. AND OCCUPATIONAL CARCINOGENESIS 9 we have measured the kinetics of removal of product from the DNA of human fibroblasts treated N-nitroso carcinogen N-ethyl-N-nitrosourea. A rate of eJimmation from DNA was found in two no fibroblast strains (GM730 and 54BR) and in the non formed xeroderma pigmentosum fibroblast strains XP3BR. This is in contrast to the SV40-transform derma pigmentosum fibroblast strain XP12RO-SV40 previously been shown to be defective in its ability 06-ethylguanine from DNA. (Author abstract) V 51. THE PROBLEM OF NITROSAMINES IN THE RESIDUAL GASES OF AMINE PRODUCTION a; Btttaraohl G, Hdif H Z GamU Hy* 2*5*270-11903 Keywords (MeSH): Air Pollutants/*analysis; Air Pollutants, Environmental/*analysis; Amines/*chemical synthesis; English Abstract; Gases/analysis; Nitrosamines/*analysis. 9 9 lM 1 U n EPIDEMIOLOGICAL STUDIES AND PUBLIC HEALTH ISSUES INVOLVING NITROSO COMPOUNDS 49. BILE ACIDS, BUT NOT NEUTRAL STEROLS, ARE TUMOR PROMOTERS IN THE COLON IN MAN AND IN RODENTS. Welsbarger JH, Reddy BS, Bane* WS. Wyader EL American Health Foundation, Valhalla, NY. Eoriroa Health Penpect; 50:101-7 1903 Analysis of the etiologic factors and relevant in volved in carcinogenesis leads to a classification of agents in volved in the carcinogenic process as genotoxic or epigenetic. Their mode of action is distinct, especially with regard to dose- response effects and reversibility. The genotoxic carcinogens for colon cancer are unknown, but mutagenic components found in fried beef and fish are under study. Epigenetic agents as promoting factors play a major role in the development of cancer of the colon, Specific nutritional elements associated with colon cancer risk are high fat diets, high cholesterol intake, and low fiber intake. The role of micronutrients as mo dulators and inhibitors needs to be explored. Through metabol ic studies in diverse populations and in reliable animal models, it is now clear that dietary fat and cholesterol control the total flow of bile acids in lumen and a high-fat, high-cholesterol diet increases the total of bile acids in the gut. Bile adds but not neutral sterols have promoting effects and are related to colon cancer risk although bile acids by themselves do not act as complete carcinogens. The effect of dietary fiber such as cereal bran is to increase stool bulk which dilutes the concentration of bile acids. Reducing the concentration of bile acids either by lower dietary fat and cholesterol or by increasing dietary fiber may effectively lower the risk for colon cancer. (Author ab stract) 50. N-NITROSO COMPOUNDS: EVIDENCE FOR THEIR PRESENCE IN AIRBORNE PARTICLES. Kadp TJ, Dalsey JM, Solomon JJ, Hmshman RJ Institute of Environmental Medicine, New York University Medical Center, New York. Science; 221(4615hl(M5-7 1993 Chemical, infrared, and thermal energy analyses have pro vided evidence for the presence of the N-nitroso functional group in extracts of airborne particles. The total molar N-nitroso concentrations in New York City air are equivalent to the total concentrations of polycyclic aromatic hydrocarbons. Since 90 percent of the N-nitroso compounds that have been tested are carcinogens, the newly discovered but untested ma terials may represent a significant environmental hazard. (Author abstract) REVIEWS INCLUDING NITROSO COMPOUNDS 52. EXPERIMENTAL CARCINOGENESIS OF THE STOMACH AND ITS MODIFIERS TakahmUM Dept. f Pathology, National lastitatc of Hysteric Sdewcos. Gaa To Dpki Ryobo; 10(2 Pt 2)421-7 1993 Modifiers of gastric carcinogenesis are reviewed with evi dence of experimental results using rats. 1) Physical modifiers: Route of administration, medium (vehicle) of carcinogens, de tergents, dosage (concentration), period (frequency) of adminis tration, exposure time, and condition of mucus. Effects of sur factants and presence of a foreign body in the stomach lumen are also sample* of physical unhanging factors. 2) Biological modifiers: Specie*, genetics, sex, hormonal factors, nutrition, and age. Moreover, effect of preexisting ulceration is impor tant. 3) Chemical modifiers: Chemical substances administered prior to, simultaneously with, or following exposure of experi mental animals to chemical carcinogens, or promoters of car cinogenesis. Chemical modifiers are: co-initiators, tumor pro moters and inhibitors. NaCl having both co-initiator and tumor promoter action on MNNG gastric carcinogenesis is clearly shown in our investigations. (Author abstract) (In JPN) 53. GENETIC FACTORS IN GASTRIC CARCINOGENESIS Obgaki H Biochemistry Division, National Clacer Center Research Institute. Gen To Kagako Ryobo; 10(2 Pt 2*429-32 1993 Genetic control of susceptibility of rats to gastro-carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI strain rats, resistant Buffalo strain rats, and their FI and F2 offsprings. Rats were given MNNG at a concentration of 83 micrograms/ml in drinking water for 32 weeks and sacrificed on week 72. The incidence of gastric adenocarcinomas in FI was as low as that in Buffalo rats. The results showed that susceptibility to MNNG was controlled ge netically and that the resistance of Buffalo strain rats was auto somal dominant. To clarify the mechanisms which determine susceptibility to MNNG, some biochemical parameters such as pH of gastric juice, glutathione content in the gastric mucosa and the binding of MNNG to DNA, were analysed. No differ ence was observed between ACI and Buffalo strains in regard to the events leading to the binding of MNNG to DNA. (Author abstract) (In JPN) CHEMICAL CARCIN0CENE5IS; Hltrose Compands 13 observed patterns, and further inquiries into this question, etiology/mortality/'occurrence; Female; France; Human; therefore, may be useful. (Author abstract) Male; Middle Age; Nutrition; Risk; Sex Factors; Smoking; ; United States. 95. LUNG CANCER IN NONSMOKERS. Kabat GC, Wynder EL Dirtsion of Epidemiology, Mahoney Institute for Health Maintenance, American Health Foundation, New York, New York. Cancer; 53<5):1214-21 1984 Among 2668 patients with newly diagnosed lung cancer interviewed between 1971 and 1980, 134 cases occurred in `validated' nonsmokers. The proportion of nonsmokers among all cases was 1.9% (37 of 1919) for men and 13.0% (97 of 749) for women, giving a sex ratio of 1:2.6. Kreyberg Type II (mainly adenocarcinoma) was more common among nonsmok ing cases, especially women, than among all lung cancer cases. Comparison of cases with equal numbers of age-, sex-, race-, and hospital-matched nonsmoking controls showed no differ ences by religion, proportion of foreign-bom, marital status, residence (urban/rural), alcohol consumption or Queteiet's index. Male cases tended to have higher proportions of profes sionals and to be more educated than controls. No differences in occupation or occupational exposure were seen in men. Among women, cases were more likely than controls to have worked in a textile-related job (relative risk -- 3.10, 95% confi dence interval 1.11-8.64), but the significance of this finding is not clear. Preliminary data on exposure to passive inhalation of tobacco smoke, available for a subset of cases and controls, showed no differences except for more frequent exposure among male cases than controls to sidestream tobacco smoke at work. The need for more complete information on exposure to secondhand tobacco smoke is discussed. (Author abstract) 96. EPIDEMIOLOGY OF CEREBRAL GLIOMAS 99. EPIDEMIOLOGY OF BREAST CANCER AT KENT GENERAL HOSPITAL. Ford J Jr Del Med J; 56<2):67-9 1984 Keywords (MeSH): Adult; Aged; Breast Neoplasms/*occurrence/pathology; Carcinoma, Ductal/occurrence; Carcinoma, Scirrhous/occurrence; Delaware; Female; Human; Middle Age, 100. EPIDEMIOLOGIC ASPECTS OF AN OUTBREAK OF ACQUIRED IMMUNODEFICIENCY IN RHESUS MONKEYS (MACACA MULATTA). Lercbe NW, Hearickaoa RV, Meal DH, Gardner MB California Primate Research Center, University of California, Deris. Lab Alim Sd; 34(21:146-50 1984 Since August 25, 1981, an outbreak of simian acquired im munodeficiency syndrome (SAIDS) has been recognized in a single outdoor corral housing 77 rhesus monkeys (Macaca mulatta) over a 16-month period. The etiology of this syndrome is unknown but epidemiologic evidence suggests an infectious agent. Thirty-two cases of SAIDS have been identified (31 female, 1 male), and 27 of these animals have died (case fatality rate = 84%). Three of these deaths occurred among 13 infants bom in the corral. All 27 deaths were females. For animals in Sceld R _ Uiirereita dcgll Stadi dl Pavia, Serrlzio dl Nenropatologia della CUa- tea Neurologtea *C. Moadiao4. Mlaerva Mad; 75(21):1259- 1984 the original cohort, sex was not a statistically significant risk factor. For animals bom in the corral females were at greater risk (p = 0.0489; Fisher's Exact Test). SAIDS mortality rates were highest for animals entering the corral at less than 30 In the present review the results of the main epidemiologic studies on cerebral gliomas are reported. Various characteris tics of patients, i.e. endogenous factors including age, sex, familiality and constitutional factors, and exogenous factors includ ing perinatal and infectious diseases, trauma and geographic and environmental findings, are considered in turn. (Author ab stract) (In ITA) months of age (4.4 deaths per 100 monkey months of follow up) and for animals bom into the cage (3.3 deaths per 100 monkey-months of follow-up). The mortality rate was lowest for animals entering the corral at greater than 30 months of age, (0.32 deaths per 100 monkey-months of follow-up). No significant associations were found for the factors weaning his tory, cage-move history, parentage, generation, and medical 97. STATISTICS AND VARIOUS ASPECTS OF THE EPIDEMIOLOGY OF LYMPHATIC AND HEMATOLOGIC NEOPLASMS (59 REFS) Lebedev VN Vopr Oskol; 3(X4h82-96 1984 Keywords (MeSH): Adolescence; Adult; Age Factors; Aged; Child; Child, Preschool; Comparative Study; Epidemio logic Methods; Female; Human; Infant; Leukemia/'occurrence; Lymphoma/*occurrence; Male; Middle Age; Review; Sex Factors; USSR. history, including history of bite-wound trauma. Nine of the original 64 animals entering the corral on August 25, 1981, were previously associated with a group of 110 rhesus mon keys occupying this same corral from September 1976 to August 1981. Though less dramatic, a similar pattern of mor bidity and high mortality was recognized retrospectively in this group.(ABSTRACT TRUNCATED AT 250 WORDS) (Author abstract) 101. EPIDEMIOLOGY OF AIDS Seale J 98. EPIDEMIOLOGY OF CANCER OF THE ESOPHAGUS. Z Hautkr; 59<8):525-8 1984 ScbottesfeU D Department of Epidemiology and Preventive Medicine, Memorial Sloas-Ketterisg Caacer Center, New York, NY. Semin Oncol; 11(2)^2-100 1984 Keywords (MeSH): Adult; Africa; Age Factors; Alcohol Drinking; Asia; Disease Susceptibility; Esophageal Neoplasms/ Keywords (MeSH): Acquired Immunodeficiency Syndrome/ *occurrence/transmission; Animal; Blood Transfusion/adverse effects; English Abstract; Female; Haiti; Homosexuality; Human; Kuru/occurrence; Male; New Guinea; Sarcoma, Kaposi's/occurrencc; Scrapie/occurrence; Sex Behavior; Sheep; Slow Virus Diseases/occurrence; United States. ENVIRONMENTAL AN0 OCCUPATIONAL CARCINOGENESIS 19 who had been exposed to 'high1 levels of formaldehyde. There 47. AN EVALUATION OF THE ASSOCIATIONS OF were no trends of increasing mortality with duration of work --LEUKEMIA AND RUBBER INDUSTRY SOLVENT or interval since first exposure. This result may be a chance EXPOSURES. finding or reflect the influence of smoking or some other factor. Although a carcinogenic action of formaldehyde seems less likely as an explanation it cannot be excluded. The statist!cal power of the study to detect various risks of nasal cancer is Checkoway H, Wilcosky T, Wolf P, Tyroler H Occupational Health Studies Group, University of North Carolina, Chapel HilL Am J Ind Med; 5(3)039-49 1984 described. (Author abstract) Excessive leukemia mortality has appeared consistently in epidemiological studies of British and U.S. rubber industry 45. HUMAN HEALTH EFFECTS OF EXPOSURE TO CADMIUM. workers. Attempts to identify causative factors have focused on exposure to benzene and other solvents. Interpretations of findings from these studies have often been influenced by ex Hallenbeck WH School of Public Health, University of Illinois at Chicago. Expertentia; 40(2>:I3642 1984 pectations of a benzene/nonlymphocytic leukemia association, seen from previous work in other settings. However, data from the rubber industry studies have not been consistent with this expectation, as lymphocytic and nonlymphocytic leukemia The health effects of human exposure to cadmium are dis cussed with emphasis on intake, absorption, body burden, and excretion; osteomalacia in Japan; hypertension; and proteinuria, emphysema, osteomalacia, and cancer in workers. Elevated blood pressure has not been observed as a result of excessive exposures to cadmium in Japan or the workplace. Renal tubu lar dysfunction and consequent proteinuria is generally accept have shown similar mortality excesses. Data from a small casecontrol study of lymphocytic leukemia are presented to illus trate an approach that considers multiple solvent exposures. The associations with lymphocytic leukemia risk observed for a number of solvents, most notably carbon tetrachloride and carbon disulfide, were stronger than those detected for ben zene. (Author abstract) ed as the main effect following long-term, low-level exposure to cadmium. Studies of workers show that proteinuria may de 48. DOES AGENT ORANGE CAUSE BIRTH DEFECTS? velop after the first year of exposure or many years after the last exposure. Proteinuria and deterioration of renal function may continue even after cessation of exposure. The immediate health significance of low-level proteinuria is still under debate. Friedman JM Department of Obstetrics and Gynecology, University of Texas Health Science Center, Southwestern Medical School, Dallas. Teratology; 29<2):193-221 1984 However, there is evidence that long-term renal tubular dys Large quantities of the defoliant, Agent Orange, were function may lead to abnormalities of calcium metabolism and sprayed in Vietnam during the war. Agent Orange was com osteomalacia. The few autopsy and cross-sectional studies of posed of two herbicides: 2,4-D and 2,4,5-T, the latter contami workers do not permit conclusions to be drawn regarding the relationship between cadmium exposure and emphysema. Ret rospective and historical-prospective studies are needed to settle this important question. No conclusive evidence has been published regarding cadmium-induced cancer in humans. How ever, there is sufficient evidence to regard cadmium as a sus pect renal and prostate carcinogen. Because of equivocal re sults and the absence of dose-response relationships, the studies reviewed should be used with caution in making regulatory de cisions and low-dose risk assessments. (Author abstract) (62 Refs) nated by small amounts of a highly toxic dioxin (TCDD). The constituents of Agent Orange are capable of producing gene mutations and chromosomal aberrations, at least in some exper imental circumstances. TCDD and 2,4,5-T are teratogenic in mice and perhaps in other mammals, but the teratogenicity of these chemicals has not been convincingly demonstrated in humans. There is currently no scientific evidence which indi cates that men who were previously exposed to Agent Orange are at increased risk of having children with birth defects, but available data are inadequate to assess this possibility critically. (Author abstract) (105 Refs) 46. FORMALDEHYDE TOXICITY. PART II. REVIEW OF ACUTE AND CHRONIC EFFECT'S ON HEALTH. Solomons K, Cochraae JW Department of Occupational Medicine, National Centre for Occupa tional Health, Johannesburg. S Afr Med J; 66(3):I09-6 1984 Inhaled formaldehyde has acute effects on the respiratory tract, central nervous system, skin and eyes and also chronic effects on the respiratory tract, particularly on pulmonary function. Formaldehyde has also been associated with adverse reproductive and mutagenic effects, and there is evidence of carcinogenic effects from two important animal studies. Some data, largely indirect, suggest a carcinogenic risk for man. The reactions of some international scientific bodies to the accumu lated data are noted, and steps taken by a number of countries to control formaldehyde exposure in the workplace and other environments are discussed. (Author abstract) (51 Refs) 49. A REVIEW OF WORLD LITERATURE FINDS IRON OXIDES NONCARCINOGENIC. Stokinger HE Am Ind Hyg Asoc J; 45(2):127-33 1984 Iron oxide appeared in the first list of 154 Threshold Limit Values adopted by the American Conference of Governmental Industrial Hygienists at its April 1949 annual meeting. It was set to control dust and fume at the recommended value of 15 mg/M3, at the time, the limit for an inert or `nuisance' dust, and was based on studies of welders made earlier by the U.S. Dept, of Labor and by Drinker and Nelson. By 1964, the TLV was tentatively reduced to 10 mg/M3 after a considerable body of literature had accumulated not only on the health ex perience of welders, but of other occupations involving iron oxides as well. As a group, these studies indicated (hat 15 mg/ M3 permitted too great accumulations of iron pigmentation in the lung whose chronic retention effects were not known with certainty. Also, an occasional report of cancer of the lungs ap peared particularly among British hematite miners, although 10 ENVIRONMENTAL AND OCCUPATIONAL CARCINOGENESIS URL 14168 it tigated, most of them handling glass fibers. Several thousands of this workforce had a duration of exposure of 20 years or more and a latency time of 30 years or more. No case of meso thelioma was found. A most of the identified cases of pneumo coniosis could be attached to a prior or a concomitant expo sure to silica if the occupational exposure was carefully exam ined. At the recent time there is no wellfounded suspicion that pneumoconiosis is caused by the exposure in the MMF-industries. A few authors supposed, that unspecific structural changes of the lung as occuring also in a greater amount in de pendency of smoking habits and age are found more frequently among the employees of this industry than among the common population. Neither the workers with such unspecific structural changes of the lung nor the other members of the workforces had prejudices of lung function. At present time a risk due to MMF to get sick with cancer of the bronchopulmonic system, especially with lung cancer can neither be proved nor be ex cluded. Tlie epidemiological studies carried out until now were not capable to point out a possibly existing risk in such a ordner of magnitude. It is uncertain if it will be feasable to prove such a risk by using more subtilized methods. This de pends at one side on the possibility of clearing up and register ing the confounding risk factors. On the other side it must be considered, that the exposure with fibrous dusts even in the old MMF-factories was very much lower than the exposure in the asbestos-industry. It is indispensable to take into account the most important confounding risk factors (smoking habits, preexposure and concomitant exposure with dangerous work ing materials) in further epidemiological investigations. (Author abstract) (41 Refs) (In GER) lected partly by means of questionnaires and partly by abstract ing information from the medical records of cases. Workers ex posed to welding fumes had a slightly increased risk of cancer of the larynx, most predominantly of cancer of the subglottic area. (Author abstract) 58. LUNG CANCER MORTALITY IN A COHORT OF ENGLISH FOUNDRY WORKERS. Fletcher AC, Ades A Department of Environmental and Occupational Health, University of Aston in Birmingham, United Kingdom. Scand J Work Environ Health; 10(1>:7-M 1984 A cohort of males who started work between 1946.and 1965 inclusive in nine English steel foundries and who worked in these foundries at least one year has been followed prospec tively until 1978. Mortality from lung cancer was significantly raised among workers employed in the foundry and fettling shop areas (standardized mortality ratios 142 and 173, respec tively). Most occupational categories in these two areas had more lung cancer deaths than expected, but the standardized mortality ratios were the largest for the furnace bricklayers, fettlers, and heat treatment fumacemen. There was some evi dence of risk increasing with length of employment. There were marked differences in the standardized mortality ratio for lung cancer between study foundries. By year of entry the lung cancer risk was fairly constant, in contrast to the improvement in mortality from diseases of the respiratory system over the same period. (Author abstract) 56. OCCUPATIONAL EXPOSURES AS RISK INDICATOR OF MALE BLADDER CARCINOMA IN A PREDOMINANTLY RURAL AREA. Mommsen S, Aagard J Department of Oncology and Radiotherapy, University of Aarhus, Denmark. Acta Radiol (Oncol]; 23(2-3):147-52 1984 A case-control study was performed on 212 bladder carcino ma patients (165 men and 47 women) and 259 control persons (165 men and 94 women) matched according to age and geo graphical area. Bivariate associations among the males revealed an increased relative risk (RR) of developing bladder carcino ma associated with occupational exposure to oil or gasoline, chemical materials, kerosene or asphalt. A significantly in creased RR of developing bladder carcinoma was associated with blacksmiths and mechanics. A logistic regression analysis did not reveal an independent statistical effect of this parame ter. Among the occupational factors, exposure to oil or gaso line was the most informative aetiologic determinant. (Author abstract) 57. WELDING AND CANCER OF THE LARYNX: A CASE- CONTROL STUDY. Olsen J, Sabroe S, Later M Department of Social Medicine, University of Odense. Eur J Cancer Clin Oncol; 20(5):639-43 1984 The purpose of the study was to examine the occupational history of laryngeal cancer patients, and especially their expo sure to welding. The investigation was conducted as a casecontrol study where all newly diagnosed patients less than 75 yr of age with cancer of the larynx in Denmark during March 1980 to March 1982 were selected as cases. For each case, four age- and sex-matched controls were identified from the munici pal person register in which the case was listed. Data were col 59. RESPIRATORY IMPAIRMENT IN COKE OVEN WORKERS: RELATIONSHIP TO WORK EXPOSURE AND BRONCHIAL INFLAMMATION DETECTED BY SPUTUM CYTOLOGY. Madison R, Aftft AA, Mittman C Occupational Health Section, City of Hope National Medical Center, Duarte, California. J Chronic Dis; 37(3):167-76 1984 Coke oven workers are at excess risk of developing lung cancer and may be at risk for chronic obstructive lung disease (COLD). We have studied 3799 male workers to assess the re lationship between the two diseases. Repeated lung function and sputum cytology tests were obtained over a 3-year period. Sputum samples were assessed using standardized methods; in addition to metaplastic and neoplastic changes, we reproducibly assessed the presence and extent of acute and chronic in flammatory changes. Spirometric flow rates (FEVI) were sig nificantly reduced in workers most exposed to coke oven emis sions, particularly in those with excessive inflammatory cells and regular metaplasia in sputum. The presence of reactive bronchial epithelial cells and metaplasia were potent predictors of an abnormal FEV1/FVC. Studies like these may offer a means to investigate the relationship between COLD and lung cancer. Such changes in sputum may identify individuals at risk of developing both diseases, (Author abstract) 60. APPLICATION OF URINE MUTAGENICITY TO MONITOR COAL LIQUEFACTION WORKERS. Recio L, Enoch HG, Hannan MA, Hill RH Graduate Center for Toxicology, University of Kentucky, Lexington. Mutat Res; 133):201-7 1984 The Salmonella/microsomal assay was used to monitor workers' urine for mutagenicity as a potential indicator of human exposure to mutagens/carcinogens. Urine samples from 12 ENVIRONMENTAL AND OCCUPATIONAL CARCINOGENESIS URL 14169 } 1C :'l ;.i i , **; Kr 57 workers at a coal liquefaction pilot plant in Catlettsburg, Kentucky, were assayed for mutagenicity during work periods. Urine samples were collected twice during plant operations and once when the individuals were away from the plant for at least 48 h. In 7 individual smokers (5 operator/maintenance workers and 2 administrative staff workers) there was an indi cation of enhanced urine mutagenicity during work periods. Urine mutagenicity of nonsmokers from the pilot plant was sig nificantly higher than that of an additional control group of nonsmokers from Lexington, Kentucky. While cigarette smok ing was the major factor affecting urine mutagenicity, no sig nificant mutagenicity that could be directly attributed to the pilot plant workers' environment was evident. (Author ab stract) 61. CANCER MORTALITY PATTERNS BY WORK CATEGORY IN THREE TEXAS OIL REFINERIES. Thomas TL, Waxweiler RJ, Crandall MS, White DW, Moure-Eraso R, Fraumeni JF Jr Occupational Studies Section, National Cancer Institute, Betbesda, Maryland. Am J Ind Med; 6(1):3-16 1984 A previous proportionate mortality ratio analysis revealed elevated mortality from brain tumors, stomach cancer, leuke mia, and other cancers among OCAW members employed in three Texas oil refineries. In order to evaluate these findings, complete work histories of cases and a matched set of controls who died from other causes of death were obtained from com pany personnel records. Work histories were summarized by classifying each job title and department entry into one of sev eral broad work categories of refinery unit operations. A worker was considered `exposed' to a work category if he was known to have worked at least 1 day in the category 15 or more years prior to his death. Maximum likelihood estimates of the relative risk for brain tumor, stomach cancer, and leukemia were calculated by work category using a procedure for matched case-control data. No strong associations for brain tumor risk were seen with any work categories. A slight asso ciation for leukemia was seen among workers in the Treating category, which included unit operations that reduce the level of aromatic and sulfur constituents of petroleum products and combine them with additives to improve their quality. Stomach cancer risk was elevated among maintenance workers and workers exposed to lubricating oils and paraffin wax process ing. (Author abstract) 62. RISK OF LUNG CANCER IN WORKERS BELONGING TO THE OCCUPATIONAL GROUP OF MINING AND STONE PROCESSING Vutuc C Hyneoe-lnstitnt der Uaivenltat Wien. Zentralbl Bakteriol Mikrobloi Hyg (B]; 177(3-4):183-7 1983 their anamnesis) was R =s 2.0a. Significantly higher risks (adj. for age. TE) were in relation to years of occupation, less than 10 years: R = 2.2a, 11-20 years: R = 2.7a, 21-30 years: R = 2.6a. a P less than 1%; b P less than 5%. (Author abstract) (In GER) 63. CANCER OF THE BLADDER OCCURRING IN OCCUPATIONAL DYE USERS: REPORT OF TWO CASES Ando M, Takeda H, Mizuo T, Yokokawa M, Ushiyaraa T Department of Urology, Tokyo Rosa! Hospital. Hinyokika Kiyo; 30(21:223-8 1984 Two cases of occupational dye users were found to have bladder tumors. Case 1 was a 32-year-old male, who had worked at the Yuzen process for the last 7 years. Multiple pap illary tumors were seen on the whole wall of the bladder endoscopically and total cysto-urethrectomy and ileal conduit were performed. The pathological examination of the bladder tumors revealed non-invasive transitional cell carcinoma grade I--II- His post-operative course has been uneventful without any signs of tumor recurrence for 31 months. Case 2 was a 46year-old male, who had worked at the throwing stained silk for the last 28 years. He suffered from severe hematuria for six months. A big egg-sized nonpapillary tumor on the posterior wall of the bladder was found and bilateral cutaneous-ureteros tomy was performed but severe gross hematuria remained. Total cysto-urethrectomy was performed but the patient died of progressive disease 5 months later. The bladder tumor was a grade III invasive transitional cell carcinoma. The fact that process workers in the dye manufacturing industry have a high risk of bladder cancer has been well known and mass screening examination on them has been systematically performed. Though there is a higher relative risk of bladder cancer in oc cupational dye users, systematic screening examination has not been done. We emphasize the necessity for establishing system atic mass screening examination of occupational dye users for the early diagnosis of bladder cancer. (Author abstract) (In JPN) OCCUPATIONAL FACTORS: GENERAL 64. THE BIOSOCIAL ELEMENTS OF RISK IN THE INVASIVE CERVICAL CANCER INCIDENCE AMONG A STATIONARY AND MIGRATORY WOMAN POPULATION. A CASE-CONTROL STUDY. Zema B Institute of Oncology, Cancer Epidemiology Unit, Gliwice, Poland. Nooplnamn; 31(l):119-27 1984 Out of 1580 male lung cancer patients and 3160 controls (data collected in a nationwide study) 177 patients and 197 controls belonged to the occupation `mining and processing of stone' (asbestos, metals and coal excluded). 164 (92.6%) pa tients had a Kreyberg I tumor, 13 patients a Kreyberg II tumor. There are significant more smokers among patients (98-9%a), all patients with a K I tumor were smokers, com pared to the controls (82.2%). Patients had a significant longer smoking career (40.9 yearsa) and a higher tar exposure (TE = 2544)b compared to the controls (36.2 years, TE = 2223). Lung cancer risk (adj, for age, yean of occupation, TE) of smokers belonging to occupation `stone' compared to smokers belonging to group 'white collar' (no occupational exposure in The incidence risk of invasive cervical cancer has been ana lyzed in two groups of women-autochthones and migrantsand the higher risk-rate has been proved for the latter. The es sential interdependence between the incidence risk of invasive cervical cancer and the danger of industrial dusts and gases in fluence have been proved for both fractions of women. The higher incidence risk of invasive cervical cancer has been ob served among those who had suffered from lithiasis, diabetes, arterial hypertension before, among those who while undergo ing the cancer treatment might have also been operated on re productive organs because of myoma or erosion, or had suf fered from syphilis (this has been observed only in relation to the autochthones' population). (Author abstract) ENVIRONMENTAL AND OCCUPATIONAL CARCINOGENESIS 13 URL 14170 # 77. ANALYSIS OF THE PREVALENCE OF HEREDITARY ADENOMATOSIS OF THE GASTROINTESTINAL TRACT AMONG THE POPULATION OF MOSCOW TatishviU GG, Nikitin AM, Ai'tstauler BA Genetika (Moskva); 20(5):85763 1984 The prevalence of hereditary autosomal dominant gastrointestinal adenomatosis in the Moscow population was estimated on the basis of elaboration of an indirect method. This estimate was found to be 1:48000. The prevalence observed is discussed in terms of ascertainment problems and peculiarities of the method of calculation proposed, (Author abstract) (In RUS) 78. TRENDS IN THE DISTRIBUTION OF STOMACH CANCER AND CANCER OF THE LARGE INTESTINE AMONG THE POPULATION Tikhonova NA, Simklna ES, Kozlova EV, Zaseev VK Vopr Onkol; 30(2):45-51 1984 An inverse correlation in stomach and large bowel cancer distribution was established as a result of an evaluation of cancer morbidity statistics for the City of Moscow in 19651980. The structure of gastrointestinal neoplasms in the next five years is likely to undergo changes in female population in which large bowel cancer is leading at present. (Author ab stract) (In RUS) ' 797)8OCTAL FACTORS, DIET AND BREAST CANCER IN A ---NORTHERN ITALIAN POPULATION. Talamlai R. La Vecchia C, Decarli A, Franceschi S, Grattoni E, Grigoletto E, Liberati A, Togaoai G Laboratory of CUaical Pharmacology, Institnto di Ricercbe Farmacologicbe `Mario Negri*, Milan, Italy. Br J Cancer 49(0:723-9 1984 The relation of breast cancer to social and dietary variables was evaluated in a case-control study of 368 women with breast cancer admitted to the General Hospital of Pordenone (a town in the eastern side of Northern Italy) and 373 agematched controls. Occupation was related to the risk of breast cancer, housewives and non-manual workers (teachers and other professionals, clerical workers, etc.) showing relative risks of 1.7 and 2.4 respectively when compared to women oc cupied in agriculture. The role of education was apparently less important, and not statistically significant. The risk was higher in women who were obese, the trend of increasing risk with increasing body mass index being confined to post-menopausal women. When indicators of dietary fat intake were ana lysed, a significantly increased risk was found with more fre quent consumption of milk and dairy products but the risk esti mates were only slightly above unity with reference to meat consumption. Women who drank alcoholic beverages showed a relative risk of 2.5 compared to women who had never drunk, when allowance was made for all identified potential confounding factors. The association between alcohol and breast cancer was not explained by the other dietary variables considered, and the risk estimates were higher for women who drank more wine, or more than one type of alcoholic beverage. Thus, the findings of the present study give evidence in favour of the hypothesis that alcohol consumption is related to the risk of breast cancer. (Author abstract) 80. BIOSOCIAL CORRELATES OF COLORECTAL CANCER IN GREECE. Papadimitriou C, Day N, Tzonou A, Gerovassilis F, Manousos O, Tricbopoulos D Department of Gastroenterology, Evangelismos Hospital, Athens, Greece. Int J Epidemiol; 13(2):15S-9 1984 One hundred consecutive patients with histologically con firmed colorectal cancer and an equal number of age- and sexmatched orthopaedic patients as hospital controls were inter viewed about demographic, socioeconomic, biometric and medical variables. Cholecystectomy was significantly more fre quent among cases than controls, but there was no side-predi lection of the post-cholecystectomy tumours. The frequency of bowel evacuation was significantly higher among cases, par ticularly those with rectal cancer, an observation which ap pears contradictory to the `prolonged bowel transit time-high colorectal cancer risk' hypothesis. No significant differences were found between cases and controls with respect to socio economic status, height and weight, smoking habits, use of lax atives and (for females) parity, age at first pregnancy, and age at menopause; however, cases appeared to be younger at mcnarche. (Author abstract) 81. INCIDENCE OF LUNG CANCER IN FIVE TOWNS IN ISRAEL, 1960-74. Epstein LM, Katz L, Tamil A, Rfchpon S Department of Family and Conununity Health, Faculty of Medicine, Teckniou-Ixrael Institute of Technology, Haifa. Isr J Med Sd; 20(1)^7-32 1984 Age-standardized incidence rates of lung cancer, based on data from the Israel Cancer Registry, were calculated in five urban areas in Israel during three 5-year periods: 1960-64, 196569 and 1970-74. The rates in these towns and during the differ ent periods were compared. For both sexes the incidence was lowest in Jerusalem, the city with the lowest air pollution. The incidence rate of lung cancer in males during the entire period reviewed fell in all towns except for Tel Aviv, where it rose. Cancers of the urinary bladder and of the pancreas did not dis play these trends. Possible explanations for the differences are discussed. (Author abstract) 82. CARCINOMA OF THE PROSTATE IN ISRAEL: SOME EPIDEMIOLOGICAL AND THERAPEUTIC CONSIDERATIONS. Serrudio C, Mukunel E, Kalian E Department of Urology, BeiUnaon Medical Center, Sackler School of Medicine, Td Ariv University, Israel. Prostate; 5(4)^75-82 1984 Analysis of the different rate of prostatic cancer in Israel among Jews from various countries of origin reveals some very interesting and marked varieties in incidence, which are studied more closely now. Aggressive, combined treatment for the invasive cases of prostatic cancer has been used since 1975. This was based on orchiectomy, DES, and chemotherapy for the stage D2 disease, and on radiotherapy and hormonal ther apy for the stage C, and possibly also the stage Dl disease. Re sults so far have been very encouraging indeed, and with con siderably better results than obtained with the individual, more conventional forms of therapy. Five-year survival in the stage D2 disease has been 63.5%, and 87.6% in the stage C (+D1?) disease. It appears that this approach is more justified, certainly in the advanced stages of this disease. (Author abstract) 16 ENVIRONMENTAL ANO OCCUPATIONAL CARCIN06ENESI5 URL 14172 cancer was 2,1 and the occupational etiologic fraction was 0.33 (95% confidence interval 0.19-0.47). The tobacco etiologic fraction was 0.81, while the two exposures together accounted for 89% of the total burden of incident cases. If 33% of all male lung cancers were of occupational aetiology, then this alone would represent 5% of all cancer deaths. (Author ab stract) 66. A CASE-CONTROL STUDY OF CANCERS OF THE NASAL CAVITY AND PARANASAL SINUSES. Brintou LA, Blot WJ, Becker JA, Winn DM, Browder JP, Farmer JC Jr, Fraumeni JF Jr Environmental Epidemiology Branch, National Cancer Institute, Betbeada, MD. Am J Epidemiol; 119<6):896-906 1984 64. MYELOPROLIFERATIVE AND LYMPHOPROLIFERATTVE DISORDERS IN TASMANIA, 1972-40: OCCUPATIONAL AND FAMILIAL ASPECTS. GQes GG, Lickiaa JN, Baikie MJ, Lowcnthal RM, Panton J Department of Community Health, University of Tasmania Clinical School, Australia. JNCh 72(0:1233^0 1984 All cases in a population-based series of myeloproliferative and lymphoproliferative (LP) disorders diagnosed in usual resi dents of Tasmania between 1972 and 1980 were asked for oc cupational histories and the occurrence of similar diseases in their close relatives. Occupational risks were observed for males who had farmed, mined, or worked in foundries and for women who had fanned or had been hairdressers. For individ ual diagnoses, the risk to farmers was seen to vary with age at diagnosis, sex, and region. With regard to familial risks, the LP and MP groups seemed to breed true, relatives being affected with a disorder from the other group not more often than would be expected by chance. The risks were of two kinds: Those to siblings and that between parent and child, particular ly between mother and son. Occupational risks for the familial cases were limited to farming particularly in males diagnosed at 65 years of age or older. Females possessed elevated risks for the LP group only, and their highest relative risk was for those diagnosed before age 65. This evidence suggests that fa milial clustering of these disorders partly may be due to common environmental exposures in males from rural kindreds. (Author abstract) To examine occupation, smoking, and other risk factors for nasal cancer, a case-control study was conducted among 160 patients, who were admitted to four hospitals in North Caroli na and Virginia between 1970 and 1980, and 290 controls. Em ployment in the furniture industry was not associated with squamous cell tumors, but such employment increased the risk of nasal adenocarcinoma by fivefold. In addition, approximate ly threefold excess risks of adenocarcinoma were observed for those employed in other industries involving possible exposure to wood dust. Elevated risks among males were also associated with occupational exposures to chromates (relative risk (RR) -- 5.1) and chemicals (RR -- 2.7). Among females, an excess risk was associated with employment in the textile industry, particularly for jobs involving dust exposure (RR 2.3). Al though there was no evidence that alcohol consumption affect ed risk, heavy cigarette smokers were at a two- to threefold excess risk (predominantly for squamous cell tumors); in addi tion, there was evidence that there was an elevated risk associ ated with the use of snuff. Elevated risks were also associated with histories of nasal polyps (RR = 8.3), recurrent nose bleeds (RR = 2.0), and sinus trouble (RR = 2.7). These find ings provide leads for further studies, and underscore the im portance of distinguishing between histologic types. (Author abstract) 67. MORTALITY STUDY OF BRITISH PATHOLOGISTS 1974-80. Harrington JM, Oakes D Institute of Occupational Health, University of Birmingham, UK. Br J lad Med; 41(2):i88-91 1944 65. USE OF JOB-EXPOSURE MATRIX IN AN OCCUPATIONAL ANALYSIS OF LUNG AND BLADDER CANCERS ON THE BASIS OF DEATH CERTIFICATES. Coggon D, Pannett B, Acbesoa ED Environmental Epidemiology Unit, Medical Research Council, Univer sity of Southampton, England. JNCh 72(1)41-5 1984 A job-exposure matrix has been applied in a case-control study of lung and bladder cancer on the basis of occupational information abstracted from British death certificates. The ex pected association between lung cancer and jobs entailing ex posure to asbestos was clearly demonstrated (relative risk, 1.5; 95% confidence interval, 1.2-1.9). The effects of three other known industrial carcinogens were not apparent, and reasons for this were discussed. Also included in the matrix were five substances whose carcinogenicity in humans has not been es tablished. Formaldehyde, diesel fumes, and cutting oils were all associated with carcinoma of the bronchus, but the absence of a risk in `high-exposure' occupations was against a causal rela tionship. Bladder cancer was more common in jobs involving high exposure to printing inks (relative risk, 5.0; 95% confi dence interval, 1.0-25.8) and cutting oils (relative risk, 1.5; 95% confidence interval, 0.8-2.8). Use of the job-exposure matrix added considerably to the conventional analysis of cancer risk in individual occupational categories. (Author abstract) Membership lists of the Royal College of Pathologists from 1974 to 1980 were used to establish a population of 2307 men and 413 women. During the period of study 126 of these patho'ogists died and death certificates were obtained for 121. The standardised mortality ratios (SMR) for all causes in men were 56 and in women 99. Deaths from accidents, poisoning, violence, and especially suicide, were noted to be in excess of that expected from the general population but similar to that for medical practitioners. Drug overdose was the cause of each suicide. Excess deaths from lymphatic and haemopoietic neo plasms noted in a previous study were not present but an excess of brain tumours was found. Including 1981 data thus far collected, deaths from brain tumour were apparently in excess (observed 6, expected less than 2.0, p less than 0.02). Possible aetiological hypotheses include previous exposure to organic solvents or tuberculosis infection. In view of the pa thologists' exposure to formaldehyde it is interesting to note that no nasal or nasal sinus tumours were reported and the SMR for lung cancer was 41. (Author abstract) 68. ADMINISTRATION OF ANTINEOPLASTIC AGENTS: A PRACTICE WHICH CARRIES A PROFESSIONAL RISK Zaccara A Riv Inferm; 2(3>:198-201 1983 Keywords (MeSH): Antineoplastic Agents/'adverse effects; Human; Occupational Diseases/*chemically induced; Risk. ENVIRONMENTAL AND OCCUPATIONAL CARC1N06ENESIS 13 6* y *\ men age ! 5-24 and 25-34 experienced biphasic mortality trends, case of lung cancer, the spatial distribution showed district gra with a rise peaking in 1971 and then a fall. (3) The mortality dients of occurrence between the central-city and the suburbs. ratios, non-white to white men, age 25-34 and 35-44, were far (Author abstract) (In FRE) higher then those of other age groups. (4) The mortality ratios, non-white males to females, increased steadily for all age groups, and those of age groups 15-24 and 25-34 turned up 89. CANCER MORTALITY AMONG IMMIGRANT sharply. Selected causes of death (1960-1977) were reviewed to POPULATIONS IN ONTARIO, 1969 THROUGH 1973. uncover reasons for the unfavorable mortality trends among males. The following causes contributed to rising mortality among males: (a) accidents, suicide, and homicide for white and non-white teenagers and young adults, age 15-24, 25-34 Newman AM, Spengler RF Department of Preventive Medicine and Bioctatistics, University of Toronto, Oat. Coa Med Assoc J; 130(4)^99-405 1994 and 35-44; (b) suicide and homicide for non-white men age 45- Ontario is home to a sizeable, recently established immigrant 54; (c) cirrhosis of the liver for white men age 35-44 and for population whose cancer mortality has until now remained un non-white 25-34, 35-44 and 45-54; (d) malignant neoplasms for examined. The province's six largest immigrant groups (British, white men age 35-44 and for non-white age 45-54. (Author ab Italian, German, Dutch, Polish and Soviet) were investigated stract) to compare their cancer mortality experience with that prevail ing in Ontario and in their countries of birth for the period 87. CANCER MORTALITY AMONG PUERTO RICANBORN RESIDENTS IN NEW YORK CITY. 1969 through 1973. Standardized mortality ratios (SMRs) were computed from data from Statistics Canada and the World Health Organization (for 1971) for five sites of cancer. The Rmenwaike I University of Pennsylvania, Population Studies Center, Philadelphia. An J Epidemiol; 119<Z):177-*5 1964 rates of death from stomach cancer were significantly higher for the immigrant groups (except the Germans) than for the Canadian-born (SMRs 158.6 to 256.1) and were significantly More than half the 800,000 Puerto Rican migrants living in lower for the immigrants (except the Dutch) than for the pop the United Slates resided in New York City in 1970. Mortality ulations of their countries of birth (SMRs 26.5 to 72.9). The statistics from 1969-1971 indicate that Puerto Rican natives in rates of death from colorectal cancer and cancer of the breast the metropolis have a standardized mortality ratio for cancer tended to be lower among the immigrants. Most male immi which is 77% of that of non-Puerto Rican white males and grants had high rates of death from lung cancer relative to the 81% of that of non-Puerto Rican white females. The age-ad- Canadian-born, whereas their female counterparts had relative justed death rates of the Puerto Rican-bora residing in New ly low rates. For most of the immigrant groups the rates of York City for cancers of the lung, prostate, bladder, ovary, death from prostate cancer closely resembled those prevailing and rectum are low, ranging from 43-70% of those of non- in the country of birth. Displacement of cancer mortality expe Puerto Rican whites; rates for breast cancer and colon cancer rience towards that in Ontario was most evident for Polish im are somewhat lower relative to those for non-Puerto Rican migrants. It may have been too soon to see trends among the whites. As is true for Puerto Ricans on the island, migrants to more recent immigrants (Italian, German and Dutch), who, for New York City have excessive levels of cancer of the cervix the most part, had not yet reached the age of highest cancer and esophagus (each roughly three times that of non-Puerto risk. Ontario should provide a valuable resource for further Rican whites) and cancer of the stomach (almost twice that of studies of lifestyle and environmental determinants of cancer. non-Puerto Rican whites). (Author abstract) (Author abstract) URL 14173 88. MORTALITY DIFFERENTIAL FOR CANCER BASED ON SOCIAL CLASS: THE METROPOLITAN REGION OF MONTREAL, 1971 OlHER EPIDEMIOLOGICAL FINDINGS ThODCZ JP Departement dt Geographic, Universite rfe Montreal, Quebec, Canada. Soc Sci Med; 18(1):73-81 1984 90. EPIDEMIOLOGY OF KIDNEY CANCER. Cancer mortality rates vary from area to area. Part of this -- Dayal H, Kiaman J variation is due to socio-economic characteristics of the area and part to other factors including the availability of health Statistical Laboratory, Fox Chase Cancer Center, Philadelphia, Pa. Semin Oncol; 10(4)366-77 1983 services. Three social indicators associated with cancer mortal Renal-cell carcinoma usually affects those over 40 years old, ity are used to estimate variations between low and high and, in any age group, the disease occurs about twice as fre census sectors within the metropolitan region of Montreal. The quently among men as it does among women. The incidence of components of socio-economic status which have been used the disease has been steadily increasing over the years. In the are revenue (median family income), education (college and United States, the probability of surviving after diagnosis of university level) and occupation (higher status profession). For renal cancer has been improving since 1940 regardless of race, each of the three zones of the metropolitan area - the city of sex, and age at diagnosis. The relationship between SES and Montreal, the island of Montreal not including the city of the chance of developing the disease is sporadic with an indica Montreal, the north and south shores of the metropolitan area - tion of a slightly higher risk in the upper socioeconomic class twenty-five census sectors have been chosen which have es. Urban/rural comparisons consistently suggest that a higher 1 higher or lower positions for each of the socio-economic com risk is associated with urban residence. Tobacco use is prob i ponents. For each group standardized death rates were evalu ably the only environmental factor that could be considered to ated for each type of cancer and the Poisson test was applied be etiologicaliy related to cancer of the kidney. A variety of to judge whether the differences between the projected rate studies point to a moderate but consistent association with to and the observed rate were significant. The results indicate a bacco use in the form of cigarette, cigar, or pipe smoking. The strong indirect relation between the standardized mortality excess of the disease in males compared to females and the rates and the socio-economic status in the central city. In the lower incidence in Mormons may partly be due to the con- ENVIRONMENTAl AND OCCUPATIONAL CARCINOGENESIS 17 % founding effect of smoking. Dietary vitamin A or vitamin A supplements may have an antipromoting effect in the develop* ment of kidney cancer. Hypotheses implicating fat and/or cho lesterol intake in the etiology of cancer of the kidney appear to be too tenuous. The evidence of a relationship between con centrations of certain trace metals in drinking water and inci dence of renal cancer is weak. Similarly, there is no strong in dication of an increased risk among individuals exposed to ra diation. In general, with the exception of the observation of an unusually high risk among coke-oven workers, occupational studies have not identified any high-risk groups. Familial ag gregation, though rare, occurs with peculiar disease character istics that may predict similar cancers in the proband's relatives with a high degree of accuracy. In conclusion, the etiology of cancer of the kidney is poorly understood. The descriptive epi demiology of the disease provides some interesting insights into the correlates of the distribution of the diseasedABSTRACT TRUNCATED AT 400 WORDS) (Author abstract) 91. A POPULATION-BASED CASE-CONTROL STUDY OF RENAL CELL CARCINOMA. McLnogbUn JK, Mantel JS, Blot WJ. Scknmm LM, Mehl ES, Franmeal JF Jr Department of Epidemiology, Johns Hopkins University School of Hy giene and PubUc Health, Baltimore, Md. JNCk 72(21:275-84 1984 Statistics are not available; the mortality rates reported from the United States and Canada are considerably lower. The inci dence of and mortality from prostatic cancer have increased in most countries, in particular in areas with an initially low fre quency of this disease- The ratio of mortality to incidence for prostatic cancer varies rather widely, being low in North America, Hawaii and Scandinavia. It is suggested that the ob served variation in the mortality to incidence ratio for prostatic cancer could be due to differences in diagnostic practices be tween countries. This could explain, at least in pan, the fact that the increasing trends of prostatic cancer incidence in North America are not accompanied by an increase in mortali ty from this tumour. This notion, however, does not exclude advances in treatment as possible determinants of the improved survival rate from prostatic cancer in this part of the world. The available statistics on prostatic cancer are based on the sum of clinically diagnosed carcinomas and those latent tu mours found unexpectedly at prostatectomy and autopsy. The proportion of latent carcinomas among all prostatic cancer cases depends on the detection rate and varies from country to country, thus casting uncertainty on the comparability of pros tatic cancer statistics from different areas. To avoid confusion in the statistics of prostatic cancer, it would be useful to con sider introducing latent prostatic cancer as a separate entity in the next revision of the International Classification of Diseases (ICD). (Author abstract) A population-based case-control study of renal cell carcino ma (495 cases and 697 controls) in the Minneapolis-St. Paul seven-county metropolitan area implicated cigarette smoking as a risk factor with an odds ratio (OR) among men of 1.6 (95% confidence intervals: 1.1-2.4) and among women of 1.9 (1.33.Q). A statistically significant dose response was observed in bod) sexes for pack-years of cigarette use. On the basis of cal culations of attributable risk, it was estimated that 30% of renal cell cancers among men and 24% among women were due to smoking. High relative adult weight as measured by the body mass index (BMI) was found to be a major risk factor among women but not among men, with those in the highest 5% of the BMI having an OR of 5.9 (1.8-20.4) in comparison to the lowest quartile. This association with excess weight was not seen at age 20, but it became more pronounced with increasing age, suggesting that the primary influence of weight gain is during the late stages of renal carcinogenesis. Excess risks were also related to ethnic background (particularly, German), which may account in part for the elevated incidence of renal cancer in the North Central area of the United States. In addi tion, positive associations were observed for long-term use of phenacetin-containing analgesics, heavy meat consumption, and heavy tea drinking (females only). An occupational clue was provided by an increased risk for exposure to petroleum, tar, and pitch products. Excesses of certain urologic and cardiovas cular diseases were also observed among the cases compared to controls. (Author abstract) 92, INTERNATIONAL TRENDS IN PROSTATIC CANCER. Zartdse DG, Boyle P. Snuus M Ualt of Analytical Epidemiology, International Agency for Research _ on Cancer, Lyon, France. Iat J Cancer; 33(2*223-30 1984 The most recent data available demonstrate a 120-fold differ ence between the lowest and highest incidence rates of prostat ic cancer, the disease being very common in North America, particularly among Blacks, and in Scandinavia, while it is rare m Japan and other oriental countries. The highest mortality for prostatic cancer is reported from St. Vincent and Grenadines, Martinique and Bermuda, from countries where the morbidity 93. OVARIAN CANCER. GEOGRAPHICAL, HOST AND ENVIRONMENTAL FACTORS. AN OVERVIEW. Anteby SO, Mor Yosef S, Scbeaker JG Department of Obstetrics and Gynecology, Hadaaaah University Medi cal Center, Ein Karan, Jerusalem, Israel. Arch Gynecol; 234<2):137-48 1983 The incidence of ovarian cancer is reviewed among different races and ethnic groups. We present the effect of socio-eco nomic class, age, endocrinological factors, menstrual cycle, re productive history, familial, and genetic factors, viral infec tions, chemical carcinogtds, and previous exposure to radiation on the incidence of ovarian cancer. There is evidence that en vironmental factor affects the distribution of various types of ovarian cancer. Migration may also change the susceptibility to this disease and the mean age was varied between countries being lowest where incidence was highest. The disease ap peared to have a familial incidence. The protective effect of oral contraceptive steroids and the role of asbestos as a chemi cal carcinogen are discussed. (Author abstract) (86 Refs) 94. PREDILECTION OF LUNG CANCER FOR THE UPPER LOBES: AN EPIDEMIOLOGIC INQUIRY. Byert TE, Vena JE, Raepka TF Department of Social and Preventive Medicine, School of Medicine, State University of New York at Buffalo. JNCIi 72(6*1271-5 1984 Data from 24,798 cases of primary neoplasm of the lung reg istered by the Surveillance, Epidemiology, and End Results Program between 1973 and 1977 were examined for the demo graphic determinants of lobe of origin. Lung cancer occurred predominantly in the upper lobes in both sexes, in both blacks and whites, and at all ages. This pattern was observed for squa mous cell and small cell carcinoma as well as adenocarcinoma. The predominance of lung cancer in the upper lobes was much stronger in the young and somewhat stronger in blacks. These findings are discussed in light of current theories of pulmonary carcinogenesis. Current theories may not explain entirely these IS ENVIRONMENTAL AND OCCUPATIONAL CARCINOGENESIS j{ l | a I I s*