Document MomQB9obMNyQj9DoBMzDyOYzL

*c-tt3, 1167 Mr. J. M. Barnhart national Xaoolatloo Mfcnofaaturara liioolttloQ bill Lodogtoo Aranaa tov Tort, Umt Xork 10017 . Daar Jaefc* * SUBJECT* J.A.M.A. Artlela, "Maothallo-- and Zta Aasoolatloo With Ilbaitoall* A copy of tha attaobad artlola aboald ba aact to Noteri of tha Hoalth and Safatf Co--ittaa. It la a good rtrlav on --aothalio-- SlDoartljr, X-- B. Qraat, H.O. boot Mr. Small lrltttnfh-- 02 212 0540 =? 587 Mesothelioma and Its Association With Asbestosis Maxwell Borov, MD, Alfred Conston, MD, Lawrence L. Livomese, MD, and Sorbert Schalet, MD Within a three-year period in a community hospital, exist. Since Godwin1 in 1957 laid down strict cri 17 casts of mesothelioma, nine of the pleura and tight teria for the diagnosis of pleural tumors and Wins of the peritoneum, were found at surgery. Two of our low and Taylor* in 1960 for oeritoneal tumors, the patients contracted this malignancy with only environ* diagnosis of these neoplasms has become more com mental exposure consisting of living in a community mon. The incidence of primary mesothelioma has adjacent to the asbestos mill. In the same hospital, there varied statistically from\02% to .2% of aU autop has been a high incidence of bronchogenic carcinoma sies. with a ratio of one to two in favor of the male. with asbestosis. A review of the autopsy material of the The first large series of cases of diffuse meso past decade brought to light only one additional case. thelioma was diagnosed histologically in 1957 at the It is our belief that the incidence of mesothelioma is Pneumoconiosis Research Unit at Johannesburg, increasing as is the incidence of asbestosis. with the South Africa. In trying to explain this mysterious increasing application of this product in many different epidemic, Wagner et al/ noting that asbestos bodies industries. could be found in the )un?s of some of their pa tients. obtained detailed life histories of these pa Primary tumors of the serosal surfaces are so rare that for years they were considered to be pathologic curiosities. The first reference to such mors can be found in a report by Von Rokitansky,1 who in 1854 described primary tumor; of the peri* toneum which he called "colloid cancer/' During the next 100 years, there were sporadic reports of similar types of tumors. However, this entity re* raained so ill defined that there was much doubt as to its precise nature. Brown and Johnson* in 1951 considered these mesothelial tumor* (mesothelio ma) to be the end result of an inflammatory pro cess, with organization of the exudate. Willis' in his pathologic text made the following statement: "To the present day accounts of supposedly primary serosal tumors continue to be descriptively inade quate and insufficiently critical, displaying a lack of awareness of the possible behavior of small unde tected carcinomas," and he also cautioned the read er to preserve an open mind Regarding the exact histogenesis of these tumors. In 1954, Ackerman4 stated that it was the majority opinion that al though primary mesotheliomas are rare they do tients. By 1960, they were able to establish an as sociation with the Cape of Good Hope asbestos tu3fi3eldpsa,tieonr tsthweitihndhuissttorlioagl iucsaellyopfroavsebnesptoles,urianl 32 of meso theliomas. The m'/ority of these patients had not actually worked with asbestos but had lived in the vicinity of the mines and mills and some had left these areas of exposure as young children. The aver age period between exposure and develooment of the tumor was 20 to 40 years. By 1962, Wagner et al* had diagnosed a total of 87 pleural and two peritoneal mesotheliomas. In only two esses was it not possible to establish a history of exposure to the asbestos dust Of these 87 cases, 12 had bad industrial exposure and the remainder had had en vironmental exposure from living in the vicinity of the mills and dumps. This association between mesothelioma and asbestosis was made even more intriguing when, in 1955, Bonser et al* described a series of 72 autopsies on patients with asbestosis, in which four cases of peritoneal mesothelioma were found. Subsequently, Mancuso and Coulter'9 found five peritoneal mesotheliomas in autopsies on 1,495 asbestos workers, and Hourihane," upon reviewing From the department* of eurfery tad patholofy. Somerset Hot* pittl. Somerville. NJ. Reprint requests to SIS Church St. Botmd Brook. NJ 06805 (Dr. Borow>. the necropsy files of the London Hospital from 1917 to 1962. found 34 cases of mesothelioma. 17 of the pleura and an eoual number of the peri- JAMA. Aug 21. 1967 Vol 201. No B 02 212 0541 93 su drftSOTHELlOMA AND ASBESTOSIS--BOROV, Al. toneum. All of these patients bed pulmonary as bestosis, even though in a few there was no his tory of exposure to the ashestoa dust. In the same year, Enticknap and Smither1 *Reported 11 cases of peritoneal mesothelioma in patients exposed to as hestosis. In an attempt to determine whether mesothelio ma of the serosal surfaces had any relationship with asbestos exposure in the United States, Selikoff et al'* studied 307 consecutive deaths among asbestos insulation workers in Northeastern United States. They found ten deaths caused by mesothelioma, four pleural and six peritoneal mesotheliomas. In addition, these workers had an extremely high death rate attributed to cancer of the stomach, colon, and rectum. Of the 307 deaths, 40.4% were attributed to cancer, 5.5% to asbestosis, and 54.1% to other causes. In a second study where they re viewed 26 consecutive autopsies of patients with asbestosis, they found four mesotheliomas of the pleura and three of the peritoneum. One of us (M.B.) has had the unique experience of operating, within the past two years, on II patients who proved to have mesothelioma. Six of these were of the peritoneum and five of the pleura. These cases added to those diagnosed previously made a total of 17 cases of mesothelioma, of which eight were peritoneal and nine were pleural mesotheliomas. All 17 cases were diagnosed within the past three years. A review cf tve autopsy material at Somerset Hos pital, Somerville, NJ, from 1948 through 1965 did not disclose any additional cases of mesothelioma. This high concentration of what is considered to be a rare tumor can be explained by the close proximity of a major asbestos mill. Approximately 75% of all the asbestos fiber which is mined in North America is converted to commercial use in an industrial fa cility which is located only two miles from Somerset Hospital. The association between pulmonary cancer and asbestosis has been recognized at this institution for many years. The number of patients admitted with these conditions is difficult to determine, as in ear lier years many of them wire diagnosed as pulmo nary fibrosis or silicosis. The only accurate statis tics could be obtained from the autopsy material of the past decade, 1955 to 1965, when 1,330 autop sies were performed. In this group, there were 22 cases of bronchogenic cancer with pulmonary asbes tosis, as well as the 17 cases of mesothelioma. An interesting observation is that, despite the fact there were large numbers of women also employed at this industrial facility and many contracted as bestosis, there is only one female with mesothelio ma in our series, and she never worked in the as bestos plant but lived nearby. This experience is in contrast to other reported series, particularly those from South Africa where there was a significant number of females afflicted with mesothelioma. Newbouse and Thompson,'4 in studying the occu pational histories of 83 patients with mesothelio ma, noted that 42 of these patients were female. We might attribute our absence of femaJes involved with this disease due to a difference in occupational exposure between the male and female workers. However, other studies would not substantiate this, as there appears to be a high incidence of meso theliomas in people just living in the vicinity of the asbestos mines or industries. In Wagner's series from South Africa, more than half of the people had not been employed by the asbestos industry. These people had htd environmental exposure due to liv ing in the vicinity of the mills and dumps. The sta tistics from the London Hospital, as reported by Newhouse and Thompson14 are very much the same, with one half of the patients having only an en vironmental exposure to asbestos. With this infor mation, one wonders why we have not seen similar circumstances in our community, especially since there is a large asbestos dump adjacent to a resi dential area. Another interesting observation in our series is the fact that 16 of the 17 patients with mesothelio ma were diagnosed within the past three years. A re view of the autopsy material for the previous decade brought to light only one additional case which .initially had been misdiagnosed. Since the refine ment of the asbestos fiber has been one of the ma jor industries in this geographic area for over 60 years, it is difficult to explain why we are only now aware of this disease. One possible explanation is that in our group of patients, once the diagnosis was suspected, an intensified effort was made to obtain an autopsy when the patient died. However, prior to our recognition of this entity, patients with mesothelioma were most likely diagnosed as having a generalized carcinomatosis and little effort was made to obtain an autopsy when they did. Regard less whether this reasoning is correct or not, it is our distinct impression that there has been a defi nite increase in incidence.of this malignancy within the last few years. 1. Tubulopepiltary type mesothelioma (case 1, slightly reduced from x!20). 02 212 054294 JAMA. Aug 21. 1957 * V;' 2Z\. N: 3 p ' ./* >"? ix-` .# ./ /4 f *^ ` / . , * " ,'?' v*;,*-f-,-' - .. -. /.<v*, '->.: . ~ r vv. <l` ' '4 t~ v. . * *-*- . ^ /.V-. r--:=. .* -t ,, , *\ .. ^ t ` , s' ^ : v.'.1 2. Asbestosis of the lung (case 1, Xl20). Report of Cam Cab t.--A 52-year-old whit* min vu admitted to tb* hospital with increasing constipation, an enlarged abdomen of one month's duration, and an ill-defined abdominal pain. He had been retired with a medical disability from pulmo nary asbestosis after working 2S yean at an asbestos milL He suffered a myocardial infarction two yean before ad mission. He smoked only occasionally. Physical examination revealed a slightly emphysematous chest with harsh breath sounds and abdominal distention. No intra-abdominal masses could be palpated at that time. Chest x-ray of the lungs demonstrated basilar fibrosis, bilaterally, interpreted as most likely due to asbestosis. An anteroposterior x-ray film, without contrast material, of the abdomen demonstrated a ground glass appearance suggestive of asdtet. Some attenuation of the rectosig moid on the x-ray film taken after evacuation of the barium enema raised tne possibility of a pelvic main A paracentesis yielded approximately 1,500 ec of straw-col ored fluid. Surgical exploration revealed the visceral and parietal serosal surfaces to be studded with fin* papillary, almost granular-like, projections. A diagnosis of papilloma mesothelioma was made from a biopsy specimen (Fig 1). Following an intraperitoneal injeirtion of gold AU-19S, he remained symptom free and ascitic free for nine months. Fourteen months after surgery he died from a myocardial infarction. Autopsy examination revealed pleural cavities to be free of tumor. Pleural plaques were present at the bases and there were multiple adhesions. The lungs demonstrat ed bullae emphysema with an irregular delicate fibroeis throughout. The heart was enlarged with old ecarring and a fresh infarct. The peritoneal cavity yielded 1,000 cc of slightly mucoid yellowish fluid, and all the coelomic cav ity organs as well as the parietal peritoneum were cov ered with white hard nodules, varying from 5 am to 5 cm in diameter and having a mucoid appearance on the cut surface. In many areas there was a tendency for these nodules to coalesce to fora larger tumor msserr The tu mors did not penetrate for any appreciable be- 3. Serosel tumor encasing loops of bowel (case 2). ' 519 neath the surface, and all other organs were unremarkable. Microscopic examination demonstrated an extensive in terstitial fibrosis of the lungs with many asbestoe bodiw (Fig 3). The hypertrophied heart showed areas of fibrosis and acute necrosis. The tumor was characteristic of meso thelioma with cuboidal cells showing tome pleomorphism and superficial papillatioa. Cab 2-A $l-year<ld white man was admitted to Som erset Hospital because of abdominal pain. For 25 yean he was an employee at an asbestos refining plant He smoked less than one pack of cigarettes per day. Results of physical examination were normal, and all laboratory studies were unrevealing. Chest x-ray showed a fibrotic infiltration of both lower lobes. An upper gastro intestinal roentgenographic series demonstrated duodeni tis and gastritis. He was discharged on a regimen for ul cer convalescence only tb be readmitted seven months later with postprandial abdominal pain and a 10-lb weight loes. On palpation the abdomen appeared board-like, though there was no tenderness, and an extraluminal mass could be palpated through the anterior portion of the rectal wall. A barium enema demonstrated rigidity and narrowing of the sigmoid colon. At surgery, the abdominal cavity was found to be almost completely obliterated by large masses of neo plastic tissue which had enveloped the intra-abdominal or gans and was infiltrating the parietal peritoneum. A diag nosis of mesothelioma was mad* from a biopsy specimen The patient died (our months later. Pertment findings at autopsy included numerous large plaquAon the parietal pleura and congestion at the bases of both lungs. The peritoneal cavity was virtually obliterat ed by a large, yellowish-white hafld tumor whieh was com pletely encasing the abdominal organs (Fig 3). Except for this surface involvement the organs were unremark able. Microscopic examination demonstrated bronchial pneu monia with a mild pulmonary fibrosis and many asbestos bodies. The tumor consisted of fusiform cells in a hyaiinixed stroma with papillary formation characteristic of mesothelioma (Fig 4). Cab 3.-A 47-year-old white man was admitted to the hospital with a nonproductive cough and ill-defined dis comfort in the right lower lobe of the lung. The initial chest x-ray film was normal, but a second one taken two days before admission demonstrated a small pleural effu sion in the right costophrenic angle. Though he had been an insurance agent and more recently a liquor salesman, he had worked as a stock boy in an asbestos refining plant for 16 months. 24 yaan ago. Physical examination and complete work-up were unre vesting, including scalene node and two needle pleural biopsies. Thoracocentesis yielded 100 cc of straw<oiored fluid with some mceothelial cells. At exploratory thoraco tomy the patient was found to have a greatly thickened parietal and visceral pleura with encasement of e partial ly atelectatic lung. In certain areas the parietal and vis ceral pleura were intimately adherent to one another and could not be separated. There was no nodularity of the serosal surfaces. A diagnosis of pulmonary' asbestosis and mesothelioma was made {torn a biopsy specimen. Postoperatively be re ceived steroids and cobalt radiation with a poor response, and he died ten months later with bilateral pleural in volvement Clinical Features Our patients with peritoneal mesothelioma pre sented themselves in one of two ways. Four had as cites of unknown origin and the other three com* plained of vague abdominal pain and weight loss. In this latter gToup an ill-defined mass was usually palpated either through the abdominal wall or on rectal examination. Laboratory* work-up and roent genographic examination of the gastrointestinal JAMA Aug 21. 1967 # Vl 201, No S *5 990 MESOTHELIOMA AND AS8LSTOSIS--BOROV., CT AL tract were unrevealing. The diagnosis ytu made there is a coalaectnce of these nodules, so that cither by surgery or peritoneoscopy and biopsy, the terminal state usually consists of solid, broad, Tboae patients with ascites- were found to have thick hands wldch encompass the viscera and Ax *ma\\ papillary projections studding the visceral them within a dense mate Often the delineation and parietal peritoneum. The ascitic fluid varied between parietal and visceral peritoneum is lost, so from a clear syrupy to a thin straw-colored consis that the usual autopsy dissection is impossible duo 1 tency. Those patients with the palpable masses . to this encasement The tumor is generally white ware found on exploration to have complete ob and Arm and may have a mucinous appearance on literation of the peritoneal cavity by large tumor the cut surface._ trustee which were occupying most of the coeto- Histologic Characteristic*.-Vft have seen two mic cavity and invading the parietal peritoneum. major histologic types of mesothelioma. The most We believe that this picture is but the end stage of common variety is the epithelial form where there the disease, while those patients with ascites repre are cuboidal or polyhedral cells producing s tubulo- sent an earlier stage. This is substantiated by the papillary appearance or a solid group of cells with finding of papillary projections at surgery in several of our patients who having presented with ascites and in whom obliteration of the peritoneal cavity out a dear tubular formation. Usually there is a fair ly uniform cellular structure, but occasionally bizarre nudeated cells can be seen. Pathologic mito with large tumor masses developed later, as seen at tic cells are rarriy found, but doubly nucleated autopay. Patients with pleural mesotheliomas all present ed with varying degrees of chest pain and pleural and multinudeated tumor cells are often seen. The other variety is the mesenchymal or Abrous type of mesothelioma in which spindle cells are arranged effusion. A work-up was likewise unrewarding with in an almost fasdcular pattern within a stroma of the exception of positive findings from a pleural abundant hyaline collagen. Occasionally the cells biopsy in one patient The fluid in the pleural cavi may be aranged loosely in indistinct fasciculi or may ty varied from a gross bloody effusion to straw-col- ** occur in solid nests. The most striking histologic ored fluid, and the tumor involvement varied from characteristic of mesothelioma is the structural papillary projections on the parietal and visceral variation which may occur from area to area within pleura to a generalized thickened pleura. In areas the same tumor,*so that in one area the growth may the visceral and parietal pleura were intimiteiy ad have epithelial structure, while in another a purely herent and could be separated only with difficulty. mesenchymal appearance or in between combina Treatment with cobalt radiation therapy, radio tions. active gold and chromium, and chemotherapy, used alone or in combination, had little effect on the Pathogenesis course of this disease. Fifty percent of the patients The mode of action of asbestos in produdng neo suffering either from pleural or peritoneal meso plasia is at present poorly understood. Furthermore, thelioma died within one year and the remainder by a puzzling feature has been the presence of meso the second year. Criteria for Diagnosis thelioma in one mining area, while in another min ing area a few miles distant, the disease has as yet to be identified. There are two major mining dis Although it is now accepted that mesothelial tricts in the Republic of South Africa. In the north tumors of the serosal surfaces do exist and possess west Cape of Good Hope province, crocidolite is the a number of characteristics which justify their seg fiber mined, whereas in the Transvaal asbestos field, regation as an entity, the criteria for the identifica both crocidolite and more importantly amosite are tion of these tumors are stiff largely imprecise. The mined. Up to the present time there has been a currently accepted criteria for the diagnosis of these tumors are that: (1) The diagnosis should be ap plied to those groups which show an unequivocal 4. Spindle ceil type mesothelioma (ease 2. xW). predilection to spread along the serosal membranes, with either none or only a shallow invasion of the underlying organs. (2) All other sources for the tu mor have been excluded. <3) If metastases are pres ent, they should be limited to the regional lymph nodes, rarely occurring in liver, bone, and lung. Special staining or histologic techniques msy aid in a diagnosis of this disease. Wagner et aT* have suggested that metachromatic staining (removable by exposure to byaluronidase) within a tumor is strong evidence for the diagnosis of mesothelioma i in a patient Pathologic Characteristic*.-In the earlier stages, * * ** the tumor is made up of many small, rounded. Ann nodules on the visceral and parietal surfaces. Later, i f* j, '02 212 05 4 4 96 JAMA. Aug 21.196? Vot 201. No 8 I MESOTHELIOMA AND ASBE$TO$l$-BOROW CT AL 991 high prevalence of mesothelioma. of the pleura and peritoneum in northwest Cape of Gbod Hope. On the other hand no case as yet has been reported from the Transvaal asbestos area or its surround* ings. Sluis-Cremer" has studied the geographical and environmental differences in these two areas and has come to the conclusion that none of the fac tors examined explained satisfactorily the absence of mesothelioma in the Transvaal region. Other than for the mineralogic difference between the two areas, he found no variation in the intensity or length of production of these fields or in the extent of the environmental pollution and incidence of pul monary asbestosis. In North America, chrysotile is the main fiber mined although crocidolite and amosite are present in lesser amounts. Both pleura and peritoneal mesothelioma have been found in work' ers exposed to these fibers. Wagner*' in 1962 induced mesothelioma by inocu lating various dusts into the pleural cavity of rata. Pleural tumors developed in those inoculated with crocidolite, chrysotile, and a finely divided silicon powder (99.9% silicon dioxide). Recently Skidmore and Wagner*' showed that crocidolite, chrysotile, silica powder, and to a lesser extent, amosite, all induced pleural mesotheliomata in guinea pigs after interpleural injection. Peacock and Peacock" in duced malignant tumors in fowls with crocidolite and amosite. A number of hypotheses to explain the pathogenesis of this disease have been proposed, but none of them have been widely accepted. Hie first theory was that of physical irritation due to the presence of asbestos fibers deposited in the ter minal lymphatics of the serosal surfaces or dus to the migration of the asbestos fiber from the lung following inhalation or from the gut as a result of ingestion. Fibers have been demonstrated in a num ber of tissues, including parietal pleura, gastric mu cosa, and spleen, but there have been no reports of fibers in the peritoneal surfaces. Another concept is the auto-immune theory in which the presence of asbestos bodies in the lung is said to elicit the production of an abnormal globu lin. Up to the present time, there is little positive evidencs for this concept The serum of pttieat*. with either asbestosis or neoplasia shows only a lightly raised titer for the rheumatoid factor, and immunodkiorescent staining has not shown evidence of as antigen-antibody aggregate Recently, Har* ington and Rot** suggested that the carcinogenicity of asbestos may be related to the presence of nat ural and contaminated oils associated with the as bestos fiber or to certain carcinogenic metals or metal complexes in the fibers. They found that crocidolite and amosite contained appreciable amounts of natural oils. Furthermore, ail the as bestos fibers, including chrysotile, may contain sec ondary oils as a result of an addition of oil to the asbestos during the processing or as a result of con tamination. Furthermore, almost universally, the asbestos is transported and stored in jute bags and the oil from the jute fiber is absorbed to s great ex tent |k all three types of asbestos fiber. Bom chrysotile and amosite have t significant ferrous content, particularly tff certain macromolecular complexes of iron, gpch as iron-dextzan which is known to be highly carcinogenic in animals. The iron content of chrysotile is much lower than the other two fibers. It is proposed by Harington and Roe*9 that the carcinogenic agent or agents may n*L be the fiber themselves but either the natural oil or secondary oils which are present on the fiber and or possibly the iron complex. The authors are currently performing biologic tests for the carcinogenidty of these materials. However, these studies were in s preliminary form at the time of the report. Gantrie and Trade Names of Orug Gold Au 19S-.Auraotoid>2M, Aur*o<ope-Au 194. Auraoscea-191. Rtdietoid Colloidal Au 194, Aur--topo. ftoferanees 1. Rokitansky, C. Voc: Manuel of Path. Amt. Sydwhia Sac. Tran*. Landes p 265. ISM. 2. Brawn. WJ,, and Johnson. LG: Peat Inffammatory 'Tu mor*" of PIturn: 3 run a4 Pleural Fibroma of Interlobar FImu*. Milit Surg 109:415-425 <Oet) 196L 3. Willi*. R.A.: P*tholsy el Tumor*. Washington, DC* Butterworth Inc. 1960. p 185. 4. Ackerman. L.V.: Atlas of Tumor Pathology, Wsahtoftcn. DC: Armed Force* Inetitute of Pathoiefy, section S, part 23.1956. P 100. _ 5. Godwin. M.C: Diffuse Maootbalioau With Ccrnmont to Their Relation to Localized Fibrous Mreothiliomsi. Cancer 19: 290-319 (March-April) 1957. S. Winslow. D.4.. and Taylor. HA.: Malifnant Peritoneal Mesothelioma*. Concur 13:127-136 (Jeo-Feb) I960. 7. Wapner. J.C: S3etc*. C.A.: and March*ad. P,,* Diffuse Pleu ral Mesothelioma and Asbestosis Exposure to North Western Cepe Province. Brit J Jnduttr Med 17:260-271 (Oct) I960. 8. Warner. J.C: Epidemiolocy of Diffuse Meootbelto) Turnon: Evidence of ea Association From Studies in South Africa and Doited Kinpdem. Ann SY Acad Sei 131^75-578 (Doe 81) 1965. 9. Benaer. G.M.: Faulds. JS.. end Stewart. MJ.: Occupational Cancer cf Urinary Bladder u> Dyeetuffe Operatives and of Lunf to Asbestos Textile Workers and Iron Ore Minas. Amor J Clin Path 25:126-184 (Feb) 1955. 10. Mancueo. TT_ and Coulter. E.J.: Methodolofy in Industrial Health Studies. Areh Environ Health I10-226 (Feb) 1968. 11. Hourihsne. D.O- Ths Petboiofy of Mssothsliomsta sad JAMA Aug 21. 1967 Vpl 201. No t as Analysis of Their Aasodatioo With Asbestos Exposure. Thorax 19368-278 (May) 1964. 12. Enticknap. 43- and Smither. W.FJ.: Peritoneal Tumors to Asbestosis. Brit J loduttr Mod *120-31 (Jan) 1964 13. Selikoff. U.; Charf. 4a and Hammond. F.C: Relations Betwees Exposure to Asbestos end Mesothelioma. New* Eng 4 Mod 272560-565 (March) I960 14. Newhoum. ML. *ad Thompaom. *H.: Epidemiolofy f Maaothelial Tumor* is the Inratira Aron. Asa Mr' Acad Set 132: 579-568 (Doe 31) 1965. 15. Wafser. 4.C.; Monday, DJE.; and Kahnfton. 4S.: Hiato- chemical Demorutrstioo of Hyaluronic Add in Pleural -Maao- thritomes. 4 Path Baer 84:73-78 (July) 1962. 16. Sluis-Cremer. G.K.: Atoedosts in South Afriea. Certain Geofnphica] and Environ:ante) Ceodderadona. Asa NY Acad Sei 182*15-234 (Dec 81) 1966. 17. Wafner. 4.C.: Experimental Projection of Mesothelial Tu mours of the Pleura by Imptoatatzon of IXsta in Laboratory Animals. Nature 196:180-181 (Oct 18) 1962. 18. Wayner. J.C. and Skidmore. 4Ma Asbestos Dust Deposi tion and Retention to Rats. Ana NY Aend Set 138:77-86 (Dee 31) 1965. 19. Peacock. A. and Pmcock. PPL: Asbestos induced Tumors in Fault, abstract*. Fifth Annual Mootmr British Auonitioa lor Cancer. Scotland: R- & Edtotovfh. 1964. 20. Harinften. 4&. and Roe. TJCa Btudie* of Carrinofseens of Asbestos Fibers sod Their Natural Oft* am w Set 132: 43~i0,D",l,u"- 02 212 0545 SI