Document peeGz9b7Q2QLRgBX5vnO0G3vB

effect was not ron^C, which )-ai^Pacridine SCE induction aver, the differ-aken into conyte test system flying the acriof the results, technical assis- ler Programme of sub-populations 31-prophase of the v. Hum. Genet., 35 elds in the human and^ajl kinetics in n cu^H measured unda, XII. Biologic s, Arch. Immunol. >. A search for antiaminoacridines and chromatids. Nature -nosome aberration sU, 9 (1977) 289-- f phytohaemagglu7--376. lanees of restricted biting compounds. 51 (1977) 1725-- Mutation Research, 67 (1979) 97--100 Elsevier/North-Holland Biomedical Press %M 97 Short Communication COMPARATIVE EVALUATION OF THE FREQUENCY OF CHROMOSOMAL ABERRATIONS AND THE SCE NUMBERS IN PERIPHERAL LYMPHOCYTES OF WORKERS OCCUPATIONALLY EXPOSED TO VINYL CHLORIDE MONOMER M. KUCEROVA. Z. POLIVKOVA and J. BATORA * Pediatric Department of Postgraduate Medical Institute, Institute of Hygiene and Epidemiology, Prague, Srobaroua 48 (Czechoslovakia) (Received 31 March 1978) (Revision received 15 November 1978) (Accepted 23 November 1978) There are now available plenty of authorative data on the carcinogenic [1--3, 13] and mutagenic [1,2,10] activity of vinyl chloride monomer. Increased frequency of chromosomal aberrations detectable in peripheral lymphocytes of chronically exposed workers has been reported by numerous authors [4--6, 11,12]. We have repeatedly analysed, using routine cytogenetic techniques [8], 3 blood samples from each of 9 workers occupationally exposed for 10--27 years to relatively high mean annual doses of vinyl chloride monomer (about 20--150 ppm of air). In the third blood sample series we also used the SCE technique [14] and compared the frequency of detected chromosomal aberrations with the number of SCEs in each sample. The blood samples from 8 healthy persons were used as controls and were collected with the 3rd blood sampling from the vinyl chloride (VC) workers. The control persons were matched for age and sex and they were not exposed to known mutagens during 3 months before the time of blood collection. The results are summarized in three tables. Tables 1 and 2 show the instabil ity and non-homogeneity in the frequency of chromosomal aberrations over a period of two years. Mostly chromatid and chromosome breaks were detected; chromatid and chromosome exchanges occurred only sporadically. Table 2 compares the frequency of chromosomal aberrations and the num ber of SCE per cell in 7 blood samples. There is an apparent increase in both parameters in comparison with control levels. The mathematical evaluation of our results was calculated only for the 3rd collection. Conventional aberrations in VC workers were non-homogeneous. * District Hygienic Station. Prievjdza. 98 tablei CHROMOSOMAL ANALYSES OF 9 WORKERS OCCUPATIONALLY EXPOSED TO VINYL CHLO RIDE (TYPES OF ABERRATION) Exposure (years) Aberrant cell* (%> Number of chromatid breaks /l 00 cells Number of chromatid exchange* /100 cell* Number of chromoeome break* /100 cell* Number of chromoeome exchange* /100 cell* Number of deipirahzalion* /100 cell* E.H. 1 11 5 1 4 25--27 2 0 0 0 0 3 11 5 0 4 01 00 30 JJ\ 14 4 0 0 16--18 2 2 0 0 1 32 1 0 0 00 10 10 K.K. 12 2 0 0 0 0 16--17 2 7 6 1 0 0 0 33 3 0 0 0 0 A.H. 11 1 0 0 00 14-16 2 1 1 0 0 0 0 36 2 0 4 0 0 M.M. 10 0 0 0 13--15 2 1 0 0 0 37 3 0 4 00 10 00 EJ. 13 1 1 0 12-14 2 6 4 0 2 3 11 2 1 8 10 00 00 J.K. 11 0 0 1 00 12-14 2 4 3 0 1 00 33 3 0 0 0 0 F.M. 11 1 0 0 0 0 11--13 2 2 1 0 1 00 31 1 0 0 0 0 A.T. 1 10--12 2 3 8 controls (mean) 4 1 3 i!b 2 0 0 1 0 0 0 0 1 01 1 00 3 00 0.8 0.2 0 The frequency of SCEs was significantly higher in cells of VC workers in com parison with controls. The level of significance was P < 0.001, according to the t test. The detailed control data are in Table 4. The medical histories, and the smoking and drinking habits of workers tested are presented in Table 3. Smok ing and other habits of workers appeared to have no effect on the frequency of any chromosomal changes. Our positive results are contradictory to findings reported by Hansteen [7] who did not observe any increase either in the frequency of aberrations or in the SCE numbers. However, the subjects examined by this author had been exposed to very low doses of vinyl chloride (0.1 ppm) and only for the rela tively short period of two years. This can be taken as a further proof that VCM- TABLE 2 CHROMOSOM RIDE Expi year E.H. J.P. K.K. A.H. M.M. EJ. J.K, F.M, A.T. 251615-- 14131212-- 11- 10- 31 '& (me. fio b wet CO were O antly o -p* 03 a00t 3 ch /I cl uur resi routine am mutagenici The sensiti about the TABLE 3 MEDICAL HU E.H. J.P. K.K. A.H. M.M. EJ. J.K. F.M. A.T. NYL CHLONuffiher. of desplrali rations /100 cellt rs in com ing to the , and the 3. Smokquency of isteen [7] ions or in had been : the relahat VCM- 99 TABLE 2 CHROMOSOMAL ANALYSES OF 9 WORKERS OCCUPATIONALLY EXPOSED TO VINYL CHLO RIDE Exposure 1st collection 2nd collection 3rd collection yean ppm <%) E.H. J.P. K.K. A.H. M.M. EJ. J.K. F.M. A.T. 25--27 16--18 15--17 14--16 13--15 12--14 12--14 11--13 10--12 Mean 8 controls (mean) 20--150 20--80 15--70 20-1 50 20--90 20-150 20--90 20--90 20--90 11 4 2 i 0 3 i i 4 0 2 7 i i 6 4 2 i aberrant cells (%)* ii 2 3 6 76 11 e 3 1 3 5.2 + 1.3 1.8 + 0.4 SCE/ccll b 17.60 c 9.56 16.02 c -- 15.26 c 16.41 c 10.60 12.22 e 13.80 1.13 9.41 + 0.40 * 100 cells were scored per sample, b 50 cells were scored per sample. c Significantly increased in comparison with control values. induced chromosomal changes depend both on dose and length of exposure to the vinyl chloride monomer. Our results seem to lead to a conclusion that the two cytogenetic methods -- routine and SCE -- are equally suitable for testing of high-dose vinyl chloride mutagenicity in vivo. The increase of SCEs in our results is more homogeneous. The sensitivities of the two methods to detect mutagenic activity seem to be about the same. TABLE 3 MEDICAL HISTORY, AND SMOKING AND DRINKING HABITS OF WORKERS TESTED Diagnostic radiation Smoking Drinking Drugs E.H. J.P. K.K. A.H. M.M. EJ, J.K. F.M. A.T. - + -- -- -- -- -- + 4 Meprobamat Papaverin 4 ++ Chloramphenicol --4 Syntophyllin -- --4 --4 44 --4 Solutan Syntophyllin -- Bellaspon -- 4+ t* Superpyrin Thiospasmin --4 Ketaron 100 TABLE 4 CHROMOSOMAL ANALYSIS OF 8 CONTROLS M.K. J.K. V.B. J.. K.B. M.Ku. 2.P. R.S. Mean Aberrant cells * (*) 3 0 3 3 i 1 2 1 1.8 0.4 SCE/cell b Smoking 10.88 8.22 10.30 10.16 10.46 8.26 7.94 9.02 9.41 0.40 -- * 44 44 -- -- 4 -- Drinking -- 4 4 -- -- -- 4 * 100 cells were scored per sample, b &o cells were scored per sample. The controls were not exposed to X-rays and drugs at the time of blood collection. References 1 Bartsch. H., C. Malaveille and R. Montcsano, Human, rat and mouse liver-mediated mutagenicity of vinyl chloride in S. typhimurium strains. Int. J. Cancer, 15 (1975) 429--437. 2 Bartsch, H., and R. Montesano, Mutagenic and carcinogenic effects of vinyl chloride. Mutation Res., 32(1975) 93-114. 3 Creech, J.L., and M.N. Johnson, Angiosarcoma of the liver in the manufacture of polyvinyl chloride, J. Occup. Med,, 16 (1974) 150--151. 4 Ducatman, V., K. Hirschhom and I.J. Selikoff, Vinyl chloride exposure and human chromosome aber rations, Mutation Res., 31 (1975) 163--169. 5 Funes-Craviolo. F,, B. Lambert, J. Lindsten, L. Ehrenberg, A.T. Natarajan and S. Osterm an-Golkar, Chromosome aberrations in workers exposed to vinyl chloride. Lancet, 1 (1975) 459. 6 Hansteen. I.L.. L, Hillestad and E, Thiis-Evensen, Chromosome studies in workers exposed to vinyl chloride. Mutation Res., 38 (1976) 112. 7 Hansteen. I.L., Chromosome breakage frequency and sister chromatide exchanges in PVC workers two years after exposure, A follow-up study. Abstract of 6th International Chromosome Conference, Helsinki, August 1977. 8 Hungerford. D.A., Leukocytes cultured from small inocula of whole blood and preparation of meta phase chromosomes by treatment with hypotonic KC1, Stain Technol.. 40 (1965) 333--338. 9 Kucerova, M., Cytogenetic analysis of human chromosomes and its value for the estimation of genetic risk. Mutation Res., 41 (1976) 123--130. 10 Loprieno, N.. R. Barale, S. Baroncelli, C. Bauer, G. Bronzetti, A. Cammellini, G, Cercignani, C. Coral, G. Gervasi, C. Leporini, R. Nieri, A.M. Rossi, G. Stretti and G. Turchi, Evaluation of the genetic effects induced by vinyl chloride monomer (VCM) under mammalian metabolic activation: in vitro and in vivo studies. Mutation Res., 40 (1976) 85--96. 11 Purchase, I.F.H., C. Richardson and D. Anderson, Chromosomal and dominant lethal effects of vinyl chloride. Lancet, II (1975) 410--411. 12 Purchase, I.F.H., C. Richardson and D. Anderson, Chromosomal effects in peripheral lymphocytes, Proc. Roy. Soc. Med.. 69 (1976) 290--291. 13 Viola, P.L., A. Bigotti and A. Caputo, Oncogenic response of rat skin, lungs and bones to vinyl chlo ride. Cancer Res., 31 (1971) 516--522. 14 Wolff, S.. and P. Perry. Differential Giemsa staining of sister chromatids and the study of sister chro matid exchanges without autoradiography. Chromosoma, 48 (1974) 341--353. Subst Am Advei