Genetic Bioassay Data on Some Known or Suspected Human Carcinogens

  • Michael D. Waters
  • Neil E. Garrett
  • Christine M. Covone-de Serres
  • Barry E. Howard
  • H. Frank Stack
Chapter

Abstract

The purpose of this report is to summarize the currently available qualitative information, obtained from genetic and related bioassay systems, on 24 agents or groups of agents. These agents have been classified by the International Agency for Research on Cancer (IARC) as (1) known human carcinogens, (2) probable human carcinogens, or (3) unclassified carcinogens.1,2 The intent is to examine the performance of genetic bioassay systems in the detection and evaluation of compounds for which there is some evidence of human carcinogenic potential. These compounds are of particular interest, in a retrospective sense, for purposes of relating evidence of carcinogenic effects in man and in experimental animals with the qualitative data base being assembled using short-term genetic bioassays. Ideally, it would be important to determine the quantitative response of genetic bioassays as a function of chemical dose and to relate these responses to quantitative evidence of carcinogenic and mutagenic effects in experimental animals. Such a quantitative evaluation is essential if we are to properly select from among the many chemicals active in short-term genetic bioassays those that should be subjected to further evaluation. Ultimately, quantitative evaluations of genetically mediated effects must be coupled with accurate estimates of dose to the DNA, since this combination of information forms the basis of all current models for quantitative risk assessment.

Keywords

Ethylene Oxide Vinyl Chloride Human Carcinogen Micronucleus Test Vinyl Chloride Monomer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    IARC, “Chemicals and Industrial Processes Associated with Cancer in Humans,” Supplement I to Vols. 1–20 of IARC Monographs IARC, Lyon, France (1979).Google Scholar
  2. 2.
    IARC Working Group, An evaluation of chemicals and industrial processes associated with cancer in humans based on human and animal data: IARC Monographs 1 to 20, Cancer Res. 40: 1 (1980).Google Scholar
  3. 3.
    S. Green and A. Auletta, Editorial introduction to the reports of “The Gene-Tox Program.” An evaluation of bioassays in genetic toxicology, Mutat. Res. 76: 165 (1980).PubMedCrossRefGoogle Scholar
  4. 4.
    M. D. Waters and A. Auletta, The GENE-TOX Program: Genetic activity evaluation, J. Chem. Inf. Comput. Sci. 21: 35 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    B. S. Pasternack, R. E. Shore, and R. E. Albert, Occupational exposure to chloromethyl ethers, J. Occup. Med. 19: 741 (1977).PubMedGoogle Scholar
  6. 6.
    A. M. Thiess, W. Hey, and H. Zeller, Zur toxikologie von dichlordimethylather-Verdacht auf kanzerogene wirkung auch beim menschen, Zbl. Arbeitsmed. 23: 97 (1973).PubMedGoogle Scholar
  7. 7.
    IARC Monographs, Vol. 4, IARC, Lyon, France (1974), pp. 231–245.Google Scholar
  8. 8.
    W. G. Figueroa, R. Raszkowski, and W. Weiss, Lung cancer in chloromethyl methyl ether workers, New England J. Med. 288: 1096 (1973).Google Scholar
  9. 9.
    D. Anderson and J. A. Styles, An evaluation of 6 short-term tests for detecting organic chemical carcinogens. Appendix II. The bacterial mutation test, Br. J. Cancer 37:924 (1978).Google Scholar
  10. 10.
    B. C. Casto, Detection of chemical carcinogens and mutagens in hamster cells by enhancement of adenovirus transformation, in: “Mammalian Cell Transformation by Chemical Carcinogens,” N. Mishra, V. Dunkel, and M. Mehlman, eds., Advances in Modern Environmental Toxicology Vol. 1, Princeton Junction, NJ (1981), p. 241.Google Scholar
  11. 11.
    S. Wada, M. Miyanish, Y. Nishimoto, S. Kambe, and R. W. Miller, Mustard gas as a cause of respiratory neoplasia in man, Lancet 1: 1161 (1968).PubMedCrossRefGoogle Scholar
  12. 12.
    J. E. Norman, Lung cancer mortality in World War I veterans with mustard-gas injury: 1919–1965, JNCI 54: 311 (1975).Google Scholar
  13. 13.
    R. A. Case and A. J. Lea, Mustard gas poisoning, chronic bronchitis and lung cancer: Investigation into the possibility that poisoning by mustard gas in 1914–18 war might be a factor in production of neoplasia, Br. J. Prey. Soc. Med. 9: 62 (1955).Google Scholar
  14. 14.
    R. L. Capizzi, B. Papirmeister, J. M. Mullins, and E. Cheng, The detection of chemical mutagens using the L5178Y/Asn murine leukemia in vitro and in a host-mediated assay, Cancer Res. 34: 3073 (1974).PubMedGoogle Scholar
  15. 15.
    C. M. Stevens and A. Mylroie, Biological action of ‘mustard gas’ compounds. Mutagenic activity of beta-chloroalkyl amines and sulphides, Nature 166: 1019 (1950).PubMedCrossRefGoogle Scholar
  16. 16.
    C. Auerbach and J. M. Robson, The production of mutations by chemical substances, Proc. Royal Soc. Edinburgh Sect. B 62: 271 (1947).Google Scholar
  17. 17.
    l7. P. D. Lawley and P. Brookes, Cytotoxicity of alkylating agents towards sensitive and resistant strains of Escherichia coli in relation to extent and mode of alkylation of cellular macromolecules and repair of alkylation lesions in deoxyribonucleic acids, Biochem. J. 109: 433 (1968).Google Scholar
  18. 18.
    D. Scott, M. Fox, and B. W. Fox, The relationship between chromosomal aberrations, survival and DNA repair in tumour cell lines of differential sensitivity to X-rays and sulphur mustard, Mutat. Res. 22: 207 (1974).PubMedCrossRefGoogle Scholar
  19. 19.
    I. I. Oster, Interactions between ionizing radiation and chemical mutagens, Z. Indukt. Abstamm. Vererbungsl. 89:1 (1958).Google Scholar
  20. 20.
    P. Milvy and M. Wolff, Mutagenic studies with acrylonitrile, Mutat. Res. 48: 271 (1977).PubMedCrossRefGoogle Scholar
  21. 21.
    M. N. Rabello-Gay and A. E. Ahmed, Acrylonitrile: In vivo cytogenetic studies in mice and rats, Mutat. Res. 79:249 (.1980).Google Scholar
  22. 22.
    Pestic. Toxic Chem. News 5:21 (1977).Google Scholar
  23. 23.
    National Institute for Occupational Safety and Health, “A Recommended Standard for Occupational Exposure to Acrylonitrile,” Publication 78–116, Department of Health, Education and Welfare, Cincinnati, OH (1978).Google Scholar
  24. 24.
    A. M. Thiess and I. Fleig, Analysis of chromosomes of workers exposed to acrylonitrile, Arch. Toxicol. 41: 149 (1978).PubMedCrossRefGoogle Scholar
  25. 25.
    M. T. O’Berg, Epidemiologic study of workers exposed to acrylonitrile, J. Occup. Med. 22: 245 (1980).PubMedGoogle Scholar
  26. 26.
    J. B. Werner and J. T. Carter, Mortality of United Kingdom acrylonitrile polymerization workers, Br. J. Ind. Med. 38: 247 (1981).PubMedGoogle Scholar
  27. 27.
    C. de Meester, F. Poncelet, M. Roberfroid, and M. Mercier, Mutagenicity of acrylonitrile, Toxicology 11: 19 (1978).PubMedCrossRefGoogle Scholar
  28. 28.
    S. Venitt, C. T. Bushell, and M. Osborne, Mutagenicity of acrylonitrile (cyanoethylene) in Escherichia coli, Mutat. Res. 45: 283 (1977).PubMedCrossRefGoogle Scholar
  29. 29.
    M. Lambotte-Vandepaer, M. Duverger-van Bogaert, C. de Meester, F. Poncelet, and M. Mercier, Mutagenicity of urine from rats and mice treated with acrylonitrile, Toxicology 16: 67 (1980).PubMedCrossRefGoogle Scholar
  30. 30.
    R. A. Parent and B. C. Casto, Effect of acrylonitrile on primary Syrian golden hamster embryo cells in culture: Transformation and DNA fragmentation, JNCI 62: 1025 (1979).PubMedGoogle Scholar
  31. 31.
    J. Hutchinson, Br. Med. J. 11:1280 (1887); J. Hutchinson, Trans. Path. Soc. London 39: 352 (1888).Google Scholar
  32. 32.
    R. J. Pye-Smith, Proc. Royal Soc. Med. Clin. Sect. 6: 229 (1913).Google Scholar
  33. 33.
    O. Neubauer, Arsenical cancer: A review, Br. J. Cancer 1: 192 (1947).Google Scholar
  34. 34.
    M. Kuratsune, S. Tokudome, T. Shirakusa, M. Yoshida, Y. Tokumitsu, T. Hayano, and M. Seita, Occupational lung cancer among copper smelters, Int. J. Cancer 13: 552 (1974).PubMedCrossRefGoogle Scholar
  35. 35.
    P. O. Wester, D. Brune, and G. Nordberg, Arsenic and selenium in lung, liver, and kidney tissue from dead smelter workers, Br. J. Ind. Med. 38: 179 (1981).PubMedGoogle Scholar
  36. 36.
    IARC Monographs Vol. 23, IARC, Lyon, France (1980), pp. 39–141.Google Scholar
  37. 37.
    A. Leonard and R. R. Lauwerys, Carcinogenicity, teratogenicity and mutagenicity of arsenic, Mutat. Res. 75: 49 (1980).PubMedCrossRefGoogle Scholar
  38. 38.
    W. J. Blot and J. F. Fraumeni, Jr., Arsenical air pollution and lung cancer, Lancet 2: 142 (1975).PubMedCrossRefGoogle Scholar
  39. 39.
    G. M. Matanoski, E. Landau, and J. Seifter, “Cancer Mortality in an Industrial Area of Baltimore,” U.S. Environmental Protection Agency (in press).Google Scholar
  40. 40.
    C. E. Piper, N. E. McCarroll, and T. J. Oberly, Mutagenic activity of an organic arsenical compound detected with L5178Y mouse lymphoma cells, Environ. Mutagen. 1:165 (1978).Google Scholar
  41. 41.
    H. Nishioka, Mutagenic activities of metal compounds in bacteria, Mutat. Res. 31: 185 (1975).PubMedCrossRefGoogle Scholar
  42. 42.
    G. Dugatova, S. Podstavkova, and M. Trebaticka, Influence of arsenic on Drosophila melanogaster. II. Test on recessive lethal and other mutations affecting vitality and located in X chromosome and on the occurrence of chromosome aberations, Acta F.R.N. Univ. Comend. Genetica 9:79 (1978).Google Scholar
  43. 43.
    R. Valencia, “Mutagenesis Screening of Pesticides Using Drosophila” (unpublished).Google Scholar
  44. 44.
    V. F. Simmon, A. D. Mitchell, and T. A. Jorgenson, “Evaluation of Selected Pesticides as Chemical Mutagens: In Vitro and In Vivo Studies,” EPA–600/1–77–028, U.S. Environmental Protection Agency (1977).Google Scholar
  45. 45.
    W. Burgdorf, K. Kurvink, and J. Cervenka, Elevated sister-chromatid exchange rate in lymphocytes of subjects treated with arsenic, Hum. Genet. 36: 69 (1977).PubMedCrossRefGoogle Scholar
  46. 46.
    R. J. Sram, Relationship between acute and chronic exposures in mutagenicity studies in mice, Mutat. Res. 41: 25 (1976).PubMedCrossRefGoogle Scholar
  47. 47.
    J. Petres, D. Baron, and M. Hagedorn, Effects of arsenic cell metabolism and cell proliferation: Cytogenetic and biochemical studies, Environ. Health Perspect. 19:223 (1977).Google Scholar
  48. 48.
    K. Nakamuro and Y. Sayato, Comparative studies of chromosomal aberration induced by trivalent and pentavalent arsenic, Mutat. Res. 88: 73 (1981).PubMedCrossRefGoogle Scholar
  49. 49.
    M. De Brabander, R. Van deVeire, F. Aerts, S. Geuens, and J. Hoebeke, A new culture model facilitating rapid quantitative testing of mitotic spindle inhibition in mammalian cells, JNCI 56: 357 (1976).PubMedGoogle Scholar
  50. 50.
    J. A. DiPaolo and B. C. Casto, Quantitative studies of in vitro morphological transformation of Syrian hamster cells by inorganic metal salts, Cancer Res. 39: 1008 (1979).PubMedGoogle Scholar
  51. 51.
    B. C. Casto, J. Meyers, and J. A. DiPaolo, Enhancement of viral transformation for evaluation of the carcinogenic or mutagenic potential of inorganic metal salts, Cancer Res. 39: 193 (1979).PubMedGoogle Scholar
  52. 52.
    Bureau of National Affairs, Inc., National Wildlife Federation seeks defense phase-out of cadmium dust, Environ. Reporter Aug. 29:703 (1975).Google Scholar
  53. 53.
    IARC Monographs Vol. 2, IARC, Lyon, France (1972), pp. 74–99.Google Scholar
  54. 54.
    IARC Monographs, Vol. 11, IARC, Lyon, France (1976), pp. 39–74.Google Scholar
  55. 55.
    C. L. Potts, Cadmium proteinuria-The health of battery workers exposed to cadmium oxide dust, Ann. Occup. Hyg. 8:55 (1965).Google Scholar
  56. 56.
    M. D. Kipling and J. A. H. Waterhouse, Cadmium and prostatic carcinoma, Lancet 1: 730 (1967).CrossRefGoogle Scholar
  57. 57.
    R. Lernen, J. S. Lee, J. K. Wagoner, and H. P. Blejer, Cancer mortality survey of workers exposed to cadmium, Ann. N.Y. Acad. Sci. 271: 273 (1976).CrossRefGoogle Scholar
  58. 58.
    L. N. Kolonel, Association of cadmium with renal cancer, Cancer 37: 1782 (1976).PubMedCrossRefGoogle Scholar
  59. 59.
    W. R. Bruce and J. A. Heddle, The mutagenic activity of 61 agents as determined by the micronucleus, Salmonella and sperm abnormality assays, Can. J. Genet. Cytol. 21: 319 (1979).PubMedGoogle Scholar
  60. 60.
    A. W. Hsie, J. P. O’Neill, J. R. San Sebastian, D. B. Couch, P. A. Brimer, W. N. C. Sun, J. C. Fuscoe, N. L. Forbes, R. Machanoff, J. C. Riddle, and M. H. Hsie, Quantitative mammalian cell genetic toxicology: Study of the cytotoxicity and mutagenicity of seventy individual environmental agents related to energy technologies and three subfractions of a crude synthetic oil in the CHO/HGPRT system, in: “Application of Short-Term Bioassays in the Fractionation and Analysis of Complex Environmental Mixtures,” M. D. Waters, S. Nesnow, J. L. Huisingh, S. S. Sandhu, and L. Claxton, eds., Plenum Press, New York (1978), P. 291.Google Scholar
  61. 61.
    N. Kanematsu, M. Hara, and T. Kada, Rec assay and mutagenicity studies on metal compounds, Mutat. Res. 77: 109 (1980).PubMedCrossRefGoogle Scholar
  62. 62.
    L. L. Deaven and E. W. Campbell, Factors affecting the induction of chromosomal aberrations by cadmium in Chinese hamster cells, Cytogenet. Cell Genet. 26: 251 (1980).PubMedCrossRefGoogle Scholar
  63. 63.
    D. W. R. Bleyl and H. J. Lewerenz, Dominant lethal test in the mouse with repeated oral application of cadmium chloride, Arch. Exp. Vet. Med. Leipzig 34: 399 (1980).Google Scholar
  64. 64.
    N. Gilliavod and A. Leonard, Mutagenicity tests with cadmium in the mouse, Toxicology 5: 43 (1975).PubMedCrossRefGoogle Scholar
  65. 65.
    S. Sutou, K. Yamamoto, H. Sendota, and M. Sugiyama, Toxicity, fertility, teratogenicity, and dominant lethal tests in rats administered cadmium subchronically. II. Fertility, teratogenicity, and dominant lethal tests, Ecotoxicol. Environ. Safety 4:51 (1980).Google Scholar
  66. 66.
    H. A. Schroeder, A sensible look at air pollution by metals, Arch. Environ. Health 21:798 (1970).Google Scholar
  67. 67.
    A. M. Baetjer, Pulmonary carcinoma in chromate workers. I. A review of literature and report of cases, Arch. Ind. Hyg. 2:487 (1950).Google Scholar
  68. 68.
    A. M. Baetjer, Pulmomary carcinoma in chromate workers. II. Incidence on basis of hospital records, Arch. Ind. Hyg. 2: 505 (1950).Google Scholar
  69. 69.
    W. Machle and F. Gregorius, Cancer of the respiratory system in the United States chromate-producing industry, Pub. Health Rep. (Washington) 63: 1114 (1948).CrossRefGoogle Scholar
  70. 70.
    P. L. Bidstrup and R. A. M. Case, Carcinoma of the lung in workmen in the bichromates-producing industry in Great Britain, Br. J. Ind. Med. 13: 260 (1956).PubMedGoogle Scholar
  71. 71.
    M. R. Alderson, N. S. Rattan, and L. Bidstrup, Health of workmen in the chromate-producing industry in Britain, Br. J. Ind. Med. 38: 117 (1981).PubMedGoogle Scholar
  72. 72.
    Y. Ohsaki, S. Abe, K. Kimura, Y. Tsuneta, H. Mikami, and M. Murao, Lung cancer in Japanese chromate workers, Thorax 33: 372 (1978).Google Scholar
  73. 73.
    F. L. Petrilli and S. De Flora, Toxicity and mutagenicity of hexavalent chromium on Salmonella typhimurium, Appl. Environ. Microbiol. 33:805 (1977).Google Scholar
  74. 74.
    E. R. Nestmann, T. I. Matula, G. R. Douglas, K. C. Bora, and D. J. Kowbel, Detection of the mutagenic activity of lead chromate using a battery of microbial tests, Mutat. Res. 66: 357 (1979).PubMedCrossRefGoogle Scholar
  75. 75.
    S. Bonatti, M. Meini, and A. Abbondandolo, Genetic effects of potassium dichromate in Schizosaccharomyces pombe, Mutat. Res. 38:147 (1976).Google Scholar
  76. 76.
    I. Knudsen, The mammalian spot test and its use for the testing of potential carcinogenicity of welding fume particles and hexavalent chromium, Acta Pharmacol. Toxicol. 47:66 (1980).Google Scholar
  77. 77.
    G. Raffetto, S. Parodi, C. Parodi, M. De Ferrari, R. Troiano, and G. Brambilla, Direct interaction with cellular targets as the mechanism for chromium carcinogenesis, Tumori 63: 503 (1977).PubMedGoogle Scholar
  78. 78.
    R. F. Whiting, H. F. Stich, and D. J. Koropatnick, DNA damage and DNA repair in cultured human cells exposed to chromate, Chem.-Biol. Interact. 26:267 (1979).Google Scholar
  79. 79.
    W. D. Macrae, R. F. Whiting, and H. F. Stich, Sister chromatid exchanges induced in cultured mammalian cells by chromate, Chem.-Biol. Interact. 26:281 (1979).Google Scholar
  80. 80.
    A. G. Levis and F. Majone, Cytotoxic and clastogenic effects of soluble chromium compounds on mammalian cell cultures, Br. J. Cancer 40: 523 (1979).PubMedCrossRefGoogle Scholar
  81. 81.
    M. Umeda and M. Nishimura, Inducibility of chromosomal aberrations by metal compounds in cultured mammalian cells, Mutat. Res. 67: 221 (1979).PubMedCrossRefGoogle Scholar
  82. 82.
    L. Fabry, Relationship between the induction of micronuclei in marrow cells by chromium salts and their carcinogenic properties, C.R. Soc. Biol. 174: 889 (1980).Google Scholar
  83. 83.
    D. Wild, Cytogenetic effects in the mouse of 17 chemical mutagens and carcinogens evaluated by the micronucleus test, Mutat. Res. 56: 319 (1978).PubMedCrossRefGoogle Scholar
  84. 84.
    L. J. Cralley, R. G. Keenan, and J. R. Lynch, Exposure to metals in the manufacture of asbestos textile products, Am. Ind. Hyg. Assoc. J. 28: 452 (1967).PubMedCrossRefGoogle Scholar
  85. 85.
    F. W. Sunderman, Jr., A review of the carcinogenicities of nickel, chromium and arsenic compounds in man and animals, Prey. Med. 5: 279 (1976).CrossRefGoogle Scholar
  86. 86.
    R. Doll, Cancer of the lung and nose in nickel workerPrey. Br. J. Ind. Med. 15: 217 (1958).PubMedGoogle Scholar
  87. 87.
    R. Doll, L. G. Morgan, and F. E. Speizer, Cancers of the lung and nasal sinuses in nickel workers, Br. J. Cancer 24: 623 (1970).PubMedCrossRefGoogle Scholar
  88. 88.
    E. Pedersen, A. C. Hogetveit, and A. Anderson, Cancer of respiratory organs among workers at a nickel refinery in Norway, Int. J. Cancer 12: 32 (1973).PubMedCrossRefGoogle Scholar
  89. 89.
    J. A. Virtue, The relationship between the refining of nickel and cancer of the nasal cavity, Can. J. Otolaryng. 1: 37 (1972).Google Scholar
  90. 90.
    IARC Monographs Vol. 2, IARC, Lyon, France (1973), pp. 126–149.Google Scholar
  91. 91.
    IARC Monographs Vol. 11, IARC, Lyon, France (1976), pp. 75–112.Google Scholar
  92. 92.
    J. E. Cox, R. Doll, W. A. Scott, and S. Smith, Mortality of nickel workers: Experience of men working with metallic nickel, Br. J. Ind. Med. 38: 235 (1981).PubMedGoogle Scholar
  93. 93.
    E. Mastromatteo, Nickel: A review of its occupational health aspects, J. Occup. Med. 9: 127 (1967).PubMedCrossRefGoogle Scholar
  94. 94.
    F. W. Sunderman, Nickel carcinogenesis, in: “Nickel,” F. W. Sunderman, Jr., F. Coulston, G. L. Eichorn, J. A. Fellows, E. Mastromatteo, H. T. Reno, and M. H. Samitz, eds., National Academy of Science, Washington, DC (1975), p. 144.Google Scholar
  95. 95.
    M. H. L. Green, W. J. Muriel, and B. A. Bridges, Use of a simplified fluctuation test to detect low levels of mutagens, Mutat. Res. 38: 33 (1976).Google Scholar
  96. 96.
    V. W. Buselmaier, G. Rohrborn, and P. Propping, Mutagenicity investigations with pesticides in the host-mediated assay and the dominant lethal test in mice, Biol. Zbl. 91: 311 (1972).Google Scholar
  97. 97.
    M. Nishimura and M. Umeda, Induction of chromosomal aberrations in cultured mammalian cells by nickel compounds, Mutat. Res. 68: 337 (1979).PubMedCrossRefGoogle Scholar
  98. 98.
    S. H. H. Swierenga and P. K. Basrur, Effect of nickel on cultured rat embryo muscle cells, Lab. Invest. 19: 663 (1968).PubMedGoogle Scholar
  99. 99.
    K. M. Lynch and W. A. Smith, Pulmonary asbestosis: Carcinoma of the lung in asbestos-silicosis, Am. J. Cancer 24: 56 (1935).Google Scholar
  100. 100.
    S. R. Gloyne, Two cases of squamous carcinoma of the lung occurring in asbestosis, Tubercle 17: 5 (1935).CrossRefGoogle Scholar
  101. 101.
    R. Doll, Mortality from lung cancer in asbestos workers, Br. J. Ind. Med. 12: 81 (1955).PubMedGoogle Scholar
  102. 102.
    J. C. Wagner, C. A. Sleggs, and P. Marchand, Diffuse plural mesothelioma and asbestos exposure in the North-Western Cape Province, Br. J. Ind. Med. 17: 260 (1960).PubMedGoogle Scholar
  103. 103.
    I. J. Selikoff, J. Churg, and E. C. Hammond, Asbestos exposure and neoplasia, JAMA 188: 22 (1964).PubMedCrossRefGoogle Scholar
  104. 104.
    E. C. Hammond, I. J. Selikoff, and J. Churg, Neoplasia among insulation workers in the United States with special reference to intra-abdominal neoplasia, Ann. N.Y. Acad. Sci. 132: 519 (1965).PubMedCrossRefGoogle Scholar
  105. 105.
    M. Kleinfeld, J. Messíte, and O. Kooymann, Mortality experience in a group of asbestos workers, Arch. Environ. Health 15:177 (1967).Google Scholar
  106. 106.
    M. A. Gerber, Asbestosis and neoplastic disorders of the hematopoietic system, Am. J. Clin. Pathol. 53: 204 (1970).PubMedGoogle Scholar
  107. 107.
    IARC Monographs Vol. 14, IARC, Lyon, France (1977), pp. 11–106.Google Scholar
  108. 108.
    I. J. Selikoff, E. C. Hammond, and J. Churg, Asbestosis exposure, smoking and neoplasia, JAMA 204: 106 (1968).PubMedCrossRefGoogle Scholar
  109. 109.
    M. Chamberlain and E. M. Tarmy, Asbestos and glass fibers in bacterial mutation tests, Mutat. Res. 43: 159 (1977).PubMedCrossRefGoogle Scholar
  110. 110.
    S. L. Huang, Amosite, chrysotile, and crocidolite asbestos are mutagenic in Chinese hamster lung cells, Mutat. Res. 68: 265 (1979).PubMedCrossRefGoogle Scholar
  111. 111.
    K. S. Lavappa, M. M. Fu, and S. S. Epstein, Cytogenetic studies on chrysotile asbestos, Environ. Res. 10: 165 (1975).PubMedCrossRefGoogle Scholar
  112. 112.
    A. Sincock and M. Seabright, Induction of chromosome changes in Chinese hamster cells by exposure to asbestos fibers, Nature 257: 56 (1975).PubMedCrossRefGoogle Scholar
  113. 113.
    S. L. Huang, D. Saggioro, H. Michelmann, and H. V. Malling, Genetic effects of crocidolíte asbestos in Chinese hamster lung cells, Mutat. Res. 57: 225 (1978).PubMedCrossRefGoogle Scholar
  114. 114.
    F. Valerio, M. De Ferrari, L. Ottaggío, E. Repetto, and L. Santi, Cytogenetic effects of Rhodesian chrysotile on human lymphocytes in vitro, IARC Scí. Publ. 30: 485 (1980).Google Scholar
  115. 115.
    A. M. Sincock, Preliminary studies of the in vitro cellular effects of asbestos and fine glass dusts, in: “Origins of Human Cancer,” Book B, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (1977), p. 941.Google Scholar
  116. 116.
    IARC Monographs Vol. 7, IARC, Lyon, France (1974), pp. 203–221.Google Scholar
  117. 117.
    T. J. Haley, Evaluation of the health effects of benzene inhalation, Clin. Toxicol. 11:531 (1977).Google Scholar
  118. 118.
    The Merck Index,“ 8th ed., Merck and Co., Rahway, NJ (1968), p. 128.Google Scholar
  119. 119.
    P. F. Infante, R. A. Rinski, J. K. Wagoner, and R. J. Young, Leukemia in benzene workers, Lancet 2: 76 (1977).PubMedCrossRefGoogle Scholar
  120. 120.
    P. Delore and C. Borgomano, Leucemie aigue au cours de l’intoxication benzenique: Sur l’origine toxique de certains leucemies aigues et leur relations avec les anemies graves, J. Med. Lyon 9: 227 (1928).Google Scholar
  121. 121.
    A. Forni and E. C. Vigliani, Chemical leukemogenesis in man, Ser. Haemat. 7: 211 (1974).Google Scholar
  122. 122.
    E. C. Vigliani and A. Forni, Benzene and leukemia, Environ. Res. 11: 122 (1976).PubMedCrossRefGoogle Scholar
  123. 123.
    T. Ishimaru, H. Okada, T. Tomiyasu, T. Tsuchimoto, T. Hoshino, and M. Ichimaru, Occupational factors in the epidemiology of leukemia in Hiroshima and Nagasaki, Am. J. Epidemiol. 93: 157 (1971).PubMedGoogle Scholar
  124. 124.
    P. H. Wolf, D. Andjelkovich, A. Smith, and H. Tyroler, A case-control study of leukemia in the U.S. rubber industry, J. Occup. Med. 23: 103 (1981).PubMedCrossRefGoogle Scholar
  125. 125.
    M. Aksoy, S. Erdem, and G. Din Col, Leukemia in shoe-workers exposed chronically to benzene, Blood 44: 837 (1974).Google Scholar
  126. 126.
    M. Aksoy and S. Erdem, Follow-up study on the mortality and the development of leukemia in 44 pancytopenic patients with chronic exposure to benzene, Blood 52: 285 (1978).PubMedGoogle Scholar
  127. 127.
    A. Forni, E. Pacifico, and A. Limonta, Chromosome studies in workers exposed to benzene or toluene or both, Arch. Environ. Health 22:373 (1971).Google Scholar
  128. 128.
    B. J. Dean, Genetic toxicology of benzene, toluene, xylenes and phenols, Mutat. Res. 47: 75 (1978).PubMedCrossRefGoogle Scholar
  129. 129.
    R. Snyder and J. J. Kocsis, Current concepts of chronic benzene toxicity, CRC Crit. Rev. Toxicol. 3: 265 (1975).CrossRefGoogle Scholar
  130. 130.
    J. A. Cotruvo, V. F. Simmon, and R. J. Spanggord, Investigation of mutagenic effects of products of ozonation reactions in water, Ann. N.Y. Acad. Sci. 298: 124 (1977).CrossRefGoogle Scholar
  131. 131.
    L. A. Schairer, J. Van’t Hof, C. G. Hayes, R. M. Burton, and F. J. de Serres, Measurement of biological activity of ambient air mixtures using a mobile laboratory for in situ exposures: Preliminary results from the Tradescantia plant test system, in: “Application of Short-Term Bioassays in the Fractionation and Analysis of Complex Environmental Mixtures,” M. D. Waters, S. Nesnow, J. L. Huisingh, S. S. Sandhu, and L. Claxton, eds., Plenum Press, New York (1978), p. 419.CrossRefGoogle Scholar
  132. 132.
    P. Nylander, H. Olofsson, B. Rasmuson, and H. Svahlin, Muta-genic effects of petrol in Drosophila melanogaster. I. Effects of benzene and 1,2-dichloroethane, Mutat. Res. 57: 163 (1978).PubMedCrossRefGoogle Scholar
  133. 133.
    H. Tanooka, Development and applications of Bacillus subtilis test systems for mutagens, involving DNA repair, deficiency and suppressible auxotrophic mutations, Mutat. Res. 42: 19 (1977).PubMedCrossRefGoogle Scholar
  134. 134.
    M. Diaz, N. Fijtman, V. Carricarte, L. Braier, and J. Diez, Effect of benzene and its metabolites on SCE in human lymphocyte cultures, In Vitro 15:172 (1979).Google Scholar
  135. 135.
    A. Koizumi, Y. Dobashi, Y. Tachibana, K. Tsuda, H. Katsunuma, Cytokinetic and cytogenetic changes in cultured human leukocytes and Hela cells induced by benzene, Ind. Health 12: 23 (1974)Google Scholar
  136. 136.
    P. Gerner-Smidt and U. Friedrich, The mutagenic effect of benzene, toluene and xylene studied by the SCE technique, Mutat. Res. 58: 313 (1978).PubMedCrossRefGoogle Scholar
  137. 137.
    J. Meyne and M. S. Legator, Sex-related ditterences in cytogenetic effects of benzene in the bone marrow of Swiss mice, Environ. Mutagen. 2:43 (1980).Google Scholar
  138. 138.
    R. R. Tice, D. L. Costa, and R. T. Drew, Cytogenetic effects of inhaled benzene in murine bone marrow: Induction of sister chromatid exchanges, chromosomal aberrations, and cellular proliferation in DBA/2 mice, Proc. Natl. Acad. Sci. U.S.A. 77:2148 (1980).Google Scholar
  139. 139.
    D. Picciano, Cytogenetic study of workers exposed to benzene, Environ. Res. 19: 33 (1979).PubMedCrossRefGoogle Scholar
  140. 140.
    M. Hite, M. Pecharo, I. Smith, and S. Thornton, The effect of benzene in the micronucleus test, Mutat. Res. 77: 149 (1980).PubMedCrossRefGoogle Scholar
  141. 141.
    J. C. Topham, Do induced sperm-head abnormalities in mice specifically identify mammalian mutagens rather than carcinogens?, Mutat. Res. 74: 379 (1980).PubMedCrossRefGoogle Scholar
  142. 142.
    B. C. Casto and G. G. Hatch, “In Vitro Study of the Nature of the Interaction Between Chemical and Viral Carcinogens” (unpublished).Google Scholar
  143. 143.
    F. Wesley, B. Rourke, and O. Darbishire, The formation of persistent toxic chlorohydrins in foodstuffs by fumigation with ethylene oxide and with propylene oxide, J. Food Sci. 30: 1037 (1965).CrossRefGoogle Scholar
  144. 144.
    The Merck Index,“ 8th ed., Merck and Co., Rahway, NJ (1968), p. 435.Google Scholar
  145. 145.
    J. W. Embree, J. P. Lyon, and C. H. Hine, The mutagenic potential of ethylene oxide using the dominant-lethal assay in rats, Toxicol. Appl. Pharmacol. 40:261 (1977).Google Scholar
  146. 146.
    L. Ehrenberg and A. Gustafsson, On the mutagenic action of ethylene oxide and diepoxylbutane in barley, Hereditas 43: 595 (1957).Google Scholar
  147. 147.
    L. Ehrenberg, U. Lundquist, and G. Strom, On the mutagenic action of ethyleneimine in barley, Hereditas 44: 330 (1958).CrossRefGoogle Scholar
  148. 148.
    C. Hogstedt, N. Malmgvist, and B. Wadman, Leukemia in workers exposed to ethylene oxide, JAMA 241: 1132 (1979).PubMedCrossRefGoogle Scholar
  149. 149.
    S. De Flora, Study of 106 organic and inorganic compounds in the Salmonella/microsome test, Carcinogenesis 2: 283 (1981).PubMedCrossRefGoogle Scholar
  150. 150.
    B. J. Kilbey and H. G. Kolmark, A mutagenic after-effect associated with ethylene oxide in Neurospora crassa Mol. Gen. Genet. 101: 185 (1968).PubMedCrossRefGoogle Scholar
  151. 151.
    K. Krell, E. D. Jacobson, and K. Selby, Mutagenic effect on L5178Y mouse lymphoma cells by growth in ethylene oxide-sterilized polycarbonate flasks, In Vitro 15:326 (1979).Google Scholar
  152. 152.
    M. J. Bird, Chemical production of mutations in Drosophila: Comparison of techniques, J. Genet. 50: 480 (1952).CrossRefGoogle Scholar
  153. 153.
    R. B. Cumming and T. A. Michaud, Mutagenic effects of inhaled ethylene oxide in male mice, Environ. Mutagen. 1:166 (1979).Google Scholar
  154. 154.
    E. G. Star, Mutagenic and cytotoxic effect of ethylene oxide on human cell cultures, Zbl. Bakt. En. I. Abt. Orig. B170: 548 (1980).Google Scholar
  155. 155.
    V, F. Garry, J. Hozier, D. Jacobs, R. L. Wade, and D. G. Gray, Ethylene oxide: Evidence of human chromosomal effects, Environ. Mutagen. 1:375 (1979).Google Scholar
  156. 156.
    J. W. Embree and C. H. Hine, Mutagenicity of ethylene oxide, Toxicol. Appl. Pharmacol. 33:172 (1975).Google Scholar
  157. 157.
    A. M. Thiess, H. Schwegler, I. Fleig, and W. G. Stocker, Mutagenicity study of workers exposed to alkylene oxides (ethylene oxide/propylene oxide) and derivatives, J. Occup. Med. 23: 343 (1981).PubMedGoogle Scholar
  158. 158.
    L. E. Appelgren, G. Eneroth, C. Grant, L. E. Landstrom, and K. Tenghagen, Testing of ethylene oxide for mutagenicity using the micronucleus test in mice and rats, Acta Pharmacol. Toxicol. 43:69 (1978).Google Scholar
  159. 159.
    W. M. Generoso, K. T. Cain, M. Krishna, C. W. Sheu, and R. M. Gryder, Heritable translocation and dominant-lethal mutation induction with ethylene oxide in mice, Mutat. Res. 73: 133 (1980).PubMedCrossRefGoogle Scholar
  160. 160.
    Y. Nakao and C. Auerbach, Test of a possible correlation between cross-linking and chromosome breaking abilities of chemical mutagens, Zeitschrift für Vererbungslehre 92: 457 (1961).PubMedGoogle Scholar
  161. 161.
    W. A. F. Watson, Further evidence of an essential difference between the genetical effects of mono-and bifunctional alkylating agents, Mutat. Res. 3: 455 (1966).PubMedCrossRefGoogle Scholar
  162. 162.
    R. K. Karchmer, M. Amare, W. E. Larsem, A. G. Mallouk, and G. G. Caldwell, Alkylating agents as leukemogens in multiple myeloma, Cancer 33: 1103 (1974).PubMedCrossRefGoogle Scholar
  163. 163.
    R. F. K. De Bock and M. E. Peetermans, Leukemia after prolonged use of melphalan for non-malignant disease, Lancet 1: 1208 (1977).Google Scholar
  164. 164.
    N. Einhorn, Acute leukemia after chemotherapy (melphalan), Cancer 41: 444 (1978).PubMedCrossRefGoogle Scholar
  165. 165.
    I. P. Law and J. Blom, Second malignancies in patients with multiple myeloma, Oncology 34: 20 (1977).PubMedCrossRefGoogle Scholar
  166. 166.
    R. A. Kyle, R. V. Pierre, and E. D. Bayrd, Multiple myeloma and acute leukemia associated with alkylating agents, Arch. Int. Med. 135: 185 (1975).CrossRefGoogle Scholar
  167. 167.
    IARC Monographs Vol. 9, IARC, Lyon, France (1975), pp. 167–180.Google Scholar
  168. 168.
    W. F. Benedict, M. S. Baker, L. Haroun, E. Choi, and B. N. Ames, Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test, Cancer Res. 37: 2209 (1977).PubMedGoogle Scholar
  169. 169.
    V. Minnich, M. E. Smith, D. Thompson, and S. Kornfeld, Detection of mutagenic activity in human urine using mutant strains of Salmonella typhimurium, Cancer 38:1253 (1976).Google Scholar
  170. 170.
    D. Matheson, D. Brusick, and R. Carrano, Comparison of the relative mutagenic activity for eight antineoplastic drugs in the Ames Salmonella/microsome and TK +/- mouse lymphoma assays, Drug Chem. Toxicol. 1:277 (1978).Google Scholar
  171. 171.
    G. Fahmy and M. J. Fahmy, Cytogenetic analysis of the action of carcinogens and tumor inhibitors in Drosophila melanogaster. V. Differential genetic response to the alkylating mutagens and X-radiation, J. Genet. 54: 146 (1956).CrossRefGoogle Scholar
  172. 172.
    D. S. Longnecker, T. J. Curphey, S. T. James, D. S. Daniel, and N. J. Jacobs, Trial of a bacterial screening system for rapid detection of mutagens and carcinogens, Cancer Res. 34: 1658 (1974).PubMedGoogle Scholar
  173. 173.
    R. Lewensohn and U. Ringborg, Induction of unscheduled DNA synthesis in human bone marrow cells by bifunctional alkylating agents, Blood 54: 1320 (1979).PubMedGoogle Scholar
  174. 174.
    B. Lambert, U. Ringborg, A. Lindblad, E. Harper, M. Nordenskjold, and B. Werelius, Sister-chromatid exchanges in smoking and non-smoking control subjects, patients receiving cancer chemotherapy and laboratory workers exposed to organic solvents, Mutat. Res. 64: 138 (1979).Google Scholar
  175. 175.
    A. Banerjee and W. F. Benedict, Production of sister chromatid exchanges by various cancer chemotherapeutic agents, Cancer Res. 39: 797 (1979).PubMedGoogle Scholar
  176. 176.
    W. F. Benedict, A. Banerjee, A. Gardner, and P. A. Jones, Induction of morphological transformation in mouse C3H/10T11 clone 8 cells and chromosomal damage in hamster A(T1)C1–3 cells by cancer chemotherapeutic agents, Cancer Res. 37: 2202 (1977).PubMedGoogle Scholar
  177. 177.
    M. Nordenskjold, S. Soderhall, and P. Moldeus, Studies of DNA-strand breaks induced in human fibroblasts by chemical mutagens/carcinogens, Mutat. Res. 63: 393 (1979).PubMedCrossRefGoogle Scholar
  178. 178.
    IARC Monographs Vol. 10, IARC, Lyon, France (1976), pp. 85–98.Google Scholar
  179. 179.
    R. 0. Wallerstein, P. K. Condit, C. K. Kasper, J. W. Brown, and F. R. Morrison, State wide study of chloramphenicol therapy and fatal aplastic anemia, JAMA 208: 2045 (1969).PubMedCrossRefGoogle Scholar
  180. 180.
    P. S. Mukherji, Acute myeloblastic leukemia following chloramphenicol treatment, Br. Med. J. ií: 1286 (1957).Google Scholar
  181. 181.
    H. S. Rosenkranz, B. Gutter, and W. T. Speck, Mutagenicity and DNA-modifying activity: A comparison of two microbial assays, Mutat. Res. 41: 61 (1976).PubMedCrossRefGoogle Scholar
  182. 182.
    J. Hemmerly and M. Demerec, Tests of chemicals for mutagenicity, Cancer Res. 15: 69 (1955).Google Scholar
  183. 183.
    A. J. Müller, A survey on agents tested with regard to their ability to induce recessive lethals in Arabidopsis, Arabidopsis Information Service 2:22 (1965).Google Scholar
  184. 184.
    G. E. Nasrat, K. A. Ahmed, H. A. Nafei, and A. H. Abdel-Rahman, Mutagenic action of certain therapeutic drugs on Drosophila melanogaster, Zanco 3:214 (1977).Google Scholar
  185. 185.
    H. S. Rosenkranz and Z. Leifer, Determining the DNA-modifying activity of chemicals using DNA-polymerase-deficient Escherichia colí in: “Chemical Mutagens: Principles and Methods for Their Detection,” Vol. 6, F. J. de Serres and A. Hollaender, eds., Plenum Press, New York (1980), p. 109.Google Scholar
  186. 186.
    K. Goh, Chloramphenicol and chromosomal morphology, J. Med. 10: 159 (1979).PubMedGoogle Scholar
  187. 187.
    G. K. Manna and S. Bardhan, Some aspects of chloramphenicol induced bone marrow chromosome aberrations in mice, J. Cytol. Genet. 12:10 (1977).Google Scholar
  188. 188.
    R. J. Sram, Effect of chloramphenicol and puromycin on the dominant lethals induced by TEPA in mice, Fol. Biol. 18: 367 (1972).Google Scholar
  189. 189.
    R. R. Monson, L. Rosenberg, S. C. Hartz, S. Shapiro, O. P. Heinonen, and D. Slone, Diphenylhydantoin and selected congenital malformations, New England J. Med. 289: 1049 (1973).CrossRefGoogle Scholar
  190. 190.
    IARC Monographs Vol. 13, IARC, Lyon, France (1977), pp. 201–225.Google Scholar
  191. 191.
    F. P. Li, D. R. Willard, R. Goodman, and G. Vawter, Malignant lymphoma after diphenylhydantoin (Dilantin) therapy, Cancer 36: 1359 (1975).Google Scholar
  192. 192.
    J. Clemmesen and S. Hjalmgrim-Jensen, Is phenobarbital carcinogenic? A follow-up of 8078 epileptics, Ecotoxicol. Environ. Safety 1:457 (1978).Google Scholar
  193. 193.
    L. S. Goodman and A. Gilman, “The Pharmacological Basis of Therapeutics,” Macmillan, New York (1975), pp. 204–208.Google Scholar
  194. 194.
    J. Alving, M. K. Jensen, and H. Meyer, Diphenylhydantoin and chromosome morphology in man and rat-A negative report, Mutat. Res. 40: 173 (1976).PubMedCrossRefGoogle Scholar
  195. 195.
    T. V. Ramaniah, S. D. Nandan, K. P. Rao, and M. S. Rao, Mutagenicity of phenytoin in the male germ cells of Swiss mice, ICRS Med. Sci. 8: 853 (1980).Google Scholar
  196. 196.
    IARC Monographs Vol. 1, IARC, Lyon, France (1972), pp. 74–79.Google Scholar
  197. 197.
    W. F. Melick, H. M. Escue, J. J. Naryka, R. A. Mezera, and E. R. Wheeler, The first reported case of human bladder tumors due to a new carcinogen-Xenylamine, J. Urol. (Baltimore) 74: 760 (1955).Google Scholar
  198. 198.
    W. F. Melick, J. J. Naryka, and R. E. Kelly, Bladder cancer due to exposure to para-aminobiphenyl: A 17-year follow up, J. Urol. (Baltimore) 106: 220 (1971).Google Scholar
  199. 199.
    V. F. Simmon, In vitro mutagenicity assays of chemical carcinogens and related compounds with Salmonella typhimurium, JNCI 62:893 (1979).Google Scholar
  200. 200.
    J. L. Radomski, W. L. Hearn, T. Radomski, H. Moreno, and W. E. Scott, Isolation of the glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl from dog urine and its mutagenic activity, Cancer Res. 37: 1757 (1977).PubMedGoogle Scholar
  201. 201.
    D. F. Krahn, Rat liver homogenate-mediated toxicity and induction of 6-thioguanine-resistance in V79 Chinese hamster cells by chemical carcinogens, Diss. Abstr. Int. B37:3726 (1977).Google Scholar
  202. 202.
    R. P. Bos, R. M. E. Brouns, R. Van Doorn, J. L. G. Theuws, and P. T. Henderson, The appearance of mutagens in urine of rats after the administration of benzidine and some other aromatic amines, Toxicology 16: 113 (1980).CrossRefGoogle Scholar
  203. 203.
    V. F. Simmon, H. S. Rosenkranz, E. Zeiger, and L. A. Poirier, Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host-mediated assay, JNCI 62: 911 (1979).Google Scholar
  204. 204.
    H. S. Rosenkranz and L. A. Poirier, Evaluation of the mutagenicity and DNA-modifying activity of carcinogens and noncarcinogens in microbial systems, JNCI 62: 873 (1979).PubMedGoogle Scholar
  205. 205.
    V. F. Simmon, In vitro assays for recombinogenic activity of chemical carcinogens and related compounds with Saccharomyces cerevisiae D3, JNCI 62:901 (1979).Google Scholar
  206. 206.
    G. M. Williams, Further improvements in the hepatocyte primary culture DNA repair test for carcinogens: Detection of carcinogenic biphenyl derivatives, Cancer Lett. 4: 69 (1978).Google Scholar
  207. 207.
    R. J. Trzos, G. L. Petzold, M. N. Brunden, and J. A. Swenberg, The evaluation of sixteen carcinogens in the rat using the micronucleus test, Mutat. Res. 58: 79 (1978).PubMedCrossRefGoogle Scholar
  208. 208.
    R. J. Pienta, A hamster embryo cell model system for identifying carcinogens, in: “Carcinogens: Identification and Mechanisms of Action” A. C. Griffin and C. R. Shaw, eds., Raven Press, New York (1979), p. 121.Google Scholar
  209. 209.
    J. S. Rhim, D. K. Park, E. K. Weisburger, and J. H. Weisburger, Evaluation of an in vitro assay system for carcinogens based on prior infection of rodent cells with nontransforming RNA tumor virus, JNCI 52: 1167 (1974).PubMedGoogle Scholar
  210. 210.
    A. E. Freeman, E. K. Weisburger, J. H. Weisburger, R. G. Wolford, J. M. Maryak, and R. J. Huebner, Transformation of cell cultures as an indication of the carcinogenic potential of chemicals, JNCI 51: 799 (1973).PubMedGoogle Scholar
  211. 211.
    Chem. Eng. News Feb. 11:12 (1974).Google Scholar
  212. 212.
    IARC Monographs Vol. 1, IARC, Lyon, France (1972), pp. 80–86.Google Scholar
  213. 213.
    L. Rehn, Blasengeschwulste bei fuchsin-arbeitern, Arch. Klin. Chirugie 50:588 (1895).Google Scholar
  214. 214.
    R. A. M. Case, M. E. Hosker, D. B. McDonald, and J. T. Pearson, Tumors of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. Part I. The role of aniline, benzidine, a-naphthylamine and ß-naphthylamine, Br. J. I.d. Med. 11: 75 (1954).Google Scholar
  215. 215.
    T. J. Haley, Benzidine revisited: A review of the literature and problems associated with the use of benzidine and its congeners, Clin. Toxicol. 8:13 (1975).Google Scholar
  216. 216.
    T. S. Scott and M. H. C. Williams, The control of industrial bladder tumors, Br. J. Ind. Med. 14: 150 (1957).PubMedGoogle Scholar
  217. 217.
    M. R. Zavon, U. Hoegg, and U. Bingham, Benzidine exposure as a cause of bladder tumors, Arch. Environ. Health 27:1 (1973).Google Scholar
  218. 218.
    P. F. Meal, J. Cocker, H. K. Wilson, and J. M. Gilmour, Search for benzidine and its metabolites in urine of workers weighing benzidine-derived dyes, Br. J. Ind. Med. 38: 191 (1981).PubMedGoogle Scholar
  219. 219.
    W. C. Hueper, “Occupational and Environmental Cancers of the Urinary System,” Yale University Press, New Haven, CT (1969).Google Scholar
  220. 220.
    K. Tanaka, S. Marui, and T. Mii, Mutagenicity of extracts of urine from rats treated with aromatic amines, Mutat. Res. 79: 173 (1980).PubMedCrossRefGoogle Scholar
  221. 221.
    R. C. Garner, A. L. Walpole, and F. L. Rose, Testing of some benzidine analogues for microsomal activation to bacterial mutagens, Cancer Lett. 1: 39 (1975).PubMedCrossRefGoogle Scholar
  222. 222.
    M. J. Fahmy and 0. G. Fahmy, Mutagenicity of hair dye components relative to the carcinogen benzidine in Drosophila melanogaster, Mutat. Res. 56:31 (1977).Google Scholar
  223. 223.
    V. F. Simmon, S. L. Eckford, and A. F. Griffin, Ozone methods and ozone chemistry of selected organics in water. 2. Mutagenic assays, in: “Proceedings of a Conference: Ozone/Chlorine Dioxide Oxidation Products of Organic Materials” (1978), p. 126.Google Scholar
  224. 224.
    C. N. Martin, A. C. McDermid, and R. C. Garner, Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells, Cancer Res. 38: 2621 (1978).PubMedGoogle Scholar
  225. 225.
    R. B. Painter, DNA synthesis inhibition in HeLa cells as a simple test for agents that damage human DNA, J. Environ. Pathol. Toxicol. 2:65 (1978).Google Scholar
  226. 226.
    R. Cihak, Evaluation of benzidine by the micronucleus test, Mutat. Res. 67: 383 (1979).PubMedCrossRefGoogle Scholar
  227. 227.
    R. J. Pienta, J. A. Polley, and W. B. Lebherz, III, Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens, Int. J. Cancer 19: 642 (1977).PubMedCrossRefGoogle Scholar
  228. 228.
    K. A. Traul and J. S. Wolff, report under Contract NO1–CP55703, John L. Smith Memorial on Cancer, Pfizer, Inc. (1979).Google Scholar
  229. 229.
    IARC Monographs Vol. 1, IARC, Lyon, France (1972), pp. 69–73.Google Scholar
  230. 230.
    A. von Mueller, Blasenveranderungen durch amine, erfahrungen aus dem industriegebeit basel, Z. Urol. Chir. 36:202 (1933).Google Scholar
  231. 231.
    R. A. M. Case and J. T. Pearson, Tumors of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. Part II. Further consideration of the role of aniline and of the manufacture of auramine and magenta (fuchsin) as possible causative agents, Br. J. Ind. Med. 11: 213 (1954).PubMedGoogle Scholar
  232. 232.
    D. E. Amacher, S. C. Paillet, G. N. Turner, V. A. Ray, and D. S. Salsburg, Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells. II. Test validation and interpretation, Mutat. Res. 72: 447 (1980).PubMedCrossRefGoogle Scholar
  233. 233.
    T. Tsuchimoto and B. E. Matter, Activity of coded compounds in the micronucleus test, in: “Evaluation of Short-Term Tests for Carcinogenesis: Report of the International Collaborative Program,” Progress in Mutation Research Vol. 1, F. J. de Serres and J. Ashby, eds., Elsevier/ North-Holland Biomedical Press, New York (1981), p. 705.Google Scholar
  234. 234.
    H. G. Treibl, Naphthalene derivatives, in: “Encyclopedia of Chemical Toxicology,” 2nd ed., R. E. Kirk and D. F. Othmer, eds., Vol. 13, John Wiley and Sons, New York (1967), p. 708.Google Scholar
  235. 235.
    The Merck Index,“ 8th ed., Merck and Co., Rahway, NJ (1968), p. 717.Google Scholar
  236. 236.
    W. C. Hueper, “Occupational Tumors and Allied Diseases,” Thomas, Springfield, IL (1942).Google Scholar
  237. 237.
    IARC Monographs Vol. 4, IARC, Lyon, France (1974), pp. 97–111.Google Scholar
  238. 238.
    L. J. Goldwater, A. J. Rosso, and M. Kleinfeld, Bladder tumors in a coal-tar dye plant, Arch. Environ. Health 11:814 (1965).Google Scholar
  239. 239.
    T. Sugimura, S. Sato, M. Nagao, T. Yahagi, T. Matsushima, Y. Seino, M. Takeuchi, and T. Kawachi, Overlapping of carcinogens and mutagens, in: “Fundamentals in Cancer Prevention,” P. N. Magee et al., eds., University of Tokyo Press and University Park Press, Tokyo and Baltimore, MD (1976), p. 191.Google Scholar
  240. 240.
    D. Ichinotsubo, H. F. Mower, J. Setliff, and M. Mandel, The use of rec bacteria for testing of carcinogenic substances, Mutat. Res. 46: 53 (1977).PubMedCrossRefGoogle Scholar
  241. 241.
    V. W. Mayer, Mutagenic effects induced in Saccharomyces cerevisiae by breakdown products of 1-naphthylamine and 2-naphthylamine formed in an enzyme-free hydroxylation system, Mutat. Res. 15: 147 (1972).PubMedCrossRefGoogle Scholar
  242. 242.
    T. Ong and F. J. de Serres, Mutagenicity of chemical carcinogens in Neurospora crassa, Cancer Res. 32:1890 (1972).Google Scholar
  243. 243.
    V. W. Mayer, Induction of mitotic crossing over in Saccharomyces cerevisiae by breakdown products of dimethylnitrosamine, diethylnitrosamine, 1-naphthylamine and 2-naphthylamine formed by an in vitro hydroxylation system, Genetics 74: 433 (1973).PubMedGoogle Scholar
  244. 244.
    D. F. Callen and R. M. Philpot, Cytochrome P-450 and the activation of promutagens in Saccharomyces cerevisiae, Mutat. Res. 45:309 (1977).Google Scholar
  245. 245.
    A. D. Mitchell, “Potential Prescreens for Chemical Carcinogens: Unscheduled DNA Synthesis,” Task 2, Final Report under Contract N01/CP-33394, Stanford Research Institute, Stanford, CA (1976).Google Scholar
  246. 246.
    M. F. Salamone, J. A. Heddle, and M. Katz, Mutagenic activity of 41 compounds in the in vivo micronucleus assay, in: “Evaluation of Short-Term Tests for Carcinogenesis: Report of the International Collaborative Program,” Progress in Mutation Research Vol. 1, F. J. de Serres and J. Ashby, eds., Elsevier/North-Holland Biomedical Press, New York (1981), p. 686.Google Scholar
  247. 247.
    B. Kirkhart, Micronucleus test on 21 compounds, in: “Evaluation of Short-Term Tests for Carcinogenesis: Report of the International Collaborative Program,” Progress in Mutation Research Vol. 1, F. J. de Serres and J. Ashby, eds., Elsevier/North-Holland Biomedical Press, New York (1981), p. 698.Google Scholar
  248. 248.
    A. Videbaek, Chlornaphazin (Erysan) may induce cancer of the urinary bladder, Acta Med. Scand. 176: 45 (1964).PubMedCrossRefGoogle Scholar
  249. 249.
    N. I. Sax, “Cancer Causing Chemicals,” Van Nostrand Reinhold, New York (1981).Google Scholar
  250. 250.
    T. Thiede, E. Chievitz, and B. C. Christensen, Chlornaphazine as a bladder carcinogen, Acta Med. Scand. 175: 721 (1964).PubMedCrossRefGoogle Scholar
  251. 251.
    E. Chievitz and T. Thiede, Acta Med. Scand. 172: 513 (1962).PubMedCrossRefGoogle Scholar
  252. 252.
    T. Thiede and B. C. Christensen, Bladder tumors induced by chlornaphazine, Acta Med. Scand. 185: 133 (1969).PubMedCrossRefGoogle Scholar
  253. 253.
    IARC Monographs Vol. 4, IARC, Lyon, France (1974), pp. 119–124.Google Scholar
  254. 254.
    G. Fahmy and M. J. Fahmy, Gene elimination in carcinogenesis: Reinterpretation of the somatic mutation theory, Cancer Res. 30: 195 (1970).PubMedGoogle Scholar
  255. 255.
    R. L. Wall and K. P. Clausen, Carcinoma of the urinary bladder in patients receiving cyclophosphamide, New England J. Med. 293: 271 (1975).CrossRefGoogle Scholar
  256. 256.
    IARC Monographs Vol. 9, IARC, Lyon, France (1975), pp. 135–156.Google Scholar
  257. 257.
    A. D. Steinberg, P. H. Plotz, S. M. Wolff, V. G. Wong, S. G. Agus, and J. L. Decker, Cytotoxic drugs in treatment of nonmalignant diseases, Ann. Int. Med. 76: 619 (1972).CrossRefGoogle Scholar
  258. 258.
    J. C. Cline and R. E. McMahon, Detection of chemical mutagens: Use of concentration gradient plates in a high capacity screen, Res. Commun. Chem. Pathol. Pharmacol. 16: 523 (1977).PubMedGoogle Scholar
  259. 259.
    V. W. Mayer, C. J. Hybner, and D. J. Brusick, Genetic effects induced in Saccharomyces cerevisiae by cyclophosphamide in vitro without liver enzyme preparations, Mutat. Res. 37: 201 (1976).Google Scholar
  260. 260.
    D. Siebert and U. Simon, Genetic activity of metabolites in the ascitic fluid and in the urine of a human patient treated with cyclophosphamide, Mutat. Res. 21: 257 (1973).Google Scholar
  261. 261.
    D. Siebert, A new method for testing genetically active metabolites: Urinary assay with cyclophosphamide (Endoxan, Cytoxan) and Saccharomyces cerevisiae, Mutat. Res. 17:307 (1973).Google Scholar
  262. 262.
    W. J. Suling, R. F. Struck, C. W. Woolley, and W. M. Shannon, Comparative disposition of phosphoramide mustard and other cyclophosphamide metabolites in the mouse using the Salmonella/mutagenesis assay, Cancer Treat. Rep. 62:1321 (1978).Google Scholar
  263. 263.
    A. Schubert, Host-mediated assay and urinary assay with the same mice for the detection of chemical mutagens in Saccharomyces cerevisiae Biol. Zbl. 94: 451 (1975).Google Scholar
  264. 264.
    A. A. Shapiro and L. M. Fonshtein, Study of the mutagenic action of cyclophosphamide on bacteria in host-mediated assay, Izv. Akad. Nauk SSSR, Ser. Biol. 6: 371 (1979).Google Scholar
  265. 265.
    S. R. Sirianni, M. Furukawa, and C. C. Huang, Induction of 8-azaguanine-and ouabain-resistant mutants by cyclophosphamide and 1-(pyridyl-B)-3,3-dimethyltriazene in Chinese hamster cells cultured in diffusion chambers in mice, Mutat. Res. 64: 259 (1979).PubMedCrossRefGoogle Scholar
  266. 266.
    D. Clive, K. O. Johnson, J. F. S. Spector, A. G. Batson, and M. M. Mwn, Validation and characterization of the L5178Y/TK mouse lymphoma mutagen assay system, Mutat. Res. 59: 61 (1979).PubMedCrossRefGoogle Scholar
  267. 267.
    E. Vogel, W. R. Lee, A. Schalet, and F. Wurgler, Drosophila test system, in: “Proceedings of the Comparative Chemical Mutagen Conference” (in press).Google Scholar
  268. 268.
    R. B. Cumming and M. F. Walton, Genetic effects of cyclophosphamide in the germ cells of male mice, Genetics 68: S14 (1971).Google Scholar
  269. 269.
    R. E. Sotomayor, G. A. Sega, and R. B. Cumming, Unscheduled DNA synthesis in the germ cèlls of male mice treated in vivo with chemical mutagens requiring metabolic activation, Mutat. Res. 38: 395 (1976).Google Scholar
  270. 270.
    W. F. Benedict, A. Banerjee, and N. Venkatesan, Cyclophosphamide-induced oncogenic transformation, chromosomal breakage, and sister chromatid exchange following microsomal activation, Cancer Res. 38: 2922 (1978).PubMedGoogle Scholar
  271. 271.
    A. Korte, Comparative analysis of chromosomal aberrations and sister-chromatid exchanges in bone marrow cells of Chinese hamsters after treatment with aflatoxin B1, patulin and cyclophosphamide, Mutat. Res. 74: 164 (1980).Google Scholar
  272. 272.
    T. Ikeuchi, K. Sugimura, and M. Sasaki, Evaluation of mutagenmetabolizing capacity of cultured mammalian cells, as revealed by the induction of chromosome aberrations and sister chromatid exchanges, Jpn. J. Hum. Genet. 24: 186 (1979).Google Scholar
  273. 273.
    C. C. Huang, K. McKernan, J. R. Pantano, and S. R. Sirianni, An in vitro metabolic activation assay using liver microsomes in diffusion chambers: Induction of sister chromatid exchanges and chromosome aberrations by cyclophosphamide or ifosfamide in cultured human and Chinese hamster cells, Carcinogenesis 1: 37 (1980).PubMedCrossRefGoogle Scholar
  274. 274.
    A. N. Chebotarev, L. Y. Telegin, and E. M. Derzhavets, Cytogenetic effect of cyclophosphamide in a culture of human lymphocytes after its activation in the mouse organism, Genetika 12: 151 (1976).PubMedGoogle Scholar
  275. 275.
    I. Hansmann, Chromosome aberrations in metaphase II Oocytes stage sensitivity in the mouse oogenesis to amethopterin and cyclophosphamide, Mutat. Res. 22: 175 (1974).PubMedCrossRefGoogle Scholar
  276. 276.
    P. Goetz, A. M. Malashenko, and N. I. Surkova, Chromosome aberrations induced by cyclophosphamide in meiotic cells of male mice, Tsitologiya i Genetika 14: 29 (1980).Google Scholar
  277. 277.
    G. Rohrborn and A. Basler, Cytogenetic investigations of mammals. Comparison of the genetic activity of cytostatics in mammals, Arch. Toxicol. 38: 35 (1977).PubMedCrossRefGoogle Scholar
  278. 278.
    I. Sykora, K. Rezabek, D. Pokorna, and D. Gandalovicova, Experiences with methods testing the mutagenic and antifertility effects of the model drug cyclophosphamide, in: “Evaluation of Embryotoxic, Mutagenic, and Carcinogenic Risks of New Drugs, Proceedings of a 1976 Symposium” (1979), p. 263.Google Scholar
  279. 279.
    P. K. Datta, H. Frigger, and E. Schleiermacher, The effect of chemical mutagens on the mitotic chromosomes of the mouse in vivo, in: “Chemical Mutagenesis in Mammals and Man,” F. Vogel and G. Rohrborn, eds., Springer-Verlag, Berlin and New York (1970), p. 194.Google Scholar
  280. 280.
    W. M. Generoso, K. T. Cain, S. W. Huff, and D. G. Gosslee, Inducibility by chemical mutagens of heritable translocations in male and female germ cells of mice, in: “Advances in Modern Toxicology,” Vol. 5, Hemisphere Publishing Corporation, Washington, DC and London (1978), p. 109.Google Scholar
  281. 281.
    E. Vogel, Mutagenic activity of cyclophosphamide, trofosfamide, and ifosfamide in Drosophila melanogaster. Specific induction of recessive lethals in the absence of detectable chromosome breakage, Mutat. Res. 33: 221 (1975).PubMedCrossRefGoogle Scholar
  282. 282.
    T. Hirakawa, M. Tanaka, and S. Takayama, Morphological transformation of hamster embryo cells by cancer chemotherapeutic agents, Toxicol. Lett. 3: 55 (1979).CrossRefGoogle Scholar
  283. 283.
    V. C. Dunkel, R. J. Pienta, A. Sivak, and K. A. Traul, Comparative neoplastic transformation responses of Balb/3T3 cells, Syrian hamster embryo cells, and Rauscher murine leukemia virus-infected Fischer 344 rat embryo cells to chemical carcinogens, JNCI 67: 1303 (1981).PubMedGoogle Scholar
  284. 284.
    P. M. Adams, J. D. Fabricant, and M. S. Legator, Cyclophosphamide-induced spermatogenic effects detected in the F1 generation by behavioral testing, Science 211: 80 (1981).PubMedCrossRefGoogle Scholar
  285. 285.
    E. K. Inskeep, J. C. Herrington, and I. L. Lindahl, Effects of cyclophosphamide in rams, J. Animal Sci. 33: 1022 (1971).Google Scholar
  286. 286.
    A. J. Pennisi, C. M. Grushkin, and E. Lieberman, Gonadal function in children with nephrosis treated with cyclophosphamide, Am. J. Dis. Child. 129: 315 (1975).PubMedGoogle Scholar
  287. 287.
    J. C. Topham, Chemically-induced transmissible abnormalities in sperm-head shape, Mutat. Res. 70: 109 (1980).PubMedCrossRefGoogle Scholar
  288. 288.
    R. C. Shank, G. N. Wogan, and J. B. Gibson, Dietary aflatoxins and human liver cancer. I. Toxigenic moulds in foods and foodstuffs of tropical South-east Asia, Food Cosmetic Toxicol. 10: 51 (1972).CrossRefGoogle Scholar
  289. 289.
    R. C. Shank, G. N. Wogan, J. B. Gibson, and A. Nondasuta, Dietary aflatoxins and human liver cancer. II. Aflatoxins in market foods and foodstuffs of Thailand and Hong Kong, Food Cosmetic Toxicol. 10: 61 (1972).CrossRefGoogle Scholar
  290. 290.
    R. C. Shank, J. E. Gordon, G. N. Wogan, A. Nondasuta, and B. Subhamani, Dietary aflatoxins and human liver cancer. III. Field survey of rural Thai families for ingested aflatoxins, Food Cosmetic Toxicol. 10: 71 (1972).CrossRefGoogle Scholar
  291. 291.
    R. C. Shank, N. Bhamarapravati, J. E. Gordon, and G. N. Wogan, Dietary aflatoxins and human liver cancer. IV. Incidence of primary liver cancer in two municipal populations of Thailand, Food Cosmetic Toxicol. 10: 171 (1972).CrossRefGoogle Scholar
  292. 292.
    S. J. Van Rensburg, J. J. Van Der Watt, I. F. H. Purchase, L. Pereira Continho, and R. Markham, Primary liver cancer rate and aflatoxin intake in a high cancer area, S. Afr. Med. J. 48: 2508a (1974).Google Scholar
  293. 293.
    F. G. Peers and C. A. Linsell, Dietary aflatoxins and liver cancer-A population based study in Kenya, Br. J. Cancer 27: 473 (1973).Google Scholar
  294. 294.
    M. E. Alpert, M. S. R. Hutt, G. N. Wogan, and C. S. Davidson, Association between aflatoxin content of food and hepatoma frequency in Uganda, Cancer 28: 253 (1971).PubMedCrossRefGoogle Scholar
  295. 295.
    G. N. Wogan, Dietary factors and special epidemiological situations of liver cancer in Thailand and Africa, Cancer Res. 35: 3499 (1975).Google Scholar
  296. 296.
    G. E. Deger, Aflatoxin-Human colon carcinogenesis?, Ann. Int. Med. 85: 204 (1976).PubMedCrossRefGoogle Scholar
  297. 297.
    T. C. Campbell and L. Stoloff, Implication of mycotoxins for human health, J. Agr. Food Chem. 22:1006 (1974).Google Scholar
  298. 298.
    T. C. Campbell, R. O. Sinnhuber, D. J. Lee, J. H. Wales, and L. Salamat, Hepatocarcinogenic material in urine specimens from humans consuming aflatoxin, JNCI 52: 1647 (1974).PubMedGoogle Scholar
  299. 299.
    F. W. Larimer, A. A. Hardigree, D. W. Ramey, and J. L. Epler, Genetic activity of pro-mutagens in logarithmic phase cultures of Saccharomyces cerevisiae, Environ. Mutagen. 1:124 (1979).Google Scholar
  300. 300.
    T. Ong, Mutagenic activities of aflatoxin B1 and G1 in Neurospora crassa Mol. Gen. Genet. 111: 159 (1971).CrossRefGoogle Scholar
  301. 301.
    D. F. Krahn and C. Heidelberger, Liver homogenate-mediated mutagenesis in Chinese hamster V79 cells by polycyclic aromatic hydrocarbons and aflatoxins, Mutat. Res. 46: 27 (1977).PubMedCrossRefGoogle Scholar
  302. 302.
    M. J. Lamb and L. J. Lilly, Induction of recessive lethals in Drosophila melanogaster by aflatoxin B1, Mutat. Res. 11: 430 (1971).PubMedGoogle Scholar
  303. 303.
    Y. Ueno and K. Kubota, DNA-attacking ability of carcinogenic mycotoxins in recombination-deficient mutant cells of Bacillus subtilis, Cancer Res. 36:445 (1976).Google Scholar
  304. 304.
    M. H. Kuczuk, P. M. Benson, H. Heath, and A. W. Hayes, Evaluation of the mutagenic potential of mycotoxins using Salmonella typhimurium and Saccharomyces cerevisiae, Mutat. Res. 53:11 (1978).Google Scholar
  305. 305.
    D. F. Callen, G. R. Mohn, and T. Ong, Comparison of the genetic activity of aflatoxins B1 and G1 in Escherichia coli and Saccharomyces cerevisiae, Mutat. Res. 45:7 (1977).Google Scholar
  306. 306.
    G. M. Williams, Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures, Cancer Res. 37: 1845 (1977).PubMedGoogle Scholar
  307. 307.
    C. N. Martin, A. C. McDermid, and R. C. Garner, Measurement of ‘unscheduled’ DNA synthesis in HeLa cells by liquid scintillation counting after carcinogen treatment, Cancer Lett. 2: 355 (1977).PubMedCrossRefGoogle Scholar
  308. 308.
    H. F. Stich and B. A. Laishes, The response of Xeroderma pigmentosum cells and controls to the activated mycotoxins, aflatoxins and sterigmatocystin, Int. J. Cancer 16: 266 (1975).Google Scholar
  309. 309.
    H. J. Freeman and R. H. C. San, Use of unscheduled DNA synthesis in freshly isolated human intestinal mucosal cells for carcinogen detection, Cancer Res. 40: 3155 (1980).PubMedGoogle Scholar
  310. 310.
    L. Wheeler, M. Halula, and M. DeMeo, Comparison of prophage induction and mutagenicity in Ames tester strain TA1535 by aflatoxins and nitrosamines, Environ. Mutagen. 1:121 (1979).Google Scholar
  311. 311.
    S. Wolff and S. Takehisa, Induction of sister-chromatid exchange in mammalian cells by low concentrations of muta-genic carcinogens that require metabolic activation as well as those that do not, in: “Progress in Genetic Toxicology,” D. Scott, B. A. Bridges, and F. H. Sobels, eds., Elsevier/ North-Holland Biomedical Press, New York (1977), p. 193.Google Scholar
  312. 312.
    M. El-Zawahri, A. Moubasher, M. Morad, and I. El-Kady, Muta-genic effect of aflatoxin B1, Ann. Nutr. Alim. 31:859 (1977).Google Scholar
  313. 313.
    Y. Nakanishi and E. L. Schneider, In vivo sister-chromatid exchange: A sensitive measure of DNA damage, Mutat. Res. 60:329 (1979).Google Scholar
  314. 314.
    A. Korte and G. Ruckert, Chromosomal analysis in bone-marrow cells of Chinese hamsters after treatment with mycotoxins, Mutat. Res. 78: 41 (1980).PubMedCrossRefGoogle Scholar
  315. 315.
    M. A. Friedman and J. Staub, Induction of micronuclei in mouse and hamster bone-marrow by chemical carcinogens, Mutat. Res. 43: 255 (1977).PubMedCrossRefGoogle Scholar
  316. 316.
    B. C. Casto, N. Janosko, and J. A. DiPaolo, Development of a focus assay model for transformation of hamster cells in vitro by chemical carcinogens, Cancer Res. 37: 3508 (1977).PubMedGoogle Scholar
  317. 317.
    B. C. Casto, W. J. Pieczynski, N. Janosko, and J. A. DiPaolo, Significance of treatment interval and DNA repair in the enhancement of viral transformation by chemical carcinogens and mutagens, Chem.-Biol. Interact. 13:105 (1976).Google Scholar
  318. 318.
    J. A. DiPaolo, K. Takano, and N. C. Popescu, Quantitation of chemically induced neoplastic transformation of BALB/3T3 cloned cell lines, Cancer Res. 32: 2686 (1972).PubMedGoogle Scholar
  319. 319.
    G. N. Egbunike, The effects of microdoses of aflatoxin B1 on sperm production rates, epididymal sperm abnormality, and fertility in the rat, Zentralbi. Vet. Med. A26: 66 (1979).Google Scholar
  320. 320.
    IARC Monographs Vol. 13, IARC, Lyon, France (1977), pp. 131–139.Google Scholar
  321. 321.
    G. C. Farrell, D. E. Joshua, R. F. Uren, P. J. Baird, K. W. Perkins, and H. Kronenberg, Androgen-induced hepatoma, Lancet 1: 430 (1975).PubMedCrossRefGoogle Scholar
  322. 322.
    F. L. Johnson, J. R. Feagler, K. G. Lerner, P. W. Majerus, M. Siegel, J. R. Hartmann, and E. D. Thomas, Association of androgenic-anabolic steroid therapy with development of hepatocellular carcinoma, Lancet 2: 1273 (1972).PubMedCrossRefGoogle Scholar
  323. 323.
    IARC Monographs Vol. 7, IARC, Lyon, France (1974), pp. 291–318.Google Scholar
  324. 324.
    IARC Monographs Vol. 19, IARC, Lyon, France (1979), pp. 377–438.Google Scholar
  325. 325.
    J. L. Creech, Jr. and M. N. Johnson, Angiosarcoma of liver in the manufacture of polyvinyl chloride, J. Occup. Med. 16: 150 (1974).PubMedGoogle Scholar
  326. 326.
    R. Spirtas and R. Kaminski, Angiosarcoma of the liver in vinyl chloride/polyvinyl chloride workers. Update of NIOSH Register, J. Occup. Med. 20: 427 (1978).PubMedGoogle Scholar
  327. 327.
    R. R. Monson, J. M. Peters, and M. N. Johnson, Proportional mortality among vinyl-chloride workers, Lancet 2: 397 (1974).PubMedCrossRefGoogle Scholar
  328. 328.
    W. J. Nicholson, E. C. Hammond, H. Seidman, and I. J. Selikoff, Mortality experience of a cohort of vinyl chloride-polyvinyl chloride workers, Ann. N.Y. Acad. Sci. 246: 225 (1975).PubMedCrossRefGoogle Scholar
  329. 329.
    R. J. Waxweiler, W. Stringer, J. K. Wagoner, J. Jones, H. Falk, and C. Carter, Neoplastic risk among workers exposed to vinyl chloride, Ann. N.Y. Acad. Sci. 271: 40 (1976).PubMedCrossRefGoogle Scholar
  330. 330.
    A. J. Fox and P. F. Collier, Mortality experience of workers exposed to vinyl chloride monomer in the manufacture of polyvinyl chloride in Great Britain, Br. J. Ind. Med. 34: 1 (1977).PubMedGoogle Scholar
  331. 331.
    W. von Renl, H. Weber, and E. Greiser, Epidemiological study on mortality of VC-exposed workers in the Federal Republic of Germany, Medichem. (Germany), September 2–8 (1977).Google Scholar
  332. 332.
    J. McCann, V. Simmon, D. Streitwieser, and B. N. Ames, Mutagenicity of chloroacetaldehyde, a possible metabolic product of 1,2-dichloroethane (ethylene dichloride), chloroethanol (ethylene chlorohydrin), vinyl chloride, and cyclophosphamide, Proc. Natl. Acad. Sci. U.S.A. 72: 3190 (1975).PubMedCrossRefGoogle Scholar
  333. 333.
    M. M. Shahin, The non-mutagenicity and -recombinogenicity of vinyl chloride in the absence of metabolic activation, Mutat. Res. 40: 269 (1976).PubMedCrossRefGoogle Scholar
  334. 334.
    N. Loprieno, R. Barale, S. Baroncelli, C. Bauer, G. Bronzetti, A. Cammellini, G. Cercignani, C. Corsi, 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: Studies in vitro and in vivo, Mutat. Res. 40:85 (1976).Google Scholar
  335. 335.
    B. Z. Drozdowicz and P. C. Huang, Lack of mutagenicity of vinyl chloride in two strains of Neurospora crassa, Mutat. Res. 48:43 (1977).Google Scholar
  336. 336.
    I. E. Mattern and W. B. Van der Zwaan, Mutagenicity testing of urine from vinylchloride (VCM) treated rats using the Salmonella test system, Mutat. Res. 46: 230 (1977).Google Scholar
  337. 337.
    F. C. Barsky, J. D. Irr, and D. F. Krahn, Mutagenicity of gases in the Chinese hamster ovary cell assay, Environ. Mutagen. 1:167 (1979).Google Scholar
  338. 338.
    C. Drevon and T. Kuroki, Mutagenicity of vinyl chloride, vinylidene chloride and chloroprene in V79 Chinese hamster cells, Mutat. Res. 67: 173 (1979).PubMedCrossRefGoogle Scholar
  339. 339.
    F. G. Verburgt and E. Vogel, Vinyl chloride mutagenesis in Drosophila melanogaster, Mutat. Res. 48:327 (1977).Google Scholar
  340. 340.
    S. Peter and G. Ungvary, Lack of mutagenic effect of vinyl chloride monomer in the mammalian spot test, Mutat. Res. 77: 193 (1980).PubMedCrossRefGoogle Scholar
  341. 341.
    J. D. Elmore, J. L. Wong, A. D. Laumbach, and U. N. Streips, Vinyl chloride mutagenicity via the metabolites chlorooxirane and chloroacetaldehyde monomer hydrate, Biochem. Biophys. Acta 442:405 (1976).Google Scholar
  342. 342.
    I. Hansteen, L. Hillestad, E. Thiis-Evensen, and S. S. Heldaas, Effects of vinyl chloride in man: A cytogenetic follow-up study, Mutat. Res. 51: 271 (1978).PubMedCrossRefGoogle Scholar
  343. 343.
    D. Anderson, C. R. Richardson, I. F. H. Purchase, H. J. Evans, and M. L. O’Riordan, Chromosomal analysis in vinyl chloride exposed workers: Comparison of the standard technique with the sister-chromatid exchange technique, Mutat. Res. 83: 137 (1981).PubMedCrossRefGoogle Scholar
  344. 344.
    A. Basler and G. Röhrborn, Vinyl-chloride: An example for evaluating mutagenic effects in mammals in vivo after exposure to inhalation, Arch. Toxicol. 45:1 (1980).Google Scholar
  345. 345.
    I. F. H. Purchase, C. R. Richardson, and D. Anderson, Chromosomal and dominant lethal effects of vinyl chloride, Lancet 2: 410 (1975).PubMedCrossRefGoogle Scholar
  346. 346.
    D. Jenssen and C. Ramel, The micronucleus test as part of a short-term mutagenicity test program for the prediction of carcinogenicity evaluated by 143 agents tested, Mutat. Res. 75: 191 (1980).PubMedCrossRefGoogle Scholar
  347. 347.
    R. D. Short, J. L. Minor, J. M. Winston, and C. Lee, A dominant lethal study in male rats after repeated exposures to vinyl chloride or vinylidene chloride, J. Toxicol. Environ. Health 3:965 (1977).Google Scholar
  348. 348.
    D. Anderson, M. C. E. Hodge, and I. F. H. Purchase, Vinyl chloride: Dominant lethal studies in male CD-1 mice, Mutat. Res. 40: 359 (1976).PubMedCrossRefGoogle Scholar
  349. 349.
    C. L. Young, “Cancer Control Monograph: Diethylstilbestrol,” Project 4418, SRI International, Stanford, CA (1978).Google Scholar
  350. 350.
    A. L. Herbst, H. Ulfelder, and D. C. Poskanzer, Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women, New England J. Med. 284: 878 (1971).Google Scholar
  351. 351.
    S. J. Robboy, R. E. Scully, W. R. Welch, and A. L. Herbst, Intrauterine diethylstilbestrol exposure and its consequences, Arch. Pathol. Lab. Med. 101: 1 (1977).PubMedGoogle Scholar
  352. 352.
    A. L. Herbst, P. Cole, T. Colton, S. J. Robboy, and R. E. Scully, Age-incidence and risk of diethylstilbestrol-related clear cell adenocarcinoma of the vagina and cervix, Am. J. Obstet. Gynecol. 128: 43 (1977).PubMedGoogle Scholar
  353. 353.
    IARC Monographs Vol. 21, IARC, Lyon, France (1979), pp. 173–231.Google Scholar
  354. 354.
    C. Drevon, C. Piccoli, and R. Montesano, Mutagenicity assays of estrogenic hormones in mammalian cells, Mutat. Res. 89: 83 (1981).PubMedCrossRefGoogle Scholar
  355. 355.
    H. W. Rudiger, F. Haenisch, M. Metzler, F. Oesch, and H. R. Glatt, Metabolites of diethylstilboestrol induce sister-chromatid exchange in human cultured fibroblasts, Nature 281: 392 (1979).Google Scholar
  356. 356.
    S. Abe and M. Sasaki, Chromosome aberrations and sister-chromatid exchanges in Chinese hamster cells exposed to various chemicals, JNCI 58: 1635 (1977).PubMedGoogle Scholar
  357. 357.
    J. L. Ivett and R. R. Tice, Cytogenetic effects of diethystilbestrol-diphosphate (DES-dp) in murine bone marrow, Environ. Mutagen. 1:184 (1979).Google Scholar
  358. 358.
    A. J. F. Griffiths, Neurospora and environmentally induced aneuploidy, in: “Short-Term Tests for Chemical Carcinogens,” H. F. Stich and R. H. C. Sans, eds., Springer-Verlag, New York/Berlin (1981), p. 187.Google Scholar
  359. 359.
    N. P. Bishun, N. Smith, H. Eddie and D. C. Williams, Cytogenetic studies and diethylstilboestrol, Mutat. Res. 46: 211 (1977).CrossRefGoogle Scholar
  360. 360.
    N. Bishun, S. Forster, N. Valera, and D. C. Williams, The clastogenic effects of diethylstilboestrol on ascitic tumour cells in vivo, Microbiol. Lett. 13: 27 (1980).Google Scholar
  361. 361.
    L. Molina, S. Rinkus, and M. S. Legator, Evaluation of the micronucleus procedure over a 2-yr period, Mutat. Res. 53: 125 (1978).CrossRefGoogle Scholar
  362. 362.
    R. J. Pienta, In vitro carcinogenesis, in: “Frederick Cancer Research Center Annual Progress Report,” Vol. 11-D (1979), P 7 Google Scholar
  363. 363.
    J. C. Topham, The detection of carcinogen-induced sperm head abnormalities in mice, Mutat. Res. 69: 149 (1980).PubMedCrossRefGoogle Scholar
  364. 364.
    A. Wyrobek, L. Gordon, and G. Watchmaker, Effect of 17 chemical agents including 6 carcinogen/noncarcinogen pairs on sperm shape abnormalities in mice, in: “Evaluation of Short-Term Tests for Carcinogenesis: Report of the International Collaborative Program,” Progress in Mutation Research Vol. 1, F. J. de Serres and J. Ashby, eds., Elsevier/North-Holland Biomedical Press, New York (1981), p. 712.Google Scholar
  365. 365.
    R. W. Andonian and R. Kessler, Transplacental exposure to diethylstibestrol in men, Urology 13: 276 (1979).PubMedCrossRefGoogle Scholar
  366. 366.
    M. Bibbo, W. B. Gill, F. Azizi, R. Blough, V. S. Fang, R. L. Rosenfeld, G. F. B. Schumacher, K. Sleeper, M. G. Sonek, and G. L. Wied, Follow-up study of male and female offspring of DES-exposed mothers, Obstet. Gynecol. 49:1 (1977).Google Scholar
  367. 367.
    The Merck Index,“ 8th ed., Merck and Co., Rahway, NJ (1968), p. 410.Google Scholar
  368. 368.
    IARC Monographs Vol. 11, IARC, Lyon, France (1976), pp. 131–139.Google Scholar
  369. 369.
    B. A. Bridges, On the detection of volatile liquid mutagens with bacteria: Experiments with dichlorvos and epichlorohydrin, Mutat. Res. 54: 367 (1978).PubMedCrossRefGoogle Scholar
  370. 370.
    D. J. Kilian, T. G. Pullin, T. H. Conner, M. S. Legator, and H. N. Edwards, Mutagenicity of epichlorohydrin in the bacterial assay system: Evaluation by direct in vitro activity and in vivo activity of urine from exposed humans and mice, Mutat. Res. 53: 72 (1978).Google Scholar
  371. 371.
    K. Hemminki and K. Falck, Correlation of mutagenicity and 4-(p-nitrobenzyl)-pyridine alkylation by epoxides, Toxicol. Lett. 4: 103 (1979).CrossRefGoogle Scholar
  372. 372.
    R. E. McMahon, J. C. Cline, and C. Z. Thompson, Assay of 855 test chemicals in ten tester strains using a new modification of the Ames test for bacterial mutagens, Cancer Res. 39: 682 (1979).Google Scholar
  373. 373.
    R. K. Vashishat, M. Vasudeva, and S. N. Kakar, Induction of mitotic crossing over, mitotic gene conversion and reverse mutation by epichlorohydrin in Saccharomyces cerevisiae, Indian J. Exp. Biol. 18: 1337 (1980).Google Scholar
  374. 374.
    H. Heslot, A quantitative study of biochemical reversions induced in the yeast Schizosaccharomyces pombe by radiations and radiomimetic substances, Abhand der Deutschen Akademie der Wissenschaften zu Berlin Klasse fur Medizin 1: 193 (1962).Google Scholar
  375. 375.
    H. E. Brockman, “Report on Epichlorohydrin (ECH) Using the ad–3 Test System (Heterocaryon–12) of Neurospora crassa,” report under Contract NIH–75–0–17300, National Institutes of Health (unpublished).Google Scholar
  376. 376.
    A. D. Laumbach, S. Lee, J. Wong, and U. N. Streips, Studies on the mutagenicity of vinyl chloride metabolites and related chemicals, in: “Proceedings of the Third International Symposium on Prevention and Detection of Cancer,” Vol. 1 (1977), p. 155.Google Scholar
  377. 377.
    A. D. White, In vitro induction of SCE in human lymphocytes by epichlorohydrin with and without metabolic activation, Mutat. Res. 78:171 (1980).Google Scholar
  378. 378.
    R. J. Sram, M. Cerna, and M. Kucerova, The genetic risk of epichlorohydrin as related to the occupational exposure, Biol. Zbl. 95: 451 (1976).Google Scholar
  379. 379.
    M. Kucerova and Z. Polivkova, Banding technique used for the detection of chromosomal aberrations induced by radiation and alkylating agents TEPA and epichlorohydrin, Mutat. Res. 34: 279 (1976).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Michael D. Waters
    • 1
  • Neil E. Garrett
    • 2
  • Christine M. Covone-de Serres
    • 3
  • Barry E. Howard
    • 1
  • H. Frank Stack
    • 2
  1. 1.Genetic Toxicology Division Health Effects Research LaboratoryU.S. Environmental Protection AgencyResearch Triangle ParkUSA
  2. 2.Environmental SciencesNorthrop Services, Inc.Research Triangle ParkUSA
  3. 3.Genetics CurriculumUniversity of North CarolinaChapel HillUSA

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