Evaluation in Man and Animals of Tests for the Detection of Population Exposures to Genotoxic Chemicals

  • Jonathan B. WardJr.
  • Marvin S. Legator
  • Michael A. Pereira
  • Lina W. Chang
Part of the Environmental Science Research book series (ESRH, volume 27)


Over the past several decades, our increasing use of and reliance upon fossil fuels and synthetic chemicals have resulted in rapidly increasing human contact with chemicals not previously found in the environment. Acute toxic effects of chemical exposure have usually been recognized quickly and steps taken to minimize hazards. The effects of chronic exposures or delayed effects of exposure have been more difficult to recognize.


Chromosome Aberration Sister Chromatid Exchange Mutagenic Agent Sperm Morphology Chromosome Damage 
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  1. Ames, B.N., J. McCann, and E. Yamasaki. 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutation Res. 31:347–364.Google Scholar
  2. Auerbach, C., M. Moutschen-Dahmen, and J. Moutschen. 1977. Genetic and cytogenetical effects of formaldehyde and related compounds. Mutation Res. 39:317–362.Google Scholar
  3. Beckman, G., L. Beckman, I. Nordenson, and S. Nordstrom. 1979. Chromosomal aberrations in workers exposed to arsenic. In: Genetic Damage Caused by Environmental Agents. Academic Press: New York. pp. 205–211.Google Scholar
  4. Bloom, A.D., S. Neriishi, N. Kamada, T. Iseki, and R.J. Kehha. 1966. Cytogenetic investigation of survivors of the atomic bombings of Hiroshima and Nagasaki. Lancet 11:672–674.CrossRefGoogle Scholar
  5. Buckton, K.E., P.G. Smith, and W.M. Court-Brown. 1967. Estimation of life span from studies on males treated with X rays for ankelosing spondylitis. In: Human Cytogenetics. H.J. Evans, W. Court-Brown, and A.S. McLean, eds. North Holland: Amsterdam, pp. 106–114.Google Scholar
  6. Calleman, C.J., L. Ehrenberg, B. Jansson, S. Osterman-Golkar, D. Segerbach, K. Svennson, and CA. Wachtmeister. 1978. Monitoring and risk assessment by means of alkyl groups in hemoglobin in persons occupâtionally exposed to ethylene oxide. J. Environ. Pathol. Toxicol. 2:427–442.Google Scholar
  7. Commoner, B., A.J. Vithayathil, and J.I. Henry. 1974. Detection of metabolic carcinogen intermediates in urine of carcinogen-fed rats by means of bacterial mutagenesis. Nature 249:850–852.ADSCrossRefGoogle Scholar
  8. Connor, T.H., M. Stoeckel, J. Evrard, and M.S. Legator. 1977. The contribution of metronidazole and two metabolites to the mutagenic activity detected in urine of treated humans and mice. Cancer Res. 37:629–633.Google Scholar
  9. Dolphin, G.W., D.C. Lloyd, and R.J. Purrot. 1973. Chromosome aberration analysis as a dosimetric technique in radiological protection. Health Physics 25:7–15.CrossRefGoogle Scholar
  10. Ducatman, A.K., K. Hirschhorn, and I.V. Selikoff. 1975. Vinyl chloride exposure and human chromosome aberrations. Mutation Res. 31:163–168.Google Scholar
  11. Durston, W.E., and B.N. Ames. 1974. A simple method for the detection of mutagens in urine: studies with the carcinogen 2-acetylaminofluorene. Proc. Natl. Acad. Sci. USA 71:737–741.ADSCrossRefGoogle Scholar
  12. Ehrenberg, L., and S. Osterman-Golkar. 1980. Alkylation of macromolecules for detecting mutagenic agents. Teratogen. Carcinogen. Mutagen. 1:105–127.CrossRefGoogle Scholar
  13. Etteldorf, J.N., C.D. West, J.A. Pitcock, and D.L. Williams. 1976. Gonadal function testicular history and meiosis following cyclophosphamide therapy in patients with nephrotic syndrome. J. Pediat. 88:206–212.CrossRefGoogle Scholar
  14. Evans, H.J., and M.L. O’Riordan. 1977. In: Handbook of Mutagenicity Test Procedures. B.J. Kilby, M.S. Legator, W. Nichols, and C. Ramel, eds. Elsevier Scientific Publishing Co.: New York. pp. 261–274.Google Scholar
  15. Forni, A., and G.C. Secci. 1972. Chromosome changes in preclinical and clinical lead poisoning: correlation with biochemical findings. Proceedings of the International Symposium Environmental Health Aspects of Lead, Amsterdam.Google Scholar
  16. Funes-Cravioto, F., B. Lambert, J. Lindsten, L. Ehrenberg, A.T. Natarajan, and S. Osterman-Golkar. 1975. Chromosome aberrations in workers exposed to vinyl chloride. Lancet 1:459.CrossRefGoogle Scholar
  17. Gabridge, M.C., A. Denuzio, and M.S. Legator. 1969. Microbial mutagenicity of streptozotocin in animal-mediated assays. Nature 221:68–70.ADSCrossRefGoogle Scholar
  18. Garry, V.F., J. Hozier, D. Jacobs, R.L. Wade, and D.G. Gray. 1979. Ethylene oxide: evidence of human chromosomal effects. Environ. Mutagen. 1:375–382.CrossRefGoogle Scholar
  19. Garza-Chapa, R., C.H. Leal-Garza, and G. Molina-Ballestros. 1977. Archivos de Investigacion Mexicol (Mexico) 8:11–20.Google Scholar
  20. Green, M.H.L. 1979. Mutagenic consequences of chemical reaction with DNA. In: Chemical Carcinogens and DNA, Volume II. P.L. Grover, ed. CRC Press, Inc.: Boca Raton, Florida, pp. 95–132.Google Scholar
  21. IARC, 1979. IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans. International Agency for Research on Cancer, Lyons, France. IARC Monographs Supplement 1.Google Scholar
  22. Kapp, R.W., Jr., and C.B. Jacobson. 1980. Analysis of spermatozoa for Y chromosome non-disjunction. Teratogen. Carcinogen. Mutagen. 12:193–212.Google Scholar
  23. Katosova, L.D. 1973. Cytogenetic analysis of peripheral blood of workers engaged in the production of chloroprene. Gigiera. fuda i professional nye Zabolevaniia 10:30–32.Google Scholar
  24. Kissane, J.M., and E. Robins. 1958. The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J. Biol. Chem. 233:184–188.Google Scholar
  25. Kohn, K.W., L.C. Erickson, R.A.G. Ewig, and C.A. Friedman. 1976. Fractionation of DNA from mammalian cells by alkaline elution. Biochemistry 15:4629–4637.CrossRefGoogle Scholar
  26. Kucerova, M., V.S. Zhurkor, L. Polivkova, and J.E. Ivanove. 1977. Mutagenic effect of epichlorohydrin, II; analysis of chromosomal aberrations in lymphocytes of persons occupationally exposed to epichlorohydrin. Mutation Res. 48:355–360.CrossRefGoogle Scholar
  27. Latt, S.A. 1974. Localization of sister chromatid exchanges in human chromosomes. Science 185:74–76.ADSCrossRefGoogle Scholar
  28. Latt, S.A., J.W. Allen, W.E. Rogers, and L.A. Juergens. 1977. In vitro and in vivo analysis of sister chromatid exchange formation. In: Handbook of Mutagenicity Test Procedures. B.J. Kilbey, M.S. Legator, W. Nichols, and C. Ramel, eds. Elsevier Scientific Publishing Co.: New York. pp. 275–291.Google Scholar
  29. Legator, M.S., T.H. Connor, and M. Stoeckel. 1975. Detection of mutagenic activity of metronidazole and niridazole in body fluids of humans and mice. Science 188:1188–1189.CrossRefGoogle Scholar
  30. Meretoja, T., H. Vainio, M. Sorse, and H. Harkonen. 1977. Occupational styrene exposure and chromosomal aberrations. Mutation Res. 56:193–197.CrossRefGoogle Scholar
  31. Minnich, V., M.E. Smith, D. Thompson, and S. Kornfeld. 1976. Detection of mutagenic activity in human urine using mutant strains of Salmonella typhimurium. Cancer 31:1253–1258.CrossRefGoogle Scholar
  32. NIOSH, 1977. National Institute of Occupational Safety and Health Manual of Analytical Methods. 2nd edition, Volume 1.Google Scholar
  33. Nordenson, I., G. Beckman, L. Beckman, and S. Nordstrom. 1978. Occupational and environmental risks in and around smelter in northern Sweden, II; chromosomal aberrations in workers exposed to arsenic. Hereditas 88:47–50.CrossRefGoogle Scholar
  34. Normal, A., M.S. Sasaki, and R.E. Ottoman. 1966. Elimination of chromosome aberrations from human lymphocytes. Blood 27:706–714.Google Scholar
  35. Nowell, P.C. 1965. Unstable chromosome changes in tuberculin-stimulated leukocyte cultures from irradiated patients; evidence for immunologically committed, long-lived lymphocytes in human blood. Blood 26:798–804.Google Scholar
  36. Osterman-Golkar, S., L. Ehrenberg, D. Segerback, and I. Hallstrom. 1976. Evaluation of genetic risks of alkylating agents, II: haemoglobin as a dose monitor. Mutation Res. 34:1–10.CrossRefGoogle Scholar
  37. Osterman-Golkar, S., D. Hultmark, D. Segerback, C.J. Calleman, R. Gothe, L. Ehrenberg, and C.A. Wachtmeister. 1977. Alkylation of DNA and proteins in mice exposed to vinyl chloride. Biochem. Biophys. Res. Commun. 76:259–266.CrossRefGoogle Scholar
  38. Parodi, S., M. Taningher, L. Santi, M. Cavanna, L. Sciaba, A. Maura, and G. Brambilla. 1978. A practical procedure for testing DNA damage in vivo, proposed for a pre-screening of chemical carcinogens. Mutation Res. 54:39–46.Google Scholar
  39. Pereira, M.A., L.-H.C. Lin, and L.W. Chang. 1981. Dose dependence of 2-aminofluorene binding to liver DNA and hemoglobin in mice and rats. Toxicol. Appl. Pharmacol. 60:472–478.CrossRefGoogle Scholar
  40. Pereira, M.A., and L.W. Chang, (in press). Binding of bromoform and chloroform to mouse and rat hemoglobin. Chem.-Biol. Int.Google Scholar
  41. Petzgold, G.L., and J.A. Swenberg. 1978. Detection of DNA damage induced in vivo following exposure of rats to carcinogens. Cancer Res. 38:1589–1594.Google Scholar
  42. Picciano, D.J. 1979. Cytogenetic investigation of occupational exposure to epichlorohydrin. Mutation Res. 66:169–173.CrossRefGoogle Scholar
  43. Picciano, D.J. 1979. Cytogenetic study of workers exposed to benzene. Environ. Res. 19:33–38.CrossRefGoogle Scholar
  44. Ross, W.E., and N. Shipley. 1980. Relationship between DNA damage and survival in formaldehyde-treated mouse cells. Mutation Res. 79:277–283.CrossRefGoogle Scholar
  45. Sanotskii, I.V. 1976. Aspects of the toxicity of chloroprene: immediate and long-term effects. Environ. Health Perspect. 17:85–93.CrossRefGoogle Scholar
  46. Siebert, D., and A. Simon. 1973. Genetic activity of metabolites in the ascitic fluid and in the urine of a human patient treated with cyclophosphamide: induction of mitotic gene conversion in Saccharomyces cerevisiae. Mutation Res. 21:257–262.CrossRefGoogle Scholar
  47. Silezneva, T.G., and N.P. Korman. 1973. Analysis of chromosomes of somatic cells in patients treated with anti-tumor drugs. Soviet Genet. 9:1575–1579.Google Scholar
  48. Swenberg, J.A., W.D. Kerns, R.I. Mitchell, E.J. Gralla, and K.L. Pavkov. 1980. Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. Cancer Res. 40:3398–3402.Google Scholar
  49. Tough, I.M., P.G. Smith, W.M. Court-Brown, and D.G. Hardner. 1970. Chromosome studies on workers exposed to atmospheric benzene: the possible influence of age. Eur. J. Cancer 6:49.Google Scholar
  50. Truong, L., J.B. Ward, Jr., and M.S. Legator. 1978. Detection of alkylating agents by the analysis of amino acid residues in hemoglobin and urine, 1; the in vivo and in vitro effects of ethylmethanesulfonate, methyl methanesulfonate, hycanthone methanesulfonate, and naltrexone. Mutation Res. 54:271–281.Google Scholar
  51. Whorton, E.B., Jr., D.B. Bee, and D.J. Kilian. 1979. Variations in the proportion of abnormal cells and required sample sizes for human cytogenetic studies. Mutation Res. 64:79–86.Google Scholar
  52. Wilson, J.G. 1977. Current status of teratology; general principles and mechanisms derived from animal studies. In: Handbook of Teratology, Volume 1. J.G. Wilson and F.C. Fraser, eds. Plenum Press: New York. pp. 47–74.Google Scholar
  53. Wyrobek, A.J., and W.R. Bruce. 1978. Tne induction of sperm shape abnormalities in mice and humans. In: Chemical Mutagens: Principles and Methods for Their Detection, Volume 5. A. Hollaender and F.J. deSerres, eds. Plenum Press: New York. pp. 257–285.Google Scholar
  54. Wyrobek, A.J. 1979. Changes in mammalian sperm morphology after x-ray and chemical exposures. Genetics 92:sl04-sll9.Google Scholar
  55. Yamasaki, E., and B.N. Ames. 1977. Concentration of mutagens from urine with the non-polar resin XAD-2: cigarette smokers have mutagenic urine. Proc. Natl. Acad. Sci. USA 74:3555–3559.ADSCrossRefGoogle Scholar
  56. Zundova, Z., and K. Landa. 1977. Genetic risk of occupational exposures to haloethers. Mutation Res. 46:242–243.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Jonathan B. WardJr.
    • 1
  • Marvin S. Legator
    • 1
  • Michael A. Pereira
    • 2
  • Lina W. Chang
    • 2
  1. 1.Division of Environmental Toxicology, Department of Preventive Medicine and Community HealthUniversity of Texas Medical BranchGalvestonUSA
  2. 2.Health Effects Research LaboratoryU.S. Environmental Protection AgencyCincinnatiUSA

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