An Overview of Animal and Microbial Test Systems for Carcinogenesis and Mutagenesis

Problems with Human Variation
  • G. R. Mohn
Part of the Human Genetics, Supplement book series (HUMAN GENETICS, volume 1)


In preventive medicine, the early and efficient detection of environmental carcinogens and mutagens and the evaluation of their genetic effects have become matters of great priority during the past few years. Reason is the very high and ever increasing number of synthetic and natural substances present in the human environment. According to estimates of the United Nations Environment Programme, some half a million chemicals are in current use throughout the world and about ten thousand are produced annually in amounts of between 500 and 1,000,000 kg (UNEP, 1975). While for most of these substances there is a priori no reason for assuming harmful genetic activity, some have been recently and unexpectedly shown to possess mutagenic properties in experimental animals. An increase of the human spontaneous or natural mutation rate will be at best neutral but more probably deleterious (leading to embryonic death and to more or less severe malformations and metabolic diseases) for subsequent generations. Enhanced frequency of mutations in somatic cells is also very likely to contribute to cancerogenic ill-health in man, as empirically demonstrated by the recent findings that most carcinogens are also mutagens (McCann et al. , 1975). In view of the high number of chemicals to be tested for genetic effects and because of the present impossibility of predicting the mutagenicity of a given compound, testing strategies have been developed (Flamm, 1974; Bridges, 1976; Bora, 1976).


Chemical Mutagen Mutagenic Property Polycyclic Hydrocarbon Methyl Methane Sulfonate Aryl Hydrocarbon Hydroxylase 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ames, B. N., McCann, J., Yamasaki, E.: Methods for detecting carcinogens and mutagens with the Salmonella/Mammalian-microsome mutagenicity test. Mutation Res. 31, 347–364 (1975)PubMedGoogle Scholar
  2. Baars, A. J., Zijlstra, J. A., Vogel, E., Breimer, D. D.: The occurence of cytochrome P-450 and aryl hydrocarbon hydroxylase activity in Drosophila microsomes, and the importance of this metabolizing capacity for the screening of carcinogenic and mutagenic properties of foreign compounds. Mutation Res. 44, 257–268 (1977)PubMedCrossRefGoogle Scholar
  3. Baker, R. M., Brunette, D. M., Mankovitz, R., Thompson, L. H., Whitmore, G. F., Siminovich, L., Till, J. E.: Ouabain-resistant mutants of mouse and hamster cells in culture. Cell 1, 9–21 (1974)CrossRefGoogle Scholar
  4. Bateman, A.: The dominant lethal assay in the male mouse. In: Handbook of mutagenicity test procedures, B.J. Kilbey et al. , eds., pp. 325–334. Amsterdam: Elsevier 1977Google Scholar
  5. Bora, K. C.: A hierarchical approach to mutagenicity testing and regulatory control of environmental chemicals. Mutation Res. 41, 73–82 (1976)PubMedCrossRefGoogle Scholar
  6. Bridges, B. A.: Evaluation of mutagenicity and carcinogenicity using a three-tier system. Mutation Res. 41, 71–72 (1976)CrossRefGoogle Scholar
  7. Busbee, D. L., Guy den, J., Kingston, T., Rose, F. L., Cantrell, E. T.: Metabolism of benzo(a)-pyrene in animals with high aryl hydrocarbon hydroxylase levels and high rates of spontaneous cancer. Cancer Letters 4, 61–67 (1978)PubMedCrossRefGoogle Scholar
  8. Cleaver, J. E.: DNA repair processes and their impairment in some human diseases. In: Progress in genetic toxicology, D. Scott et al. , eds., pp. 29–42. Amsterdam: Elsevier/North-Holland 1977 aGoogle Scholar
  9. Cleaver, J. E.: Methods for studying excision repair of DNA damaged by physical and chemical mutagens. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 19–48. Amsterdam: Elsevier 1977 bGoogle Scholar
  10. Czygan, P., Greim, H., Garro, A. J., Hutterer, F., Rudick, J., Schaffner, F., Popper, H.: Cytochrome P-450 content and the ability of liver microsomes from patients undergoing abdominal surgery to alter the mutagenicity of a primary and a secondary carcinogen. J. Natl. Cancer Inst. 51, 1761– 1764 (1973)PubMedGoogle Scholar
  11. Dean, B. J., Senner, K. R.: Detection of chemically-induced mutations in tissues of Chinese hamsters. In: Progress in genetic toxicology, D. Scott et al. , eds., pp. 201–206. Amsterdam: Elsevier/North-Holland 1977Google Scholar
  12. Evans, H. J.: Cytological methods for detecting chemical mutagens. In: Chemical mutagens, A. Hollaender, ed., pp. 1–30. New York: Plenum 1976Google Scholar
  13. Fahrig, R.: The mammalian spot test (Fellfleckentest) with mice. Arch. Toxicol. 38, 87–98(1977)PubMedCrossRefGoogle Scholar
  14. Flamm, W. G.: A tier system approach to mutagen testing. Mutation Res. 26, 329–333 (1974)PubMedCrossRefGoogle Scholar
  15. Frantz, C. N., Mailing, H. V.: The quantitative microsomal mutagenesis assay method. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 49–64. Amsterdam: Elsevier 1977Google Scholar
  16. Gabridge, M. G., DeNunzio, A., Legator, M. S.: Microbial mutagenicity of streptozotocin in animal-mediated assays. Nature 221, 68–70 (1969)PubMedCrossRefGoogle Scholar
  17. Green, M. H. L., Muriel, W. J.: Mutagen testing using trp+ reversion in Escherichia coli. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 65–94. Amsterdam: Elsevier 1977Google Scholar
  18. Heinemann, B.: Prophage induction in lysogenic bacteria as a method of detecting potential mutagenic, carcinogenic, carcinostatic, and teratogenic agents. In: Chemical mutagens, A. Hollaender, ed., Vol. 1, pp. 235–266. New York: Plenum Press 1971Google Scholar
  19. Jacobs, L., DeMars, R.: Chemical mutagenesis with diploid human fibroblasts. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 193–220. Amsterdam: Elsevier 1977Google Scholar
  20. Kada, T., Tutikawa, K., Dadaie, Y.: In vitro and host-mediated “rec-assay” procedures for screening chemical mutagens; and phloxine, a mutagenic red dye detected. Mutation Res. 16, 165–174 (1972)PubMedCrossRefGoogle Scholar
  21. Klose, J.: The protein-mapping method employed to test for chemically induced point mutations in mice. Arch. Toxicol. 38, 53–60 (1977)PubMedCrossRefGoogle Scholar
  22. Knaap, A. G. A. C., Simons, J. W. I. M.: A mutational assay system for L5178Y mouse lymphoma cells using hypoxanthine-guanine-phosphoribosyl-transferase(HGPRT)-deficiency as marker. The occurence of a long expression time for mutations induced by X-rays and EMS. Mutation Res. 30, 97–110 (1975)PubMedCrossRefGoogle Scholar
  23. Kohn, H. I., Melvold, R. W.: Divergent X-ray induced mutation rates in the mouse for H and “7 locus” groups of loci. Nature 259, 209–210 (1976)PubMedCrossRefGoogle Scholar
  24. Latt, S. A., Allan, J. W., Rogers, W. E., Jeurgens, L. A.: In vitro and in vivo analysis of sister chromatid exchange formation. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 275–292. Amsterdam: Elsevier 1977Google Scholar
  25. Legator, M. S., Zimmering, S., Connor, T. H.: The use of indirect indicator systems to detect mutagenic activity in human subjects and experimental animals. In: Chemical mutagens, A. Hollaender, ed., Vol. IV, pp. 171–192. New York: Plenum 1976Google Scholar
  26. Léonard, A.: Tests for heritable translocations in male mammals. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 293–300. Amsterdam: Elsevier 1977Google Scholar
  27. Malling, H. V., Valcovie, L. R.: Gene mutations in mammals. In: Progress in genetic toxicology, D. Scott et al. , eds., pp. 155–164. Amsterdam: Elsevier/North-Holland 1977Google Scholar
  28. McCann, J., Choi, E., Yamasaki, E., Ames, B. N.: Detection of carcinogens as mutagens in the Salmonella/microsome test: Assay of 300 chemicals. Proc. Natl. Acad. Sei. USA 72, 5135–5139 (1975)CrossRefGoogle Scholar
  29. Mohn, G. R.: Actual status of mutagenicity testing with the host-mediated assay. Arch. Toxicol. 38, 109–133 (1977)PubMedCrossRefGoogle Scholar
  30. Mohn, G. R., Ellenberger, J.: The use of Escherichia coli K-12/343/113 (A) as a multipurpose indicator strain in various mutagenicity testing procedures. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 95–118. Amsterdam: Elsevier 1977Google Scholar
  31. Pero, R. W., Bryngelsson, K., Mitelman, F., Thulin, T., Nordén, A.: High blood pressure related to carcinogen-induced unscheduled DNA synthesis, DNA carcinogen binding, and chromosomal aberrations in human lymphocytes. Proc. Natl. Acad. Sei. USA 73, 2496– 2500 (1976)CrossRefGoogle Scholar
  32. Russell, W. L.: X-ray induced mutations in mice. Cold Spring Harb. Symp. Quant. Biol. 16, 327–336 (1951)PubMedGoogle Scholar
  33. Schmid, W.: The micronucleus test. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 235–242. Amsterdam: Elsevier 1977Google Scholar
  34. Searle, A. G.: The specific locus test in the mouse. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 311–324. Amsterdam: Elsevier 1977Google Scholar
  35. Siebert, D., Simon, U.: Genetic activity of metabolites in the ascites 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 (1973)PubMedCrossRefGoogle Scholar
  36. Slater, E. E., Andersen, M. D., Rosenkranz, H. S.: Rapid detection of mutagens and carcinogens. Cancer Res. 31, 970–973 (1971)PubMedGoogle Scholar
  37. Sobels, F. H.: Some problems associated with the testing for environmental mutagens and a perspective for studies in “comparative mutagenesis.” Mutation Res. 46, 245–260 (1977)PubMedGoogle Scholar
  38. Strauss, G. H., Albertini, R. J.: 6-Thioguanine resistant lymphocytes in human peripheral blood. In: Progress in genetic toxicology, D. Scott et al. , eds., pp. 327–334. Amsterdam: Elsevier/ North-Holland 1977Google Scholar
  39. Tates, A. D., Natarajan, A. T., DeVogel, N., Meijers, M.: A correlative study on the genetic damage induced by chemical mutagens in bone marrow and spermatogonia of mice. III. l,3-bis(2-chloroethyl)-3-nitrosourea (BCNU). Mutation Res. 44, 87–95 (1977)PubMedCrossRefGoogle Scholar
  40. Tang, T., Friedman, M. A.: Carcinogen activation by human liver enzymes in the Ames mutagenicity test. Mutation Res. 46, 387–394 (1977)PubMedGoogle Scholar
  41. Thompson, L. H., Baker, R. M.: Isolation of mutants of cultures mammalian cells. In: Methods in cell biology, D.M. Prescott, ed., Vol. VI, pp. 209–281. New York: Academic Press 1973Google Scholar
  42. Thorgeirsson, S. S., Nebert, D. W.: The Ah locus and the metabolism of chemical carcinogens and other foreign compounds. Adv. Cancer Res. 25, 149–193 (1977)PubMedCrossRefGoogle Scholar
  43. UNEP: The international register of potentially toxic chemicals. UNEP brochure, September 1975Google Scholar
  44. Vogel, E., Sobels, F. H.: The function of Drosophila in genetic toxicology testing. In: Chemical mutagens, A. Hollaender, ed., Vol. IV, pp. 93–142. New York: Plenum Press 1976Google Scholar
  45. Van Zeeland, A. A., Simons, J. W. I. M.: Linear dose-response relationships after prolonged expression times in V-79 chines hamster cells. Mutation Res. 35, 129–138 (1976)PubMedCrossRefGoogle Scholar
  46. Würgler, F. E., Sobels, F. H., Vogel, E.: Drosophila as assay system for detecting genetic changes. In: Handbook of mutagenicity test procedures, B. Kilbey et al. , eds., pp. 335–374. Amsterdam: Elsevier 1977Google Scholar
  47. Zimmermann, F. K.: Detection of genetically active chemicals using various yeast systems. In: Chemical mutagens, A. Hollaender, ed., pp. 209–240. New York: Plenum Press 1973Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1978

Authors and Affiliations

  • G. R. Mohn
    • 1
  1. 1.State University of LeidenLeidenNetherlands

Personalised recommendations