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. 1987 Nov;75:87–95. doi: 10.1289/ehp.877587

Comparative evaluation of genetic toxicity patterns of carcinogens and noncarcinogens: strategies for predictive use of short-term assays.

R W Tennant 1, J W Spalding 1, S Stasiewicz 1, W D Caspary 1, J M Mason 1, M A Resnick 1
PMCID: PMC1474441  PMID: 3319571

Abstract

The results of a recent comprehensive evaluation of the relationship between four measures of in vitro genetic toxicity and the capacity of the chemicals to induce neoplasia in rodents carry some important implications. The results showed that while the Salmonella mutagenesis assay detected only about half of the carcinogens as mutagens, the other three in vitro assays (mutagenesis in MOLY cells or induction of aberrations or SCEs in CHO cells) did not complement Salmonella since they failed to effectively discriminate between the carcinogens and noncarcinogens found negative in the Salmonella assay. The specificity of the Salmonella assay for this group of 73 chemicals was relatively high (only 4 of 29 noncarcinogens were positive). Therefore, we have begun to evaluate in vivo genetic toxicity assays for their ability to complement Salmonella in the identification of carcinogens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Durston W. E., Yamasaki E., Lee F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281–2285. doi: 10.1073/pnas.70.8.2281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ames B. N. Identifying environmental chemicals causing mutations and cancer. Science. 1979 May 11;204(4393):587–593. doi: 10.1126/science.373122. [DOI] [PubMed] [Google Scholar]
  3. Barrett J. C., Shelby M. D. Mechanisms of multistep carcinogenesis: keys to developing in vitro approaches for assessing the carcinogenicity of chemicals. Food Chem Toxicol. 1986 Jun-Jul;24(6-7):657–661. doi: 10.1016/0278-6915(86)90153-5. [DOI] [PubMed] [Google Scholar]
  4. Haseman J. K., Huff J. E., Zeiger E., McConnell E. E. Comparative results of 327 chemical carcinogenicity studies. Environ Health Perspect. 1987 Oct;74:229–235. doi: 10.1289/ehp.8774229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hatch G. G., Anderson T. M., Lubet R. A., Kouri R. E., Putman D. L., Cameron J. W., Nims R. W., Most B., Spalding J. W., Tennant R. W. Chemical enhancement of SA7 virus transformation of hamster embryo cells: evaluation by interlaboratory testing of diverse chemicals. Environ Mutagen. 1986;8(4):515–531. doi: 10.1002/em.2860080404. [DOI] [PubMed] [Google Scholar]
  6. Haworth S., Lawlor T., Mortelmans K., Speck W., Zeiger E. Salmonella mutagenicity test results for 250 chemicals. Environ Mutagen. 1983;5 (Suppl 1):1–142. [PubMed] [Google Scholar]
  7. 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 Sci U S A. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Miller J. A., Miller E. C. Some historical aspects of N-aryl carcinogens and their metabolic activation. Environ Health Perspect. 1983 Mar;49:3–12. doi: 10.1289/ehp.83493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mirsalis J. C., Butterworth B. E. Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents: an in vivo- in vitro assay for potential carcinogens and mutagens. Carcinogenesis. 1980 Jul;1(7):621–625. doi: 10.1093/carcin/1.7.621. [DOI] [PubMed] [Google Scholar]
  10. Nishizumi M. Enhancement of diethylnitrosamine hepatocarcinogenesis in rats by exposure to polychlorinated biphenyls or phenobarbital. Cancer Lett. 1976 Sep;2(1):11–15. doi: 10.1016/s0304-3835(76)80004-3. [DOI] [PubMed] [Google Scholar]
  11. Oldham J. W., Casciano D. A., Cave M. D. Comparative induction of unscheduled DNA synthesis by physical and chemical agents in non-proliferating primary cultures of rat hepatocytes. Chem Biol Interact. 1980 Mar;29(3):303–314. doi: 10.1016/0009-2797(80)90149-0. [DOI] [PubMed] [Google Scholar]
  12. Pitot H. C., Goldsworthy T., Campbell H. A., Poland A. Quantitative evaluation of the promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamine. Cancer Res. 1980 Oct;40(10):3616–3620. [PubMed] [Google Scholar]
  13. Purchase I. F., Longstaff E., Ashby J., Styles J. A., Anderson D., Lefevre P. A., Westwood F. R. Evaluation of six short term tests for detecting organic chemical carcinogens and recommendations for their use. Nature. 1976 Dec 16;264(5587):624–627. doi: 10.1038/264624a0. [DOI] [PubMed] [Google Scholar]
  14. Shelby M. D., Stasiewicz S. Chemicals showing no evidence of carcinogenicity in long-term, two-species rodent studies: the need for short-term test data. Environ Mutagen. 1984;6(6):871–878. doi: 10.1002/em.2860060613. [DOI] [PubMed] [Google Scholar]
  15. Suk W. A., Poiley J. A., Raineri R., Steuer A. F., Tennant R. W. Chemical enhancement of survival in aggregation of retrovirus-infected rat cells: an interlaboratory comparison. Environ Mutagen. 1985;7(5):727–746. doi: 10.1002/em.2860070511. [DOI] [PubMed] [Google Scholar]
  16. Tennant R. W., Margolin B. H., Shelby M. D., Zeiger E., Haseman J. K., Spalding J., Caspary W., Resnick M., Stasiewicz S., Anderson B. Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science. 1987 May 22;236(4804):933–941. doi: 10.1126/science.3554512. [DOI] [PubMed] [Google Scholar]
  17. Tennant R. W., Stasiewicz S., Spalding J. W. Comparison of multiple parameters of rodent carcinogenicity and in vitro genetic toxicity. Environ Mutagen. 1986;8(2):205–227. doi: 10.1002/em.2860080204. [DOI] [PubMed] [Google Scholar]
  18. Tu A., Hallowell W., Pallotta S., Sivak A., Lubet R. A., Curren R. D., Avery M. D., Jones C., Sedita B. A., Huberman E. An interlaboratory comparison of transformation in Syrian hamster embryo cells with model and coded chemicals. Environ Mutagen. 1986;8(1):77–98. doi: 10.1002/em.2860080108. [DOI] [PubMed] [Google Scholar]
  19. Waters M. D., Auletta A. The GENE-TOX program: genetic activity evaluation. J Chem Inf Comput Sci. 1981 Feb;21(1):35–38. doi: 10.1021/ci00029a007. [DOI] [PubMed] [Google Scholar]
  20. Weisburger J. H., Williams G. M. Carcinogen testing: current problems and new approaches. Science. 1981 Oct 23;214(4519):401–407. doi: 10.1126/science.7291981. [DOI] [PubMed] [Google Scholar]
  21. Zimmering S., Mason J. M., Valencia R., Woodruff R. C. Chemical mutagenesis testing in Drosophila. II. Results of 20 coded compounds tested for the National Toxicology Program. Environ Mutagen. 1985;7(1):87–100. doi: 10.1002/em.2860070105. [DOI] [PubMed] [Google Scholar]

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