Short-Term Methods for Assessing in Vivo Carcinogenic Activity of Complex Mixtures

  • Michael A. Pereira
  • Richard J. Bull
Part of the Environmental Science Research book series (ESRH, volume 22)


The carcinogenic activity of a chemical or a complex mixture derived from an environmental sample is assessed most efficiently through a three-tier decision scheme (Bridges, 1973; Weisburger and Williams, 1977; Bull and Pereira, in press). In tier 1, the samples are screened for evidence of carcinogenic and mutagenic activity. The Ames Salmonella mutation bioassay and in vitro and in vivo cytogenetic assays appear to sucessfully identify most chemicals and samples with carcinogenic activity. These two types of assays detect the two major classes of genotoxic agents, mutagens and clastogens, and would therefore form the backbone of tier 1. Other possible assays for tier 1 include mammalian cell mutation, sister-chromatid exchange, micronuclei, and unscheduled DNA synthesis. The nature of tier 1 bioassays--especially their lack of correlation to carcinogenic potency, the absence of a direct demonstration of cancer or neoplasia, and the number of false positives--requires that carcinogenic activity be confirmed in tier 2.


Environmental Sample Partial Hepatectomy Mouse Skin Ames Test Drinking Water Sample 
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. Andrews, A.W., L.H. Thibault, and W. Lijinsky. 1978x. The relationship between carcinogenicity and mutagenicity of some polynuclear hydrocarbons. Mutation Res. 51: 311–318.CrossRefGoogle Scholar
  2. Andrews, A.W., L.H. Thibault, and W. Lijinsky. 1978b. The relationship between mutagnicity and carcinogenicity of some nitrosamines. Mutation Res. 51: 319–326.CrossRefGoogle Scholar
  3. Bridges, B.A. 1973. Some general principles of mutagenicity screening and possible framework for testing procedures. Environ. Hlth. Perspect. 6: 221–227.MathSciNetCrossRefGoogle Scholar
  4. Bull, R.J., and M.A. Pereira. (in press). Development of a short-term testing matrix for estimating relative carcinogenic risk. J. Environ. Pathol. Toxicol.Google Scholar
  5. Bull, R.J., M.A. Pereira, and K.L. Blackburn. (in press). Bioassay techniques for evaluating the possible carcinogenicity of absorber effluents. In: Conference on Practical Application of Adsorption Techniques.Google Scholar
  6. DiPaolo, J.A. 1979. Quantitative transformation by carcinogens of cells in early passage. In: Environmental Carcinogenesis. P. Emmelot and E. Kriek, eds. Elsevier Press: Amsterdam. pp. 365–380.Google Scholar
  7. Druckrey, H., A. Schildback, D. Schmahl, R. Preusmann, and S. Ivankovic. 1963. Quantitative Analyse der carcinogenen Wirkung von Diathynitrosamin. Arzneimittel-Forsch. 13: 841–851.Google Scholar
  8. Ford, J.O., and M.A. Pereira. (in press). Short-term in vivo initiation/promotion bioassay for hepatocarcinogens. J. Environ. Pathol. Toxicol.Google Scholar
  9. IRLG, Interagency Regulatory Liaison Group, Work Group on Risk Assessment. 1979. Scientific basis for identification of potential carcinogens and estimation of risks. J. Natl. Cancer Inst. 63: 241–248.Google Scholar
  10. Latt, S.A., R.R. Schreck, K.S. Loveday, and C.R. Shuler. 1979. In vitro and in vivo analysis of sister chromatid exchange. Pharmacol. Rev. 30: 501–535.Google Scholar
  11. Loper, J.C., D.R. Lang, R.S. Schoeny, B.B. Richmond, P.M. Gallagher, and C.C. Smith. 1978. Residue organic mixtures from drinking water show in vitro mutagenic and transforming activity. J. Toxicol. Environ. Hlth. 4: 919–938.CrossRefGoogle Scholar
  12. Meselson, M., and K. Russell. 1977. Comparisons of carcinogenic and mutagenic potency. In: Origins of Human Cancer, Book C. H.H. Hiatt, J.D. Watson, and J.A. Winsten, eds. Cold Spring Harbor Laboratory: Cold Spring Harbor, NY. pp. 604–628.Google Scholar
  13. Pereira, M.A. (in press). Rat liver foci bioassay. J. Environ. Pathol. Toxicol.Google Scholar
  14. Robinson, M., J.W. Glass, D. Cmehil, R.J. Bull, and J.G. Orthoefer. 1980. Initiating and promoting activity of chemicals isolated from drinking waters in the SENCAR mouse: a five-city survey. Presented at the U.S. Environmental Protection Agency SecondGoogle Scholar
  15. Symposium on the Application of Short-term Bioassays in the Fractionation and Analysis of Complex Environmental Mixtures, Williamsburg, VA.Google Scholar
  16. Scherer, E., and P. Emmelot. 1976. Kinetics of induction and growth of enzyme-deficient islands involved in hepatocarcinogenesis. Cancer Res. 36: 2544–2554.Google Scholar
  17. Shimkin, M.B., and G.D. Stoner. 1975. Lung tumors in mice: Application to carcinogenesis bioassay. Adv. Cancer Res. 21: 1–58.CrossRefGoogle Scholar
  18. Slags, T.J., S.M. Fischer, L.L. Triplett, and S. Nesnow. (in press). Comparison of complete carcinogenesis and tumor initiation in mouse skin: Tumor initiation-promotion, a reliable short-term assay. J. Environ. Pathol. Toxicol.Google Scholar
  19. Stoner, G.D., and M.B. Shimkin. (in press). Strain A mouse lung tumor bioassay. J. Environ. Pathol. Toxicol.Google Scholar
  20. Syles, J.A. 1979. Cell transformation assays. In: Mutagenesis in Sub-mammalian Systems. G.E. Paget, ed. Baltimore University Press: Baltimore. pp. 53–71.Google Scholar
  21. Weisburger, J.H., and G.M. Williams. 1977. Decision point approach to carcinogen testing. In: Structural Correlates of Carcinogenesis and Mutagenesis. HEW Publication No. (FDA) 78–1046. Rockville, MD. pp. 45–52.Google Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Michael A. Pereira
    • 1
  • Richard J. Bull
    • 1
  1. 1.Health Effects Research LaboratoryU.S. Environmental Protection AgencyCincinnatiUSA

Personalised recommendations