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Relationship(S) between Mutation and Cytotoxicity Induced inVitro

  • J. H. Carver
  • A. D. Mitchell
  • M. D. Waters
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Part of the Environmental Science Research book series (ESRH, volume 27)

Abstract

Rapid, short-term tests are currently used to identify compounds mutagenic in vitro. In vivo tests are then used to confirm a compound’s activity in the intact animal and to assess oncogenic and genetic risk. Carver et al. (1979) presented the hypothesis that cytotoxicity induced by an agent in vitro might estimate potential mutagenicity in vivo. They compared the induced mutation frequency per unit exposure dose (M) of 22 known mutagens with the unit decrease in survival; a relative increase in cytotoxicity (defined as the failure of cultured cells to undergo continued cell division) was usually accompanied by a proportional increase in mutagenicity. The correlation between cytotoxicity and mutagenicity does not necessarily imply that lethal and mutagenic events arise from the same type of lesion; factors such as (de)toxification, biochemical reactions, and repair mechanisms may affect both end points. The relationship implies, however, that the maximum potential mutagenic potency of agents in vitro might be estimated from measurement of cytotoxic potency. Some compounds highly toxic in vitro are not significantly mutagenic in vitro, but agents rarely induce mutation in the complete absence of a dose-related increase in toxicity.

Keywords

Chinese Hamster Ovary Cell Coke Oven Chinese Hamster Cell Methyl Methanesulfonate Environmental Emission 
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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Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • J. H. Carver
    • 1
  • A. D. Mitchell
    • 2
  • M. D. Waters
    • 3
  1. 1.Chevron Environmental Health CenterRichmondUSA
  2. 2.Biochemical Genetics DepartmentSRI InternationalMenlo ParkUSA
  3. 3.Genetic Toxicology Division, Health Effects Research LaboratoryU.S. Environmental Protection AgencyResearch Triangle ParkUSA

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