In vitro mutagenesis assays as predictors of chemical carcinogenesis in mammals

Abstract

In vitro microbial mutagenesis assays coupled with mammalian activation systems offer promising technique to screen chemicals for their potential carcinogenic activity. The correlation between mutagenic and carcinogenic properties for a large array of chemicals is approximately 0.9. The best correlation exists for those carcinogens which are themselves highly electrophilic or produce electrophilic metabolites. Correlation between mutagenicity and carcinogenicity for hormonal, metallic, or physical carcinogens has been disappointing but not unexpected based on their proposed mechanisms of action. In addition to the application of in vitro mutagenesis techniques to screening chemicals for the identification of potential carcinogens, they are useful tools for investigating genetic, biochemical, and pharmacologic properties of different animal species. Studies with the chemical carcinogen dimethylnitrosamine have been conducted and show a functional relationship between mutagenesis and carcinogenesis. The assays can also be conducted using activation systems prepared from the tissues of any mammalian species. This permits a direct assessment of phylogenic extrapolation by comparing the metabolic activation capabilities of tissues from several mammalian species, including human samples. The advantages of mutagenicity testing are the short period of time required for results, the high sensitivity of the assay (microgram of nanogram quantities of chemicals can be used), and the fact that the ultimate agent can be detected biologically without first necessitating chemical identification and isolation. It appears from current studies that in vitro mutagenesis techniques may well open new avenues of investigation into some old toxicologic problems.