Tests for Biologic Markers of Genotoxic Exposure and Effect

Abstract

Markers of genetic damage are being used increasingly to understand and prevent environmentally related human adverse health effects. A major example has been the application of such markers to the prediction of chemical carcinogenicity. Over the past 15 years, hundreds of test systems in microorganisms, cell cultures and animals were devised and applied to this end. In spite of early successes, recent results show a discouragingly low, 60% agreement between the genetic tests and conventional, whole animal, long-term carcinogenicity assays. Corresponding efforts to predict the heritable mutagenicity of chemicals using genetic tests that do not involve heritability have given similar results. New technologic developments for the first time are letting us make such genotoxicity measurements directly in human subjects. Examples include detection of DNA adducts, measurement of somatic mutations and improved cytogenetic methods. There is also the possibility of soon finding sufficiently sensitive methods to estimate heritable mutagenicity as a predictor of damage to future generations. These biologic markers of genotoxicity are useful for estimating human exposure and effect, for identifying toxic environments, for monitoring cancer chemotherapy and for identifying susceptible populations. They offer a major new challenge to epidemiology and public health.