Short‐Term Testing for Genotoxicity

Abstract

Exposure to particular chemicals or complex mixtures can lead to cancer in later life, and it is now believed that many cancers can arise from damage to DNA and the resulting mutations. As a consequence of this, it has become necessary to determine whether widely used chemicals or potentially useful new chemicals possess the ability to damage DNA. Data concerning the genotoxicity of a new chemical have become part of the basic toxicological information package. In this chapter, the individual test systems that are required for genotoxicity screening are described together with a discussion on how the results obtained should be interpreted. The test systems described are the bacterial mutation assay (commonly termed the Ames test ), in vitro mammalian cell assays for the detection of chromosome damage and gene mutations, and in vivo rodent assays for the detection of micronuclei and unscheduled DNA repair synthesis. As well as these primary test systems, there is also a description of the supplementary assays that may be required when investigating positive effects, including the comet assay and gene mutation assays using transgenic animals. Detailed guidance on the performance of any of these tests is not given, but this information is referenced at the end of the chapter. The chapter concludes with a brief overview of some of the recent developments in the field, specifically the use of modified assays for high‐throughput screening, the application of expert computer systems for predicting genotoxicity, and the possible impact of toxicogenomics on genotoxicity screening in the future.