Methods for genotoxicity testing of environmental pollutants

Abstract

Genetic hazard assessment deals with changes in genetic material of organisms, either human or other natural origin. Although considered an important element of the basic mechanisms of evolution, mutations often have a more detrimental effect on individuals and their offspring, and may adversely affect populations. There is consensus about a close association of DNA damage, mutations and the induction of various types of cancer. In eco-genotoxicity, possible effects of mutagenic/genotoxic substances on populations and ecosystems are investigated. Mutagenicity testing has been performed with all types of organisms. For monitoring purposes higher organisms (eukaryotes) are exposed to the environmental compartment “in situ” or in laboratory tests “in vivo”. Mutagenicity represents permanent changes to single genes or chromosomes, while genotoxicity focuses on primary damage of DNA. The bacterial Ames, umuC and SOS chromo assays have been predominantly used. Tests with eukaryotic cells or organisms might be more relevant for human and ecological risk assessment, but generally they are much more time-consuming. Several tests have been developed using the integrity of DNA as a non-specific endpoint of genotoxicity e.g. comet assay, alkaline DNAelution assay, DNA alkaline unwinding assay, UDS-assay; the comet assay probably the most cost-efficient test among them. Most eukaryotic genotoxicity tests detect macro damage of chromosomes in the visible light microscope following appropriate staining (chromosomal aberration, micronucleus assay, SCE assay). Plants, amphibians, fish and water mussels as well as permanent mammalian cell lines such as V79, CHO or CHL have been used as the test organisms. Newer technologies such as transcriptomics, proteomics and metabolomics provide the opportunity to gain insight into genotoxic mechanisms and also to provide new markers in vitro and in vivo. There is also an increasing number of animal models with relevance to genotoxicity testing. These types of models will undoubtedly have an impact on genotoxicity testing in the future.