Genotoxicology

Genotoxicology

Genotoxic chemicals cause damage to DNA, which if is non-lethal and not repaired, causes heritable changes in the genetic material in germ cells and can lead to cancer.

Genotoxins can have a number of effects, including forming DNA adducts, DNA cross-linking, DNA breaks and gene mutations, as well as causing larger structural effects such as sister chromatid exchange, micronuclei, chromosomal aberrations, and chromosome mutations. These effects can all be detected using different assays and, since genotoxins can act by one or more of a broad spectrum of effects, a battery of tests (including the Ames, Micronucleus and Comet assays) is needed to increase the sensitivity of their detection.

Moreover, pro-genotoxins, which require metabolic activation to the ultimate genotoxin, need the test system (e.g. PBMC, lymphocytes, TK6 etc) to include an exogenous metabolism source e.g. liver S9, or the target cells should themselves be metabolically active (only HepaRG™ cells fit this criterion so far).