Past, Present and Future Directions of gpt delta Rodent Gene Mutation Assays.

Genotoxicity is a critical endpoint of toxicity to regulate environmental chemicals. Genotoxic chemicals are believed to have no thresholds for the action and impose genotoxic risk to humans even at very low doses. Therefore, genotoxic carcinogens, which induce tumors via genotoxic mechanisms, are regulated more strictly than non-genotoxic carcinogens, which induce tumors through non-genotoxic mechanisms such as hormonal effects, cell proliferation and cell toxicity. Although Ames bacterial mutagenicity assay is the gold standard to identify genotoxicity of chemicals, the genotoxicity should be further examined in rodents because Ames positive chemicals are not necessarily genotoxic in vivo. To better evaluate the genotoxicity of chemicals in a whole body system, gene mutation assays with gpt delta transgenic mice and rats have been developed. A feature of the assays is to detect point mutations and deletions by two distinct selection methods, ie, gpt and Spi- assays, respectively. The Spi- assay is unique in that it allows analyses of deletions and complex DNA rearrangements induced by double-strand breaks in DNA. Here, I describe the concept of gpt delta gene mutation assays and the application in food safety research, and discuss future perspectives of genotoxicity assays in vivo. ©2016 Food Safety Commission, Cabinet Office, Government of Japan.