Spontaneous and Induced gpt and Spi− Mutant Frequencies in gpt delta Transgenic Rodents

Abstract

Transgenic rodent mutation assays are useful models for investigating the genotoxicity of chemicals in vivo. Transgenic gpt delta mice contain multiple copies of chromosomally integrated lambda EG10 phage shuttle vector, which contains reporter genes that allow detection of mutations. This system can identify both point mutations by the gpt assay (6-thioguanine selection) and certain types of deletions using the Spi− assay. Transgenic gpt delta rats, which have the same lambda EG10 DNA copies as gpt delta mice, have also been developed. The average spontaneous gpt mutant frequency (MF) in both gpt delta mice and rats is approximately 4.5×10-6. In the Spi− assay, the average spontaneous Spi− MF is approximately 2.7×10-6 in gpt delta mice, similar to that of gpt delta rats. More than 20 chemicals and irradiations have been analyzed with these systems, and this review summarizes the MFs and treatment conditions. The data demonstrate that these transgenic rodent models are useful for detection and analysis of point mutations and deletions in vivo.