The Pig‐a Gene Mutation Assay in Mice and Human Cells: A Review

This MiniReview describes the principle of mutation assays based on the endogenous Pig‐a gene and summarizes results for two species of toxicological interest, mice and human beings. The work summarized here largely avoids rat‐based studies, as are summarized elsewhere. The Pig‐a gene mutation assay has emerged as a valuable tool for quantifying in vivo and in vitro mutational events. The Pig‐a locus is located at the X‐chromosome, giving the advantage that one inactivated allele can give rise to a mutated phenotype, detectable by multicolour flow cytometry. For in vivo studies, only minute blood volumes are required, making it easily incorporated into ongoing studies or experiments with limited biological materials. Low blood volumes also allow individuals to serve as their own controls, providing temporal information of the mutagenic process, and/or outcome of intervention. These characteristics make it a promising exposure marker. To date, the Pig‐a gene mutation assay has been most commonly performed in rats, while reports regarding its usefulness in other species are accumulating. Besides its applicability to in vivo studies, it holds promise for genotoxicity testing using cultured cells, as shown in recent studies. In addition to safety assessment roles, it is becoming a valuable tool in basic research to identify mutagenic effects of different interventions or to understand implications of various gene defects by investigating modified mouse models or cell systems. Human blood‐based assays are also being developed that may be able to identify genotoxic environmental exposures, treatment‐ and lifestyle‐related factors or endogenous host factors that contribute to mutagenesis.