Autosomal mutation in somatic cells of the mouse.

Tumor suppressor genes are located on autosomal chromosomes. Therefore, an understanding of how cancer-related mutations occur in somatic cells requires a detailed understanding of spontaneous and induced autosomal mutagenesis. This review will present recent advances in the study of how autosomal mutations form in somatic cells by focusing on the mouse Aprt and Tk model systems that have been developed to examine the formation of autosomal mutations in vivo. These loci can detect the entire spectrum of mutations known to inactivate tumor suppressor genes. Studies with these models have provided novel information on the frequencies and types of spontaneous autosomal mutations that occur in different cell types. They also show great promise for the screening of genotoxic effects resulting from environmental exposures and for the study of mutation when DNA repair pathways are compromised. Continued use of the mouse Aprt and Tk models will have a significant impact on our understanding of some of the earliest steps in the conversion of normal cells to those with malignant phenotypes.