Genomic instability and radiation mutagenesis

An increase in the frequency of spontaneous mutations occurs in some cell populations arising from single cells surviving radiation exposure. This mutator phenotype may persist over many cell divisions. The spectrum of DNA. structural changes at the hprt locus observed in these delayed mutations differs significantly from that occurring in direct X-ray-induced mutations. In other experiments, an increased frequency of coincident, second-site mutations was found in minisatellite and microsatellite loci in cells selected for mutations of the thymidine kinase (tk) gene. Together these results suggest that radiation may induce a genome-wide mutational process that can persist over many generations of cell replication. It is tempting to speculate that such a global, trans-acting mutagenic process would enhance the possibility of the occurrence of mutational events at the multiple loci required for the development of cancer.