A cell line selected for resistance to ionizing radiation exhibits cross resistance to other genotoxic agents and a mutator phenotype for loss of heterozygosity events.

An ionizing radiation resistant derivative was obtained from the mouse P19H22 (aprt hemizygote) embryonal carcinoma cell line by repeated exposure to 137Cs gamma radiation. Ionizing radiation resistance in the 6Gy-R cell line was not correlated with a failure to undergo cell cycle arrest or a loss of the p53 response after exposure to 137Cs gamma radiation. Moreover, the cells did not display increased resistance to bleomycin, a double strand break inducing agent. However, the cells did display increased resistance to ultraviolet radiation, ethyl methanesulfonate, and 95% oxygen. A mutational analysis demonstrated a > 700 fold-fold increase in the frequency of aprt mutants for the 6Gy-R cells, but no change in the frequency of hprt or dhfr mutants. A molecular analysis suggested that the aprt mutations in the 6Gy-R cells arose by recombinational events. A possible association between radiation resistance, DNA repair, and a mutator phenotype for large-scale mutational events is discussed.