Characterization of a UV-resistant mutant of CHO-K1 with normal repair activity

Abstract

The biological and repair responses of Mut 8–16, an ultraviolet radiation (UV)-resistant derivative of CHO-K1, were characterized with respect to UV and to the active chemical carcinogen, benzo[ a]pyrene-4,5-oxide. In comparison to the parent, the UV-survival response curve of this mutant showed a significantly larger shoulder but little or no difference in the slope of the exponential survival region. In addition, the mutant cell line demonstrated significantly larger mutation frequencies at high survival UV fluences, but smaller mutation frequencies at high survival equitoxic concentrations of the carcinogen benzo[ a]pyrene-4,5-epoxide relative to the parent cell. However, these relative differences in mutation frequencies between parent and mutant appeared to decrease as survival decreased. Despite these observations there were no measurable differences in excision-repair, or in post-replication repair although the mutant appeared to show a nominal reduction (not an enhancement) of replication-repair activity following the UV exposure. These data imply there is another lesion recognition system in CHO cells whose effects on survival and mutation are best observed at low doses of carcinogen and/or radiation but which are masked at higher doses where major repair processes dominate. The dissimilar relationship of cytotoxicity to mutation induction frequency observed in UV and carcinogen treated mutant vs. parent cell lines, imply that the probabilities for lethality and mutation are independent of one another in the presence of otherwise unrepaired (residual) damage.