Inhibition of repair of premutational lesions in plateau phase Chinese hamster cells exposed to gamma radiation.
Induction and repair of forward mutations to 8-azaguanine resistance were studied in gamma irradiated, plateau phase Chinese hamster ovary cells. Mutation induction increased with dose with a relatively low induction for doses below 4 Gy and a steep increase thereafter. A close correlation between the ability of radiation to induce both lethality and mutations in plateau phase cells was evident. Recovery from potentially lethal damage resulted in a significant decrease in mutation frequency suggesting the possible involvement of an error free repair pathway. Mutation response at the end of recovery period was approximately linear with a slope of 2 X 10(-5) mutants per viable cells per Gy. This difference as compared to the immediate plating response supports the involvement of two types of damage in the induction of mutations: the nonrepairable, single hit component and a repairable component resulting from the interaction of lesions. Post-irradiation nonlethal hyperthermic treatment (42.5 degrees C; 30 min) sensitized the cells to killing as seen by the thermal enhancement ratio of 1.37. Interaction of hyperthermia, however, did not alter the mutation frequency obtained on immediate plating. Both post-irradiation hyperthermia and incubation at 4 degrees C inhibited most of the recovery from potentially lethal damage and also the repair of premutational lesions. These treatments resulted in a mutation frequency decrease of only 10-15% as compared to 50% seen in cells which actively repaired potentially lethal damage. The temperature dependence for the repair of premutational lesions suggests that the process is mediated by metabolically active steps.
D000818:Animals; D001375:Azaguanine / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D002588:Cesium Radioisotopes; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D006358:Hot Temperature; D009154:Mutation; D010053:Ovary; D011831:Radiation Genetics
D002588:Cesium Radioisotopes; D001375:Azaguanine