Relationship of DNA Repair Processes to Mutagenesis and Carcinogenesis in Mammalian Cells. Final Report, August 1, 1977-January 31, 1985

摘要

We have compared the lethal, mutagenic, and carcinogenic effects of radiation and alkylating agents in several types of cells. In C3H 10T 1/2 cells, lethal effects decreased, while the frequency of ouabain-resistant mutants and of transformed cells increased during a 4-hour holding period following EMS treatment. To isolate repair-deficient mutants, we used diploid BHK cells which were characterized with regard to reactivation of uv- and x-irradiated Herpes Simplex virus (HSV). Three radiation-sensitive BHK strains were isolated using a host cell viral-reactivation suicide procedure. Two of these strains were sensitive to the cytotoxic effects of alkylating agents. One strain was hypermutable and one hypomutable following treatment with EMS. Mouse lymphoma strain L5178Y-S (LY-S), though more sensitive to the lethal effects of X radiation and alkylating agents than strain L5178Y-R (LY-R), was less mutable by these agents at the Na exp + /K exp + ATPase and hypoxanthine/guanine phosphoribosyltransferase (HGPRT) loci. Strain LY-S exhibited less dose-rate dependence for lethal effects than strain LY-R, but no dose-rate dependence was observed in radiation-induced mutagenesis for either strain. Repair of x ray-induced potentially lethal damage (PLD) at 25 exp 0 was observed for strain LY-S but not LY-R. Addition of 3-aminobenzamide (2 mm) to the medium sensitized both strains to x radiation, uv radiation and MNU, and inhibited repair of x ray-induced PLD in strain LY-S. (ERA citation 10:021876)