Effects of inhibitors of de novo protein synthesis on UV-mutagenesis in Chinese hamster cells. Evidence against mutagenesis via inducible, error-prone DNA repair.
Experiments were designed to test whether UV-mutagenesis in animal cells requires an inducible error-phone DNA-repair system similar to the "SOS system" in E. coli. Chinese hamster (V79) cells were exposed to either 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB, a transcription inhibitor), cycloheximide, or puromycin for various times (3-6 h) following UV-irradiation (2-8 J/m2). Post-irradiation treatment with DRB resulted in a reproducible enhancement of UV-induced mutagenesis, whereas post-irradiation treatment with either cycloheximide or puromycin resulted in decreased UV-mutagenesis. Thus, the frequency of UV-mutagenesis does not appear to be dependent on an inducible error-prone DNA-repair pathway, since all 3 agents share the ability to inhibit de novo protein synthesis. In order to understand the effects of these inhibitors on mutation frequency, DNA synthesis in the presence of these agents was examined. DRB stimulated DNA synthesis in both irradiated and unirradiated cells. On the other hand, cycloheximide and puromycin caused an immediate inhibition of DNA synthesis in both irradiated and unirradiated cells. Therefore, it appears that UV-mutagenesis reflects changes in post-irradiation DNA synthesis rather than post-irradiation de novo protein synthesis.
D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects*; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D009154:Mutation / Q000187:drug effects*; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology; D014466:Ultraviolet Rays
D011691:Puromycin; D004004:Dichlororibofuranosylbenzimidazole; D004247:DNA; D003513:Cycloheximide