Relationship between chemical damage of DNA and mutations in mammalian cells. I. Dose-response curves for the induction of 6-thioguanine-resistant mutants by low doses of monofunctional alkylating agents, X-rays and UV radiation in V79 Chinese hamster cells.

The shape of the dose-response curve for mutations induced at low doses of mutagenic agents in mammalian cells was studied. With the exception of X-rays and MMS, which are very toxic in relation to their mutagenic potency, dose-response studies with EMS, MNU, ENU and UV radiation were performed at doses giving about 100% survival. The results from several experiments were pooled for each agent to get higher resolution power at low doses, and the result was compared with what could be expected when linear interpolation is performed from higher doses. The dose response for induction of mutations by UV- and X-irradiation did not deviate from linearity at low doses. In contrast with irradiation and the ethylating agents EMS and ENU, the methylating agents MMS and MNU showed a significantly lower effect at low doses as compared with estimation from a dose 5 times as high. The extent of alkylation of DNA by various doses of MMS was linear in the same dose intervals. It is suggested that the decreased response at low doses of the methylating agents found here may be connected with changes in the mechanism of repair of the lesions induced at different dose levels.