A model for the mechanism of alkylation mutagenesis.

The phenomenology of mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine and related alkylating agents is reviewed and a three-step model for the molecular events of mutagenesis is presented. The first step is the production of miscoding lesions, especially O6-methylguanine, and the induction and synthesis of methyltransferase. The second step is the generation of DNA sequences in which O6-methylguanine is paired with thymine. The third step is the conversion of this abnormal base pair to an adenine-thymine pair completing the production of a transition mutation. At each of these steps, factors which affect the ultimate mutation frequency are outlined. The model is then described formally and the limits of the model are discussed.