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.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D004260:DNA Repair; D004261:DNA Replication; D004790:Enzyme Induction; D007700:Kinetics; D008433:Mathematics; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D008780:Methyltransferases / Q000235:genetics; D008957:Models, Genetic; D009153:Mutagens; D009154:Mutation
D000477:Alkylating Agents; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D008780:Methyltransferases