Mutation site specificity of A^nitroso-A^methyl-A^o;- acetoxybenzylamine: a model derivative of an esophageal carcinogen

'To whom correspondence should be addressed A total of 171 mutations induced by Ar-nitroso-A'-methyl-A'-a-acetoxybenzy lamine within the first 180 base pairs of the lacl gene of Escherichia coli were characterized at the DNA sequence level. Consistent with the methylating ability of this compound and the predicted mutagenic specificity of the 0^-methylguanine lesion, all but two of these mutations were G:C — A:T transitions. An analysis of neighboring sequences reveakd the same 5 ' flanking sequence influence on mutability reported for other SNl-type direct-acting alkylating agents. G:C — A:T transitions were found to be six times more likely to occur at G:C base pairs at which the guanine residues were flanked (5') by a purine than at those preceded by a pyrimidine. This mutagenic and site specificity appeared to be independent of the dose and likely reflects the behaviour of the activated parent carcinogen, Af-nitroso-W-methyl-W-benzylamine in the esophagus