Mutational specificities of environmental carcinogens in the lacI gene of Escherichia coli: IV. The tobacco-specific nitrosamine 4-(methylnitosamino)-1-(3-pyridy)-1-butanone

Abstract

We have determined the mutational specificity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyrldyl)-1-butanone (NNK) by the characterization of 58 induced Escherichia coli lacl^−d mutants at the DNA sequence level. Metabolic activation of NNK was carried out using the S9 fraction from Aroclor 1254-treated rats. G:C → A:T transitions dominated the spectrum, accounting for 55% of the mutations recovered. The other base substitutions recovered Include three A:T → G:C transitions as well as two A:T → T:A, three A:T → C:G, five G:C → C:G and five G:C → T:A transversions. Other classes of mutational events included two deletions, three duplications and three frame-shifts. The complexity of the NNK mutational spectrum appears consistent with a model that this compound induces mutations by both the methylation and the pyridoloxobutylation of DNA.