MUTATIONAL SPECIFICITIES OF ENVIRONMENTAL CARCINOGENS IN THE LACI GENE OF ESCHERICHIA-COLI .4. THE TOBACCO-SPECIFIC NITROSAMINE 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE

We have determined the mutational specificity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by the characterization of 58 induced Escherichia coli lacI(-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 frameshifts. 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.