Mutational specificities of environmental carcinogens in the lacI gene of Escherichia coli: IV. 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 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.
Jiao
J L
JL
Department of Biology, York University, Toronto, Ontario, Canada.
Zielenska
M
M
Anderson
M W
MW
Glickman
B W
BW
D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D004781:Environmental Exposure; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D008969:Molecular Sequence Data; D009154:Mutation; D009602:Nitrosamines / Q000633:toxicity*; D012097:Repressor Proteins / Q000235:genetics*
D001426:Bacterial Proteins; D002273:Carcinogens; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D009602:Nitrosamines; D012097:Repressor Proteins; C051577:4-(methylnitrosoamino)-4-(3-pyridyl)-1-butanol