Jiao J L, Zielenska M, Anderson M W, Glickman B W
Department of Biology, York University, Toronto, Ontario, Canada.
Carcinogenesis. 1991 Feb;12(2):221-4. doi: 10.1093/carcin/12.2.221.
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.
我们通过对58个诱导产生的大肠杆菌lacI-d突变体进行DNA序列水平的表征，确定了烟草特异性致癌物4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮(NNK)的突变特异性。使用来自经多氯联苯混合物1254处理的大鼠的S9组分进行NNK的代谢活化。G:C→A:T转换在突变谱中占主导地位，占恢复突变的55%。其他恢复的碱基替换包括三个A:T→G:C转换以及两个A:T→T:A、三个A:T→C:G、五个G:C→C:G和五个G:C→T:A颠换。其他类型的突变事件包括两个缺失、三个重复和三个移码。NNK突变谱的复杂性似乎与该化合物通过DNA甲基化和吡啶氧丁基化诱导突变的模型一致。
