Horsfall M J, Glickman B W
Department of Biology, York University, Toronto, Ontario, Canada.
Carcinogenesis. 1988 Sep;9(9):1529-32. doi: 10.1093/carcin/9.9.1529.
A total of 171 mutations induced by N-nitroso-N-methyl-N-alpha-acetoxybenzylamine within the first 180 base pairs of the lacI 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 O6-methylguanine lesion, all but two of these mutations were G:C----A:T transitions. An analysis of neighboring sequences revealed the same 5' flanking sequence influence on mutability reported for other SN1-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, N-nitroso-N-methyl-N-benzylamine in the esophagus.
对由N-亚硝基-N-甲基-N-α-乙酰氧基苄胺诱导的大肠杆菌lacI基因前180个碱基对内的总共171个突变进行了DNA序列水平的表征。与该化合物的甲基化能力以及O6-甲基鸟嘌呤损伤的预测诱变特异性一致，这些突变中除两个外均为G:C→A:T转换。对相邻序列的分析揭示了与其他SN1型直接作用烷基化剂报道的相同的5'侧翼序列对可突变性的影响。发现G:C→A:T转换在鸟嘌呤残基5'侧翼为嘌呤的G:C碱基对处发生的可能性是在嘧啶之前的那些碱基对处的六倍。这种诱变和位点特异性似乎与剂量无关，并且可能反映了活化的母体致癌物N-亚硝基-N-甲基-N-苄胺在食管中的行为。
