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N-亚硝基二甲胺的突变特异性:体内和体外试验的比较。

Mutational specificity of N-nitrosodimethylamine: comparison between in vivo and in vitro assays.

作者信息

Jiao J, Glickman B W, Anderson M W, Zielinska M

机构信息

Department of Biology, York University, Toronto, Ont., Canada.

出版信息

Mutat Res. 1993 Jan;301(1):27-31. doi: 10.1016/0165-7992(93)90052-w.

DOI:10.1016/0165-7992(93)90052-w
PMID:7677940
Abstract

We have determined the DNA alterations recovered after treatment with Aroclor 1254-treated rat S9-activated N-nitrosodimethylamine (NDMA) in the N-terminal region of the lacI gene of E. coli. A total of 125 independent LacI-d mutants of E. coli were characterized by DNA sequencing. Consistent with the known methylating ability of this compound, the predominant mutation was the G:C-->A:T transition, which accounted for 90% of all the mutations recovered. Non G:C-->A:T events include 2 G:C-->T:A, 2 G:C-->C:G, 2 A:T-->G:C, 3 A:T-->T:A and 3 frameshifts. Contingency analysis reveals that NDMA-induced mutations recovered after in vitro activation (S9) have a spectrum very similar to that previously obtained after in vivo activation employing a mouse host-mediated assay. In both systems, G:C-->A:T events clearly dominate and their distribution reveals similar site-specificity. Moreover, the proportion and kind of non-G:C-->A:T events are also similar.

摘要

我们已经确定了用阿罗氯丹1254处理的大鼠S9激活的N-亚硝基二甲胺(NDMA)处理后,在大肠杆菌lacI基因N端区域恢复的DNA改变。通过DNA测序对总共125个独立的大肠杆菌LacI-d突变体进行了表征。与该化合物已知的甲基化能力一致,主要突变是G:C→A:T转换,占所有恢复突变的90%。非G:C→A:T事件包括2个G:C→T:A、2个G:C→C:G、2个A:T→G:C、3个A:T→T:A和3个移码突变。列联分析表明,体外激活(S9)后恢复的NDMA诱导突变的谱与先前通过小鼠宿主介导试验体内激活后获得的谱非常相似。在这两个系统中,G:C→A:T事件明显占主导,并且它们的分布显示出相似的位点特异性。此外,非G:C→A:T事件的比例和种类也相似。

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