Mochizuki M, Suzuki E, Anjo T, Wakabayashi Y, Okada M
Gan. 1979 Oct;70(5):663-70.
Mutagenic and DNA-damaging effects of a series of N,N-dialkylnitrosamines monosubstituted at the alpha-carbon with an acetoxyl group were tested in Salmonella typhimurium, Escherichia coli, and Bacilus subtilis in the absence of metabolic activation system. The compounds comprised 8 N-alkyl-N-(acetoxymethyl)nitrosamines (alkyl=methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, or tert-butyl) and N-butyl-N-(1-acetoxybutyl)nitrosamine. All the compounds, except one with a tert-butyl group, gave positive results in these mutagenicity and repair tests. Presumed release of alkyl cations from the corresponding alpha-acetoxy derivatives by hydrolysis and heterolysis caused mutagenic and DNA-damaging effects in the bacteria. Structure-activity correlation of the compounds was noted in these tests and discussed in regard to the mutagenicity with metabolic activation and carcinogenicity of N,N-dialkylnitrosamines. The results support the hypothesis that alpha-carbon hydroxylation is one probable mechanism involved in the metabolic activation of N,N-dialkylnitrosamines.
在缺乏代谢活化系统的情况下，我们在鼠伤寒沙门氏菌、大肠杆菌和枯草芽孢杆菌中测试了一系列在α-碳上被乙酰氧基单取代的N,N-二烷基亚硝胺的致突变和DNA损伤作用。这些化合物包括8种N-烷基-N-(乙酰氧基甲基)亚硝胺（烷基=甲基、乙基、丙基、异丙基、丁基、异丁基、仲丁基或叔丁基）和N-丁基-N-(1-乙酰氧基丁基)亚硝胺。除了一种含叔丁基的化合物外，所有这些化合物在这些致突变性和修复测试中均给出了阳性结果。通过水解和异裂作用，相应的α-乙酰氧基衍生物可能释放出烷基阳离子，从而在细菌中产生致突变和DNA损伤作用。在这些测试中观察到了这些化合物的构效关系，并就N,N-二烷基亚硝胺的代谢活化致突变性和致癌性进行了讨论。结果支持了α-碳羟基化是N,N-二烷基亚硝胺代谢活化所涉及的一种可能机制这一假说。
