Fronza G, Campomenosi P, Iannone R, Abbondandolo A
Laboratory of Mutagenesis, National Institute for Research on Cancer (IST), Genova, Italy.
Nucleic Acids Res. 1992 Mar 25;20(6):1283-7. doi: 10.1093/nar/20.6.1283.
4-Nitroquinoline-1-oxide is a potent mutagen and carcinogen which induces two main guanine adducts at positions C8 and N2. In ds or ss damaged DNA the ratio C8/N2 adducts is 1:2 and 8-10:1, respectively. In bacteria and yeast 4NQO has been shown to be a base substitution mutagen acting at G residues inducing mainly G to A transitions. We determined the mutational spectrum induced by the 4NQO metabolite, acetoxy-4-aminoquinoline 1-oxide, in the M13lacZ'/E. coli lacZ delta M15 alpha complementation assay using ssDNA. Among 68 Ac-4HAQO induced mutants, G to Pyr transversion was the most frequent base substitution observed. By comparison with dsDNA based systems, our data suggest that dGuo-C8-AQO induces G to Pyr transversions. A mechanism to explain how this lesion may induce transversions is proposed.
4-硝基喹啉-1-氧化物是一种强效诱变剂和致癌物,它会在鸟嘌呤的C8和N2位置诱导产生两种主要的加合物。在双链或单链受损DNA中,C8/N2加合物的比例分别为1:2和8 - 10:1。在细菌和酵母中,4NQO已被证明是一种碱基置换诱变剂,作用于鸟嘌呤残基,主要诱导G到A的转换。我们在使用单链DNA的M13lacZ'/大肠杆菌lacZ delta M15α互补试验中,测定了4NQO代谢物乙酰氧基-4-氨基喹啉1-氧化物诱导的突变谱。在68个由Ac - 4HAQO诱导的突变体中,G到嘧啶的颠换是观察到的最常见的碱基置换。通过与基于双链DNA的系统进行比较,我们的数据表明dGuo - C8 - AQO会诱导G到嘧啶的颠换。本文提出了一种机制来解释这种损伤如何诱导颠换。