Daubersies P, Galiègue-Zouitina S, Koffel-Schwartz N, Fuchs R P, Loucheux-Lefebvre M H, Bailleul B
Unité 124 INSERM, Institut de Recherches sur le Cancer de Lille, France.
Carcinogenesis. 1992 Mar;13(3):349-54. doi: 10.1093/carcin/13.3.349.
When the chemical carcinogen 4-nitroquinoline 1-oxide binds to DNA in vitro, two major adducts are formed, both at guanine residues, but at different positions, i.e. the C8 or the N2 position. Well-defined adducts (either C8 or N2 guanine adducts) can be formed in vitro by reacting DNA with 4-actoxyaminoquinoline 1-oxide (Ac-4HAQO) under different reaction conditions. Forward mutations induced by each of both main 4NQO adducts in the tetracycline resistance gene of pBR322 were determined. In total, 30 independent 4NQO-induced mutations were characterized, showing mainly base-pair substitution mutations and some frameshift mutations. We have observed that the 5' neighbouring base influences the specificity of dGuo-N2-AQO induced base-pair substitutions mutagenesis; a similar effect does not occur with dGuo-C8-AQO. This study reveals the importance of the N2 guanine adduct in the mutagenesis induced by 4NQO in vivo.
当化学致癌物4-硝基喹啉1-氧化物在体外与DNA结合时，会形成两种主要加合物，均位于鸟嘌呤残基上，但位置不同，即C8或N2位。通过在不同反应条件下使DNA与4-乙酰氧基氨基喹啉1-氧化物（Ac-4HAQO）反应，可在体外形成明确的加合物（C8或N2鸟嘌呤加合物）。测定了pBR322四环素抗性基因中两种主要4NQO加合物各自诱导的正向突变。总共对30个独立的4NQO诱导突变进行了表征，主要显示碱基对替换突变和一些移码突变。我们观察到5'相邻碱基会影响dGuo-N2-AQO诱导的碱基对替换诱变的特异性；dGuo-C8-AQO则不会出现类似效应。本研究揭示了N2鸟嘌呤加合物在体内4NQO诱导的诱变中的重要性。
