Barbin A, Laib R J, Bartsch H
Cancer Res. 1985 Jun;45(6):2440-4.
Chloroethylene oxide, an ultimate carcinogenic metabolite of vinyl chloride, was reacted with poly(deoxyguanylate-deoxycytidylate); the nucleic acid base adducts, 7-(2-oxoethyl)guanine and 3,N4-ethenocytosine, were analyzed by reverse-phase high-performance liquid chromatography. Chloroethylene oxide-modified poly(deoxyguanylate-deoxycytidylate) was assayed as template in a replication fidelity assay with Escherichia coli DNA polymerase I, and the newly synthesized product was subjected to nearest-neighbor analysis. Misincorporation rates of deoxyadenosine monophosphate and thymidine monophosphate were found to increase with the level of template modification. About 80% of the mispairing events were located opposite minor cytosine lesions. 7-(2-Oxoethyl)guanine, the major adduct identified (greater than 98% of the adducts), did not miscode for either thymine or adenine, failing to support an earlier hypothesis that the cyclic hemiacetal form, O6,7-(1'-hydroxyethano)guanine, could, by analogy with O6-methyl- and O6-ethylguanine, simulate adenine. Our results indicate that direct miscoding of 7-(2-oxoethyl)-guanine may contribute only slightly to the induction of mutations by chloroethylene oxide or vinyl chloride.
氯乙烷氧化物是氯乙烯的一种最终致癌代谢物，它与聚（脱氧鸟苷酸-脱氧胞苷酸）发生反应；通过反相高效液相色谱法分析核酸碱基加合物7-(2-氧代乙基)鸟嘌呤和3,N4-乙烯基胞嘧啶。在使用大肠杆菌DNA聚合酶I的复制保真度测定中，将氯乙烷氧化物修饰的聚（脱氧鸟苷酸-脱氧胞苷酸）作为模板进行测定，并对新合成的产物进行邻位分析。发现单磷酸脱氧腺苷和单磷酸胸苷的错误掺入率随模板修饰水平的增加而增加。约80%的错配事件位于与次要胞嘧啶损伤相对的位置。鉴定出的主要加合物7-(2-氧代乙基)鸟嘌呤（占加合物的98%以上）既不会错编码为胸腺嘧啶也不会错编码为腺嘌呤，这与早期的假设不符，即环状半缩醛形式的O6,7-(1'-羟基乙醇)鸟嘌呤可以类比O6-甲基鸟嘌呤和O6-乙基鸟嘌呤来模拟腺嘌呤。我们的结果表明，7-(2-氧代乙基)鸟嘌呤的直接错编码可能仅对氯乙烷氧化物或氯乙烯诱导的突变贡献很小。
