1,3-丁二烯与DNA交联致癌机理的研究——代谢产物与鸟嘌呤反应及与DNA交联作用的AM1计算  

STUDIES ON INTERACTION OF 1,3-BUTADIENE WITH DNA——COMPUTATIONS OF METABOLITES OF 1,3-BUTADIENE REACTING WITH GUANINE AND CROSS-LINKING WITH DNA BY AM1

作　　者：周志刚[1] 戴乾圜[2] 钟儒刚 

机构地区：[1]北京大学环境科学中心,北京100871 [2]北京工业大学癌化学与生物工程中心,北京100022

出　　处：《环境化学》1999年第5期427-431,共5页Environmental Chemistry

基　　金：国家自然科学基金(批准号:29377269)资助项目

摘　　要：采用AMI方法计算了环境致癌物1.2-环氧3,4-丁烯(EB)和1,2,3,4二环氧丁烷(DEB)与DNA鸟嘌呤反应过程速率控制步骤的活化能及DEB与DNA片段生成烷化交联产物的结构和能量、结果得出:用烷化反应的难易程度难以解释DEB的致突性比EB大100倍的实验事实;强致突的DEB可与鸟嘌吟发生两次烷化反应,生成DNA交联产物,交联后的DNA结构稳定、变形小:而EB则不能交联.这可能为两者基因毒性差异巨大的分子机制.The reaction of 1,2-epoxy-3,4-butene(EB)and l,2,3,4-diepoxybutane(DEB),the metabolites of rodent carcinogenic 1,3-butadiene, and guanine and fragment of DNA have been computed. The results show that those activation energies have not big difference, so it is difficult to explain the fact that the mutagenicity of DEB is 100 times greater than that of EB by the activity of alkylating reaction . It is also show that DEB can cross-h'nking with DNA through two times alkylating reactions with guanine and cross-linking DNA deforms little comparing with nature DNA. But EB cannot. So, this difference may contributes to the significant different carcinogenicity of two agents.

关 键 词：丁二烯 致癌机理 分子轨道计算 AM1 

分 类 号：X503.1[环境科学与工程—环境工程] R730.231.1[医药卫生—肿瘤]