| 1,3-丁二烯与DNA交联机理的研究——代谢产物在DNA大沟股间交联反应的AM1计算 |
| 摘要点击 661 全文点击 1320 投稿时间：1998-10-07 |
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| 中文关键词 1,3－丁二烯 致癌作用 致突作用 股间交联 双区理论 AM1 |
| 英文关键词 Butadiene carcinogenesis mutagenesis cross-linking with DNA Diregion theory AM1 |
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| 中文摘要 |
| 采用AM1方法计算了环境致癌物1,3-丁二烯(BD)的代谢产物1,2-环氧-3,4-丁烯(EB)和1,2,3,4-二环氧丁烷(DEB)与DNA腺嘌呤和胞嘧啶烷化反应过程速率控制步骤的活化能,以及DEB在DNA大沟侧与不同序列DNA片断生成烷化股间横向交联产物的结构和能量。结论认为:用烷化反应的难易程度难以解释DEB的致突性比EB约大100倍的实验事实;强致突的DEB可与碱基发生2次烷化反应,生成DNA交联产物;而EB则不能交联,这可能为2者基因毒性差异巨大的分子机制;同时DEB在DNA大沟侧可与多种不同的DNA序列发生股间横向交联,对比在小沟侧只与2种序列交联,此发生股间横交联几率的差异合理地解释了DEB致突的碱基选择性。 |
| 英文摘要 |
| The alkylating reaction of 1,2-Epoxy-3,4-Butene(EB)and 1,2,3,4-DiEpoxy-Butane(DEB),the metabolites of rodent carcinogenic 1,3-Butadiene,with Adenine and Cytosine and interaction with fragment of DNA have been computedThe results show that it is difficult to explain the fact that the mutagenicity of DEB is 100 times greater than that of EB by the ability of alkylation,and also show that DEB can interstrand crosslink with DNA through two times alkylating reactions,but EB cannot.So,this difference may contribute to the significant different carcinogenicity of two agents.Meanwhile,it is known that DEB can interstrand cross-link with many sequences of DNA in major groove vstwo in minor groove.This increases opportunities of interstrand cross-link with DNA.This difference may be the reason of base selection of DEB mutation.The deformation of some cross-linked DNA may also contribute to this selection in some degree. |
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