MOLECULAR MODELING IN CHEMICAL CARCINOGENESIS

诱变剂/致癌物的结构是它们的重要决定因素 与DNA有效反应生成DNA加合物的能力，以及 这些加合物的构象可能对它们的能力很重要 以有效地诱导导致癌症的突变。的结构 DNA中的诱变剂/致癌物可以通过分子模拟进行研究 技巧。在这里，研究各种不同物种的相互作用 提出了具有DNA的诱变剂/致癌物，包括；胸腺嘧啶二醇， 亚乙基腺嘌呤、O_2烷基胸腺嘧啶、O_4烷基胸腺胺、甲基大黄烯和 黄曲霉毒素。在所有情况下，都取得了令人鼓舞的初步结果 获得：胸腺嘧啶二醇诱导THY产生细胞的机制 突变已经被描述；这是更快的 D(O2iPrThy)TP与d(O2MeThy)TP反式Ade在DNA中掺入的比较 由DNA聚合酶在体外已发现；5-甲基大黄烯具有拥挤 海湾地区，这对它与DNA AS的相互作用有影响 通过分子模拟揭示了黄曲霉毒素之间的五个结合位点 B1和DNA已被描述。 这些项目中的每一个都将延长。

The structures of mutagens/carcinogens are important determinants of their ability to react efficiently with DNA to give DNA adducts, and the conformations of these adducts are likely to be important in their ability to induce effectively the mutations that lead to cancer. The structures of mutagens/carcinogens in DNA can be studied by molecular modeling techniques. Herein, the study of the interaction of a variety of mutagen/carcinogens with DNA is proposed, including; thymine glycol, ethenoadenine, O2alkylthymines, O4alkylthymines, methylchrysenes and aflatoxins. In all cases encouraging preliminary results have been obtained: a mechanism by which thymine glycol might induce Thy to Cyt mutations has been described; a sensible rationale for the more rapid incorporation of d(O2iPrThy)TP compared to d(O2MeThy)TP opposite Ade in DNA by DNA polymerase in vitro has been found; 5-methylchrysene has a crowded bay region, and this has implications for its interaction with DNA as revealed by molecular modeling; and, five binding sites between aflatoxin B1 and DNA have been described. Each of these projects will be extended.