THEORETICAL STUDY OF POLYCYCLIC AROMATIC HYDROCARBON-DIOL-EPOXIDE-DNA ADDUCTS

在这项正在进行的研究中，研究了二醇-环氧化物与DNA的结合。我们 通过建模和模拟， 致癌的多环芳烃-二醇-环氧化物与DNA结合。 本文试图回答的两个主要问题是：（1） 相似加合物致癌活性的巨大差异可以解释 从理论研究？和（2）之间的交叉反应性数据 加合物和针对不同加合物生长的抗体能解释吗？的 我们的研究结果表明， 致癌活性和碳氢化合物的方向 DNA的凹槽。这项工作也提供了一个可能的解释， 针对一种加合物生长并结合DNA的抗体的交叉反应性数据 不同的加合物，也就是抗体识别不同的加合物， 扭曲的DNA骨架，而不是加合物本身， 引起类似磷酸基团运动的结构具有高的 交叉反应这项研究还表明， 多环芳烃致癌活性的序列依赖性 烃二醇环氧化物。

In this ongoing study, the binding of diol-epoxides to DNA is studied. We have approached this project by the modelling and simulation of carcinogenic polycyclic aromatic hydrocarbon-diol-epoxide binding to DNA. The two main questions that this work attempts to answer are: (1) Can the wide difference in carcinogenic activity of similar adducts be explained from a theoretical study? and (2) Can the cross-reactivity data between adducts and antibodies grown against different adducts be explained? The results of our work indicate that there is a strong correlation between carcinogenic activity and orientation of the hydrocarbon in the minor groove of DNA. This work also provides a possible explanation to observed cross reactivity data of antibodies grown against one adduct and DNA bound to different adducts, which is that the antibodies recognize the dis- tortion of the DNA backbone rather than the adduct itself and that structures that cause similar phosphate group movements have high cross-reactivities. This study also suggests that there is a strong DNA sequence dependence for carcinogenic activity of polycyclic aromatic hydrocarbon-diol-epoxides.