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

在这项正在进行的研究中，研究了二元醇-环氧化物与DNA的结合。我们 我通过建模和仿真来接近这个项目 致癌的多环芳烃二醇环氧化物与DNA结合。 这项工作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 从一项理论研究？和(2)之间的交叉反应数据 针对不同加合物生长的加合物和抗体可以解释吗？这个 我们的工作结果表明，两者之间存在很强的相关性 次生烃的致癌活性和定向 DNA的纹路。这项工作也提供了一种可能的解释 针对一种加合物和DNA结合的抗体的交叉反应数据 对不同的加合物，即抗体识别不同的加合物。 DNA骨架的扭曲，而不是加合物本身 导致类似磷酸基团移动的结构具有很高的 交叉反应。这项研究还表明，有很强的DNA 多环芳香族化合物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.