Agarwal R, Canella K A, Yagi H, Jerina D M, Dipple A
Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Chem Res Toxicol. 1996 Apr-May;9(3):586-92. doi: 10.1021/tx950148+.
P-Postlabeling assays were used to monitor the binding to epidermal DNA that resulted from the application of each of the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide to mouse skin in vivo. For three of these configurational isomers, there was a reasonable correlation between the relative level of binding to epidermal DNA and the known tumorigenic effects of these compounds. However, for the 4(S),3(R)-dihydrodiol 2(S),1(R)-epoxide, the tumorigenic response was considerably greater in relation to the level of DNA modification than was the case for the other isomers. This greater tumorigenic response was consistent with previous observations indicating that this isomer was more mutagenic, at equivalent levels of DNA modification, than the other two tumorigenic dihydrodiol epoxides. Additionally, the 4(S),3(R)-dihydrodiol 2(S),1(R)-epoxide reacts with DNA to generate predominantly (approximately 80%) adducts on the amino group of adenine residues. These findings might imply a greater intrinsic biological effect of such adenine adducts with respect to the other major adduct formed on the amino group of guanine residues.
采用后标记分析方法监测苯并[c]菲3,4 - 二氢二醇1,2 - 环氧化物的四种构型异构体分别应用于小鼠皮肤后与表皮DNA的结合情况。对于其中三种构型异构体，与表皮DNA的相对结合水平和这些化合物已知的致癌作用之间存在合理的相关性。然而，对于4(S),3(R)-二氢二醇2(S),1(R)-环氧化物，相对于DNA修饰水平，其致癌反应比其他异构体大得多。这种更大的致癌反应与先前的观察结果一致，即表明在同等DNA修饰水平下，该异构体比其他两种致癌二氢二醇环氧化物更具致突变性。此外，4(S),3(R)-二氢二醇2(S),1(R)-环氧化物与DNA反应主要在腺嘌呤残基的氨基上生成加合物（约80%）。这些发现可能意味着相对于在鸟嘌呤残基氨基上形成的其他主要加合物，此类腺嘌呤加合物具有更大的内在生物学效应。
