Cavalieri E L, Rogan E G
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Pharmacol Ther. 1992;55(2):183-99. doi: 10.1016/0163-7258(92)90015-r.
Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activation for the most potent carcinogenic PAH, whereas monooxygenation to form bay-region diol epoxides is generally a minor pathway. For benzo[a]pyrene and 7,12-dimethylbenz[a]-anthracene, 80% and 99%, respectively, of the DNA adducts formed by rat liver microsomes or in mouse skin arise via the radical cation. Therefore, studies of PAH activation should begin by considering one-electron oxidation as the primary mechanism.
多环芳烃（PAH）是致癌物，需要代谢激活才能与细胞大分子发生反应，这是致癌过程中的初始事件。细胞色素P450通过两种激活途径介导PAH与DNA的结合。单电子氧化形成自由基阳离子是最具致癌性的PAH的主要激活途径，而单加氧反应形成湾区二醇环氧化物通常是次要途径。对于苯并[a]芘和7,12-二甲基苯并[a]蒽，大鼠肝微粒体或小鼠皮肤形成的DNA加合物分别有80%和99%是通过自由基阳离子产生的。因此，PAH激活的研究应首先将单电子氧化视为主要机制。
