THE APPROACH TO UNDERSTANDING AROMATIC HYDROCARBON CARCINOGENESIS - THE CENTRAL ROLE OF RADICAL CATIONS IN METABOLIC-ACTIVATION

被引:187
作者
CAVALIERI, EL
ROGAN, EG
机构
[1] Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805
关键词
D O I
10.1016/0163-7258(92)90015-R
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页码:183 / 199
页数:17
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