Role of radical cations in aromatic hydrocarbon carcinogenesis.
Role of radical cations in aromatic hydrocarbon carcinogenesis.
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DOI：
10.1289/ehp.856469
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发表时间：
1985-12
影响因子：
10.4
通讯作者：
Rogan E
中科院分区：
文献类型：
--
作者：
Cavalieri E;Rogan E
多环芳烃（PAH）的致癌活化主要涉及两条途径：单电子氧化和单加氧。单电子氧化产生PAH自由基阳离子，其可与细胞亲核试剂反应。生化和生物学实验结果表明，只有电离势低于约1000的多环芳烃才能被释放。7.35 eV可以通过单电子氧化代谢活化。此外，致癌PAH的自由基阳离子必须具有相对高的电荷定位，以有效地与靶细胞中的大分子反应。多环芳烃醌的代谢形成通过自由基阳离子中间体进行。苯并[a]芘（BP）与小鼠皮肤DNA的结合主要发生在C-6，BP自由基阳离子中最高电荷定位的位置，6-甲基BP与小鼠皮肤DNA的结合产生主要加合物，其中6-甲基与脱氧鸟苷的2-氨基结合。通过将PAH直接应用于大鼠乳腺的致癌性研究表明，只有电离电位低到足以通过单电子氧化激活的PAH才能在该靶组织中产生肿瘤。这些构成了一些结果，提供证据的参与PAH致癌的单电子氧化。
Carcinogenic activation of polycyclic aromatic hydrocarbons (PAH) involves two main pathways: one-electron oxidation and monooxygenation. One-electron oxidation produces PAH radical cations, which can react with cellular nucleophiles. Results from biochemical and biological experiments indicate that only PAH with ionization potentials below ca. 7.35 eV can be metabolically activated by one-electron oxidation. In addition, the radical cations of carcinogenic PAH must have relatively high charge localization to react effectively with macromolecules in target cells. Metabolic formation of PAH quinones proceeds through radical cation intermediates. Binding of benzo[a]pyrene (BP) to mouse skin DNA occurs predominantly at C-6, the position of highest charge localization in the BP radical cation, and binding of 6-methyl BP to DNA in mouse skin yields a major adduct with the 6-methyl group bound to the 2-amino group of deoxyguanosine. Studies of carcinogenicity by direct application of PAH to rat mammary gland indicate that only PAH with ionization potentials low enough for activation by one-electron oxidation produce tumors in this target tissue. These constitute some of the results which provide evidence for the involvement of one-electron oxidation in PAH carcinogenesis.