The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation.

Abstract:

: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.

journal_name

Pharmacol Ther

authors

Cavalieri EL,Rogan EG

doi

10.1016/0163-7258(92)90015-r

subject

Has Abstract

pub_date

1992-01-01 00:00:00

pages

183-99

issue

2

eissn

0163-7258

issn

1879-016X

pii

0163-7258(92)90015-R

journal_volume

55

pub_type

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