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

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209 Scopus citations

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-electon oxidation to form radical cations is the major pathway of activation for the moset potent carcinogenic PAH, whereas monooxygenation to form bay-region diol epoxides is generally a minor pathway. For benzo[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.

Original languageEnglish (US)
Pages (from-to)183-199
Number of pages17
JournalPharmacology and Therapeutics
Volume55
Issue number2
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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