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

Research output: Contribution to journalArticle

204 Citations (Scopus)

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 - Jan 1 1992

Fingerprint

Aromatic Hydrocarbons
Polycyclic Aromatic Hydrocarbons
Cations
Carcinogenesis
DNA Adducts
Epoxy Compounds
Liver Microsomes
Carcinogens
Cytochrome P-450 Enzyme System
Electrons
Skin
Metabolic Activation
DNA

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{e905a965720d4d218423d375969909dd,
title = "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-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.",
author = "Ercole Cavalieri and Rogan, {Eleanor G}",
year = "1992",
month = "1",
day = "1",
doi = "10.1016/0163-7258(92)90015-R",
language = "English (US)",
volume = "55",
pages = "183--199",
journal = "Pharmacology and Therapeutics",
issn = "0163-7258",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation

AU - Cavalieri, Ercole

AU - Rogan, Eleanor G

PY - 1992/1/1

Y1 - 1992/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027093718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027093718&partnerID=8YFLogxK

U2 - 10.1016/0163-7258(92)90015-R

DO - 10.1016/0163-7258(92)90015-R

M3 - Article

VL - 55

SP - 183

EP - 199

JO - Pharmacology and Therapeutics

JF - Pharmacology and Therapeutics

SN - 0163-7258

IS - 2

ER -