Abstract

Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species that bind covalently with cellular macromolecules to trigger the cancer process. Metabolic activation of PAH can be understood in terms of two main pathways: one-electron oxidation to yield reactive intermediate radical cations and monooxygenation to produce bay-region diol epoxides. The reason we have postulated that one-electron oxidation plays an important role in the activation of PAH derives from certain common characteristics of the radical cation chemistry of the most potent carcinogenic PAH. Two main features common to these PAH are: 1) a relatively low ionization potential, which allows easy metabolic removal of one electron, and 2) charge localization in the PAH radical cation that renders this intermediate specifically and efficiently reactive toward nucleophiles. Equally important, cytochrome P-450 and mammalian peroxidases catalyze one-electron oxidation. This mechanism plays a role in the binding of PAH to DNA. Chemical, biochemical and biological evidence will be presented supporting the important role of one-electron oxidation in the activation of PAH leading to initiation of cancer.

Original languageEnglish (US)
Pages (from-to)77-87
Number of pages11
JournalFree Radical Research
Volume11
Issue number1-3
DOIs
StatePublished - Jan 1 1990

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Aromatic Hydrocarbons
Polycyclic Aromatic Hydrocarbons
Cations
Carcinogenesis
Electrons
Chemical activation
Oxidation
Peroxidases
Nucleophiles
Ionization potential
Epoxy Compounds
Macromolecules
Carcinogens
Cytochrome P-450 Enzyme System
Neoplasms
DNA

Keywords

  • Carcinogenic activity
  • Cellular nucleophiles
  • Cytochrome P-450
  • DNA adducts
  • Ionization potential
  • Mechanisms of carcinogenesis
  • Mouse skin
  • One-electron oxidation
  • Peroxidases
  • Radical cations
  • Rat mammary gland

ASJC Scopus subject areas

  • Biochemistry

Cite this

Radical cations in aromatic hydrocarbon carcinogenesis. / Cavalieri, Ercole; Rogan, Eleanor G.

In: Free Radical Research, Vol. 11, No. 1-3, 01.01.1990, p. 77-87.

Research output: Contribution to journalArticle

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AB - Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species that bind covalently with cellular macromolecules to trigger the cancer process. Metabolic activation of PAH can be understood in terms of two main pathways: one-electron oxidation to yield reactive intermediate radical cations and monooxygenation to produce bay-region diol epoxides. The reason we have postulated that one-electron oxidation plays an important role in the activation of PAH derives from certain common characteristics of the radical cation chemistry of the most potent carcinogenic PAH. Two main features common to these PAH are: 1) a relatively low ionization potential, which allows easy metabolic removal of one electron, and 2) charge localization in the PAH radical cation that renders this intermediate specifically and efficiently reactive toward nucleophiles. Equally important, cytochrome P-450 and mammalian peroxidases catalyze one-electron oxidation. This mechanism plays a role in the binding of PAH to DNA. Chemical, biochemical and biological evidence will be presented supporting the important role of one-electron oxidation in the activation of PAH leading to initiation of cancer.

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