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Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: A review

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [1]
  1. Department of Environmental Health, University of Cincinnati Medical Center, PO Box 670056, 3223 Eden Avenue, Cincinnati, OH 45267-0056 (United States)
Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic compounds (HACs) constitute a major class of chemical carcinogens present in the environment. These compounds require activation to electrophilic metabolites to exert their mutagenic or carcinogenic effects. There are three principal pathways currently proposed for metabolic activation of PAH and HAC: the pathway via bay region dihydrodiol epoxide by cytochrome P450 enzymes (CYPs), the pathway via radical cation by one-electron oxidation, and the ortho-quinone pathway by dihydrodiol dehydrogenase (DD). In addition to these major pathways, a brief description of a minor metabolic activation pathway, sulfonation, for PAHs that contain a primary benzylic alcoholic group or secondary hydroxyl group(s) is included in this review. The DNA damages caused through the reactive metabolites of PAH/HAC are described involving the DNA covalent binding to form stable or depurinating adducts, the formation of apurinic sites, and the oxidative damage. The review emphasizes the chemical/biochemical reactions involved in the metabolic processes and the chemical structures of metabolites and DNA adducts.
OSTI ID:
20721836
Journal Information:
Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 206; ISSN TXAPA9; ISSN 0041-008X
Country of Publication:
United States
Language:
English