Electrophilic Intermediates Produced by Bioactivation of Furan

• Published in: Drug metabolism reviews Vol. 38; no. 4; pp. 615 - 626
• Main Author: Peterson, Lisa A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Informa UK Ltd 01.01.2006; Taylor & Francis; Informa Healthcare
• Subjects: Animals; Biological and medical sciences; Biotransformation; Carcinogenesis; Carcinogens - metabolism; Carcinogens - toxicity; Chemical and Drug Induced Liver Injury - physiopathology; Environmental Pollutants - metabolism; Environmental Pollutants - toxicity; Furan; Furans - metabolism; Furans - toxicity; Glutathione conjugates; Humans; Medical sciences; Metabolism; Pharmacology. Drug treatments; Stable isotope methods; Toxicity; α,β-Unsaturated aldehyde; Furan; Toxicity; Method; Aldehyde; Metabolism; Carcinogenesis; Stable isotope methods; Metabolic activation; Glutathione conjugates; Pharmacokinetics; Conjugated compound; Isotopes; α,β-Unsaturated aldehyde; Glutathione
• ISSN: 0360-2532; 1097-9883
• DOI: 10.1080/03602530600959417

The industrial and environmental chemical, furan, is a liver toxicant and carcinogen in laboratory animals. It has been classified as a possible human carcinogen. The mechanism of tumor induction is unknown. However, toxicity is initiated by cytochrome P450 catalyzed oxidation of furan to an α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial. This metabolite reacts readily with protein and DNA nucleophiles and is a bacterial mutagen in Ames assay strain TA104. Metabolism studies indicate that this reactive metabolite is formed in vivo. It is also an intermediate leading to other metabolites whose role in furan-derived toxicities has yet to be explored.