Electrophilic Intermediates Produced by Bioactivation of Furan

Abstract

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.

Key Words :

• Furan
• Carcinogenesis
• Toxicity
• Metabolism
• Glutathione conjugates
• Stable isotope methods
• α,β-Unsaturated aldehyde

Notes

*Presented at the Seventh International Symposium on Biological Reactive Intermediates, Tucson, Arizona, January 4–7, 2006.