PT  - JOURNAL ARTICLE
AU  - Leah A. Gates
AU  - Martin B. Phillips
AU  - Brock A. Matter
AU  - Lisa A. Peterson
TI  - Comparative Metabolism of Furan in Rodent and Human Cryopreserved Hepatocytes
AID  - 10.1124/dmd.114.057794
DP  - 2014 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 1132--1136
VI  - 42
IP  - 7
4099  - http://dmd.aspetjournals.org/content/42/7/1132.short
4100  - http://dmd.aspetjournals.org/content/42/7/1132.full
SO  - Drug Metab Dispos2014 Jul 01; 42
AB  - Furan is a liver toxicant and carcinogen in rodents. Although humans are most likely exposed to furan through a variety of sources, the effect of furan exposure on human health is still unknown. In rodents, furan requires metabolism to exert its toxic effects. The initial product of the cytochrome P450 2E1-catalyzed oxidation is a reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA). BDA is toxic and mutagenic and consequently is considered responsible for the toxic effects of furan. The urinary metabolites of furan in rats are derived from the reaction of BDA with cellular nucleophiles, and precursors to these metabolites are detected in furan-exposed hepatocytes. Many of these precursors are 2-(S-glutathionyl)butanedial-amine cross-links in which the amines are amino acids and polyamines. Because these metabolites are derived from the reaction of BDA with cellular nucleophiles, their levels are a measure of the internal dose of this reactive metabolite. To compare the ability of human hepatocytes to convert furan to the same metabolites as rodent hepatocytes, furan was incubated with cryopreserved human and rodent hepatocytes. A semiquantitative liquid chromatography with tandem mass spectrometry assay was developed for a number of the previously characterized furan metabolites. Qualitative and semiquantitative analysis of the metabolites demonstrated that furan is metabolized in a similar manner in all three species. These results indicate that humans may be susceptible to the toxic effects of furan.