Metabolic activation of furfuryl alcohol: formation of 2-methylfuranyl DNA adducts in Salmonella typhimurium strains expressing human sulfotransferase 1A1 and in FVB/N mice

Bernhard H. Monien, Kristin Herrmann, Simone Florian, Hansruedi Glatt
2011 Carcinogenesis  
Furfuryl alcohol, formed by acid-and heat-induced dehydration from pentoses, is found in many foodstuffs. It induced renal tubule neoplasms in male B6C3F1 mice and nasal neoplasms in male F344/N rats in a study of the National Toxicology Program (NTP). However, furfuryl alcohol was negative in the standard Ames test and in a battery of in vivo mutagenicity tests. Here, we show that furfuryl alcohol is mutagenic in Salmonella typhimurium TA100 engineered for expression of human sulfotransferase
more » ... SULT) 1A1. This finding suggests that furfuryl alcohol is converted by intracellular sulfo conjugation to 2-sulfooxymethylfuran, an electrophile reacting with DNA. We detected nucleoside adducts of 2#-deoxyadenosine, 2#-deoxyguanosine and 2#-deoxycytidine in porcine liver DNA incubated with freshly prepared 2-sulfo-oxymethylfuran. The main adducts, N 2 -((furan-2-yl)methyl)-2#-deoxyguanosine (N 2 -MFdG) and N 6 -((furan-2-yl)methyl)-2#-deoxyadenosine (N 6 -MFdA) were synthesized. Their structures were verified by NMR and mass spectrometry. Liquid chromatography-tandem mass spectrometry methods for the quantification of both adducts were devised. N 2 -MFdG and N 6 -MFdA were detected in DNA of furfuryl alcohol-exposed S.typhimurium TA100 expressing SULT1A1 and in DNA of liver, lung and kidney of FVB/N mice that had received $390 mg furfuryl alcohol/kg body wt/day via the drinking water for 28 days. In summary, furfuryl alcohol is converted by sulfo conjugation to a mutagen. The detection of N 2 -MFdG and N 6 -MFdA in renal DNA of furfuryl alcohol-treated mice suggests that the neoplasms observed in this tissue in the study of the NTP may have been induced by 2-sulfo-oxymethylfuran.
doi:10.1093/carcin/bgr126 pmid:21729924 fatcat:ij4uy42hwjhc3ca2r52mvdw7cq