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 (SULT) 1A1. This finding suggests that
furfuryl alcohol is converted by intracellular sulfo conjugation to 2-sulfo-oxymethylfuran, 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.