A reactive metabolite of furan, cis-2-butene-1,4-dial, is mutagenic in theames assay

Furan is classified as a nongenotoxic hepatocarcinogen. It is thought to be activated to a toxic metabolite, cis-2-butene-1,4-dial, which is acutely t oxic to liver cells. The resulting cytotoxicity is followed by compensatory cell proliferation, increasing the likelihood of tumor production. We exam ined the genotoxic activity of cis-2-butene-1,4-dial in several strains of Salmonella typhimurium commonly used in the Ames assay. This reactive compo und tested positive in TA104, a strain that is sensitive to aldehydes. Muta genic activity was concentration-dependent (1000 +/- 180 revertants/mu mol) . Incubation of cis-2-butene-1,4-dial with glutathione prior to addition of bacteria inhibited both the acute toxic and genotoxic activity of this com pound. No evidence of mutagenic activity was seen at nontoxic concentration s in TA97, TA98, TA100, and TA102. Our findings are consistent with the hyp othesis that cis-2-butene-1,4-dial reacts with DNA to form mutagenic adduct s. Our data suggest that cis-2-butene-1,4-dial may be an important genotoxi c as well as toxic intermediate in furan-induced tumorigenesis.