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

Lisa A Peterson, Kim C. Naruko, Daniel P. Predecki

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

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 toxic to liver cells. The resulting cytotoxicity is followed by compensatory cell proliferation, increasing the likelihood of tumor production. We examined the genotoxic activity of cis-2-butene-1,4-dial in several strains of Salmonella typhimurium commonly used in the Ames assay. This reactive compound tested positive in TA104, a strain that is sensitive to aldehydes. Mutagenic activity was concentration dependent (1000 ± 180 revertants/μmol). 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 compound. No evidence of mutagenic activity was seen at nontoxic concentrations in TA97, TA98, TA100, and TA102. Our findings are consistent with the hypothesis that cis-2-butene-1,4-dial reacts with DNA to form mutagenic adducts. Our data suggest that cis-2-butene-1,4-dial may be an important genotoxic as well as toxic intermediate in furan-induced tumorigenesis.

Original languageEnglish (US)
Pages (from-to)531-534
Number of pages4
JournalChemical research in toxicology
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2000

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