Co-mutagenicity of coumarin (1,2-benzopyrone) with aflatoxin B1 and human liver S9 in mammalian cells

D. E. Goeger, A. W. Hsie, K. E. Anderson

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    30 Scopus citations


    Coumarin (1,2-benzopyrone), a natural dietary constituent and drug currently under evaluation for treatment of certain cancers and lymphedema, reduces polycyclic aromatic hydrocarbon-induced neoplasms in rodents. Because most rodents metabolize coumarin through 3,4-epoxidation, whereas 7-hydroxylation predominates in humans, their suitability as a model for coumarin effects in humans has been questioned. We examined coumarin chemoprotection against the promutagen and dietary contaminant aflatoxin B1 with human liver S9 bioactivation in the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyltransferase mutation assay. Coumarin in the absence of aflatoxin B1 was not mutagenic or cytotoxic up to 500 μM. When included with either 1 or 10 μM aflatoxin B1, coumarin produced a dose-dependent increase in mutant frequency and cytotoxicity. At concentrations greater than 50 μM, coumarin stimulated human liver S9 bioactivation of aflatoxin B1 to the mutagenic 8,9-epoxide. This increase was 12- and fivefold at 500 μM coumarin with 1 and 10 μM aflatoxin B1, respectively, compared with incubations with aflatoxin B1 alone. These findings differ from previous results with liver S9 from other species, and indicate that coumarin co-mutagenicity with aflatoxin B1 and human liver S9 is through increased aflatoxin B1 bioactivation. Copyright (C) 1999 Elsevier Science Ltd.

    Original languageEnglish (US)
    Pages (from-to)581-589
    Number of pages9
    JournalFood and Chemical Toxicology
    Issue number6
    StatePublished - Jun 1999


    • Aftatoxin B
    • CHO/HPRT mutation assay
    • Coumarin
    • Liver S9

    ASJC Scopus subject areas

    • Food Science
    • Toxicology


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