Contribution of the glutathione S-transferases to the mechanisms of resistance to aflatoxin B1

J D Hayes, D J Judah, L I McLellan, G E Neal

    Research output: Contribution to journalReview article

    109 Citations (Scopus)

    Abstract

    The harmful effects of Aflatoxin B1 (AFB1) are a consequence of it being metabolized to AFB1-8,9-epoxide, a compound that serves as an alkylating agent and mutagen. The toxicity of AFB1 towards different cells varies substantially; sensitivity can change significantly during development, can be modulated by treatment with xenobiotics and is decreased markedly in preneoplastic lesions as well as in tumors. Three types of resistance, namely intrinsic, inducible and acquired, can be identified. The potential resistance mechanisms include low capacity to form AFB1-8,9-epoxide, high detoxification activity, increase in AFB1 efflux from cells and high DNA repair capacity. Circumstantial evidence exists that amongst these mechanisms the glutathione S-transferases, through their ability to detoxify AFB1-8,9-epoxide, play a major role in determining the sensitivity of cells to AFB1.

    Original languageEnglish
    Pages (from-to)443-72
    Number of pages30
    JournalPharmacology & Therapeutics
    Volume50
    Issue number3
    DOIs
    Publication statusPublished - 1991

    Keywords

    • Aflatoxin B1/analogs & derivatives
    • Amino Acid Sequence
    • Animals
    • Drug Resistance/physiology
    • Glutathione Transferase/physiology
    • Humans
    • Liver/enzymology
    • Molecular Sequence Data
    • Species Specificity

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