Glutathione S-transferase localization in aflatoxin B1-treated rat livers

D J Harrison, L May, J D Hayes, G E Neal

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    Overexpression of detoxication enzymes is associated with the development of drug-resistant, preneoplastic nodules in the carcinogen-treated rat liver. The most consistent marker of preneoplasia in many experimental models is increased expression of the pi-class glutathione S-transferase (GST) YfYf. We have confirmed by immunostaining that the pi-class GST is overexpressed in aflatoxin B1-induced preneoplastic nodules and liver tumours in rats. However, pi-class GST YfYf has low activity against aflatoxin B1-8,9-epoxide, and most activity against this cytotoxic and genotoxic metabolite is associated with the alpha-class GSTs YaYa, YaYc and YcYc. We have demonstrated that there is also a consistent increase in the alpha-class GSTs in this model. It seems likely that the overexpression of the Ya and Yc subunits, rather than increased levels of the pi-class GST YfYf, is responsible for the acquisition of a drug-resistant phenotype in rat liver preneoplastic nodules and tumours induced by aflatoxin B1.

    Original languageEnglish
    Pages (from-to)927-31
    Number of pages5
    JournalCarcinogenesis
    Volume11
    Issue number6
    Publication statusPublished - Jun 1990

    Keywords

    • Aflatoxin B1
    • Aflatoxins/toxicity
    • Animals
    • Cells, Cultured
    • Gene Expression
    • Glutathione Transferase/genetics
    • Immunohistochemistry
    • Liver/drug effects
    • Liver Neoplasms/chemically induced
    • Macromolecular Substances
    • Male
    • Precancerous Conditions/chemically induced
    • Rats
    • Rats, Inbred F344
    • Reference Values

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