Cloning of cDNAs from fetal rat liver encoding glutathione S-transferase Yc polypeptides. The Yc2 subunit is expressed in adult rat liver resistant to the hepatocarcinogen aflatoxin B1

John D. Hayes (Lead / Corresponding author), Truyen Nguyen, David J. Judah, David G. Petersson, Gordon E. Neal

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    Abstract

    Fetal rat liver possesses substantial levels of glutathione S-transferase (GST) activity toward aflatoxin B1-8,9-epoxide. The enzyme responsible for this activity is an Alpha-class GST heterodimer comprising Yc1 and Yc2 subunits. The cDNAs encoding these polypeptides have been cloned and shown to share approximately 91% identity over 920 base pairs, extending from nucleotide -23 to the AATAAA polyadenylation signal. GST Yc2Yc2 expressed in Escherichia coli was found to exhibit 150-fold greater activity toward aflatoxin B1-8,9-epoxide than GST Yc1Yc1. Comparison between the structures of Alpha-class GST suggests that tyrosine at residue 108 and/or aspartate at residue 208 is responsible for the high aflatoxin B1 detoxication capacity of Yc2. Immunoblotting and enzyme assays have shown that liver from adult female rats contains about 10-fold greater levels of Yc2 than is found in liver from adult male rats. This sex-specific expression of Yc2 in adult rat liver may contribute to the relative insensitivity of female rats to aflatoxin B1. Dietary administration of oltipraz, a synthetic antioxidant which protects against aflatoxin-hepatocarcinogenesis, serves as an inducer of GST Yc2.

    Original languageEnglish
    Pages (from-to)20707-17
    Number of pages11
    JournalJournal of Biological Chemistry
    Volume269
    Issue number32
    Publication statusPublished - 12 Aug 1994

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    Keywords

    • Aflatoxin B1/analogs & derivatives
    • Amino Acid Sequence
    • Animals
    • Base Sequence
    • Carcinogens/toxicity
    • Cloning, Molecular
    • DNA, Complementary
    • Drug Resistance
    • Enzyme Induction
    • Escherichia coli/genetics
    • Female
    • Glutathione Transferase/chemistry
    • Humans
    • Inactivation, Metabolic
    • Liver/embryology
    • Male
    • Molecular Sequence Data
    • Peptide Fragments/genetics
    • Rats
    • Rats, Inbred F344
    • Sequence Homology, Amino Acid

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