Age-dependent change of metabolic capacity and genotoxic injury in rat intestine

H. R. H. Patela, A. Hewer, J. D. Hayes, D. H. Phillips, F. C. Campbell

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    The ontogeny of intestinal phase I and II xenobiotic metabolising enzymes and influence on susceptibility to genotoxic injury, are unclear. This study assessed expression of cytochrome P450 monooxygenases (CYP1A, CYP2B, CYP2C, CYP3A, CYP4A), glutathione-S-transferase (GSTA1/2, GSTA3, GSTA4, AND GSTM1), and uridine diphosphate glucuronosyl transferase (UGT) in rat intestine, between fetal life and maturity. Enzyme induction and DNA adduct formation were assessed after 3-methylcholanthrene (MC) exposure. Untreated rat intestine expressed CYP2B, GSTA1/2, GSTA4 and UGT at all stages of maturation, although CYP2B and GSTA1/2 increased in postnatal life. MC induced new expression of CYP1A, GSTA3 and enhanced expression of GSTA1/2 and UGT. Age-dependent differences of enzyme induction and DNA adduct formation between pre- and postnatal intestine and during postnatal maturation, were observed. Rat intestinal epithelium shows variable competence for MC metabolism and sustains disparate levels of DNA adducts during pre- and postnatal development.

    Original languageEnglish
    Pages (from-to)27-37
    Number of pages11
    JournalChemico-Biological Interactions
    Volume113
    Issue number1
    DOIs
    Publication statusPublished - 1 May 1998

    Keywords

    • Aging/genetics
    • Animals
    • Cytochrome P-450 Enzyme System/metabolism
    • DNA Adducts/biosynthesis
    • Enzyme Induction/drug effects
    • Female
    • Glucuronosyltransferase/metabolism
    • Glutathione Transferase/metabolism
    • Intestines/drug effects
    • Male
    • Methylcholanthrene/metabolism
    • Mutagens/toxicity
    • Pregnancy
    • Rats
    • Rats, Inbred Strains

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