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 language | English |
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Pages (from-to) | 27-37 |
Number of pages | 11 |
Journal | Chemico-Biological Interactions |
Volume | 113 |
Issue number | 1 |
DOIs | |
Publication status | Published - 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