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

Chem Biol Interact. 1998 May 1;113(1):27-37. doi: 10.1016/s0009-2797(98)00016-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • DNA Adducts
  • Mutagens
  • Methylcholanthrene
  • Cytochrome P-450 Enzyme System
  • Glucuronosyltransferase
  • Glutathione Transferase