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

TY - JOUR

T1 - Age-dependent change of metabolic capacity and genotoxic injury in rat intestine

AU - Patela, H. R. H.

AU - Hewer, A.

AU - Hayes, J. D.

AU - Phillips, D. H.

AU - Campbell, F. C.

PY - 1998/5/1

Y1 - 1998/5/1

N2 - 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.

AB - 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.

KW - Aging/genetics

KW - Animals

KW - Cytochrome P-450 Enzyme System/metabolism

KW - DNA Adducts/biosynthesis

KW - Enzyme Induction/drug effects

KW - Female

KW - Glucuronosyltransferase/metabolism

KW - Glutathione Transferase/metabolism

KW - Intestines/drug effects

KW - Male

KW - Methylcholanthrene/metabolism

KW - Mutagens/toxicity

KW - Pregnancy

KW - Rats

KW - Rats, Inbred Strains

U2 - 10.1016/S0009-2797(98)00016-7

DO - 10.1016/S0009-2797(98)00016-7

M3 - Article

C2 - 9630845

SN - 0009-2797

VL - 113

SP - 27

EP - 37

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

IS - 1

ER -