![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
New York State Department of Health, Wadsworth Center
The predominant inducible cytochrome P450 (CYP) in rat small
intestine is CYP1A1, which, when induced to elevated levels by xenobiotics or dietary constituents, has the potential to metabolize and consequently reduce the systemic uptake of low concentrations of
orally ingested, bioactivatable polycyclic aromatic hydrocarbons and
heterocyclic aromatic amines. We investigated the regulation of small
intestinal CYP1A1 in an effort to develop its anticancer potential. The
time courses of hepatic and intestinal CYP1A1 induction by
-naphthoflavone (BNF) were compared quantitatively at the protein
and mRNA levels by immunoblot and competitive RNA-polymerase chain
reaction analyses. CYP1A1 mRNA levels in both organs increased sharply
and were maximal at ~6 hr and returned to near basal levels by 12 hr
after BNF treatment. In contrast, hepatic CYP1A2 mRNA levels increased
much more gradually. Small intestinal CYP1A2 mRNA concentrations were
insufficient to support translation of detectable protein. Maximal
levels of intestinal and hepatic CYP1A1 protein occurred between 12 and
24 hr, and 24 and 48 hr, respectively, after BNF. Intestinal CYP1A1
protein was detectable earlier and for a shorter duration than hepatic
CYP1A1. CYP1A1 induction was first detected in crypt cells 3 hr before
the appearance of activity in villous cells, and maximal levels of
activity were reached in crypt cells 12 to 18 hr before maximal and
1.5-fold (per mg protein) higher responses in villous cells
induction
thus occurs in both villous and crypt cells. Previously detected
decreases in CYP1A1 inducibility from duodenum to ileum correlated with decreases in immunoblot determined-Ah receptor levels. Intestinal CYP1A1 induction does not involve the glucocorticoid receptor in
contrast to hepatic induction. These studies have revealed several
novel features of small intestinal CYP1A1 regulation.
This article has been cited by other articles:
|
|
 |
|
  R. Kitamura, Y. Yamamoto, S. Nagayama, and M. Otagiri Decrease in Plasma Concentrations of Antiangiogenic Agent TSU-68 ((Z)-5-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-propanoic acid) during Oral Administration Twice a Day to Rats Drug Metab. Dispos., September 1, 2007; 35(9): 1611 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. van de Kerkhof, I. A. M. de Graaf, M. H. de Jager, and G. M. M. Groothuis Induction of Phase I and II Drug Metabolism in Rat Small Intestine and Colon in Vitro Drug Metab. Dispos., June 1, 2007; 35(6): 898 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. M. de Graaf, R. de Kanter, M. H. de Jager, R. Camacho, E. Langenkamp, E. G. van de Kerkhof, and G. M. M. Groothuis EMPIRICAL VALIDATION OF A RAT IN VITRO ORGAN SLICE MODEL AS A TOOL FOR IN VIVO CLEARANCE PREDICTION Drug Metab. Dispos., April 1, 2006; 34(4): 591 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. van de Kerkhof, I. A. M. de Graaf, M. H. de Jager, D. K. F. Meijer, and G. M. M. Groothuis CHARACTERIZATION OF RAT SMALL INTESTINAL AND COLON PRECISION-CUT SLICES AS AN IN VITRO SYSTEM FOR DRUG METABOLISM AND INDUCTION STUDIES Drug Metab. Dispos., November 1, 2005; 33(11): 1613 - 1620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Kaminsky and Q.-Y. Zhang THE SMALL INTESTINE AS A XENOBIOTIC-METABOLIZING ORGAN Drug Metab. Dispos., December 1, 2003; 31(12): 1520 - 1525. [Full Text] [PDF]
|
|
|
|
|
|
Q.-Y. Zhang, D. Dunbar, and L. S. Kaminsky CHARACTERIZATION OF MOUSE SMALL INTESTINAL CYTOCHROME P450 EXPRESSION Drug Metab. Dispos., November 1, 2003; 31(11): 1346 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Lin, M. Chiba, and T. A. Baillie Is the Role of the Small Intestine in First-Pass Metabolism Overemphasized? Pharmacol. Rev., June 1, 1999; 51(2): 135 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Brooks, N. J. Gooderham, R. J. Edwards, A. R. Boobis, and D. J. Winton The mutagenicity of benzo[a]pyrene in mouse small intestine Carcinogenesis, January 1, 1999; 20(1): 109 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. O. Mueller, H. Stopper, and W. Dekant Biotransformation of the Anthraquinones Emodin and Chrysophanol by Cytochrome P450 Enzymes. Bioactivation to Genotoxic Metabolites Drug Metab. Dispos., June 1, 1998; 26(6): 540 - 546. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
