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Toxicol Appl Pharmacol. 2002 Sep 15;183(3):168-78.

Interaction between metabolism and transport of benzo[a]pyrene and its metabolites in enterocytes.

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  • 1Department of Food Toxicology, School for Veterinary Medicine, Bischofsholer Damm 15, 30173 Hannover, Germany.


Epithelial cells of the small intestine are responsible for the resorption of different food components as well as potentially toxic agents such as benzo[a]pyrene (B[a]P), a particular contaminant of charcoal-grilled meat. This study was undertaken to investigate any functional relationship between the metabolism of B[a]P and the unidirectional transport of metabolites back into the intestinal lumen mediated by ATP-binding cassette (ABC) transport proteins. The human intestinal Caco-2 cell line was used. In addition, mdr1- and mrp2-transfected MDCK cells were employed to characterize the possible role of these ABC transport proteins in the polarized transport. After incubations of Caco-2 cells with B[a]P, HPLC analysis revealed that the primary metabolites of B[a]P were B[a]P-1-sulfate and B[a]P-3-sulfate. Other metabolites, such as B[a]P-3-glucuronide, B[a]P-9,10-diol, or B[a]P-3,6-quinone, could be detected only in small amounts. The transport experiments using Transwell chambers clearly showed that B[a]P-1- and B[a]P-3-sulfate were actively transported toward the apical (luminal) region. This transport increased after induction of CYP1A1/CYP1B1 (Phase 1)-metabolism, although a decrease was observed during concomitant inhibition. Inhibition studies using chemical inhibitors of P-glycoprotein, MRPs, showed no effects. A comparison between the transport of B[a]P-1- and B[a]P-3-sulfate in wild-type and mrp2-transfected MDCKII cells revealed no differences at all. The results indicate that B[a]P is metabolized by Caco-2 cells mainly to B[a]P-1- and B[a]P-3-sulfate, which are subject to an apically directed transport. Furthermore ABC transport proteins P-glycoprotein, MRP1, and MRP2 are not involved in this polarized B[a]P-sulfate secretion.

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