Identification of BCRP as transporter of benzo[ a ]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists

摘要: Breast cancer resistance protein (BCRP/ABCG2) is known to actively transport various anticancer drugs and restrict the uptake of food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine from gut lumen. The present study reveals that BCRP involved in phase-2 metabolites benzo[a]pyrene (BP) human intestinal cell line Caco-2. Treatment with selective inhibitor Ko 143 (5 microM) inhibited apical BP-3-sulfate (BP3S) 83% control levels TC7 cells 64% Caco-2 cells. BP-3-glucuronide was by 76% Furthermore, expression most likely aryl hydrocarbon receptor (AhR) dependent, as treatment AhR agonists including 2,3,7,8-tetrachlorodibenzo-p-dioxin, BP, indolo[3,2-b]carbazole benzo[k]fluoranthene increased both mRNA BCRP. Induced found be functionally active, since pre-treatment oltipraz, or amount apically transported BP3S much 180% controls. induction (mRNA expression) co-incubation antagonist PD98059 (2'-amino-3'-methoxyflavone). In summary, this provides strong evidence an important part barrier protecting body food-associated contaminants such BP.