All-trans retinoic acid enhances the transport of phase II metabolites of benzo[a]pyrene by inducing the Breast Cancer Resistance Protein expression in Caco-2 cells.
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Hessel S, Lampen A
All-trans retinoic acid enhances the transport of phase II metabolites of benzo[a]pyrene by inducing the Breast Cancer Resistance Protein expression in Caco-2 cells.
Toxicol Lett. 2010 Aug 16;197(2):151-5. doi: 10.1016/j.toxlet.2010.05.018. Epub 2010 Jun 1.
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- 20562004 [ View in PubMed]
- Abstract
All-trans retinoic acid (atRA) is the most active metabolite of vitamin A. It is a ligand of retinoic acid receptors (RAR) as well as of retinoid X receptors (RXR) and effectively stimulates the RAR/RXR signalling pathway. In this study effects of atRA on the detoxification of the food contaminant benzo[a]pyrene (B[a]P) was elucidated by using the Caco-2 cell line as model system for the human small intestine. Caco-2 cells express a number of phase I and II xenobiotic-metabolising enzymes as well as several transport proteins of the ATP-binding cassette (ABC) superfamily. Pre-treatment of the cells with atRA resulted in enhanced apical excretion of B[a]P-3-sulfate, a phase II metabolite of B[a]P. Gene expression analysis revealed that the Breast Cancer Resistance Protein (BCRP), an ABC-transporter known to be involved in B[a]P-3-sulfate excretion, was strongly stimulated already at low concentrations of atRA. Furthermore co-incubation of the intestinal cell with RAR agonist and RXR agonist resulted in a strong additive induction of mRNA expression of BCRP. Thus, atRA was shown to induce BCRP gene expression probably via the RAR/RXR signalling pathway, resulting in effective removal of B[a]P metabolites from intestinal cells.