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EFFECTS OF RESVERATROL ON AHR ACTIVITY IN CELLS TREATED WITH BENZO[A]PYRENE OR INDIGO

Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. AHR regulates many cellular pathways, including expression of the CYP1A1 gene, which is responsible for metabolizing compounds such as B[a]P. While limited research has been done with indigo and its effects on the AHR, B[a]P is a known inducer of CYP1A1 via the AHR. Resveratrol, a stilbenoid found in grapes and other food items, has been shown to inhibit tumor growth and modulates other cellular pathways that involve the AHR. We here examined the effects of resveratrol on AHR activity in mouse hepatocytes, specifically looking at its effects on B[a]P- and indigo-mediated activity of the receptor. Previous finding have indicated that using different concentration of resveratrol to treat cells can illicit varying responses. In this study we report that low concentrations of resveratrol in combination with either B[a]P or indigo results in increased AHR activity compared to B[a]P or indigo alone, with maximal activity observed with 50nM of resveratrol. However, at higher concentrations (~200nM), resveratrol can act as an inhibitor of the receptor activity in the presence of B[a]P or indigo. Based on these findings, we suggest that high concentrations of resveratrol are required to inhibit AHR activity, which could cause the metabolic activation of B[a]P into a carcinogen. It is fortunate that resveratrol is well-tolerated and easily absorbed; however, it is rapidly metabolized, which could make it difficult to obtain the required intercellular concentrations in vivo.

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