@article {Schreiber1096, author = {Thomas D. Schreiber and Christoph K{\"o}hle and Felicitas Buckler and Stefan Schmohl and Albert Braeuning and Alexander Schmiechen and Michael Schwarz and Peter A. M{\"u}nzel}, title = {REGULATION OF CYP1A1 GENE EXPRESSION BY THE ANTIOXIDANT TERT-BUTYLHYDROQUINONE}, volume = {34}, number = {7}, pages = {1096--1101}, year = {2006}, doi = {10.1124/dmd.106.009662}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {CYP1A1, a major phase I enzyme, plays an important role in the metabolism of polycyclic aromatic hydrocarbons and in the chemical activation of xenobiotics to carcinogenic derivatives. The phenolic antioxidant tert-butylhydroquinone (tBHQ), often used as a food preservative, is generally considered to act only as a mono-functional inducer of phase II enzymes, thereby exerting chemo-protection. However, we recently observed that tBHQ elevated the activity of an aryl hydrocarbon receptor (AhR) response element (DRE)-driven luciferase reporter in human colon carcinoma cells (Caco-2). Therefore, we studied the effects of tBHQ on the activity of a DRE-driven reporter, CYP1A1 mRNA expression, and CYP1A enzyme activity in Caco-2 cells and human HepG2 hepatoma cells. We found tBHQ caused induction of reporter activity and CYP1A1 expression and activity in Caco-2 and HepG2 cells. Moreover, tBHQ combined with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased reporter activity and mRNA expression in Caco-2 cells in an additive manner. By contrast, tBHQ decreased TCDD-mediated induction of reporter activity and CYP1A1 mRNA expression in HepG2 cells. Resveratrol, an AhR antagonist, repressed the induction of CYP1A1 by tBHQ. Cotransfection of HepG2 cells with a dominant negative AhR nuclear translocator mutant abolished the tBHQ-induced CYP1A1 reporter activity. These findings indicate that CYP1A1 may be induced by the antioxidant tBHQ via an AhR-dependent mechanism. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/34/7/1096}, eprint = {https://dmd.aspetjournals.org/content/34/7/1096.full.pdf}, journal = {Drug Metabolism and Disposition} }