author={Thomas D. Schreiber and Christoph Koehle and Felicitas Buckler and Stefan Schmohl and Albert Braeuning and Alexander Schmiechen and Michael Schwarz and Peter A. Münzel},
  journal={Drug Metabolism and Disposition},
  pages={1096 - 1101}
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… 

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It is shown that a second level of transcriptional control exists in hepatocytes, which is tightly linked to the Wnt/β-catenin/T-cell factor (TCF) signaling pathway, and signaling through β- catenin activates basal CYP1A1 expression and augments CYP 1A1 induction by AhR ligands through enhancement of the transactivation potential of the AhR.

The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tert-butylhydroquinone or 3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate of sodium

Change in gene expression of phase I, II, and III drug metabolizing enzymes/transporters as well as protein levels and activities of cytochromes P450 (CYPs) elicited by tBHQ and its structural homolog TS-13 in the mouse liver are studied.

DMD064667 1781..1787

A comprehensive characterization of xenobiotic metabolism in HC-AFW1 cells is presented along with studies on the functionality of the most important transcriptional regulators of drug-metabolizing enzymes.

Propiconazole is an activator of AHR and causes concentration additive effects with an established AHR ligand

The results demonstrate that the triazole Pi is an activator of AHR in silico, in vitro and in vivo and causes additive effects with an established AHR ligand.

Signal integration by the CYP1A1 promoter — a quantitative study

This study exemplifies how statistical mechanical modeling together with combinatorial reporter assays has the capacity to disentangle the promoter logic that establishes physiological gene expression patterns.

Comparative Analysis and Functional Characterization of HC-AFW1 Hepatocarcinoma Cells: Cytochrome P450 Expression and Induction by Nuclear Receptor Agonists

A comprehensive characterization of xenobiotic metabolism in HC-AFW1 cells is presented along with studies on the functionality of the most important transcriptional regulators of drug-metabolizing enzymes.

Effects of dietary tert-butylhydroquinone on domoic acid metabolism and transcription of detoxification-related liver genes in red sea bream Pagrus major

The findings in this research suggested that the dietary intake of tBHQ accelerated DA metabolism in fish, through mechanisms involving altered transcription of detoxification-related liver genes.

Mixture effects of two plant protection products in liver cell lines.

  • E. ZahnJ. Wolfrum S. Rieke
  • Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2018




This is the first demonstration that the phenolic antioxidant, tBHQ, can directly induce Cyp1a1 gene expression in an AHR-dependent manner and may represent a novel mechanism by which tB HQ promotes carcinogenicity.

Transcriptional Induction of CYP1A1 by Oltipraz in Human Caco-2 Cells Is Aryl Hydrocarbon Receptor- and Calcium-dependent*

It is shown here that, as previously found in rat lung and kidney, CYP1A1 is inducible by oltipraz in both rat intestine and Caco-2 cells, a cell line originated from a human colon adenocarcinoma.

Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor.

It is demonstrated that resveratrol inhibits CYP1A1 expression in vitro, and that it does this by preventing the binding of the AHR to promoter sequences that regulate CYP 1A1 transcription.

Pivotal role of electrophilicity in glutathione S-transferase induction by tert-butylhydroquinone.

It is concluded that an electrophilic quinone oxidation product that reacts with intracellular nucleophiles including protein thiol or GSH plays a major role in the GSTP1 gene expression.

Functional analysis of the human cytochrome P4501A1 (CYP1A1) gene enhancer.

The data show that, besides some similarities in the regulation of the human and mouse CYP1A1 genes, there also exist some distinct differences, including number, location, and functional consensus sequences of DRE motifs, as well as quantity and location of footprinted G-rich domains.

Oltipraz Inhibits 3-Methylcholanthrene Induction of CYP1A1 by CCAAT/Enhancer-binding Protein Activation*

Evidence is provided that oltipraz suppresses 3-MC induction of CYP1A1 gene expression and that activation of C/EBPβ by oldipraz contributes to suppression of 3- MC-inducible AhR-mediated CYP 1A1 expression.

Protein Kinase C Modulates Regulation of the CYP1A1 Gene by the Aryl Hydrocarbon Receptor*

Inhibition of PKC activity blocked directly the transcriptional activation and the transactivation of the CYP1A1 gene, indicating a role for PKC in the AhR-mediated transcriptionalactivation process.

Butylated Hydroxyanisole and Its Metabolitetert-Butylhydroquinone Differentially Regulate Mitogen-activated Protein Kinases

It is demonstrated that BHA is capable of activating distinct mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 2 (ERK2), and c-Jun N-terminal kinase 1 (JNK1), and oxidative stress due to the generation of reactive intermediates, possibly phenoxyl radicals but not H2O2, is responsible for the ERK2 activation by BHA and tBHQ.