The efforts for therapeutic targeting of the aryl hydrocarbon receptor (AhR) have emerged in recent years. We investigated the effects of available antimigraine triptan drugs, having an indole core in their structure, on AhR signaling in human hepatic and intestinal cells. Activation of AhR in reporter gene assays was observed for Avitriptan and to a lesser extent for Donitriptan, while other triptans were very weak or no activators of AhR. Using competitive binding assay and by homology docking, we identified Avitriptan as a low-affinity ligand of AhR. Avitriptan triggered nuclear translocation of AhR and increased binding of AhR in CYP1A1 promotor DNA, as revealed by immune-fluorescence microscopy and chromatin immune-precipitation assay, respectively. Strong induction of CYP1A1 mRNA was achieved by Avitriptan in wild type but not in AhR-knockout, immortalized human hepatocytes, implying that induction of CYP1A1 is AhR-dependent. Increased levels of CYP1A1 mRNA by Avitriptan were observed in human colon carcinoma cells LS180 but not in primary cultures of human hepatocytes. Collectively, we show that Avitriptan is a weak ligand and activator of human AhR, which induces the expression of CYP1A1 in a cell-type specific manner. Our data warrant the potential off-label therapeutic application of Avitriptan as an AhR-agonist drug.

• MeSH
• Enzyme Activation drug effects   MeSH
• Cytochrome P-450 CYP1A1 genetics   MeSH
• Hepatocytes metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Ligands MeSH
• Models, Molecular MeSH
• Organ Specificity MeSH
• Drug Repositioning MeSH
• Promoter Regions, Genetic drug effects   MeSH
• Receptors, Aryl Hydrocarbon agonists   chemistry   metabolism   MeSH
• Molecular Docking Simulation MeSH
• Intestinal Mucosa metabolism   MeSH
• Sulfonamides pharmacology   MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   chemistry   metabolism   MeSH
• Tryptamines pharmacology   MeSH
• Up-Regulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

We examined the effects of gut microbial catabolites of tryptophan on the aryl hydrocarbon receptor (AhR). Using a reporter gene assay, we show that all studied catabolites are low-potency agonists of human AhR. The efficacy of catabolites differed substantially, comprising agonists with no or low (i3-propionate, i3-acetate, i3-lactate, i3-aldehyde), medium (i3-ethanol, i3-acrylate, skatole, tryptamine), and high (indole, i3-acetamide, i3-pyruvate) efficacies. We displayed ligand-selective antagonist activities by i3-pyruvate, i3-aldehyde, indole, skatole, and tryptamine. Ligand binding assay identified low affinity (skatole, i3-pyruvate, and i3-acetamide) and very low affinity (i3-acrylate, i3-ethanol, indole) ligands of the murine AhR. Indole, skatole, tryptamine, i3-pyruvate, i3-acrylate, and i3-acetamide induced CYP1A1 mRNA in intestinal LS180 and HT-29 cells, but not in the AhR-knockout HT-29 variant. We observed a similar CYP1A1 induction pattern in primary human hepatocytes. The most AhR-active catabolites (indole, skatole, tryptamine, i3-pyruvate, i3-acrylate, i3-acetamide) elicited nuclear translocation of the AhR, followed by a formation of AhR-ARNT heterodimer and enhanced binding of the AhR to the CYP1A1 gene promoter. Collectively, we comprehensively characterized the interactions of gut microbial tryptophan catabolites with the AhR, which may expand the current understanding of their potential roles in intestinal health and disease.

• MeSH
• Cytochrome P-450 CYP1A1 genetics   MeSH
• Gene Expression MeSH
• Indoles MeSH
• Humans MeSH
• Ligands MeSH
• Metabolic Networks and Pathways MeSH
• Protein Multimerization MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Promoter Regions, Genetic MeSH
• Receptors, Aryl Hydrocarbon agonists   metabolism   MeSH
• Genes, Reporter MeSH
• Gastrointestinal Microbiome * drug effects   MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   metabolism   MeSH
• Tryptophan metabolism   MeSH
• Protein Binding MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Mono-methylindoles (MMI) were described as agonists and/or antagonists of the human aryl hydrocarbon receptor (AhR). Here, we investigated the effects of MMI on AhR-CYP1A pathway in human hepatocytes and HepaRG cells derived from human progenitor hepatic cells. All MMI, except of 2-methylindole, strongly induced CYP1A1 and CYP1A2 mRNAs in HepaRG cells. Induction of CYP1A genes was absent in AhR-knock-out HepaRG cells. Consistently, CYP1A1 and CYP1A2 mRNAs and proteins were induced by all MMIs (except 2-methylindole), in human hepatocytes. The enzyme activity of CYP1A1 was inhibited by MMIs in human hepatocytes and LS180 colon cancer cells in a concentration-dependent manner (IC50 values from 1.2 μM to 23.8 μM and from 3.4 μM to 11.4 μM, respectively). Inhibition of CYP1A1 activity by MMI in human liver microsomes was much weaker as compared to that in intact cells. Incubation of parental MMI with human hepatocytes either diminished (4-methylindole, 6-methylindole) or enhanced (7-methylindole) their agonist effects on AhR in AZ-AHR reporter cells. In conclusion, overall effects of MMI on AhR-CYP1A pathway in human cells comprise the induction of CYP1A genes through AhR, the inhibition of CYP1A catalytic activity and possibly the metabolic transformation causing loss or gain of AhR agonist activity of parental compounds.

• MeSH
• Cytochrome P-450 CYP1A1 antagonists & inhibitors   biosynthesis   genetics   MeSH
• Enzyme Induction MeSH
• Hepatocytes drug effects   enzymology   MeSH
• Indoles pharmacology   MeSH
• Cytochrome P-450 Enzyme Inducers pharmacology   MeSH
• Cytochrome P-450 Enzyme Inhibitors pharmacology   MeSH
• Microsomes, Liver drug effects   enzymology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Cell Line, Tumor MeSH
• Colonic Neoplasms enzymology   MeSH
• Receptors, Aryl Hydrocarbon agonists   genetics   metabolism   MeSH
• Aged MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   genetics   metabolism   MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Essential oils (EOs) of culinary herbs and spices are used to flavor, color and preserve foods and drinks. Dietary intake of EOs is significant, deserving an attention of toxicologists. We examined the effects of 31 EOs of culinary herbs and spices on the transcriptional activity of human aryl hydrocarbon receptor (AhR), which is a pivotal xenobiotic sensor, having also multiple roles in human physiology. Tested EOs were sorted out into AhR-inactive ones (14 EOs) and AhR-active ones, including full agonists (cumin, jasmine, vanilla, bay leaf), partial agonists (cloves, dill, thyme, nutmeg, oregano) and antagonists (tarragon, caraway, turmeric, lovage, fennel, spearmint, star anise, anise). Major constituents (>10%) of AhR-active EOs were studied in more detail. We identified AhR partial agonists (carvacrol, ligustilide, eugenol, eugenyl acetate, thymol, ar-turmerone) and antagonists (trans-anethole, butylidine phtalide, R/S-carvones, p-cymene), which account for AhR-mediated activities of EOs of fennel, anise, star anise, caraway, spearmint, tarragon, cloves, dill, turmeric, lovage, thyme and oregano. We also show that AhR-mediated effects of some individual constituents of EOs differ from those manifested in mixtures. In conclusion, EOs of culinary herbs and spices are agonists and antagonists of human AhR, implying a potential for food-drug interactions and interference with endocrine pathways.

• MeSH
• Cytochrome P-450 CYP1A1 genetics   metabolism   MeSH
• Origanum MeSH
• Food-Drug Interactions MeSH
• Spices analysis   MeSH
• Humans MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Myristica MeSH
• Cell Line, Tumor MeSH
• Oils, Volatile pharmacology   MeSH
• Plant Oils pharmacology   MeSH
• Receptors, Aryl Hydrocarbon agonists   antagonists & inhibitors   MeSH
• Gene Expression Regulation drug effects   MeSH
• Thymus Plant MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   antagonists & inhibitors   MeSH
• Cooking MeSH
• Laurus MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants.

• MeSH
• Transcriptional Activation drug effects   MeSH
• Azo Compounds toxicity   MeSH
• Benzo(a)pyrene toxicity   MeSH
• A549 Cells MeSH
• Time Factors MeSH
• Fluorenes toxicity   MeSH
• Transcription, Genetic drug effects   MeSH
• Gene Regulatory Networks drug effects   MeSH
• Indoles toxicity   MeSH
• Carbazoles toxicity   MeSH
• Environmental Pollutants toxicity   MeSH
• Humans MeSH
• Ligands MeSH
• Lung Neoplasms genetics   metabolism   MeSH
• Polychlorinated Dibenzodioxins toxicity   MeSH
• Pyrazoles toxicity   MeSH
• Receptors, Aryl Hydrocarbon agonists   metabolism   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Signal Transduction drug effects   MeSH
• Gene Expression Profiling methods   MeSH
• Thiazoles toxicity   MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   metabolism   MeSH
• Transcriptome drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Novel methylindoles were identified as endobiotic and xenobiotic ligands of the human aryl hydrocarbon receptor (AhR). We examined the effects of 22 methylated and methoxylated indoles on the transcriptional activity of AhRs. Employing reporter gene assays in AZ-AHR transgenic cells, we determined full agonist, partial agonist, or antagonist activities of tested compounds, having substantially variable EC50, IC50, and relative efficacies. The most effective agonists (EMAX relative to 5 nM dioxin) of the AhR were 4-Me-indole (134%), 6-Me-indole (91%), and 7-MeO-indole (80%), respectively. The most effective antagonists of the AhR included 3-Me-indole (IC50; 19 μM), 2,3-diMe-indole (IC50; 11 μM), and 2,3,7-triMe-indole (IC50; 12 μM). Reverse transcription polymerase chain reaction analyses of CYP1A1 mRNA in LS180 cells confirmed the data from gene reporter assays. The compound leads, 4-Me-indole and 7-MeO-indole, induced substantial nuclear translocation of the AhR and enriched binding of the AhR to the CYP1A1 promoter, as observed using fluorescent immunohistochemistry and chromatin immunoprecipitation assays, respectively. Molecular modeling and docking studies suggest the agonists and antagonists likely share the same binding pocket but have unique binding modes that code for their affinity. Binding pocket analysis further revealed that 4-methylindole and 7-methoxyindole can simultaneously bind to the pocket and produce synergistic interactions. Together, these data show a dependence on subtle and specific chemical indole structures as AhR modulators and furthermore underscore the importance of complete evaluation of indole compounds as nuclear receptor ligands.

• MeSH
• Hep G2 Cells MeSH
• Cytochrome P-450 CYP1A1 metabolism   MeSH
• Indoles pharmacology   MeSH
• Humans MeSH
• Ligands MeSH
• RNA, Messenger metabolism   MeSH
• Cell Line, Tumor MeSH
• Promoter Regions, Genetic drug effects   MeSH
• Receptors, Aryl Hydrocarbon agonists   antagonists & inhibitors   MeSH
• Genes, Reporter drug effects   MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   antagonists & inhibitors   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

The effects of four copper(II) mixed-ligand complexes [Cu(qui1)(L)]NO3·H2O (1-3) and [Cu(qui2)(phen)]NO3 (4), where qui1=2-phenyl-3-hydroxy-4(1H)-quinolinone, Hqui2=2-(4-amino-3,5-dichlorophenyl)-N-propyl-3-hydroxy-4(1H)-quinolinone-7-carboxamide, L=1,10-phenanthroline (phen) (1), 5-methyl-1,10-phenanthroline (mphen) (2), bathophenanthroline (bphen) (3), on transcriptional activities of steroid receptors, nuclear receptors and xenoreceptors have been studied. The complexes (1-4) did not influence basal or ligand-inducible activities of glucocorticoid receptor, androgen receptor, thyroid receptor, pregnane X receptor and vitamin D receptor, as revealed by gene reporter assays. The complexes 1 and 2 dose-dependently induced luciferase activity in stable gene reporter AZ-AhR cell line, and this induction was reverted by resveratrol, indicating involvement of aryl hydrocarbon receptor (AhR) in the process. The complexes 1, 2 and 3 induced CYP1A1 mRNA in LS180 cells and CYP1A1/CYP1A2 in human hepatocytes through AhR. Electrophoretic mobility shift assay EMSA showed that the complexes 1 and 2 transformed AhR in its DNA-binding form. Collectively, we demonstrate that the complexes 1 and 2 activate AhR and induce AhR-dependent genes in human hepatocytes and cancer cell lines. In conclusion, the data presented here might be of toxicological importance, regarding the multiple roles of AhR in human physiology and pathophysiology.

• MeSH
• Transcriptional Activation drug effects   MeSH
• Cytochrome P-450 CYP1A1 biosynthesis   genetics   MeSH
• Cytochrome P-450 CYP1A2 biosynthesis   genetics   MeSH
• Adult MeSH
• Nitrates toxicity   MeSH
• Enzyme Induction MeSH
• Phenanthrolines toxicity   MeSH
• Transcription, Genetic drug effects   MeSH
• Hepatocytes drug effects   enzymology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Ligands MeSH
• Copper toxicity   MeSH
• RNA, Messenger biosynthesis   genetics   MeSH
• MCF-7 Cells MeSH
• Primary Cell Culture MeSH
• Receptors, Aryl Hydrocarbon agonists   genetics   metabolism   MeSH
• Aged MeSH
• Transfection MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   genetics   metabolism   MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

Polycyclic aromatic hydrocarbons (PAHs) with lower molecular weight exhibit lesser genotoxicity and carcinogenicity than highly carcinogenic PAHs with a higher number of benzene rings. Nevertheless, they elicit specific effects linked with tumor promotion, such as acute inhibition of gap junctional intercellular communication (GJIC). Although inflammatory reaction may alter bioactivation and toxicity of carcinogenic PAHs, little is known about the impact of pro-inflammatory cytokines on toxic effects of the low-molecular-weight PAHs. Here, we investigated the impact of a pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), on the effects associated with tumor promotion and with induction of the aryl hydrocarbon receptor (AhR)-dependent gene expression in rat liver epithelial cells. We found that a prolonged incubation with TNF-α induced a down-regulation of GJIC, associated with reduced expression of connexin 43 (Cx43), a major connexin isoform found in liver epithelial cells. The Cx43 down-regulation was partly mediated by the activity of the mitogen-activated protein (MAP) p38 kinase. Independently of GJIC modulation, or p38 activation, TNF-α potentiated the AhR-dependent proliferative effect of a model low-molecular-weight PAH, fluoranthene, on contact-inhibited cells. In contrast, this pro-inflammatory cytokine repressed the fluoranthene-induced expression of a majority of model AhR gene targets, such as Cyp1a1, Ahrr or Tiparp. The results of the present study indicate that inflammatory reaction may differentially modulate various toxic effects of low-molecular-weight PAHs; the exposure to pro-inflammatory cytokines may both strengthen (inhibition of GJIC, disruption of contact inhibition) and repress (expression of a majority of AhR-dependent genes) their impact on toxic endpoints associated with carcinogenesis.

• MeSH
• Enzyme Activation MeSH
• Cell Line MeSH
• Time Factors MeSH
• Epithelial Cells drug effects   metabolism   pathology   MeSH
• Fluorenes toxicity   MeSH
• Transcription, Genetic drug effects   MeSH
• Liver drug effects   metabolism   pathology   MeSH
• Connexin 43 genetics   metabolism   MeSH
• Rats MeSH
• Gap Junctions drug effects   metabolism   pathology   MeSH
• Cell Communication drug effects   MeSH
• p38 Mitogen-Activated Protein Kinases metabolism   MeSH
• Molecular Weight MeSH
• Cell Transformation, Neoplastic chemically induced   metabolism   pathology   MeSH
• Liver Neoplasms chemically induced   metabolism   pathology   MeSH
• Cell Proliferation drug effects   MeSH
• Receptors, Aryl Hydrocarbon agonists   genetics   metabolism   MeSH
• Gene Expression Regulation drug effects   MeSH
• Signal Transduction drug effects   MeSH
• Tumor Necrosis Factor-alpha toxicity   MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   genetics   metabolism   MeSH
• Dose-Response Relationship, Drug MeSH
• Inflammation chemically induced   genetics   metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Cytochrome P450 (CYP) expression and activity are not homogeneous in the liver lobules. Indeed, CYPs are mainly expressed and induced in centrilobular hepatocytes. The wingless-type MMTV integration site family (WNT)/β-catenin pathway was identified as a major regulator of this zonal organization. We have recently demonstrated that in primary human hepatocytes (PHHs), the expression of CYP2E1, CYP1A2, and aryl hydrocarbon receptor (AhR), but not of CYP3A4, is regulated by the WNT/β-catenin pathway in response to WNT3a, its canonical activator. Here, we investigated whether glycogen synthase kinase 3β (GSK3β) inhibitors, which mimic the action of WNT molecules, could be used in PHHs to activate the β-catenin pathway to study CYP expression. We assessed the activity of 6BIO (6-bromoindirubin-3'-oxime), CHIR99021 (6-((2-((4-(2,4-dichlorophenyl)-5-(4methyl-1H-imidazol-2-yl)pyrimidin-2-yl)amino)ethyl)amino) nicotinonitrile), and GSK3iXV (Pyridocarbazolo-cyclopentadienyl Ruthenium complex GSK3 inhibitor XV) that belong to structurally different families of GSK3β inhibitors. Using small interfering RNAs, reporter gene assays, and molecular docking predictions, we demonstrated that GSK3β inhibitors can activate the WNT/β-catenin pathway in PHHs to regulate CYP2E1 expression. We also found that 6BIO and GSK3iXV are AhR full agonists that participate, through AhR signaling, to CYP1A2 induction. Conversely, CHIR99021 is an AhR partial agonist, and a pregnane X receptor ligand and partial agonist, thus regulating CYP1A2 and CYP3A4 gene expression in a β-catenin-independent manner. In conclusion, GSK3β inhibitors can activate the WNT/β-catenin pathway in PHHs. Nevertheless, their role in CYP regulation should be analyzed with caution as these molecules can interact with xenosensors.

• MeSH
• beta Catenin agonists   antagonists & inhibitors   genetics   metabolism   MeSH
• Enzyme Induction drug effects   MeSH
• Hepatocytes cytology   drug effects   metabolism   MeSH
• Indoles pharmacology   MeSH
• Cytochrome P-450 Enzyme Inducers chemistry   metabolism   pharmacology   MeSH
• Protein Kinase Inhibitors chemistry   metabolism   pharmacology   MeSH
• Glycogen Synthase Kinase 3 antagonists & inhibitors   metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Organometallic Compounds pharmacology   MeSH
• Oximes pharmacology   MeSH
• Pyridines pharmacology   MeSH
• Pyrimidines pharmacology   MeSH
• Receptors, Aryl Hydrocarbon agonists   chemistry   genetics   metabolism   MeSH
• Recombinant Fusion Proteins chemistry   metabolism   MeSH
• Genes, Reporter drug effects   MeSH
• RNA Interference MeSH
• Wnt Signaling Pathway drug effects   MeSH
• Molecular Docking Simulation MeSH
• Receptors, Steroid agonists   genetics   metabolism   MeSH
• Cytochrome P-450 Enzyme System chemistry   genetics   metabolism   MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   chemistry   genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Inhibition of apoptosis by the ligands of the aryl hydrocarbon receptor (AhR) has been proposed to play a role in their tumor promoting effects on liver parenchymal cells. However, little is presently known about the impact of toxic AhR ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on apoptosis in other liver cell types, such as in liver epithelial/progenitor cells. In the present study, we focused on the effects of TCDD on apoptosis regulation in a model of liver progenitor cells, rat WB-F344 cell line, during the TCDD-elicited release from contact inhibition. The stimulation of cell proliferation in this cell line was associated with deregulated expression of a number of genes known to be under transcriptional control of the Hippo signaling pathway, a principal regulatory pathway involved in contact inhibition of cell proliferation. Interestingly, we found that mRNA and protein levels of survivin, a known Hippo target, which plays a role both in cell division and inhibition of apoptosis, were significantly up-regulated in rat liver epithelial cell model, as well as in undifferentiated human liver HepaRG cells. Using the short interfering RNA-mediated knockdown, we confirmed that survivin plays a central role in cell division of WB-F344 cells. When evaluating the effects of TCDD on apoptosis induction by camptothecin, a genotoxic topoisomerase I inhibitor, we observed that the pre-treatment of WB-F344 cells with TCDD increased number of cells with apoptotic nuclear morphology, and it potentiated cleavage of both caspase-3 and poly(ADP-ribose) polymerase I. This indicated that despite the observed up-regulation of survivin, apoptosis induced by the genotoxin was potentiated in the model of rat liver progenitor cells. The present results indicate that, unlike in hepatocytes, AhR agonists may not prevent induction of apoptosis elicited by DNA-damaging agents in a model of rat liver progenitor cells.

• MeSH
• Apoptosis drug effects   MeSH
• Cell Line MeSH
• Time Factors MeSH
• Epithelial Cells drug effects   metabolism   pathology   MeSH
• Transcription, Genetic drug effects   MeSH
• Inhibitor of Apoptosis Proteins genetics   metabolism   MeSH
• Topoisomerase I Inhibitors toxicity   MeSH
• Liver drug effects   metabolism   pathology   MeSH
• Camptothecin toxicity   MeSH
• Caspase 3 metabolism   MeSH
• Contact Inhibition drug effects   MeSH
• Humans MeSH
• Poly(ADP-ribose) Polymerases metabolism   MeSH
• Polychlorinated Dibenzodioxins toxicity   MeSH
• Rats, Inbred F344 MeSH
• Microtubule-Associated Proteins genetics   metabolism   MeSH
• Receptors, Aryl Hydrocarbon agonists   metabolism   MeSH
• RNA Interference MeSH
• Signal Transduction drug effects   MeSH
• Transfection MeSH
• Basic Helix-Loop-Helix Transcription Factors agonists   metabolism   MeSH
• Up-Regulation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH