ArticleToxicological sciences : an official journal of the Society of Toxicology2013
Comparative analysis of temporal and dose-dependent TCDD-elicited gene expression in human, mouse, and rat primary hepatocytes.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
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- Evolutive emergence and divergence of an Ig regulatory node: An environmental sensor getting cues from the aryl hydrocarbon receptor?Frontiers in immunology · 2023Review
- Species-Specific Differences in Aryl Hydrocarbon Receptor Responses: How and Why?International journal of molecular sciences · 2021Review
- Review
- Thioesterase induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin results in a futile cycle that inhibits hepatic β-oxidation.Scientific reports · 2021Article
- Evolution of Hominin Detoxification: Neanderthal and Modern Human Ah Receptor Respond Similarly to TCDD.Molecular biology and evolution · 2021Article
- Skeletal Toxicity of Coplanar Polychlorinated Biphenyl Congener 126 in the Rat Is Aryl Hydrocarbon Receptor Dependent.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Skeletal toxicity resulting from exposure of growing male rats to coplanar PCB 126 is associated with disruption of calcium homeostasis and the GH-IGF-1 axis and direct effects on bone formation.Archives of toxicology · 2020Article
- Genome-Scale Characterization of Toxicity-Induced Metabolic Alterations in Primary Hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food.EFSA journal. European Food Safety Authority · 2018Article
- PCB126 Inhibits the Activation of AMPK-CREB Signal Transduction Required for Energy Sensing in Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Aryl hydrocarbon receptor (AhR) mediated short-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid homeostasis in mice.Toxicology and applied pharmacology · 2018Article
- Aryl hydrocarbon receptor inhibition promotes hematolymphoid development from human pluripotent stem cells.Blood · 2017Article
- Identification of a unique gene expression signature in mercury and 2,3,7,8-tetrachlorodibenzo-Toxicology research · 2017Article
- Lipidomic Evaluation of Aryl Hydrocarbon Receptor-Mediated Hepatic Steatosis in Male and Female Mice Elicited by 2,3,7,8-Tetrachlorodibenzo-p-dioxin.Chemical research in toxicology · 2017Article
- Beyond the Aryl Hydrocarbon Receptor: Pathway Interactions in the Hepatotoxicity of 2,3,7,8-Tetrachlorodibenzo-Current opinion in toxicology · 2017Article
- Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells.Toxicology and applied pharmacology · 2017Article
- Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems.BMC genomics · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited time- and dose-dependent differential gene expression was compared in human, mouse, and rat primary hepatocytes. Comprehensive time course (10 nM TCDD or dimethyl sulfoxide vehicle control for 1, 2, 4, 8, 12, 24, and 48h) studies identified 495, 2305, and 711 differentially expressed orthologous genes in human, mouse, and rat hepatocytes, respectively. However, only 16 orthologs were differentially expressed across all three species, with the majority of orthologs exhibiting species-specific expression (399 human, 2097 mouse, and 533 rat), consistent with species-specific expression reported in other in vitro and in vivo comparative studies. TCDD also elicited the dose-dependent induction of 397 human, 100 mouse, and 443 rat genes at 12h and 615 human, 426 mouse, and 314 rat genes at 24h. Comparable EC50 values were obtained for AhR battery genes including Cyp1a1 (0.1 nM human, 0.05 nM mouse, 0.08 nM rat at 24h) and Tiparp (0.97 nM human, 0.63 nM mouse, 0.14 nM rat at 12h). Overrepresented functions and pathways included amino acid metabolism in humans, immune response in mice, and energy homeostasis in rats. Differentially expressed genes functionally associated with lipid transport, processing, and metabolism were overrepresented in all three species but exhibited species-specific expression consistent with the induction of hepatic steatosis in mice but not in rats following a single oral gavage of TCDD. Furthermore, human primary hepatocytes showed lipid accumulation following 48h of treatment with TCDD, suggesting that AhR-mediated steatosis in mice more closely resembles human hepatic fat accumulation compared with that in rats. Collectively, these results suggest that species-specific gene expression profiles mediate the species-specific effects of TCDD despite the conservation of the AhR and its signaling mechanism.
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