ArticleToxicology and applied pharmacology2011
Non-additive hepatic gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) co-treatment in C57BL/6 mice.
Article in Toxicology and applied pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Classifying polycyclic aromatic hydrocarbons by carcinogenic potency using in vitro biosignatures.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Understanding Environmental Contaminants' Direct Effects on Non-alcoholic Fatty Liver Disease Progression.Current environmental health reports · 2019Review
- Identification of lipidomic markers of chronic 3,3',4,4',5-pentachlorobiphenyl (PCB 126) exposure in the male rat liver.Toxicology · 2017Article
- Complexities of gene expression patterns in natural populations of an extremophile fish (Poecilia mexicana, Poeciliidae).Molecular ecology · 2017Article
- A framework for the use of single-chemical transcriptomics data in predicting the hazards associated with complex mixtures of polycyclic aromatic hydrocarbons.Archives of toxicology · 2017Article
- The role of AHR-inducible cytochrome P450s in metabolism of polyunsaturated fatty acids.Drug metabolism reviews · 2016Review
- 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Alters Lipid Metabolism and Depletes Immune Cell Populations in the Jejunum of C57BL/6 Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Alcoholic, Nonalcoholic, and Toxicant-Associated Steatohepatitis: Mechanistic Similarities and Differences.Cellular and molecular gastroenterology and hepatology · 2015Review
- Development of a computational high-throughput tool for the quantitative examination of dose-dependent histological features.Toxicologic pathology · 2015Article
- Toxicogenomic evaluation of long-term hepatic effects of TCDD in immature, ovariectomized C57BL/6 mice.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Comparison of TCDD-elicited genome-wide hepatic gene expression in Sprague-Dawley rats and C57BL/6 mice.Toxicology and applied pharmacology · 2013Article
- Toxicant-associated steatohepatitis.Toxicologic pathology · 2013Review
- Dietary fat is a lipid source in 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD)-elicited hepatic steatosis in C57BL/6 mice.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- Aryl hydrocarbon receptor-mediated induction of Stearoyl-CoA desaturase 1 alters hepatic fatty acid composition in TCDD-elicited steatosis.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Interactions between environmental contaminants can lead to non-additive effects that may affect the toxicity and risk assessment of a mixture. Comprehensive time course and dose-response studies with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), non-dioxin-like 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and their mixture were performed in immature, ovariectomized C57BL/6 mice. Mice were gavaged once with 30 μg/kg TCDD, 300 mg/kg PCB153, a mixture of 30 μg/kg TCDD with 300 mg/kg PCB153 (MIX) or sesame oil vehicle for 4,12, 24,72 or 168 h. In the 24h dose-response study, animals were gavaged with TCDD (0.3,1, 3, 6, 10, 15, 30, 45 μg/kg), PCB153 (3,10, 30, 60, 100, 150, 300, 450 mg/kg), MIX (0.3+3, 1+10, 3+30, 6+60, 10+100, 15+150, 30+300, 45 μg/kg TCDD+450 mg/kg PCB153, respectively) or vehicle. All three treatments significantly increased relative liver weights (RLW), with MIX eliciting significantly greater increases compared to TCDD and PCB153 alone. Histologically, MIX induced hepatocellular hypertrophy, vacuolization, inflammation, hyperplasia and necrosis, a combination of TCDD and PCB153 responses. Complementary lipid analyses identified significant increases in hepatic triglycerides in MIX and TCDD samples, while PCB153 had no effect on lipids. Hepatic PCB153 levels were also significantly increased with TCDD co-treatment. Microarray analysis identified 167 TCDD, 185 PCB153 and 388 MIX unique differentially expressed genes. Statistical modeling of quantitative real-time PCR analysis of Pla2g12a, Serpinb6a, Nqo1, Srxn1, and Dysf verified non-additive expression following MIX treatment compared to TCDD and PCB153 alone. In summary, TCDD and PCB153 co-treatment elicited specific non-additive gene expression effects that are consistent with RLW increases, histopathology, and hepatic lipid accumulation.
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