PCB153-elicited hepatic responses in the immature, ovariectomized C57BL/6 mice: Comparative toxicogenomic effects of dioxin and non-dioxin-like ligands
| Autor: | Anna K. Kopec, Lyle D. Burgoon, Jack R. Harkema, Bonnie Sharratt, Timothy R. Zacharewski, Colleen Tashiro, Bryan D. Mets, Dave Potter, Daher Ibrahim-Aibo |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Polychlorinated Dibenzodioxins Tissue Fixation Ovariectomy Dioxins Ligands Toxicology Toxicogenetics Gas Chromatography-Mass Spectrometry Article Mice chemistry.chemical_compound Internal medicine medicine Animals Receptor Triglycerides Oligonucleotide Array Sequence Analysis Pharmacology Pregnane X receptor Dose-Response Relationship Drug biology Reverse Transcriptase Polymerase Chain Reaction Chemistry Body Weight DNA Organ Size Aryl hydrocarbon receptor Polychlorinated Biphenyls Fold change Mice Inbred C57BL Dose–response relationship Endocrinology Liver Biochemistry ABCC3 Ovariectomized rat biology.protein RNA Environmental Pollutants Female Androstane |
| Zdroj: | Toxicology and Applied Pharmacology. 243:359-371 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2009.12.003 |
| Popis: | Polychlorinated biphenyls (PCBs) are ubiquitous contaminants found as complex mixtures of coplanar and non-coplanar congeners. The hepatic temporal and dose-dependent effects of the most abundant non-dioxin-like congener, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153), were examined in immature, ovariectomized C57BL/6 mice, and compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical aryl hydrocarbon receptor (AhR) ligand. Animals were gavaged once with 300 mg/kg PCB153 or sesame oil vehicle and sacrificed 4, 12, 24, 72 or 168 h post dose. In the dose-response study, mice were gavaged with 1, 3, 10, 30, 100 or 300 mg/kg PCB153 or sesame oil for 24 h. Significant increases in relative liver weights were induced with 300 mg/kg PCB153 between 24 and 168 h, accompanied by slight vacuolization and hepatocellular hypertrophy. The hepatic differential expression of 186 and 177 genes was detected using Agilent 4 x 44 K microarrays in the time course (|fold change|> or =1.5, P1(t)> or =0.999) and dose-response (|fold change|> or =1.5, P1(t)> or =0.985) studies, respectively. Comparative analysis with TCDD suggests that the differential gene expression elicited by PCB153 was not mediated by the AhR. Furthermore, constitutive androstane and pregnane X receptor (CAR/PXR) regulated genes including Cyp2b10, Cyp3a11, Ces2, Insig2 and Abcc3 were dose-dependently induced by PCB153. Collectively, these results suggest that the hepatocellular effects elicited by PCB153 are qualitatively and quantitatively different from TCDD and suggestive of CAR/PXR regulation. |
| Databáze: | OpenAIRE |
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