PCB153-elicited hepatic responses in the immature, ovariectomized C57BL/6 mice: Comparative toxicogenomic effects of dioxin and non-dioxin-like ligands

Journal Article · Mon Mar 15 04:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.12.003· OSTI ID:21344894

Kopec, Anna K ^[1]; Burgoon, Lyle D ^[1]; Ibrahim-Aibo, Daher ^[2]; Mets, Bryan D ^[1]; Tashiro, Colleen; Potter, Dave; Sharratt, Bonnie ^[3]; Harkema, Jack R ^[2]

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1. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319 (United States)
2. Center for Integrative Toxicology, Michigan State University, East Lansing MI 48824-1319 (United States)
3. Wellington Laboratories Inc., Guelph, ON, Canada N1G 3M5 (Canada)

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| >= 1.5, P1(t) >= 0.999) and dose-response (|fold change| >= 1.5, P1(t) >= 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.

• OSTI ID: 21344894
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 243; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
AROMATICS
BODY
CHLORINATED AROMATIC HYDROCARBONS
DIGESTIVE SYSTEM
DIOXIN
DOSES
GENES
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYPERTROPHY
LIVER
MAMMALS
MEMBRANE PROTEINS
MICE
OILS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OTHER ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
POLYCHLORINATED BIPHENYLS
PROTEINS
RECEPTORS
RODENTS
SESAME OIL
VEGETABLE OILS
VERTEBRATES