| 2,3,7,8 Tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in cultured rat and human hepatocytes. | |
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MedLine Citation:
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PMID: 10728777 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We report here a novel observation that 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) induced predominantly cytochrome P4501A1 (CYP1A1) in rat hepatocytes and predominantly CYP1A2 in human hepatocytes. As part of our research program to evaluate species-differences in response to CYP inducers, we studied the effects of TCDD on CYP1A activity, protein, and gene expression in primary cultures of rat and human hepatocytes. TCDD was found to induce CYP1A activity, measured as ethoxyresorufin-O-deethylase (EROD) activity, in both rat and human hepatocytes. TCDD induction of EROD activity in human hepatocytes (2-5 fold of concurrent solvent control), was significantly lower than that found in rat hepatocytes ( 20-fold of concurrent solvent control). Two structural analogs of TCDD, 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 6-nitro-1,3,8-trichlorodibenzofuran (6-NCDF), were also evaluated. As observed for TCDD, human hepatocytes consistently showed a lower response than rat hepatocytes. As most TCDD-related effects are believed to be mediated via binding of the TCDD-Ah receptor (AhR) complex to DNA, nuclear AhR levels were measured in rat and human hepatocytes after TCDD treatment. We found that the nuclear AhR levels in TCDD-treated rat hepatocytes were approximately 4 times higher than found in TCDD-treated human hepatocytes. However, the estimated binding affinity of [3H]TCDD to nuclear AhR from rat hepatocytes was similar. The species difference in response to TCDD was further evaluated by analysis of CYP1A1 and CYP1A2 mRNA levels using Northern analysis, and P4501A1 and 1A2 protein levels using Western immunoblotting. Results showed that, at both gene expression and protein levels, TCDD induced predominantly CYP1A1 in rat hepatocytes and CYP1A2 in human hepatocytes. |
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Authors:
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L Xu; A P Li; D L Kaminski; M F Ruh |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Chemico-biological interactions Volume: 124 ISSN: 0009-2797 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2000 Feb |
Date Detail:
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Created Date: 2000-04-14 Completed Date: 2000-04-14 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: IRELAND |
Other Details:
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Languages: eng Pagination: 173-89 Citation Subset: IM |
Affiliation:
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Department of Biology, St Louis University School of Medicine, MO 63104, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cells, Cultured Cytochrome P-450 CYP1A1 / biosynthesis*, genetics, metabolism Cytochrome P-450 CYP1A2 / biosynthesis*, genetics, metabolism Environmental Pollutants / metabolism, toxicity* Enzyme Induction / drug effects Gene Expression Regulation, Enzymologic / drug effects Humans Kinetics Liver / cytology, drug effects*, enzymology* Male Rats Rats, Sprague-Dawley Receptors, Aryl Hydrocarbon / metabolism Species Specificity Tetrachlorodibenzodioxin / metabolism, toxicity* Tritium |
| Grant Support | |
ID/Acronym/Agency:
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DK 27695/DK/NIDDK NIH HHS; ES05968/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Environmental Pollutants; 0/Receptors, Aryl Hydrocarbon; 10028-17-8/Tritium; 1746-01-6/Tetrachlorodibenzodioxin; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.14.1/Cytochrome P-450 CYP1A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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