Document Detail

Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
MedLine Citation:
PMID:  16984957     Owner:  NLM     Status:  MEDLINE    
Chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lead to the development of hepatotoxicity and carcinogenicity in the liver of female rats. In this study, we investigated hepatic gene downregulation in response to acute and subchronic TCDD exposure. We identified 61 probes which exhibited a downregulation of twofold or greater following subchronic (13 weeks) exposure to TCDD. Comparative analysis of the hepatic expression of these 61 probes was conducted with rats subchronically exposed to PeCDF, PCB126, PCB153, and a mixture of PCB126 and PCB153. PCB153 produced little or no alteration in these probes, while the binary mixture mimicked most closely the downregulation observed with TCDD. To discern if the repression of genes within this probe set occur as a primary response to TCDD exposure, we analyzed the early responsiveness of 11 genes at 6, 24, and 72 h following a single exposure to TCDD. We observed early repression of the 11 genes within this early time course, indicating that the repression of this subset of genes occurs as a primary response to TCDD exposure and not as a secondary response to 13 weeks of subchronic treatment. In addition, the gender, species, and AhR dependence of these responses were also investigated. Gender- and species-dependent repression was observed within this subset of genes. Furthermore, utilizing AhR knockout mice, we were able to determine the AhR-dependent downregulation of seven of 11 genes. Together these results assist efforts to understand the multitude of effects imposed by TCDD and AhR ligands on gene expression.
Bladimir J Ovando; Chad M Vezina; Barbara P McGarrigle; James R Olson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-09-19
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  94     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-14     Completed Date:  2007-01-09     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  428-38     Citation Subset:  IM    
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 14214, USA.
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MeSH Terms
Down-Regulation / drug effects*
Environmental Pollutants / toxicity*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects*
Liver / drug effects*,  metabolism
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Polychlorinated Biphenyls / toxicity
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
Tetrachlorodibenzodioxin / toxicity*
Grant Support
Reg. No./Substance:
0/Environmental Pollutants; 0/Polychlorinated Biphenyls; 0/RNA, Messenger; 1746-01-6/Tetrachlorodibenzodioxin
Comment In:
Toxicol Sci. 2007 Feb;95(2):297-9   [PMID:  17297723 ]

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