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Title: Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells.

Authors: Dere, Edward; Lee, Andrea W; Burgoon, Lyle D; Zacharewski, Timothy R

Published In BMC Genomics, (2011)

Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that elicits a broad spectrum of toxic effects in a species-specific manner. Current risk assessment practices routinely extrapolate results from in vivo and in vitro rodent models to assess human risk. In order to further investigate the species-specific responses elicited by TCDD, temporal gene expression responses in human HepG2, mouse Hepa1c1c7 and rat H4IIE cells were compared.Microarray analysis identified a core set of conserved gene expression responses across species consistent with the role of AhR in mediating adaptive metabolic responses. However, significant species-specific as well as species-divergent responses were identified. Computational analysis of the regulatory regions of species-specific and -divergent responses suggests that dioxin response elements (DREs) are involved. These results are consistent with in vivo rat vs. mouse species-specific differential gene expression, and more comprehensive comparative DRE searches.Comparative analysis of human HepG2, mouse Hepa1c1c7 and rat H4IIE TCDD-elicited gene expression responses is consistent with in vivo rat-mouse comparative gene expression studies, and more comprehensive comparative DRE searches, suggesting that AhR-mediated gene expression is species-specific.

PubMed ID: 21496263 Exiting the NIEHS site

MeSH Terms: Animals; Base Sequence; Cell Line, Tumor; Gene Expression Profiling*; Gene Regulatory Networks; Humans; Lipid Metabolism/genetics; Mice; Multigene Family; Oligonucleotide Array Sequence Analysis; Rats; Tetrachlorodibenzodioxin/toxicity*

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