| Summary: | <p>Abstract</p> <p>Background</p> <p>2,3,7,8-Tetrachlorodibenzo-<it>p</it>-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 <it>in vivo </it>and <it>in vitro </it>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.</p> <p>Results</p> <p>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 <it>in vivo </it>rat vs. mouse species-specific differential gene expression, and more comprehensive comparative DRE searches.</p> <p>Conclusions</p> <p>Comparative analysis of human HepG2, mouse Hepa1c1c7 and rat H4IIE TCDD-elicited gene expression responses is consistent with <it>in vivo </it>rat-mouse comparative gene expression studies, and more comprehensive comparative DRE searches, suggesting that AhR-mediated gene expression is species-specific.</p>
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