title: Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Dere
authors.forename: Andrea W
authors.initials: AW
authors.lastname: Lee
authors.forename: Lyle D
authors.initials: LD
authors.lastname: Burgoon
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Zacharewski
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats
chemical_list: D000072317:Polychlorinated Dibenzodioxins