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Background   In vitro  systems have inherent limitations in their ability to model whole organism gene responses, which must be identified and appropriately considered when developing predictive biomarkers of  in vivo  toxicity. Systematic comparison of  in vitro  and  in vivo  temporal gene expression profiles were conducted to assess the ability of Hepa1c1c7 mouse hepatoma cells to model hepatic responses in C57BL/6 mice following treatment with 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD).    Results  Gene expression analysis and functional gene annotation indicate that Hepa1c1c7 cells appropriately modeled the induction of xenobiotic metabolism genes  in vivo . However, responses associated with cell cycle progression and proliferation were unique to Hepa1c1c7 cells, consistent with the cell cycle arrest effects of TCDD on rapidly dividing cells. In contrast, lipid metabolism and immune responses, representative of whole organism effects  in vivo , were not replicated in Hepa1c1c7 cells.    Conclusion  These results identified inherent differences in TCDD-mediated gene expression responses between these models and highlighted the limitations of  in vitro  systems in modeling whole organism responses, and additionally identified potential predictive biomarkers of toxicity.

In vivo – in vitro toxicogenomic comparison of TCDD-elicited gene expression in Hepa1c1c7 mouse hepatoma cells and C57BL/6 hepatic tissue