Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.
BMC Genomics. 2011 Apr 15;12:193. doi: 10.1186/1471-2164-12-193.
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.
2,3,7,8-四氯二苯并对二恶英（TCDD）是一种环境污染物，以物种特异性的方式引起广泛的毒性作用。目前的风险评估实践通常从体内和体外啮齿动物模型中推断结果，以评估人类风险。为了进一步研究 TCDD 引起的物种特异性反应，比较了人 HepG2、鼠 Hepa1c1c7 和大鼠 H4IIE 细胞中的时间基因表达反应。
微阵列分析确定了一组跨物种保守的基因表达反应，这与 AhR 在介导适应性代谢反应中的作用一致。然而，也确定了显著的物种特异性和物种分歧反应。对物种特异性和物种分歧反应的调控区的计算分析表明，二恶英反应元件（DRE）参与其中。这些结果与体内大鼠与小鼠的物种特异性差异基因表达以及更全面的比较 DRE 搜索一致。
人 HepG2、鼠 Hepa1c1c7 和大鼠 H4IIE 的 TCDD 诱导的基因表达反应的比较分析与体内大鼠-小鼠比较基因表达研究以及更全面的比较 DRE 搜索一致，表明 AhR 介导的基因表达是物种特异性的。
