The transcriptional signature of dioxin in human hepatoma HepG2 cells.
The transcriptional signature of dioxin in human hepatoma HepG2 cells.
复制标题
人肝癌 HepG2 细胞中二恶英的转录特征。
DOI：
10.1016/s0006-2952(00)00403-2
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发表时间：
2000
影响因子：
5.8
通讯作者：
Medvedovic,M
中科院分区：
文献类型：
--
作者：
Puga,A;Maier,A;Medvedovic,M
我们利用高密度微阵列杂交技术研究了人肝癌细胞HepG 2对2，3，7，8-四氯二苯并-对-二恶英（TCDD）的转录反应。我们发现，暴露于10 nM TCDD 8小时改变了至少2.1的因素的表达310个已知的基因和相同数量的表达序列标签。在存在20 μg/mL放线菌酮的情况下用TCDD处理阻断了对这些基因中的202个的影响，使我们能够区分TCDD暴露的主要影响（无论放线菌酮是否存在）和次要影响（通过抑制蛋白质合成来阻断）。在已知的310个受TCDD影响的基因中，无论放线菌酮处理与否，30个基因上调，78个基因下调，84个基因上调，118个基因仅在蛋白质合成不受抑制时下调。由TCDD调控的基因的功能聚类揭示了许多潜在的生理相互作用，可能揭示了这种化合物的多种生物学效应。然而，我们的研究结果表明，达到一个良好的理解的分子机制，TCDD暴露的生物学结果的承诺是数量级更复杂的比以前想象的。
We have used a high density microarray hybridization approach to characterize the transcriptional response of human hepatoma HepG2 cells to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We find that exposure to 10 nM TCDD for 8 hr alters by at least a factor of 2.1 the expression of 310 known genes and of an equivalent number of expressed sequence tags. Treatment with TCDD in the presence of 20 μg/mL of cycloheximide blocked the effect on 202 of these genes, allowing us to distinguish between primary effects of TCDD exposure, which take place whether cycloheximide is present or not, and secondary effects, which are blocked by inhibition of protein synthesis. Of the 310 known genes affected by TCDD, 30 are up-regulated and 78 are down-regulated regardless of cycloheximide treatment, and 84 are up-regulated and 118 are down-regulated only when protein synthesis is not inhibited. Functional clustering of genes regulated by TCDD reveals many potential physiological interactions that might shed light on the multiple biological effects of this compound. Our results, however, suggest that arriving at a sound understanding of the molecular mechanisms governing the biological outcome of TCDD exposure promises to be orders of magnitude more complicated than might have been previously imagined.