Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive genes in mouse liver by serial analysis of gene expression

Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive genes in mouse liver by serial analysis of gene expression
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DOI:
10.1006/bbrc.2002.6669
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发表时间:
2002-03-29
影响因子:
3.1
通讯作者:
Matsushima, K
Matsushima, K
中科院分区:
生物学4区
文献类型:
--
作者:
Kurachi, M;Hashimoto, S;Matsushima, K

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2,3,7,8-四氯二苯并对二恶英(托德)是一种毒性最大的环境污染物,对哺乳动物具有多种生物学效应。为了确定基因参与的肝毒性和肝癌诱导的托德,我们在这里进行了一系列的基因表达分析,小鼠肝脏处理后7天,单次口服剂量为20 μ g TCDD/kg体重。我们总共测序了113,067个标签,其中包括56,420个标签和56,647个标签,分别来自正常肝脏和TODD处理的肝脏文库。统计分析表明,托德显著改变了346个转录本(p < 0.05),其中94个EST。受TCDD调控的基因不仅包括药物代谢酶基因和应激反应基因,还包括细胞骨架相关蛋白、信号转导和血浆蛋白等基因。通过对TCDD基因表达谱的分析,为阐明TCDD对哺乳动物肝脏的作用机制提供了新的基因,也为TCDD的防治提供了新的思路。(C)2002 Elsevier Science(美国)。
2,3,7,8-tetrachlorodibenzo-p-dioxin (TODD) is one of the most toxic environmental pollutants that causes various biological effects on mammals. To identify the genes involved in hepatotoxicity and hepatocarcinogenesis induced by TODD, we have conducted here serial analysis of gene expression of mouse liver 7 days after treatment with a single oral dose of 20 jig TCDD/kg body weight. We have sequenced total of 113,067 tags, including 56,420 tags and 56,647 tags from normal liver and TODD-treated liver library, respectively. Statistical analysis showed that TODD significantly altered 346 transcripts (p < 0.05) including 94 ESTs. The genes regulated by TCDD were not only the genes encoding drug metabolizing enzymes and stress response genes but also a wide variety of genes encoding cytoskeleton related proteins, signal transduction, and plasma proteins. This comprehensive gene expression analysis would provide novel genes that may help to clarify the mechanism of TCDD effects on mammalian liver, and also give a new approach for prevention and treatment. (C) 2002 Elsevier Science (USA).