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使用cDNA微阵列分析过氧化物酶体增殖物和苯妥英诱导的肝毒性的基因表达

Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray.

作者信息

Jung Jin-Wook, Park Joon-Suk, Hwang Jae-Woong, Kang Kyung-Sun, Lee Yong-Soon, Song Bog-Soo, Lee Gyoung-Jae, Yeo Chan-Dong, Kang Jong-Soo, Lee Wan-Seon, Jeon Ki-Seon, Um Chan-Hwi, Kim Yang-Suk, Oh Moon-Ju, Youn Jong-Pil, Li Peng, Park Jung-Eun, Hwang Seung Yong

机构信息

Department of Biochemistry and Molecular Biology, Hanyang University & Genocheck Co., Ltd., South Korea.

出版信息

J Vet Med Sci. 2004 Nov;66(11):1329-33. doi: 10.1292/jvms.66.1329.

Abstract

The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF(+) albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds.

摘要

最近的DNA微阵列技术使我们能够了解大量的基因表达谱。该技术有可能理解多个基因与生物系统中具有毒性的化合物相关的机制。因此,通过这项技术的毒理基因组学对于理解生物系统中未知毒性机制的作用可能非常强大。我们使用DNA微阵列研究了体内系统中与肝毒素相关的化合物的作用,并对已充分表征的化学物质进行了分类。我们研究了三种化合物:2种过氧化物酶体增殖剂:氯贝丁酯(对氯苯氧异丁酸乙酯)、吉非贝齐(5-2[2,5-二甲基苯氧基]2-2-二甲基戊酸),以及一种抗癫痫药物:苯妥英(5,5-二苯基乙内酰脲)。对5-6周龄的雄性斯普拉格-道利VAF(+)白化大鼠用每种化合物处理24小时和2周。已使用自制的4.8K cDNA微阵列进行基因表达谱分析。我们发现基因表达的聚类与化合物的毒性表型具有相似性。

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