Gene expression analysis reveals chemical-specific profiles
Gene expression analysis reveals chemical-specific profiles
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DOI：
10.1093/toxsci/67.2.219
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发表时间：
2002-06-01
影响因子：
3.8
通讯作者：
Afshari, CA
中科院分区：
文献类型：
--
作者：
Hamadeh, HK;Bushel, PR;Afshari, CA
应用基因表达谱技术同时检测多种基因和信号通路，有望在理解毒性机制方面取得重大进展，最终有助于保护公众健康。在毒物基因组学的新领域，公共和私人的努力集中在用毒理学和病理终点得到很好表征的化合物的基因表达谱填充数据库。毒物基因组学的有效性和实用性取决于是否可以区分对应于不同化学物质的基因表达谱。毒物基因组学或药物基因组学策略的主要假设是，通过对暴露生物体的组织进行高密度微阵列分析，可以揭示基因表达改变的化学特异性模式。对这些模式的分析将有助于对毒物进行分类，并提供重要的机理见解。这份报告证实了这一假设。化学暴露大鼠肝脏组织的基因表达模式显示，用不同药物处理过氧化物酶体增殖剂[氯贝特（乙基-对氯苯氧基异丁酸酯），惠氏14643([4-氯-6(2,3-二甲-苯氧基]2-2-二甲基戊酸]]的动物之间的基因表达谱相似。但是，使用另一类化合物——酶诱导剂（苯巴比妥）产生了非常独特的基因表达谱。
The application of gene expression profiling technology to examine multiple genes and signaling pathways simultaneously promises a significant advance in understanding toxic mechanisms to ultimately aid in protection of public health. Public and private efforts in the new field of toxicogenomics are focused on populating databases with gene expression profiles of compounds where toxicological and pathological endpoints are well characterized. The validity and utility of a toxicogenomics is dependent on whether gene expression profiles that correspond to different chemicals can be distinguished. The principal hypothesis underlying a toxicogenomic or pharmacogenomic strategy is that chemical-specific patterns of altered gene expression will be revealed using high-density microarray analysis of tissues from exposed organisms. Analyses of these patterns should allow classification of toxicants and provide important mechanistic insights. This report provides a verification of this hypothesis. Patterns of gene expression corresponding to liver tissue derived from chemically exposed rats revealed similarity in gene expression profiles between animals treated with different agents from a common class of compounds, peroxisome proliferators [clofibrate (ethyl-p-chlorophenoxyisobutyrate), Wyeth 14,643 ([4-chloro-6(2,3-xylidino)-2-pyrimidinylthio]acetic acid), and gemfibrozil (5-2[2,5-dimethyl-phenoxy] 2-2-dimethylpentanoic acid)], but a very distinct gene expression profile was produced using a compound from another class, enzyme inducers (phenobarbital).