Genomic interrogation of mechanism(s) underlying cellular responses to toxicants
Genomic interrogation of mechanism(s) underlying cellular responses to toxicants
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DOI：
10.1016/s0300-483x(02)00481-x
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发表时间：
2002-12-27
期刊：
影响因子：
4.5
通讯作者：
Paules, RS
中科院分区：
文献类型：
--
作者：
Amin, RP;Hamadeh, HK;Paules, RS
评估外源性物质暴露对人类健康和疾病进展的影响是复杂的。了解作用方式，包括导致毒性和疾病进展的机制，对于评估化合物很有价值。毒理基因组学是基因组学与毒理学相结合的分支学科，通过研究外源性物质的全基因组效应，有望为阐明外源性物质的作用机制做出重要贡献。全球基因表达谱，革命性的微阵列技术和毒理基因组学研究的一个重要方面，允许测量数以千计的基因的转录调制后暴露于异生质。我们使用我们的结果从以前的研究化合物代表两个不同类别的外源性物质（巴比妥酸盐和过氧化物酶体增殖剂），讨论应用计算方法分析微阵列数据，阐明机制（S）的细胞反应毒物。特别是，我们的实验室证明，化学特定的基因表达模式可以使用cDNA微阵列揭示。转录谱分析提供了毒物类别之间的区分，以及对毒性和疾病进展机制的全基因组洞察。最后，我们期望从这些信息中找到预测生物外源性物质对人类毒性的新方法。出版社：Elsevier Science爱尔兰有限公司
Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information. Published by Elsevier Science Ireland Ltd.