Kerns Robnet T, Bushel Pierre R
Microarray and Genome Informatics, National Institute of Environmental Health Sciences Research Triangle Park, NC, USA.
Front Genet. 2012 Feb 7;3:14. doi: 10.3389/fgene.2012.00014. eCollection 2012.
The era of toxicogenomics has introduced a new way of monitoring the effect of environmental stressors and toxicants on biological systems via quantification of changes in gene expression. Because the liver is one of the major organs for synthesis and secretion of substances which metabolize endogenous and exogenous materials, there has been a great deal of interest in elucidating predictive and mechanistic genomic markers of hepatotoxicity. This mini-review will bring context to a limited number of toxicogenomics studies which used genomics to evaluate the transcriptional changes in blood and liver in response to acetaminophen (APAP) or other liver toxicants, but differed according to the classification of interest (COI), i.e., the partitioning of the samples a priori according to a common toxicological characteristic. The toxicogenomics studies highlighted are characterized by a classification of either no/low vs. high APAP dose exposure, none vs. observed necrosis, and severity of necrosis. The overlap or lack thereof between the gene classifiers and the modulated biological processes that are elucidated will be discussed to enhance the understanding of the effect of the particular COI model and experimental design used for prediction.
毒理基因组学时代引入了一种通过量化基因表达变化来监测环境应激源和毒物对生物系统影响的新方法。由于肝脏是合成和分泌代谢内源性和外源性物质的主要器官之一，人们对阐明肝毒性的预测性和机制性基因组标志物产生了浓厚兴趣。本综述将围绕少数毒理基因组学研究展开，这些研究利用基因组学评估对乙酰氨基酚（APAP）或其他肝脏毒物产生反应时血液和肝脏中的转录变化，但根据感兴趣的分类（COI）有所不同，即根据共同的毒理学特征对样本进行先验划分。所强调的毒理基因组学研究的特点是按APAP剂量暴露无/低与高、无与观察到的坏死以及坏死严重程度进行分类。将讨论基因分类器与所阐明的受调节生物过程之间的重叠或缺乏情况，以增进对用于预测的特定COI模型和实验设计效果的理解。
