Merrick B Alex, Bruno Maribel E
National Center for Toxicogenomics, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA.
Curr Opin Mol Ther. 2004 Dec;6(6):600-7.
Toxicity profiling measures and compares all gene expression changes among biological samples after toxicant exposure. Toxicity profiling with DNA microarrays to measure all mRNA transcripts (transcriptomics), or by global separation and identification of proteins (proteomics), has led to the discovery of better descriptors of toxicity, toxicant classification and exposure monitoring than current indicators. A shared goal in transcript and proteomic profiling is the development of biomarkers and signatures of chemical toxicity. In this review, biomarkers and signature profiles are described for specific chemical toxicants that affect target organs such as liver, kidney, neural tissues, gastrointestinal tract and skeletal muscle, for specific disease models such as cancer and inflammation, and for unique chemical-protein adducts underlying cell injury. The recent introduction of toxicogenomics databases support researchers in sharing, analyzing, visualizing and mining expression data, assist the integration of transcriptomics, proteomics and toxicology datasets, and eventually will permit in silico biomarker and signature pattern discovery.
毒性分析可测量并比较毒物暴露后生物样品之间所有的基因表达变化。利用DNA微阵列进行毒性分析以测量所有mRNA转录本(转录组学),或通过蛋白质的全面分离和鉴定(蛋白质组学),已发现了比当前指标更好的毒性描述符、毒物分类方法及暴露监测手段。转录组和蛋白质组分析的一个共同目标是开发化学毒性的生物标志物和特征图谱。在本综述中,描述了针对影响肝脏、肾脏、神经组织、胃肠道和骨骼肌等靶器官的特定化学毒物、针对癌症和炎症等特定疾病模型以及针对细胞损伤潜在的独特化学-蛋白质加合物的生物标志物和特征图谱。毒性基因组学数据库的最新引入有助于研究人员共享、分析、可视化和挖掘表达数据,协助整合转录组学、蛋白质组学和毒理学数据集,并最终将实现计算机模拟生物标志物和特征图谱的发现。