Smith Martyn T, Vermeulen Roel, Li Guilan, Zhang Luoping, Lan Qing, Hubbard Alan E, Forrest Matthew S, McHale Cliona, Zhao Xin, Gunn Laura, Shen Min, Rappaport Stephen M, Yin Songnian, Chanock Stephen, Rothman Nathaniel
School of Public Health, 140 Warren Hall, University of California, Berkeley, CA 94720-7360, USA.
Chem Biol Interact. 2005 May 30;153-154:123-7. doi: 10.1016/j.cbi.2005.03.017. Epub 2005 Apr 19.
'Omic' technologies include genomics, transcriptomics (gene expression profiling), proteomics and metabolomics. We are utilizing these new technologies in an effort to develop novel biomarkers of exposure, susceptibility and response to benzene. Advances in genomics allow one to study hundreds to thousands of single nucleotide polymorphisms simultaneously on small quantities of DNA using array-based technologies. We are currently utilizing these technologies to examine genetic variation in pathways relating to biotransformation, DNA repair, folate metabolism and immune response with the goal of finding biomarkers of susceptibility to benzene hematotoxicity. Transcriptomics is used to measure the full complement of activated genes, mRNAs or transcripts in a particular tissue at a particular time typically using microarray technology. We have applied microarrays to the study of global gene expression in the peripheral blood cells of benzene-exposed workers. More than 100 genes were identified as being potentially differentially expressed, with genes related to apoptosis and immune function being the most significantly affected. Initial studies employing proteomics have also shown that several proteins are altered in the serum of exposed compared to control subjects and these proteins are potential biomarkers of benzene exposure. Omic technologies therefore have significant potential in generating novel biomarkers of exposure, susceptibility and response to benzene.
“组学”技术包括基因组学、转录组学(基因表达谱分析)、蛋白质组学和代谢组学。我们正在利用这些新技术努力开发苯暴露、易感性和反应的新型生物标志物。基因组学的进展使人们能够使用基于阵列的技术在少量DNA上同时研究数百到数千个单核苷酸多态性。我们目前正在利用这些技术研究与生物转化、DNA修复、叶酸代谢和免疫反应相关途径中的基因变异,目的是找到对苯血液毒性易感性的生物标志物。转录组学通常使用微阵列技术来测量特定组织在特定时间激活基因、mRNA或转录本的完整互补序列。我们已将微阵列应用于苯暴露工人外周血细胞中全局基因表达的研究。超过100个基因被鉴定为可能存在差异表达,其中与细胞凋亡和免疫功能相关的基因受影响最为显著。最初采用蛋白质组学的研究也表明,与对照受试者相比,暴露者血清中有几种蛋白质发生了改变,这些蛋白质是苯暴露的潜在生物标志物。因此,组学技术在生成苯暴露、易感性和反应的新型生物标志物方面具有巨大潜力。