Gant Timothy W
Medical Research Council Toxicology Unit, University of Leicester, Systems Toxicology Group, Lancaster Road, Leicester, LE1 9HN, UK.
Expert Opin Drug Metab Toxicol. 2007 Aug;3(4):599-608. doi: 10.1517/17425225.3.4.599.
Microarray technologies have both fascinated and frustrated the toxicological community since their introduction around a decade ago. Fascination arose from the possibility offered by the technology to gain a profound insight into the cellular response to chemically mediated stress, and the potential that this genomic signature would be indicative of the biological mechanism by which that stress was induced. Frustrations have arisen primarily from technical factors such as data variance, the requirement for the application of advanced statistical and mathematical analysis, and difficulties associated with actually recognising signature gene expression patterns, and discerning mechanisms. Toxicogenomics was predicted to make toxicological assessment and extrapolation easier, faster and cheaper. The reality has been somewhat different; toxicogenomics is difficult. However, its potential when properly applied has been indicated by some well designed toxicogenomics studies, particularly in the differentiation of genotoxins from non-genotoxins. Technology waits though for no man. While the toxicological community has been working to apply transcriptomics (mRNA levels) in toxicology, the technology has moved beyond this application into new arenas. Some have application to toxicology and are reviewed here, except transcriptomics which has been extensively written about before. This review discusses the application of microarray technologies applied to the genome per se (amplifications, deletions, epigenetic change), mRNA translation and its control mechanisms through miRNA. Which of the new genomics technoï¿(1/2)logies will find most application in toxicology? In the opinion of the author there are three potentially major applications: i) arrayCGH in assessment and recognition of genotoxicity; ii) epigenetic assessment in developmental and transgenerational toxicology; and iii) miRNA assessment in all toxicology types, but particularly developmental toxicology.
大约十年前微阵列技术问世以来，它既让毒理学界为之着迷，又让其感到沮丧。着迷之处在于该技术能够深入洞察细胞对化学介导应激的反应，以及这种基因组特征可能指示应激诱导生物学机制的潜力。而沮丧主要源于技术因素，比如数据差异、需要应用先进的统计和数学分析、难以识别特征基因表达模式以及辨别机制等。人们曾预测毒理基因组学将使毒理学评估和外推变得更容易、更快且更便宜。但实际情况有所不同，毒理基因组学很难。然而，一些精心设计的毒理基因组学研究已表明了其合理应用时的潜力，尤其是在区分基因毒素和非基因毒素方面。不过技术不会等人。当毒理学界致力于将转录组学（mRNA水平）应用于毒理学时，该技术已超越此应用进入新领域。这里对一些与毒理学相关的应用进行综述，转录组学此前已有大量论述，故除外。本综述讨论了微阵列技术在基因组本身（扩增、缺失、表观遗传变化）、mRNA翻译及其通过miRNA的调控机制方面的应用。哪种新的基因组学技术将在毒理学中得到最广泛应用呢？作者认为有三个潜在的主要应用方向：i）阵列比较基因组杂交（arrayCGH）用于基因毒性的评估和识别；ii）表观遗传学评估用于发育和跨代毒理学；iii）miRNA评估用于所有类型的毒理学，尤其是发育毒理学。
