Denslow Nancy D, Garcia-Reyero Natàlia, Barber David S
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, USA.
Mol Biosyst. 2007 Mar;3(3):172-7. doi: 10.1039/b612802p. Epub 2006 Dec 7.
Gene expression analysis is changing the way that we look at toxicity, allowing toxicologists to perform parallel analyses of entire transcriptomes. While this technology is not as advanced in aquatic toxicology as it is for mammalian models, it has shown promise for determining modes of action, identifying biomarkers and developing "signatures" of chemicals that can be used for field and mixture studies. A major hurdle for the use of microarrays in aquatic toxicology is the lack of sequence information for non-model species. Custom arrays based on gene libraries enriched for genes that are expressed in response to specific contaminants have been used with excellent success for some non-model species, suggesting that this approach will work well for ecotoxicology and spurring on the sequencing of cDNA libraries for species of interest. New sequencing technology and development of repositories for gene expression data will accelerate the use of microarrays in aquatic toxicology. Notwithstanding the preliminary successes that have been achieved even with partial cDNA libraries printed on arrays, ecological samples present elevated challenges for this technology due to the high degree of variation of the samples. Furthermore, recent studies that show nonlinear toxic responses for ecological species underscore the necessity of establishing time and dose dependence of effects on gene expression and comparing these results with traditional markers of toxicity. To realize the full potential of microarrays, researchers must do the experiments required to bridge the gap between the 'omics' technologies and traditional toxicology to demonstrate that microarrays have predictive value in ecotoxicology.
基因表达分析正在改变我们看待毒性的方式,使毒理学家能够对整个转录组进行并行分析。虽然这项技术在水生毒理学中的发展程度不如在哺乳动物模型中那样先进,但它已显示出在确定作用模式、识别生物标志物以及开发可用于野外和混合物研究的化学物质“特征”方面的潜力。在水生毒理学中使用微阵列的一个主要障碍是缺乏非模式物种的序列信息。基于针对响应特定污染物而表达的基因富集的基因文库定制的阵列,已成功用于一些非模式物种,这表明这种方法在生态毒理学中会发挥良好作用,并促使人们对感兴趣物种的cDNA文库进行测序。新的测序技术和基因表达数据储存库的开发将加速微阵列在水生毒理学中的应用。尽管即使使用印在阵列上的部分cDNA文库也取得了初步成功,但由于样本的高度变异性,生态样本对这项技术提出了更高的挑战。此外,最近显示生态物种存在非线性毒性反应的研究强调了确定基因表达效应的时间和剂量依赖性以及将这些结果与传统毒性标志物进行比较的必要性。为了充分发挥微阵列的潜力,研究人员必须进行必要的实验,以弥合“组学”技术与传统毒理学之间的差距,从而证明微阵列在生态毒理学中具有预测价值。