Yang Lixin, Kemadjou Jules R, Zinsmeister Christian, Bauer Matthias, Legradi Jessica, Müller Ferenc, Pankratz Michael, Jäkel Jens, Strähle Uwe
Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe, Postfach 3640, 76021 Karlsruhe, Germany.
Genome Biol. 2007;8(10):R227. doi: 10.1186/gb-2007-8-10-r227.
Early life stages are generally most sensitive to toxic effects. Our knowledge on the action of manmade chemicals on the developing vertebrate embryo is, however, rather limited. We addressed the toxicogenomic response of the zebrafish embryo in a systematic manner by asking whether distinct chemicals would induce specific transcriptional profiles.
We exposed zebrafish embryos to a range of environmental toxicants and measured the changes in gene-expression profiles by hybridizing cDNA to an oligonucleotide microarray. Several hundred genes responded significantly to at least one of the 11 toxicants tested. We obtained specific expression profiles for each of the chemicals and could predict the identity of the toxicant from the expression profiles with high probability. Changes in gene expression were observed at toxicant concentrations that did not cause morphological effects. The toxicogenomic profiles were highly stage specific and we detected tissue-specific gene responses, underscoring the sensitivity of the assay system.
Our results show that the genome of the zebrafish embryo responds to toxicant exposure in a highly sensitive and specific manner. Our work provides proof-of-principle for the use of the zebrafish embryo as a toxicogenomic model and highlights its potential for systematic, large-scale analysis of the effects of chemicals on the developing vertebrate embryo.
生命早期阶段通常对毒性作用最为敏感。然而,我们对人造化学物质对发育中的脊椎动物胚胎作用的了解相当有限。我们通过询问不同的化学物质是否会诱导特定的转录谱,以系统的方式研究了斑马鱼胚胎的毒理基因组反应。
我们将斑马鱼胚胎暴露于一系列环境毒物中,并通过将互补DNA(cDNA)与寡核苷酸微阵列杂交来测量基因表达谱的变化。数百个基因对所测试的11种毒物中的至少一种有显著反应。我们获得了每种化学物质的特定表达谱,并且能够以高概率从表达谱中预测毒物的身份。在未引起形态学效应的毒物浓度下观察到了基因表达的变化。毒理基因组谱具有高度的阶段特异性,并且我们检测到了组织特异性的基因反应,这突出了该检测系统的敏感性。
我们的结果表明,斑马鱼胚胎的基因组对毒物暴露以高度敏感和特异的方式做出反应。我们的工作为将斑马鱼胚胎用作毒理基因组模型提供了原理证明,并突出了其在系统、大规模分析化学物质对发育中的脊椎动物胚胎影响方面的潜力。