Distinguishing toxic from adaptive responses in fish using 'omics' - a key need for integration of toxicogenomics into environmnetal risk assessment

监测环境中潜在有害化学物质的影响对《国家环境监测与控制委员会》非常重要。到目前为止，用于评估环境质量的方法主要是基于毒性测试、化学测量和使用常规生物标记物。然而，自1990年代末以来，可用于协助进行化学风险评估和环境监测的分子生物学技术和方法的范围迅速增加。这些技术在分子水平上调查环境中的有机体对压力的反应的能力具有相当大的潜力来补充现有的评估和监测战略。然而，世界各地的监管机构确定的主要需求之一是证明分子反应可以准确地反映或预测一种化学品对环境中生物的毒性。这项提议旨在提供一个案例研究，作为原则证明，使这些分子技术的实施能够更有信心地取得进展。该提案是由一个国际财团在一个由NERC资助的研讨会上提出的，将涉及广泛的国际合作和共同资助。鱼类(在基因组上有大量信息的斑马鱼)将在一定剂量范围内暴露于一种模型污染物(二硝基苯酚)，并在一定范围的时间点进行分析。将对肝脏中发生的多种代谢物和基因表达变化进行详细分析，并确定与影响鱼类生存和生长的关系。计算机辅助信息学方法将允许确定特定的关联，从而使我们能够表征分子反应，这些分子反应可以真正预测那些简单的适应性变化的毒性。将向包括英国环境署在内的广泛的最终用户举办一次研讨会，讨论这些结果及其对未来环境质量评估的影响。

Monitoring the environment for the effects of potentially harmful chemicals is of major importance to the NERC. Until now the methods used for assessing environmental quality have been based largely on tests for toxicity, chemical measurements and the use of conventional biomarkers. However, since the late 1990s there has been a rapid increase in the range of molecular biology techniques and approaches available to assist in chemical risk assessment and environmental monitoring. The ability of these techniques to investigate the responses of organisms in the environment to stress at a molecular level has considerable potential to complement existing assessment and monitoring strategies. However, one of the major needs identified by the regulatory bodies worldwide is the demonstration that the molecular responses can accurately reflect or predict the toxicity of a chemical towards organisms in the environment. This proposal intends to provide a case-study that will serve as a proof-of-principle allowing progress in the implementation of these molecular techniques to be made with more confidence. The proposal was devised by an international consortium at a workshop funded by the NERC and will involve extensive international collaboration and co-funding. Fish (Zebrafish for which there is extensive information on the genome) will be exposed to a model pollutant (dinitrophenol) at a range of doses and analysed at a range of time points. A detailed analysis of the multiple metabolite and gene expression changes that occur in the liver will be assessed and the relationship to effects on the survival and growth of the fish will be determined. Computer-assisted informatic approaches will allow specific associations to be determined allowing us to characterise the molecular responses that are truely predictive of toxicity from those changes that are simply adaptive. A seminar will be presented to a wide range of end-users including the UK Environment Agency on the results and their implications for future environmental quality assessments.