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

监测环境中潜在有害化学物质的影响对NERC至关重要。到目前为止，用于评估环境质量的方法主要基于毒性测试、化学测量和传统生物标志物的使用。然而，自20世纪90年代末以来，可用于协助化学品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研究环境中生物体对应激反应的能力具有相当大的潜力，可以补充现有的评估和监测策略。然而，全球监管机构确定的主要需求之一是证明分子反应能够准确反映或预测化学物质对环境中生物体的毒性。本提案旨在提供一个案例研究，作为原理证明，使这些分子技术的实施取得更大的进展。该建议是由NERC资助的一个国际财团在一个讲习班上提出的，将涉及广泛的国际合作和共同供资。鱼（斑马鱼，其基因组信息丰富）将以一定剂量暴露于一种模型污染物（二硝基苯酚），并在一定时间点进行分析。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，并确定其对鱼的生存和生长的影响的关系。计算机辅助的信息方法将允许确定特定的关联，使我们能够描述分子反应的特征，这些反应真正预测了那些简单的适应性变化的毒性。将向包括英国环境局在内的广泛的最终用户介绍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.