Mechanisms of interactions of hypoxia and temperature with metal stress in fish

拟议研究的总体目标是从机理上了解低氧和温度与金属胁迫之间的相互作用，以便更好地评估水生系统中的金属风险。水生生物通常受到多种应激源的影响，这些应激源可能相互作用，改变生理反应。然而，现有的风险评估方案主要基于单一应激源的数据，这种方法未能考虑同时存在的应激源和反应随暴露条件的变化的交互影响。事实上，美国环境保护署(U.S.EPA)已确定，对应激源之间相互作用机制的了解不足是开发有效的风险评估工具以保护水生生物的主要障碍。特别令人关注的是，共存的应激源可引起相加或协同的毒理反应，从而在低于当前评估程序预测的应激源浓度时对环境造成影响。在这些应激源中，由自然现象或人类活动以及全球气候变化引起的缺氧和温度波动在水生系统中是常见的。因此，为了更准确地评估和预测污染物在水生系统中构成的风险，有必要清楚地了解这些应激源的混杂影响。这项应用试图了解低氧和温度与鱼类中金属胁迫的相互作用。其目的是：(I)阐明金属、低氧和热应激相互作用的机制，以期确定不受环境溶解氧和温度波动影响的敏感的金属特定毒理学终点；(Ii)确定在同时存在的低氧和/或温度胁迫期间改变的金属毒性的原因和机制；以及(Iii)确定与用于生态风险评估的毒性适宜终点相关的生化扰动。拟议的研究将有助于实现我的研究计划的长期目标-开发有效的、具有科学依据的工具，以监测、预测和监管金属对环境的影响。

The overall goal of the proposed research is to gain mechanistic understanding of the interactions between hypoxia and temperature with metals stress for better assessment of metals risk in aquatic systems. Aquatic organisms are generally impacted by multiple stressors that may interact with each other to alter physiological responses. However, extant risk assessment protocols are based largely on data from single stressors, an approach that fails to account for interactive effects of concurrent stressors and variation of responses with conditions of exposure. Indeed, inadequate understanding of the mechanisms of interactions between stressors has been identified by the United States Environmental Protection Agency (U.S. EPA) as a major obstacle to the development of effective risk assessment tools to protect aquatic life. Of particular concern is the fact that co-occurring stressors can cause additive or synergistic toxicological responses resulting in environmental impacts at lower stressor concentrations than predicted by current assessment procedures. Among these stressors, hypoxia and temperature fluctuations resulting from natural phenomena or human activities and global climate change are commonly encountered in aquatic systems. A clear understanding of the confounding effects of these stressors is therefore necessary for more accurate assessment and prediction of the risk posed by pollutants in aquatic systems. This application seeks to understand interactions of hypoxia and temperature with metals stress in fish. The objectives are: (i) to elucidate the mechanisms of interactions of metals, hypoxia and thermal stress with a view to identifying sensitive metal-specific toxicological endpoints that are immune to fluctuations in environmental dissolved oxygen and temperature, (ii) to identify the causes and mechanisms of altered metals toxicity during concurrent hypoxia and/or temperature stress, and (iii) to identify biochemical perturbations that correlate with fitness endpoints of toxicity used in ecological risk assessment. The proposed research will contribute to the realization of the long term goal of my research program- the development of effective and scientifically defensible tools to monitor, predict and regulate environmental impacts of metals.