Biotransformation of environmental contaminants in biota

加拿大人关注环境和化学污染物对人类和野生动物的影响。我的研究项目是环境毒理学领域，重点是多溴联苯醚(PBDEs)、多氯联苯(PCbs)、杀虫剂和内分泌干扰物等化学污染物的生物转化、去向和毒理学。其中许多污染物是持久性的，在食物链中积累，经常在人类和野生动物的组织中检测到。这些污染物产生的不良影响包括肝脏毒性、免疫抑制、神经行为障碍和内分泌改变。这些化合物在动物体内的代谢(即生物转化)和消除的主要途径是羟基化反应。羟化反应发生在肝脏，由一系列称为细胞色素P450(CYP)酶的酶催化。因此，CYP酶催化了化学污染物生物转化的最初关键步骤。 我的研究计划的长期目标是评估生物转化的重要性，作为化学污染物生物累积和毒性的决定因素，调查化学污染物及其代谢物引发的生化和毒性反应背后的分子事件，并调查单个肝酶在化学污染物生物转化中的作用和调控。在我目前的NSERC拨款任期内，我们开发了一种测定多溴二苯醚羟基化的方法，并使用啮齿动物和人类的肝脏制剂进行了生物转化研究。我们建议将研究范围扩大到包括鱼类、鸟类和海洋哺乳动物在内的野生动物物种，以比较占据不同生态系统和食物链不同层面的动物的生物转化能力。我们还将扩大研究范围，包括额外的多溴二苯醚和化学污染物。此外，我们还将研究羟基代谢物的毒性影响。环境毒理学研究生培训仍然是这些研究的重要组成部分。 加强对化学污染物生物转化的了解，对于评估可能的毒性机制和评估生物体积累或消除这些化学物质的能力是重要的。这些研究产生的信息将提供野生动物物种应对污染物暴露能力的衡量标准，并有助于确定污染物暴露的可容忍水平。这些信息还可能使我们能够预测哪些物种面临的风险最大。这项研究与所有加拿大人有关，特别是那些通过饮食或工作场所接触到高水平的这些化学污染物之一的人。

Canadians are concerned about the environment and about the effects of chemical contaminants on humans and wildlife. My research program is in the area of environmental toxicology and focuses on the biotransformation, fate and toxicology of chemical contaminants such as polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), pesticides and endocrine disruptors. Many of these contaminants are persistent, accumulate in food chains and are routinely detected in tissues from humans and wildlife. Adverse effects produced by these contaminants include liver toxicity, immune suppression, neuro-behavioural disturbances and endocrine alterations. The main route for the metabolism (i.e. biotransformation) and elimination of these chemicals in animals starts with hydroxylation reactions. Hydroxylation reactions occur in the liver and are catalyzed by a family of enzymes called the cytochrome P450 (CYP) enzymes. Thus, CYP enzymes catalyze the initial critical step in the biotransformation of chemical contaminants. The long-tem goals of my research program are to assess the importance of biotransformation as a determinant of the bioaccumulation and toxicity of chemical contaminants, to investigate the molecular events underlying the biochemical and toxic responses elicited by chemical contaminants and their metabolites, and to investigate the role and regulation of individual hepatic enzymes in the biotransformation of chemical contaminants. During the tenure of my current NSERC grant, we developed an assay to measure the hydroxylation of PBDEs and we carried out biotransformation studies with liver preparations from rodents and humans. We propose to extend the studies to wildlife species including fish, birds and marine mammals, in order to compare the biotransformation capacity of animals occupying different ecosystems and at different levels of the food chain. The studies will be expanded to include additional PBDEs and chemical contaminants. In addition, we will study the toxic effects of the hydroxylated metabolites. Graduate student training in environmental toxicology continues to be an essential component of these studies. Increased understanding of the biotransformation of chemical contaminants is important for evaluating possible mechanisms of toxicity and for assessing an organism's ability to accumulate or eliminate these chemicals. Information generated from these studies will provide a measure of how well wildlife species are able to cope with contaminant exposure and help define a tolerable level of contaminant exposure. This information might also enable us to predict which species are most at risk. This research is relevant to all Canadians and especially those who are exposed, via diet or workplace, to high levels of one of more of these chemical contaminants.