Biotransformation of environmental contaminants in biota

生物群中环境污染物的生物转化

• 批准号: RGPIN-2015-06301
• 负责人: Bandiera, Stelvio
• 金额: $ 2.04万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614067
• 关键词: Biotransformation; environmental; contaminants; biota

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.

加拿大人关注环境以及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，重点是化学污染物的生物转化，归宿和毒理学，如多溴联苯醚（PBDEs），多氯联苯（PCB），杀虫剂和内分泌干扰物。这些污染物中有许多是持久性的，在食物链中积累，并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毒性、免疫抑制、神经行为紊乱和内分泌改变。这些化学品在动物体内代谢（即生物转化）和消除的主要途径始于羟基化反应。羟基化反应发生在肝脏中，由称为细胞色素P450（CYP450）酶的酶家族催化。因此，生物降解酶催化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作为化学污染物的生物累积和毒性的决定因素的重要性，研究化学污染物及其代谢产物引起的生化和毒性反应的分子事件，并研究单个肝酶在化学污染物生物转化中的作用和调节。在我目前的任期内，在NSERC的资助下，我们开发了一种测定多溴联苯醚羟基化的方法，并对啮齿动物和人类的肝脏进行了生物转化研究。我们建议将研究范围扩大至野生生物，包括鱼类、雀鸟及海洋哺乳动物，以比较不同生态系统及食物链不同层次的动物的生物转化能力。研究范围亦会扩大至多溴联苯醚及化学污染物，此外，我们亦会研究羟基化代谢物的毒性。研究生培训环境毒理学仍然是这些研究的一个重要组成部分。 增加对化学污染物生物转化的了解对于评价可能的毒性机制和评估生物体积累或消除这些化学品的能力非常重要。从这些研究中产生的信息将提供一个衡量野生动物物种如何能够科普污染物暴露，并帮助确定一个可容忍的污染物暴露水平。这些信息也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暴露于高水平的一种或多种化学污染物的人。