短链氯化石蜡的代谢过程及其毒性效应的代谢组学评价

项目名称： 短链氯化石蜡的代谢过程及其毒性效应的代谢组学评价

项目编号： No.21277141

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 环境科学、安全科学

项目作者： 张海军

作者单位： 中国科学院大连化学物理研究所

项目金额： 78万元

中文摘要： 短链氯化石蜡（SCCPs）具有环境持久性和生物累积性，可长距离迁移，对水生动物有较高毒性，已被列为持久性有机污染物（POPs）的候选者；并且在国的环境介质中存量较高。但有关其毒理机制、生态风险和人体健康风险的研究仍十分有限。本项目将代谢组学研究方法引入到SCCPs的毒性效应研究，通过鱼类（斑马鱼和虹鳟鱼）、大鼠和人体细胞（肝癌细胞和成体干细胞）暴露试验，借助色质联用分析技术，研究生物体代谢对SCCPs的应答，鉴定生物标志物；并通过代谢流量分析的方法，研究SCCPs对人体细胞主要代谢通路的影响，揭示其毒性作用方式。同时，通过模式动物暴露试验，测试SCCPs毒代动力学，鉴定主要代谢降解产物；并比较其与母体化合物的毒性效应差别，推断SCCPs毒性作用机制。研究的开展可在代谢组研究层次上认识SCCPs的毒性效应和毒性机制，为其中毒症状的诊断和治疗提供依据，并为其生态和人体健康风险评估提供科学基础。

中文关键词： 短链氯化石蜡；代谢组学；毒代动力学；脂肪酸代谢；脂类代谢

英文摘要： Short chain chlorinated paraffins (SCCPs) have been listed as the candidate of persistent organic pollutants (POPs) due to their potential for the persistence in the environment, bioaccumulation, long-range transport, and the high toxicity to aquatic organisms; meanwhile they exist at higher levels in the Environments of China. However, only a limited number of studies focused on their toxic mechanisms, ecological risk and human health risk. In this project, metabolomic approach will be adopted for studying the toxic effects of SCCPs. Zebra fish, rainbow trout, mice, human hepatoma cells and human adult stem cells will be selected as model organisms to conduct the SCCPs exposure tests. Using chromatography-mass spectrometry combined technique, the responses of biological metabolism to the SCCPs stress will be demonstrated, and the biomarkers for SCCPs stress will be identified. Furthermore, metabolic flux analysis method will be used to indicate the influence of SCCPs on the metabolic pathways in human cells, in order to get better understanding for the types of toxicity mechanism. Moreover, the metabolic kinetics of SCCPs in model animals will be tested, and the main metabolic products will be identified; and thereafter the mechanisms of toxicity will be deduced through comparing the toxic effects of SCCPs and

英文关键词： short-chain chlorinated paraffins；metabolomics；toxicokinetics；fatty acid metabolism；lipid metabolism