Molecular screening for target of action and mode of action of toxic chemical

• 作 者: Jinmiao Zha Zijian Wang
• 机 构: State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Scien
• 出 处: 2016(第二届)毒性测试替代方法与转化毒理学(国际)学术研讨会暨有害结局路径(AOP)与风险评估培训会议
• 发表日期: 2016年12期

　　Development of adverse outcome pathway (AOP) is aiming at providing high efficiency screening tool for hazard assessment of chemicals.In AOP, the most important step is to find the initial molecular events (IME), which may result in the consequential ecological and health deterioration.Searching for IME is actually a search for the mode of action of a toxic chemical within a defined toxic pathway or target, mostly based on OMICs technologies and in connection with evidences of biochemical, histological and toxic ones from in-vivo testing.In the presentation, we present our recent work on molecular screening for target of action and mode of action of selected known toxic contaminants in aquatic environment.Two approaches have been used for targeting the pathway.A gen-array constructed from major functional gens in endocrine system for screening the pathways involved in the endocrine disruption process by the environmental disruptors, especially including those mediated by receptors of the nucleus super family.While the gen-array provides the transcriptional information, the reconstructed hybrid receptor recombinant yeast bioassay could provide more direct evidences on the ligand-receptor interaction.For biochemical, histological and toxic evidences, in-vivo static and flowing-through tests with Chinese rare-minnow as model animal was performed to build up the chain of evidences.The second approach that we are developing is based on high-throughput sequencing (HTS) technology for wild aquatic animals such as Chinese rare-minnow and Corbiculafluminea.This technology, in connection with technologies of proteomics, could result in broad field of vision on the whole genome.Examples were given on some selected chemicals that we tested in our laboratory.