典型抗生素多世代毒性效应及其表观遗传学机理研究

项目名称： 典型抗生素多世代毒性效应及其表观遗传学机理研究

项目编号： No.21307095

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 环境科学、安全科学

项目作者： 于振洋

作者单位： 同济大学

项目金额： 25万元

中文摘要： 环境化学物质低浓度、长期暴露的毒性效应研究是目前生态毒理学的热点，而世代毒性、传递规律及其机制研究是一个优先领域。本项目选择新兴污染物磺胺类抗生素作为典型抗生素，以秀丽线虫为模式动物，通过单世代暴露与多世代多次暴露等方法，对秀丽线虫子三代进行行为学、生长、繁殖量、世代时间、化学趋向性、寿命、凋亡、触感反应等指标的检测，研究与甄别多世代毒性效应；采用化学分析（LC-MS-MS）与生态毒性（生物体染色观察）相结合，研究毒性在不同世代间的传递及规律；采用染色质免疫共沉淀-测序（ChIP-seq）等表观遗传学方法，根据秀丽线虫DNA甲基化、组蛋白修饰、转录因子等指标，从表观遗传学角度阐述毒性效应在世代间的传递机制。研究项目旨在探索化学污染物在低浓度长期暴露下多世代毒性及其机制，建立和发展多世代毒性研究方法，为新兴污染物的生态风险评价、环境标准制定提供科学依据和方法。

中文关键词： 秀丽线虫；跨世代；表观遗传调控；磺胺抗生素；重金属

英文摘要： The adverse effects of chemicals in long-term exposure to low concentrations are one heated topic in environmental toxicology. Meanwhile, the multi-generational effects and the underlying mechanisms are one of the priorities. The present proposal chooses sulfonamides as the representative antibiotics to investigate the multi-generational effects on Caenorhabditis elegans and to primarily study the epigenetic mechanism. After the parental generation of C. elegans is exposed to single exposure in one generation, or to repeated exposures in multiple generations, the 3rd generation offspring will be measured for indicators of growth/development, feeding/behavior, reproduction, generation time, chemical plasticity, longevity and apoptosis. The results will be used to directly indicate the multi-generational effects of sulfonamides. The nematodes will be stained and observed under microscope, and also be used to determine the sulfonamide concentrations using LC-MS-MS. The combination will be used to determine whether and how the sulfonamides can be transferred from the parent to the offspring generations. Furthermore, nematodes will be analyzed by chromatin immunoprecipitation to find related DNA methylation, histone modification and microRNA which are used to elucidate the epigenetic mechanisms of the multi-generatio

英文关键词： Caenorhabditis elegans；Transgeneration；Epigenetic regulation；Sulfonamide；Heavy metal