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。

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-generational effects. The accomplishment of the present proposal will explain the multi-generational effects of antibiotics at low concentrations and the underlying mechanism, and establish a standard test method for the multi-generational effect studies, and provide more accurate and sound information for the ecological risk assessment and environmental criteria for emerging pollutants.