基于普通人群的环境甲状腺功能干扰物质暴露组表征及毒性效应研究

环境中多种污染物会干扰甲状腺功能，但与甲状腺疾病关系及潜在机制一直缺乏深入研究。课题组前期研究首次发现普通人群中甲状腺功能干扰物质（TDCs）如高氯酸盐、DEHP和BPF与乳头状甲状腺癌正相关且具有统计学意义，提示特定TDCs会导致甲状腺疾病发生发展，但因果关系和潜在机理尚不明确。鉴于我国环境污染加剧和甲状腺疾病高发现状，本课题拟在代表性地区建立研究队列，以横断面研究和纵向研究相结合，通过靶向和非靶向检测技术综合应用，实现普通人群致甲状腺疾病主要TDCs暴露组表征。以此为基础，依据普通人群真实暴露，开展人源甲状腺细胞染毒试验，揭示毒性作用和潜在毒性通路。借鉴代谢组学技术手段，挖掘早期效应标志物，探索TDCs致甲状腺病变机理，构建剂量效应关系模型，提出基于人群暴露数据的基准剂量，实现甲状腺毒性效应定量评价。课题实施有助于填补TDCs毒性效应研究中空白，为环境管理、疾病防治等提供重要参考。

Many environment pollutants could disrupt thyroid function. But there is very limited information on the relationships between pollutants and thyroid diseases and their underlying mechanism. In our previous studies, for the first time, significant positive associations of some thyroid-function disrupting chemicals (TDCs), like perchlorate, DEHP, and BPF, with risk of papillary thyroid cancer (PTC) in general population. These results suggested specific TDCs may cause and/or promote the development of PTC, although the underlying mechanisms remain unclear. At present, environment pollution is increasing, and incidences of thyroid diseases are elevating. Therefore, we will recruit volunteers to build study cohorts with the combination design of cross-section study and longitudinal study for characterization of TDCs exposome in non-occupational population. Environment pollutants in human biological specimens will determined using series analysis methods including targeting methods and non-targeting methods, and major TDCs that could contribute to thyroid diseases were identified through running statistical models. Based on data of human exposure in the cohort study, cell experiment will be conducted applying human normal thyroid cells, nthy-ori 3-1 cell, to reveal cytotoxic effect and potential toxicity pathway. Methodologies of metabolomics are to be applied for dig early effect biomarkers for investigate underlying mechanisms of thyroid lesion caused by TDCs exposure. Subsequently, dose-response models will be fitted to calculated benchmark dose (BMD) based on real levels of human exposure to major TDCs. Thyrotoxicity effect on human could be quantitatively evaluated by using BMD methods. The implementation of the project will help to fill the gaps, and provide important scientific data for environmental protection and disease control and prevention.