作为一种明确的肺癌危险因素，大气细颗粒物（PM2.5）致肺癌风险的毒性组分和机制尚不清楚。雌激素受体（ER）信号通路在肺癌发生发展中的作用已被证实，含有多种环境雌激素类物质的PM2.5有机组分可能通过ER信号通路导致肺癌发生。本项目在前期基础上，首先对冬夏两季PM2.5有机组分进行化学组分分析，获得典型季节PM2.5有机组分中环境雌激素类物质含量与特征的基础数据；其次构建体外技术模型，定量评价PM2.5有机组分对不同亚型ER的激活作用；进一步建立PM2.5有机组分对人肺正常上皮BEAS-2B细胞的慢性暴露诱导模型和慢性整体动物暴露模型，在不同时间点从ER信号途径、上皮间质转化、肺癌干细胞和肿瘤恶性行为表型四方面，揭示ER信号引发的上皮间质转化和肺癌干细胞在PM2.5有机组分致肺癌中的作用，以阐明PM2.5肺癌风险的毒性组分及相关机制，并探索敏感的生物标志为PM2.5健康风险评价提供参考。

Ambient fine particulate matter (PM2.5) has been known as human carcinogen of lung cancer. However, the toxic components and the underlying biological mechanisms are still unclear. The effect of estrogen receptor (ER) signaling pathway on the development of lung cancer has been confirmed. As the organic components of PM2.5 (Po) contain a variety of estrogen-like substances, ER signaling pathways may be involved in the mechanisms for lung cancer risk induced by Po. Firstly, we will analyze the chemical composition of Po from summer and winter PM2.5, to obtain basic data about estrogen-like substances in Po. Then we will establish the in vitro technology model to evaluate the activating effects of Po on different subtypes of ER. Furthermore, we will expose the human normal lung epithelial BEAS-2B cells and C57BL/6 mice to Po to establish the chronic model, and estimate the effects of Po on ER signaling pathways, epithelial-mesenchymal transition (EMT), lung cancer stem cell (CSC) properties and malignant behaviors of cancer at different time points. We aim to reveal the role of ER-EMT/CSC pathway in lung cancer risk induced by Po and further elucidate the toxic components and toxic mechanisms for PM2.5-induced lung cancer, and search possible biomarker based on ER pathway and CSC properties to promote health risk assessment of related groups.