大气污染是我国面临的重要社会问题，特别是在京津冀地区尤为严重。阐明大气污染对健康的作用机制是制定有针对性的防治策略和研发有效防治手段的关键。IARC的研究报告将大气细颗粒物确定为人类I类致癌物，但其作用机制仍为阐明。本项目采集污染典型地区北京市和石家庄市大气细颗粒物（PM2.5）样品，对其组分进行分析，同时建立动式吸入染毒的小鼠模型、气-液染毒细胞模型，以课题组前期发现的颗粒物诱导的损伤与氧化应激因子FOXO信号有关的研究结果为切入点，采用基因克隆、ChIP、流式细胞分选等技术，探讨大气细颗粒物致DNA损伤、基因突变等遗传毒性，寻找大气细颗粒物在致呼吸系统疾病和遗传损伤终点出现之前的早期健康效应指标，阐明FOXO介导的信号途径在大气细颗粒物遗传毒性中的作用机制。

Atmospheric pollution is a serious social problem in China, particularly in the Beijing-Tianjin-Hebei Region. Clarification of the health impact of key air pollutants and the underlying mechanisms is essential for policy-making and development of specific intervention strategies. In the evaluation report of IARC, atmospheric particles are carcinogenic to humans (group 1). However, the carcinogenic mechanism is not known very clearly. In the present project, the airborne fine particulate matter （PM 2.5） samples will be collected from Beijing and Shijiazhuang city and detected the ingredients, respectively. At meantime, the mouse and cell line will be used to establish the PM2.5 exposure models. In our previous study, we found the mechanism of damages induced by particles was regulated by FOXO. Based on these results, the cell colony and flow cytometry sorting were used to evaluate the ability of cell transformation and gene mutation. The gene recombination、kinase activity analysis、ChIP、qRT-PCR, Western blot was used to test the genotoxicity and the mechanism through FOXO signal induced by PM2.5. The present project will look for the sensitive biomarkers and early health effect indexes induced by PM2.5 particles before the advent of respiratory diseases and genetic damages end point by combination of field and laboratory research. The regulation of FOXO will be studied to explore the mechanism of genotoxicity induced by PM2.5.