呼吸系统是大气细颗粒物（PM2.5）健康危害的主要靶部位，存在多种特异表达的肝外细胞色素P450酶（CYP），推测这些CYP酶可通过原位代谢活化PM2.5重要组分而导致呼吸系统早期严重的损伤，但未见相关研究。结合课题组多年来在环境污染物生物转化和PM2.5健康危害研究方面的积累和优势，本项目以呼吸系统CYP酶及原位代谢为切入点，利用特定细胞、动物和人群系统解析PM2.5中重要致癌和非致癌有机组分及其经代谢活化导致呼吸系统的急慢性损伤及致癌效应，深入研究circRNA-miRNA-mRNA轴调控炎症通路介导PM2.5致呼吸系统损伤的分子机制。PM2.5重要毒性组分甄别、早期健康危害评估、关键非编码RNA等生物标志筛选、系列实验模型、PM2.5和人群健康数据库的构建等，不仅可为PM2.5呼吸系统的危害评价及精准预防提供有效支撑，也可为PM2.5的健康风险评估和早期预警提供科学依据。

Respiratory system is the main target of ambient fine particulate matter (PM2.5), it exists some extrahepatic cytochrome P450 enzymes (CYPs), which lead to be speculated that these specific CYP enzymes in the respiratory system could mediate the in situ metabolic activation of the important components in PM2.5, resulting in early and serious injuries. However, the role and mechanism are still ambiguous and elaborate investigation is urgently required. Based on our past several years’ accumulation and scientific advantage in the study on biotransformation of pollutants and human health hazard, in the present study, taking the respiratory CYP enzymes and their in situ metabolic activation as a breakthrough, we will systematically evaluate the respiratory damages and carcinogenicity by non-carcinogenic and carcinogenic components using specific cell models, animal models and populations. Moreover, we will still explore the potential mechanism on PM2.5-induced respiratory toxicity mediated by circRNA-miRNA-mRNA axis following the inflammatory pathways. As a result, the identification of the important toxic components of PM2.5, assessment of early human health risk, screening of key biomarkers including non-coding RNA, a series of new experimental models, and the establishment of the database of PM2.5 and human health will not only provide a new strategy on respiratory injuries evaluation and precise prevention of PM2.5, but also provide the scientific basis for health risk assessment and early warning of ambient fine particulate matter.