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However, the pathophysiological mechanisms of PM<jats:sub>2.5<\/jats:sub>\u2010induced pulmonary injury after different exposure times are poorly understood. In this study, we exposed male ICR mice to a whole\u2010body PM<jats:sub>2.5<\/jats:sub> inhalation system at daily mean concentration range from 92.00 to 862.00\u2009\u03bcg\/m<jats:sup>3<\/jats:sup> for 30, 60, and 90\u2009days. We found that following prolonged exposure to PM<jats:sub>2.5<\/jats:sub>, pulmonary injury was increasingly evident with significant histopathological alterations. Notably, the pulmonary inflammatory response and fibrosis caused by PM<jats:sub>2.5<\/jats:sub> after different exposure times were closely associated with histopathological changes. In addition, PM<jats:sub>2.5<\/jats:sub> exposure caused oxidative stress, DNA damage and impairment of DNA repair in a time\u2010dependent manner in the lung. Importantly, exposure to PM<jats:sub>2.5<\/jats:sub> eventually caused apoptosis in the lung through upregulation of cleaved\u2010caspase\u20103 and downregulation of Bcl\u20102. Overall, our data demonstrated that PM<jats:sub>2.5<\/jats:sub> led to pulmonary injury in a time\u2010dependent manner via upregulation of proinflammatory and fibrosis\u2010related genes, and activation of the DNA damage response. Our findings provided a novel perspective on the pathophysiology of respiratory diseases caused by airborne pollution.<\/jats:p>","DOI":"10.1002\/tox.23985","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T17:49:27Z","timestamp":1696268967000},"page":"377-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Temporal analysis of lung injury induced by real\u2010ambient <scp>PM<sub>2<\/sub><\/scp><sub>.5<\/sub> exposure in mice"],"prefix":"10.1002","volume":"39","author":[{"given":"Huixian","family":"Zeng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Disease The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"},{"name":"Institute for Chemical Carcinogenesis Guangzhou Medical University  Guangzhou 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