Fine particle matters induce DNA damage and G2/M cell cycle arrest in human bronchial epithelial BEAS-2B cells
2017
Wu, Jing | Shi, Yanfeng | Asweto, Collins Otieno | Feng, Lin | Yang, Xiaozhe | Zhang, Yannan | Hu, Hejing | Duan, Junchao | Sun, Zhiwei
There is compelling evidence that exposure to particulate matter (PM) is linked to lung tumorigenesis. However, there is not enough experimental evidence to support the specific mechanisms of PM₂.₅-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM₂.₅ on bronchial epithelial (BEAS-2B) cells. PM₂.₅ exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM₂.₅ dosage. A significant increase in MDA content and a decrease in GSH-Px activity were observed. The generation of ROS was enhanced obviously, while apoptosis increased in BEAS-2B cells exposed to PM₂.₅ for 24 h. DNA damage was found to be more severe in the exposed groups compared with the control. For in-depth study, we have demonstrated that PM₂.₅ stimulated the activation of HER2/ErbB2 while significantly upregulating the expression of Ras/GADPH, p-BRAF/BRAF, p-MEK/MEK, p-ERK/ERK, and c-Myc/GADPH in a dose-dependent manner. In summary, we suggested that exposure to PM₂.₅ sustained the activation of HER2/ErbB2, which in turn promoted the activation of the Ras/Raf/MAPK pathway and the expression of the downstream target c-Myc. The overexpression of c-Myc may lead to G2/M arrest and aggravate the DNA damage and apoptosis in BEAS-2B after exposure to PM₂.₅.
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