Fine particle matters induce DNA damage and G2/M cell cycle arrest in human bronchial epithelial BEAS-2B cells

Abstract

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.