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 PM-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM on bronchial epithelial (BEAS-2B) cells. PM exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM 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 PM 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 PM 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 PM 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 PM.

A Review of Recent Advances in Research on PM2.5 in China

“…In addition, the indoor PM 2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead and wrinkle on upper lip [ 140 ]. PM 2.5 may lead to induced DNA damage and cell cycle arrest in lung tumorigenesis [ 141 ]. Repeated exposure to PM 2.5 induces vascular inflammation [ 142 ].…”

Variation in doses and duration of particulate matter exposure in bronchial epithelial cells results in upregulation of different genes associated with airway disorders

“…Bronchial epithelial cells line the respiratory airways and are the first cells of the lung exposed to PM 2.5 . Studies of bronchial epithelial cells directly exposed to PM 2.5 have shown that PM 2.5 impairs bronchial epithelial cell function (Zhang et al, 2017), causes mitochondrial dysfunction (Lavrich et al, 2018), and at high doses, induces cell toxicity and death (Dergham et al, 2015; Wu et al, 2017). PM 2.5 has also furthermore been shown to induce bronchial epithelial cells to synthesize proinflammatory cytokines, including interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α (Ovrevik et al, 2009; Wang et al, 2017).…”

Particulate Matter Exposure During Oocyte Maturation: Cell Cycle Arrest, ROS Generation, and Early Apoptosis in Mice

“…Here, we found that PM exposure induces cell cycle arrest in maturing oocytes by blocking the degradation of cyclin B1. Similarly, evidence regarding alteration of cell cycle by PM exposure also supports the PM-induced arrest of G2/M phase and regulation of spindle organization (Longhin et al, 2013;Wu et al, 2017). Therefore, exposure to PM can arrest oocyte maturation at the metaphase stage and may regulate maturation such as spindle organization.…”