PM_2.5-induced DNA oxidative stress in A549 cells and regulating mechanisms by GST DNA methylation and Keap1/Nrf2 pathway

Abstract

Fine particulate matter (PM_2.5) increases the risks of lung cancer. Epigenetics provides a new toxicology mechanism for the adverse health effects of PM_2.5. However, the regulating mechanisms of PM_2.5 exposure on candidate gene DNA methylation changes in the development of lung cancer remain unclear. Abnormal expression of the glutathione S transferase (GST) gene is associated with cancer. However, the relationship between PM_2.5 and DNA methylation-mediated GST gene expression is not well understood. In this study, we performed GST DNA methylation analysis and GST-related gene expression in human A549 cells exposed to PM_2.5 (0, 50, 100 µg/mL, from Taiyuan, China) for 24 h (n = 4). We found that PM_2.5 may cause DNA oxidative damage to cells and the elevation of GSTP1 promotes cell resistance to reactive oxygen species (ROS). The Kelch-1ike ECH-associated protein l (Keap1)/nuclear factor NF-E2-related factor 2 (Nrf2) pathway activates the GSTP1. The decrease in the DNA methylation level of the GSTP1 gene enhances GSTP1 expression. GST DNA methylation is associated with reduced levels of 5-methylcytosine (5mC), DNA methyltransferase 1 (DNMT1), and histone deacetylases 3 (HDAC3). The GSTM1 was not sensitive to PM_2.5 stimulation. Our findings suggest that PM_2.5 activates GSTP1 to defend PM_2.5-induced ROS and 8-hydroxy-deoxyguanosine (8-OHdG) formation through the Keap1/Nrf2 signaling pathway and GSTP1 DNA methylation.

Keywords:

• Fine particulate matter
• A549 cell
• GST DNA methylation
• DNA oxidative damage
• Keap1/Nrf2 pathway

Disclosure statement

The authors declare that they have no competing interests.

Data availability statement

All data generated or analyzed during this study are included in this published article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (91543202).