Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PM10) through XPA Deregulation in Lung Epithelial Cells

Airborne particulate matter with a diameter size of ≤10 µm (PM₁₀) is a carcinogen that contains polycyclic aromatic hydrocarbons (PAH), which form PAH–DNA adducts. However, the way in which these adducts are managed by DNA repair pathways in cells exposed to PM₁₀ has been partially described. We evaluated the effect of PM₁₀ on nucleotide excision repair (NER) activity and on the levels of different proteins of this pathway that eliminate bulky DNA adducts. Our results showed that human lung epithelial cells (A549) exposed to 10 µg/cm² of PM₁₀ exhibited PAH–DNA adducts as well as an increase in RAD23 and XPD protein levels (first responders in NER). In addition, PM₁₀ increased the levels of H4K20me2, a recruitment signal for XPA. However, we observed a decrease in total and phosphorylated XPA (Ser196) and an increase in phosphatase WIP1, aside from the absence of XPA–RPA complex, which participates in DNA-damage removal. Additionally, an NER activity assay demonstrated inhibition of the NER functionality in cells exposed to PM₁₀, indicating that XPA alterations led to deficiencies in DNA repair. These results demonstrate that PM₁₀ exposure induces an accumulation of DNA damage that is associated with NER inhibition, highlighting the role of PM₁₀ as an important contributor to lung cancer.