The role of ATF3 in ZnO nanoparticle-induced genotoxicity and cytotoxicity in bronchial epithelial cells.

ZnO nanoparticle (ZnO NP) exposure causes oxidative stress in the respiratory system, leading to pulmonary damage. Activating transcription factor 3 (ATF3) participates in a variety of cellular stress responses. However, the role of ATF3 in ZnO NP genotoxicity and cytotoxicity remains to be explored. Here we reported that ZnO NP treatment dramatically induced the expression of ATF3 in human bronchial epithelial (HBE) cells, which was mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2). ATF3 was required for the repair of ZnO NP-induced DNA damage as gamma foci number increased when endogenous ATF3 was silenced. Moreover, ATF3 also contributed to ZnO NP-induced cell apoptosis. Mechanistic study revealed that ATF3 interacted with the p53 protein and upregulated its expression under ZnO NP treatment. Collectively, our findings demonstrated ATF3 as an important regulator of epithelial homeostasis by promoting both DNA repair and the death of damaged cells under ZnO NP-induced genotoxic stress.