Low-dose-rate gamma radiation aggravates titanium dioxide nanoparticle-induced lung injury in mice

Background: Radiation damage and the cellular response has been studied in various direction, however, the synergic effects of radiation damage with environmental pollution on cells or tissues remained poorly understood. In particular, gene and pathway regulation by low-dose radiation exposure remains unclear. Dust and air pollution in Asian countries contains metal oxide and titanium dioxide nanoparticles (TiO₂NPs), which exacerbate respiratory distress. Objective: To explore the synergic injury of radiation damage with air pollution, we examined the effects of low-dose-rate radiation with TiO2NPs on pulmonary response in mice. Results: Thirty-six mice (C57bl/6) were divided into six groups: sham, 0.1 Gy, 0.3 Gy, TiO₂NPs, TiO₂NPs + 0.1 Gy, and TiO₂NPs + 0.3 Gy group. Mice were irradiated at a low-dose-rate at a dose of 0.1 Gy (0.182 mGy/h) and 0.3 Gy (0.554 mGy/h) for 24 days and exposed to TiO₂NPs by intranasal injection at a dose of 0.1 mg daily for 4 days (from day 21 to 24). The combination of low-dose-rate radiation and TiO₂NPs caused significantly more pulmonary inflammation via MAPK phosphorylation in mice than did each stimulus alone. Conclusion: We conclude that while exposure to each of these two distinct stimuli alone does not cause notable lung damage, they may potentially cause lung damage when combined owing to their synergistic effects. Therefore, we should pay attention to the possible combined effects of low-dose radiation and exposure to TiO₂NPs, considering their potential danger in patients with respiratory problems.