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OBJECTIVE Exposure to the ambient particulate matters has been associated with cardiopulmonary morbidity and mortality.However, the interactive effects and health impacts of combinations of UFP and air pollutants are still not well understood.In the present study, we investigated the combined effects of amorphous silica nanoparticles (nano-SiO2) and methyl mercury (MeHg) in a cellular system to understand their potential joint action type and underlying mechanisms of combined toxicity.METHODS A co-exposure model of nano-SiO2 and MeHg was established.Lung adenocarcinoma cells (A549) were exposed to nano-SiO2 only, mercury only, or a combination of nano-SiO2 and MeHg.Factorial design was applied to analyze the potential interactions between nano-SiO2 and MeHg.RESULTS Our results showed that co-exposure of nano-SiO2 and MeHg could induce significantly enhanced reactive oxygen species (ROS) generation, lipid peroxidation and activity reduction of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).The increasing oxidative stress resulted in oxidative DNA damage as well as cellular apoptosis.Additive and synergistic interactions were responsible for the combined toxicity of nano-SiO2 and MeHg.CONCLUSION By providing information on combined toxicity research, our work takes a future step toward the studies investigating interactive effects and health impacts of co-exposure of UFP and air pollutants.