Cytotoxicity and genotoxicity of low-dose vanadium dioxide nanoparticles to lung cells following long-term exposure.

Vanadium dioxide nanoparticles (VO NPs) have been massively produced and widely applied due to their excellent metal-insulator transition property, making it extremely urgent to evaluate their safety, especially for low-dose long-term respiratory occupational exposure. Here, we report a comprehensive cytotoxicity and genotoxicity study on VO NPs to lung cell lines A549 and BEAS-2B following a long-term exposure. A commercial VO NP, S-VO, was used to treat BEAS-2B (0.15-0.6 μg/mL) and A549 (0.3-1.2 μg/mL) cells for four exposure cycles, and each exposure cycle lasted for 4 consecutive days; then various bioassays were performed after each cycle. Significant proliferation inhibition was observed in both cell lines after long-term exposure of S-VO at low doses that did not cause apparent acute cytotoxicity; however, the genotoxicity of S-VO, characterized by DNA damage and micronuclei, was only observed in A549 cells. These adverse effects of S-VO were exposure time-, dose- and cell-dependent, and closely related to the solubility of S-VO. The oxidative stress in cells, i.e., enhanced reactive oxygen species (ROS) generation and suppressed reduced glutathione, was the main toxicity mechanism of S-VO. The ROS-associated mitochondrial damage and DNA damage led to the genotoxicity, and cell proliferation retard, resulting in the cellular viability loss. Our results highlight the importance and urgent necessity of the investigation on the long-term toxicity of VO NPs.