Short-term and long-term toxicological effects of vanadium dioxide nanoparticles on A549 cells†
The massive production and wide application of vanadium dioxide nanoparticles (VO2 NPs) has raised safety concerns of VO2 NPs exposure through various routes, especially via inhalation. To determine the pulmonary toxicity of VO2 NPs in vitro, we report here on short-term (1 day) and long-term (20 days) comparative toxicity studies of VO2 NPs (denoted as C-VO2, 20–30 nm) and VO2 microparticles (denoted as M-VO2, ∼1 μm) on the lung cell line A549. Different toxic effects were observed under different durations of exposures to VO2 particles. VO2 particles induced cell growth inhibition and death in a dose- and size-dependent style after short-term exposure. The cell viability dropped when the concentration of C-VO2 was 2.5 μg ml−1, C-VO2 causing much more severe cell viability loss than M-VO2 at the same concentration. For long-term exposure, the cell viability dropped to less than 50% after exposure to C-VO2 at a dose of 0.2 μg ml−1, while cells exposed to M-VO2 under the same conditions remained normal, confirming the higher toxicity of C-VO2 than that of M-VO2. Moreover, the long-term exposure to C-VO2 only inhibited the cell proliferation. We found that 0.05 μg ml−1 was the highest non-toxic dose of C-VO2 to A549 cells for long-term exposure. The dissolution of VO2 contributed to the cytotoxicity of VO2. In addition, reactive oxygen species (ROS) generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation were observed in the cells after short-term exposure to VO2 particles in the concentration range tested, indicating that the possible toxicological mechanism might be ROS generation and cell cycle arrest in the G0/G1 phase. ROS generation, mitochondrial damage, and inflammation in cells were also observed during the long-term exposure to C-VO2 at concentrations of 0.1 μg ml−1 and 0.2 μg ml−1, but the cells recovered after a subsequent 5 day recovery period. Our results show that there are significant differences between the short-term and long-term cytotoxicities of VO2.