Cytotoxicity and genotoxicity of titanium dioxide nanoparticles in UVA-irradiated normal peripheral blood lymphocytes

The phototoxicity of ultraviolet A irradiation (UVA) can be enhanced by photosensitizing agents, such as titanium dioxide nanoparticles (100 nm in diameter, normal-TiO2). Nano-TiO2 treatment in the absence of UVA caused a slight decrease in cell viability, but in the presence of UVA, it caused a significant decrease in cell viability. In the presence of UVA, nano-TiO2 also significantly increased the percentage of the cell population in the sub-G 1 phase, induced activation of the proapoptotic proteins, caspase-9, caspase-3, and poly(ADP) ribose polymerase, significantly increased the production of reactive oxygen species (ROS), and induced the loss of the mitochondrial membrane potential (MMP), suggesting that UVA and nano-TiO2 synergistically promoted apoptosis via a mitochondrial pathway. In the presence of UVA, but not in its absence, nano-TiO2 treatment also caused a significant increase in DNA damage. Normal-TiO2 used at the same concentrations did not cause DNA damage, induce ROS generation, trigger mitochondrial membrane depolarization, or increase apoptotic cell death, regardless of UVA exposure. Taken together, these results suggest that nano-TiO2 and UVA synergistically promote rapid ROS generation and MMP collapse, triggering apoptosis. Additionally, they show that small TiO2 particles are more phototoxic than larger ones.