In order to elucidate the nanoparticle-induced cytotoxicity and its mechanism, the effects of 20 and 50 nm silica nanoparticles on cultured human embryonic kidney (HEK293) cells were investigated. Cell viability, mitochondrial function, cell morphology, reactive oxygen species (ROS), glutathione (GSH), thiobarbituric acid reactive substance (TBARS), cell cycle and apoptosis were assessed under control and silica exposed conditions. Exposure to 20 or 50 nm SiO(2) nanoparticles at dosage levels between 20 and 100 microg/ml decreased cell viability in a dose-dependent manner. Median lethal dose (LD(50)) of 24h exposure was 80.2+/-6.4 and 140.3+/-8.6 microg/ml for 20 and 50 nm SiO(2) nanoparticles, respectively. Morphological examination revealed cell shrinkage and nuclear condensation after SiO(2) nanoparticle exposure. Increase in intracellular ROS level and reduction in GSH content were also observed in SiO(2) nanoparticle-exposed HEK293 cells. Increase in the amount of TBARS suggested an elevated level of lipid peroxidation. Flow cytometric analysis showed that SiO(2) nanoparticles can cause G2/M phase arrest and apoptotic sub-G1 population increase in a dose-dependent manner. In summary, exposure to SiO(2) nanoparticles resulted in a dose-dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.