['Titanium dioxide (TiO(2)) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO(2) particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO(2) has yet to be defined.', 'In this study, we demonstrated that combined treatment with TiO(2) nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO(2) nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO(2) (P25-70)) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO(2)-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO(2) (P25-70) and ultraviolet A irradiation.'] Does titanium dioxide induce apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation?