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Titanium dioxide (TiO₂) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO₂ particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO₂ has yet to be defined.

In this study, we demonstrated that combined treatment with TiO₂ 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 TiO₂ nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO₂^P25–70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and …