Aging-independent and size-dependent genotoxic response induced by titanium dioxide nanoparticles in mammalian cells.

Titanium dioxide nanoparticles (TiO NPs) are subjected to various transformation processes (chemical, physical and biological processes) in the environment, potentially affecting their bioavailability and toxic properties. However, the size variation of TiO NPs during aging process and subsequent effects in mammalian cells are largely unknown. The aim of this study was to illustrate the adverse effects of TiO NPs in different sizes (5, 15 and <100 nm) during aging process on human-hamster hybrid (A) cells. There was an aging-time dependent enhancement of average hydrodynamic size in TiO NPs stock suspensions. The cytotoxicity of fresh TiO NPs increased in a size-dependent manner; in contrast, their genotoxicity decreased with the increasing sizes of NPs. No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO NPs. Both Fresh and aged TiO NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner. Using mitochondrial-DNA deficient (ρ) A cells, we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO NPs during the aging process. Taken together, our data indicated that TiO NPs could significantly induced the cytotoxicity and genotoxicity in an aging time-independent and size-dependent manner, which were triggered by mitochondrial dysfunction. Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO NPs disposal before entering the environment.