ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells

Titanium dioxide nanoparticles (TiO2 NPs) are among the top five NPs used in consumer products, paints and pharmaceutical preparations. Since, exposure to such nanoparticles is mainly through the skin and inhalation, the present study was conducted in the human epidermal cells (A431). A mild cytotoxic response of TiO2 NPs was observed as evident by the MTT and NR uptake assays after 48 h of exposure. However, a statistically significant (p < 0.05) induction in the DNA damage was observed by the Fpg-modified Comet assay in cells exposed to 0.8 mu g/ml TiO2 NPs (2.20 +/- 0.26 vs. control 1.24 +/- 0.04) and higher concentrations for 6 h. A significant (p < 0.05) induction in micronucleus formation was also observed at the above concentration (14.67 +/- 1.20 vs. control 9.33 +/- 1.00). TiO2 NPs elicited a significant (p < 0.05) reduction in glutathione (15.76%) with a concomitant increase in lipid hydroperoxide (60.51%; p < 0.05) and reactive oxygen species (ROS) generation (49.2%; p < 0.05) after 6 h exposure. Our data demonstrate that TiO2 NPs have a mild cytotoxic potential. However, they induce ROS and oxidative stress leading to oxidative DNA damage and micronucleus formation, a probable mechanism of genotoxicity. This is perhaps the first study on human skin cells demonstrating the cytotoxic and genotoxic potential of TiO2 NPs. (C) 2010 Elsevier Ltd. All rights reserved.