title: ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells.
abstract: Titanium dioxide nanoparticles (TiO(2) 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 TiO(2) 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 μg/ml TiO(2) 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). TiO(2) 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 6h exposure. Our data demonstrate that TiO(2) 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 TiO(2) NPs.
authors.affiliation: Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India.
authors.forename: Ritesh K
authors.initials: RK
authors.lastname: Shukla
authors.forename: Vyom
authors.initials: V
authors.lastname: Sharma
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
authors.forename: Shashi
authors.initials: S
authors.lastname: Singh
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
authors.forename: Alok
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay / Q000379:methods; D003257:Consumer Product Safety; D004249:DNA Damage / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D015162:Micronucleus Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014025:Titanium / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D008054:Lipid Peroxides; D009153:Mutagens; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D005978:Glutathione