title: TiO(2) nanoparticles induce oxidative DNA damage and apoptosis in human liver cells.
abstract: Titanium dioxide nanoparticles (TiO(2) NPs), widely used in consumer products, paints, pharmaceutical preparations and so on, have been shown to induce cytotoxicity, genotoxicity and carcinogenic responses in vitro and in vivo. The present study revealed that TiO(2) NPs induce significant (p < 0.05) oxidative DNA damage by the Fpg-Comet assay even at 1 µg/ml concentration. A corresponding increase in the micronucleus frequency was also observed. This could be attributed to the reduced glutathione levels with concomitant increase in lipid peroxidation and reactive oxygen species generation. Furthermore, immunoblot analysis revealed an increased expression of p53, BAX, Cyto-c, Apaf-1, caspase-9 and caspase-3 and decreased the level of Bcl-2 thereby indicating that apoptosis induced by TiO(2) NPs occurs via the caspase-dependent pathway. This study systematically shows that TiO(2) NPs induce DNA damage and cause apoptosis in HepG2 cells even at very low concentrations. Hence the use of such nanoparticles should be carefully monitored.
authors: CSIR-Indian Institute of Toxicology Research, Nanomaterial Toxicology Group, Lucknow-226001, Uttar Pradesh, India.
authors: Ritesh K
authors: RK
authors: Shukla
authors: Ashutosh
authors: A
authors: Kumar
authors: Deepak
authors: D
authors: Gurbani
authors: Alok K
authors: AK
authors: Pandey
authors: Shashi
authors: S
authors: Singh
authors: Alok
authors: A
authors: Dhawan
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D020552:Comet Assay; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D053768:Metal Nanoparticles / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*
chemical_list: D017304:Annexin A5; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D005978:Glutathione