title: Titanium dioxide nanoparticle-induced oxidative stress triggers DNA damage and hepatic injury in mice.
abstract: BACKGROUND
  The use of metal oxide nanoparticles (titanium dioxide) in consumer and industrial products improves their quality but also underscores the possible adverse effects to human and environmental health.
  
  
  METHODS
  Mice were exposed orally for 14 consecutive days and analyzed for alteration in different hepatic enzymes, histopathological changes, oxidative stress, DNA damage, tumor suppressor and proapoptotic protein expression in liver cells.
  
  
  RESULTS
  We observed a significant alteration in the level of hepatic enzymes and liver histopathology at a dose of 100 mg/kg body weight. Significant oxidative DNA damage was observed in liver cells, which could be attributed to oxidative stress. In addition, the increased expression of p53, BAX, caspase-3 and -9 proteins and decreased expression of antiapoptotic protein Bcl-2, suggest activation of the intrinsic pathway of apoptosis.
  
  
  CONCLUSIONS
  High accumulation of titanium dioxide nanoparticles in the liver tissue would cause DNA damage and apoptosis through the intrinsic pathway.
authors.affiliation: Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, PO Box 80, Lucknow-226001, Uttar Pradesh, India.
authors.forename: Ritesh K
authors.initials: RK
authors.lastname: Shukla
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.forename: Naga Veera Srikanth
authors.initials: NV
authors.lastname: Vallabani
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
authors.forename: Alok
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004249:DNA Damage; D006360:Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D015162:Micronucleus Tests; D050997:Nanomedicine; D018384:Oxidative Stress / Q000187:drug effects; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D006360:Heat-Shock Proteins; C009495:titanium dioxide; D014025:Titanium
keywords: DNA damage; apoptosis; fpg Comet assay; histopathological changes; liver; mouse; oxidative stress; titanium dioxide nanoparticles