title: Estimation of TiO₂ nanoparticle-induced genotoxicity persistence and possible chronic gastritis-induction in mice.
abstract: Titanium dioxide (TiO2) nanoparticles are widely used as a food additive and coloring agent in many consumer products however limited data is available on the nano-TiO2 induced genotoxicity persistence. Thus, this study investigated the persistence of nano-TiO2 induced genotoxicity and possible induction of chronic gastritis in mice. The mice were orally administered 5, 50 or 500 mg/kg body weight nano-TiO2 for five consecutive days, and then mice from each dosage group were sacrificed 24 h or one or two weeks after the last treatment. The administration of nano-TiO2 resulted in persistent apoptotic DNA fragmentation and mutations in p53 exons (5-8) as well as significant persistent elevations in malondialdehyde and nitric oxide levels and decreases in the reduced glutathione level and catalase activity compared with the control mice in a dose- and time-dependent manner. Necrosis and inflammation were evident upon histological examination. These findings could be attributed to the persistent accumulation of nano-TiO2 at the tested doses at all three time points. Based on these findings, we conclude that the administration of nano-TiO2, even at low doses, leads to persistent accumulation of nano-TiO2 in mice, resulting in persistent inflammation, apoptosis and oxidative stress, ultimately leading to the induction of chronic gastritis.
authors.affiliation: Zoology Department, Faculty of Science, Cairo University, Giza, Egypt. Electronic address: hananesresm@yahoo.com.
authors.forename: Hanan Ramadan Hamad
authors.initials: HR
authors.lastname: Mohamed
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D014018:Tissue Distribution; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*; D066007:Toxicokinetics; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D005765:Gastrointestinal Agents; D009153:Mutagens; D014874:Water Pollutants, Chemical; C009495:titanium dioxide; D014025:Titanium
keywords: Chronic gastritis; Genotoxicity; Mice; TiO(2) nanoparticles; p53