title: Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes.
abstract: Titanium dioxide nanoparticles (nano-TiO2) are widely used as a photocatalyst in air and water remediation. These nanoparticles are known to induce toxicity; however, their cytotoxic mechanism is not fully understood. In this study, we investigated the underlying mechanism of nano-TiO2-induced cytotoxicity in peripheral blood lymphocytes. We examined the genotoxic effects of nano-TiO2 in lymphocytes using alkaline single-cell gel electrophoresis (Comet) and cytokinesis-block micronucleus (CBMN) assays. Lymphocytes treated with nano-TiO2 showed significantly increased micronucleus formation and DNA breakage. Western-blot analysis to identify proteins involved in the p53-mediated response to DNA damage revealed the accumulation of p53 and activation of DNA damage checkpoint kinases in nano-TiO2-treated lymphocytes. However, p21 and bax, downstream targets of p53, were not affected, indicating that nano-TiO2 does not stimulate transactivational activity of p53. The generation of reactive oxygen species (ROS) in nano-TiO2-treated cells was also observed, andN-acetylcysteine (NAC) supplementation inhibited the level of nano-TiO2-induced DNA damage. Given that ROS-induced DNA damage leads to p53 activation in the DNA damage response, our results suggest that nano-TiO2 induces ROS generation in lymphocytes, thereby activating p53-mediated DNA damage checkpoint signals.
authors.affiliation: School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kang
authors.forename: Byeong Mo
authors.initials: BM
authors.lastname: Kim
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hai Won
authors.initials: HW
authors.lastname: Chung
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D053758:Nanoparticles; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D009153:Mutagens; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C009495:titanium dioxide; D014025:Titanium