Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes

Environ Mol Mutagen. 2008 Jun;49(5):399-405. doi: 10.1002/em.20399.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Western
  • Cell Survival / drug effects
  • Cells, Cultured
  • Comet Assay
  • DNA Damage*
  • Female
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Micronuclei, Chromosome-Defective / chemically induced
  • Micronucleus Tests
  • Mutagens / toxicity*
  • Nanoparticles*
  • Particle Size
  • Reactive Oxygen Species / metabolism
  • Titanium / toxicity*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Mutagens
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • titanium dioxide
  • Titanium