Molecular mechanisms of nanosized titanium dioxide-induced pulmonary injury in mice

PLoS One. 2013;8(2):e55563. doi: 10.1371/journal.pone.0055563. Epub 2013 Feb 7.


The pulmonary damage induced by nanosized titanium dioxide (nano-TiO2) is of great concern, but the mechanism of how this damage may be incurred has yet to be elucidated. Here, we examined how multiple genes may be affected by nano-TiO2 exposure to contribute to the observed damage. The results suggest that long-term exposure to nano-TiO2 led to significant increases in inflammatory cells, and levels of lactate dehydrogenase, alkaline phosphate, and total protein, and promoted production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse lung tissue. We also observed nano-TiO2 deposition in lung tissue via light and confocal Raman microscopy, which in turn led to severe pulmonary inflammation and pneumonocytic apoptosis in mice. Specifically, microarray analysis showed significant alterations in the expression of 847 genes in the nano-TiO2-exposed lung tissues. Of 521 genes with known functions, 361 were up-regulated and 160 down-regulated, which were associated with the immune/inflammatory responses, apoptosis, oxidative stress, the cell cycle, stress responses, cell proliferation, the cytoskeleton, signal transduction, and metabolic processes. Therefore, the application of nano-TiO2 should be carried out cautiously, especially in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Down-Regulation
  • Gene Expression Profiling
  • Lipid Peroxidation
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Metal Nanoparticles / toxicity*
  • Mice
  • Microscopy, Confocal
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Titanium / toxicity*
  • Up-Regulation


  • Reactive Oxygen Species
  • titanium dioxide
  • Titanium

Grant support

This work was supported by the National Natural Science Foundation of China (grant numbers 81273036, 30901218, 81172697), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Major State Basic Research Development Program of China (973 Program) (grant number 2006CB705602), National Important Project on Scientific Research of China (grant number 2011CB933404), National Natural Science Foundation of China (grant numbers 30671782, 30972504) and the National Ideas Foundation of Student of Soochow University (grant number 111028534). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.