Short- and long-term gene expression profiles induced by inhaled TiO 2 nanostructured aerosol in rat lung

Toxicol Appl Pharmacol. 2018 Oct 1;356:54-64. doi: 10.1016/j.taap.2018.07.013. Epub 2018 Aug 4.


The number of workers potentially exposed to nanoparticles (NPs) during industrial processes is increasing, although the toxicological properties of these compounds still need to be fully characterized. As NPs may be aerosolized during industrial processes, inhalation represents their main route of occupational exposure. Here, the short- and long-term pulmonary toxicological properties of titanium dioxide were studied, using conventional and molecular toxicological approaches. Fischer 344 rats were exposed to 10 mg/m3 of a TiO2 nanostructured aerosol (NSA) by nose-only inhalation for 6 h/day, 5 days/week for 4 weeks. Lung samples were collected up to 180 post-exposure days. Biochemical and cytological analyses of bronchoalveolar lavage (BAL) showed a strong inflammatory response up to 3 post-exposure days, which decreased overtime. In addition, gene expression profiling revealed overexpression of genes involved in inflammation that was maintained 6 months after the end of exposure (long-term response). Genes involved in oxidative stress and vascular changes were also up-regulated. Long-term response was characterized by persistent altered expression of a number of genes up to 180 post-exposure days, despite the absence of significant histopathological changes. The physiopathological consequences of these changes are not fully understood, but they should raise concerns about the long-term pulmonary effects of inhaled biopersistent NPs such as TiO2.

Keywords: Gene expression profile; Lung inflammation; Short- and long-term response; Titanium dioxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Animals
  • Blood Vessels / drug effects
  • Bronchoalveolar Lavage Fluid
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects
  • Inhalation Exposure / adverse effects
  • Lung / pathology*
  • Lymph Nodes / pathology
  • Male
  • Microarray Analysis
  • Nanostructures / toxicity*
  • Oxidative Stress / genetics
  • Rats
  • Rats, Inbred F344
  • Titanium / administration & dosage
  • Titanium / toxicity*


  • Aerosols
  • titanium dioxide
  • Titanium