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

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...

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Published in:Toxicology and applied pharmacology 2018-10, Vol.356, p.54
Main Authors: Chézeau, Laëtitia, Sébillaud, Sylvie, Safar, Ramia, Seidel, Carole, Dembélé, Doulaye, Lorcin, Mylène, Langlais, Cristina, Grossmann, Stéphane, Nunge, Hervé, Michaux, Sylvie, Dubois-Pot-Schneider, Hélène, Rihn, Bertrand, Joubert, Olivier, Binet, Stéphane, Cosnier, Frédéric, Gaté, Laurent
Format: Article
Language:English
Subjects:
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
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Summary: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/m of a TiO 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 TiO .
ISSN:1096-0333
DOI:10.1016/j.taap.2018.07.013