TiO2-induced gene expression and protein profiles in rat lung: a subacute inhalation study

Due to the growing use of nanoparticles in industrial processes, the number of workers potentially exposed is increasing while the toxicological properties of these compounds are not fully known. Inhalation represents the main route of occupational exposure. In this respect, the experimental toxicology studies conducted by inhalation in animals appear to be the most relevant for the early evaluation of the hazard associated with exposure to nanoaerosols.
In this work we study the pulmonary toxicological properties of titanium dioxide using conventional and molecular toxicological approaches. For this, we exposed Fischer 344 rats by nose-only inhalation 6 hours/day, 5 days/week for 4 weeks to a nanoaerosol of TiO2 (10 mg/m3).
Lung samples have been collected up to 180 days after the end of exposure. Biochemical and cytological analyses of the broncho-alveolar lavage fluid (BALF) showed a strong inflammatory response up to 3 days which decreased overtime but persisted 180 days after exposure. In addition, a gene expression profiling experiment showed an overexpression of genes involved in inflammation that persisted in the chronic phase. These observations are consistent with physiopathological changes. Moreover, this experimental approach revealed also an overexpression of genes involved in vasodilatation and oxidative stress. This transcriptomics approach has been completed with proteomics analysis in the BALF. The preliminary data also showed an overexpression of proteins involved in inflammation and oxidative stress.
To confirm these data, additional experiments will be performed at the protein level using western blot or ELISA. Finally, analysis of long-term epigenetic modifications (DNA methylation, acetylation) will be performed to observe possible chronic gene expression modification, involved in physio-pathological processes.