Genotoxic impact of nanoparticles on lung models

As nanosciences and nanotechnologies develop, nanoparticles (NP) are introduced in a wider range of daily-used products. Titanium dioxide particles are among the most produced mineral particles in the world, which increases the probability of occupational exposure of workers, especially by inhalation, in NP production plants.

 

We are involved for several years in projects aiming at identifying the impact of nanoparticles on in vitro lung models.

 

Our experiments, mainly carried out with TiO2 and SiC-NPs as well as carbon nanotubes (NTC), showed that these nanomaterials induce moderate toxic effects on lung cells. Mortality never exceeds 40% of the cell population, even after 48 h of exposure to very high concentrations, in vitro (Simon-Deckers et al., 2008; Barillet et al., 2011a; Barillet et al., 2011b). The smallest NPs, whatever their crystalline phase, induce the strongest cell response. All the NPs that we tested accumulate in cell cytoplasm, where they are sequestered in vacuoles or compartments resembling lysosomes or autophagosomes. As a consequence, oxidative stress appears in exposed cells. The smallest NPs induce genotoxic effects, by means of DNA strand breaks which are mainly single-strand breaks, and oxidative DNA damage (Jugan et al., 2012). These lesions accumulate in exposed cells, and this may be explained by the drastic reduction of DNA repair ability in NP-exposed cells (Jugan et al., 2012).

 

Our current work aims at identifying the mechanisms that lead to such genotoxic impact and DNA repair impairment in NP-exposed cells. We also investigate the genotoxic impact of NPs upon chronic in vitro exposure, i.e. exposure to low concentrations of NPs for long times. Finally, in collaboration with Karlsruhe Institute of Technology (KIT, Germany), we assess the impact of NPs on lung cell upon exposure to aerosols of NPs, at the air-liquid interface.

 

These projects are funded by the Labex SERENADE, by CEA internal Toxicology and Nanoscience programs and by the European Commission (FP7-NMP, Nanomile project). They were previously funded by ANR (Signanotox project) and ANSES (NanoPIST project).

 

References:

M.-L. Jugan, S. Barillet, A. Simon-Deckers, N. Herlin, S. Sauvaigo, T. Douki and M. Carrière. Titanium dioxide nanoparticles induce genotoxic effects and impair DNA repair activity in vitro. Nanotoxicology, 6: 501-513, 2012.

 

M.-L. Jugan, S. Barillet, A. Simon-Deckers, S. Sauvaigo, T. Douki, N. Herlin and M. Carrière. Cytotoxic and genotoxic impact of TiO2 nanoparticles on A549 cells. J Biomed Nanotechnol, 7(1), 22-23, 2011.

 

S. Barillet, ML. Jugan, M. Laye, Y. Leconte, N. Herlin-Boime, C. Reynaud, M. Carrière. In vitro evaluation of SiC nanoparticles impact on A549 pulmonary cells: cyto-, genotoxicity and oxidative stress. Toxicol Lett, 198(3): 324-30, 2010.

 

S. Barillet, A. Simon-Deckers, N. Herlin-Boime, M. Mayne-l’Hermite, C. Reynaud, D. Cassio, B. Gouget, M. Carrière. TiO2, SiC nanoparticles and multi-walled carbon nanotubes cyto- and genotoxicity. J Nanopart Res, 12: 61-73, 2010.

 

A. Simon-Deckers, B. Gouget, M. Mayne-L’Hermite, N. Herlin-Boime, C. Reynaud, M. Carrière. In vitro investigation of oxide nanoparticles and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes. Toxicology, 253: 137-146, 2008.

 

Maj : 27/03/2014 (907)

 

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