Study of TiO2 P25 nanoparticles genotoxicity on lung, blood and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats

Charlène Relier, Marielle Dubreuil, Omar Lozano Garcia, Eugenia Cordelli, Jorge Humberto Mejia Mendoza, Patrizia Eleuteri, Franck Robidel, Thomas Loret, Francesca Pacchierotti, Stéphane Lucas, Ghislaine Lacroix, Bénédicte Trouiller

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Résumé

Inhaled titanium dioxide (TiO 2) nanoparticles (NPs) can have negative health effects, and have been shown to cause respiratory tract cancer in rats. Inflammation has been linked to oxidative stress, and both have been described as possible mechanisms for genotoxicity of NPs, but rarely examined side-by-side in animal studies. In the present study, a wide range of complementary endpoints have been performed to study TiO 2 P25NP-induced genotoxicity in lung overload and non-overload conditions. Additionally, lung burden, inflammation, cytotoxicity and oxidative stress have also been evaluated in order to link genotoxicity with these responses. To assess quick and delayed responses after recovery, endpoints were evaluated at two time points: 2 h and 35 days after three repeated instillations. This study confirmed the previously described lung overload threshold at approximately 200-300cm 2 of lung burden for total particle surface area lung deposition or 4.2 ml/kg for volume-based cumulative lung exposure dose, above which lung clearance is impaired and inflammation is induced. Our results went on to show that these overload doses induced delayed genotoxicity in lung, associated with persistent inflammation only at the highest dose. The lowest tested doses had no toxicity or genotoxicity effects in the lung. In blood, no lymphocyte DNA damage, erythrocytes chromosomal damage or gene mutation could be detected. Our data also demonstrated that only overload doses induced liver DNA lesions irrespective of the recovery time. Tested doses of TiO 2 P25 NPs did not induce glutathione changes in lung, blood or liver at both recovery times.

langue originaleAnglais
Numéro d'articlekfx006
Pages (de - à)527-537
Nombre de pages11
journalToxicological Sciences
Volume156
Numéro de publication2
Date de mise en ligne précoce13 janv. 2017
Les DOIs
Etat de la publicationPublié - 1 avr. 2017

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    Relier, C., Dubreuil, M., Lozano Garcia, O., Cordelli, E., Mejia Mendoza, J. H., Eleuteri, P., Robidel, F., Loret, T., Pacchierotti, F., Lucas, S., Lacroix, G., & Trouiller, B. (2017). Study of TiO2 P25 nanoparticles genotoxicity on lung, blood and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats. Toxicological Sciences, 156(2), 527-537. [kfx006]. https://doi.org/10.1093/toxsci/kfx006