Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro |
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| Institution: | 1. Institut National de l''Environnement Industriel et des Risques (INERIS), Unité de Toxicologie Expérimentale, Parc Technologique ALATA-BP 2, F-60550 Verneuil-en-Halatte, France;2. Université de Technologie de Compiègne (UTC), Laboratoire BioMécanique et BioIngénierie (BMBI), UMR CNRS 7338, 60205 Compiègne, France;3. Institut National de l''Environnement Industriel et des Risques (INERIS), Unité d''Ecotoxicologie in vitro et in vivo, Parc Technologique ALATA-BP 2, F-60550 Verneuil-en-Halatte, France;1. Università del Salento, Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Via Arnesano, 73100 Lecce, Italy;2. Euromediterranean Center for Nanomaterial Modelling and Technology (ECMT) of Consiglio Nazionale delle Ricerche (CNR), Institute of Nanoscience, via Arnesano, 73100 Lecce, Italy;3. Center for Biomolecular Nanotechnologies, Istituto Italiano di Tecnologia (CBN-IIT), via Barsanti, 73010, Arnesano, Lecce, Italy;1. Université Grenoble-Alpes, INAC-LCIB, Laboratoire Lésions des Acides Nucléiques, 17 rue des Martyrs, F-38000 Grenoble, France;2. CEA, INAC-SCIB, Laboratoire Lésions des Acides Nucléiques, 17 rue des Martyrs, F-38054 Grenoble, France;3. CEA Grenoble, iRTSV/CBM, Laboratory of Chemistry and Biology of Metals, Grenoble, France;4. Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Université de Strasbourg, IPHC, 25 rue Becquerel 67087 Strasbourg, France;5. CNRS, UMR7178, 67037 Strasbourg, France;6. UMR3685 CEA-CNRS, NIMBE, LEDNA, CEA Saclay, F-91191 Gif sur Yvette, France;7. CNRS UMR 5249, Laboratory of Chemistry and Biology of Metals, Grenoble, France |
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| Abstract: | The health risks of nanoparticles remain a serious concern given their prevalence from industrial and domestic use. The primary route of titanium dioxide nanoparticle exposure is inhalation. The extent to which nanoparticles contribute to cellular toxicity is known to associate induction of oxidative stress. To investigate this problem further, the effect of titanium dioxide nanoparticles was examined on cell lines representative of alveolo-capillary barrier.The present study showed that all nanoparticle-exposed cell lines displayed ROS generation. Macrophage-like THP-1 and HPMEC-ST1.6R microvascular cells were sensitive to endogenous redox changes and underwent apoptosis, but not alveolar epithelial A549 cells. Genotoxic potential of titanium dioxide nanoparticles was investigated using the activation of γH2AX, activation of DNA repair proteins and cell cycle arrest. In the sensitive cell lines, DNA damage was persistent and activation of DNA repair pathways was observed. Moreover, western blot analysis showed that specific pathways associated with cellular stress response were activated concomitantly with DNA repair or apoptosis.Nanoparticles-induced oxidative stress is finally signal transducer for further physiological effects including genotoxicity and cytotoxicity. Within activated pathways, HSP27 and SAPK/JNK proteins appeared as potential biomarkers of intracellular stress and of sensitivity to endogenous redox changes, respectively, enabling to predict cell behavior. |
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