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Identification de marqueurs d’exposition et d’effets de nanoparticules métalliques sur modèle in vitro

Abstract : As a consequence of the extension of the use of nanoparticles in different industrial sectors, the number of potentially exposed workers continues to grow, without fully knowing the toxicological properties of these materials. Since nanoparticles can be aerosolized in the occupational atmosphere, inhalation is the major occupational exposure route. For this reason, risk assessment of exposure to nanomaterials requires toxicology studies to be conducted on cellular models of the airways. In this manuscript, the cellular and molecular responses of rat alveolar macrophages (NR8383) exposed to metallic oxide nanoparticles: ZnO, ZnFe2O4, NiZnFe2O4, Fe2O3, TiO2-NM105 and TiO2-NRCWE001, were studied, combining conventional toxicological analyzes (characterization of nanoparticles by transmission electron microscopy and dynamic light scattering, evaluation of cytotoxicity by WST-1 assays and LDH release); and high throughput molecular screening (transcriptomic and proteomic analyzes). NR8383 cells were exposed to the ZnO, ZnFe2O4, NiZnFe2O4, Fe2O3, TiO2-NM105 and TiO2-NRCWE001 nanoparticles for 24 h which allowed for the determination of a sub-toxic dose for each nanoparticle to which the macrophages were exposed for molecular analysis. Four hours after exposue NR8383 to nanoparticles, many genes and proteins were differentially expressed. Oxidative stress was the adverse biological response following exposure of cells to nanoparticles composed of zinc. In contrast, inflammation was the main activated pathway in cells exposed to the anatase and rutile form of TiO2 nanoparticles. In conclusion, this study exposes the "biological fingerprints" of the two groups of nanoparticles of interest. Finally, our study, combined with previous literature studies, could also be beneficial in validating biomarkers of exposure and effects of nanomaterials suggested in order to predict adverse biological effects.
Document type :
Theses
File URL :
http://docnum.univ-lorraine.fr/ulprive/DDOC_T_2019_0067_DOUMANDJI.pdf
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https://hal.univ-lorraine.fr/tel-02478147
Contributor : Thèses Ul <>
Submitted on : Thursday, February 13, 2020 - 5:27:58 PM
Last modification on : Friday, February 14, 2020 - 1:36:58 AM

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  • HAL Id : tel-02478147, version 1

Citation

Zahra Doumandji. Identification de marqueurs d’exposition et d’effets de nanoparticules métalliques sur modèle in vitro. Toxicologie. Université de Lorraine, 2019. Français. ⟨NNT : 2019LORR0067⟩. ⟨tel-02478147⟩

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