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Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model

(1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic resp...

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Autores principales: Elje, Elisabeth, Mariussen, Espen, Moriones, Oscar H., Bastús, Neus G., Puntes, Victor, Kohl, Yvonne, Dusinska, Maria, Rundén-Pran, Elise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153628/
https://www.ncbi.nlm.nih.gov/pubmed/32197356
http://dx.doi.org/10.3390/nano10030545
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author Elje, Elisabeth
Mariussen, Espen
Moriones, Oscar H.
Bastús, Neus G.
Puntes, Victor
Kohl, Yvonne
Dusinska, Maria
Rundén-Pran, Elise
author_facet Elje, Elisabeth
Mariussen, Espen
Moriones, Oscar H.
Bastús, Neus G.
Puntes, Victor
Kohl, Yvonne
Dusinska, Maria
Rundén-Pran, Elise
author_sort Elje, Elisabeth
collection PubMed
description (1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO(2)), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC(50) 3.8 µg/cm(2)) than in 3D cultures (EC(50) > 30 µg/cm(2)), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC(50) 10.1–16.2 µg/cm(2)). Ag- and ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO(2)-NPs showed no toxicity (EC(50) > 75 µg/cm(2)). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs.
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spelling pubmed-71536282020-04-20 Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model Elje, Elisabeth Mariussen, Espen Moriones, Oscar H. Bastús, Neus G. Puntes, Victor Kohl, Yvonne Dusinska, Maria Rundén-Pran, Elise Nanomaterials (Basel) Article (1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO(2)), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC(50) 3.8 µg/cm(2)) than in 3D cultures (EC(50) > 30 µg/cm(2)), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC(50) 10.1–16.2 µg/cm(2)). Ag- and ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO(2)-NPs showed no toxicity (EC(50) > 75 µg/cm(2)). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs. MDPI 2020-03-18 /pmc/articles/PMC7153628/ /pubmed/32197356 http://dx.doi.org/10.3390/nano10030545 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elje, Elisabeth
Mariussen, Espen
Moriones, Oscar H.
Bastús, Neus G.
Puntes, Victor
Kohl, Yvonne
Dusinska, Maria
Rundén-Pran, Elise
Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model
title Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model
title_full Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model
title_fullStr Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model
title_full_unstemmed Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model
title_short Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model
title_sort hepato(geno)toxicity assessment of nanoparticles in a hepg2 liver spheroid model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153628/
https://www.ncbi.nlm.nih.gov/pubmed/32197356
http://dx.doi.org/10.3390/nano10030545
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