Titanium dioxide nanoparticles translocate through differentiated Caco-2 cell monolayers, without disrupting the barrier functionality or inducing genotoxic damage
Vila Vecilla, Laura (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
García-Rodríguez, Alba (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Marcos, Ricard (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Hernández, Alba (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date:	2018
Abstract:	The widespread use of titanium dioxide nanoparticles (TiO2NPs) in commercial food products makes intestinal cells a suitable target. Accordingly, we have used the human colon adenocarcinoma Caco-2 cells to detect their potential harmful effects. Caco-2 cells can differentiate in to enterocytic-like cells, forming consistent cell monolayers and are used as a model of the intestinal barrier. Using both undifferentiated and differentiated Caco-2 cells, we have explored a set of biomarkers, aiming to evaluate undesirable effects associated to TiO2NP exposure. Results indicate non-toxic effects in exposures ranging 1-200 μg ml-1. Significant differences were observed in cell uptake, with a higher amount of incorporated TiO2NPs in undifferentiated cells, as visualized using confocal microscopy. In well-established monolayers, translocation was detected using both confocal microscopy and transmission electron microscopy with energy-dispersive X-ray spectroscopy. In spite of the observed uptake and translocation, TiO2NP exposures did not modify the integrity of the monolayer, as measured using the transepithelial electrical resistance and Lucifer yellow methods. The potential genotoxic effects in differentiated cells were evaluated in the comet assay, with and without formamidopyrimidine DNA glycosylase enzyme to detect oxidatively the damaged DNA bases. Although some changes were detected at the lower dose (10 μg ml-1), no effects were observed at higher doses.
Grants:	Ministerio de Economía y Competitividad SAF2015-63519-R European Commission 310584
Rights:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Differentiated Caco-2 cells ; Genotoxicity ; Monolayer-integrity ; Titanium dioxide nanoparticles ; Translocation ; Uptake
Published in:	Journal of Applied Toxicology, Vol. 38, Num. 9 (September 2018) , p. 1195-1205, ISSN 1099-1263

DOI: 10.1002/jat.3630

Postprint 35 p, 749.6 KB

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