title: Toxicity, genotoxicity and proinflammatory effects of amorphous nanosilica in the human intestinal Caco-2 cell line.
abstract: Silica (SiO2) in its nanosized form is now used in food applications although the potential risks for human health need to be evaluated in further detail. In the current study, the uptake of 15 and 55nm colloidal SiO2 NPs in the human intestinal Caco-2 cell line was investigated by transmission electron microscopy. The ability of these NPs to induce cytotoxicity (XTT viability test), genotoxicity (γH2Ax and micronucleus assay), apoptosis (caspase 3), oxidative stress (oxidation of 2,7-dichlorodihydrofluorescein diacetate probe) and proinflammatory effects (interleukin IL-8 secretion) was evaluated. Quartz DQ12 was used as particle control. XTT and cytokinesis-block micronucleus assays revealed size- and concentration-dependent effects on cell death and chromosome damage following exposure to SiO2 nanoparticles, concomitantly with generation of reactive oxygen species (ROS), SiO2-15nm particles being the most potent. In the same way, an increased IL-8 secretion was only observed with SiO2-15nm at the highest tested dose (32μg/ml). TEM images showed that both NPs were localized within the cytoplasm but did not enter the nucleus. SiO2-15nm, and to a lower extent SiO2-55nm, exerted toxic effects in Caco-2 cells. The observed genotoxic effects of these NPs are likely to be mediated through oxidative stress rather than a direct interaction with the DNA. Altogether, our results indicate that exposure to SiO2 NPs may induce potential adverse effects on the intestinal epithelium in vivo.
authors.affiliation: Agence Nationale de Sécurité Sanitaire, Unité de Toxicologie des Contaminants, Bâtiment BioAgroPolis, 10B rue C, Bourgelat, BP 40608, 35306 Fougères, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Tarantini
authors.affiliation: Agence Nationale de Sécurité Sanitaire, Unité de Toxicologie des Contaminants, Bâtiment BioAgroPolis, 10B rue C, Bourgelat, BP 40608, 35306 Fougères, France.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Lanceleur
authors.affiliation: Agence Nationale de Sécurité Sanitaire, Unité de Toxicologie des Contaminants, Bâtiment BioAgroPolis, 10B rue C, Bourgelat, BP 40608, 35306 Fougères, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Mourot
authors.affiliation: PF Mric TEM, BIOSIT Université de Rennes 1, 2 avenue Léon Bernard, 35043 Rennes, France.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Lavault
authors.affiliation: Equipe "Ingénierie Chimique et Molécule pour le Vivant", Institut des Sciences chimiques de Rennes, UMR 6226, Bat 10A, Bureau 210, Campus Beaulieu, Rennes 35000, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Casterou
authors.affiliation: Agence Nationale de Sécurité Sanitaire, Unité de Toxicologie des Contaminants, Bâtiment BioAgroPolis, 10B rue C, Bourgelat, BP 40608, 35306 Fougères, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Jarry
authors.affiliation: Agence Nationale de Sécurité Sanitaire, Unité de Toxicologie des Contaminants, Bâtiment BioAgroPolis, 10B rue C, Bourgelat, BP 40608, 35306 Fougères, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hogeveen
authors.affiliation: Agence Nationale de Sécurité Sanitaire, Unité de Toxicologie des Contaminants, Bâtiment BioAgroPolis, 10B rue C, Bourgelat, BP 40608, 35306 Fougères, France. Electronic address: valerie.fessard@anses.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Fessard
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D015162:Micronucleus Tests; D046529:Microscopy, Electron, Transmission; D009153:Mutagens / Q000633:toxicity*; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D018384:Oxidative Stress; D010316:Particle Size; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: C468783:H2AX protein, human; D006657:Histones; D016209:Interleukin-8; D009153:Mutagens; D012822:Silicon Dioxide; D053148:Caspase 3
keywords: Caco-2; Genotoxicity; Inflammation; Nanoparticle; Oxidative stress; Silica