Toxicity, genotoxicity and proinflammatory effects of amorphous nanosilica in the human intestinal Caco-2 cell line

• Published in: Toxicology in vitro 2015-03, Vol.29 (2), p.398-407
• Main Authors: Tarantini, Adeline, Lanceleur, Rachelle, Mourot, Annick, Lavault, Marie -Thérèse, Casterou, Gérald, Jarry, Gérard, Hogeveen, Kevin, Fessard, Valérie
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Apoptosis - drug effects; Caco-2; Caco-2 Cells; Caspase 3 - metabolism; Cell Survival - drug effects; Chemical Sciences; Cytoplasm - metabolism; Genotoxicity; Histones - metabolism; Humans; Inflammation; Interleukin-8 - metabolism; Micronucleus Tests; Microscopy, Electron, Transmission; Mutagens - toxicity; Nanoparticle; Nanoparticles - toxicity; Nanoparticles - ultrastructure; Oxidative Stress; Particle Size; Silica; Silicon Dioxide - toxicity
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2014.10.023

•Toxic effects of silica NPs (15 and 55nm) were investigated in Caco-2 cells.•Both NPs were localized within the cytoplasm but did not enter the nucleus.•15nm but not 55nm silica induced genotoxic and proinflammatory effects.•Oxidative stress is likely to be involved in the genotoxic mechanism of action.•SiO2 NPs may induce potential adverse effects on the intestinal epithelium in vivo. 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.