Titanium dioxide nanoparticles induce an adaptive inflammatory response and invasion and proliferation of lung epithelial cells in chorioallantoic membrane

• Published in: Environmental research Vol. 136; pp. 424 - 434
• Main Authors: Medina-Reyes, Estefany I., Déciga-Alcaraz, Alejandro, Freyre-Fonseca, Verónica, Delgado-Buenrostro, Norma L., Flores-Flores, José O., Gutiérrez-López, Gustavo F., Sánchez-Pérez, Yesennia, García-Cuéllar, Claudia M., Pedraza-Chaverri, José, Chirino, Yolanda I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2015
• Subjects: 60 APPLIED LIFE SCIENCES; ABUNDANCE; ACUTE EXPOSURE; Agglomerates; CARCINOGENS; CELL CULTURES; Cell Line, Tumor; Cell Proliferation - drug effects; Cellular; Chorioallantoic Membrane - drug effects; Cytokine release; Cytokines; Cytokines - metabolism; ECOLOGICAL CONCENTRATION; ENVIRONMENTAL SCIENCES; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Exposure; FETAL MEMBRANES; Humans; HYPOTHESIS; INFLAMMATION; Inflammation - chemically induced; Invasion; Lung - cytology; Lung - drug effects; Lung - metabolism; LUNGS; LYMPHOKINES; Membranes; Metal Nanoparticles; Microscopy, Electron; Nanobelts; NANOPARTICLES; Nanospheres; NANOSTRUCTURES; Nitric Oxide - metabolism; NITROGEN OXIDES; POTASSIUM IODIDES; Proliferation lung epithelial cells; SEEDS; SHAPE; Titanium - pharmacology; Titanium dioxide; Titanium dioxide nanoparticles; TITANIUM OXIDES; TRANSIENTS; Cytokine release; Proliferation lung epithelial cells; Nanospheres; Nanobelts; Titanium dioxide nanoparticles; Invasion
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2014.10.016

Titanium dioxide nanoparticles (TiO2 NPs) studies have been performed using relatively high NPs concentration under acute exposure and limited studies have compared shape effects. We hypothesized that midterm exposure to low TiO2 NPs concentration in lung epithelial cells induces carcinogenic characteristics modulated partially by NPs shape. To test our hypothesis we synthesized NPs shaped as belts (TiO2-B) using TiO2 spheres (TiO2-SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10µg/cm2) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO2-B effect on agglomerates size, cell size and granularity than TiO2-SP. Agglomerates size in cell culture medium was 310nm and 454nm for TiO2-SP and TiO2-B, respectively; TiO2-SP and TiO2-B induced 23% and 70% cell size decrease, respectively, whilst TiO2-SP and TiO2-B induced 7 and 14-fold of granularity increase. NOx production was down-regulated (31%) by TiO2-SP and up-regulated (70%) by TiO2-B. Both NPs induced a transient cytokine release (IL-2, IL-6, IL-8, IL-4, IFN-γ, and TNF-α) after 4 days, but cytokines returned to basal levels in TiO2-SP exposed cells while TiO2-B induced a down-regulation after 7 days. Midterm exposure to both shapes of NPs induced capability to degrade cellular extracellular matrix components from chorioallantoic membrane and Ki-67 marker showed that TiO2-B had higher proliferative potential than TiO2-SP. We conclude that midterm exposure to low NPs concentration of NPs has an impact in the acquisition of new characteristics of exposed cells and NPs shape influences cellular outcome. (A) Lung epithelial cells were low exposed (below 10µg/cm2) to titanium dioxide nanoparticles (TiO2-NPs) shaped as spheres (TiO2-SP) and belts (TiO2-B) for midterm (7 continuous days) separately. (B) Then, cells from each cell culture were harvested and seeded on the top of the chorioallantoic membrane (CAM) for 5 days and (C) invasion and proliferation of cells were analyzed in CAM sections. [Display omitted] •Hydrodynamic size of TiO2- SP was smaller than TiO2-B in cell culture media•TiO2- SP induced higher decrease in cell size than TiO2-B•TiO2-SP induced a transient cytokine release and TiO2-B a downregulation•TiO2-B caused higher proliferative capability than TiO2-SP