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

Journal Article · · Environmental Research
;  [1];  [1];  [1];  [2];  [3]; ;  [4];
  1. Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México (Mexico)
  2. Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria AP 70-186, CP 04510 México, DF (Mexico)
  3. Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, CP 11340 México, DF (Mexico)
  4. Instituto Nacional de Cancerología, Subdirección de Investigación Básica, San Fernando 22, Tlalpan, CP 14080 México, DF (Mexico)

Titanium dioxide nanoparticles (TiO{sub 2} 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 TiO{sub 2} NPs concentration in lung epithelial cells induces carcinogenic characteristics modulated partially by NPs shape. To test our hypothesis we synthesized NPs shaped as belts (TiO{sub 2}-B) using TiO{sub 2} spheres (TiO{sub 2}-SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10 µg/cm{sup 2}) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO{sub 2}-B effect on agglomerates size, cell size and granularity than TiO{sub 2}-SP. Agglomerates size in cell culture medium was 310 nm and 454 nm for TiO{sub 2}-SP and TiO{sub 2}-B, respectively; TiO{sub 2}-SP and TiO{sub 2}-B induced 23% and 70% cell size decrease, respectively, whilst TiO{sub 2}-SP and TiO{sub 2}-B induced 7 and 14-fold of granularity increase. NO{sub x} production was down-regulated (31%) by TiO{sub 2}-SP and up-regulated (70%) by TiO{sub 2}-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 TiO{sub 2}-SP exposed cells while TiO{sub 2}-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 TiO{sub 2}-B had higher proliferative potential than TiO{sub 2}-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. - Graphical abstract: (A) Lung epithelial cells were low exposed (below 10 µg/cm{sup 2}) to titanium dioxide nanoparticles (TiO{sub 2}-NPs) shaped as spheres (TiO{sub 2}-SP) and belts (TiO{sub 2}-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. - Highlights: • 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.

OSTI ID:
22447570
Journal Information:
Environmental Research, Vol. 136; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0013-9351
Country of Publication:
United States
Language:
English