title: Titanium dioxide nanoparticles induce an adaptive inflammatory response and invasion and proliferation of lung epithelial cells in chorioallantoic membrane.
abstract: 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 (10 µg/cm(2)) 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 310 nm and 454 nm 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.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México, Mexico.
authors.forename: Estefany I
authors.initials: EI
authors.lastname: Medina-Reyes
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Déciga-Alcaraz
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México, Mexico; Doctorado en Ciencias en Alimentos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, CP 11340 México, DF, Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Freyre-Fonseca
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México, Mexico.
authors.forename: Norma L
authors.initials: NL
authors.lastname: Delgado-Buenrostro
authors.affiliation: 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.
authors.forename: José O
authors.initials: JO
authors.lastname: Flores-Flores
authors.affiliation: Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, CP 11340 México, DF, Mexico.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Gutiérrez-López
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, San Fernando 22, Tlalpan, CP 14080 México, DF, Mexico.
authors.forename: Yesennia
authors.initials: Y
authors.lastname: Sánchez-Pérez
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, San Fernando 22, Tlalpan, CP 14080 México, DF, Mexico.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: García-Cuéllar
authors.affiliation: Laboratorio 209, Edificio F, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, CP 04510 México, DF, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, CP 54059 Estado de México, Mexico. Electronic address: irasemachirino@gmail.com.
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Chirino
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles; D008854:Microscopy, Electron; D009569:Nitric Oxide / Q000378:metabolism; D014025:Titanium / Q000494:pharmacology*
chemical_list: D016207:Cytokines; C009495:titanium dioxide; D009569:Nitric Oxide; D014025:Titanium
keywords: Cytokine release; Invasion; Nanobelts; Nanospheres; Proliferation lung epithelial cells; Titanium dioxide nanoparticles