Nano-TiO2-Induced Apoptosis by Oxidative Stress-Mediated DNA Damage and Activation of p53 in Human Embryonic Kidney Cells

Abstract

The aim of the present study is to explore the mechanism of cytotoxic and genotoxic effects of TiO(2) nanoparticles on human embryonic kidney (HEK-293) cells. Toxicity was evaluated using changes in various cellular parameters of HEK-293 cells like morphology, viability, metabolic activity, oxidative stress and apoptosis. Oxidative stress was measured by the level of reactive oxygen species (ROS), lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase. Apoptosis induced by nano-TiO(2) was characterized by PI staining and DNA ladder assay. Furthermore, apoptotic proteins such as p53 and Bax were analysed by western blot. Our results indicate that nano-TiO(2) induces cytotoxicity in a time- and dose-dependent manner. Oxidative stress and apoptosis were induced by exposure to nano-TiO(2). Moreover, the expression of p53, Bax and caspase-3 were increased in a dose-dependent pattern. In conclusion, ROS-mediated oxidative stress, the activation of p53, Bax, caspase-3 and oxidative DNA damage are involved in the mechanistic pathways of nano-TiO(2)-induced apoptosis in HEK-293 cells.

Assessment of cytotoxicity and oxidative stress induced by titanium oxide nanoparticles on Chinook salmon cells

“…Oxidative stress is induced by the nanoparticles resulting in the production of free radicals and leading to the alteration in the antioxidants. Some of the earlier researchers have shown that TiO 2 NPs induced oxidative stress which is mediated by ROS in some of the cell lines which include human lung fibroblasts (Bhattacharya et al 2009), human hepatoma HepG2 cells (Liu et al 2010), PC12 cells (Petkovic et al 2011), human HaCaT keratinocytes (Jaeger et al 2012), human embryonic kidney cells (Meena et al 2012) and mouse macrophages (Zhang et al 2012). The oxidative stress caused by TiO 2 NPs is generally due to the production of reactive oxygen species (ROS).…”

Three human cell types respond to multi-walled carbon nanotubes and titanium dioxide nanobelts with cell-specific transcriptomic and proteomic expression patterns

“…However, the downstream cellular consequences for activation of this pathway are multi-fold and may result in cell cycle arrest, DNA repair or cell death. TiO 2 NPs have previously been associated with p53-mediated genotoxicity and genetic instability as measured by increased apoptosis, accumulation of p53 and induced y-H2AX foci and 8-hydroxy-2’-deoxyguanosine, which are indicative of DNA double strand breaks and oxidative DNA damage, respectively (Kong et al 2008; Meena et al 2012; Trouiller et al 2009). TiO 2 NPs were also found to be genotoxic in HEPG2 cells through upregulation of DNA damage responsive genes (p53, MDM2, GADD45 and p21) resulting in DNA strand breaks and increased intracellular reactive oxygen species (Petkovic et al 2011).…”

Nanopesticides – Light or dark side of the force?

“…Badania in vitro na liniach komórko-wych oraz badania na modelach zwierzęcych wskazują, że nanocząstki indukują w komórkach nadmierną produkcję reaktywnych form tlenu (reactive oxygen species -ROS), co prowadzi do stresu oksydacyjnego. Ponadto wywołują proces zapalny i działają szkodliwie na materiał genetyczny, prowadząc do apoptozy i wywołując efekt cytotoksyczny [22][23][24][25]. Wszystkie te czynniki nie pozostają bez wpływu na ludzki organizm, gdyż są związane z takimi procesami jak kancerogeneza czy neurodegeneracja.…”