title: 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.
authors.affiliation: School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Ramovatar
authors.initials: R
authors.lastname: Meena
authors.forename: Madhu
authors.initials: M
authors.lastname: Rani
authors.forename: Ruchita
authors.initials: R
authors.lastname: Pal
authors.forename: Paulraj
authors.initials: P
authors.lastname: Rajamani
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D013997:Time Factors; D014025:Titanium / Q000737:chemistry* / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D003603:Cytotoxins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C009495:titanium dioxide; D014025:Titanium; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3