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Titanium dioxide nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid pathway.
Zhao-J; Bowman-L; Zhang-X; Ding-M
Toxicologist 2008 Mar; 102(1):72
Titanium dioxide (TiO2) nanoparticles are manufactured worldwide in large quantities for use in a wide range of applications. Early studies have shown that the pathogenic effects of TiO2 depend on particle size. However, the molecular mechanisms involved in TiO2-induced cytotoxicity and carcinogenicity have not been clearly defined. The present study investigates TiO2 nanoparticle-induced cytotoxicity and the mechanism involved in this process in a mouse epidermal cell line, JB6 cells. For comparison, an equivalent concentration range of TiO2 fine particles was used in this study. We found that same mass of TiO2 nanoparticles exhibited stronger cytotoxity than that induced by TiO2 fine particles tested using the MTT assay. Moreover, a dual fluorescence dye assay indicated that TiO2 induced cell death through apoptosis in a time- and dose-dependent manner. Fluorescence staining using YO-PRO-1 or fluorescein isothiocyanate (FITC)-dextran dye demonstrated that TiO2 nanoparticles induced remarkable mitochondrial and lysosomal membrane injury. These results suggest the involvement of mitochondria and lysosomes in apoptosis induced by TiO2 nanoparticles. The signaling pathway involved in TiO2 particle- induced apoptosis was also investigated. Western-blot analysis showed an activation of caspase-8, caspase-3, Bid and Bax, and a decrease of Bcl-2, in JB6 cells treated with TiO2 particles. In conclusion, we have determined that caspase-8/Bid signaling may play a major role in TiO2-induced apoptosis and that mitochondrial and lysosomal injury may also be involved. Unraveling the complex mechanisms associated with these events may provide insights into TiO2-induced pathogenicity.
Occupational-exposure; Metal-compounds; Metal-dusts; Metal-fumes; Metal-industry; Metal-oxides; Metal-poisoning; Metallic-dusts; Metallic-fumes; Metallic-poisons; Toxic-vapors; Toxic-effects; Toxicopathology; Pathogenesis; Pathogenicity; Particle-aerodynamics; Particulate-dust; Particulates; Cytotoxic-effects; Carcinogens; Skin-disorders; Skin; Time-weighted-average-exposure; Cell-biology; Cell-transformation; Cellular-reactions; Cell-alteration; Nanotechnology
Issue of Publication
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington