Titanium Dioxide Nanoparticles Induce JB6 Cell Apoptosis Through Activation of the Caspase-8/Bid Pathway

Details

• Personal Author:
  Bowman L ; Ding M ; Zhang X ; Zhao J
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Carcinogens Cytotoxins Dust Hazardous Substances Metals Metal Workers Occupational Exposure Occupational Health Particulate Matter Poisoning Safety Skin Skin Diseases Toxicology

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• Keywords:
  Cell-alteration Cell-biology Cell-transformation Cellular-reactions Cytotoxic-effects Metal-compounds Metal-dusts Metal-fumes Metal-industry Metal-oxides Metal-poisoning Metallic-dusts Metallic-fumes Metallic-poisons Nanotechnology Occupational-exposure Particle-aerodynamics Particulate-dust Particulates Pathogenesis Pathogenicity Skin-disorders Time-weighted-average-exposure Toxic-effects Toxic-vapors Toxicopathology

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  72
• Volume:
  102
• Issue:
  1
• NIOSHTIC Number:
  nn:20033546
• Citation:
  Toxicologist 2008 Mar; 102(1):72
• CAS Registry Number:
  Titania (CAS RN 13463-67-7)
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ae7c0c870923b8fe9bbef02d1c15367b7e184f057dfa3c3af50eebb5bcdf3c41efe309805f84945364d762d4017a5afaf5f8439b4bc395e6e229fc1ff791301e
• Download URL:
  https://stacks.cdc.gov/view/cdc/189080/cdc_189080_DS1.pdf
• File Type:
  [PDF - 7.71 MB ]