Titanium Dioxide Nanoparticle Induced AP-1 Activation via ERKs and p38 Kinase

Details

• Personal Author:
  Aldinger, Jeffrey A. ; Barber T ; Ding M ; Leonard, Stephanie
• Description:
  Titanium dioxide (TiO2) is a white mineral used in the manufacturing of paint, paper, plastics, sun tan lotion, and other products. Recent studies indicated that TiO2 nanoparticles cause chronic inflammation and lung tumor formation in rats. It is believed that the toxicity and carcinogenesis of TiO2 is associated with particle size. Since activator protein-1 (AP-1) is known to play an important role in the induction of neoplastic transformation and regulation of multiple genes involved in cell proliferation and inflammation, we investigate the potency of TiO2 nanoparticles on reactive oxygen species (ROS) generation and AP-1 signaling in a mouse epithermal cell line, JB6 cells. Incubation of JB6 cells with TiO2 nanoparticles resulted in a dose dependent generation of ·OH radicals. TiO2 nanoparticles caused a 3-fold increase in AP-1 activity in the cells. The induction of AP-1 activity in cultured cells was dose-dependent. The signal transduction pathways for AP-1 activation were also investigated and the results demonstrate that TiO2 stimulates mitogen-activated protein kinase (MAPK) family members, including extracellular signal-regulated protein kinases (ERKs), p38 kinase, and C-Jun N-terminal kinase (JNKs). Inhibition of ERKs, p38 kinase, but not JNKs with specific inhibitors SB203580, PD98059, and SP 600125, inhibited TiO2 nanoparticles-induced AP-1 activation, respectively. These findings demonstrate that TiO2 nanoparticles stimulated the generation of ·OH radicals and induces AP-1 activation, which may be mediated through p38 kinase and ERKs pathways. [Description provided by NIOSH]
• Subjects:
  Carcinogens Cells, Cultured Environmental Exposure Enzymes Hazardous Substances Immune System Laboratories Lung Neoplasms Occupational Health Particulate Matter Respiratory System Safety Titanium Toxicology

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• Keywords:
  Carcinogenesis Cell Cultures Cell Culture Techniques Cell Proliferation Cell Signaling Chronic Inflammation Dose Response Enzyme Activity Enzyme Inhibitors Exposure Assessment Exposure Levels Gene Regulation Hydroxides Immune Reaction Laboratory Animals Laboratory Testing Nanoparticles Nanotechnology Nanotoxicology Neoplastic Transformation Particle Size Proteins Reactive Oxygen Species ROS Signaling Pathways Titanium Dioxide Toxic Materials Tumors

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20055001
• Citation:
  Toxicologist 2019 Mar; 168(1):284
• CAS Registry Number:
  Titania (CAS RN 13463-67-7)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9980335d51aeaf58a8694fffa38917756f165bb82399871747ba9a12061693820d2284faf2ff8867e35f16d5095cd1270a70fb746164ae7e7727c8c2e9d0b151
• Download URL:
  https://stacks.cdc.gov/view/cdc/217405/cdc_217405_DS1.pdf
• File Type:
  [PDF - 867.96 KB ]