Carbon nanotubes induce apoptosis resistance through FLICE-inhibitory protein

Details

• Personal Author:
  Lu Y ; Luanpitpong S ; Pongrakhananon V ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L
• Description:
  Our studies have shown that chronic exposure to single-walled carbon nanotubes (SWCNT) induces apoptosis resistance and malignant transformation of human lung epithelial cells. Since resistance to apoptosis is a foundation of neoplastic evolution and selection of malignant transformed phenotype, we investigated the apoptosis pathway underlying the resistance its mechanisms to aid the understanding of SWCNT-induced carcinogenesis. As compared to passage-matched control cells, SWCNT-transformed BEAS-2B cells exhibited resistance to apoptosis induced by death ligands, e.g., tumor necrosis factor-a and Fas ligand, but not by inducers of mitochondria-mediated apoptosis, e.g., antimycin A and cisplatin, suggesting death receptor pathway as the primary pathway of defective apoptosis in SWCNT-transformed cells. The results were confirmed using caspase specific inhibitors and caspase activity assays. DNA microarray and Western blot analyses of key apoptosis-regulatory proteins in the transformed cells revealed FLICE-inhibitory protein (FLIP) as an important target of regulation by SWCNT. Overexpression of FLIP increased apoptosis resistance of the cells, whereas RNAi knockdown of FLIP reversed the apoptosis resistance of cells in response to death ligands. Together, our study demonstrated a novel mechanism of apoptosis resistance induced by chronic exposure to SWCNT in human lung epithelial cells and identified FLIP as a key regulator of apoptosis avoidance that contributes to the development of malignant transformed phenotype. [Description provided by NIOSH]
• Subjects:
  Carcinogens Environmental Monitoring Irritants Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Biological-effects Cancer Carcinogenicity Cell-biology Cell-function Cell-metabolism Cell-morphology Cell-transformation Cellular-reactions Exposure-assessment Inhalation-studies Laboratory-testing Lung-cancer Lung-cells Lung-disease Lung-disorders Lung-irritants Nanotechnology Physiological-effects Pulmonary-function Pulmonary-system Pulmonary-system-disorders Quantitative-analysis Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders Risk-analysis Risk-factors Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  District of Columbia ; 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:
  120
• NIOSHTIC Number:
  nn:20038517
• Citation:
  Toxicologist 2011 Mar; 120(Suppl 2):254
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Cisplatin (CAS RN 15663-27-1)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
• Supplement:
  2
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c85a1755e6aeec95e2cb93f26ff319d6520356dd63acd532b021771551206861680f18622f46f923e845d617f7e1e2558a51ae7fa0cfc48d813dea2fad832ffa
• Download URL:
  https://stacks.cdc.gov/view/cdc/192203/cdc_192203_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]