Comparative In Vitro Study of Adverse Pro-Neoplastic Potential of Tremolite Asbestos and Its Cleavage Fragments in Human Epithelial (BEAS-2B) and Mesothelial (MET-5A) Cells

Details

• Personal Author:
  Guppi S ; Khaliullin T ; Kisin E ; Shvedova A ; Yanamala N
• Description:
  The fibrous form of tremolite is one of the six recognized types of asbestos. It is known that inhalation of respirable tremolite fibers (TF) can cause asbestosis, lung cancer and both pleural and peritoneal mesothelioma. Tremolite also occurs in a non-fibrous habitat that can be mechanically broken into cleavage fragments (CF) which can meet the criteria for fibers. Despite the considerable amount of work showing that CF are less potent in their damaging effects than asbestos fibers, little data exists on the adverse effects of well-characterized tremolite CF. The present study was designed to reveal the potential pro-carcinogenic manifestations of respirable TF and corresponding CF (with similar median length but different width/aspect ratio) using in vitro models. Sub-chronic exposures of human epithelial (BEAS-2B) and mesothelial (MET-5A) cells - both target cells of the respective lung cancer and malignant mesothelioma - to TF and CF were employed in the current study. Cells were evaluated for the presence of several cancer hallmarks indicating the neoplastic transformation following continuous exposure to the sub-toxic concentration of TF and CF for 5 weeks. TF-exposed cells, both BEAS-2B and MET-5A, revealed a neoplastic-like transformation phenotype characterized by significant increase in proliferation, morphological transformation, invasion/migration and anchorage-independent growth compared to controls. In contrast, no anchorage-independent growth was observed in CF-exposed cells although an increase in proliferation, morphological transformation and migration/invasion was detected albeit at lower intensity compared to TF. Additionally, CF had no impact on apoptosis susceptibility while TF caused increased apoptosis in MET-5A cells and its inhibition in BEAS-2B cells. Both TF and CF induced oxidative DNA damage albeit with a stronger effect in TF-exposed cells. Analysis of inflammatory responses using a cytokines/chemokines clustering approach suggested cell-type specific effects to TF and CF exposures as well as treatment related differences. Overall, our data are compatible with the interpretation that tremolite asbestos fibers demonstrated higher neoplastic transformation potential compared to CF (at the same mass dose) in both epithelial and mesothelial cells. [Description provided by NIOSH]
• Subjects:
  Asbestos Cells, Cultured Hazardous Substances Immune System Inorganic Chemicals Laboratories Lung Lung Diseases Neoplasms Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Asbestos Fibers Asbestosis Cancer Cell Cultures Cell Culture Techniques Cell Death Cell Growth Cell Migration Cell Morphology Cell Proliferation Cell Transformation Cytokines DNA Damage Exposure Assessment Fibers Humans Immune Reaction Inhalation In Vitro Study Laboratory Testing Lung Cancer Mesothelial Cells Mesothelioma Neoplastic Agents Neoplastic Transformation Toxic Materials

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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
• Pages in Document:
  285-286
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20054998
• Citation:
  Toxicologist 2019 Mar; 168(1):285-286
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Tremolite (Ca2[(Mg0.9-1Fe0-0.1)4.5-5Al0-0.5](Si7.5-8Al0-0.5)(OH)2O22) (CAS RN 14567-73-8)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Mining
• 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:e3ad42ffb1a6166d35a1c6adeb71d23d584ecabac57a72e23e65a5083420d4c2e94489aa4a7ba2df802e2ef0d2a3fabac8bcd14a24579ada0c28851f83259690
• Download URL:
  https://stacks.cdc.gov/view/cdc/217402/cdc_217402_DS1.pdf
• File Type:
  [PDF - 901.86 KB ]