Neoplastic Transformation and Changes in Transcriptome Induced by Riebeckite/Tremolite Asbestiform and Nonasbestiform Elongate Mineral Particles in Human Mesothelial Cells

Details

• Personal Author:
  Guppi S ; Kagan VE ; Khaliullin TO ; Kisin ER ; Shrivastava IH ; Shvedova AA ; Yanamala N
• Description:
  Inhalation of respirable amphibole asbestiform elongate mineral particles (EMPs) can cause asbestosis, lung cancer as well as pleural and peritoneal mesothelioma. Amphiboles can also occur in a non-asbestiform habit that can be mechanically broken into so-called cleavage fragments (CF) which can meet the mineralogical/ regulatory criteria for fibers. While the health effects of riebeckite (RF) and tremolite (TF) asbestos are well documented, there is uncertainty regarding the toxicity of their CF. In this work, we evaluated several neoplastic-like transformation hallmarks and changes in the gene expression profiles in immortalized human mesothelial (MET-5A) cells after continuous long-term exposure to sub-toxic (2.5 µg/cm2) concentrations of RF, TF and corresponding CF. TF- and RF-exposed MET-5A cells acquired a neoplastic-like transformed phenotype characterized by significant morphological changes accompanied by an increase in anchorage-independent growth (AIG), invasion/migration and proliferation. No AIG was observed in cells treated with riebeckite and tremolite CF, although an increase in migration and invasion parameters were detected. Hierarchical cluster analysis and ingenuity pathway analysis revealed altered gene expression profiles common for asbestos fibers and corresponding cleavage fragments. RF and riebeckite CF had enriched pathways pertaining to cellular development, cellular growth, proliferation, as well as cancer and organismal injury disease categories. RF exposure alone induced pronounced upregulation of genes governing cell-to-cell signaling and interactions related to cell death and survival. Genes regulated by TF and its CF were also associated with cell-to-cell signaling and interactions, cell development, growth and proliferation, whereas only TF caused enrichment of immune cell trafficking and cancer-related pathways. In conclusion, at equal mass-based doses, asbestiform amphiboles had greater potential for the neoplastic transformation of mesothelial cells than corresponding CF. Discrete mineral-specific responses were also induced in MET-5A cells by non-asbestiform EMPs. [Description provided by NIOSH]
• Subjects:
  Asbestos Environmental Exposure Hazardous Substances Inorganic Chemicals Lung Lung Diseases Neoplasms Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Asbestosis; Lung cancer; Mesothelioma; Fibers; Health effects; Asbestos; Toxins; Gene expression; Exposure levels; Risk factors; Cellular function; Cancer
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  New Jersey ; Ohio ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; Pennsylvania ; 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:
  186
• NIOSHTIC Number:
  nn:20064933
• Citation:
  Toxicologist 2022 Mar; 186(S1):221
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4)
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Mining
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 61st Annual Meeting & ToxExpo, March 27-31, 2022, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2a9b9ee95de2fc037150157aa25993354fca19163c453ed05a0bc03e68efbd1a9db6a40723a6d855bc28ccd69522bde9a3b03f768baa8e539bc9cdc515192fa4
• Download URL:
  https://stacks.cdc.gov/view/cdc/248924/cdc_248924_DS1.pdf
• File Type:
  [PDF - 242.12 KB ]