Phenotypic anchoring of subchronic carbon nanotube and asbestos exposure to small airway epithelial cells: linking toxicogenomic and neoplastic transformation responses

Details

• Personal Author:
  Castranova, Vincent ; Derk R ; Meighan T ; Mishra A ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L
• Description:
  Recent studies reported that inhaled carbon nanotube (CNT) exposure results in elevated risk for rapid interstitial fibrosis and persistence within exposed tissues. To our knowledge, no study has yet evaluated long-term human health risks associated with chronic pulmonary CNT exposures compared to asbestos, a known lung carcinogen with similar shape. To address this knowledge gap, we conducted subchronic in vitro exposures of dispersed single-walled CNT (D-SWCNT), multiwalled CNT (D-MWCNT) and crocidolite asbestos (ASB) to human small airway epithelial cells (SAEC). Ultrafine carbon black (D-UFCB) and dispersant-only exposed cells (DISP) served as negative controls. SAEC were exposed for 25 weeks to 0.02 microg/cm2 and evaluated for cancer cell phenotype. Next, mRNA samples were subjected to whole genome microarray and rtPCR analyses for toxicogenomic evaluation. Differentially expressed genes were uploaded to Ingenuity Pathway Analysis to identify novel mechanisms promoting neoplastic transformation. Both DSWCNT and D-MWCNT-treated cells exhibited increased proliferation, invasion, anchorage-independent cell growth and angiogenesis compared to other treatments. Hierarchical cluster analysis revealed that D-SWCNT and D-MWCNT cells shared the most similar genome expression profile while ASB, D-UFCB and DISP cells expressed dissimilar genome profiles. Both D-SWCNT and DMWCNT cells expressed significant changes in genes associated with cell death, movement, proliferation and cancer. Top ranked pathway along with western blot analyses identified several altered signaling pathways and transcription factors associated with oncogenesis. Phenotypic anchoring of toxicogenomic response to neoplastic cell transformation following in vitro subchronic nanomaterial exposure can potentially serve to identify novel mechanisms of action and provide human health risk assessment data. [Description provided by NIOSH]
• Subjects:
  Asbestos Environmental Monitoring Genetics Hazardous Substances Immune System 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:
  Asbestos-fibers Cancer Cell-alteration Cell-function Cell-growth Cell-transformation Cellular-uptake Exposure-assessment Exposure-methods Genes Genotoxic-effects Health-hazards Immune-reaction Immune-system In-vitro-study Inhalation-studies Long-term-study Lung-cells Lung-disorders Lung-function Lung-tissue Nanotechnology Oncogenesis Particulates Pulmonary-clearance Pulmonary-system-disorders Respiratory-system-disorders Risk-analysis Risk-factors Toxic-effects Toxic-materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  272-273
• Volume:
  126
• NIOSHTIC Number:
  nn:20040562
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):272-273
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Carbon (CAS RN 7440-44-0) ; Carbon black (CAS RN 1333-86-4) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f970a51d7e99927f17c5d886abcb62f0d48542e0c73a275289c5118dab3570a350942b93ae33ae3a245c86b39554ac66c1efe82505240db16485ba7019444684
• Download URL:
  https://stacks.cdc.gov/view/cdc/193367/cdc_193367_DS1.pdf
• File Type:
  [PDF - 488.21 KB ]