Dose- and time-dependent assessment of human mesothelial cell neoplastic transformation potential after functionalized MWCNT exposure

Details

• Personal Author:
  Davidson DC ; Derk R ; Gracheck P ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L ; Wu N
• Description:
  MWCNTs are characterized by asbestos-like fiber morphology, large surface area and surface chemistries. Exposure results in pulmonary fibrosis, biopersistence, extrapulmonary transport and promotion of adenocarcinoma and sarcomatous mesothelioma. As MWCNTs become widely used, elevated cancer risk in pleural mesothelium following inhalation exposure is a concern. Long-term exposure risks resulting from surface functionalization of MWCNT on pleural mesothelioma potential is largely unknown, but critically needed. We hypothesized that the effect of MWCNT surface functionalization on human mesothelial cell neoplastic transformation potential depends on dose and duration of exposure. Human immortalized mesothelial cells were continuously exposed to fully characterized prepared (pMWCNT), carboxylated (MW-COOH) and aminated (MW-NH2) for 6 months (M) at 0.002 and 0.02 microg/cm2 which are relevant to animal exposure doses. Saline (SAL), dispersant (DISP) and crocidolite asbestos (ASB) exposed cells served as controls. At regular intervals during exposure, each treatment group was assessed for several cancer hallmarks. Results indicated that 1) low dose MW-COOH and MW-NH2 exposure caused significant increases in cell proliferation compared to controls starting at 1 M and persisted over 6 M exposure. High dose exposure alleviated this effect. 2) pMWCNT, MW-NH2 and ASB cells exhibited significantly greater numbers of soft agar colonies at both doses compared to controls starting at 4 M. Low dose fMWCNT treatment resulted in a more potent colony-forming effect than high dose, while both doses of asbestos possessed an equipotent effect. 3) Only MW-COOH cells at 6 M exhibited a significant increase in invasion ability compared to all treatments. Lastly, ASB cells displayed the largest transformation frequency while all fMWNCT exposures caused moderate effect. In summary, exposure dose, duration and type of surface functionalization determine MWCNT neoplastic transformation potential in pleural mesothelial cells. [Description provided by NIOSH]
• Subjects:
  Asbestos Chemistry Environmental Monitoring Inorganic Chemicals Laboratories Lung Lung Diseases Neoplasms Nervous System Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Adenocarcinomas Asbestos-fibers Biotransformation Carbon-compounds Cell-transformation Cellular-reactions Chemical-properties Dose-response Exposure-assessment Humans Laboratory-testing Lung-cancer Lung-cells Lung-fibrosis Mesothelial-cells Morphology Nanotechnology Neoplastic-transformation Pleural-cavity Pulmonary-function Pulmonary-system-disorders Sarcomagenicity

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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
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045928
• Citation:
  Toxicologist 2015 Mar; 144(1):266
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Carbon (CAS RN 7440-44-0) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0fbc7024b9bc9f7c84bbf5441a9973b5b3bfbaf6e41f39ddf50066eb751453f280222d585642bbd8d6941c80c5313950d262d717def2d645c5a6fa1b466e907f
• Download URL:
  https://stacks.cdc.gov/view/cdc/201155/cdc_201155_DS1.pdf
• File Type:
  [PDF - 218.38 KB ]