Evaluation of tumorigenic potential of CeO2 and Fe2O3 engineered nanoparticles by a human cell in vitro screening model

Details

• Personal Author:
  Davidson DC ; Deloid G ; Demokritou P ; Derk R ; Kornberg TG ; Luanpitpong S ; Pirela SV ; Rojanasakul Y ; Schwegler-Berry D ; Stueckle, Todd A. ; Wang L
• Description:
  With rapid development of novel nanotechnologies that incorporate engineered nanomaterials (ENMs) into manufactured products, long-term, low dose ENM exposures in occupational settings is forecasted to occur with potential adverse outcomes to human health. Few ENM human health risk assessment efforts have evaluated tumorigenic potential of ENMs. Two widely used nano-scaled metal oxides (NMOs), cerium oxide (nCeO2) and ferric oxide (nFe2O3) were screened in the current study using a sub-chronic exposure to human primary small airway epithelial cells (pSAECs).Multi-walled carbon nanotubes (MWCNT), a known ENM tumor promoter, was used as a positive control. Advanced dosimetry modeling was employed to ascertain delivered vs. administered dose in all experimental conditions. Cells were continuously exposed in vitro to deposited doses of 0.18 microg/cm2 or 0.06 microg/cm2 of each NMO or MWCNT, respectively, over 6 and 10 weeks, while saline- and dispersant- only exposed cells served as passage controls. Cells were evaluated for changes in several cancer hallmarks, as evidence for neoplastic transformation. At 10 weeks, nFe2O3- and MWCNT-exposed cells displayed a neoplastic-like transformation phenotype with significant increased proliferation, invasion, and soft agar colony formation ability compared to controls. nCeO2-exposed cells showed increased proliferative capacity only. Isolated nFe2O3 and MWCNT clones from soft agar colonies retained their respective neoplastic-like phenotypes. Interestingly, nFe2O3-exposed cells, but not MWCNT cells, exhibited immortalization and retention of the neoplastic phenotype after repeated passaging (12-30 passages) and after cryofreeze and thawing. High content screening and protein expression analyses in acute exposure ENM studies vs. immortalized nFe2O3 cells, and isolated ENM clones, suggested that long-term exposure to the tested ENMs resulted in iron homeostasis disruption, an increased labile ferrous iron pool, and subsequent reactive oxygen species generation, a well-established tumorigenesis promotor. In conclusion, sub-chronic exposure to human pSAECs with a cancer hallmark screening battery identified nFe2O3 as possessing neoplastic-like transformation ability, thus suggesting that further tumorigenic assessment is needed. [Description provided by NIOSH]
• Subjects:
  Carcinogens Cells, Cultured Lung Neoplasms Occupational Health Radiation Dosimeters Respiratory System Safety
• Keywords:
  Author Keywords: Nanomaterial Cancer Cell Cultures Cell Proliferation Cell Transformation Cerium Oxides Dosimetry Exposure Assessment In Vitro Study Iron Homeostasis Iron Oxides Long Term Exposure Lung Cells Medical Screening Metal Oxides Multi-walled Carbon Nanotubes MWCNT Nano-scaled Metal Oxide Nanoscale Nanotechnology Nanotubes Neoplastic Agents Neoplastic Transformation Reactive Oxygen Species Risk Assessment ROS Tumorigenesis

  More +
• ISSN:
  2452-0748
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; 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:
  39-54
• Volume:
  6
• NIOSHTIC Number:
  nn:20049024
• Citation:
  NanoImpact 2017 Apr; 6:39-54
• Contact Point Address:
  Todd A. Stueckle, HELD, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, United States
• Email:
  tstueckle@cdc.gov
• CAS Registry Number:
  Ceria (CAS RN 1306-38-3) ; Iron oxide (Fe2O3) (CAS RN 1309-37-1)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  NanoImpact
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a2e45c479597826d4a503ddb9bee5d044a1bf349a16075f2c7e51728833ba7c4d967f404a06f1d9607c43f9ee2d4090825313414347665eac8f38f818ed1b120
• Download URL:
  https://stacks.cdc.gov/view/cdc/203617/cdc_203617_DS1.pdf
• File Type:
  [PDF - 2.20 MB ]