Iron Oxide Nanoparticle-Induced Changes in Epithelial-to-Mesenchymal Transition and Cellular Transformation May Be Ablated with Amorphous Silica Coating

Details

• Personal Author:
  Demokritou P ; Derk R ; Kornberg TG ; Rojanasakul LW ; Rojanasakul Y ; Stueckle, Todd A.
• Description:
  Iron oxide nanoparticles (IONP) are emerging as unique components of drug delivery systems, imaging techniques, environmental catalysts, components of thermoplastics, and more. Workers in IONP manufacturing facilities are known to be exposed to low doses of these particles over long periods of time. However, very few studies have assessed potential adverse outcomes following this type of occupationally relevant exposure. Our previous research suggests that IONPs may induce a neoplastic-like cellular transformation, likely due to particle dissolution, release of free iron ions, and disruption of iron homeostasis. Other studies suggest that an amorphous silica coating may reduce particle dissolution, thereby reducing subsequent adverse outcomes. We hypothesized that an amorphous silica coating (SiO2-nFe2O3) would ablate iron homeostasis disruption induced by an uncoated but otherwise identical particle (nFe2O3), and would therefore reduce nFe2O3-induced subsequent neoplastic-like cellular transformation and oxidative stress. To test this hypothesis, we used an occupationally relevant low dose/long term exposure in vitro model system which utilized a normal human bronchial epithelial cell line (Beas2B). The cells were continuously treated at 0.6 microg/cm2 to SiO2-nFe2O3 or nFe2O3 for six months, and were evaluated for oxidative stress, epithelial to mesenchymal transition (EMT), and neoplastic-like cellular transformation throughout. Our results show an nFe2O3 induced time dependent cellular transformation, evaluated by colony formation assay, beginning at about 3 months post exposure. nFe2O3 transformed cells also possess a pro-inflammatory phenotype, including increased oxidative stress, EMT marker proteins, and changes in select inflammatory cytokines. These outcomes are not seen with SiO2-nFe2O3 or non-treated control cells. Overall, our results show that nFe2O3-induced iron homeostasis disruption, oxidative stress, and cellular transformation may be significantly reduced with an amorphous silica coating. This may suggest this coating as being a useful component of safe by design hazard reduction strategy. [Description provided by NIOSH]
• Subjects:
  Biomarkers Hazardous Substances Immune System Lung Manufacturing And Industrial Facilities Occupational Exposure Occupational Health Respiratory System Safety Toxicology
• Keywords:
  Amorphous Silica Analytical Models Cell Transformation Coatings Cytokines Exposure Assessment Hazard Controls Health Effects Health Hazards Immune Reaction In Vitro Study Iron Oxides Manufacturing Nanoparticles Nanotechnology Nanotoxicology Neoplastic Transformation Occupational Exposure Oxidative Stress Proteins Toxic Effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 6 ; Texas ; 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:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051243
• Citation:
  Toxicologist 2018 Mar; 162(1):403
• CAS Registry Number:
  Iron oxide (Fe2O3) (CAS RN 1309-37-1) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5ff1b0abfa6457f102cf62f7baedd85b9b831d84ead523eeb75d22efe10d805d74c6ec610a751f667d06288160b128f114454c2ac7f429b77f754626246dd6dc
• Download URL:
  https://stacks.cdc.gov/view/cdc/211309/cdc_211309_DS1.pdf
• File Type:
  [PDF - 833.76 KB ]