Iron Oxide Nanoparticle-Induced Neoplastic-Like Cell Transformation In Vitro Is Reduced with a Protective Amorphous Silica Coating

Details

• Personal Author:
  Coyle J ; Demokritou P ; Derk R ; Kornberg TG ; Rojanasakul LW ; Rojanasakul Y ; Stueckle, Todd A.
• Description:
  Iron oxide nanoparticles (IONP) have recently surged in production and use in a wide variety of biomedical and environmental applications. However, their potential long-term health effects, including carcinogenesis, are unknown. Limited research suggests IONP can induce genotoxicity and neoplastic transformation associated with particle dissolution and release of free iron ions. "Safe by design" strategies involve the modification of particle physicochemical properties to affect subsequent adverse outcomes, such as an amorphous silica coating to reduce IONP dissolution and direct interaction with cells. We hypothesized that long-term exposure to a specific IONP (nFe2O3) would induce neoplastic-like cell transformation, which could be prevented with an amorphous silica coating (SiO2-nFe2O3). To test this hypothesis, human bronchial epithelial cells (Beas-2B) were continuously exposed to a 0.6 ug/cm2 administered a dose of nFe2O3 (approximately 0.58 ug/cm2 delivered dose), SiO2-nFe2O3 (approximately 0.55 ug/cm2 delivered dose), or gas metal arc mild steel welding fumes (GMA-MS, approximately 0.58 ug/cm2 delivered dose) for 6.5 months. GMA-MS are composed of roughly 80% iron/iron oxide and were recently classified as a total human carcinogen. Our results showed that low-dose/long-term in vitro exposure to nFe2O3 induced a time-dependent neoplastic-like cell transformation, as indicated by increased cell proliferation and attachment-independent colony formation, which closely matched that induced by GMA-MS. This transformation was associated with decreases in intracellular iron, minimal changes in reactive oxygen species (ROS) production, and the induction of double-stranded DNA damage. An amorphous silica-coated but otherwise identical particle (SiO2-nFe2O3) did not induce this neoplastic-like phenotype or changes in the parameters mentioned above. Overall, the presented data suggest the carcinogenic potential of long-term nFe2O3 exposure and the utility of an amorphous silica coating in a "safe by design" hazard reduction strategy, within the context of a physiologically relevant exposure scenario (low-dose/long-term), with model validation using GMA-MS. [Description provided by NIOSH]
• Subjects:
  Carcinogens Chemistry Environmental Exposure Ferrous Compounds Hazardous Substances Lung Occupational Health Respiratory System Safety Toxicology Welding

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• Keywords:
  Amorphous Silica Cell Proliferation Cell Transformation Chemical Properties Coatings Design Standards DNA Damage Dose Response Exposure Assessment Exposure Levels Genotoxicity Hazard Controls Health Hazards In Vitro Study Iron Iron Oxides Metal Fumes Metal Oxides Nanoparticles Nanotechnology Nanotoxicology Neoplastic Transformation Oxidative Stress Physical Properties Reactive Oxygen Species ROS Toxic Effects Welding Fumes

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• ISSN:
  0893-228X
• 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
• Volume:
  32
• Issue:
  12
• NIOSHTIC Number:
  nn:20057888
• Citation:
  Chem Res Toxicol 2019 Dec; 32(12):382-2397
• Contact Point Address:
  Tiffany G. Kornberg, Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, United States
• Email:
  tkornberg@cdc.gov
• CAS Registry Number:
  Iron (CAS RN 7439-89-6) ; Iron oxide (Fe2O3) (CAS RN 1309-37-1) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Chemical Research in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bbb29ddf325a4320fa8efdda613d260698e02af1c60c8bb4f9a22fc0a9f18d00f07118e882359613ec427a5268e15bb3093b88ca18d593cdb38b87823a6d5153
• Download URL:
  https://stacks.cdc.gov/view/cdc/215094/cdc_215094_DS1.pdf
• File Type:
  [PDF - 13.09 MB ]