Amorphous Silica Coating Protects Against Iron Oxide Nanoparticle-Induced Cell Transformation and Genotoxicity

Details

• Personal Author:
  Coyle J ; Demokritou P ; Derk R ; Kornberg T ; Rojanasakul L ; Rojanasakul Y ; Stueckle, Todd A.
• Description:
  Iron oxide nanoparticles (IONP) have a wide range of uses in biotechnology, medicine, and transportation. However, very little is known about their potential adverse health effects following human exposure. Some evidence suggests that dissolution of IONP following endocytosis into cells may disrupt iron homeostasis, resulting in genotoxicity and neoplastic-like cellular transformation. Surface modification of IONP, such as an amorphous silica coating, may impact subsequent adverse outcomes by reducing particle dissolution. The main objective of this study was to assess IONP low dose, long term exposure effects, including carcinogenic potential, as well as the utility of an amorphous silica coating in reducing or preventing these outcomes. Human bronchial epithelial cells (Beas2B) were continuously exposed to nFe2O3 or nano-SiO2 coated nFe2O3 (SiO2-nFe2O3) for up to 6.5 months at an occupationally relevant low dose (0.6 microg/cm2 or 2.88 microg/mL) and evaluated over time for indications of neoplastic-like transformation and its underlying mechanism. Transformation was compared to that induced by gas metal arc mild steel welding fumes (GMA-WF), which were recently re-classified as a Group 1 total human carcinogen, and are composed of roughly 80% iron/iron oxide. Our results showed that beginning at four months, nFe2O3-exposed Beas2B underwent neoplastic-like transformation, as indicated by increased cell proliferation and attachment-independent colony formation. These outcomes correlated with nFe2O3 dissolution, increased intracellular iron, and genotoxicity, as well as significant changes in pathways related to DNA damage repair and autophagic processes. nFe2O3-induced transformation also closely matched that GMA-WF induced transformation SiO2-nFe2O3 treatment, however, did not induce any changes in the above parameters. Overall, our results indicated potential carcinogenic risk of nFe2O3 associated with particle dissolution, iron homeostasis disruption, and changes in autophagy and DNA damage repair pathways, which were reduced with an amorphous silica surface coating. This study shows the potential utility of a "safe by design" hazard reduction strategy, to alter particle physicochemical properties based on mode of toxicity to reduce risk. [Description provided by NIOSH]
• Subjects:
  Carcinogens Cells, Cultured Chemistry Environmental Exposure Laboratories Occupational Health Safety Silicon Dioxide Toxicology
• Keywords:
  Amorphous Silica Biological Effects Carcinogenicity Cell Cultures Cell Culture Techniques Cell Proliferation Chemical Properties Coatings DNA Damage Exposure Assessment Exposure Levels Genotoxicity Humans Iron Oxides Laboratory Testing Long Term Exposure Nanoparticles Nanotechnology Nanotoxicology Neoplastic Transformation Physical Properties Silicon Dioxide

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; 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:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20055003
• Citation:
  Toxicologist 2019 Mar; 168(1):285
• CAS Registry Number:
  Iron oxide (Fe2O3) (CAS RN 1309-37-1) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f033adc5f9c684a11ab235c6a0f20d5c007f2ecc9390eb67b486911e9dec7858b74f6fca4990b32fd4983f1b05431e3e3cd8eea471966e5add1ba2cfb411adbe
• Download URL:
  https://stacks.cdc.gov/view/cdc/217407/cdc_217407_DS1.pdf
• File Type:
  [PDF - 867.59 KB ]