Induction of DNA Double-Strand Breaks by Asbestos, Silica and Titanium Dioxide: Do They Provide an Early Predictive Marker of Carcinogenic Potential

Details

• Personal Author:
  Castranova, Vincent ; Msiska Z ; Pacurari M ; Vallyathan V
• Description:
  Rationale: Induction of DNA double strand breaks (DSBs) is a very rapid response to DNA damage that occurs in cells subjected to many types of toxic insults, such as radiation, exposure to toxic substances and other stresses. The inability to repair these breaks can lead to tumorigenesis. Methods: One of the earliest responses to DNA DSBs is the phosphorylation of a histone, H2AX, at serine 139, yielding a focal product (g-H2AX) that can be detected by a fluorescent antibody. In this study we compared the induction of DSBs in normal lung cells (SAE) and cancer cells (A549) after exposure to crocidolite asbestos (a known carcinogen), silica (a suspected carcinogen), or titanium dioxide (an inert particle) recently alleged to be carcinogenic in animals. Results: The results indicate that asbestos induced greater DNA DSBs than silica and TiO2 regardless of cell type. DNA DSBs due to asbestos were higher in normal cells than in the cancer cells. In contrast, silica and TiO2 induced higher DNA DSBs in cancer cells than in normal cells. The production of reactive oxygen species (ROS) was also found to be highest in cells exposed to asbestos followed in potency by silica and TiO2. The generation of ROS was higher in normal cells than in cancer cells. Apoptosis, as measured by caspase 3/7 activity, was highest in asbestos-exposed cells followed in potency by TiO2 and silica. Cell viability assays indicate that asbestos caused the greatest cytotoxicity in both cell types. Conclusions: The results of this study indicate that asbestos has a greater carcinogenic potential than silica and TiO2 to exhibit by its ability to produce sustained genomic instability. [Description provided by NIOSH]
• Subjects:
  Cytotoxins Environmental Monitoring Epidemiology Hazardous Substances Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Cancer-rates Cell-damage Cytotoxic-effects Exposure-assessment Exposure-levels Exposure-methods Lung-cells Lung-disease Lung-disorders Pulmonary-disorders Pulmonary-system-disorders Quantitative-analysis Respiratory-system-disorders Statistical-analysis Toxic-effects

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• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  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:
  179
• NIOSHTIC Number:
  nn:20036373
• Citation:
  Am J Respir Crit Care Med 2009 Apr; 179(Meeting Abstracts):A5890
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Crocidolite asbestos (CAS RN 12001-28-4) ; Silica (CAS RN 7631-86-9) ; Titania (CAS RN 13463-67-7)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Services
• Peer Reviewed:
  False
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Meeting Abstracts
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:25ea3ef92b8e40701d948a8e5d8a789286753b128a9a8d5025a8b8993384233c15c3c9c567270bb767a0319e35c09bde1d73a6ab66e754fa92664b699cba99f5
• Download URL:
  https://stacks.cdc.gov/view/cdc/187831/cdc_187831_DS1.pdf
• File Type:
  [PDF - 182.61 KB ]