Inhaled Ozone Induces DNA-DNA Cross-Linking in Exposed Rat Lung

Details

• Personal Author:
  Baker K ; Bowser DH ; Cohen MD ; Salnikow K ; Schlesinger RB ; Sisco M ; Zelikoff JT
• Description:
  Ozone (03) exposure has been shown to cause a variety of debilitating respiratory disturbances including possibly cancer. The prevalence of 03 as the dominant oxidant of world-wide photochemical smog, its occupational utilization and its application as a direct or adjunct therapy for treatment of various diseases make it a global human health concern. As the major target of 03 inhalation, lung tissue has been reported to sustain both cytotoxic and genotoxic damage as well as cause neo-plastic transformation in vivo and in vitro. However, whether exposure to 03 can cause DNA-DNA cross-linking is as of yet unknown. Thus, this study examined whether long-term /chronic 03 exposure could induce pulmonary genomic DNA-DNA cross-linking. Adult male rats were exposed nose-only, 5h/d, 5d/wk for 4, 8, 12, 24 and 48 wks to filtered air or one of three different 03 concentrations (i.e., 0.1, 0.3 and 0.6 ppm). Rats were sacrificed 3d after the cessation of exposure lungs were removed and flash frozen and DNA-DNA cross-links determined by gel electrophoresis. Effects of 03 appeared to be time- and dose- dependent. Animals exposed to 0.3 ppm 03 for 8 wks demonstrated significantly elevated levels of cross-linking compared to controls and 0.1 and 0.6 ppm 03 exposed rats; exposure for twelve wks to 0.3 and 0.6 ppm 03 resulted in greater DNA cross-linking than controls or the 0.1 ppm 03 group; inhalation exposure of rats for twenty four wks to all three concentrations caused a significant dose-related increase in cross-linking; at 48 wks rats exposed to 0.3 ppm 03 demonstrated significantly elevated levels of cross-linking (compared to air controls). These findings suggest that long-term inhalation of 03 can produce genotoxic events that could be associated with neoplastic changes. [Description provided by NIOSH]
• Subjects:
  Animals Cytotoxins Environmental Exposure Hazardous Substances Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Animal Studies Cancer Cytotoxicity Exposure Levels Genotoxic Effects Health Hazards In Vitro Studies In Vivo Studies Laboratory Animals Lung Tissue Pulmonary System Disorders Respiratory System Disorders

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• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; New York ; OSHA Region 2 ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  78
• NIOSHTIC Number:
  nn:20025063
• Citation:
  Toxicologist 2004 Mar; 78(S-1):143
• CAS Registry Number:
  Ozone (CAS RN 10028-15-6)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland
• Supplement:
  S-1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:717f7eef9fb5ed2c56255d492bd5a5a44fea6f60dbbb00bda95346ab992edec8c55ebccab08e0b42c8905c33d8e9d74ff950f9d94e4c47b137eb753b25a34f38
• Download URL:
  https://stacks.cdc.gov/view/cdc/196569/cdc_196569_DS1.pdf
• File Type:
  [PDF - 88.13 KB ]