Inhaled ozone induces DNA-DNA cross-linking in exposed rat lung.
Bowser-DH; Sisco-M; Baker-K; Salnikow-K; Schlesinger-RB; Cohen-MD; Zelikoff-JT
Toxicologist 2004 Mar; 78(S-1):143
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.
Exposure-levels; Laboratory-animals; Animals; Animal-studies; Respiratory-system-disorders; Pulmonary-system-disorders; Cancer; Health-hazards; Lung-tissue; Cytotoxicity; Genotoxic-effects; In-vitro-studies; In-vivo-studies
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland