OZONE-INDUCED DNA SINGLE-STRAND BREAKS IN HUMAN AND GUINEA-PIG LUNG-CELLS IN-VIVO

Ozone (O-3) has been postulated to induce DNA damage and has been show n to be mildly tumorigenic in some studies utilizing long-term rodent exposures. We investigated lung DNA damage induced by controlled O-3 e xposure in vivo in guinea pigs and human subjects. We specifically exa mined DNA single-strand breaks (SSB) using the single-cell gel electro phoresis assay. Guinea pigs were exposed for 2 h to air, 0.4 ppm O-3, or 1.0 ppm O-3 and lung cells were collected by bronchoalveolar lavage (BAL) and bronchial scraping within I h after exposure. Both the 0.4 and 1.0 ppm O-3 exposures induced significant increases in SSB in both the BAL cells and tracheal cells as indicated by an increased cell DN A length in electrophoresized agarose gel. The increase in DNA SSB was a more sensitive biomarker of exposure compared to more traditional b iomarkers (BAL total protein and lactate dehydrogenase, alterations in BAL cell differential), which changed only at the 1.0 ppm exposure. I n an initial study with human volunteers, BAL and bronchial epithelial cells were collected from human volunteers 1-2 h after an air or 0.4 ppm O-3 exposure in vivo without exercise. BAL cells (primarily macrop hages) and bronchial epithelial cells showed no change in DNA SSB comp ared to the air-exposed controls. in a second study, DNA SSB in bronch ial epithelial cells and BAL cells collected from exercising subjects exposed to 0.4 ppm O-3 were not altered by steroid (prednisone, beclom ethasone) pretreatment compared to placebo treatment However the bronc hial epithelial cell DNA SSB values in the O-3-exposed, placebo-pretre ated group were significantly increased compared to values (air or O-3 exposed, no exercise) in the first study. The dosimetry of O-3 deposi tion in the guinea pig and human subjects appeared similar based on th e amount of O-18 (derived from O-18-labeled O-3) found in the BAL cell fraction. These data suggest that O, exposure at 0.4 ppm induces DNA SSB in rodent and human lung cells, although the effect of exercise on the increase of human lung cell SSB is unclear. Formation of DNA SSB may be an indicator of the tumorigenic potential of O-3. Additionally, DNA SSB can potentially be a good biomarker of O-3 exposure in humans and animal model systems.