ADAPTATION TO OZONE IN RATS AND ITS ASSOCIATION WITH ASCORBIC-ACID INTHE LUNG

Ozone (O-3) adaptation is a well-known, but poorly understood phenomen on that has been demonstrated in humans and laboratory animals. This s tudy examined pulmonary function and bronchoalveolar lavage fluid (BAL F) parameters in O-3-adapted F-344 rats to explore possible mechanisms of adaptation. Of particular interest was ascorbic acid (AA), an anti oxidant reported to be protective against O-3 injury and found to be i ncreased in O-3- adapted rats. Adaptation was induced by exposure to 0 .25 ppm O-3, 12 hr/day for 6 or 14 weeks and evaluated with a challeng e test, one that reexposed rats to 1.0 ppm O-3 and measured attenuatio n in the O-3 effect on frequency of breathing. Pulmonary function was assessed 1 day postexposure and adaptation and BALF were evaluated 1, 3, and 7 days postexposure. Results showed that forced vital capacity increased over time but decreased due to exposure and that the 14-week , O-3-exposed rats had an increase in forced expiratory flow rate. All of the O-3-exposed rats that were tested demonstrated adaptation on P ostexposure Days 1, 3, and 7, but it was diminished on Day 7. Adaptati on was also more pronounced in rats exposed for 14 weeks. Except for A A, BALE levels of total protein, potassium, lysozyme, uric acid, and a lpha-tocopherol were unaffected by O-3 exposure. Lactic acid dehydroge nase, alkaline phosphatase, glucose-6-phosphate dehydrogenase, and tot al glutathione were also assayed but were always below detectable limi ts. Ascorbic acid concentrations were elevated on Days 1, 3, and 7, sh owing postexposure patterns similar to those found for adaptation. Sig nificant correlation was found between AA concentration and the magnit ude of adaptation (r = 0.91, p < 0.002). We conclude that AA may play an important role in mechanisms associated with O-3 adaptation in rats . (C) 1996 Society of Toxicology