OZONE ADAPTATION IN MICE AND ITS ASSOCIATION WITH ASCORBIC ACID IN THE LUNG
Authors: Wiester, Mildred J.; Winsett, Darrell W.; Richards, Judy H.; Jackson, Mette C.; Crissman, Kay M.; Costa, Daniel L.
Source: Inhalation Toxicology, Volume 12, Number 7, 1 July 2000 , pp. 577-590(14)
Publisher: Informa Healthcare
Abstract:We have previously shown that ozone (O3) adaptation occurred in rats after daily exposure to an "urban-type" concentration. The adaptation was positively associated with an excess of ascorbic acid (AA) in bronchoalveolar lavage fluid (BALF), suggesting that AA may play a role in the adaptation mechanism. This relationship was not seen at higher and more toxic exposures. The present work exposed mice to low and high levels of O3 to see if the adaptation–AA relationship is common among rodent species. Male CD-1 mice were studied during repeated 6-h/day exposures to 0.0 or 0.25 ppm O3 for 10 days and 10 days of recovery in air (experiment 1) and to 0.0, 0.5, or 1.0 ppm O3 for 5 days (experiment 2). Approximately 20 h after each daily exposure, groups of mice were randomly selected from each concentration type and examined for patterns of response. They were anesthetized (urethane, ip), intubated, and the lungs were lavaged with 37°C saline. BALF was assayed for cells, cell differential, protein, albumin, lactate dehydrogenase, lysozymes, N-acetyl--D-glucosaminidase, gamma-glutamyl transferase, uric acid, glutathione, and AA. Body weight and total lung capacity were also measured. Mice from experiment 1 (10/exposure) were tested for adaptation on day 12 by challenging them with 1.0 ppm O3 for 6 h and collecting BALF 20 h later. In experiment 2, adaptation was assessed by evaluating the attenuation in response to continued exposure. There was only minimal response to the daily O3 exposures in experiment 1 except for AA, which was significantly increased in BALF by day 3 and remained elevated well into the recovery period. The O3-preexposed mice demonstrated adaptation when compared to their O3-naive counterparts. Daily exposure to 1.0 ppm O3 in experiment 2 caused weight loss and changes in BALF consistent with toxicity, and neither adaptation nor an excess quantity of AA was seen. The findings in mice were in agreement with those seen in rats and suggest that there may be a common O3 adaptation mechanism among rodents that involves the regulation of AA in lung lining fluid.
Document Type: Research Article
Publication date: 1 July 2000