title: Ozone adaptation in mice and its association with ascorbic acid in the lung.
abstract: We have previously shown that ozone (O(3)) 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 O(3) 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 O(3) for 10 days and 10 days of recovery in air (experiment 1) and to 0.0, 0.5, or 1.0 ppm O(3) 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 degrees C saline. BALF was assayed for cells, cell differential, protein, albumin, lactate dehydrogenase, lysozymes, N-acetyl-beta-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 O(3) 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 O(3) 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 O(3)-preexposed mice demonstrated adaptation when compared to their O(3)-naive counterparts. Daily exposure to 1. 0 ppm O(3) 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 O(3) adaptation mechanism among rodents that involves the regulation of AA in lung lining fluid.
authors.affiliation: U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Experimental Toxicology Division, Pulmonary Toxicology Branch, Research Triangle Park, NC 27711, USA. wiester.mildred@epamail.gov.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wiester
authors.forename: D W
authors.initials: DW
authors.lastname: Winsett
authors.forename: J H
authors.initials: JH
authors.lastname: Richards
authors.forename: M C
authors.initials: MC
authors.lastname: Jackson
authors.forename: K M
authors.initials: KM
authors.lastname: Crissman
authors.forename: D L
authors.initials: DL
authors.lastname: Costa
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000222:Adaptation, Physiological / Q000187:drug effects*; D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009113:Muramidase / Q000378:metabolism; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity; D011506:Proteins / Q000378:metabolism; D014109:Total Lung Capacity / Q000187:drug effects / Q000502:physiology; D014527:Uric Acid / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000418:Albumins; D011506:Proteins; D014527:Uric Acid; D010126:Ozone; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D009113:Muramidase; D000118:Acetylglucosaminidase; D005978:Glutathione; D001205:Ascorbic Acid