Pulmonary cell kinetics and morphometry after ozone exposure: day versus night and dose response in rats

Male Sprague-Dawley rats were exposed to increasing concentrations of ozone as follows: 0.12, 0.24, 0.36, 0.6, or 0.8 ppm. Controls were kept in chambers ventilated with filtered air. One-half of the animals in ozone was exposed for 12 h a day during daytime hours, and the other one-half of the animals was exposed for 12 h during nighttime. Cumulative labeling indexes were measured after 4 and 7 days in the terminal bronchioles, large intrapulmonary airways, trachea, and nasal epithelia. The penetration of the lesions from the bronchiole-alveolar junction into the alveolar zone was measured with quantitative morphometry. After 4 days of exposure, the extent of injury was dose dependent. Labeling indexes in the terminal bronchioles were 15-20% higher in animals exposed during nighttime compared with the animals exposed during daylight hours. On the other hand, depth of penetration of ozone lesions into the centriacinar region was not significantly different in animals exposed during the night compared with animals exposed during daytime. Labeling indexes in the large airways, trachea, or nasal cavity were not influenced by time of exposure. Between days 4 and 7, the lesions in the terminal bronchioles progressed only to a minimal degree (10%). It was concluded that the pattern of centriacinar tissue remodeling 1) followed a gradient based on ozone concentration and 2) was essentially complete after only 4 days of ozone exposure. Although a difference between daytime and nighttime exposure was observed, it was not considered to be large enough to invalidate conclusions drawn from studies in which animals are exposed to ozone during daylight hours.