H. Witschi et al., PULMONARY CELL-KINETICS AND MORPHOMETRY AFTER OZONE EXPOSURE - DAY VERSUS NIGHT AND DOSE-RESPONSE IN RATS, American journal of physiology. Lung cellular and molecular physiology, 16(6), 1997, pp. 1152-1160
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 kep
t 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. Cumulat
ive labeling indexes were measured after 4 and 7 days in the terminal
bronchioles, large intrapulmonary airways, trachea, and nasal epitheli
a. The penetration of the lesions from the bronchiole-alveolar junctio
n into the alveolar zone was measured with quantitative morphometry. A
fter 4 days of exposure, the extent of injury was dose dependent. Labe
ling indexes in the terminal bronchioles were 15-20% higher in animals
exposed during nighttime compared with the animals exposed during day
light hours. On the other hand, depth of penetration of ozone lesions
into the centriacinar region was not significantly different in animal
s exposed during the night compared with animals exposed during daytim
e. Labeling indexes in the large airways, trachea, or nasal cavity wer
e not influenced by time of exposure. Between days 4 and 7, the lesion
s 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 essent
ially complete after only 4 days of ozone exposure. Although a differe
nce between daytime and nighttime exposure was observed, it was not co
nsidered to be large enough to invalidate conclusions drawn from studi
es in which animals are exposed to ozone during daylight hours.