KINETICS OF NASAL EPITHELIAL-CELL LOSS AND PROLIFERATION IN F344 RATSFOLLOWING A SINGLE EXPOSURE TO 0.5 PPM OZONE

Repeated exposure to 0.5 ppm ozone (O-3) induces mucous cell metaplasi a in the nasal transitional epithelium (NTE) of rats. The cellular eve nts which commit the NTE to undergo this phenotypic alteration occur d uring the first 3 days of exposure. To examine the kinetics of the ear ly cellular responses of NTE to O-3, F344 rats were exposed to filtere d air or 0.5 ppm O-3 for 8 hr and euthanized 2, 4, 6, 8, 12, 16, 20, 2 4, and 36 hr postexposure (PE). Two hours before euthanization, rats w ere injected with bromodeoxyuridine (BrdU) to label S-phase cells. The nasal cavities were fixed and processed for light microscopy. Section s from the anterior nasal cavity were immunostained to detect BrdU-lab eled cells and analyzed to determine the numeric densities of NTE cell s and intraepithelial neutrophils, and the labeling index (LI; [BrdU-l abeled epithelial cells/total epithelial cells] x 100) and unit length labeling index (ULLI; BrdU-labeled epithelial cells/mm basal lamina) of the NTE overlying maxilloturbinates. O-3 exposure induced a transie nt influx of neutrophils 2-4 hr PE and a significant (17%) loss of NTE cells 2-4 hr PE. An increase in epithelial DNA synthesis was first de tected 12 hr PE. In this study, there was no difference in the sensiti vity of the two measures of epithelial cell DNA synthesis. Both the LI and ULLI were greatest 20-24 hr PE and were reduced, but still greate r than those of controls, by 36 hr PE. The numeric density of NTE cell s returned to control levels 20-24 hr PE. This study has defined the k inetics of acute O-3-induced NTE cell injury, loss, and proliferation in vivo. The transit time from G(0) to S, after O-3-induced injury, wa s 12-20 hr and the duration of G(2) + M was 8-12 hr. These data may be used to further explore the early cellular and molecular events that lead to ozone-induced mucous cell metaplasia. (C) 1997 Academic Press.