HYPEROXIA INCREASES AIRWAY CELL S-PHASE TRAVERSAL IN IMMATURE RATS IN-VIVO

Exposure of 21-day-old Sprague-Dawley rats to hyperoxia (> 95% O-2 for 8 days) causes thickening of the airway epithelial and smooth muscle layers. To test the hypothesis that hyperoxic exposure increases airwa y layer DNA synthesis, we labeled the nuclei of cells undergoing S-pha se by administering the thymidine analog bromodeoxyuridine (BrdU). Brd U was administered on days 3 and 4, 5 and 6, or 7 and 8 of air or O-2 exposure, and the lungs were harvested immediately thereafter. Histolo gic sections were stained with an avidin-biotin-immunoperoxidase stain that revealed BrdU incorporation into nuclei, and a hematoxylin count erstain. After 4 days of air or O-2 exposure, there was no difference in BrdU fractional labeling between control and hyperoxic animals. The reafter, fractional BrdU labeling of the small airway (circumference < 1,000 mu m) epithelium and smooth muscle layer was significantly incr eased in O-2-exposed animals (P < 0.01, unpaired t test). The fraction al labeling of larger, central airway smooth muscle layer cells was al so increased after 8 days of O-2 exposure (P < 0.01). In another cohor t of O-2-exposed animals, measurements of airway layer dimensions demo nstrated increases in small airway epithelial and smooth muscle layer thickness that paralleled the time course seen for BrdU incorporation. We conclude that O-2 exposure of immature rats increases airway epith elial and smooth muscle layer cellular DNA synthesis. These data sugge st that hyperplasia of airway epithelial and smooth muscle layer cells may contribute to hyperoxia-induced airway remodeling.