CHANGES IN STRUCTURE, MECHANICS, AND INSULIN-LIKE GROWTH FACTOR-RELATED GENE-EXPRESSION IN THE LUNGS OF NEWBORN RATS EXPOSED TO AIR OR 60-PERCENT OXYGEN

Exposure of neonatal rats to greater than or equal to 95% O-2 for 2 wk , a widely used model of oxidant/antioxidant interactions in neonatal lung injury, results in arrested lung growth without the dysplastic le sions observed in chronic human neonatal lung injury. To determine whe ther dysplastic lung cell growth would be seen at lesser O-2 concentra tions, we exposed newborn rats to either 95% O-2 for 1 wk followed by 60% O-2 for 1 wk, or to 60% O-2 for 2 wk. Exposure to 95% O-2 for 1 wk profoundly inhibited lung DNA synthesis. Recovery of synthesis did no t occur during the 2nd wk in 60% O-2, nor were areas of dysplastic gro wth evident in lung tissue. In contrast, a continuous 2-wk exposure to 60% O-2 resulted in a slight increase in lung weight with a significa nt reduction in lung volume over a range of inflation pressures. Also seen was an overall, but inhomogeneous, reduction in lung cell DNA syn thesis. A preliminary analysis of affected cell types suggested that i nhibition of DNA synthesis affected endothelial cells more than inters titial cells, whereas DNA synthesis increased in type II pneumocytes. Areas of reduced DNA synthesis were interspersed with patchy areas of parenchymal thickening and active DNA synthesis. These areas of parenc hymal thickening, but not other areas, had increased immunoreactive IG F-I and the type I IGF receptor. These data are consistent with a dire ct effect of O-2 on growth factor and growth factor receptor expressio n in causing dysplastic lung cell growth in chronic neonatal lung inju ry.