Exposure to high concentrations of
oxygen in the neonatal period may impair lung growth and is a major contributing factor to the development of
bronchopulmonary dysplasia. Cell death from hyperoxic injury may occur through either an apoptotic or nonapoptotic pathway, and we were interested in determining the type of cell death that occurs in the lung of neonatal mice exposed to
hyperoxia. We found increased levels of Bax
messenger RNA, a gene associated with apoptosis, in the lungs of neonatal mice born and raised in 92%
hyperoxia. We next determined the extent of apoptosis taking place in the lungs of neonatal mice exposed to
hyperoxia using
terminal deoxyribonucleotidyl transferase-mediated
deoxyuridine triphosphate-
biotin nick-end labeling in 3.5-, 4.5-, and 5.5-d-old neonatal lung. The number of apoptotic cells in peripheral lung was significantly higher in the 3.5-, 4.5-, and 5.5-d-old mice treated with
oxygen compared with that in the room-air control mice. Further, the number of apoptotic cells in the lung increased with longer exposure duration. In murine lung bronchus cells exposed to
hyperoxia, growth arrest occurred after 48 h of
oxygen exposure. Using
annexin V binding, necrotic cell death was found to be the major form of cell death in these cells after 72 h of hyperoxic exposure. We conclude that 92%
hyperoxia causes significant
lung injury in neonatal mice exposed to
hyperoxia, and that the number of apoptotic cells in the lung increases the longer the duration of exposure. The increase in apoptosis from hyperoxic exposure during a critical period of lung development may be an important factor in the impaired lung growth and remodeling that occur in animals exposed to high
oxygen concentrations. Finally, it appears that hyperoxic injured cells in neonatal lung undergo both apoptotic and nonapoptotic cell death.