Induction of p21^WAF/CIP1 during hyperoxia

p21^WAF/CIP1 is an important regulator of cell cycle progression (1-4). When induced, p21^WAF/CIP1 protein inhibits cell cycle progression at the G₁/S interface, resulting in growth arrest of the cell. To determine if p21^WAF/CIP1 is involved in growth arrest and lung injury during hyperoxia, several cell lines were exposed to high levels of hyperoxia. p21^WAF/CIP1 was found to be induced by 72 h in all three cell lines. Next, using an in vivo model, p21^WAF/CIP1 was found to be induced at both the mRNA and protein level in neonatal murine lung born and maintained in hyperoxia. Localization of p21^WAF/CIP1 was found in the peripheral air-way cells. Hyperoxia-induced p21^WAF/CIP1 expression was then shown to be mediated through the p53 pathway, using adult p53 mutant mice. These studies demonstrated that p21^WAF/CIP1 is induced both in cells grown in culture and in neonatal and adult lung exposed to high levels of hyperoxia. Localization of p21^WAF/CIP1 expression to the peripheral airway cells suggests that p21^WAF/CIP1 may act to inhibit growth of alveoli in neonatal lung and delay repopulation of alveolar cells during hyperoxic administration.