Oxygen Toxicity in the Newborn Lung: Reversal of Inhibition of DNA Synthesis in the Mouse

Abstract

Continuous exposure to 100% oxygen at atmospheric pressure for two weeks causes significant alterations in the growth of the lung and the body of newborn mice. These changes can be divided into three phases. The initial phase, which lasts 96 hours, is characterized by inhibition of lung DNA synthesis, diminished total lung DNA, and a decrease in the ratio of lung DNA to body weight. The intermediate phase from 96 to 144 hours is characterized by a sharp increase in mortality, a plateau in body weight, and a minimal lung DNA/body weight ratio. During this period, however, surviving animals show a reversal of the inhibition of DNA synthesis and thus an increase in total lung DNA. The third phase, occurring after 144 hours, is characterized by a continued increase in DNA synthesis and total lung DNA, a gain in body weight, a return of the lung DNA/body weight ratio to control levels, and a sharp decline in mortality. The survival rate of 54% in newborn mice over two weeks contrasts with the near total mortality reported for adult experimental animals similarly exposed. The reversal of the inhibition of lung DNA synthesis in surviving mice suggests either that some newborn animals are inherently resistant to pulmonary oxygen toxicity or that they develop, during a critical exposure period, an adaptive process necessary for their survival.