Hyperoxia is used routinely in patients suffering from pulmonary insufficiency, as is encountered in preterm infants and in adults with acute respiratory disease syndrome. The molecular mechanisms of lung injury caused by hyperoxia are not known. The central hypothesis of the research proposed here is that hyperoxia induces CYP1A enzymes in vivo and in cell culture systems by mechanisms involving transcriptional activation of the corresponding promoters, and that the induced CYP1A enzymes play protective roles in hyperoxic lung injury by catalyzing the detoxication of ROS-generated molecules (e.g., F2 isoprostanes and isofurans), whose levels are elevated in hyperoxic lungs. We proposed 2 Specific Aims. 1. To test the hypothesis that mice lacking the gene for CYP1A1, 1A2, or both genes (CYP1A1/1A2 double knockouts) will be more susceptible to hyperoxic lung injury than similarly exposed wild type mice. 2. To characterize the molecular mechanisms of modulation of CYP1A1 gene by hyperoxia in cultured mouse liver and lung cells. The proposed studies should aid in the development of novel strategies in the prevention/treatment of lung disease in humans undergoing supplemental oxygen therapy.