Acute Ozone-Induced Change in Lung Permeability of Genetically Susceptible and Resistant Mice is Differentially Mediated by Cytochrome P-450

Ozone (O₃) has become a common air pollutant in urban areas and in the workplace. Because O₃ is highly reactive and potentially toxic, it has received increasing attention regarding effects on pulmonary function. However, the precise mechanisms which lead to O3-induced lung injury are still not completely understood. A role for cytochrome P-450 enzymes in the development of oxidant-induced lung injury has recently been suggested. Rietjens et al. (1988) found that prolonged exposure to 0.8 ppm O₃ caused qualitative and quantitative changes in pulmonary cytochrome P-450-linked enzyme characteristics in whole lung and within specific lung cells of rats. Takahashi and Miura (1990) showed that prolonged exposure to 0.2 ppm O₃ caused increased content of specific isoforms of cytochrome P-450 in lungs of rats. Although these studies suggest P- 450 inducibility by O₃ may be important, a physiologic or pathologic correlate to the activity of these enzymes has not been demonstrated.