Vol. 295, Issue 3, 934-941, December 2000

Long-Term Exposure to Ozone Increases Acute Pulmonary Centriacinar Injury by 1-Nitronaphthalene: I. Region-Specific Enzyme Activity¹

Renee C. Paige, Fred H. Royce, Charles G. Plopper and Alan R. Buckpitt

Departments of Anatomy, Physiology, and Cell Biology (R.C.P., C.G.P.) and Molecular Biosciences (A.R.B.), School of Veterinary Medicine, and Department of Pediatrics (F.H.R.), School of Medicine, University of California, Davis, California

To test whether exposure to ozone alters pulmonary cytochrome P450 monooxygenase-mediated metabolism of xenobiotics, rates of 1-nitronaphthalene (1-NN) metabolism were measured in microsomes prepared from trachea, intrapulmonary airways, and distal lung of rats exposed to filtered air (FA) or ozone (O₃) (0.8 ppm 8 h/day for 90 days). Regioisomeric glutathione conjugates derived from intermediate epoxides were measured by HPLC. Compared with FA, rates of glutathione conjugate formation in distal lung (including the central acinus) were elevated 2-fold in O₃-exposed rats. Activity for cytochrome P450 2B, the isozyme thought to be responsible for the metabolic activation of 1-NN, was increased 3-fold in the distal lung of O₃- compared with FA-exposed rats. There was a 2 ± 0.5-fold increase in immunodetectable CYP 2B protein in microsomes from the same lung subcompartment (P < .05). Immunodetectable protein was expressed in nonciliated epithelial (or "Clara") cells and not associated with ciliated epithelial cells. No differences between O₃- and FA-exposed rats were noted in 1-NN metabolism or CYP 2B activity in trachea or intrapulmonary airways. This study emphasizes that cellular and biochemical alterations associated with long-term O₃ exposure vary considerably by location within the lung. Long-term exposure to O₃ elevates both CYP 2B activity and 1-NN metabolism in an airway-specific manner.