Xenobiotic-metabolizing enzyme activities in primary cultures of rat type II pneumocytes and alveolar macrophages

Because of the evidence for the involvement of xenobiotic bioactivation in pulmonary toxicity and carcinogenesis, it is important to improve our under standing of the xenoblotic-metabolizing enzymes in isolated and cultured sp ecific pulmonary cell populations. Some phase I and phase II xenobiotic-met abolizing enzyme activities, reduced glutathione (GSH), and gamma -glutamyl transferase (gamma -GT) were studied in rat type II pneumocytes and alveol ar macrophages cultured for up to 48 h and 3 h, respectively. In type II pn eumocytes, 7-ethoxyresorufin activity was not detected. 7-Benzyloxyresorufi n (BROD) and 7-pentoxyresorufin (PROD) O-dealkylation decreased at 24 h by 84 and 82%, respectively, and continued to decline over the next 24 h with no measurable PROD at 48 h. The activity of NADPH- and NADH-cytochrome c re ductase at 48 h decreased by 31 and 67%, respectively. GIST activity decrea sed by 25 and 42% at 24 and 48 h, respectively. A transient increase in DT- diaphorase activity was observed at 24 h (by 55%). GSH content and gamma -G T activity increased significantly with time in culture. In freshly isolate d alveolar macrophages, BROD activity was the only cytochrome P450-dependen t alkoxyresorufin-O-dealkylase activity measured. BROD activity decreased b y 38% in 3-h-attached macrophages. There were no changes in NADPH- and NADH -cytochrome c reductase, GST, and DT-diaphorase. An increase of GSH (by 24% ) was observed in attached macrophages. In conclusion, type II pneumocytes and to a lesser extent alveolar macrophages in primary cultures undergo cha nges in biotransformation-related enzyme activities and intracellular GSH l evel that may affect xenobiotic toxicity at different times in culture.