title: Xenobiotic-metabolizing enzyme activities in primary cultures of rat type II pneumocytes and alveolar macrophages.
abstract: Because of the evidence for the involvement of xenobiotic bioactivation in pulmonary toxicity and carcinogenesis, it is important to improve our understanding of the xenobiotic-metabolizing enzymes in isolated and cultured specific pulmonary cell populations. Some phase I and phase II xenobiotic-metabolizing enzyme activities, reduced glutathione (GSH), and gamma-glutamyl transferase (gamma-GT) were studied in rat type II pneumocytes and alveolar macrophages cultured for up to 48 h and 3 h, respectively. In type II pneumocytes, 7-ethoxyresorufin activity was not detected. 7-Benzyloxyresorufin (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 reductase at 48 h decreased by 31 and 67%, respectively. GST activity decreased 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-GT activity increased significantly with time in culture. In freshly isolated alveolar macrophages, BROD activity was the only cytochrome P450-dependent alkoxyresorufin-O-dealkylase activity measured. BROD activity decreased by 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 changes in biotransformation-related enzyme activities and intracellular GSH level that may affect xenobiotic toxicity at different times in culture.
authors.affiliation: Laboratory of Pneumology, Unit of Lung Toxicology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Dimova
authors.forename: P H
authors.initials: PH
authors.lastname: Hoet
authors.forename: B
authors.initials: B
authors.lastname: Nemery
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005982:Glutathione Transferase / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D015262:Xenobiotics; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase