Urethan-induced pulmonary adenoma as a tool for the study of surfactant biosynthesis.

Summary Mouse pulmonary adenomas induced by urethan contain significant quantities of disaturated phosphatidylcholine, the main constituent of lung surfactant. Data obtained after phospholipase C hydrolysis, acetate derivatization of the resulting diacylglycerols, and then argentation thin-layer chromatography enabled us to determine that the disaturated molecular species represent about 28% of the phosphatidylcholine present in the adenoma cells and that at least 60% of this fraction is 1,2-dipalmitoyl- sn -glycero-3-phosphorylcholine. Homogenate preparations, in the presence of added adenosine triphosphate, coenzyme A, and Mg 2+ , incorporated palmitate at positions 1 and 2 of the glycerol moiety, suggesting that the alveolar type II epithelial cells that comprise the pulmonary adenoma contain an enzymic system capable of producing disaturated phosphatidylcholine. Adenoma homogenates also produce labeled alkyl glycerolipids from hexadecanol-1- 3 H. This is characteristic of most tumors, including the lung squamous cell carcinoma that we tested. The carcinoma also actively incorporated palmitic acid into phosphatidylcholine but not to the same extent that the adenoma did. The addition of Ca 2+ did not inhibit the incorporation of palmitic acid-1- 14 C into phosphatidylcholine but decreased its total incorporation into lipids. In contrast, the formation of O -alkyl phospholipids from hexadecanol-1- 3 H was completely blocked by Ca 2+ . Since Ca 2+ is known to inhibit cytidine diphosphate-base transferase activity, these data demonstrate that the major incorporation of palmitic acid-1- 14 C into phosphatidylcholine in the adenoma homogenate does not take place via the cytidine diphosphate choline pathway or by methylation of phosphatidylethanolamine.