Metabolism of Ether-linked Glycerolipids in Cultures of Normal and Neoplastic Rat Respiratory Tract Epithelium¹

To study the mechanism of ether lipid accumulation which is characteristic of many tumors, we have compared the metabolism of lipids in primary rat tracheal epithelial cells and in a cell line derived from a benzo(a)pyrene-induced tumor. Growth of the primary epithelial cells in vitro resulted in the accumulation of alkyldiacylglycerols at levels (10% of total lipid) comparable to those found in the tumor cell line (B2-1). This class of ether lipids could not be detected in normal rat tracheal epithelium in vivo. A double isotope labeling method using [³H]- and [¹⁴C]palmitic acid was used to study metabolic stability of lipid classes in the cell cultures. Primary cells and B2-1 cells labeled with palmitic acid showed the greatest loss of label from triacylglycerols and free fatty acids during incubation in unlabeled media. A slight loss of label from the ester linkages of the alkyldiacylglycerols was observed in the primary epithelial cells but not the B2-1 cells. No label was lost from the ether linkages of the alkyldiacylglycerols of either the B2-1 or primary cells. With the exception of diradylglycerophosphocholine, phospholipids of primary and B2-1 cells labeled with palmitic acid accumulated label during incubation in unlabeled media. Similar results were observed with the B2-1 cells using labeled glycerol as the lipid precursor. The results demonstrate that alkyldiacylglycerols can be induced in nontumorigenic cells by growth in culture and can thus provide a useful model for studying the regulation of ether lipid metabolism.