Changes in Cellular Lipid Synthesis of Normal and Neoplastic Cells During Cytolysis Induced by Alkyl Lysophospholipid Analogues 1,2

ABSTRACT-Susceptibility of eight different cell types of murine or human origins to alkyl Iysophospholipid analogue (ALP)-induced cytolysis correlated well with a selective, dose-dependent inhibition of radiolabeled oleic acid incorporation into phospha-tidylcholine (PC) and a concomitant stimulation of incorporation into neutral lipids (NL), mainly triacylglycerols. In resistant cells (murine macrophages, L929S, K562, and rMeth A) a counts per minute NL/counts per minute PC ratio of 0.8-1.0 was observed with 30 J.lg ALP/ml; in sensitive tumor targets (Meth A, HL60, YAC, and ABLS-8.1) values greater than 2.7 were found with 5-10 J.lg ALP/mt. Changes in lipid metabolism preceded cytolysis in Meth A fibro-sarcoma cells. In degradation experiments the percentage of total lipid radioactivity in PC was reduced after 24 hours to 47% compared to that in controls in sensitive Meth A with 10 J.lg ALP/mt. The macrophage-PC was unaffected at the same concentration