Changes in Cellular Lipid Synthesis of Normal and Neoplastic Cells During Cytolysis Induced by Alkyl Lysophospholipid Analogues2

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Abstract
Susceptibility of eight different cell types of murine or human origins to alkyl lysophospholipid analogue (ALP)-induced cytolysis correlated well with a selective, dose-dependent inhibition of radiolabeled oleic acid incorporation into phosphatidylcholine (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 μg ALP/ml; in sensitive tumor targets (Meth A, HL60, YAC, and ABLS-8.1) values greater than 2.7 were found with 5–10 μg ALP/ml. Changes in lipid metabolism preceded cytolysis in Meth A fibrosarcoma 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 μg ALP/ml. The macrophage-PC was unaffected at the same concentration. Sensitivity to ALP was independent of cell proliferation. Resistance was not restricted to normal cells and was inducible in Meth A (and rMeth A).