Early inhibition of phospholipid synthesis in dimethyl sulfoxide (DMSO) treated Friend erythroleukemia (FL) cells

Harel, L.; Lacour, F.; Friend, C.; Durbin, P.; Semmel, M.

Journal of Cellular Physiology 101(1): 25-32

1979


ISSN/ISBN: 0021-9541
PMID: 295286
DOI: 10.1002/jcp.1041010105
Accession: 068525546

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Abstract
The present experiments were designed to gain insight into the mechanism of induction of erythroid differentiation in mouse Friend erythroleukemia cells. Phosphate metabolism in Friend erythroleukemia cells undergoing DMSO-induced differentiation was studied. Thirty minutes after the cells were exposed to DMSO in medium at pH 7, 39% of the incorporation of phosphate into phospholipids was inhibited. This decrease was not due to a change in the precursor pools since phosphate uptake and the phosphorylation of the organic soluble compounds were only inhibited 13%. Inhibition of phospholipid synthesis preceded inhibition of RNA and protein synthesis, reaching a maximum after 24 h of DMSO treatment. At this time, the phospholipid content of the cells decreased as compared to that of the control untreated cells. Phospholipid synthesis remained at a level significantly lower than in the controls over the 4-day observation period, at which time 85% of the treated cells were benzidine-positive. Separation of the different phospholipids by chromatography on thin layer silicate gel plates showed that after 1 h of DMSO treatment more than 80% of the radioactivity was in phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine. Phosphatidylethanolamine was the most inhibited. Incorporation of inositol into phospholipid significantly decreased. There was little variation in the phospholipid composition of the treated and non-treated cells other than a decrease in the percent of sphingomyelin after 48 h of DMSO treatment. These changes in phospholipid metabolism may initiate the 1st step in the complex differentiation process. The phospholipids are important components of membranes and the inducers are known to influence their fluidity.