Fatty acid composition of HL-60 cells is modified upon proliferation arrest and differentiation

The human leukemic cell line HL-60 undergoes differentiation to granulocytic-like cells in response to dimethyl sulfoxide (DMSO) or retinoic acid (RA). This differentiation is accompanied by an arrest in cell proliferation. Studies have implicated alterations in the phospholipid fatty acid (FA) composition as a result of HL-60 differentiation. However, changes in FA's are also known to occur during the arrest of cellular proliferation. Using a highly efficient capillary gas-liquid chromatography technique, the phospholipid FA composition of HL-60 and of DMSO-resistant and RA-resistant HL-60 subclones was determined in proliferating cells, in density-arrested cells, and in terminally differentiated cells. The same specific modifications in some of the FAs of the three cell lines were observed when proliferation was inhibited by cell density; 16:0 and 18:2n-6 were decreased and 22:6n-3 increased. Moreover, 16 and 18 dimetylacetals were both increased when proliferation was decreased, indicating modifications in plasmalogen contents. Granulocytic differentiation of HL-60 cells and of its subclones with DMSO and/or RA provoked modifications in phospholipid FAs different from that found in density-arrested, undifferentiated cells such as decreases in monoenoic FAs of 16 and 18 carbons as well as an increase in arachidonic acid, the major polyunsaturated FA. The biological significance of these changes upon arrest of proliferation and differentiation are discussed. These results indicate that, when arrest of proliferation accompanies differentiation, these two phenomena can be responsible for different changes and, whenever possible, they have to be considered separately in order to know which modifications are effectively due to differentiation itself.