Effect of Modificationof PlasmaMembraneFatty Acid Compositionon Fluidityand MethotrexateTransport in L1210 Murine Leukemia Cells1

The plasma membrane lipid composition in Li 210 murine leukemia cells was dependent upon the type of fat fed to the host animal. Plasma membranes prepared from cells grown in animals fed 16% sunflower oil contained 39% saturated, 14% monoenoic, and 41% polyenoic fatty acids. In contrast, those from cells grown in mice fed 16% coconut oil contained 39% saturated, 31% monoenoic, and 23% polyenoic fatty acids. Although there were 34% more unsaturated bonds in the membranes from the cells grown on polyunsaturated fat, there was no difference in the phospholipid or cholesterol content of the membranes. Studies with the spin label probes 5-nitroxide and 12-nitroxide stearic acid indicated that the order parame ters at temperatures between 15 and 40°were higher in the membranes of cells from animals fed the coconut oil diet. The transition temperature of the approximate rotational correlation time in the region of 20°was 2.5—3.5° higher in the membranes isolated from the cells grown in the mice fed coconut oil. These findings indicate that the fluidity of the membranes was altered by the diet-induced modifications in fatty acid saturation. Ap preciable differences were noted when transport of the anti neoplastic drug methotrexate by intact Li 210 leukemia cells from animals fed the sunflower or coconut oil diets was com pared. Although the apparent Vmaxwas not significantly differ ent, the apparent Kmfor transport by the cells from animals fed the sunflower oil diet was 2.90 ±0.35 @.tM as compared to 4.10 ±0. 1 ( p < 0.02) by cells from animals fed the coconut oil diet. Therefore, in the lower range of methotrexate concentrations, the cells having the more fluid membranes exhibited greater permeability to methotrexate. Taken together, these results indicate that the changes in membrane lipid structure and physical properties brought about by fatty acid modification are sufficient to affect the entry of an antineoplastic drug into the Li2iO cell.