Fatty Acid Composition Transport and Metabolism in Doxorubicin-sensitive and -resistant Rat Glioblastoma Cells1

We have studied the lipid composition and the acyl group composition, transport, and metabolism of doxorubicin-sensitive and -resistant rat glioblastoma cells in monolayercultures (C6 clone). No difference in lipid composition was evidenced; the acyl group composition was, in contrast, highly modified in resistant cells, and these modifications appeared progressively duringthe acquisition of the resistance. Resistant cells were characterized by a decrease of n-9 eicosatrienoic acid and by a 2-3-fold increase of the proportions of the polyunsaturated fatty acids of the n-6 and n-3 families, especially arachidonic acid and n-3 docosahexaenoic acid. These differences were probably due to a 2-fold increase of the uptake of fatty acids by resistant cells as compared to sensitive cells, this increase allowing the suppression of an essential fatty acid deficiency. Only small changes in the transformations of 16 and 18-carbon atoms' fatty acids to higher analogues were evidenced. A small reduction of the desaturation of stearic acid to oleic acid and of linoleic acid to arachidonic acid was the main characteristic of resistant cells; these differences can be explained as a consequence of the suppression of the essential fatty acid deficiency.