Modifications in mitochondrial metabolism and ultrastructure and their relationship to tumour growth inhibition by gamma-linolenic acid

Walker 256 tumour-bearing rats were fed pelleted chow containing low-gamma- linolenic acid (GLA) (2.98%) or high-GLA (5.55%) during the twelve-day peri od after subcutaneous implantation of the tumour. The presence of n-6, poly unsaturated GLA in the diet caused a concentration-dependent decrease in tu mour growth, reaching an almost 50% reduction in final tumour weight in the high-GLA group. The eicosatrienoic acid content of the whole tumour homoge nate and of the Percoll-purified mitochondrial fraction was increased by th e GLA-rich diets. Changes in the fatty acid composition of the cytoplasmic acyl CoA pool were also found, with increases in GLA content in both the lo w- and high-GLA groups. Additionally, increases in eicosatrienoic acid and arachidonic acid were found in the high-GLA group. Both the cytoplasmic acy l CoA content and the mitochondrial acyl CoA synthetase activity were incre ased by GLA in the diet and lipid peroxidation was also increased as determ ined by an increase in TBARS content. Changes in mitochondrial fatty acid c omposition were accompanied by a decrease in the mitochondrial membrane pot ential in the high-GLA group. Tumours from the control and GLA groups were examined by transmission electron microscopy. This revealed an increase in mitochondrial area and volume in the high-GLA group, in comparison with the control group, as well as a change in general cell ultrastructure, with ma ny cells found in an apoptotic state or in a necrotic state, possibly secon dary to apoptosis. The data presented show that the addition of GLA to the diet of Walker 256 tumour-bearing rats can greatly decrease the rate of dev elopment of the tumour burden. This may be, in part, due to the accumulatio n of poorly metabolised acyl CoA's within the tumour cell cytoplasm which, when coupled with altered mitochondrial composition, membrane potential and ultrastructure, may be a signal for cell death.