Increasing the thermosensitivity of a mammary tumor (CA755) through dietary modification

Disruption of the integrity of tumor cellular membranes has been proposed as an initiating event in hyperthermic cell death. Thermosensitivity measured by the shift in the harmonic mean of tumor regrowth delay of CA755 mammary adenocarcinomas grown in the hind legs of male BDF1, mice increased 22% when the hosts were fed a diet enriched in polyunsaturated fatty acids. Although the diet elicited the anticipated increase in tumor membrane phospholipid polyunsaturated fatty acids, the proportion of total unsaturated fatty acids decreased and the proportion of membrane-rigidifying saturated fatty acids increased. Concomitantly, the concentrations of cholesterol and phospholipid phosphorus increased and the ratio of phosphatidylethanolamine to phosphatidylcholine decreased, presumably to counter the effect of the change in the fatty acid pattern. In host liver membranes, the diet-mediated increase in proportion of polyunsaturated fatty acids was not accompanied by an increase in the proportion of rigidifying saturated fatty acids. Instead, the homeoviscous adaptation consisted of decreases in monounsaturated fatty acids and cholesterol concentration and an increase in the phosphatidylethanolamine-phosphatidylcholine ratio. Addition of a natural inhibitor of cholesterol biosynthesis to the polyunsaturated fatty acid enriched-diet reversed the diet-mediated increase in the phosphatidylethanolamine-phosphatidylcholine ratio of host liver membranes. Tumor membrane lipids from hosts fed the combined dietary factors were characterized by the formentioned rigidifying increase in saturated fatty acids and compensatory decrease in the phosphatidylethanolamine-phosphatidylcholine ratio. The inhibitor reversed the compensatory increases in cholesterol and phospholipid phosphorus concentrations. As a consequence the thermosensitivity of tumors bearing this perturbed membrane was increased.