Incorporation of [³H]acetate into the Membrane Lipids of a Murine Tumour during the Development of Thermotolerance

Summary

The incorporation of [³H]acetate into the membrane lipids of a C3H mammary adenocarcinoma, grown s.c. in the hind paw of CBA mice, was followed to estimate the effects on the de novo synthesis of membrane lipids after hyperthermic treatments. Thermotolerance developed in response to a heat treatment at 43°C for 20 min, as verified through growth rate studies of tumours exposed to fractionated heat treatments. Our results show that, during the development of thermotolerance, the relative rates of incorporation of [³H]acetate into the major lipid classes of the tumour cell membranes change significantly. The de novo synthesis of phospholipids decreased while that of cholesteryl esters plus triglycerides increased. The incorporation of [³H]acetate into cholesterol remained constant. Consequently, the ratio [³H]cholesterol/[³H]lecithin increased significantly during the development of thermotolerance. When the incorporation of [³H]acetate was followed 72–96 h after the heat treatment, i.e. at the interval at which heat resistance was observed to approach that of control tumours, the incorporation into cholesterol was significantly reduced while incorporation into phospholipids increased to control levels. Thus, the ratio [³H]cholesterol/[³H]lecithin was significantly lower, when compared to that of control tumours. The functional relationship between the heat-induced changes in the de novo synthesis of membrane lipids and the development of thermotolerance is discussed with regard to a mechanism based on homeoviscous adaptation of the membranes.