ENERGY-METABOLISM IN HUMAN-MELANOMA CELLS UNDER HYPOXIC AND ACIDIC CONDITIONS IN-VITRO

The response to treatment and the malignant progression of tumours are influenced by the ability of the tumour cells to withstand severe ene rgy deprivation during prolonged exposure to hypoxia at normal or low extracellular pH (pH(e)). The objective of the present work was to dem onstrate intertumour heterogeneity under conditions of microenvironmen t-induced energy deprivation and to investigate whether the heterogene ity can be attributed to differences in the capacity of the tumour cel ls to generate energy in an oxygen-deficient microenvironment. Culture s of four human melanoma cell lines (BEX-c, COX-c, SAX-c, WIX-c) were exposed to hypoxia in vitro at pH(e) 7.4, 7.0 or 6.6 far times up to 3 1 h by using the steel-chamber method. High-performance liquid chromat ography was used to assess adenylate energy charge as a function of ex posure time. Cellular rates of glucose uptake and lactate release were determined by using standard enzymatic test kits. The adenylate energ y charge decreased with time under hypoxia in all cell lines. The decr ease was most pronounced shortly after the treatment had been initiate d and then tapered off. BEX-c and SAX-c showed a significantly higher adenylate energy charge under hypoxic conditions than did COX-c and WI X-c whether the pH(e) was 7.4, 7.0 or 6.6, showing that tumours can di ffer in the ability to avoid energy deprivation during microenvironmen tal stress. There was no correlation between the adenylate energy char ge and the rates of glucose uptake and lactate release. Intertumour he terogeneity in the ability to withstand energy deprivation in an oxyge n-deficient microenvironment cannot therefore be attributed mainly to differences in the capacity of the tumour cells to generate energy by anaerobic metabolism. The data presented here suggest that the heterog eneity is rather caused by differences in the capacity of the tumour c ells to reduce the rate of energy consumption when exposed to hypoxia.