Nonproliferating neoplastic cells in culture: behavior of the adenine nucleotides

The intracellular concentrations of the adenine nucleotides were determined in suspension cultures of WRL-10A cells, a subline of the L-929 mouse fibroblasts, during the progression of the cells from exponential growth to high-density, nonproliferating populations. The development of the nonproliferating state was associated with a 50% reduction of the adenine nucleotide pool, whereas the energy charge remained at values above 0.90. This change was also observed in the early phase of starvation of low-density cultures and could be reproduced by selective simultaneous withdrawal of glucose and glutamine, which indicated interference with the de novo synthesis of purines. In this respect, therefore, nonproliferating populations of WRL-10A cells resemble purine-limited bacterial systems but not density-inhibited normal fibroblasts in which the size of the adenine nucleotide pool is known to remain unchanged. This difference in the physiologic state of nonproliferating normal and neoplastic cells is potentially significant for tumor chemotherapy.