Starvation, deoxy-sugars, ouabain, and ATP metabolism in normal and malignant cells

When starved of a carbon source, early passage normal cells such as chick embryo fibroblasts, human fibroblasts, mixed culture of splenic lymphocytes as well as "normal" cell lines (Nil or CHO cells grown as monolayer cultures) maintain their ATP levels for 8 to 24 h at essentially those characteristic of cells fed glucose. Several malignant or transformed cells (Py6, PyNil, Ehrlich ascites tumor cells, CHO cells in suspension and P388 lymphoblasts) exhibit a dramatic lowering in their ATP within a few hours of the removal of glucose. Normal cells exposed to 2-deoxy-D-glucose (2-DOG) in the absence of glucose lose ATP as rapidly as starved transformed cells. The loss of ATP by transformed cells on starvation is also accelerated by 2-DOG as is cell death. 2-deoxy-D-galactose (2-DOGAL) slows the loss of ATP in glucose starved transformed cells (growing as monolayer cultures) observed when the cultures are shifted to sugar-free medium. Finally, normal cells in culture are able to maintain both their ATP levels and their viability even after prolonged cultivation in a nutrient-free medium. Cultivation of malignant cells in a nutrient-free medium causes rapid loss in their ATP, a phenomenon not preventable by the presence of ouabain.