The role of adenosine triphosphate, chalones, and specific proteins in controlling tumor growth fraction.

During growth of Ehrlich ascites tumor cells in vivo, the proportion of cells in the S phase of the proliferative cell cycle decreases in a manner analogous to the decreasing growth fraction often associated with the growth of solid tumors. An examination of biochemical parameters that might regulate the growth fraction of Ehrlich ascites tumors by causing accumulation of cells in G1-G0 shows that (a) the tumor progresses from an aerobic to an anerobic state as it approaches the plateau phase of growth, as indicated by lactate dehydrogenase content, but cellular adenosine triphosphate content remains constant; (b) tumor-specific growth inhibitors (chalones) are not detectable in cell-free ascites fluid from plateau-phase tumors; (c) electrophoretically identifiable soluble proteins isolated from tumor cells that have been exposed to labeled amino acids in vivo are qualitatively identical during early and late tumor growth; and (d) ornithine decarboxylase activity increases in a bimodal fashion in the first 10 hr after transplantation of 10(7) cells and then declines rapidly during the first few days of growth. The second (and larger) of the two ornithine decarboxylase increases coincides with the surge of cells from G1-G0 into S phase, suggesting that this enzyme, or the polyamines that it synthesizes, may play a role in controlling the growth fraction of this cell population.