Identification and partial purification of a low-molecular-weight growth inhibitor formed by density-inhibited, tumorigenic V79 Chinese hamster cells.

Medium conditioned by exposure to density-inhibited, tumorigenic V79 Chinese hamster cell cultures reversibly inhibited the growth and DNA synthesis of sparse, proliferating cultures, not only of the same cell line but also of the BALB/c 3T3 A31 murine cell line. This species nonspecific inhibitory activity was found to be mediated by the soluble inhibitor produced endogenously by V79 cells at the time of density inhibition. The molecular weight of this inhibitor is approximately 2000, and production of this compound seems to be serum dependent. Partial purification was done by reverse-phase fast protein liquid chromatography. The inhibitory activity was linearly dependent on the concentration in the inhibitory fraction. This partially purified inhibitor did not include lactic acid, a growth-inhibitory metabolite. These data indicate that a growth-regulatory factor is also operant in tumorigenic V79 cells and suggest that growth of neoplastic cells cannot only be explained by an enhanced positive growth potential but rather by the balance between a positive and negative growth potential.