Early effects of medium change in cultured cells: evidences for the existence of negative modulators of cell proliferation.

Serum deprivation of cells in culture leads usually to an arrest of DNA synthesis and cell proliferation but the transfer of cultured cells from serum-containing to serum-free medium results in a transient stimulation of the incorporation of radioactive thymidine to macromolecules. This stimulation effect produced by medium change can be separated into two different phenomena: a stimulation of thymidine incorporation induced by transfer of cells from conditioned serum-containing medium to fresh serum-containing medium and an additional stimulation induced by transfer of cells from serum-containing medium to serum-free medium. Experimental results indicate that the first effect is probably due to the removal of inhibitors released by the cells even in exponentially growing cultures, and that the second effect is probably due to the removal of inhibitory molecules coexisting in serum with stimulatory factors.