Cyclic nucleotides and growth control in cultured mouse cells: correlation of changes in intracellular 3':5' cGMP concentration with a specific phase of the cell cycle.

The commencement of cell growth following serum addition to quiescent cultures of mouse fibroblasts is preceded by transient changes in intracellular concentrations of cAMP and cGMP. By artificial depletion of the culture medium for different nutrients, cell growth can be reversibly arrested in various phases of the cell cycle. Here it is shown that the major cGMP increases are only observed when cultures which are arrested in the G(0) phase are stimulated to grow or when synchronized growing cells pass through the G(1) phase. In addition to its concomitant decrease, cAMP exhibits rhythmic changes during the cell cycle. This suggests that the increase in cGMP could act as a specific signal for movement of cells out of the G(0) or G(1) phase of the cell cycle by activating the pleiotypic and mitogenic program of the cell.