Inhibition of G2 phase in unsynchronized HELA cells: synergism between adenosine 3':5'-monophosphate analogues and phosphodiesterase inhibitors.

The involvement of cyclic nucleotides of G2 phase of the cell cycle was reexamined in unsynchronized HeLa cells. Two methods were employed to determine if cell cycle traverse was affected by chemical agents. The first method analyzed cell density changes a relatively early times after drug treatment. The second method entailed selection of a cohort of "tagged" G2 cells and analysis of the progress of these cells into mitosis. Synergism between the effects of low levels of cyclic nucleotide analogues and phosphodiesterase inhibitors was used as a criterion for the specificity of an agent's action. Using both methods of cell cycle analysis, synergistic inhibition of cell division was observed with adenosine 3':5'-monophosphate analogues. No synergism was observed with various control compounds or with guanosine 3':5'-monophosphate analogues. The results are interpreted to indicate that adenosine 3':5'-monophosphate exerts an inhibitory action in G2 phase of the cell cycle.