Treatment of human tumor cells with ADP or ATP yields arrest of growth in the S phase of the cell cycle

Abstract Treatment of a variety of cultured human tumor cells with low levels (40–80 μM) of adenosine 5′‐dephosphate (ADP) or adenosine 5′ ‐triphosphate (ATP) has produced arrest of these cells in the S phase of their cycle followed by cellular death. ADP and ATP are demonstrated to be incorporated into the cellular acid‐soluble nucleotide pools, presumably by permeation through the plasma membrane of these cells. Since AMP, adenosine, 3′,5′ cycle AMP, or a variety of diadenosine polyhosphates do not produce similar cytostatic effects or similar alterations of the cellular acid‐soluble nucleotide pools, we suggest that the effects of ADP and ATP are not due to their prior breakdown or modification. Cultured animal cells have been widely acknowledged not to incroporte acid‐soluble adenine nucleotides although incorporation of exogenous intact nucleoside monophosphate into cellular pools has been demonstrated in a few cases. A 48‐hour treatment of logarithmically growing human tumor cells with 40mUM of ADP or ATP produced substantial arrest of cell populations in the S phase of their cycle and a dramatic reduction in total cellular uridine 5′ ‐triphosphate (UTP) pools. AMP, adenosine, 3′,5′ cyclic AMP, Ap 3 A, Ap 4 A or Ap 5 A produced small and dissimilar effects. The experiments reported here suggest that the plasma membranes of several lines of human tumor cells are premeable to low levels of intact ADP and ATP. The suggestion of en bloc incorporation of low ADP and ATP levels into human tumor cells is supported by the almost identical effects of ADP and ATP on total cellular acid‐soluble nucleotide pools and cellular growth. The rapid conversion of intracellular ADP pools into ATP in tumor cells has been reported.