The antiproliferative effect of 8-chloro-adenosine, an active metabolite of 8-chloro-cyclic adenosine monophosphate and disturbances in nucleic acid synthesis and cell cycle kinetics

摘要: 8-Chloro-adenosine, the dephosphorylated metabolite of antineoplastic agent 8-chloro-cyclic AMP, has been proposed to act on regulatory subunits cyclic AMP-dependent protein kinase. 8-Chloro-adenosine a growth-inhibitory effect, mechanism which is unclear. We investigated effects AMP and 8-chloro-adenosine nucleic acid synthesis cell cycle kinetics in two human glioma lines. These were compared those analogue 8-(4-chlorophenyl)-thio-cyclic (8-CPTcAMP), less susceptible dephosphorylation. Whereas 8-CPTcAMP almost completely inhibited RNA DNA synthesis, both only partly at concentrations, as demonstrated by using [5-1H] uridine [14C]thymidine incorporation. Therefore, effect not (or completely) due activation kinase nor inhibition synthesis. Flow cytometric analysis revealed that probably block progression G2M phase. The largely prevented adenosine deaminase, inactivates 8-chloro-adenosine. This indicates least part its Incorporation into might contribute disturbance