ENHANCEMENT OF HEMATOPOIETIC SPLEEN COLONY FORMATION BY DRUGS ELEVATING EXTRACELLULAR ADENOSINE - EFFECTS OF REPEATED IN-VIVO TREATMENT

The potential role of adenosine receptor signalling in the amplificati on of haemopoietic stem cells in vivo was investigated. Elevation of e xtracellular adenosine in mice was induced by the joint administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, an adenosine prodrug. The response of hae mopoietic stem cells to the drug treatment was measured by endogenous spleen colony-forming assay in sublethally gamma-irradiated animals. T he combination of drugs was administered before irradiation either sin gly or repeatedly at 24 h intervals. The results demonstrated the poss ibility of enhancing the spleen colony formation by the drug treatment . The highest stimulatory effect on spleen colony counts and on the co lony sizes occurred after 3-4 injections of the drugs. Higher spleen c olony responses were observed under injection regimens terminated 3 h before irradiation, as compared to those terminated 24 h before the ra diation exposure. The results are interpreted as an evidence of the ex pansion of the stem cell pool. A tolerance to this stimulatory action developed after more than 3 injections of the drugs.