Enhancement of haemopoietic spleen colony formation by drugs elevating extracellular adenosine: effects of repeated in vivo treatment.

The potential role of adenosine receptor signalling in the amplification of haemopoietic stem cells in vivo was investigated. Elevation of extracellular 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 haemopoietic stem cells to the drug treatment was measured by endogenous spleen colony-forming assay in sublethally gamma-irradiated animals. The combination of drugs was administered before irradiation either singly or repeatedly at 24 h intervals. The results demonstrated the possibility of enhancing the spleen colony formation by the drug treatment. The highest stimulatory effect on spleen colony counts and on the colony sizes occurred after 3-4 injections of the drugs. Higher spleen colony responses were observed under injection regimens terminated 3 h before irradiation, as compared to those terminated 24 h before the radiation exposure. The results are interpreted as an evidence of the expansion of the stem cell pool. A tolerance to this stimulatory action developed after more than 3 injections of the drugs.