OBJECTIVE: Our previous studies showed that the combined administration of drugs elevating extracellular @entity859 , i.e., @entity4341 and @entity860 ( @entity860 ), enhanced @entity1210 in normal @entity19 and increased hematopoietic recovery in irradiated @entity19 . In the present study, we have examined the possibility that these effects are due to the @entity859 -induced cycling of the hematopoietic progenitor cells. MATERIALS AND METHODS: Experiments were performed under in vivo conditions using B10CBAF1 @entity19 . The cycling status of hematopoietic progenitor cells (CFU-S(day 10), @entity7419 , and BFU-E) was determined on the basis of their sensitivity to @entity1487 ( @entity1487 ), a cycle-specific cytotoxic agent. RESULTS: Pretreatment of @entity19 with @entity4341 + @entity860 enhanced the cytotoxic effects of a single bolus of @entity1487 at a dose of 3 mg per @entity19 . Sensitizing effects of drugs occurred after a delay of several hours and attained a maximum of about 40-60% reduction of the progenitor cells surviving after @entity1487 alone. The period of maximum sensitization of CFU-S by the combination of @entity4341 + @entity860 was shifted to later time intervals as compared with the effects on @entity7419 and BFU-E. Pretreatment of @entity19 with the drugs also aggravated the @entity1487 -induced lethality. Reduction of survival was found in @entity19 exposed to two cycles of 3 mg of @entity1487 following the pretreatment with @entity4341 + @entity860 at a time period characterized by the highest fraction of CFU-S in the S phase. CONCLUSIONS: The results suggest that @entity859 receptor signaling, induced by the administration of drugs elevating extracellular @entity859 , enhances cycling of the hematopoietic progenitor cells. These effects might have pharmacological implications in the therapy of @entity3459 .

Drugs elevating extracellular @entity859 enhance cell cycling of hematopoietic progenitor cells as inferred from the cytotoxic effects of XXXX .

@entity7419 :: ('MESH:C562602', 'Disease') :: ['CFC-GM'] @entity859 :: ('MESH:D000241', 'Chemical') :: ['adenosine'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity4341 :: ('MESH:D004176', 'Chemical') :: ['dipyridamole'] @entity3459 :: ('MESH:D025861', 'Disease') :: ['blood disorders'] @entity860 :: ('MESH:D000249', 'Chemical') :: ['adenosine monophosphate', 'AMP'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5-FU', '5-fluorouracil'] @entity1210 :: ('MESH:C536227', 'Disease') :: ['hematopoiesis']
@entity1487 :: (MESH:D005472,Chemical) :: ['5-fluorouracil']
