Hydroxyurea (HU) in experimental hematology. I. Characterization of in vitro and in vivo effects on progenitor and transit cells.

The lethal effect of hydroxyurea (HU) on normal and regenerating mouse bone marrow was examined in vivo and in vitro. Progenitor cells (DCPC) were assayed by their capacity to form granulocytes and macrophages in 7-day diffusion chamber (DC) cultures. Dose-response experiments showed that a plateau effect was obtained in vitro for HU concentrations above 1 mM, killing about 40% of regenerating progenitor cells or normal proliferative granulocytes. Similarly, a plateau effect was found for doses exceeding about 15 mg i.p., when lethal effects on 3-4 day DC cultures were measured. Time-response studies in vitro showed that about 60% of maximum killing was achieved after only 10 min, with a levelling off of the effect for exposure times between 1 and 3 h. Total depression of 3H-thymidine incorporation in DC cultures was achieved in less than 0.5 h, and subsided within 4-6 h, after one i.p. injection of 23 mg HU. HU had no appreciable effect on DCPC of adult normal marrow, but killed 15% of agar colony-forming cells.