The Role of Slowly Proliferating Cells in Rat Bone Marrow during. Regeneration following Hydroxyurea

Summary. Rats were labelled with 3H‐thymidine (3H‐TdR) in utero and for 6 weeks after birth to obtain 100% labelling of all the cells in the animals. 6 weeks after the last 3H‐TdR injection only cytokinetically resting cells were still labelled. In bone marrow these were cells of the bone marrow matrix and a fraction of small bone marrow lymphocytes. At this time the effect of hydroxyurea (HU) on bone marrow and especially on the resting cells of this organ was studied. Animals which had received 4x 500 mg HU/kg at 6 hr intervals showed a destruction of all proliferating cells of the bone marrow. Regeneration started 4 days after HU‐treatment and was not completed before 10 days afterwards. The resting matrix cells did not change in number or labelling intensity which shows that they were neither destroyed nor stimulated to proliferate during regeneration. In contrast, the resting small bone marrow lymphocytes showed a dilution of labelling intensity, and after an initial increase, a decrease of their number during recovery of bone marrow. At the same time a new class of labelled cells which was identified as undifferentiated blast cells appeared, and later on labelled erythroid and myeloid precursor cells could be observed. The labelling of these cells disappeared c 6 days after HU‐treatment. Animals which received a single injection of the total dose of 2000 mg/HU/kg showed essentially the same effects but a markedly smaller response to the drug.