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

Abstract

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.

Cytokinetic Studies on Slowly-Renewing Bone Marrow and Spleen Lymphocytes in Rats During a Primary and a Secondary Immune Response

“…Therefore, the interpretation would again be that only few, if any, of these cells did react to antigen stimula tion. Similar findings could be demonstrated under regeneratory demand [6,7]. However, the reticular cells and histiocytes of the spleen showed a decrease of their labelling index without a marked diminuation of the mean grain count.…”

“…In the spleen of mice only 0.10-0.20 immuno competent cells for a specific antigen could be detected per 10° cells [1,2,8], Therefore, the conclusion would be that under immune stimulation, the mass of long-living lymphocytes does not react in the sense of a trans formation or proliferation. In contrast to that behaviour, as could be shown in previous work, the mass of bone-marrow lymphocytes did react under regeneratory stimulus [6,7].…”

“…mation of such resting bone-marrow lymphocytes during regeneration of an aplastic bone marrow were shown [6,7].…”

Alteration of Rat Bone Marrow Megakaryocytes Following Administration of Cytosine Arabinoside, Daunomycin and Hydroxyurea

“…[1] and T alley and Vaitkevicius [17] who observed chromo somal abnormalities in bone marrow red cell and white cell precursors in patients treated with Ara-C, with the finding of R u sco n i el al. [16] of incor poration of D into rat bone marrow cells, with the demonstration by M illa r and B la c k ett [11] of sensitivity to D of rat bone marrow erythropoietin response cells and maturing erythroid cells, and with the destruction of pro liferating bone marrow of HU-treated rats shown by Bohne et al [3], Similarly, the decreased lobulation of M-III nuclei found in rats treated with Ara-C or D may reflect an impairment of endomitosis resulting from the action of these drugs on megakaryoblasts' DNA and/or its synthesis. Bell et al [1] found abnormally large red cell precursors with gigantic indented nuclei having irregular borders in Ara-C treated patients.…”

“…The effects of various cytotoxic agents on hema topoietic precursor cells in rat bone marrow was studied by several investi gators [3,11,14,16], It has been found that D is taken up by rat bone marrow elements [16] and affects erythroid precursors [11] and that HU destroys proliferating rat bone marrow cells [3], To our knowledge no reports have appeared on the effects of Ara-C, D and HU on bone marrow mega karyocytes in the rat. The present study was undertaken to investigate the effects of these drugs on this cell line in this animal.…”