Erythroid stem cell regeneration in normal and plethoric mice treated with hydroxyurea.

Hydroxyurea (4 x 500 mg/kg at 6 hour intervals) was used to study hemopoietic regeneration in normal and in hypertransfused mice. All recognizable granuloid and erythroid cells, most granulopoietic (CFU-C) and all erythroid (CFU-E) precursors and about 80% of the pluripotent stem cells were eliminated after this treatment. Regeneration started between days 2 and 3 in the marrow and 1 day later in the spleen. An overshoot in CFU-C and CFU-E per femur was seen at day 4. In parallel to their committed precursors granulopoietic cells reappeared between days 2 and 4, erythroblasts between days 3 and 5. In the spleen a maximum CFU-S and CFU-C concentration was seen at day 7. The early increase of CFU-E in the marrow was followed by a fall to low levels, then the CFU-E concentration in the spleen increased. The regeneration was further studied in hypertransfused mice. CFU-S and also CFU-E in the marrow regenerated in exactly the same way as in normal mice and erythroblasts were found in marrow smears. The further maturation of erythroblasts to reticulocytes was impaired in hypertransfused mice, but not in normal mice. The role of erythropoietin (Ep) in the regulation of the CFU-E regeneration is discussed; early differentiation steps seem to be possible without Ep.