The effects of calusterone on hemopoiesis in mice after busulfan-induced suppression of hemopoietic stem cells.
Studies were undertaken in mice to determine the effect of calusterone (a weakly androgenic steroid) on hemopoiesis. Animals were myelosuppressed with a single injection of the alkylating agent busulfan and subsequently treated with varying courses of calusterone. Simultaneous injection of calusterone did not prevent the rapid decline in CFU-S or CFU-C. Daily administration of calusterone for 12 to 14 days after busulfan had little influence on bone marrow cellularity; however, a twofold increase in peripheral blood neutrophils was observed. Bone marrow CFU-S and CFU-C were twofold to threefold higher after 8 to 14 days of treatment with calusterone, but there were no progressive increments in these hemopoietic stem cells during this time interval. In contrast to the granulocyte series, erythroid recovery was rapid after busulfan. Marrow erythroid precursors and CFU-E returned to normal levels by day 8. Daily treatment with calusterone accelerated recovery and led to an overshoot in these parameters of marrow erythropoiesis. Although an early course of calusterone treatment had only modest effects on CFU-S and CFU-C, delayed treatment was clearly stimulatory. A 10-day course of calusterone from days 14 to 24 after busulfan increased bone marrow CFU-S and CFU-C from 5% to 23% of controls to near normal values. Thus calusterone appears to stimulate all classes of hemopoietic progenitor cells. Its effects after busulfan are highly time-dependent, with greatest activity observed in those cellular compartments undergoing proliferative expansion.
D000818:Animals; D002066:Busulfan / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004334:Drug Administration Schedule; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects*; D008777:Methyltestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D013997:Time Factors
D002066:Busulfan; D008777:Methyltestosterone