EFFECTS OF RHG-CSF, 5-FLUOROURACIL AND EXTRAMEDULLARY IRRADIATION ON MURINE MEGAKARYOCYTOPOIESIS IN-VIVO

The aim of this study was to systematically characterize possible rhG- CSF effects on the murine megakaryocyte-platelet system (untreated and recovering from chemotherapy or extramedullary irradiation). In untre ated, splenectomized male B6D2F1 mice, rhG-CSF treatment (50 mu g/kg/d for up to 8 d) markedly decreased femoral megakaryocytopoiesis. CFU-M eg, small acetylcholinesterase-positive (SAChE) cells, and megakaryocy tes were significantly reduced to 35-70%; platelets, however, were not affected. Peripheral CFU-Meg and CFU-GM increased up to 200-fold. Fol lowing a single injection of 5-FU (150 mg/kg) on day 0, rhG-CSF (50 mu g/kg/d) on days 1-8 suppressed the megakaryocytopoietic recovery as i ndicated by significantly lower platelet numbers on day 9. Granulopoie tic recovery was accelerated by rhG-CSF. When rhG-CSF treatment was st arted on day 5, no beneficial effect on granulopoietic recovery was ob served, but again platelet levels were significantly lower on day 9, i ndicating that within the first 4 d of rhG-CSF application, recruitmen t or lineage competition was not a critical event. To test for the eff ects of extramedullary irradiation on circulating progenitors, mice pr etreated with 50 mu g/kg/d of rhG-CSF for 8 d received irradiation to the chest with 500 cGy resulting in a substantial kill of circulating CFU-Meg and CFU-GM of up to 99%. However, this striking decrease of bl ood progenitors did not significantly affect their total body contents . This study indicates that rhG-CSF treatment can impair bone marrow m egakaryocytopoiesis, which might be an important consideration for tho se clinical situations that carry a high potential for treatment-induc ed thrombocytopenia.