EFFECTS OF GRANULOCYTE COLONY-STIMULATING FACTOR ON HEMATOPOIETIC INJURY INDUCED BY ANTICANCER DRUGS IN MICE

The in vivo effects of the subcutaneous administration of the granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced hematopoietic injury were evaluated in BALB/c mice. Mice treated with chemotherapeutic drugs were injected once a day for up to 12 days with 2-mu-g of recombinant human G-CSF, and following this, bone marrow cellularity, spleen weight, and peripheral blood cell counts were measured 24 h after cessation of the G-CSF treatment. Treatment of normal mice had minimal effect on the elevation of the white blood cell (WBC) count or on the hosts' resistance to K. pneumoniae infection. Spleen weight was significantly higher in normal mice treated with G-CSF, and the platelet counts were slightly lower. In mice treated with cyclophosphamide (150 mg/kg), G-CSF treatment caused an elevation of WBC and an enhancement of antibacterial resistance. Variable amounts of an accelerated recovery of neutrophils by G-CSF treatment was also observed in nimustine hydrochloride (50 mg/kg)-, mitomycin c (MMC) (8 mg/kg)-, or vindesine sulfate (VDS) (4 mg/kg)-treated mice. A significant decrease in PLT counts was observed in MMC- or VDS-treated hosts given G-CSF. These results indicate that administration of G-CSF may facilitate hematopoietic recovery in chemotherapy-treated cancer patients and that it may help them to increase their resistance to life-threatening infection. Conversely, treatment with G-CSF and chemotherapeutic drugs may cause a more severe thrombocytopenia than is observed with only chemotherapy treatment.