Effects of granulocyte colony-stimulating factor on hematopoietic injury induced by anticancer drugs in mice.

Y Mizushima, T Morikage, T Kuwahara, S Yano
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Abstract

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 micrograms 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.

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粒细胞集落刺激因子对抗癌药物致小鼠造血损伤的影响。
在BALB/c小鼠中评估皮下给药粒细胞集落刺激因子(G-CSF)对化疗诱导的造血损伤的体内影响。接受化疗药物治疗的小鼠每天一次注射2微克重组人G-CSF,持续12天,然后在G-CSF治疗停止24小时后测量骨髓细胞量、脾脏重量和外周血细胞计数。正常小鼠的治疗对白细胞(WBC)计数的升高或宿主对肺炎克雷伯菌感染的抵抗力的影响微乎其微。正常小鼠经G-CSF处理后,脾脏重量明显增加,血小板计数略低。在用环磷酰胺(150 mg/kg)处理的小鼠中,G-CSF处理导致白细胞升高和抗菌药物耐药性增强。在盐酸尼莫司汀(50mg /kg)-、丝裂霉素c (8mg /kg)-或硫酸长春地碱(4mg /kg)处理的小鼠中,G-CSF处理对中性粒细胞的加速恢复也有不同程度的影响。在给予G-CSF的MMC或vds处理的宿主中,观察到PLT计数显著减少。这些结果表明,给予G-CSF可能促进化疗癌症患者的造血功能恢复,并可能帮助他们增强对危及生命的感染的抵抗力。相反,与单纯化疗相比,G-CSF和化疗药物治疗可能导致更严重的血小板减少症。
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