Nowrousian M R, Schmidt C G
Br J Cancer. 1982 Sep;46(3):397-402. doi: 10.1038/bjc.1982.216.
The effects of Cisplatin on marrow haemopoietic progenitor cells, WBC and RBC were measured and compared in F1 (CBA x C57BL) female mice. Dose/survival curves of Cisplatin for CFU-S, CFU-C and BFU-E were found to be simply exponential, indicating that the effect of the drug has no cell-cycle dependency. BFU-E also appeared significantly (P less than 0.001) more sensitive to Cisplatin than CFU-S and CFU-C. After a single dose of 12 mg/kg of Cisplatin, WBC, MNC and CFU-E were seen to be markedly less reduced and to recover much earlier than CFU-C, and particularly BFU-E and CFU-S. Results suggest that the drug is more toxic for earlier haemopoietic progenitor cells than for the more mature cells, and that the latter are not reliable parameters for complete haemopoietic recovery in mice after treatment with this agent. In the animals treated, there was also a subsequent significant decrease of the RBC count, accompanied by a marked increase of the marrow CFU-E concentration. Possible underlying mechanisms (e.g. alterations of RBC after exposure to Cisplatin) were discussed.
在F1(CBA×C57BL)雌性小鼠中测量并比较了顺铂对骨髓造血祖细胞、白细胞和红细胞的影响。发现顺铂对脾集落形成单位(CFU-S)、粒系集落形成单位(CFU-C)和爆式红系集落形成单位(BFU-E)的剂量/存活曲线呈简单指数关系,表明该药物的作用无细胞周期依赖性。BFU-E对顺铂的敏感性也显著高于CFU-S和CFU-C(P小于0.001)。单次给予12mg/kg顺铂后,白细胞、单核细胞和BFU-E的减少程度明显低于CFU-C,尤其是BFU-E和CFU-S,且恢复得更早。结果表明,该药物对早期造血祖细胞的毒性大于对更成熟细胞的毒性,并且在小鼠经该药物治疗后,后者并非完全造血恢复的可靠指标。在接受治疗的动物中,红细胞计数随后也显著下降,同时骨髓BFU-E浓度显著升高。文中讨论了可能的潜在机制(如接触顺铂后红细胞的改变)。