Fried W, Johnson C
Department of Medicine, Veterans Administration West Side Hospital.
Radiat Res. 1968 Dec;36(3):521-7.
The effects of cyclophosphamide on hematopoietic stem cells (HSC) and on hematopoiesis was studied. Administration of 5 mg of cyclophosphamide to mice resulted in a rapid decrease in the number of HSC in the leg and spleen. The exocolonizing potential of HSC in the spleen recovered and reached supranormal levels in 7 days. That of HSC in the legs recovered to pretreatment values after 15 days. The endocolonizing potential of HSC in the leg, however, recovered in less than 4 days. The peripheral blood counts all dropped to a fraction of normal except for the platelet count, which was affected to a minimal degree. We suggest that cyclophosphamide irreparably damages most of the body's HSC. Those remaining in the leg then proliferate rapidly and repopulate other sites. HSC cannot, however, accumulate in the leg for more than a week after cyclophosphamide administration. Erythropoiesis does not recover until after this occurs. Platelets are least affected because of their resistance to the effects of the drug and because of the ability of megakaryocytes to increase their output of platelets without requiring differentiation of HSC into their compartment.
研究了环磷酰胺对造血干细胞(HSC)及造血作用的影响。给小鼠注射5毫克环磷酰胺后,腿部和脾脏中的HSC数量迅速减少。脾脏中HSC的外植潜力在7天内恢复并达到超正常水平。腿部HSC的外植潜力在15天后恢复到预处理值。然而,腿部HSC的内植潜力在不到4天内就恢复了。除血小板计数受影响最小外,外周血细胞计数均降至正常水平的几分之一。我们认为环磷酰胺会对机体的大多数HSC造成不可修复的损伤。留在腿部的HSC随后迅速增殖并重新填充其他部位。然而,在给予环磷酰胺后,HSC在腿部的积聚不会超过一周。直到这种情况发生后,红细胞生成才会恢复。血小板受影响最小,这是因为它们对药物的作用具有抗性,还因为巨核细胞能够在不需要HSC分化进入其区室的情况下增加血小板的产量。