Speth P A, Raijmakers R A, Boezeman J B, Linssen P C, de Witte T J, Wessels H M, Haanen C
Department of Hematology, St. Radboud University Hospital, Nijmegen, The Netherlands.
Eur J Cancer Clin Oncol. 1988 Apr;24(4):667-74. doi: 10.1016/0277-5379(88)90297-0.
Inhibition of clonogenicity of normal and leukemic human hematopoietic progenitor cells was studied after in vivo and in vitro exposure of bone marrow to adriamycin (ADM). Flow cytometric determination of cellular ADM concentrations in blast cells, expressed in fluorescence units/cell (FU/cell), correlated well with the extent of cytotoxicity. After 2 h in vitro exposure to 500 ng ADM/ml, the ADM concentration of leukemic (n = 7) and normal (n = 4) bone marrow blast cells amounted to 231 +/- 180 and 249 +/- 53 FU/cell respectively, producing moderate decreases in clonogenicity by 44 +/- 30 and 54 +/- 27%. Exposure to 2000 ng/ml produced ADM concentrations of 1184 +/- 472 FU/cell for leukemic blast cells and 1024 +/- 281 FU/cell for normal blast cells. Inhibition of clonogenicity was 96 +/- 7% in leukemic blasts and 99 +/- 1% in normal blasts. In vivo ADM concentrations in leukemic blast cells at 1-2 h after administration were 216 +/- 98 FU/cell (n = 8 patients). This implies that inhibition of clonogenicity after administration of conventional dosages of ADM will be approx. 60-70% for both leukemic and normal bone marrow progenitor cells. Such values were noted in four patients of whom bone marrow was cultured, which was obtained shortly after ADM monotherapy.
研究了骨髓在体内和体外暴露于阿霉素（ADM）后对正常和白血病人类造血祖细胞克隆形成能力的抑制作用。通过流式细胞术测定原始细胞中的细胞ADM浓度，以荧光单位/细胞（FU/细胞）表示，与细胞毒性程度密切相关。体外暴露于500 ng ADM/ml 2小时后，白血病（n = 7）和正常（n = 4）骨髓原始细胞的ADM浓度分别为231±180和249±53 FU/细胞，克隆形成能力分别适度降低44±30%和54±27%。暴露于2000 ng/ml时，白血病原始细胞的ADM浓度为1184±472 FU/细胞，正常原始细胞为1024±281 FU/细胞。白血病原始细胞的克隆形成抑制率为96±7%，正常原始细胞为99±1%。给药后1 - 2小时白血病原始细胞的体内ADM浓度为216±98 FU/细胞（n = 8例患者）。这意味着给予常规剂量的ADM后，白血病和正常骨髓祖细胞的克隆形成抑制率约为60 - 70%。在4例接受ADM单一疗法后不久获取骨髓进行培养的患者中观察到了这样的值。
