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Cancer Chemotherapy and Pharmacology

, Volume 29, Issue 1, pp 7–12 | Cite as

Intracellular uptake and cytotoxic effect in vitro of doxorubicin and epirubicin in human leukemic and normal hematopoietic cells

  • Ulf Tidefelt
  • Britt Sundman-Engberg
  • Christer Paul
Original Articles Doxorubicin, Epirubicin, Cytotoxicity, Leukemia

Summary

Leukemic cells from patients presenting with acute nonlymphoblastic leukemia and normal hematopoietic bone marrow cells from healthy donors for allogeneic bone marrow transplantation were incubated for 3 h with doxorubicin and epirubicin at different concentrations. The intracellular uptake at the end of the incubation was determined by photofluorometry in leukemic cells from 15 patients and in normal cells from 9 donors for bone marrow transplantation. Cytotoxicity in vitro against granulocyte/macrophage colony-forming units (CFU-GM) was determined in normal cells from 7 donors, and in vitro toxicity against leukemic cells was determined by a clonogenic technique in cells from 6 patients and by vital dye staining (DiSC) following 4 days' culture in cells from 15 patients. Epirubicin was significantly less toxic than doxorubicin to normal hematopoetic cells (72%±20% survival of cells for epirubicin vs 45%±13% for doxorubicin at a concentration of 0.2 μm;P≤0.005). As analyzed by the DiSC assay, 0.2 μm epirubicin was slightly more toxic to leukemic cells than was the same concentration of doxorubicin (47% vs 61% survival,P≤0.01), but the clonogenic assay revealed no difference in toxicity to leukemic cells. At a concentration of 0.2 μm, the mean intracellular uptake of epirubicin in leukemic cells was 0.43±0.26 nmol/mg protein as compared with 0.33±0.14 nmol/mg protein for doxorubicin (not significant). In normal cells, the uptake of epirubicin at a concentration of 0.2 μm was 0.47±0.25 nmol/mg protein as compared with 0.31±0.21 nmol/mg protein for doxorubicin (not significant). The reduced myelotoxicity observed in vitro together with the retained toxicity to leukemic cells indicates that the therapeutic index of epirubicin is better than that of doxorubicin.

Keywords

Doxorubicin Normal Cell Leukemic Cell Bone Marrow Transplantation Bone Marrow Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Ulf Tidefelt
    • 1
    • 2
  • Britt Sundman-Engberg
    • 1
    • 2
  • Christer Paul
    • 1
    • 2
  1. 1.Division of Clinical Hematology and Oncology, Department of MedicineHuddinge HospitalHuddingeSweden
  2. 2.Karolinska InstitutetHuddingeSweden

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