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Uptake and metabolism of daunorubicin by human leukemia cells

  • Original Articles
  • Daunorubicin Leukemia
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Summary

Radiolabeled daunorubicin was used to study in vitro uptake of daunorubicin (DNR) by the human promyelocytic leukemia cell line HL-60 and by leukemic cells from five previously untreated patients with acute nonlymphocytic leukemia (ANLL). Uptake of the metabolite daunorubicinol (DOL) and the metabolism of DNR were examined using high-performance liquid chromatography (HPLC). Uptake of DNR and DOL by HL-60 and ANLL cells exhibited a similar kinetic pattern. The uptake of DOL was 35%–50% of the uptake of DNR at the same test concentration in both HL-60 and ANLL cells. Approximately 5%–10% of intracellular DNR was metabolized to DOL by HL-60 and ANLL cells after 24 h of drug exposure. Measurements of DNR or DOL derived from liquid scintillation spectrometry and HPLC permit a sensitive and accurate assessment of the pharmacokinetics of these drugs in human leukemia cells. In addition, the HL-60 cell line can be used as a model for studying in vitro pharmacokinetics of the anthracyclines.

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Authors and Affiliations

  1. Children's Cancer Research Institute, S-512 Pacific Medical Center, 94115, San Francisco, CA, USA

    Michael W. DeGregorio & Jordan R. Wilbur

  2. Institute of Cancer Research, Medical Research Institute, Paclfic Medical Center, 94115, San Francisco, CA, USA

    John C. Klock

  3. Cancer Research Institute, University of California, 94143, San Francisco, CA, USA

    Michael W. DeGregorio & Carlos J. Carrera

Authors
  1. Michael W. DeGregorio
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  2. Carlos J. Carrera
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  3. John C. Klock
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  4. Jordan R. Wilbur
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DeGregorio, M.W., Carrera, C.J., Klock, J.C. et al. Uptake and metabolism of daunorubicin by human leukemia cells. Cancer Chemother. Pharmacol. 10, 29–32 (1982). https://doi.org/10.1007/BF00257233

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  • DOI: https://doi.org/10.1007/BF00257233

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