Uptake and metabolism of daunorubicin by human leukemia cells

Abstract

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.