title: 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.
mesh_terms: D000208:Acute Disease; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D013997:Time Factors
chemical_list: D003630:Daunorubicin