Uptake and metabolism of daunorubicin by human myelocytic cells

Abstract

Daunorubicin uptake and metabolism were studied in vitro with human myeloid leukemia cell lines (KG1, ML1); erythroleukemia cell line (K562); and myeloblasts from two untreated patients with acute myelogenous leukemia (AML). Uptake of daunorubicin by all the above was very similar, but metabolism of daunorubicin to daunorubicinol and the levels of reductase activity were extremely variable. We believe that this heterogeneity accurately reflects the in vivo situation in humans with acute leukemia. In vivo anthracyclines are subject to extensive metabolism, and the majority of patients do metabolize the drug to some extent; it is important, therefore, to use cell lines that reflect the in vivo metabolism. Conversely, rodent cell lines, which apparently lack one of the two major classes of daunorubicin reductase and do not appreciably metabolize daunorubicin, appear to be inadequate as models for studies designed to evaluate the enzymatic mechanisms of daunorubicin metabolism.