Comparative uptake, retention and cytotoxicity of daunorubicin by human myeloid cells

We studied the cellular uptake and retention of daunorubicin (D1) in two human leukemic cell lines (ML1 and K562) and myecloblasts from an untreated patient with acute myelogenous leukemia (AML). The rate of uptake and the steady-state level of D1 were not temperature dependent but increased markedly with increases in the pH of the medium. Also, saturation kinetics were not demonstrable using concentrations of D1 up to 111 microM. Together, these observation suggest a transport mechanism for D1 compatible with passive diffusion. Accumulation of D1 was increased only in cells from the AML patient with addition of sodium azide, whereas drug efflux was not increased significantly in the presence of glucose in MLI or K562 cells. Although the rate of uptake and steady-state levels of D1 were the same in these cells, metabolism and cytotoxicity of D1 differed. Our results indicate that ML1 cells can be used as a pharmacologic model for studying the metabolism and resistance of D1 in vivo.