Summary
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.
Similar content being viewed by others
References
Ahmed NK, Felsted RL, Bachur NR (1978) Heterogenity of anthracycline antibiotic carbonyl reductases in mammalian livers. Biochem Pharmacol 27: 2713
Ahmed NK, Felsted RL, Bachur NR (1979) Comparison and characterization of mammalian xenobiotic ketone reductases. J Pharmacol Exp Ther 209: 12
Ahmed NK, Felsted RL, Bachur NR (1981) Daunorubicin reduction mediated by aldehyde and ketone reductases. Xenobiotics 11: 131
Andersson LC, Nilsson K, Gahmberg G (1979) K562 A human erythroleukemic cell line. Int J Cancer 23: 143
Bachur NR (1974) Adriamycin-daunorubicin cellular pharmacodynamics. Biochem Pharmacol 2: 207
Bachur NR, Cradock JC (1970) Daunomycin metabolism in rat tissue slices. J Pharmacol Exp Ther 175: 331
Bachur NR, Gee M (1971) Daunorubicin metabolism by rat tissue preparation. J Pharmacol Exp Ther 177: 567
Bachur NR, Moore AL, Bernstein JG, Liu A (1970) Tissue distribution and dispositin of daunomycin (NSC-82151) in mice: fluorometric and isotopic methods. Cancer Chemother Rep 54: 89
Bachur NR, Egorin MJ, Hildebrand RC (1973) Daunorubicin and adriamycin metabolism in the golden syrian hamster. Biochem Med 8: 353–361
Blum RH, Carter SK (1974) A new anticancer drug with significant clinical activity. Ann Intern Med 80: 249
Dano K (1973) Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta 327: 466
DeGregorio WM, Carrera JC, Klock CJ, Wilbur RJ (1982) Uptake and metabolism of daunorubicin by human leukemic cells. Cancer Chemother Pharmacol 10: 29
Felsted RL, Gee M, Bachur NR (1974) Rat liver daunorubicin reductase, an aldo-keto reductase. J Biol Chem 249: 3672
Felsted RL, Richter DR, Bachur NR (1977) Rat aldehyde reductase. Biochem Pharmacol 26: 1117
Huffman DH, Benjamin RS, Bachur NR (1972) Daunorubicin in acute nonlymphocytic leukemia. Clin Pharmacol Ther 13: 895
Ichikawa Y (1969) Differentiation of a cell line of myeloid leukemia. J Cell Physiol 74: 223
Inaba M, Johnson RK (1978) Uptake and retention of adriamycin and daunorubicin by sensitive and anthracycline-resistant sublines of P388 leukemia. Biochem Pharmacol 27: 2123
Inaba M, Kobayashi H, Sakurai Y, Johnson RK (1979) Active efflux of daunorubicin and adriamycin in sensitive and resistant subline of P388 leukemia. Cancer Res 39: 2200
Koeffler HP, Golde DW (1978) Acute myelogenous leukemia: A human cell line responsive to colony-stimulating activity. Science 200: 1153
Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood 45: 321
Minowada J, Sagawa K, Lok MS, Kubonishi I, Nakazawa S, Tatsumi E, Ohnuma T, Goldblum N (1980) A model of lymphoma-myeloid cell differentiation based on the study of marker profiles of 50 human leukemia-lymphoma cell lines. In: Serrou B, Rosenfeld C (eds) International Symposium of New Trends in Human Immunology and Cancer Immunotherapy. Doin, Paris, pp 188–199
Nishimura T, Suzuki H, Muto K, Tanaka N (1979) Mechanism of adriamycin resistance in a subline of mouse lymphoblastoma L5178Y cells. J Antibiot (Tokyo) 32: 518
Nyegaard Co. As. Oslo (1977) Sodium metrizoate solution for isolation of blood cells (Bulletin).
Skovsgaard T (1977) Transport and binding of daunorubicin, adriamycin and rubidazone in Ehrlich ascites tumor cells. Biochem Pharmacol 26: 215
Takanashi S, Bachur NR (1970) Daunorubicin metabolites in human urine. J Pharmacol Exp Ther 175: 331
Takanashi S, Bachur NR (1975) Daunorubicin metabolism in human urine. J Pharmacol Exp Ther 195: 41
Turner AJ, Hick PE (1976) Metabolism of daunorubicin by a barbiturate sensitive aldehyde reductase from rat liver. Biochem 159: 819
Yesair DW, Thayer PS, McNitt S, Teague K (1980) Comparative uptake, metabolism and retention of anthracyclines by tumors growing in vitro and in vivo. Eur J Cancer 16: 901
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vasanthakumar, G., Ahmed, N.K. Uptake and metabolism of daunorubicin by human myelocytic cells. Cancer Chemother. Pharmacol. 15, 35–39 (1985). https://doi.org/10.1007/BF00257291
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00257291