Summary
Leukemic cells from seven patients with acute nonlymphoblastic leukemia and granulocytes, and mononuclear cells from three healthy controls were isolated by centrifugation on metrozoate-dextran. The intracellular accumulation of both the free and DNA-bound forms of daunorubicin and doxorubicin was studied in vitro. The uptake of unbound daunorubicin was higher than that of doxorubicin. At drug concentrations of 1.75 μM and higher the uptake of the free drugs was greater than that of the bound forms, but at lower drug concentrations the uptake was about the same. This could at least partly be explained by a greater dissociation of the DNA-drug complexes at lower drug concentrations. The uptake into normal leukocytes was of the same order of magnitude as that into leukemic cells. There was a great interindividual variation in the accumulation of both free and DNA-bound drugs in the cells from leukemic patients. This variation might be of importance for the prediction of individual sensitivity to the different drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bachur, N. R., Steele, M., Meriwether, W. D., Hildebrand, R. C.: Cellular pharmacodynamics of several anthracycline antibiotics. J. Med. Chem. 19, 651 (1976)
Baurain, R., Zenebergh, A., Trouet, A.: Cellular uptake and metabolism of daunorubicin as determined by high pressure liquid chromatography: Application to L 1210 cells. J. Chromatogr. (In press, 1978)
Böyum, A: Isolation of leucocytes from human blood. Further observation. Scand. J. Clin. Lab. Invest. [Suppl.] 97, 1 (1968)
Calendi, E., Marco, A., Reggiani, M. di, Scarpinati, B., Valenti, L.: On physico-chemical interaction between daunomycin and nucleic acids. Biochim. Biophys. Acta 103, 25 (1965)
Chervinsky, D. S., Wang, J. J.: Uptake of adriamycin and daunorubicin in L 1210 and human leukemia cells: A comparative study. J. Med. 7, 63 (1976)
Duve, C. de, Pressman, B. C., Gianetto, R., Wattiaux, R., Appelmans, F.: Intracellular distribution patterns of enzymes in ratliver tissue. Biochem. J. 60, 604 (1955)
Duve, C. de, Barsy, T. de, Poole, B., Trouet, A., Tulkens, P., Hoof, F. van: Lysosomotropic agents. Biochem. Pharmacol. 23, 2495 (1974)
Eksborg, S., Ehrsson, H., Andersson, B., Beran, M.: Liquid chromatographic determination of daunorubicin and daunorubicinol in plasma from leukemic patients. J. Chromatogr. 153, 211 (1978)
Ferrant, A., Hulhoven, R., Bosly, A., Cornu, G., Michaux, J. L., Sokal, G.: Clinical trials with daunorubicin-DNA and adriamycin-DNA in acute lymphoblastic leukemia and bronchogenic carcinoma. Cancer Chemother. Pharmacol. 2, 67–71 (1979)
Lowry, O. M., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265 (1951)
Noël, G., Peterson, C., Trouet, A., Tulkens, P.: Uptake and subcellular localization of daunorubicin and adriamycin in cultured fibroblasts. Eur. J. Cancer 14, 363 (1978)
Pigram, W. J., Fuller, W., Hamilton, L. D.: Stereochemistry of intercalation interaction of daunomycin with DNA. Nature [New Biol.] 235, 17 (1972)
Skovsgaard, T.: Transport and binding of daunorubicin, adriamycin and rubidazone in Ehrlich ascites tumor cells. Biochem. Pharmacol. 26, 215 (1977)
Trouet, A., Deprez-de Campeneere, D., Duve, C. de: Chemotherapy through lysosomes with a DNA-daunorubicin complex. Nature [New Biol.] 239, 110 (1972)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Paul, C., Peterson, C., Gahrton, G. et al. Uptake of free and DNA-bound daunorubicin and doxorubicin into human leukemic cells. Cancer Chemother. Pharmacol. 2, 49–52 (1979). https://doi.org/10.1007/BF00253105
Issue Date:
DOI: https://doi.org/10.1007/BF00253105