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Differences in uptake of adriamycin and daunomycin by normal BM cells and acute leukemia cells determined by flow cytometry

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Author: Sonneveld, P. · Engh, G.J. van den
Type:article
Date:1981
Institution: Radiobiologisch Instituut TNO
Source:Leukemia Research, 3, 5, 251-257
Identifier: 229054
Keywords: Pharmacology · Acute leukemia · Animal experiment · Blood and hemopoietic system · Drug absorption · Drug comparison · Flow cytometry · Granulocyte · Human cell · In vitro study · Lymphatic system · Lymphoblast · Myeloblast · Pharmacokinetics · Acute Disease · Animal · Bone Marrow · Bone Marrow Cells · Colony-Forming Units Assay · Daunorubicin · Doxorubicin · Fluorometry · Hematopoietic Stem Cells · Human · Leukemia · Lymphocytes · Rats

Abstract

Flow cytometry was used to measure the uptake of adriamycin (AM) and daunomycin (DM) by various cell types of the haemopoietic organs and by acute myeloid leukemia (AML) cells. For this purpose, the spontaneous fluorescence of the drugs upon excitation with laser light at 488 nm was measured. The difference in the uptake of these two drugs correlates with their cytotoxicity. Myeloid progenitor cells from mouse bone marrow (CFU-C) are ten times more sensitive for DM than AM [ED10=0.85 ??g/ml (DM); 6.40 ??g/ml (AM)]. The cytotoxicity of DM is correlated with a higher fluorescence intensity of blast cells, lymphocytes and granulocytes when treated with DM as compared to AM. In contrast to this, the fluorescence of AML blast cells is significantly lower after treatment with DM than with AM. The uptake of both drugs seems to occur following active membrane transport, although to a different extent. Chemicals/CAS: daunorubicin, 12707-28-7, 20830-81-3, 23541-50-6; doxorubicin, 23214-92-8, 25316-40-9; Daunorubicin, 20830-81-3; Doxorubicin, 23214-92-8