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Doxorubicin-resistant friend erythroleukemia cells are less resistant towards N,N-dimethylated antracylines


American Association for Cancer Research:
American Association for Cancer Research. Annual Meeting 1991. Proceedings
Baltimore, 1991 (Proceedings of the American Association for Cancer Research 32)
American Association for Cancer Research (Annual Meeting) <82, 1991, Houston/Tex.>
Fraunhofer ITA ( ITEM) ()
anthracycline; cell; daunorubicin; DNA; doxorubicin; Leukämiezelle; leukemia cell; Zelle

The growth inhibitory effect of doxorubicin (DOX), daunorubicin (DNR), N, N-dimethylDOX (DMDOX), and N, N-dimethylDNR (DMDNR), was investigated in Friend erythroleukemia cells (F4-6/MDR). These cells were obtained by exposure of F4-6 cells to doxorubicin up to a concentration of 1Myg/ml. Extensive expression of the MDR1 gene was demonstrated by Northern blot analysis. In wild type cells, all four anthracyclines inhibited cell growth to 50% at concentrations between 3 and 6 ng/ml. In F4-6/MDR cells, the following IC sub 50 values were obtained: DOX (1155 ng/ml), DNR (463 ng/ml), DMDOX (127 ng/ml), DMDNR (26 ng/ml). Using 14C-labelled compounds, significant differences in drug accumulation between F4-6 and F4-6/MDR cells were observed with DNR but not with DMDNR. Thus the decreased resistance of F4-6/MDR cells towards the N-alkylated anthracyclines may be due to the failure of the efflux pump to extrude these compounds. The results should be of clinical importance. This work was supporte d by Deutsche Forschungsgemeinschaft, Bonn.