DIFFERENCES IN DAUNOMYCIN RETENTION IN SENSITIVE AND RESISTANT P388 LEUKEMIC-CELLS AS DETERMINED BY DIGITIZED VIDEO FLUORESCENCE MICROSCOPY

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (9) , 4167-4171
Abstract
Cellular uptake and binding of daunomycin was studied using the digitized video fluorescence microscopy technique, in a sensitive and a resistant subline of P388 leukemic ascites tumor cells. When a 60 min time course of uptake was monitored, the sensitive cells had a 4-fold greater uptake than did the resistant cells. When the cells were perfused with drug-free medium, identical exchangeable levels of the drug were lost from both sublines. The difference in drug uptake could be accounted for entirely on the basis of differences in a slowly exchanging drug fraction which probably represents bound intracellular drug. In glucose-free medium, uptake of daunomycin was accelerated by metabolic inhibition to a greater extent in resistant than in sensitive cells. Furthermore, there was minimal decrease in the fluorescence when both sublines were perfused with drug-free medium. The addition of glucose to this medium induced a significant decrease in fluorescence in resistant but not in sensitive cells. Apparently, decreased drug uptake in resistant cells associated with decreased slowly exchanging drug fraction may be associated with an inherent defect in drug binding which is reversed by inhibition of energy metabolism.