The modification of adriamycin(ADM)with oxidized dextran (OXD) make it possible to obtain high local concentration of ADM in the tumors. The intracellular behavior of ADM-OXD was studied to elucidate the mechanism of the cytotoxic action. Intracellular distribution of ADM was detected by fluorescence microscopy. The fluorescence of the cells treated with ADM-OXD was detected mainly in the cytosol 30min after treatment, and then it was shifted to the nuclei 6 hrs after treatment. On the other hand the fluorescece of the cells treated with ADM was detected mainly in the nuclei 30 min after treatment. [14C] ADM-OXD was prepared using 14C-ADM and the cell lysate following [14C] ADM-OXD treatment was subjected to GPC. The radioactivities were eluted at low molecular fraction which was similar to the case of ADM treatment. However, this shift to low molecular fraction was not observed by the addition of NH4Cl in the medium. Adriamycin-oxidized dextran conjugate prepared by amide bond which is stable under acidic condition had very low cytotoxic activity as compared with ADM-OXD, prepared by Schiff's base, which had a characteristics to release ADM under acidic condition. These findings suggested that ADM-OXD was uptaked into cells in the conjugated form and then ADM was released from ADM-OXD in the cells.
