INTRACELLULAR-DISTRIBUTION AND INTRACELLULAR DYNAMICS OF A SPIN-LABELED ANALOG OF DOXORUBICIN BY FLUORESCENCE AND EPR SPECTROSCOPY

Fluorescence spectroscopy revealed a dramatic difference between the i ntracellular distributions of doxorubicin (DOX) and its paramagnetic a nalogue, ruboxyl (Rb). Modification of the anthracyclin structure by i ntroduction of a paramagnetic label at position 14 in the DOX molecule resulted in reduced DNA binding and enhanced partitioning into phosph olipid membranes, as evidenced by the fluorescence-quenching experimen ts. Higher partitioning into cell membranes resulted in stronger intra cellular fluorescence of Rb. In addition, a paramagnetic label on the Rb molecule provided a unique opportunity for an EPR investigation of the drug's intracellular distribution and dynamics. The observed chang es in the EPR spectra of drug-containing cells during their life cycle suggested either a progressive release of the intercalated drug, cell membrane fluidization, or both.