Phenotypic variations dictate the intracellular compartmentalization of doxorubicin in normal human bone marrow cells.

In vitro accumulation of doxorubicin in intracellular compartments of normal bone marrow cells was studied with the use of fluorescent microscopy. Both the cytoplasmic and nuclear compartments had distinguishable drug accessibility in the diverse hemopoietic series and in different stages of maturation of each lineage. Nuclei appeared to be more sheltered in the myelogranulocytic series than in the nucleated erythroid cells. Nuclei of activated phagocytic cells of the myelogranulocytic series and macrophages appeared to be the least accessible to doxorubicin uptake. These observations establish that phenotypic variations dictate the patterns of anthracyclines' subcellular compartmentalization. They also suggest that the molecular mechanism contributing to the intracellular trafficking of doxorubicin deserves more substantial investigation that may contribute to our understanding of drug resistance and sensitivity.