Cellular pharmacology of detorubicin and doxorubicin in L1210 cells

Detorubicin (DET), a semi-synthetic analog of daunorubicin, releases at neutral pH doxorubicin (DOX) upon hydrolysis. DET enters faster than DOX into the cultured L1210 cells and reaches higher intracellular levels. When the cells are incubated for 120 min at pH 6.5, in spite of its rapid hydrolysis, one third of the intracellular fluorescence was due to undegraded DET. DET, like the Other anthracyclines studied, is found associated intracellularly only to the lysosomes and to the nuclei. Unchanged DET is found mainly inside the lysosomes where the drug is stabilized, while DOX is found essentially associated to the nuclear DNA of L1210 cells. DET can therefore be viewed as an hydrophobic prodrug of DOX characterized, however, by a distinct subcellular localization in L1210 cells.