Uptake of the daunorubicin-DNA complex in cultured fibroblasts

The uptake and fate of the daunorubicin-DNA complex have been studied in cultured rat embryo fibroblasts. 125I-DNA was digested by the cells and appeared as low molecular weight fragments in the incubation medium. Subcellular fractionation of fibroblasts, previously incubated with the complex, showed that daunorubicin was localized to nuclei and lysosomes. At a high incubation concentration (17.5 microM), the accumulation of the free drug exceeded that of the complex. However, at a lower concentration (1.75 microM), the accumulation of the complex was as high as that of the free drug. The results are consistent with an uptake of the complex into cultured rat embryo fibroblasts by endocytosis. However, it cannot be excluded that the complex partly dissociates in the incubation medium, and that daunorubicin and DNA thereafter enter the cells separately.