Uptake and intracellular distribution of doxorubicin metabolites in B-lymphocytes of chronic lymphocytic leukemia.

作者：EN Dessypris, Dean E. Brenner, MR Baer, Kenneth R. Hande · 发表于：PubMed · 年份：1988 · 被引用次数：22 · 研究领域：Chronic Lymphocytic Leukemia Research、Cancer Treatment and Pharmacology、HER2/EGFR in Cancer Research

The toxicity of doxorubicin metabolites was evaluated on lymphocytes of B-cell chronic lymphocytic leukemia. Only doxorubicinol was found to be cytotoxic for these lymphocytes, whereas exposure to aglycones at concentrations as high as 5 microM for 1 h had no effect on the proliferative capacity of these cells. After exposure of cells to isomolar concentrations of doxorubicin or its metabolites, uptake/retention of doxorubicinol was 23% of doxorubicin, and uptake/retention of aglycones was 5 to 13% of doxorubicin. Seventy to 90% of doxorubicin and 60 to 90% of doxorubicinol taken up/retained by the cells were detected in the cell nuclear fraction, whereas only 20 to 40% of the aglycones were localized in the cell nucleus. Cytotoxicity of metabolites was generally related to the proportion of drug taken up/retained by the cells and localized to the nuclei. The low uptake and nuclear localization may be at least partially responsible for the lack of cytotoxicity of aglycones on B-lymphocytes from chronic lymphocytic leukemia.