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Hemin Enhances the Sensitivity of Erythroleukemia Cells to 1-ß-D-Arabinofuranosylcytosine by Both Activation of Deoxycytidine Kinase and Reduction of Cytidine Deaminase Activity¹

Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina, Saitama-362, Japan

The sensitivity of human myelogenous leukemia cells to 1-ß-D-arabinofuranosylcytosine (ara-C) during induction of differentiation was examined. Treatment with hemin greatly increased the sensitivity of erythroid leukemia cells to ara-C. The enhancement of ara-C sensitivity by hemin was not as remarkable in nonerythroid leukemia cells. Hemin altered the metabolism of ara-C in human erythroleukemia K562 cells by reducing ara-C deaminase activity, increasing intracellular accumulation of ara-C, and activating the nucleoside kinases. These alterations may be involved in the enhancing effect of hemin on sensitivity of ara-C. These results suggest that some inducers of differentiation potentiate the antileukemic effect of ara-C on human erythroleukemia cells.

¹ This work was supported by Grants-in-Aid for Cancer Research from the Ministery of Education, Science and Culture, and from the Ministry of Welfare and Health, Japan.

² To whom requests for reprints should be addressed.

Received 1/ 2/91. Accepted 6/13/91.

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