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Daunorubicin Metabolism by Human Hematological Components¹

Biochemistry Section, Laboratory of Pharmacology, Baltimore Cancer Research Center, National Cancer Institute, USPHS Hospital, Baltimore, Maryland 21211

Daunorubicin, an antitumor antibiotic that is widely used in the treatment for acute leukemia, is converted to daunorubicinol by a cytoplasmic enzyme, daunorubicin reductase, in rat tissues. We find that intact human blood elements, as well as homogenates, can catalyze this reaction. In both leukocytes and erythrocytes, enzymatic activity is cytoplasmic and heat labile, requires NADPH, and does not require molecular oxygen. Of formed blood components, specific activities (per mg protein) rate as follows: lymphocyte > whole WBC > bone marrow > RBC > platelet. No activity is detected in cell-free plasma. The characteristics of daunorubicin reductase show it to be a constitutive enzyme unlike the classic drug-metabolizing system.

¹ A preliminary report of this work was presented at the Meeting of the American Federation for Clinical Research, May 3, 1970, in Atlantic City, N. J.

² Present address: Clinical Pharmacology Study Unit, University of Kansas Medical Center, Kansas City, Kan. 66103.

³ To whom reprint requests should be addressed at the Biochemistry Section, Laboratory of Pharmacology, Baltimore Cancer Research Center, National Cancer Institute, USPHS Hospital, 3100 Wyman Park Drive, Baltimore, Md. 21211.

Received 9/29/71. Accepted 12/ 8/71.

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