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Comparative Biochemical Studies of Adriamycin and Daunomycin in Leukemic Cells¹

Department of Pediatrics [J. J. W., D. S. C.] and Experimental Therapeutics [J. M. R.], Roswell Park Memorial Institute, Buffalo, New York 14203

Adriamycin (AM) and daunomycin (DM) were compared as inhibitors of nucleic acid and protein biosynthesis in L1210 leukemic cells. In vivo, both antibiotics markedly inhibited, without significant difference, the incorporation of the labeled precursors into DNA and RNA. In vitro, at a concentration of 5 or 10 g/ml, DM was significantly more effective than AM in inhibiting DNA and RNA synthesis in L1210 leukemic cells. Results of studies with leukemic cells isolated from the blood of patients are the same as those obtained with L1210 cells in vitro.

The reaction catalyzed in vitro by DNA polymerase, isolated from L1210 cells, was equally inhibited by AM and DM, although no effect on the enzyme was seen when the drugs were given in vivo. Studies with L1210 cells, resistant to AM or DM, suggest cross-resistance between the drugs.

¹ This work was supported in part by United Health Fund Grant C1-7-RP-70, and by American Cancer Society Institutional Research Grant IN-54-K5.

² To whom reprint requests should be addressed at the Department of Pediatrics, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, N. Y. 14203.

³ Present address: Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tenn.

Received 7/30/71. Accepted 12/ 3/71.