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Effect of Adriamycin on DNA, RNA, and Protein Synthesis in Cell-free Systems and Intact Cells¹

Department of Pediatrics, University of Southern California School of Medicine, Los Angeles 90033, and Division of Hematology-Oncology, Childrens Hospital of Los Angeles, Los Angeles, California 90027

The effect of adriamycin on DNA, RNA, and protein synthesis was investigated in cell-free systems and intact cells. In studies with purified mammalian cell enzymes, adriamycin produced a greater inhibition of DNA-dependent DNA polymerase than of RNA polymerase. The extent of inhibition of both these enzymes was decreased by increasing the concentration of the DNA template in the reaction mixture. In studies with isolated nuclei, adriamycin was also a more potent inhibitor of DNA synthesis than of RNA synthesis. However, with intact cells, adriamycin inhibited both DNA and RNA synthesis to about the same extent. The inhibition produced by adriamycin on RNA synthesis in intact cells was greater than that observed in the cell-free systems. Adriamycin inhibited protein synthesis in a cell-free system consisting of polyribosomes, transfer RNA, and enzymes but did not inhibit protein synthesis in intact cells. These differences in the pattern of inhibition may be due to biotransformation of the drug and/or preferential binding to chromosomal DNA in the intact cell.

¹ This investigation was supported by Grant CI-85-D from the American Cancer Society and USPHS Grant CA-11050 from the National Cancer Institute.

² Scholar of Leukemia Society of America. Deceased November 16, 1974.

Received 1/ 5/76. Accepted 4/23/76.

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