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Inhibition of DNA and RNA Metabolism by Daunorubicin and Adriamycin in L1210 Mouse Leukemia¹

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

Effects of daunorubicin and its new analog, adriamycin, on nucleic acid metabolism were studied in vitro in L1210 mouse leukemia cells with labeled nucleoside precursors and were compared with the established effects of actinomycin D. L1210 ascites tumor cells incubated with daunorubicin under physiological conditions of pH, temperature, and tonicity showed significantly greater inhibition of tritiated thymidine incorporation into DNA and ¹⁴C-labeled uridine incorporation into RNA than cells treated with equimolar concentrations of adriamycin.

Investigation of cell-drug interaction showed that uptake of daunorubicin by L1210 cells was substantially greater than adriamycin uptake at 37°; also, daunorubicin was metabolized to daunorubicinol whereas adriamycin did not undergo a similar conversion. Differences in cellular uptake of drug probably play a significant role in the inhibition of nucleic acid metabolism by daunorubicin and adriamycin in L1210 cells in vitro. The importance of other mechanisms operative in determining difference in overall therapeutic efficacy in vivo remains to be established.

¹ Presented in part at the Sixth Joint Meeting of the Clinical Society and the Commissioned Officer Association of the USPHS, Galveston, Texas, April 1971, Abstract 40b.

² Clinical Associate, Baltimore Cancer Research Center, National Cancer Institute, NIH, Baltimore, Md. 21211. Present address: Harvard Medical Unit, Thorndike Memorial Laboratory, Boston City Hospital, Boston, Mass. 02118.

³ To whom reprint requests should be addressed, at the Biochemistry Section, Baltimore Cancer Research Center, 3100 Wyman Park Drive, Baltimore, Md. 21211.

Received 12/ 1/71. Accepted 2/25/72.

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