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[Cancer Research 39, 4396-4400, November 1, 1979]
© 1979 American Association for Cancer Research

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Cellular Accumulation and Disposition of Aclacinomycin A

Merrill J. Egorin1, Ronald E. Clawson, Louis A. Ross, Norman M. Schlossberger and Nicholas R. Bachur

Laboratory of Clinical Biochemistry, Baltimore Cancer Research Program, Division of Cancer Treatment, National Cancer Institute, NIH, Baltimore, Maryland 21201

The cellular accumulation and disposition of the anthracycline antitumor antibiotic aclacinomycin A (ACM) were compared to those of daunorubicin. Although both drugs were avidly accumulated by cells, intracellular concentrations of ACM were two to three times those of daunorubicin. Whereas lowered temperature (0°) reduced intracellular accumulation of both drugs, 10 mM sodium azide had no effect on accumulation of either ACM or daunorubicin. Both drugs exited from cells placed in drug-free medium, a process that was reduced at 0° but not altered by 10 mM sodium azide. Unlike whole cells, isolated nuclei accumulated more daunorubicin than ACM. This process was not altered at 0°. Both drugs were lost from nuclei placed in drug-free buffer, a process that was reduced at 0°. Unlike daunorubicin, which localized in cell nuclei, ACM localized in the cytoplasm with no detectable nuclear fluorescence. Although both drugs produced dose-dependent inhibitions of [3H]thymidine and [3H]uridine incorporation by L1210 and P388 cells, ACM inhibited both processes at lower concentrations than did daunorubicin. While daunorubicin inhibited [3H]thymidine incorporation more effectively than [3H]uridine incorporation, the reverse was observed with ACM.

1 To whom requests for reprints should be addressed, at National Cancer Institute, Baltimore Cancer Research Program, 655 West Baltimore Street, Baltimore, Md. 21201.

Received 4/16/79. Accepted 8/ 8/79.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Copyright © 1979 by the American Association for Cancer Research.