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Molecular Pharmacology, Vol 11, 640-646, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Mechanism of Daunorubicin Inhibition of Hog Spleen Acid Deoxyribonuclease

VÉRONIQUE BARTHELEMY-CLAVEY 1, GENEVIÈVE SERROS 1, and GENEVIÈVE AUBEL-SADRON 1

1 Centre de Biophysique Moléculaire, Centre National de la Recherche Scientifique, 45045 Orléans Cedex, France

The inhibitory effect of daunorubicin on the enzymatic degradation of DNA was studied in vitro. The initial kinetics of acid deoxyribonuclease (deoxyribonucleate 3'-nucleotidohydrolase, EC 3.1.4.6) degradation was investigated using analytical ultracentrifugation to determine the ratio of single-strand to double-strand breaks. The late phase of the degradation was followed by hyperchromicity. Evidence is presented that the mechanism of inhibition of DNase activity involves nonproductive binding of daunorubicin-intercalated DNA. Calculations show that total inhibition occurs when 1 molecule of the antibiotic binds per 10 nucleotides.

Submitted on October 21, 1974






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