Effect of Chelating Agents and Metal Ions on the Degradation of DNA by Bleomycin

Edward A. Sausville, Jack Peisach, Susan B. Horwitz

Research output: Contribution to journalArticlepeer-review

369 Scopus citations


The degradation of DNA by bleomycin was studied in the absence and in the presence of added reducing agents, including 2-mercaptoethanol, dithiothreitol, reduced nicotinamide adenine dinucleotide phosphate, H2O2, and ascorbate, and in the presence of a superoxide anion generating system consisting of xanthine oxidase and hypoxanthine. In all cases, breakage of DNA was inhibited by low concentrations of chelators; where examined in detail, deferoxamine mesylate was considerably more potent than (ethylenedinitrilo)tetraacetic acid. Iron was found to be present in significant quantities in all reaction mixtures. Thus, the pattern of inhibition observed is attributed to the involvement of contaminating iron in the degradation of DNA by bleomycin. Cu(II), Zn(II), and Co(II) inhibit degradation of DNA by bleomycin and Fe(II) in the absence of added reducing agents. A model is proposed in which the degradation of DNA in these systems is dependent on the oxidation of an Fe(II)-bleomycin-DNA complex.

Original languageEnglish (US)
Pages (from-to)2740-2746
Number of pages7
Issue number14
StatePublished - 1978
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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