Effect of chelating agents and metal ions on the degradation of dna by bleomycin

Edward A. Sausville, Jack Peisach, Susan Band Horwitz

Research output: Contribution to journalArticle

357 Citations (Scopus)

Abstract

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
JournalBiochemistry
Volume17
Issue number14
StatePublished - 1978

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Bleomycin
Chelating Agents
Metal ions
Ions
Degradation
DNA
Reducing Agents
Iron
Deferoxamine
Mercaptoethanol
Xanthine Oxidase
Dithiothreitol
NADP
Superoxides
Oxidation
Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Effect of chelating agents and metal ions on the degradation of dna by bleomycin. / Sausville, Edward A.; Peisach, Jack; Band Horwitz, Susan.

In: Biochemistry, Vol. 17, No. 14, 1978, p. 2740-2746.

Research output: Contribution to journalArticle

Sausville, Edward A. ; Peisach, Jack ; Band Horwitz, Susan. / Effect of chelating agents and metal ions on the degradation of dna by bleomycin. In: Biochemistry. 1978 ; Vol. 17, No. 14. pp. 2740-2746.
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