Oxidation-reduction reactions of iron bleomycin in the absence and presence of DNA

Sara Goldstein*, Gidon Czapski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Using the pulse radiolysis technique, we have demonstrated that bleomycin-Fe(III) is stoichiometrically reduced by CO2- to bleomycin-Fe(II) with a rate of (1.9 ± 0.2) × 108M-1s-1. In the presence of calf thymus DNA, the reduction proceeds through free bleomycin-Fe(III) and the binding constant of bleomycin-Fe(III) to DNA has been determined to be (3.8 ± 0.5) x 104 M-1. It has also been demonstrated that in the absence of DNA O2-1 reacts with bleomycin-Fe(III) to yield bleomycin-Fe(II)O2, which is in rapid equilibrium with molecular oxygen, and decomposes at room temperature with a rate of (700 ± 200) s-1. The resulting product of the decomposition reaction is Fe(III) which is bound to a modified bleomycin molecule. We have demonstrated that during the reaction of bleomycin-Fe(II) with O2, modification or self-destruction of the drug occurs, while in the presence of DNA no destruction occurs, possibly because the reaction causes degradation of DNA.

Original languageEnglish
Pages (from-to)259-270
Number of pages12
JournalFree Radical Research
Volume2
Issue number4-6
DOIs
StatePublished - 1987

Keywords

  • Bleomycin
  • DNA Damage
  • Iron
  • Radiolysis
  • Superoxide

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