Oxidation-Reduction Reactions of Iron Bleomycin in the Absence and Presence of DNA

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.

Key Words:

• Bleomycin
• Iron
• DNA Damage
• Radiolysis
• Superoxide
• CO₂⁻