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Related Experiment Videos

Ascorbate both activates and inactivates bleomycin by free radical generation.

G R Buettner1, P L Moseley

  • 1Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242.

Biochemistry
|October 13, 1992
PubMed
Summary

Reducing agents activate bleomycin (BLM) to damage DNA, yet protect cells. This study reveals that pre-reacting BLM with ascorbate generates a redox-inactive form, preventing DNA damage.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • Bleomycin (BLM) is a chemotherapeutic agent that induces DNA damage.
  • Reducing agents paradoxically activate BLM for DNA cleavage while protecting cellular DNA.

Purpose of the Study:

  • To resolve the paradox of reducing agent effects on bleomycin-induced DNA damage.
  • To investigate the reaction mechanism between Fe(III)BLM, DNA, and ascorbate.

Main Methods:

  • Studied the reaction of Fe(III)BLM with DNA in the presence of ascorbate.
  • Quantified ascorbate oxidation and oxygen consumption during the reaction.
  • Investigated the reaction in buffered solutions and plasma.

Main Results:

Related Experiment Videos

  • Ascorbate augments Fe(III)BLM-induced DNA damage when added to DNA.
  • Pre-incubation of Fe(III)BLM with ascorbate generates a redox-inactive BLM.
  • This inactivation reaction occurs in both buffer and plasma, consuming ascorbate and oxygen.
  • Iron acts as a catalyst in the reaction.

    • Conclusions:

    • The activation of BLM and generation of redox-inactive BLM involve the same reaction pathway.
    • Bleomycin-induced DNA damage is dependent on BLM reaching DNA before interacting with reducing agents.