PMID: 6172560Dec 1, 1981Paper

Iron--dioxygen-dependent changes to the biological activities of bleomycin

Journal of Inorganic Biochemistry
J M Gutteridge, D J Shute

Abstract

Antitumor antibiotic bleomycin can bind to and degrade DNA, both in vivo and in vitro. This DNA damaging property in vitro can be related to its ability to chelate ferrous ions under aerobic conditions leading to the formation of "active oxygens," which are thought to be directly responsible for the damage. At present, evidence points to the hydroxyl radical formed by an iron-catalyzed Haber-Weiss reaction as the free radical most likely to be involved in this damage. When these same reactions occur in the absence of DNA, the free radicals then damage the bleomycin molecule, resulting in changes to its DNA-degrading activity, antibacterial properties, and chemical composition. Attempts to protect both bleomycin and DNA with a variety of specific and nonspecific scavengers have been unsuccessful, with several even showing pro-oxidant activity towards the iron-dependent damage. Only the metal chelators were effective inhibitors of bleomycin-iron-dependent damage to DNA. The damaged bleomycin lost some 50% of its ability to degrade DNA in vitro. This activity was closely paralleled by a loss in antibacterial activity against two different strains of bacteria.

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Citations

Apr 1, 1994·Applied Biochemistry and Biotechnology·P Prabhakar, A M Kayastha
Jan 1, 1991·The International Journal of Biochemistry·R A Løvstad
Jul 1, 1994·Antimicrobial Agents and Chemotherapy·C W Moore
Mar 5, 2011·Microbiology and Molecular Biology Reviews : MMBR·Dea Slade, Miroslav Radman
Jul 30, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Satoshi ItoYutaka Kohgo
Jan 1, 1986·Free Radical Research Communications·J M Gutteridge, Y Y Hou
Mar 5, 1991·Biochemistry·E GajewskiB Halliwell

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