Oxygen Bleomycin

Goldiner PL, Shams A. Bleomycin-oxygen interaction. Semin Anesth 1993 12 79-82. 

Bleomycin Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks Hodgkin s and non-Hodgkin s lymphoma, germ cell cancer, head and neck cancer Allergic reactions, fever, hypotension Skin toxicity, pulmonary fibrosis, mucositis, alopecia... 

Neese F, Zaleski JM, Zaleski KL, Solomon El (2000) Electronic structure of activated bleomycin oxygen intermediates in heme versus non-heme iron. J Am Chem Soc 122 11703-11724... 

Sugiura Y, Kikuchi T. 1978. Formation of superoxide and hydroxy radicals in iron (Il)-bleomycin-oxygen system electron spin resonance detection by spin trapping. J. Antibiot. 31 1310-12... 

In the presence of ferrous ions and oxygen, copper-free bleomycin causes a double-stremd scission of The bleomycin-Cu ... 

Bleomycin is a naturally occurring fermentation product of Streptomyces verticillus. It is a basic glycoprotein, complexed with Cu++. It intercalates between DNA base pairs, and it also chelates iron, generating oxygen radicals which further damage the DNA. It is the only cell-cycle specific agent among the antibiotics as it causes accumulation of cells in the G2 phase of the cell cycle. 

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

Rashid R, Langfinger D, Wagner R, Schuchmann H-P, von Sonntag C (1999) Bleomycin vs. OH-radi-cal-induced malonaldehydic-product formation in DNA. Int J Radiat Biol 75 110-109 Rothkamm K, Lobrich M (2003) Evidence for the lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Nat Acad Sci USA 100 5057-5082 Sapora O, Fielden EM, LoverockPS (1975) The application of rapid lysis techniques in radiobiology. I. The effect of oxygen and radiosensitizers on DNA strand break production and repair in E. coli B/r. Radiat Res 64 431-442... 

Bleomycins are thought to react with DNA and cause strand scission they have also been shown to have a type of oxygen transferase activity.1... 

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