Bleomycin drug interactions

Antibiotics such as streptonigrin and the anthracycUnes also bind metals and cleave DNA and metal ion involvement through similar mechanisms to that of bleomycin is possible. In the case of the clinically-used adriamycin, the acute cardiotoxicity may have as a chemical cause free radical damage produced by an iron—drug interaction. 

Steighner RJ, Povirk LF (1990) Bleomycin-induced DNA lesions at mutational hot spots imphcations for the mechanism of double-strand cleavage. Proc Natl Acad Sci USA 87(21) 8350-8354 Straney DC, Crothers DM (1987) Effect of drug-DNA interactions upon transcription initiation at the lac promoter. Biochemistry 26(7) 1987-1995... 

Natrajan A, Hecht SM (1994) Bleomycins mechanism of polynucleotide recognition and oxydative degradation. In Neidle S, Waring M (eds) Molecular aspects of anticancer drug-DNA interactions. MacMillan, London, pp 197-242... 

The interaction of bleomycin with metal ions and the chemistry associated with this interaction has been the focus of numerous studies aimed at elucidating the detailed mechanism of action of this drug. A recent paper notes that the interaction of bleomycin with iron gives a reactive intermediate which cleaves DNA. Ferrous ion-bleomycin interaction results in chemiluminescence suggesting that the activated intermediate may be electronically excited, Mossbauer studies of the ferrous and ferric bleomycin complexes indicated that the latter complex may exist in two distinct conformations. In a study of cobalt-bleomycin complexes, the existence of a cobalt-bleomycin-hydroperoxide complex capable of nicking DNA has been demonstrated. ... 

While most drugs do not directly interact with endogenous metals, two clinically used antineoplastic agents are distinguished by this attribute bleomycin and doxorubicin. Metals also have a role in the treatment of cancer. The platinum-based antineoplastic agents, cw-diamminedichloro-platinum(II) (cisplatin) and cw-diamminedicarboxylatocyclobutaneplatinum... 

Common to all the effects summarized is the need to understand the nature of the physical interactions between metal complexes and polynucleotides. With respect to the identification of DNA as a plausible target for metal-based drugs, the interpretation of the interaction of species such as cisplatin (Chapter 4), and indeed bleomycin (Chapter 7), will hopefully allow the application of such findings to drug development and further, if only slightly, the goal of rational drug synthesis. 

---