Action of Bleomycin

The Fe—bleomycin system has been described in detail and the mechanism of action with DNA in vitro substantially clarified [1,2]. 

---

Cooperative work with Prof. Nobuo Tanaka (Professor Emeritus of the University of Tokyo) in 1969 showed the mechanism of action of bleomycin to involve DNA strand-scission. The difficult total synthesis of bleomycin was accomplished (1981) in cooperation with Takita and others, including Hamao s son, Yoji Umezawa. H. Umezawa was very satisfied with the success of this total synthesis, and his sustained enthusiasm for improved bleomycins led to peplomycin (1978 used clinically since 1981) and libro-mycin(1985). 

The antitumour action of the natural antibiotic bleomycin is thought to involve the aerobic degradation of DNA by the Fe2+-bleomycin complex. In order to probe the mechanism of antitumour action of bleomycin, the 4-ethylamido[5,(2 -thienyl)-2-thiophene] imidazole iron(II) complex was synthesized [129]. It was studied in non-aqueous solution using cyclic voltammetry and showed antitumour activity in vitro, its action causing cleavage of the double helical DNA. 

During Studies dealing with the action of bleomycin on DNA, four analogous degradation products were described, two of which are 31 and 32. ... 

One family of antitumorigenic compounds used in practice are the bleomycins, natural products that contain iron isolated from Streptomyces cultures. Bleomycin sulfate is used in combination chemotherapy for treatment of head and neck cancer. The mechanism of action of bleomycin is believed to include the binding of oxygen to form 02-Fe(II)-BLM. This complex can accept an electron to produce an active species, 02 -Fe(III)-BLM, which can cleave DNA and RNA, ultimately killing the cancer cell. 

Bleomycin sulfate is used alone or in combination with other antineoplastic dmgs. Using this DNA-cleaving dmg, disease-free (possibly cured) survivors of some cancers have been seen, especially with the use of bleomycin in multidmg regimens. General reviews of bleomycin (234,242—245) and its mechanism of action (246—249) are available. 

A 34-year-old male with Hodgkin s disease is treated with the adri-amycin, bleomycin, vinblastine, and decarbazine (ABVD) regimen. What is the mechanism of action of vinblastine ... 

Thuong N, Helene C (1993) Sequence specific recognition and modification of double helical DNA by oligonucleotides. Angew. Chem Int Ed Engl 32 666-690 Tien Kuo M, Hsu TC (1978) Biochemical and cytological studies of bleomycin actions on chromatin and chromosomes. Chromosoma 68(3) 229-240... 

The presently accepted model1555 for the reaction of bleomycin with DNA involves the binding of an Fen-bleomycin complex to DNA, and the reduction of iron-bound dioxygen. Cleavage of DNA is known to occur by the action of the 1,10-phenanthroline complex of Cu1 in the presence of hydrogen peroxide, and this reaction is sustained by the presence of NADH.1556 This provides a useful parallel for the bleomycin reaction. 

Rabow LE, Stubbe J, Kozarich JW (1990) Identification and quantitation of the lesion accompanying base release in bleomycin-mediated DNA degradation. J Am Chem Soc 112 3196-3203 Raleigh JA, Blackburn BJ (1978) Substrate conformation in 5 -AMP-utilizing enzymes 8,5 -cycloadenosine 5 -monophosphate. Biochem Biophys Res Commun 83 1061-1066 Ramakrishnan N, Clay ME, Xue L-Y, Evans El El, Rodriguez-Antunez A, Oleinick NL (1988) Induction of DNA-protein cross-links in Chinese hamster cells by photodynamic action of chloroaluminium phthalocyanine and visible light. Photochem Photobiol 48 297-303 Ramakrishnan N, Chiu S-M, Oleinick NL (2003) Yield of DNA-protein cross-links in y-irradiated Chinese hamster cells. Cancer Res 47 2032-2035... 

Laughton, M. J., Halliwell, B., Evans, P. J., and Hoult, J. R. (1989). Antioxidant and prooxidant actions of the plant phenolics quercetin, gossypol and myricetin. Effects on lipid peroxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA. Biochem. Pharmacol. 38, 2859-2865. 

Viral warts are common, particularly in children. Without treatment, warts will eventually disappear due to actions of the immune system. There are treatments available, but their use can be tedious, painful and prolonged. Many chemical treatments containing keratolytics are sold as over-the-counter preparations. Other more specialized treatments are cryotherapy, using liquid nitrogen, electrosurgery, surgical excision, bleomycin injections and carbon dioxide laser. 

---