Description
Bleomycin sulfate (9041-93-4) coordinates with metals producing reactive oxygen species which causes oxidative damage to DNA1and RNA2. Induces double-strand DNA damage.3Commonly used to induce lung fibrosis in animal disease models.4,5Anticancer agent in clinical use.6
Chemical Properties
White Powder
Uses
Bleomycin sulfate binds to DNA, and can inhibit DNA synthesis and causes scission of DNA. Cleaves DNA, requires binding to oxygen and a metal ion, such as copper or iron. Able to cleave RNA, but at less and more selective degree. Also reported to induce and regulate apoptosis in a variety of cells, and inhibit tumor angiogenesis.
Mechanism of action
Bleomycin is a complex of 11 glycopeptide antitumor antibiotics originally isolated from Streptomyces verticillus in 1972. The dominant components of the complex are bleomycin A2 and B2, which typically represent >90% of the total weight. Bleomycins have found clinical application in the treatment of a range of tumors. Bleomycins act by intercalation of DNA and RNA. In the presence of oxygen and metal ions, notably copper and iron, bleomycins form a pseudo-enzyme that induces DNA cleavage.
brand name
Blenoxane (Bristol-Myers Squibb).
General Description
Bleomycin occurs as a white powder and is available in 15-and 30-U vials for reconstitution in water. It may be givenintravenously, intramuscularly, or subcutaneously. It is used in the treatment of squamous cell carcinoma of the headneck, cervix, penis, and vulva. It is also used in Hodgkin’sand non-Hodgkin’s lymphoma as well as testicular carcinoma.Unlabeled uses include the treatment of mycosis fungoides,osteosarcoma, and AIDS-related Kaposi sarcoma.
Biochem/physiol Actions
Bleomycin sulfate binds to DNA, causes ssDNA scission at specific base sequences and inhibits DNA synthesis. This inhibitory action requires bleomycin to bind oxygen and a metal ion. It can also cleave RNA, to a lesser degree but more selectively. It acts as an inducer and regulator of apoptosis and inhibits tumor angiogenesis.
Clinical Use
Bleomycin is used IV in the palliative treatment of squamous cell head and neck cancers, testicular and other genital carcinomas, and Hodgkin's and non-Hodgkin's lymphoma.
Side effects
It is excreted via the kidneys, and serum concentrations of active drug are increased in patients with renal disease. The elimination half-life can rise from 2 to 4 hours to more than 20 hours in renal failure, resulting in significant toxicity, especially pulmonary toxicity.
Veterinary Drugs and Treatments
Bleomycin has occasionally been used as adjunctive treatment of
lymphomas, squamous cell carcinomas, teratomas, and nonfunctional
thyroid tumors in both dogs and cats. Recent work has demonstrated
that bleomycin may be promising for intralesional treatment
for a variety of localized tumors with or without concomitant
electropermeabilization.
References
[1] DAVID H. PETERING William E A Robert W Byrnes. The role of redox-active metals in the mechanism of action of bleomycin[J]. Chemico-Biological Interactions, 1990, 73 2: Pages 133-182. DOI:
10.1016/0009-2797(90)90001-4[2] A. HÜTTENHOFER. Cleavage of tRNA by Fe(II)-bleomycin.[J]. The Journal of Biological Chemistry, 1992, 81 1: 24471-24475. DOI:
10.1016/s0021-9258(18)35790-9[3] KYUNG YONG LEE. ASF1a Promotes Non-homologous End Joining Repair by Facilitating Phosphorylation of MDC1 by ATM at Double-Strand Breaks.[J]. Molecular Cell, 2017, 68 1: 61-75.e5. DOI:
10.1016/j.molcel.2017.08.021[4] YAN XIE. Upregulation of RGS2: a new mechanism for pirfenidone amelioration of pulmonary fibrosis.[J]. Respiratory Research, 2016: 103. DOI:
10.1186/s12931-016-0418-4[5] MINORU INOMATA. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis.[J]. Respiratory Research, 2014: 16. DOI:
10.1186/1465-9921-15-16[6] TOSHIKO TANAKA. Increased glutathione level is not involved in enhanced bleomycin sensitivity in cisplatin-resistant 2780CP cells.[J]. Anticancer research, 2008, 28 5A: 2663-2668.
