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Bleomycin

Bleomycin is an anti-cancer agent. It is a glycosylated linear nonribosomal peptide antibiotic produced by the bacterium Streptomyces verticillus. The drug is used in the treatment of lymphomas (especially Hodgkin's disease), squamous cell carcinomas, and testicular cancer as well as pleurodesis. more...

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History

Bleomycin was first discovered in 1962 when the Japanese scientist Hamao Umezawa found anti-cancer activity while screening culture filtrates of S. verticullus. Umezawa published his discovery in 1966. The drug was launched in Japan by Nippon Kayaku in 1969. In the US bleomycin gained FDA approval in July 1973. It was initially marketed in the US by the Bristol-Myers Squibb precursor Bristol Laboratories under the brand name Blenoxane.

Suppliers

Bristol-Myers Squibb still supplies Blenoxane. There are also generic versions of bleomycin available from Bedford, Sicor and Mayne Pharma.

Mechanism of action

Bleomycine acts by induction of DNA strand breaks. Some studies suggest that bleomycin also inhibits incorporation of thymidine into DNA strands. Bleomycin is a metal-chelating molecule that is also thought to produce superoxide and hydroxide free radicals, through action as a pseudoenzyme, which also damage the DNA.

Side effects

The most serious complication of bleomycin is pulmonary fibrosis and impaired lung function. Other side-effects include fever, rash, hyperpigmentation, alopecia, and Raynaud's phenomenon.

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Influence of inhaled dexamethasone on the bleomycin-induced lung fibrosis in rats
From CHEST, 10/1/05 by Li Xia

PURPOSE: To compare the effect and mechanism of inhaled with systemic dexamethasone on the bleomycin-induced lung fibrosis in rats.

METHODS: 60 Sprague-Dawley rats were divided randomly into three groups including bleomycin-induced lung fibrosis group (Group A,n=20), inhaled dexamethasone group (Group B, n=20) and dexamethasone group (Group B, n=20). Each group was again divided into four subgroups, which were sacrificed on 1, 7, 14 or 28 day. Bronchoalveolar lavage fluid (BALF)was got and the cells counting aswell as differentiation were figured out, HE stain was performed on the lung tissue sections to observe the extent of alveolitis and fibrosis, the semi-quantity of apoptosis cells in lung tissue was assay by in situ TUNEL(terminal deoxynucleotidy transferase-mediated UTP nick endlabeling).

RESULTS: (1)Compared group B and C with group. A got lower percentage of neutrophils (P<0.05). (2)More severe fibrotic lesion was shown in the histological examination of the lung tissue sections of group A Compared with group B and C. (3)the apoptosis index (AI) of inflammatory cells in each subgroups of group B and C was higher than in group A, and there were no significance compared group B with C.

CONCLUSION: Inhaled dexamethasone can induce apoptosis of pulmonary inflammatory cells and ameliorate the formation of bleomycin-induced pulmonary fibrosis as well as systemic dexamethasone.

CLINICAL IMPLICATIONS: Inhaled steroid drugs maybe improve interstial lung disease.

DISCLOSURE: Li Xia, None.

Li Xia MD * Shanghai pulmonary hospital, Shanghai, Peoples Rep of China

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