Medline ® Abstracts for References 2,6,7
of 'Bleomycin-induced lung injury'
Bleomycin-induced pulmonary toxicity.
Jules-Elysee K, White DA
Clin Chest Med. 1990;11(1):1.
Bleomycin is recognized to cause an interstitial pneumonitis that can lead to fibrosis. Although its occurrence may be sporadic, some factors may increase the risk of such a pulmonary reaction. In this article the clinical setting and presentation, radiographic manifestations, pathologic findings, and the prognosis of bleomycin-induced interstitial fibrosis are described. Additionally, the role of pulmonary function tests in monitoring patients for toxicity is discussed.
Division of Pulmonary Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Biochemical and cellular determinants of bleomycin cytotoxicity.
Cancer Surv. 1986;5(1):81.
Bleomycin is a mixture of cytotoxic glycopeptides which function as mininucleases, binding to DNA and producing single and double strand breaks by the formation of an activated oxygen complex. Bleomycin is an effective agent against a few human cancers, notably lymphomas, testicular and ovarian germ cell cancers and certain squamous carcinomas. Most human cancers are resistant to bleomycin a priori, however, and those which are initially sensitive frequently develop resistance to the drug during therapy. Several potential modes of resistance to bleomycin have been identified in cell culture and animal tumour models, although their relative importance in determining the responsiveness of human cancers to the drug is not well understood. Bleomycin is selectively toxic to cells in the M and G2 phases of the cell cycle, and generally more effective against actively dividing rather than resting cells. Thus, the cytokinetic state of the tumour cell population is an important determinant of drug activity. Oxygen is an essential substrate for bleomycin's action, with the degree of cytotoxicity directly related to ambient oxygen. Both acutely and chronically hypoxic cells form a substantial fraction of the cell population of many tumours, and may serve as a reservoir of cells resistant to bleomycin on this epigenetic basis. Metabolic inactivation of bleomycin is a mechanism of resistance to the drug in some cells and may influence toxicity in normal tissues. Bleomycin hydrolase activity is low in lungs and skin, the two major sites of normal tissue toxicities, and levels of this enzymehave been elevated in some but not all tumour cell lines selected for resistance to bleomycin. The capacity to repair or withstand single and double strand DNA breaks may also be an important determinant of resistance to the drug. Most yeast and mammalian cell mutants, which are hypersensitive to ionizing radiation because of defects in DNA repair, are also more sensitive to bleomycin than wild-type cells. A number of agents which interact with membranes or inhibit DNA repair, such as ethanol, lidocaine, verapamil and caffeine, have been reported to sensitize cells to bleomycin in vitro.
Possible mechanisms of bleomycin-induced fibrosis.
Clin Chest Med. 1990;11(1):21.
Bleomycin-induced fibrosis is probably the composition of several mechanisms working in sequence and simultaneously. The role(s) and interaction of the cellular, biochemical, and molecular elements of bleomycin-induced fibrosis are examined.
Oregon Health Sciences University, Portland.