Pulmonary Metabolic Inactivation of Bleomycin and Protection from Drug-Induced Lung Injury

Many conventional antineoplastic agents and investigational biological response modifiers produce pulmonary injury. The pulmonary fibrosis associated with the glycopeptide-like antibiotics of the bleomycin class is, however, one of the most life-threatening. This untoward effect is characterized by an increased pulmonary content of fibronectin, glycosaminoglycans, and collagen, especially type III relative to type I collagen. It is generally assumed that bleomycin-induced pulmonary fibrosis is caused by a bleomycin-iron-oxygen ternary complex, which results either in cleavage of genomic DNA or lipid peroxidation (1, 2). In this manuscript we will focus upon one major biochemical factor responsible for the preferential damage to the lungs: the lack of a protective enzyme called bleomycin hydrolase.