Ultrastructure of pulmonary bleomycin toxicity

Abstract

Three cancer patients developed pulmonary distress during treatment with bieomycin. Light microscopic examination of lung tissue obtained by percutaneous biopsy revealed a diffuse alveolar damage progressing to interstitial pneumonitis. With electron microscopy, interstitial adema and collagen deposition, accumulation of fibroblasts, disappearance of type I, and proliferation of type II alveolar epithelial cells were noted. Alveoli contained proteinaceous material and a mixture of macrophages and type II cells. A peculiar alteration was noted in some type II cells consisting of shortening of the microvilli and extrusion of cytoplasmic lamellar bodies with possible surfactant impairment. These findings are consistent with the drug's effect upon the alveolar epithelium. Bleomycin, therefore, can be considered another etiologic agent of iatrogenic interstitial pneumonitis.

Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene.

“…The overall incidence of clinically apparent toxicity is 10%, with a 1% incidence of lethality (7). Bleomycin produces lung parenchyma injury and interstitial fibrosis in man (8) and a similar condition in animal models (9). Histologic studies of human and animal lung have demonstrated evidence of injury to a variety of cell types, including a denuding of the vascular basement membrane.…”

Elastic recoil pressure arising from surface tension in hamster lungs treated with intratracheal bleomycin.

“…There have been several reports concernig bleomycin-induced morphological or biochemical alterations in surfactant secretion systems (Bedrossian et al 1973;Aso et al 1976), with possible impairment of surfactant production. However, this is the first paper describing the effects of intratracheally administered bleomycin, which is in wide use for inducing experimental pulmonary fibrosis, on in situ function of surfactant.…”

Pulmonary Toxicity of Cytotoxic and Immunosuppressive Agents: A Review

“…Desquamation, proliferation, and metaplasia of the alveolar epithelium, which are common features of desquamative interstitial pneumonitis and usual interstitial pneumonitis, are the most striking histopathological effects of alkylating agents (47)(48)(49)(50), nitrosoureas (5 1-53), and antitumor antibiotics (54,55) according to lung biopsy and autopsy. However, fibrinous exudation, hyaline membranes, and interstitial fibrosis occur in most cases, and are diagnostic of usual interstitial pneumonitis (46).…”

“…Peripheral eosinophilia and eosinophilic infiltrates, as in eosinophilic pneumonitis, characterize the pneumonitis induced by methotrexate (22,26,64), procarbazine (13,65,66), and occasionally bleomycin (14, IS), and suggest an allergic etiology. Fibroblast proliferation and interstitial fibrosis are particularily prevailing in pneumonitis produced by alkylating agents (3, 47,48,53,[67][68][69], and the antibiotic agents bleomycin (55,70,71), peplomycin (6) and mitomycin (72).…”