Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung.
- 1 August 1979
- journal article
- Vol. 96 (2), 531-44
Abstract
Metaplastic epithelial cells are often observed lining alveoli in bleomycin-induced pulmonary fibrosis. The hypothesis that these cellular changes are induced by the direct action of the drug on differentiating Type 2 cells is now examined in a sequential study to correlate the presence of 3H bleomycin in the lung with the pattern of injury and repair of the alveolar epithelium. A single intravenous dose or multiple small intraperitoneal doses induce focal necrosis of Type 1 epithelial cells followed by Type 2 cell regeneration. At the time of maximal deoxyribonucleic acid (DNA) synthesis in these cells, significant amounts of 3H bleomycin are demonstrable in the lung by scintillation counting; and in autoradiographs, the drug appears to concentrate in epithelial cells. Subsequently many abnormal Type 2 cells are seen. Some are binucleate, and others show nuclear disruption. The usual process of differentiation to Type 1 cells does not occur; instead, a variety of epithelial forms are found, including fetal-like tubular structures and ciliated and squamous metaplastic cells. The correlation of epithelial injury and repair with the direct demonstration of bleomycin in the lung indicates that Type 2 cells are susceptible to injury in the division and differentiation phases of the cell cycle and may then produce a variety of inappropriate alveolar lining cells.This publication has 20 references indexed in Scilit:
- Pulmonary injury and repair. Organ culture studies of murine lung after oxygen.1976
- Chemistry and mechanism of action of bleomycin.1974
- The pathogenesis of bleomycin-induced pulmonary fibrosis in mice.1974
- The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen.1974
- Ultrastructure of pulmonary bleomycin toxicityCancer, 1973
- Renewal of alveolar epithelium in the rat following exposure to NO2.1973
- Oxygen pneumonitis in man. Ultrastructural observations on the development of alveolar lesions.1972
- Oxygen poisoning in mice. Ultrastructural and surfactant studies during exposure and recovery.1970
- THE DISTRIBUTION OF 3H-BLEOMYCIN IN MOUSE TISSUEThe Journal of Antibiotics, 1968
- Studies on bleomycinCancer, 1967