Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung.
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.
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle; D002454:Cell Differentiation; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000187:drug effects; D008679:Metaplasia; D051379:Mice; D008938:Mitosis; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology
D001761:Bleomycin; D004247:DNA