BLEOMYCIN-INDUCED INJURY AND METAPLASIA OF ALVEOLAR TYPE-2 CELLS - RELATIONSHIP OF CELLULAR-RESPONSES TO DRUG PRESENCE IN THE LUNG

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 96  (2) , 531-544
Abstract
Metaplastic epithelial cells are often observed lining alveoli in bleomycin[an antitumor agent]-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 [in mice]. A single i.v. dose or multiple small i.p. doses induce focal necrosis of Type 1 epithelial cells followed by Type 2 cell regeneration. At the time of maximal 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.