Adamson I Y, Bowden D H
Am J Pathol. 1979 Aug;96(2):531-44.
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.
在博来霉素诱导的肺纤维化中，常可见化生的上皮细胞衬于肺泡内。在一项连续性研究中，现对这些细胞变化是由药物直接作用于分化中的Ⅱ型细胞所诱导这一假说进行检验，以将肺中³H博来霉素的存在与肺泡上皮的损伤和修复模式联系起来。单次静脉注射剂量或多次小剂量腹腔内注射可诱导Ⅰ型上皮细胞局灶性坏死，随后Ⅱ型细胞再生。在这些细胞中脱氧核糖核酸（DNA）合成达到最大值时，通过闪烁计数可在肺中检测到大量的³H博来霉素；在放射自显影片中，药物似乎集中在上皮细胞中。随后可见许多异常的Ⅱ型细胞。一些是双核的，另一些则显示核破裂。向Ⅰ型细胞的正常分化过程未发生；相反，发现了多种上皮形式，包括胎儿样管状结构以及纤毛化生和鳞状化生细胞。肺中上皮损伤和修复与博来霉素的直接显示之间的相关性表明，Ⅱ型细胞在细胞周期的分裂和分化阶段易受损伤，然后可能产生各种不适当的肺泡内衬细胞。
