Paige R, Wong V, Plopper C
Department of Anatomy, School of Veterinary Medicine, University of California, Davis, USA.
Toxicol Appl Pharmacol. 1997 Dec;147(2):224-33. doi: 10.1006/taap.1997.8297.
Nonciliated ("Clara") cells of terminal bronchioles are one of the principal targets of bioactivated pulmonary toxicants. However, we have recently observed cytotoxicity in proximal tracheobronchial airways with high doses of naphthalene. To test if this was true for other xenobiotics, 1-nitronaphthalene (25, 50, 100, or 150 mg/kg) was injected i.p. into male Sprague-Dawley rats and cytotoxicity characterized 24 hr later by high-resolution histopathology along a defined airway path extending from the trachea to the terminal bronchioles. At 25 mg/kg, only nonciliated cells in minor daughter airways were swollen and necrotic. At 50 mg/kg there was near complete loss of nonciliated cells in most bronchioles, minor daughter airways, and tracheas. Marked damage to ciliated cells was observed at doses of 100 and 150 mg/kg. Denudation of the basement membrane was common in the trachea. We conclude for 1-nitronaphthalene cytotoxicity in the lung that: (1) nonciliated cells of the distal bronchioles are not the only target, (2) the threshold for injury in nonciliated cells is lower than that for ciliated cells, (3) the response is airway selective, (4) the response is dose-related.
终末细支气管的无纤毛（“克拉拉”）细胞是生物活化肺毒物的主要靶细胞之一。然而，我们最近观察到高剂量萘可导致近端气管支气管气道出现细胞毒性。为了测试其他外源性物质是否也如此，将1-硝基萘（25、50、100或150mg/kg）腹腔注射到雄性Sprague-Dawley大鼠体内，并在24小时后通过高分辨率组织病理学对从气管到终末细支气管的特定气道路径中的细胞毒性进行表征。在25mg/kg时，仅小分支气道中的无纤毛细胞肿胀并坏死。在50mg/kg时，大多数细支气管、小分支气道和气管中的无纤毛细胞几乎完全丧失。在100和150mg/kg剂量下观察到纤毛细胞有明显损伤。气管中基底膜剥脱很常见。我们得出关于1-硝基萘在肺中的细胞毒性的结论如下：（1）远端细支气管的无纤毛细胞不是唯一的靶细胞；（2）无纤毛细胞的损伤阈值低于纤毛细胞；（3）反应具有气道选择性；（4）反应与剂量相关。
