Dose-related airway-selective epithelial toxicity of 1-nitronaphthalene in rats.
Dose-related airway-selective epithelial toxicity of 1-nitronaphthalene in rats.
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DOI：
10.1006/taap.1997.8297
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发表时间：
1997-12
影响因子：
3.8
通讯作者：
R. Paige;V. Wong;C. Plopper
中科院分区：
文献类型：
--
作者：
R. Paige;V. Wong;C. Plopper
终末细支气管的无纤毛（“Clara”）细胞是生物活化的肺毒物的主要靶标之一。然而，我们最近观察到高剂量萘对近端气管支气管气道的细胞毒性。为了测试这是否适用于其他外源性物质，将1-硝基萘（25、50、100或150 mg/kg）腹膜内注射到雄性Sprague-Dawley大鼠中，24小时后通过高分辨率组织病理学沿着从气管延伸到末端细支气管的限定气道路径表征细胞毒性。在25 mg/kg剂量下，仅子气道中的无纤毛细胞肿胀和坏死。在50 mg/kg剂量下，大多数细支气管、较小的子气道和气管中的无纤毛细胞几乎完全丧失。在100和150 mg/kg剂量下观察到对纤毛细胞的显著损伤。气管基底膜剥脱是常见的。我们得出结论，1-硝基萘在肺中的细胞毒性：（1）远端细支气管的无纤毛细胞不是唯一的目标，（2）无纤毛细胞的损伤阈值低于纤毛细胞，（3）反应是气道选择性的，（4）反应是剂量相关的。
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.