Plopper C G, Macklin J, Nishio S J, Hyde D M, Buckpitt A R
Department of Veterinary Anatomy and Cell Biology, School of Veterinary Medicine, University of California, Davis.
Lab Invest. 1992 Nov;67(5):553-65.
The purpose of this study was to define, in quantitative terms, epithelial alterations produced by the cytochrome P-450-activated Clara cell cytotoxicant, naphthalene, in lobar bronchi and terminal bronchioles of three species with differing sensitivity: mouse, rat, and hamster.
Adult mice, hamsters, and rats were treated intraperitoneally with a single dose of naphthalene ranging from 0 mg/kg up to the approximate LD50. The animals were killed 24 hours postinjection and the changes in airway epithelium characterized by light microscopic morphometry.
In mouse, bronchiolar epithelial thickness was significantly elevated by low, but not high, doses; ciliated cell number increased and Clara cell number decreased in a dose-dependent fashion. Vacuolated Clara cell number increased in all treated mice. In rat and hamster, bronchiolar epithelial thickness or cell number did not change. In mice, bronchial epithelial thickness was unchanged except at high doses, but both ciliated and Clara cell number was decreased. In bronchi of rats, epithelial thickness and numbers of nonciliated, ciliated, and basal cells were unchanged. In bronchi of hamsters, both ciliated and nonciliated cell number were decreased.
(a) In mice, naphthalene-induced acute bronchiolar toxicity involves not only Clara cells, but also affects the purported nontarget cell type (ciliated cells). (b) In rats and hamsters, bronchiolar epithelium is insensitive to naphthalene injury. (c) In mice, injury to bronchi occurs at higher doses than in bronchioles and involves both ciliated and nonciliated cells. (d) In rats, bronchi are insensitive. (e) In hamsters, bronchi are more sensitive than bronchioles. This study emphasizes the variability of response by species, airway and epithelial cell type to cytochrome P-450-mediated pulmonary toxicants and the need for precise quantitative methods of defining both cytotoxic and metabolic events.
本研究的目的是定量确定细胞色素P - 450激活的克拉拉细胞细胞毒性剂萘在三种敏感性不同的物种（小鼠、大鼠和仓鼠）的叶支气管和终末细支气管中所引起的上皮改变。
成年小鼠、仓鼠和大鼠腹腔注射单剂量的萘，剂量范围从0毫克/千克到接近半数致死量（LD50）。注射后24小时处死动物，通过光学显微镜形态计量学对气道上皮的变化进行表征。
在小鼠中，低剂量而非高剂量显著增加了细支气管上皮厚度；纤毛细胞数量增加，克拉拉细胞数量呈剂量依赖性减少。所有接受治疗的小鼠中，空泡化克拉拉细胞数量均增加。在大鼠和仓鼠中，细支气管上皮厚度或细胞数量未发生变化。在小鼠中，除高剂量外支气管上皮厚度未改变，但纤毛细胞和克拉拉细胞数量均减少。在大鼠的支气管中，上皮厚度以及非纤毛细胞、纤毛细胞和基底细胞数量均未改变。在仓鼠的支气管中，纤毛细胞和非纤毛细胞数量均减少。
（a）在小鼠中，萘诱导的急性细支气管毒性不仅涉及克拉拉细胞，还影响所谓的非靶细胞类型（纤毛细胞）。（b）在大鼠和仓鼠中，细支气管上皮对萘损伤不敏感。（c）在小鼠中，支气管损伤发生的剂量高于细支气管，且涉及纤毛细胞和非纤毛细胞。（d）在大鼠中，支气管不敏感。（e）在仓鼠中，支气管比细支气管更敏感。本研究强调了不同物种、气道和上皮细胞类型对细胞色素P - 450介导的肺毒物反应的变异性，以及定义细胞毒性和代谢事件的精确定量方法的必要性。
