Giuliani I, Boivieux-Ulrich E, Houcine O, Guennou C, Marano F
Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris VII Denis Diderot, France.
Cell Biol Toxicol. 1994 Aug;10(4):231-46. doi: 10.1007/BF00756763.
Mechlorethamine (HN2) is an alkylating agent usually used in cancer chemotherapy. Nevertheless, HN2 is extremely toxic and its use is accompanied by severe side-effects that may cause lung complications. Many studies report the morphological and biochemical modifications induced by sulfur mustard (SM) but no report has been published concerning the toxic effects of HN2 on the ultrastructural and functional activity of surface respiratory epithelial cells. This study was performed on rabbit tracheal epithelium (RTE) cells in primary culture. The functional activity of the culture was evaluated by measuring the ciliary beating frequency (CBF) of the ciliated cells using a videomicroscopic method, and the culture growth was determined by an image analysis system. The morphological aspects of the cells were analyzed by light, scanning electron, and transmission electron microscopy. An important inhibition of cell growth was observed associated with a detachment of the outgrowth cells. Morphological changes were expressed by vacuolization, increases in the intercellular spaces, and by disorganization of the cytoskeleton associated with a specific attack of the ciliated cells that show ciliary blebbing. The sudden CBF inhibition is more likely due to the detachment and the death of the ciliated cells than to a specific ciliotoxic effect of HN2. All these observations demonstrated the high sensitivity of respiratory epithelial cells to HN2 and showed that HN2-induced injuries were irreversible, and time- and dose-dependent.
氮芥（HN2）是一种通常用于癌症化疗的烷化剂。然而，HN2具有极高的毒性，其使用会伴随严重的副作用，可能导致肺部并发症。许多研究报告了硫芥（SM）引起的形态学和生化改变，但尚未有关于HN2对表面呼吸上皮细胞超微结构和功能活性毒性作用的报道。本研究在原代培养的兔气管上皮（RTE）细胞上进行。通过视频显微镜法测量纤毛细胞的纤毛摆动频率（CBF）来评估培养物的功能活性，并通过图像分析系统确定培养物的生长情况。通过光学显微镜、扫描电子显微镜和透射电子显微镜分析细胞的形态学方面。观察到细胞生长受到重要抑制，同时伴随生长细胞的脱离。形态学变化表现为空泡化、细胞间隙增加以及细胞骨架紊乱，伴有纤毛细胞的特异性损伤，表现为纤毛起泡。CBF的突然抑制更可能是由于纤毛细胞的脱离和死亡，而不是HN2的特异性纤毛毒性作用。所有这些观察结果表明呼吸上皮细胞对HN2高度敏感，并表明HN2诱导的损伤是不可逆的，且具有时间和剂量依赖性。
