Sekiya K, Futaesaku Y, Nakase Y, Danbara H
Department of Microbiology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Kitasato Arch Exp Med. 1992 Dec;65(4):187-98.
A cytotoxic effect of antitumor agents (mitomycin C;MMC, adriamycin;ADM, bleomycin;BLM, 5-fluorouracil;5-FU, and cisplatin;CDDP) on ciliated epithelial cells of mouse tracheal organ cultures was studied in transmission electron microscopy. Mouse tracheal rings incubated with each agent in a concentration of 1 microgram/ml or 10 micrograms/ml were observed after 1, 2, and 20 hr of the incubation. After 2 hr, the ciliated epithelial with MMC or ADM of 1 microgram/ml exhibited appearance of lipid droplets in the nonciliated cells and the swelling of mitochondria and epithelial cells. Further incubation of 20 hr with those agents resulted in the pronounced degeneration including the ciliary subsidence into intracellular spaces, balloon-like ciliary swelling, and cellular destruction. Whereas, the ciliated epithelia with 5-Fu, BLM or CDDP did not show any notable change within 2 hr. After 20 hr, these exhibited the swelling of mitochondria, cilia and epithelial cells. The ciliated epithelia incubated with MMC or ADM of a greater concentration of 10 micrograms/ml showed remarkable cytotoxic effects after 1 hr of the incubation. The morphological changes in the epithelial cells with 1 hr incubation were almost similar to those of 20 hr incubation with the 1 microgram/ml. After 20 hr, the cellular degeneration proceeded to extremely flattened epithelial cells with disappearance of cilia and appearance of numerous vacuoles. Those with 5-FU, BLM or CDDP of 10 micrograms/ml exhibited ciliary swelling after 2 hr, but the morphological changes of 5-FU were more remarkable than those of BLM or CDDP. After 20 hr, the pronounced degeneration was observed, and it was similar to one of MMC or ADM of 2 hr incubation.
采用透射电子显微镜研究了抗肿瘤药物（丝裂霉素C；MMC、阿霉素；ADM、博来霉素；BLM、5-氟尿嘧啶；5-FU和顺铂；CDDP）对小鼠气管器官培养物中纤毛上皮细胞的细胞毒性作用。将小鼠气管环分别与浓度为1微克/毫升或10微克/毫升的每种药物一起孵育，在孵育1小时、2小时和20小时后进行观察。2小时后，用1微克/毫升MMC或ADM处理的纤毛上皮在非纤毛细胞中出现脂滴，线粒体和上皮细胞肿胀。用这些药物再孵育20小时导致明显的变性，包括纤毛沉入细胞内空间、气球样纤毛肿胀和细胞破坏。然而，用5-FU、BLM或CDDP处理的纤毛上皮在2小时内未显示任何明显变化。20小时后，这些上皮表现出线粒体、纤毛和上皮细胞肿胀。用浓度更高的10微克/毫升MMC或ADM孵育的纤毛上皮在孵育1小时后显示出显著的细胞毒性作用。孵育1小时后上皮细胞的形态变化与用1微克/毫升孵育20小时后的变化几乎相似。20小时后，细胞变性发展为上皮细胞极度扁平，纤毛消失，出现大量空泡。用10微克/毫升5-FU、BLM或CDDP处理的上皮在2小时后出现纤毛肿胀，但5-FU的形态变化比BLM或CDDP更显著。20小时后，观察到明显的变性，这与用MMC或ADM孵育2小时后的情况相似。
