Cytotoxic effects of antitumor agents on mouse tracheal organ cultures at ultrastructural level.

Abstract

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.