Ultrastructural observations on FUdR-induced cell death and subsequent elimination of cell debris.

Twelve-day mouse embryos were treated with fluorodeoxyuridine (FUdR) and sacrificed at various time intervals after treatment. The neuroepithelial cells were then examined to determine by electron microscopy the primary site of action of the drug. About two hours after treatment mitotic activity ceased and a number of cells were found with a normal interphase nucleus, but with a cytoplasm in which the ribosomes had lost their normal polysomal configuration and were dispersed as single ribosomes. At about the same time cells were seen with an accumulation of chromatin at the nuclear membrane and the segregation of chromatin masses within the somewhat denser karyoplasm. Concurrent with the nuclear changes was the appearance of a condensed cytosome containing monoribosomes. The condensation of the nucleus and cytoplasm was followed by fragmentation of the cell into membrane bound bodies. Since condensed cells always contained monodispersed ribosomes, it seems likely that the dispersal of the ribosomes is the first morphological sign of the action of FUdR. Since about half of the neuroepithelial population underwent cell degeneration, the second goal of this experiment was to study the fate of the dying cells. Some fragments from condensed cells were found within apparently normal neuroepithelial cells, indicating phagocytosis. In addition macrophages were seen containing phagosomes from fragmented cells. Most of the fragments, however, remained free and were not immediately phagocytosed. These unphagocytosed fragments lysed and became ghosts, thereby giving the neureopithlium a vacuolated appearance. Hence, cellular debris was eliminated partially by neuroepithelial cells, partially by macrophages and to a great extent by lysis.