APOPTOSIS IN THE CENTRAL-NERVOUS-SYSTEM OF DEVELOPING MOUSE FETUSES FROM 5-AZACYTIDINE-ADMINISTERED DAMS

To determine the effect of 5-azacytidine (5Az), a cytidine analogue, o n the developing fetus, different strains of mice were injected with v arious doses of the agent, ip, at 11 days of gestation. Light microsco pically, severely pyknotic cell death profiles were observed in differ ent layers of the developing brain and spinal cord (central nervous sy stem) on the day after the injection. Electron microscopy of the pykno tic cells revealed the shrinkage of the cell body, to various degrees margination of the nuclear chromatin, condensation of nuclear material s, fragmentation of the affected cells, and, finally, neat ''bite-size '' bodies engulfed by surrounding normal neuroepithelial cells and mac rophage-like cells. DNA fragmentation was detected in the nuclei of th e pyknotic cells by an in situ detection method for fragmented DNA end s. These changes were consistent with the criteria of apoptosis.