Possible involvement of DNA methylation in 5-azacytidine-induced neuronal cell apoptosis

Eight chemicals that are cytidine analogues or nucleosides (5-azacytidine ( 5AzC), 5-azadeoxycytidine, 6-azacytidine, 5-azacytosin, cytidine, 3-deazaad enine, 3-deazauridine and 6-azauridine) were examined for the ability to in duce neuronal apoptosis. SAzC and 5-azadeoxycytidine induced apoptosis in t he brain and spinal cord of the fetuses at 24 hr after the injection to dam s, while the other chemicals tested failed to induce apoptosis. In the syst em of PC12 cells, only SAzC induced apoptosis, and other chemicals failed t o provoke morphological and biochemical changes characteristic of apoptosis . 5AzC, 5-azadeoxycytidine and 6-azacytidine failed to induce apoptosis in C6 cells. Gel electrophoresis after MspI or HapII digestions revealed no ap parent evidence of DNA demethylation after 5AzC-treatment in either fetal b rains or PC12 cells. These results indicate that DNA demethylation is possi bly involved in 5AzC-induced neuronal apoptosis although no direct evidence of DNA demethylation was obtained.