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Possible involvement of DNA methylation in 5-azacytidine-induced neuronal
cell apoptosis
H. Nakayama, S. Kajikawa, J. Shinozuka, W-P. Su and K.
Doi
Department of Veterinary Pathology, Faculty of Agriculture,
The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Offprint requests to: Dr. H.
Nakayama, Department of Veterinary Pathology, Faculty of Agriculture, The
University of Tokyo, 1-1-1 Yoyoi, Bunkyo-ku, Tokyo 113-8657, Japan
Summary. Eight chemicals that
are cytidine analogues or nucleosides (5-azacytidine (5AzC), 5-azadeoxy-cytidine,
6-azacytidine, 5-azacytosin, cytidine, 3-deaza-adenine, 3-deazauridine and
6-azauridine) were examined for the ability to induce neuronal apoptosis.
5AzC and 5-azadeoxycytidine induced apoptosis in the brain and spinal cord
of the fetuses at 24 hr after the injection to dams, while the other chemicals
tested failed to induce apoptosis. In the system of PC12 cells, only 5AzC
induced apoptosis, and other chemicals failed to 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 apparent evidence of DNA demethylation
after 5AzC-treatment in either fetal brains or PC12 cells. These results
indicate that DNA demethylation is possibly involved in 5AzC-induced neuronal
apoptosis although no direct evidence of DNA demethylation was obtained.
Histol. Histopathol. 14, 143-150 (1999)
Key words: Apoptosis, 5-Azacytidine,
DNA methylation, Brain, PC12 cells
DOI: 10.14670/HH-14.143
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