| Literature DB >> 12383193 |
Masaki Ueno1, Kei-Ichi Katayama, Hiroyuki Nakayama, Kunio Doi.
Abstract
Mechanisms of 5-azacytidine (5AzC)-induced toxicity in the rat foetal brain were investigated. 5AzC (10 mg/kg) was injected into pregnant rats on day 13 of gestation and the protein and mRNA expressions of p53 and its transcriptional target genes, p21, bax, cyclin G1, fas, and gadd45, were examined in the foetal brain. The number of p53-positive cells peaked at 9 h after treatment (HAT) and those of apoptotic cells and p21-positive cells peaked at 12 HAT. The expressions of p21, bax, cyclin G1, and fas mRNAs were significantly elevated from 9 to 12 HAT. From the experiments using 5-bromo-2'-deoxyuridine (BrdU), as compared with controls, the migration of neuroepithelial cells significantly delayed and BrdU-positive signals were observed in many apoptotic cells from 9 to 24 HAT in the 5AzC-group. In addition, the number of S phase cells significantly decreased at 12 HAT. The present results indicate that 5AzC induced apoptosis and cell cycle arrest probably at G1 phase in the rat foetal brain and they might be mediated by p53 in response to DNA damage.Entities:
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Year: 2002 PMID： 12383193 PMCID： PMC2517675 DOI： 10.1046/j.1365-2613.2002.00225.x
Source DB: PubMed Journal: Int J Exp Pathol ISSN： 0959-9673 Impact factor: 1.925