Publication: Expression of p53 and its transcriptional target genes
mRNAs in the ethylnitrosourea-induced apoptosis and
cell cycle arrest in the fetal central nervous system
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Date
2002
Authors
Katayama, K. ; Ohtsuka, R. ; Takai, H. ; Nakayama, Hiroyuki ; Doi, K.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Ethylnitrosourea (ENU) is an alkylating
agent and we previously clarified that it induced
apoptosis and cell cycle arrest in the fetal central
nervous system (CNS). In the present study, we studied
the expression of p53 and its transcriptional target genes
to investigate the role of p53 in the ENU-induced
apoptosis and cell cycle arrest in the fetal CNS following
the administration to dams on day 13 of gestation
(GD13). Although the enhancement of p53 mRNA
expression was not detected by reverse transcription and
polymerase chain reaction (RT-PCR), p53-positive
signals were detected immunohistochemically in the
nuclei of neuroepithelial cells of the ENU-administered
fetuses from 1 hour after treatment (HAT) to 12HAT, and
they were most intensive at 3HAT. On the other hand,
p53-positive signals were scarcely detected in the
control fetuses. Among the p53 target genes, the
expression of p21, bax, cyclinG1 and fas mRNAs
increased and peaked at 6HAT. In addition, strong
immunoreactivity for p21 was detected in the nuclei of
neuroepithelial cells of the fetuses at 6HAT. The
expression of p53 protein increased prior to the
induction of apoptosis and cell cycle arrest, and
transcription of its target genes was also activated. The
present results suggest that ENU may induce apoptosis
and cell cycle arrest in the fetal neuroepithelial cells in a
p53-dependent manner.
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