Publication: 5-Fluorouracil-induced histopathological changes in the central nervous system of rat fetuses
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Date
2009
Authors
Yamaguchi, Y. ; Aoki, A. ; Fukunaga, Y. ; Matsushima, K. ; Ebata, T. ; Ikeya, M. ; Tamura, 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
5-Fluorouracil (5-FU), a thymidylate
synthesis inhibitor, has been well known to induce
developmental anomalies in the craniofacial tissues and
limb buds. Recently it was reported that microencephaly
was also induced in rat neonates after 5-Fu-treatement in
late phase of pregnancy (Kumar et al., 2006). In this
study, pregnant rats were treated with 5-Fu (15, 30 or 50
mg/kg) on day 13 of gestation, and their fetuses were
examined for histopathological changes, especially in
the fetal central nervous system (CNS) at 12, 24 and 48
hours after treatment (HAT). At 12 HAT, an
enhancement of pyknosis of neuronal progenitor cells
and subsequent loss of dead cells were detected in the
CNS in a dose-dependent manner. The severity of such
histopathological changes in the CNS was most
prominent in the telencephalon (middle and dorsal layers
of the ventricular zone) and spinal cord (dorsal area).
Pyknotic cells decreased towards 48 HAT in the brain
while they increased towards 48 HAT in the spinal cord.
Almost all of the nuclei of pyknotic cells were positively
stained by TUNEL method and showed characteristics
of apoptotic cells under electron microscopy. Therefore,
these pyknotic cells were considered to be apoptotic
ones. Enhanced apoptosis and reduced mitosis in neuronal progenitor cells in the telencephalon seem to be
responsible for the later induction of microencephaly
reported by Kumar et al. (2006).
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