Publication: Histopathological changes in the brain of mouse fetuses by etoposide-administration
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Date
2006
Authors
Nam, C. ; Woo, G.H. ; Uetsuka, K. ; 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
Etoposide (VP-16), a topoisomerase II
inhibitor, is an anti-tumor agent which is also known to
show embryotoxicity, and teratogenicity when
administered to pregnant rodents. We examined VP-16-
induced histopathological changes in the brain of mouse
fetuses. Pregnant mice were intraperitoneally injected
with VP-16 (4 mg/kg) on day 12 of gestation (GD 12),
and fetuses were collected from 1 to 48 hours after
treatment (HAT). Mitotic neuroepithelial cells in the
telencephalic wall prominently decreased at 2 HAT, and
were hardly observed at 4 HAT. The number of pyknotic
neuroepithelial cells in the fetal brain began to increase
at 4 HAT, and became prominent from 8 to 24 HAT.
These pyknotic cells were also positively stained by
TUNEL method, which can detect fragmented DNA,
and showed ultrastructural characteristics of apoptosis.
Additionally, these cells were also positive for cleaved
caspase-3, an essential executioner of apoptosis. This
indicated that excessive neuroepithelial cell apoptosis
was induced in the brain of mouse fetuses following VP-
16 treatment on GD 12.
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