Histopathological changes in the brain of mouse fetuses by etoposide-administration
Histopathological changes in the brain of mouse fetuses by etoposide-administration
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DOI：
10.14670/hh-21.257
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发表时间：
2006-03-01
影响因子：
2
通讯作者：
Doi, K
中科院分区：
文献类型：
--
作者：
Nam, C;Woo, GH;Doi, K
依托泊苷（VP-16）是一种拓扑异构酶II抑制剂，是一种抗肿瘤药物，已知其在妊娠啮齿动物中给药时显示胚胎毒性和致畸性。我们研究了VP-16诱导的小鼠胎儿脑组织病理学变化。妊娠小鼠在妊娠第12天（GD 12）腹腔注射VP-16（4 mg/kg），并在给药后1 - 48小时（HAT）采集胎仔。端脑壁有丝分裂神经上皮细胞在2 HAT时显著减少，在4 HAT时几乎观察不到。胎脑内神经上皮细胞固缩的数量在4次HAT时开始增加，8 ~ 24次HAT时更为明显。TUNEL法染色阳性，可检测到DNA片段，并显示凋亡的超微结构特征。此外，这些细胞还对裂解的caspase-3呈阳性，caspase-3是细胞凋亡的重要执行者。这表明在GD 12时VP 16处理后，在小鼠胎儿脑中诱导了过度的神经上皮细胞凋亡。
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 (GD12), 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 VP16 treatment on GD 12.