Abstract
Etoposide (VP-16), a topoisomerase II inhibitor, is an anti-tumor agent which causes embryotoxicity, exencephaly, encephalocele, anophthalmia and major skeletal malformations of fetuses when administered to dams of rodents. We examined VP-16-induced histopathological changes in the brain of mouse fetuses. Pregnant mice were intraperitoneally treated with VP-16 (4 mg/kg) on 12th day of gestation (GD 12), and fetuses were collected from 1 to 48 hours after treatment (HAT). A moderate decrease of mitotic figures of neuroepithelial cells was observed in the telencephalic wall at 4 HAT. A moderate to marked increase of pyknotic neuroepithelial cells was detected in the brain of VP-16-treated fetuses, and being most prominent from 8 to 24 HAT. These pyknotic cells were also positively stained by TUNEL and cleaved caspase-3 immunostain. It was suggested that excessive neuronal apoptosis was induced in the brain of mouse fetuses treated with VP-16 on GD 12.
