title: Histopathological changes in the brain of mouse fetuses by etoposide-administration.
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.
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. vet0215@yahoo.co.kr
authors.forename: C
authors.initials: C
authors.lastname: Nam
authors.forename: G H
authors.initials: GH
authors.lastname: Woo
authors.forename: K
authors.initials: K
authors.lastname: Uetsuka
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Doi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology* / Q000473:pathology; D001923:Brain Chemistry; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D008938:Mitosis / Q000187:drug effects; D046569:Neuroepithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D004247:DNA; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases