Microencephaly and microphthalmia in rat fetuses by busulfan.
Microencephaly and microphthalmia in the embryos/fetuses from rats exposed to busulfan were histopathologically examined. Busulfan was intraperitoneally administered at 10 mg/kg on gestation days (Days) 12, 13 and 14, and then embryos/fetuses were harvested on Days 14.5, 15, 16 and 21. In the treated group on Day 21, all fetuses were small with reduced body weight, with microencephaly and microphthalmia. On Days 14.5, 15 and 16, apoptotic cells were increased in the neuroepithelium and the neural retina with a width reduction and a decrease in cell density, and the lens epithelial cells histopathologically. Mitotic inhibition was observed in the neuroepithelium, neural retina and equatorial zone of the lens. On Day 21, the cerebral cortex and the retina became markedly thinner. The lens fibers showed swollen, fragmentary and vacuolar formation in the cranial portion accompanied with small lens sizes. The anti-proliferative effects of busulfan brings about a lack of cell populations required for the normal organogenesis of the brain and eye, and leads to microencephaly and microphthalmia, featuring hypoplasia of cerebrum and hypoplasia of retina and lens with cataract, respectively.
Furukawa
S
S
Biological Research Laboratories, Nissan Chemical Industries, Ltd, Japan. furukawa@nissanchem.co.jp
Usuda
K
K
Abe
M
M
Ogawa
I
I
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002066:Busulfan / Q000633:toxicity*; D002452:Cell Count; D005260:Female; D007274:Injections, Intraperitoneal; D007908:Lens, Crystalline / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D008831:Microcephaly / Q000139:chemically induced / Q000196:embryology / Q000473:pathology*; D008850:Microphthalmos / Q000139:chemically induced / Q000196:embryology / Q000473:pathology*; D008938:Mitosis / Q000187:drug effects; D046569:Neuroepithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000633:toxicity*
D018906:Antineoplastic Agents, Alkylating; D013723:Teratogens; D002066:Busulfan