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Histological effects of 6-mercaptopurine on the fetal rat central nervous system: A light-microscopic study
- Source :
- Teratology. 11:297-311
- Publication Year :
- 1975
- Publisher :
- Wiley, 1975.
-
Abstract
- Wistar rats were administered single doses of 16 or 50 mg/kg 6-mercaptopurine (6-MP) on day 12 of pregnancy. Necrosis in the fetal forebrain and spinal cord was studied by light microscope 6, 12, 14, 48, 72, and 81 h and 8 days afterward. The extent of necrosis was dose dependent. The first necroses were seen after 24 h, regardless of location (brain, spinal cord) or dose; but the extent was greatest after 48 h. All necrotic cells had a typical appearance; they were ballooned and often fragmented, their nuclei were darkly colored and frequently pyknotic, and they were often karyorhexic. Necroses appeared almost exclusively at sites of beginning cellular differentiation, i.e., in the intermediate zone. In the spinal cord the ventricular zone was also necrotic and the alar plate (dorsal horn) always affected. Phagocytizing cells (macrophages) appeared in the spinal cord after 48 h and in the brain after 72 h. After 81 h all the necrotic material had been phagocytized. at which time there was a massive congestion of the extra- and intracerebral vessels. Hemorrhages appeared in denned localizations. Eight days after exposure to 16 mg/kg 6-MP fetuses no longer showed any visible deviations. Fetuses exposed to 50 mg/kg showed deviations in the cytoarchitecture of the neopallium: an extremely broadened ventricular zone, few cells in the intermediate zone, and extensive rarefaction of cells in the cortical plate with no clear layer structure. In the spinal cord, cleft formations were especially noticeable in the dorsal-horn region. All fetuses showed a hydrocephalus externus after 50 mg/kg. The mechanism leading to necrosis is discussed.
- Subjects :
- Intracranial Arteriovenous Malformations
Embryology
Pathology
medicine.medical_specialty
Necrosis
Health, Toxicology and Mutagenesis
Central nervous system
Biology
Toxicology
Phagocytosis
Pregnancy
medicine
Animals
Fetus
Dose-Response Relationship, Drug
Alar plate
Mercaptopurine
Macrophages
Abnormalities, Drug-Induced
Brain
Anatomy
Embryo, Mammalian
medicine.disease
Spinal cord
Rats
Hydrocephalus
Teratogens
medicine.anatomical_structure
Spinal Cord
Cytoarchitecture
Cerebrovascular Circulation
Female
medicine.symptom
Pyknosis
Developmental Biology
Subjects
Details
- ISSN :
- 10969926 and 00403709
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Teratology
- Accession number :
- edsair.doi.dedup.....2e38e66c48205da3fc368cadd2e6370d