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© 1990 Oxford University Press

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Diaplacental induction by ethylnitrosourea of tumours at the pial border of the central nervous system in (T x HT)F1 mice

Wolfgang Schmahl 2, Arne Luz 2, Maria Leierseder-Bauer 2 and Angelika Neuhäuser-Klaus 1

2GSF-Institut für Pathologie D-8042 Neuherberg, FRG
1GSF-Institut für Säugetiergenetik D-8042 Neuherberg, FRG

Ethylnitrosourea (ENU) was diaplacentally applied to (T x HT)F1 mice at a dose of 40 mg/kg on different gestation days during organogenesis and early fetal stages by i.p. injection to the dams. The animals were particularly sensitive to induction of tumours at the central nervous system (CNS)-skull-vertebra interface (30 and 20% in ENU-treated male and female offspring respectively, compared with 1% in controls). ENU treatment during the late organogenesis stage (gestation days 8–11) proved to be less efficient in tumour induction than during the subsequent early fetal period (gestation days 12–14). Ninety-two per cent of the CNS tumours were located at the interface between the CNS and the osseous surrounding. The distribution of these tumours at the pial border was inhomogeneous: 69% were found at the brain-skull border, 6% of the tumours occurred within the cervico-thoracal districts and 25% within the lumbo-sacral districts of the spinal cord-vertebra interface. Histological classification revealed a preferential occurrence of neuroepithelial tumours In male offspring (~20%) and only~7% Schwaim cell tumours and~3% tumours of meningo-mesenchymal origin. In female offspring neuroepithelial tumours and Schwann cell tumours were observed at about an equal rate (9–10%), in contrast to meningo-mesenchymal tumours (1%). Nearly 98% of these tumours were situated at the basal districts of the space between the CNS-skull and spinal cord-vertebra. This indicates a particular sensitivity of the basal neurothelium, a derivative of neural crest cells, for ENU-induced carcinogenesis. The pluripotency of these cells during the mid-gestation period apparently enables growth of different histopathological tumour types, which arise independently from each other.


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 Toxicol SciHome page
W. Slikker III, N. Mei, and T. Chen
N-Ethyl-N-nitrosourea (ENU) Increased Brain Mutations in Prenatal and Neonatal Mice but Not in the Adults
Toxicol. Sci., September 1, 2004; 81(1): 112 - 120.
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