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Schmahl, W. ; Luz, A. ; Leierseder-Bauer, M. ; Neuhäuser-Klaus, A.

Diaplacental Induction by Ethylnitrosourea of Tumours at the Pial Border of the Central Nervous System in (T x HT)F1 Mice.

Carcinogenesis 11, 1313-1322 (1990)

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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 (approximately 20%) and only approximately 7% Schwann cell tumours and approximately 3% tumours of meningomesenchymal 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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