Metastasis from the brain of transplanted N-ethyl-N-nitrosourea-induced central nervous system tumors in rats |
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| Affiliation: | 1. Radiobiological Institute TNO 151 Lange Kleiweg, Postbox 5815, 2280 HV Rijswijk, The Netherlands;2. Institute for Experimental Gerontology TNO, 151 Lange Kleiweg, Postbox 5815, 2280 HV Rijswijk, The Netherlands;1. Kirkland Consulting, PO Box 79, Tadcaster LS24 0AS, England, UK;2. Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger Allee 3, D-53175 Bonn, Germany;3. Novartis Institutes for Biomedical Research, Preclinical Safety, CH-4002 Basel, Switzerland;4. F. Hoffmann-La Roche Ltd., Pharmaceutical Science and Roche Innovation Center Basel, CH-4070 Basel, Switzerland;5. RIVM-National Institute for Public Health and the Environment, Bilthoven, Netherlands;6. European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Systems Toxicology Unit, Institute for Health and Consumer Protection (IHCP), European Commission—Joint Research Centre, TP 126, Via E. Fermi 2749, I-21027 Ispra, Varese, Italy;1. Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia;2. Faculty of Chemistry and Chemical Engineering, University of Ljubljana, Večna pot 113, 1000, Ljubljana, Slovenia;1. Division of Translational Toxicology, NIEHS, Research Triangle Park, NC, USA;2. Integrated Laboratory Systems, LLC (An Inotiv Company), Research Triangle Park, NC, USA;3. TwinStrand Biosciences, Inc., Seattle, WA, USA |
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| Abstract: | Two transplantable rat central nervous system (CNS) tumors induced by N-ethyl-N-nitrosourea (ENU) were employed to study the mechanisms controlling extracranial metastasis from intracranial tumors. Cells derived from a serially passaged anaplastic astrocytoma and a malignant glioma were injected intracerebrally at doses of 104, 105 and 106 cells per rat (Sprague-Dawley and WAG/Rij rats). As soon as neurological dysfunction appeared, animals were sacrificed and examined histologically for (1) extracerebral outgrowth of the intracerebral tumor, (2) the presence of distant metastases within the CNS and (3) remote metastases outside the CNS. In addition to histology, a bioassay procedure was performed. Metastases were found in cervical lymph nodes (74%), lung (21%) and liver (5%). For both tumor groups, rats with both distant CNS metastases and local extracerebral outgrowth developed remote metastases more frequently (P < 0.05) than animals with intracerebral growth only. The data indicate that both local extracranial spread due to surgical intervention as well as local and distant invasion of leptomeninges promote extracranial metastatic spread. |
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