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Evidence for an origin of ethyl-nitrosourea-induced rat central nervous system tumors from pluripotent germinal neuroepithelium

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Abstract

Brain tumors induced by transplacental application of ethyl-nitrosourea (ENU) in F344 rats were immunohistochemically demonstrated to consist of undifferentiated cells, astriocyte-like cells, oligodendroglia-like cells, and two distinct types of vimentin-expressing cell groupings termed as perivascular small cell nests (PSCNs) and large cell nests (LCNs). Co-distribution of vimentin and glial fibrillary acidic protein (GFAP) was sparsely ovserved in the astrocyte-like cells, which suggested an immature glial phenotype. PCSNs contained cells expressing GFAP, neuron-specific enolase (NSE), β-tubulin isotype III, and low-affinity nerve growth factor receptors (LNGFRs). LCNs contained cells showing a neuronal phenotype with expression of low- and middle-molecular mass neurofilament proteins (NF-L and-M) as well as NSE, β-tubulin isotype III and LNGFR. Double-labelling immunohistochemistry revealed the NF-L-expression in LNGFR-positive LCN-forming cells. Oligodendroglia-like cells and their intercellular neuropil-like structures expressed β-tubulin isotype III, synaptophysin and NSE, in addition to the expressions of vimentin and GFAP. Electron microscopically, synapse-like structures were formed between these oligodendroglia-like cells and their dendritic processes. Topographically, bidirectional cell transitions from PSCNs to astrocytes and LCNs were indicated. The present study strongly suggests that so-called ENU-induced “gliomas” originate from pluripotent germinal neuroepithelium. Furthermore, LNGFR expression may be responsible for acquisition of neuronal phenotype in these tumors.

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Authors and Affiliations

  1. Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, Kamiyoga 1-18-1, 158, Tokyo, Japan

    M. Shibutani, K. Mitsumori, T. Imazawa & M. Takahashi

  2. Division of Pharmacology, Biological Safety Research Center, National Institute of Health Sciences, Kamiyoga 1-18-1, 158, Tokyo, Japan

    K. Inoue

  3. Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, 113, Tokyo, Japan

    R. Okeda & H. Hatanaka

  4. Department of Pathology, Sasaki Institute, Kanda-Surugadai 2-2, Chiyoda-ku, 101, Tokyo, Japan

    A. Maekawa

  5. Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Yamadaoka 3-2, 565, Suita-shi, Osaka, Japan

    Y. Hayashi

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  1. M. Shibutani
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Supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10-year Strategy of Cancer Control, Japan. Dr. Shibutani is an Awardee of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research, Japan

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Shibutani, M., Mitsumori, K., Okeda, R. et al. Evidence for an origin of ethyl-nitrosourea-induced rat central nervous system tumors from pluripotent germinal neuroepithelium. Acta Neuropathol 87, 293–301 (1994). https://doi.org/10.1007/BF00296745

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  • DOI: https://doi.org/10.1007/BF00296745

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