title: Evidence for an origin of ethyl-nitrosourea-induced rat central nervous system tumors from pluripotent germinal neuroepithelium.
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 observed in the astrocyte-like cells, which suggested an immature glial phenotype. PCSNs contained cells expressing GFAP, neuron-specific enolase (NSE), beta-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, beta-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 beta-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.
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shibutani
authors.forename: K
authors.initials: K
authors.lastname: Mitsumori
authors.forename: R
authors.initials: R
authors.lastname: Okeda
authors.forename: T
authors.initials: T
authors.lastname: Imazawa
authors.forename: A
authors.initials: A
authors.lastname: Maekawa
authors.forename: H
authors.initials: H
authors.lastname: Hatanaka
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D016543:Central Nervous System Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004848:Epithelium / Q000196:embryology; D005038:Ethylnitrosourea; D005333:Fetus / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D007267:Injections; D008854:Microscopy, Electron; D009417:Nerve Tissue / Q000196:embryology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016900:Neurofilament Proteins; D005038:Ethylnitrosourea