Summary
We have recently reported that fetal BD IX-rat brain cells (FBC), transferred to long-term culture after a transplacental pulse of EtNU on the 18th day of gestation, undergo neoplastic transformation in vitro (“BT-cell lines”). Tumors developed upon s.c. reimplantation of BT-cells into baby BD IX-rats, appeared histologically as neurinoma-, glioma- or glioblastoma-like, and frequently as pleiomorphic neoplasms. In spite of a more atypic cellular morphology, these tumors grossly resembled the different types of neuroectodermal rat neoplasms induced by EtNU in vivo. Like the neoplastic cell culture lines derived from EtNU-induced, neuroectodermal BD IX-rat tumors (“V-cell lines”), the BT-lines contained multipolar glia-like cells, but also flat cells with fewer and shorter cytoplasmic processes, and occasionally giant cells. Both the V- and BT-lines showed different levels of aneuploidy. They contained multiple subpopulations of cells, as reflected, e.g., by plurimodal pulse-cytophotometric DNA distributions. All lines contained, to varying degrees, the nervous system specific protein S-100, a “marker” not yet expressed in FBC. There was no indication of more than borderline neurotransmitter activity, suggesting that proliferating (precursor) cells of glial lineages may preferentially undergo malignant transformation after exposure to EtNU during this stage of brain development.
Zusammenfassung
Gehirnzellen der fetalen (18. Tag der Gravidität) BD-IX-Ratte, nach einem transplacentaren N-Äthyl-N-Nitrosoharnstoff (ÄNH)-Puls in vivo in ein Langzeit-Zellkultursystem überführt, durchlaufen den Prozeß der neoplastischen Transformation in vitro (BT-Zellinien). Die nach s.c. Rückimplantation von BT-Zellen in neugeborene BD IX-Ratten entstandenen Tumoren (histologisch vom Neurinom-, Gliomoder Glioblastomtyp, häufig auch pleomorph) waren insgesamt den verschiedenen Arten neuroectodermaler Neoplasmen vergleichbar, die bei BD IX-Ratten nach ÄNH-Applikation in vivo beobachtet werden. Ebenso wie Zellkultur-Linien (V-Zellinien), die von ÄNH-induzierten Tumoren des Nervensystems der BD IX-Ratte abgeleitet wurden, enthielten die BT-Linien multipolare, gliaähnliche Zellen, neben wenigen Riesenzellen aber auch flache Zellen mit vergleichsweise wenigen, kürzeren cytoplasmatischen Fortsätzen. Die V- und BT-Linien waren verschiedengradig aneuploid und aus multiplen Subpopulationen von Zellen zusammengesetzt, widergespiegelt u.a. durch plurimodale impulscytophotometrische DNS-Verteilungen. Alle Linien enthielten das vorwiegend gliaspezifische „Marker”-Protein S-100, welches im fetalen Gehirn noch nicht exprimiert ist. Eine nennenswerte Neurotransmitter-Aktivität wurde nicht gefunden. Nach Applikation von ÄNH während der perinatalen Phase der Gehirnentwicklung werden offenbar vorwiegend proliferative Zellen glialer (Vorläufer-) Populationen neoplastisch transformiert.
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Abbreviations
- EtNU:
-
N-ethyl-N-nitrosourea
- i.V.:
-
intravenous
- s.c.:
-
subcutaneous
- FBC:
-
fetal BD IX-rat brain cells
- PBS:
-
phosphate buffered saline
- BSA:
-
bovine serum albumin
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This is communication No. 14 on a research program devoted to molecular and cellular mechanisms in pulse-carcinogenesis by N-ethyl-N-nitrosourea in the rat nervous system
Research supported by the Deutsche Forschungsgemeinschaft (Ra 119/5-6; SFB 51/E-13), the C. Bohnewand-Foundation and by the Norwegian Cancer Society
On leave from the Institute of Pathology, Sect. B., University of Oslo, Rikshospitalet, Oslo 1, Norway.
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Laerum, O.D., Rajewsky, M.F., Schachner, M. et al. Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. Z. Krebsforsch. 89, 273–295 (1977). https://doi.org/10.1007/BF00283783
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DOI: https://doi.org/10.1007/BF00283783