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Neoplastische und präneoplastische Veränderungen bei Ratten nach einmaliger oraler Applikation von N-Nitrosomorpholin

Neoplastic and preneoplastic lesions in rats after oral administration of a single dose of N-nitrosomorpholine

  • Original Papers
  • Experimental Oncology
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Summary

The administration of a single oral dose of 320 mg/kg body wt. N-nitrosomorpholine (NNM) to 62 Sprague-Dawley rats resulted in neoplastic and preneoplastic changes in different organs, especially in liver and kidney. After a lag period of 4 weeks, nearly all experimental animals developed preneoplastic (clear cell, acidophilic, basophilic, mixed cell) foci of the liver parenchyma. Sporadically, small neoplastic nodules were found in the liver as early as 4 weeks after the beginning of the experiment. After a lag period of 1–2 years, 4 of 13 rats showed multiple neoplastic hepatic nodules and one animal a hepatocellular carcinoma. The bile ductules of some animals responded to the carcinogen by forming mocous cholangiofibroses and cystic cholangiomas. After long lag periods, large cholangiofibromas were found in two experimental animals. One or two years after application of the carcinogen, many animals developed epithelial (clear cell, acidophilic, chromophobic, basophilic, oncocytic) kidney tumors, often cystic. Pathologically changed (clear cell, chromophobic, basophilic, oncocytic) tubules are regarded as precursors of the epithelial tumors. The altered tubules appear for the first time at about half a year after application of the carcinogen. Apart from multiple cysts of the liver and kidneys some pancreatic cysts developed in two animals. In addition, two mesenchymal kidney tumors, one malignant neurinoma, two subcutaneous fibromas, one fibroadenoma, and one squamous cell carcinoma of the skin were observed.

Zusammenfassung

Die einmalige orale Gabe von 320 mg/kg Körpergewicht N-Nitrosomorpholin (NNM) an 62 männliche Sprague-Dawley-Ratten führte zu präneoplastischen und neoplastischen Veränderungen in verschiedenen Organen, besonders in Leber und Nieren. Im Leberparenchym bildeten sich nach einer Latenzzeit von 4 Wochen bei nahezu allen Versuchstieren präneoplastische (klarzellige, acidophile, basophile, gemischtzellige) Herde aus. Vereinzelt waren nach 4 Wochen schon kleine neoplastische Knötchen in der Leber zu beobachten. Nach einer Latenzzeit von 1–2 Jahren entwickelten 4 von 13 Ratten multiple neoplastische Knoten, 1 Tier zeigte ein hepatocelluläres Carcinom. Die Gallengänge reagierten bei einem Teil der Tiere mit Ausbildung von verschleimenden Cholangiofibrosen und cystischen Cholangiomen. Bei 2 Tieren fanden sich nach langen Latenzzeiten ausgedehnte Cholangiofibrome. In den Nieren entwickelten sich 1–2 Jahre nach der Carcinogengabe epitheliale (klarzellige, acidophile, chromophobe, basophile, onkocytäre) Tumoren, die z. T. cystisch gebaut waren. Als Vorstufe der Nierenepitheliome fassen wir charakteristisch veränderte (klarzellige, chromophobe, basophile, onkocytäre) Tubuli auf, deren Ausbildung etwa ein halbes Jahr nach Versuchsbeginn einsetzt. Bei 2 Versuchstieren traten neben multiplen Leber- und Nierencysten einzelne Pankreascysten auf. Außerdem wurden 2 mesenchymale Nierentumoren, 1 malignes Neurinom des N. oculomotorius, 2 subcutane Fibrome, 1 Fibroadenom und 1 Plattenepithelcarcinom der Haut beobachtet.

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  1. Deutsches Krebsforschungszentrum, Abteilung für Cytopathologie, Institut für Experimentelle Pathologie, Im Neuenheimer Feld 280, D-6900, Heidelberg, Bundesrepublik Deutschland

    P. Bannasch, D. Mayer & R. Krech

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  1. P. Bannasch
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  2. D. Mayer
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  3. R. Krech
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Bannasch, P., Mayer, D. & Krech, R. Neoplastische und präneoplastische Veränderungen bei Ratten nach einmaliger oraler Applikation von N-Nitrosomorpholin. J Cancer Res Clin Oncol 94, 233–248 (1979). https://doi.org/10.1007/BF00419283

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