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Early sequential lesions during development of experimental gastric cancer with special reference to dysplasias

Frühveränderungen der Carcinogenese an der Magenschleimhaut im Tierexperiment unter besonderer Berücksichtigung der Dysplasien

  • Original Papers
  • Experimental Oncology
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Zusammenfassung

Es wurde tierexperimentell die Entwicklung des Magencarcinoms in seinen Frühphasen untersucht und geprüft, welche Rückschlüsse auf den Cancerisierungsablauf am menschlichen Magen möglich sind. Nach limitierter oraler Zufuhr von N-Methyl-N′-Nitro-N-Nitrosoguanidin an 174 Ratten entwickelten sich Carcinome direkt aus der sonst unveränderten Schleimhaut über mehrere aufeinanderfolgende Transformationsstadien, ohne gutartig erscheinende proliferative oder neoplastische Epithelläsionen zu durchlaufen. Als erste lichtoptisch erkennbare Veränderung ergaben sich fokal Dysplasien Grad I, die mit zunehmender Versuchszeit in Dysplasien Grad II und III übergingen. Die experimentell induzierten Dysplasien sind kausalgenetisch und in ihrem biologischen Verhalten nicht mit der Mehrzahl der am menschlichen Magen auftretenden Dysplasien gleichzusetzen. Die in der Regel im oberen Schleimhautdrittel lokalisierten Dysplasien des Menschen insbesondere des Grades I und II sind größtenteils entzündungsbedingt und reversibel. Die experimentellen Dysplasien im Bereich der Proliferationszone sind dagegen als potentiell prämaligne anzusehen, da sie irreversibel waren und sich progredient weiterentwickten. Nach den tierexperimentellen Befunden kommen beim Menschen insbesondere die Dysplasien des Grades III als mögliche Vorläufer von Carcinomen in Betracht, die sich in nicht entzündlicher Schleimhaut im Bereich der Proliferationszone entwickelt haben.

Summary

The early sequential development of gastric cancer was studied with experimental animals and examined with respect to what conclusions can be drawn for understanding carcinogenesis in man. After limited oral administration of N-methyl-N′nitro-N-nitrosoguanidine to 174 rats carcinomas developed in most cases directly from the otherwise unchanged mucosa through various successive stages of transformation, without passing through a benignappearing proliferative or neoplastic epithelial lesion. Focal dysplasia grade I was the first recognizable change observed by light microscopy, followed by dysplasia grade II, and subsequently dysplasia grade III. In spite of very similar morphological characteristics, the experimentally induced dysplasias cannot be simply equated in their etiology and biological behavior with the dysplasias of the human stomach. Dysplasias of grade I and II commonly found in man are usually associated with a chronic gastritis; they are located in the upper third of the mucosa and are for the most part reversible. The experimental dysplasias occuring in the proliferative zone of an otherwise undisturbed mucosa must be considered potentially premalignant, as they are irreversible and develop progressively. This finding points out that in man dysplasias grade III within the regenerative zone of non-inflammatory mucosa should be considered particularly as possible precursors of gastric carcinomas.

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This work was supported in part by a research grant from the Buettner Foundation (Göttingen) This work was reported in part at the Third International Symposium on Detection and Prevention of Cancer, New York, USA, 1976, and at the 62nd meeting of the Deutsche Gesellschaft für Pathologie, Vienna, Austria, 1978

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Kunze, E., Schauer, A., Eder, M. et al. Early sequential lesions during development of experimental gastric cancer with special reference to dysplasias. J Cancer Res Clin Oncol 95, 247–264 (1979). https://doi.org/10.1007/BF00410646

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