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Nucleotidveränderungen von 18 S und 28 S ribosomaler RNS aus Rattenleber bei der chemischen Carcinogenese durch N-Nitrosomorpholin

Nucleotide alterations of 18 s and 28 s ribosomal RNA from rat liver during carcinogenesis induced by N-nitrosomorpholine

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Summary

After administration of N-nitrosomorpholine (NNM) to female Wistar-rats the ribosomal RNA (18 S and 28 S rRNA) of the livers contained “abnormal” dinucleotides which were resistant against treatment with alkali or with spleen phosphodiesterase. These and further observations are discussed in view of the hypothesis that during the induction of liver tumors a metabolite of NNM causes crosslinks of nucleic acid bases. The application of this hypothesis on the effects of NNM upon DNA permits to explain the additional results that have been obtained. Observations on NNM metabolism as reported in the literature are not inconsistent with this interpretation.

Zusammenfassung

Nach längerdauernder Verabfolgung von N-Nitrosomorpholin (NNM) an weiblichen Wistar-Ratten fanden sich in der ribosomalen RNS (18 S und 28 S-rRNS) der Leber „anormale“ Dinucleotide, welche sich als resistent erwiesen gegenüber Alkali und Milz-Phosphodiesterase. Diese und weitere Befunde werden im Zusammenhang mit der Hypothese diskutiert, daß es während der durch NNM induzierten Carcinogenese in der Leber über einen NNM-Metaboliten zu Basenvernetzungen (“cross-linking”) kommt. Eine Übertragung der Basenvernetzungshypothese als carcinogenes Wirkungsprinzip des NNM auf die DNS vermag die weiteren gewonnenen Ergebnisse zu erklären. In der Literatur berichtete Beobachtungen zum NNM-Stoffwechsel stehen mit dieser Deutung nicht im Widerspruch.

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Authors and Affiliations

  1. Abteilung für Medizinische Molekularbiologie im Klinisch-Theoretischen Zentrum der Medizinischen Hochschule Lübeck, Bundesrepublik Deutschland

    M. Hümpel

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Diese Arbeit ist Teil einer Dissertation.

Die Untersuchungen wurden aus einer durch die Deutsche Forschungsgemeinschaft gewährten Sachbeihilfe gefördert. Herrn. Prof. Dr. E. Harbers danke ich sehr für die jederzeit gewährte Unterstützung der Arbeit, die auf eine Anregung von Prof. Dr. W. Frank zurückgeht. Fräulein U. Wischhöfer danke ich schr für wertvolle Mitarbeit.

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Hümpel, M. Nucleotidveränderungen von 18 S und 28 S ribosomaler RNS aus Rattenleber bei der chemischen Carcinogenese durch N-Nitrosomorpholin. Z. Krebsforsch. 84, 311–323 (1975). https://doi.org/10.1007/BF00312252

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  • DOI: https://doi.org/10.1007/BF00312252

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