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Bleomycin: Wirkung auf DNS und zellkernstrukturen in mäusefibroblasten

Bleomycin: Effects on DNA and nuclear structure in mouse-fibroblasts

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Summary

In asynchronously dividing mouse fibroblasts (L-cells) the antibiotic Bleomycin exerts a cytostatic effect by selectively inhibiting DNA-synthesis. Our experiments show scissions in DNA of double and single strands in vivo, leading to small, partly acid soluble DNA pieces. Only after fragmentation of DNA the cells accumulate in G2-phase of the cell cycle. Simultaneously, alterations in the nuclear structure occur. First, the electron-density of eu- and heterochromatic regions decreases, resulting in an over-all loss of chromatin mass. Later, also nucleolar structures are transformed into “nucleolar caps”. Apparently, the fragmentation of DNA leads to a destabilization and denaturation of DNA and consequently to conformational changes of chromatin structure.

Zusammenfassung

An asynchron wachsenden Mäusefibroblasten (L-Zellen) wurden die Effekte von Bleomycin auf die DNS, die phasenspezifische antimitotische Wirkung im Zellcyclus sowie die ultrastrukturellen Veränderungen am Zellkern untersucht.

Unsere Experimente zeigen das Auftreten von Einzel- und Doppelstrangbrüchen der DNS bei Bleomycin behandelten Zellen in vitro. Die celluläre DNS wird dadurch in kleine, teils säurelösliche Fragmente zerlegt. Die behandelten Zellen werden phasenspezifisch in der G2-Phase des Zellcyclus arretiert. Dieser Arrest ist erstnach Fragmentierung der DNS wirksam. Gleichzeitig verändert sich die Zellkernstruktur. In einem ersten Stadium vermindert sich die Elektronendichte sowohl in eu- wie heterochromatischen Bezirken. Die Gesamtmasse des Chromatins nimmt ab. Später beobachtet man eine Segregation der nucleolären Bestandteile zu “nucleolar caps”.

Offenbar führt die Fragmentierung der DNS unter Bleomycin zu einer Destabilisierung und Denaturierung der DNS mit nachfolgender Konformationsänderung der komplexen Chromatinstrukturen.

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Authors and Affiliations

  1. Pathologisches Institut, Universität Freiburg, Freiburg, BRD

    Christian Mittermayer, Reinhardt Osieka & Hermann Madreiter

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  1. Christian Mittermayer
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  2. Reinhardt Osieka
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  3. Hermann Madreiter
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Additional information

Herrn Prof. Dr. K. W. Kalkoff zum 65. Geburtstag gewidmet.

Mit Unterstützung des Sonderforschungsbereiches 46 (MOLGRUDENT) der Deutschen Forschungsgemeinschaft.

Wir danken den Herren Peter Kaden und Alfred Rombach für ausgezeichnete technische Mitarbeit.

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Mittermayer, C., Osieka, R. & Madreiter, H. Bleomycin: Wirkung auf DNS und zellkernstrukturen in mäusefibroblasten. Arch. Derm. Res. 249, 401–410 (1974). https://doi.org/10.1007/BF00557901

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