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Desoxyribonucleinsäure-Polymerase in menschlichen Leukocyten

Enzymaktivität bei Leukämien und Virusinfektionen

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Zusammenfassung

Der enzymatische Einbau von Desoxyribonucleotiden in DNS durch den partikelfreien Überstand des Cytolysats von peripheren menschlichen Leukocyten wurde bei Leukämien und Virusinfektionen untersucht.

Die optimalen Reaktionsbedingungen entsprechen denen der DNS-Polymerasen aus anderen stark proliferierenden Säugetiergeweben.

Die noch nachweisbare geringe Enzymaktivität in peripheren Leukocyten von gesunden Spendern ist auf die potentiell zur DNS-Synthese befähigten rundkernigen Zellen zurückzuführen. Bei chronischen Myelosen mit Ausschwemmung unreifer Zellelemente finden sich sehr hohe Aktivitäten der DNS-Polymerase. Dagegen liegen die Werte bei akuten Leukosen, trotz des hohen Anteils unreifer Zellen, deutlich niedriger. Das Mißverhältnis zwischen der Unreife der Zellen und der Aktivität der DNS-Polymerase bei akuten und chronischen Myelosen steht in guter Übereinstimmung mit Untersuchungen zur Proliferationsaktivität leukämischer Zellen. Die gefundenen niedrigen Einbauraten bei chronischen Lymphadenosen entsprechen ebenfalls gut der niedrigen Mitoseaktivität der Lymphocyten bei dieser Erkrankung.

Die Polymeraseaktivität der Leukocyten und die Proliferationsaktivität des malignen Prozesses gehen einander parallel. Dadurch sind prognostische Schlüsse auf den Verlauf des Krankheitsbildes möglich.

Bei akuten Virusinfektionen steigt die Enzymaktivität stark an. Dies entspricht der spezifischen Induktion der DNS-Polymerase nach Phageninfektionen bei Bakterien oder nach Virusinfektionen in Gewebekulturen.

Summary

The enzymatic incorporation of deoxyribonucleotides into DNA by particle-free extracts from peripheral human leukocytes has been investigated in leukemias and virus infections.

The reaction characteristics are similar of those of the DNA polymerases derived from other rapidly proliferating mammalian tissues.

The slight but still demonstrable enzyme activity in peripheral leukocytes from healthy donors has to be ascribed to the mononuclear cells. In chronic granulocytic leukemias with immature cells in the peripheral blood high activities of the DNA polymerase are found. On the other hand the values in acute leukemias are markedly lower in spite of the high proportion of immature cells. The discrepancy between the immaturity of the cells and the activity of the DNA polymerase in acute and chronic granulocytic leukemias is in good agreement with the results of investigations of the proliferative activity of leukemic cells. The low rates of incorporation in chronic lymphocytic leukemias likewise correspond to the low mitotic activity of the leukemic lymphocytes.

The activity of the DNA polymerase in leukocytes and the activity of the malignant process parallel each other, thus permitting a prognosis on the course of the disease to be made.

In acute viral infections the enzyme activity is high. This corresponds to the specific induction of the DNA polymerase in bacteria after phage infection or in tissue cultures after viral infections.

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Abbreviations

ATP:

Adenosintriphosphat

dATP:

Desoxyadenosin-5′-triphosphat

dAMP:

Desoxyadenosin-5′-monophosphat

dCTP:

Desoxycytidin-5′-triphosphat

dGTP:

Desoxyguanosin-5′-triphosphat

DNase:

Desoxyribonuclease

DNS:

Desoxyribonucleinsäure

EDTA:

Äthylendiamintetraessigsäure

PP:

Pyrophosphat

TTP:

Thymidin-5′-triphosphat

TRIS:

Tris(hydroxymethyl)aminomethan

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Authors and Affiliations

  1. Institut für Biochemie der Universität Köln, Germany

    K. Wilms & L. Jaenicke

  2. Medizinische Universitätsklinik, Otfried-Müller-Straße, 74 Tübingen

    K. Wilms

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Für die Überlassung von Untersuchungsmaterial danken wir der Medizinischen Klinik der Städtischen Krankenanstalten Köln-Merheim (Direktor: Prof. Dr.Buchborn), der Medizinischen Universitätsklinik Köln (Direktor: Prof. Dr.Gross), dem Städtischen Kinderkrankenhaus Köln-Riehl (Direktor: Prof. Dr.Ewerbeck), der Blutspendenzentrale an der Chirurgischen Universitätsklinik Köln (Leiter: OMR Dr.Bube) und dem Institut für gerichtliche Medizin (Direktor: Prof. Dr.Dotzauer).

Die Arbeit wurde ermöglicht durch ein Forschungsstipendium (K. W.) und eine Sachbeihilfe der Deutschen Forschungsgemeinschaft.

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Wilms, K., Jaenicke, L. Desoxyribonucleinsäure-Polymerase in menschlichen Leukocyten. Klin Wochenschr 46, 407–413 (1968). https://doi.org/10.1007/BF01736929

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