Summary
The enzyme activities of DNA polymerase and thymidine kinase were determined in peripheral leukemic leukocytes of patients with acute leukemia treated with Dauno-Rubidomycin or Adriamycin. During the first hours after the injection of each drug both enzymes are significantly augmented. After a few days there is a distinct decrease of the enzyme activities preceding the fall of the leukocyte count.
The initial increase in enzyme activity could be reproduced in PHA stimulated lymphocyte cultures of healthy donors by incubating the cells with the Anthracycline antibiotics. During this increase of DNA polymerase and thymidine kinase DNA and RNA synthesis are markedly inhibited. Experiments with inhibitors of protein synthesis make it likely that the remarkable rise in enzyme activity is caused by the synthesis of new enzyme molecules.
The DNA polymerase reaction is inhibited by Dauno-Rubidomycin or Adriamycin. To some extent this could be reversed by the addition of new primer-DNA.
Zusammenfassung
Unter der Therapie mit Dauno-Rubidomycin oder Adriamycin wird in der aus dem peripheren Blut isolierten leukämischen Zellpopulation ein Aktivitätsabfall der Enzyme DNS-Polymerase und Thymidinkinase beobachtet. In den ersten Stunden nach Injektion der Anthracyclin-Antibiotica kommt es jedoch regelmäßig zu einem ausgeprägten initialen Anstieg der Aktivität.
Dieses charakteristische Verhalten ließ sich auch in der mit Phytohämagglutinin stimulierten Lymphocytenkultur gesunder Spender reproduzieren, wenn den Kulturen im Maximum der DNS-Synthese eines der Anthracyclin-Antibiotica zugesetzt wurde. Die DNS- und RNS-Synthese war zum Zeitpunkt des Aktivitätsanstieges der genannten Enzyme schon deutlich gehemmt. Durch Hemmversuche mit Inhibitoren der Proteinsynthese konnte wahrscheinlich gemacht werden, daß der Aktivitätsanstieg auf einer Neusynthese von Enzymprotein beruht.
Die Reaktion der DNS-Polymerase wird durch Zugabe von Dauno-Rubidomycin oder Adriamycin zum Inkubationsansatz gehemmt. Diese Hemmung war durch Zugabe weiterer „primer“-DNS zum Teil reversibel.
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Mit Unterstützung der Deutschen Forschungsgemeinschaft. Sonderforschungsbereich 71 „Klinische und experimentelle Therapieforschung“, Tübingen.
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Wilms, K., Wilmanns, W. Wirkung von Dauno-Rubidomycin und Adriamycin auf Enzyme der DNS-Synthese in Leukocyten in vivo und in der Kultur. Klin Wochenschr 50, 866–870 (1972). https://doi.org/10.1007/BF01488943
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DOI: https://doi.org/10.1007/BF01488943
Key words
- Anthracycline antibiotics
- Acute leukemia
- DNA polymerase
- Thymidine kinase
- PHA-stimulated lymphocyte cultures