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Inhibition of RNA polymerase as a possible anti-leukaemic action of cytosine arabinoside

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Abstract

CYTOSINE arabinoside (ara-C, 1-β-D-arabinosylcytosine) has marked anti-tumour and anti-viral activities1,2, and is currently one of the most successful drugs used to induce remissions in acute granulocytic leukaemia3. Its cytotoxic activity is ascribed to its effect of inhibiting DNA polymerase after being phos-phorylated intracellularly to its triphosphate derivative (ara-CTP)4. Studies with murine leukaemic cells5 and mouse L cell line have indicated6, however, that acute cell death induced by ara-C does not completely correlate with the inhibition of DNA synthesis: (1) DNA polymerase activity was rapidly restored after ara-C was removed, whereas cells were still non-viable; (2) the amount of ara-C incorporation into DNA did not correlate with the degree of cell lethality. We have shown previously7 that ara-CTP could inhibit RNA polymerase II activity from chicken leukaemic cells when the enzyme was purified. This report describes results of our kinetic studies characterising the nature of this inhibition.

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Authors and Affiliations

  1. Department of Medicine and Department of Physiology and Pharmacology, Duke University Medical Center, Durham, North Carolina, 27710

    RONALD Y. CHUANG & LINDA F. CHUANG

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  1. RONALD Y. CHUANG
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  2. LINDA F. CHUANG
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CHUANG, R., CHUANG, L. Inhibition of RNA polymerase as a possible anti-leukaemic action of cytosine arabinoside. Nature 260, 549–550 (1976). https://doi.org/10.1038/260549a0

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