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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Drewinko, B., Ho, D. H. W., and Barranco, S. C., Cancer Res., 32, 2737–2742 (1972).
Nutter, R. L., and Rapp, F., Cancer Res., 33, 166–170 (1973).
Goodell, B., Leventhal, B., and Henderson, E., Clin. Pharmac. Ther., 12, 599–606 (1971).
Furth, J. J., and Cohen, S. S., Cancer Res., 28, 2061–2067 (1968).
Chu, M. Y., and Fischer, G. A., Biochem. Pharmac., 17, 753–767 (1968); 741–751 (1968).
Graham, F. L., and Whitmore, G. F., Cancer Res., 30, 2636–2644 (1970).
Chuang, R. Y., Chuang, L. F., and Laszlo, J., Cancer Res., 35, 687–693 (1975).
Müller, W. E. G., Yamazaki, Z-I., Sögtrop, H. H., and Zahn, R. K., Eur. J. Cancer, 8, 421–428 (1972).
Tuominen, F. W., and Kenney, F. T., Biochem. biophys. Res. Commun, 48, 1469–1475 (1972).
Stenstrom, M. L., Edelstein, M., and Grisham, J. W., Expl Cell Res., 89, 439–442 (1974).
Chou, T-C., Hutchinson, D. J., Schmid, F. A., and Philips, F. S., Cancer Res., 35, 225–236 (1975).
York, J. L., and LePage, G. A., Can. J. Biochem., 44, 19–26 (1966).
Shipman, C., Jr, Smith, S. H., and Drach, J. C., Proc. natn. Acad. Sci. U.S.A., 69, 1753–1757 (1972).
Müller, W. E. G., et al., Cancer Res., 35, 2160–2168 (1975).
Furth, J. J., and Cohen, S. S., Cancer Res., 27, 1528–1533 (1967).
Ho, D. H. W., Cancer Res., 33, 2816–2820 (1973).
Widnell, C. C., and Tata, J. R., Biochim. biophys. Acta, 123, 478–492 (1966).
Chu, M. Y., Biochem. Pharmac., 20, 2057–2063 (1971).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/260549a0
This article is cited by
-
Induction of fragility at the human RNU2 locus by cytosine arabinoside is dependent upon a transcriptionally competent U2 small nuclear RNA gene and the expression of p53
Somatic Cell and Molecular Genetics (1997)
-
Arabinose nucleoside triphosphates are no inhibitors for DNA-dependent RNA polymerases
Experientia (1976)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.