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Research Article Free access | 10.1172/JCI111666

Effect of uracil arabinoside on metabolism and cytotoxicity of cytosine arabinoside in L5178Y murine leukemia.

J L Yang, E H Cheng, R L Capizzi, Y C Cheng, and T Kute

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Published January 1, 1985 - More info

Published in Volume 75, Issue 1 on January 1, 1985
J Clin Invest. 1985;75(1):141–146. https://doi.org/10.1172/JCI111666.
© 1985 The American Society for Clinical Investigation
Published January 1, 1985 - Version history
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Abstract

Pretreatment of L5178Y murine leukemia cells with uracil arabinoside (ara-U) enhances the cytotoxicity of cytosine arabinoside (ara-C). This effect is mediated by the cytostatic effect of ara-U, which causes a delay of cell progression through S-phase. Consequently, the specific activity of enzymes that peak during S-phase increases, and deoxycytidine kinase increases 3.6-fold over untreated controls. This allows enhanced anabolism of ara-C to nucleotides, as well as increased incorporation into DNA with ultimate synergistic cytotoxicity. It is postulated that the systemic metabolism of high-dose ara-C to sustained high levels of ara-U in patients with acute leukemia may enhance the activity of subsequent doses of ara-C, and thus contribute to a means for pharmacologic self-potentiation, contributing to the unique therapeutic activity of high-dose ara-C.

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