Abstract
Most nucleoside analogues require intracellular metabolism, usually to the 5’-triphosphate, to produce cytotoxicity. This reflects one mechanism of action of these drugs: inhibition of DNA synthesis through effects on enzymes whose natural substrates are nucleotides. Strong correlations have been demonstrated between cytotoxity in experimental systems and the cellular pharmacology and pharmacodynamics of nucleotides of nucleoside antimetabolites [1, 2]. Recently, analytical procedures used in experimental studies, principally high-pressure liquid chromatography, have been adapted for investigations of nucleoside analogue metabolites in human leukemia cells during therapy [3].
These studies were supported by grant CA32839 from the National Cancer Institute, Department of Health and Human Services.
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Plunkett, W., Heinemann, V., Estey, E., Keating, M. (1990). Pharmacologically Directed Design of Leukemia Therapy. In: Büchner, T., Schellong, G., Hiddemann, W., Ritter, J. (eds) Acute Leukemias II. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 33. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74643-7_111
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DOI: https://doi.org/10.1007/978-3-642-74643-7_111
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