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  • Title: Inhibition of thymidylate synthase by hydroxyurea in rapidly proliferating P815 mastocytoma cells.
    Author: Boehm TL, Kreis W, Drahovsky D.
    Journal: Biochim Biophys Acta; 1982 Jan 26; 696(1):52-6. PubMed ID: 6805512.
    Abstract:
    The incorporation of [14C]deoxycytidine, [3H]deoxyuridine, and [3H]thymidine, respectively into pyrimidine bases of DNA has been measured in rapidly proliferating P815 mouse mastocytoma cells in the presence of hydroxyurea. The incorporation of [14C]deoxycytidine-derived radioactivity into DNA cytosines is increased when compared to the incorporation into DNA thymines. The [3H]deoxyuridine-derived radioactivity is incorporated solely into DNA thymines and this incorporation is inhibited by hydroxyurea in a dose-dependent manner. This suggests an inhibitory effect of hydroxyurea on the thymidylate synthase which was proved in experiments in which the conversion of deoxyuridine monophosphate into deoxythymidine monophosphate catalysed by a crude enzyme preparation from P815 cells was inhibited in the presence of hydroxyurea. Enzymatic DNA methylation as measured by the conversion of incorporated [14C]deoxycytidine into 5-methylcytosines was not affected by hydroxyurea.
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