Abstract
Ribonucleotide reductase from Ehrlich tumor cells is inhibited by hydroxyurea (HU), guanazole (GZ), pyrazolo-imidazole (IMPY), 1-formylisoquinoline thiosemicarbazone (IQ), 4-methyl-5-aminoisoquinoline thiosemicarbazone (MAIQ). and the dialdehydes of inosine and 5′-deoxyinosine. In the presence of EDTA, desferal, or 8-hydroxyquinoline (8-HQ) at a concentration that did not affect reductase activity, HU, GZ and IMPY more effectively inhibited the reductase. EDTA, desferal, or 8-HQ in combination with the nucleoside dialdehyde derivatives did not affect the inhibition caused by these compounds. The combination of these iron-chelating agents with MAIQ and IQ, however, reversed the inhibition caused by MAIQ and IQ. These data indicate that the inhibitors of the nonheme iron-containing component of mammalian ribonucleotide reductase can be subclassified, based on their response to the presence of iron-chelating agents.
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