EFFECT OF HYDROXYUREAON RIBONUCLEOTIDB REDUCTASE Howard

Hydroxyurea, an antineoplastic agent , inhibits DNA synthesis and cell proliferation without affecting RNA and protein synthesis (Gale, 1964; Young and Hodas, 19641 Yarbro et al -0' 1965 Rosenbranz and Levy, 1965). A variety of evidence, primarily in vivo, has accumulated which suggests that the mode of action of hydroxyurea is the inhibition of the conversion of ribonucleotides to deoxyribonucleotides, a critical step in DNA synthesis (Frenkel et al., 1964; Adams and Lindsay, 1967; Frenkel and Arthur, 1967; Elfora, 1967). It was decided to investigate the direct effect of hydroxyurea on a completely in vitro ribonucleotide reduction system isolated from three of the -most thoroughly studied deoxynucleotide synthesizing systems, Escherichia g, Lactobacillus leichmannii, and Novikoff hepatoma rat tumor. In addition, the effect of hydroxyurea on several animal ribonucleotide reduction systems was studied. The data from this study support the proposition that hydroxyurea inhibits DNA synthesis by interfering with ribonucleotide reduction in various animal systems and in 5 &, but has no effect on the reduction system of k. leichmannii.