Paper
Inhibition of ribonucleotide reductase, DNA synthesis, and L1210 leukemia by guanazole.
Published Sep 1, 1970 · R. W. Brockman, S. Shaddix, Laster Wr
Cancer research
85
Citations
1
Influential Citations
Abstract
Summary Guanazole (3,5-diamino-1,2,4-triazole; NSC 1895) was found to inhibit the incorporation of adenine, hypoxanthine, and uridine into DNA to a much greater extent than into RNA in L1210 leukemia cells in vivo . Thymidine incorporation into DNA was inhibited with concomitant accumulation of dTTP in L1210 cells. Leucine incorporation into protein was not inhibited. The incorporation of formate- 14 C into purine nucleotides was partially inhibited by guanazole and was accompanied by decreased labeling of nucleic acids; the effect on DNA synthesis was more pronounced than that on RNA. Similar results were obtained in human epidermoid carcinoma cells in culture. Guanazole inhibited the reduction of ribonucleotides to deoxyribonucleotides catalyzed by enzyme preparations from human epidermoid carcinoma cells. The effects of guanazole on DNA synthesis and on ribonucleotide reductase were similar to those of hydroxyurea. The experimental evaluation of guanazole against L1210 leukemia showed that dosage scheduling and route of implantation of L1210 cells were determining factors in the efficacy of the drug. When guanazole was given i.p. every 3 hr for 8 doses for a least 3 courses of treatment (Days 1, 5, and 9) after i.p. implantation of 10 5 L1210 cells, significant numbers of mice survived. In this respect also, the compound was similar to hydroxyurea.
In Vitro Study
Highly CitedGuanazole effectively inhibits DNA synthesis and ribonucleotide reductase in L1210 leukemia cells, with similar effects to hydroxyurea, and shows potential as a treatment for human epidermoid carcinoma.
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