B. Booth, E. C. Moore, A. Sartorelli
Mar 1, 1971
Citations
0
Influential Citations
51
Citations
Journal
Cancer research
Abstract
Summary 2-Formylpyridine thiosemicarbazone (PT), 3-hydroxy-2-formylpyridine thiosemicarbazone (3-HP), and 5-hydroxy-2-formylpyridine thiosemicarbazone (5-HP) are potent inhibitors of the growth of Sarcoma 180 ascites cells. PT is quite toxic to the tumor-bearing host and does not markedly extend the life-span of mice bearing Sarcoma 180; however, the therapeutic potential of 3-HP and 5-HP is considerably greater, and treatment with these agents results in a pronounced lengthening of the survival time of the tumor-bearing animals. Evidence that the heteroaromatic ring nitrogen atom is required for biological activity was provided by the finding that salicylaldehyde thiosemicarbazone is inactive. PT, 3-HP, and 5-HP cause pronounced inhibition of the incorporation of thymidine into DNA; these agents do not prevent the conversion of thymidine to the triphosphate level but inhibit the subsequent incorporation of dTTP into DNA. The inhibitory effects of 3-HP and 5-HP on the formation of DNA do not appear to result from extensive catabolism of DNA in drug-treated cells. The utilization of uridine for the formation of RNA is depressed by PT, 3-HP, and 5-HP, and slight but significant inhibition of leucine incorporation into residual protein is also produced.