Activity and Metabolism of 2-β-d-Ribofuranosylthiazole-4-carboxamide in Human Lymphoid Tumor Cells in Culture
作者： Robert I. Glazer , Martin F. Earle
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摘要: The antitumor activity of the C-nucleoside, 2-beta-D-ribofuranosylthiazole-4-carboxamide (TR), was investigated in four human lymphoid tumor cell lines culture. Exposure CCRF-CEM (T-cell leukemia), HUT-78 (cutaneous T-cell lymphoma), NALM-1 (B-cell and MOLT-4 leukemia) for 72 hr to TR resulted 50% inhibitory concentration 30, 27, 7, 6 microM, respectively. Maximum inhibition DNA RNA synthesis occurred after drug treatment. among varied from 5 8 microM 4 synthesis. Nucleotide analyses cells exposure 10 100 revealed increased inosine 5'-monophosphate concentrations which were 18- 20-fold greater than control levels a parallel reduction 82 100% guanosine concentrations. Growth by almost fully reversible addition 50 medium 18 hr. Analyses high-pressure liquid chromatography two metabolites all lines, namely, thiazolecarboxamide riboside adenine dinucleotide, latter is potent inhibitor inosine-5-'-monophosphate dehydrogenase. These results suggest that effects may relate guanine nucleotide depletion.
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