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新規抗腫瘍性ヌクレオシド, 1-(3-C-ethynyl-β-D-ribopentofuranosyl)-cytosine (ECyd, TAS-106)の癌細胞内代謝と作用機序に関する検討：東敦¹, Peng HUANG¹, Varsha GANDHI¹, William PLUNKETT¹, 松田彰², 佐々木琢磨^3,（¹テキサス大・M. D. Anderson C. C.、²北大・薬、^3,金沢大・がん研）

Intracellular metabolism and actions of a novel antitumor nucleoside, 1-(3-C-ethynyl-?-D-ribopentofuranosyl)-cytosine (ECyd, TAS-106): Atsushi AZUMA¹, Peng HUANG¹, Varsha GANDHI¹, William PLUNKETT¹, Akira MATSUDA², Takuma SASAKI^3, (¹Univ. of Texas, M. D. Anderson Cancer Center, ²Faculty of Pharm. Sci., Hokkaido Univ., ^3,Cancer Res. Inst., Kanazawa Univ.)

The newly synthesized antitumor nucleoside, ECyd showed potent antitumor activity against human tumor cells in vitro and in vivo. We used human leukemia cell, ML-1 cells and K562 cells to investigate mechanisms of antitumor activity of ECyd. ECyd showed growth inhibitory activity against ML-1 cells and K562 (IC₅₀ values were 8 nM and 20 nM for 72 h incubation). Investigating of intracellular metabolites of ECyd by using [³H]ECyd, mono-, di-, and mainly triphosphate of ECyd were readily detected by HPLC analysis. Intracellular accumulation of the analog triphosphate (ECTP) reached a plateau at 8 h in K562 cells. ECyd nucleotides were eliminated from cells very slowly; more than 80% of ECTP remained in the cells 6 h after ECyd was washed out of the culture medium. ECyd showed inhibition of adenosine incorporation into cellular RNA (IC₅₀ values were 0.7 ?M for 4 h incubation). These results suggest that the mechanism of cytotoxicity of ECyd may involve inhibition of RNA synthesis.