Cory J G, Mansell M M, Whitford T W
Cancer Res. 1976 Sep;36(9 pt.1):3166-70.
Periodate-oxidized inosine (Inox; NSC 118994) and periodate-oxidized 5'-inosinic acid (PI-IMP) were prepared and studied for their effects on ribonucleotide reductase activity in partially purified extracts from Ehrlich tumor cells and on nucleic acid synthesis in intact tumor cells in culture. Ribonucleotide reductase activity in cell-free extracts from Ehrlich tumor cells was inhibited by Inox and PI-IMP. PI-IMP was more inhibitory to the reductase activity than was Inox. Furthermore, the inhibition of ribonucleotide reductase activity by Inox and PI-IMP was greater for cytidine-5'-diphosphate reductase activity than for adenosine-5'-diphosphate reductase activity. The ribonucleotide reductase activity in cell-free extracts prepared from Ehrlich tumor cells treated with Inox or PI-IMP in culture was decreased compared with the activity in the extracts from untreated cells. Incorporation of labeled cytidine into the RNA and DNA of Ehrlich tumor cells in culture was inhibited by both Inox and PI-IMP. The conversion of cytidine to deoxycytidine nucleotides in the acid-soluble pool was likewise inhibited. These data indicate that Inox and PI-IMP inhibit the ribonucleotide reductase step as one of the sites of action of these compounds. However, the inhibition of RNA synthesis indicates that there must be additional sites of action of these nucleoside analogs.
制备了高碘酸盐氧化的肌苷（Inox；NSC 118994）和高碘酸盐氧化的5'-肌苷酸（PI-IMP），并研究了它们对艾氏腹水癌细胞部分纯化提取物中核糖核苷酸还原酶活性以及对培养的完整肿瘤细胞中核酸合成的影响。Inox和PI-IMP抑制了艾氏腹水癌细胞无细胞提取物中的核糖核苷酸还原酶活性。PI-IMP对还原酶活性的抑制作用比Inox更强。此外，Inox和PI-IMP对胞苷-5'-二磷酸还原酶活性的核糖核苷酸还原酶活性抑制作用比对腺苷-5'-二磷酸还原酶活性的抑制作用更大。与未处理细胞提取物中的活性相比，培养中用Inox或PI-IMP处理的艾氏腹水癌细胞制备的无细胞提取物中的核糖核苷酸还原酶活性降低。Inox和PI-IMP均抑制培养的艾氏腹水癌细胞中标记胞苷掺入RNA和DNA。酸溶性池中的胞苷向脱氧胞苷核苷酸的转化同样受到抑制。这些数据表明，Inox和PI-IMP抑制核糖核苷酸还原酶步骤是这些化合物的作用位点之一。然而，RNA合成的抑制表明这些核苷类似物必定还有其他作用位点。
