INHIBITION OF RIBONUCLEOTIDE REDUCTASE-ACTIVITY AND NUCLEIC-ACID SYNTHESIS IN TUMOR-CELLS BY DIALDEHYDE DERIVATIVES OF INOSINE (NSC-118994) AND INOSINIC ACID

  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (9) , 3166-3170
Abstract
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 patially purified extracts from Ehrlich [mouse] tumor cells and 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 Inox. The inhibition of ribonucleotide reductase activity by Inox and PI-IMP was greater for CDP reductase activity than ADP 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 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 1 of the sites of action of these compounds. The inhibition of RNA synthesis indicates that there must be additional sites of action of these nucleoside analogs.