EFFECT OF 5-FLUOROURACIL ON RNA-METABOLISM IN NOVIKOFF HEPATOMA-CELLS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (12) , 4905-4913
Abstract
The resistance of a Novikoff [rat] hepatoma cell line (N1-S1/FdUrd) to 5-fluorouracil (FUra) was reversed by the inclusion of inosine in the culture medium. As the concentration of inosine in the medium was increased, there was a marked increase in the uptake of [14C]FUra and conversion to nucleotides with a corresponding increase in the incorporation into RNA. While FUra alone had no effect on this resistant cell line, the combinatin of FUra plus inosine altered the levels of ribose 1-phosphate but not 5-phosphoribosyl 1-pyrophosphate, altered the maturation of precursor ribosomal RNA by blocking the formation of 18S RNA, altered the methylation of the ribosomal RNA and caused inhibition of the growth of these cells. No evidence was obtained that fluorodeoxyuridine 5''-monophosphate was formed in the N1-S1/FdUrd cells as a result of treatment with FUra plus inosine. The metabolism of [3H]deoxycytidine in the presence of FUra plus inosine in the intact N1-S1/FdUrd cells did not indicate significant inhibition of thymidylate synthetase as evidenced by the levels of deoxyuridine 5''-monophosphate or conversion to TMP.