Effects of Nucleosides and a Nucleotide on DNA and RNA Syntheses by the Salvage and De Novo Pathway in Primary Monolayer Cultures of Hepatocytes and Hepatoma Cells

Abstract

Studies were made on the effects of inosine, guanosine 5'-monophosphate (GMP), cytidine, uridine, thymidine, and their mixture (4:4:4:3:1, OG-VI) on DNA and RNA syntheses in primary monolayer cultures of normal hepatocytes and cultures of hepatoma cells, AH130, to use these compounds for total parenteral nutrition. Addition of an appropriate amount of inosine, GMP, uridine, or thymidine to primary cultures of hepatocytes enhanced both DNA and RNA syntheses by the salvage and de novo pathways. Cytidine appeared to have lower optimal concentration for enhancing these pathways. The OG-VI mixture also enhanced the syntheses of DNA and RNA, but the composition of the mixture was not optimal. Additions of inosine, GMP, uridine, and thymidine to cultured hepatoma cells also enhanced their DNA and RNA syntheses, but the cells consumed more of the added nucleic acid compounds than hepatocytes did. Addition of cytidine had no effect on proliferation of the cells. The OG-VI mixture at relatively higher concentration inhibited the syntheses of DNA and RNA by hepatoma cells. Addition of high concentrations of nucleic acid compounds was found to suppress the proliferation of both hepatocytes and hepatoma cells. These results suggest that addition of optimal amounts of nucleic acid compounds such as nucleosides and nucleotides would enhance growth of hepatocytes, particularly during liver regeneration, but that they may also enhance proliferation of tumor cells in the liver.