BIOLOGICAL EFFECTS OF INHIBITION OF GUANINE NUCLEOTIDE SYNTHESIS BY MYCOPHENOLIC-ACID IN CULTURED NEUROBLASTOMA-CELLS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (9) , 3314-3320
Abstract
Mycophenolic acid, an inhibitor of inosinate dehydrogenase, had cytostatic and cytotoxic effects on cultured [mouse] neuroblastoma cells. Proliferation was inhibited by 50% when cells were incubated with 0.07 .mu.M mycophenolic acid, and cell viability was reduced by 83% when cells were treated with 10 .mu.M mycophenolic acid for 24 h. Treatment of monolayer cultures with mycophenolic acid reduced intracellular concentrations of GTP by 70% within 3 h, whereas CTP and UTP concentrations were significantly elevated, and ATP concentrations were increased only slightly. Reduction of cellular guanine nucleotides had differential effects on rates of macromolecular synthesis: incorporation of radioactive thymidine into acid insoluble material was inhibited by mycophenolic acid to a greater extent than that of adenosine and leucine. Although proliferation of neuroblastoma cells was inhibited, differentiation, as judged by formation of neuron-like processes in serum free medium, was unaffected by decreased intracellular concentrations of GTP.