GUANOSINE POTENTIATES THE ANTIPROLIFERATIVE EFFECT OF CYTOSINE-BETA-D-ARABINOFURANOSIDE IN MELANOMA CELL-LINES

Guanosine is shown to potentiate markedly the antiproliferative effect of cytosine-beta-D-arabinoside (ara-C) on B16 F10 mouse and SKMEL-28 human melanoma cell lines. Several metabolic consequences of the syner gistic interaction between ara-C and guanosine on cell growth were det ermined in B16 F10 mouse melanoma cells. Treatment of the cells with g uanosine for 24hr resulted in an increase in the percentage of cells i n the S phase of the cell cycle, a threefold increase in intracellular GTP concentration, and an increase in the incorporation of ara-C into acid-insoluble material and phosphorylated metabolites. These finding s suggest that guanosine potentiates the growth-inhibitory effect of a ra-C in B16 F10 melanoma cells by increasing the intracellular concent ration of its active metabolites.