Purine synthetic capacities of de novo and salvage pathways in rat hepatoma 3924A cells.

Abstract

The relative contribution of denovo and salvage pathways for nucleotide synthesis in neoplastic tissues is one of the important factors in cancer chemotherapy. Although almost all antipurine and antipyrimidine I metabolites aim at denovo pathways as target sites, our previous investigations have suggested the possible role of salvage pathways in circumventing the action of the inhibitors of denovo synthesis (1-4). For purine nucleotide synthesis the denovo and the salvage synthetic enzymes, amidophosphoribosyltransferease (EC 2.4.2.14), adenine phosphoribosyl-transferase (APRT; EC 2.4.2.7) and hypoxanthine-guanine phosphoribosyl-transferase (HGPRT; EC 2.4.2.8), share the common substrate, PRPP, and are inhibited by the end products, purine nucleotides (5-7). These facts suggest that the inhibition of purine denovo synthesis might be compensated by purine salvage synthesis in chemotherapy. The purpose of this study was to compare the potential synthetic capactities of purine denovo and salvage pathways in neoplastic cells as reflected in enzyme speific activities and incorporation rates of [14C]formate, [14C]adenine, [14C] hypoxanthine and [l4C]guanine into purine nucleotides and nucleic acids.