8-azaguanosine-5'-monophosphate synthesis via nucleoside kinase in cultured Chinese hamster lung fibroblasts

Abstract

Cultured chinese hamster lung fibroblasts, and a variant clone selected for resistance to 8-azaguanine, that lacks hypoxanthine-guanine phosphoribosyl transferase (EC 2.4.2.8), have been tested for the ability to convert 8-azaguanine into 8-azaguanosine-5'-monophosphate via purine nucleoside phosphorylase and nucleoside kinase. Purine nucleoside phosphorylase of both cell types is able to synthesize 8-azaguanosine from 8-azaguanine with the same efficiency. Wild type cells possess a nucleoside kinase activity acting on 8-azaguanosine, but this activity is considerably lower in the cells displaying resistance to the base analog. Our lines of evidence demonstrate that purine nucleoside phosphorylase and nucleoside kinase constitute a possible way of synthesis of the cytotoxic mononucleotide of 8-azaguanine, and, in fact, cells selected for resistance to the base analog show an impairement in the nucleoside kinase activity.