8-azaguanosine-5'-monophosphate synthesis via nucleoside kinase in cultured Chinese hamster lung fibroblasts.
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.
Tozzi
M G
MG
Dipartimento di Fisiologia e Biochimica, Laboratori di Biochimica, Pisa, Italy.
Camici
M
M
Falcone
V
V
Turriani
M
M
Turchi
G
G
Ipata
P L
PL
D000818:Animals; D001375:Azaguanine; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000031:analogs & derivatives*; D006157:Guanosine Monophosphate / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008168:Lung; D010770:Phosphotransferases / Q000378:metabolism*; D013379:Substrate Specificity
D006150:Guanine Nucleotides; C058834:8-azaguanosine-5'-monophosphate; D006157:Guanosine Monophosphate; D010770:Phosphotransferases; C021892:nucleoside phosphotransferase; D001375:Azaguanine