The linkage of glucose to tiazofurin decreases in vitro uptake into rat glioma C6 cells.
The aim of this study was to analyse the uptake of the synthetic nucleoside tiazofurin and glucoso-linker-tiazofurin conjugate (GLTC) into rat C6 glioma cells in vitro. Results indicated that C6 cells accumulated [3H] tiazofurin slowly with time and that accumulation was reduced by the presence of unlabelled GLTC in the medium which implies that GLTC competes with tiazofurin for transport sites. Uptake of [14C] 2 deoxy-glucose into these cells was very rapid and was not affected by the presence of unlabelled GLTC. To prove the true rate of uptake, the HPLC analysis of cellular extract was performed. After the 360 min of incubation in medium that contained 0.15 mM of tiazofurin, the sum of the concentration of tiazofurin and it's metabolite thiazole-adenine dinucleotide (TAD) in the cells was a total of approximately 4.8% of the amount added to each flask. After the same period of incubation in medium which contained 0.15 mM of GLTC, the sum of concentrations of conjugate, free tiazofurin and TAD represented less than 1/3 of the total concentration measured after the incubation with free tiazofurin and was further reduced in the presence of dipyridamole. Therefore, it can be concluded that GLTC shows some affinity for the nucleoside transporter, but the actual rate of uptake is low.
Dacevic
Mirjana P
MP
ICN Galenika, R and D, Belgrade, Federal Republic of Yugoslavia.
Tasic
Jelena S
JS
Pejanovic
Vjera M
VM
Segal
Malcolm B
MB
Ugliesic-Kilibarda
Dragana D
DD
Isakovic
Aleksandra J
AJ
Begley
David J
DJ
Rakic
Ljubisa M
LM
Redzic
Zoran B
ZB
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003847:Deoxyglucose / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry*; D007700:Kinetics; D051381:Rats; D012254:Ribavirin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D012254:Ribavirin; D004176:Dipyridamole; D003847:Deoxyglucose; D005947:Glucose; C033706:tiazofurin