Isolation and characterization of cultured mouse T-lymphoma cells deficient in uridine-cytidine kinase.
Two clones were isolated from mutagenized mouse T-lymphoma cells (S49) which are over 90% deficient in uridine-cytidine kinase. The first clone, AU-200-1, was isolated in two steps by virtue of its resistance to 6-azauridine; whereas the second clone, FU3-70G, was isolated in three steps after exposure to three increasing concentrations of 5-fluorouracil. Extracts of both the AU-200-1 and the FU3-70G cell lines lacked over 90% of the capacity of those from wild type cells to phosphorylate either uridine or cytidine. Furthermore, the uptake of radioactive uridine and cytidine from the medium by intact AU-200-1 and FU3-70G cells was less than 5% of that found for intact wild type cells. By growth rate experiments, these uridine-cytidine kinase-deficient cell lines have altered sensitivities to the toxic pyrimidine analogs, 6-azauridine, 5-fluorouracil, and 5-fluorouridine and thus have been useful in elucidating the biochemical determinants involved in the metabolism of these compounds.
D000818:Animals; D002460:Cell Line; D003562:Cytidine; D014644:Genetic Variation; D008223:Lymphoma / Q000201:enzymology*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D009374:Neoplasms, Experimental / Q000201:enzymology; D010770:Phosphotransferases / Q000172:deficiency*; D014541:Uridine Kinase / Q000172:deficiency*
D008769:Methylnitronitrosoguanidine; D003562:Cytidine; D010770:Phosphotransferases; D014541:Uridine Kinase