Uridine transport and phosphorylation in mouse cells in culture: effect of growth-promoting factors, cell cycle transit and oncogenic transformation.
The rapid increase in uridine uptake produced by the addition of serum to quiescent cultures of fibroblasts is primarily caused by an enhanced rate of nucleoside phosphorylation. While quiescent and serum-stimulated cells display identical initial rates of transport, they show a considerable change in the composition of the acid-soluble pools labelled with [3H] uridine for five seconds. The radioactivity recovered in the phosphorylated pools increases 2-, 3-, 4- and 6-fold after addition of serum to cultures of Swiss 3T3 cells, tertiary mouse embryo fibroblasts, Swiss 3T6 and Balb 3T3, cells respectively. Furthermore, insulin, a growth factor isolated from medium conditioned by SV40 BHK cells (FDGF) and epidermal growth factor (EGF) also stimulate uridine phosphorylation within minutes. The initial rate of uridine uptake is 2- to 3-fold faster in rapidly growing normal and Simian virus 40 or polyoma virus transformed 3T3 cells as compared to untransformed 3T3 cells in the quiescent state. When quiescent cultures of 3T3 or mouse embryo cells are stimulated to leave G1 and enter into DNA synthesis, transport increases several hours after addition of serum and apparently coincides with the S phase of the cell cycle. The results demonstrate that an increase in uridine phosphorylation is a rapid metabolic response elicited by growth-promoting agents in a variety of cell types and that uridine transport and phosphorylation are independently regulated.
D000818:Animals; D001692:Biological Transport; D001769:Blood; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008938:Mitosis; D010766:Phosphorylation; D014529:Uridine / Q000378:metabolism*; D014541:Uridine Kinase / Q000378:metabolism
D003470:Culture Media; D006133:Growth Substances; D007328:Insulin; D003609:Dactinomycin; D003513:Cycloheximide; D014541:Uridine Kinase; D014529:Uridine