Phosphate and the regulation of DNA replication in normal and virus-transformed 3T3 cells.
3T3 cells were cultured in media with different phosphate concentrations and the effects on DNA synthesis were examined. Even a modest phosphate depletion markedly inhibited DNA synthesis and cell multiplication in proliferating cultures. Furthermore, the decrease in the proportion of DNA-synthesizing cells observed after phosphate starvation followed the same time-course as the decrease seen after serum starvation. Cells starved to quiescence in a medium with a 100-fold decrease in phosphate concentration remained viable but non-proliferating for up to 3 weeks, i.e. they had entered a state of quiescence comparable with that seen after serum starvation. Addition of phosphate to phosphate-depleted cultures restored DNA synthesis within 24h. Furthermore, the kinetics of [3H]thymidine labelling after phosphate addition were nearly identical with the labelling kinetics following addition of serum to serum-depleted cultures. In contrast, phosphate deprivation had no inhibitory effects on DNA synthesis in simian-virus-40-transformed 3T3 cells. Furthermore, the inhibitory effects on DNA synthesis in such cells caused by a complete removal of serum could not be further enhanced by decreasing the phosphate concentration in the culture medium.
D000818:Animals; D001769:Blood; D002455:Cell Division; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010710:Phosphates / Q000494:pharmacology / Q000502:physiology*; D013539:Simian virus 40
D010710:Phosphates; D004247:DNA