Phosphate and the regulation of DNA replication in normal and virus-transformed 3T3 cells

Biochem J. 1983 Sep 15;214(3):695-702. doi: 10.1042/bj2140695.


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.

MeSH terms

  • Animals
  • Blood
  • Cell Division
  • Cell Transformation, Viral*
  • Cells, Cultured
  • DNA / biosynthesis
  • DNA Replication*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Kinetics
  • Mice
  • Phosphates / pharmacology
  • Phosphates / physiology*
  • Simian virus 40


  • Phosphates
  • DNA