Mammalian Mutants Genetically Altered in CTP Synthetase Activity

  • Bruce Aronow
  • Buddy Ullman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 131)

Summary

From wildtype mouse lymphoma cells, a clone (FURT-1A), was isolated by virtue of its resistance to 1μM 5-fluorouracil. In comparative growth rate experiments, FURT-1A cells were also less sensitive than parental cells to the growth inhibitory effects of thymidine, deoxyguanosine, 5-fluorouridine, and arabinosylcytosine. The altered growth sensitivity of FURT-1A cells to cytotoxic nucleosides was directly related to their decreased ability to accumulate the corresponding triphosphate from exogenous nucleoside. FURT-1A cells contained elevated cytidylate nucleotide pools which prevented normal growth sensitivity and interfered with the salvage of nucleosides. Metabolic flux experiments with [3H]-uridine in situ indicated that FURT-1A cells had a 2-fold enhanced rate of conversion of UTP to CTP. Kinetic analyses indicated that the CTP synthetase activity in extracts of FURT-1A cells was refractory to inhibition by CTP. The genetic loss of normal allosteric inhibition of the CTP synthetase activity in FURT-1A cells could account for the unusual phenotypic properties of these cells.

Keywords

Pyrimidine Thymidine Purine Nucleoside Triphosphate 

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Bruce Aronow
    • 1
  • Buddy Ullman
    • 1
  1. 1.Department of BiochemistryUniversity of Kentucky Medical CenterLexingtonUSA

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