Mammalian mutants genetically altered in CTP synthetase activity.

B. Aronow, B. Ullman

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

From wildtype mouse lymphoma cells, a clone (FURT-1A), was isolated by virtue of its resistance to 1 microM 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.

Original languageEnglish (US)
Pages (from-to)263-269
Number of pages7
JournalAdvances in experimental medicine and biology
Volume195 Pt B
DOIs
StatePublished - 1986

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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