Mammalian mutants genetically altered in CTP synthetase activity.

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.

journal_name

Adv Exp Med Biol

authors

Aronow B,Ullman B

doi

10.1007/978-1-4684-1248-2_42

subject

Has Abstract

pub_date

1986-01-01 00:00:00

pages

263-9

eissn

0065-2598

issn

2214-8019

journal_volume

195 Pt B

pub_type

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