Altered thymidine kinase or thymidylate synthetase activities in 5-fluoro deoxyuridine resistant variants of mouse neuroblastoma

F. Baskin, R. Davis, R. N. Rosenberg

Research output: Contribution to journalArticle

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Abstract

The authors have previously described a 5-fluorodeoxyuridine (FUdR) resistant neuroblastoma variant, possessing normal levels of ATP:thymidine-5-phosphotransferase (EC 2.7.1.21) [trivial name: thymidine kinase (TK)] but an 8-fold elevation in methylenetetrahydrofolate:dUrd-5'P C-methyltransferase (EC 2.1.1b) [trivial name: thymidylate synthetase (TS)] relative to the drug-sensitive parental clone. This variant possesses elevated levels of the parental TS species, 30% of which is uninhibitable by in vivo pulses of FUdR, suggesting the subcellular compartmentalization of this enzyme. The authors contrast this variant with a second FUdR resistant clone isolated from an ethyl-methane-sulfonate mutagenized population of the parental clone. This variant displays a 96% reduction in TK specific activity, despite normal FUdR and thymidine uptake rates, demonstrating the independence of thymidine phosphorylation and uptake. Grown without drug, its resistance declines (half-life of 15 cell divisions) with its TK specific activity rising to a plateau of 16% of the parental level after 56 cell divisions. Thymidine (1.0 μM) protects the TK+ but not the TK- variants from FUdR induced growth inhibition but is without effect on TS specific activity. Unlike Tetrahymena neuroblastoma TS activities appear not to be regulated by adenosine or guanosine cyclic nucleotide levels.

Original languageEnglish (US)
Pages (from-to)1031-1037
Number of pages7
JournalJournal of Neurochemistry
Volume29
Issue number6
StatePublished - 1977

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Thymidylate Synthase
Deoxyuridine
Floxuridine
Thymidine Kinase
Neuroblastoma
Thymidine
Clone Cells
Cell Division
Names
Cells
Tetrahymena
Phosphorylation
Guanosine
Cyclic Nucleotides
Methane
Methyltransferases
Drug Resistance
Pharmaceutical Preparations
Adenosine
Half-Life

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Altered thymidine kinase or thymidylate synthetase activities in 5-fluoro deoxyuridine resistant variants of mouse neuroblastoma. / Baskin, F.; Davis, R.; Rosenberg, R. N.

In: Journal of Neurochemistry, Vol. 29, No. 6, 1977, p. 1031-1037.

Research output: Contribution to journalArticle

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