Unstable, non-mutational expression of resistance to the thymidine analogue, trifluorothymidine in CHO cells
Journal Article
·
· Mutat. Res.; (United States)
The thymidine analogue, 5-trifluoromethyl-2'-deoxyuridine, or trifluorothymidine (TFT), has been reported to be an effective selecting agent for thymidine kinase-deficient (TK/sup -/) mutants in a mutagenesis assay system employing a tk/sup + -/heterozygote of L5178Y mouse lymphoma cells. Although 5-bromo-2'-deoxyuridine (BUdR) and 5-iodo-2'-deoxyuridine (IUdR have been commonly used to select TK/sup -/ mutants, considerable cell division and slow killing of wild-type (WT) cells occur in the presence of these drugs. TFT, however, rapidly inhibits cell division, and unlike BUdR and IUdR, is not mutagenic in mammalian cells. All three analogues are mutagenic in T4. TFT is readily phosphorylated by thymidine kinase (TK), competitively inhibiting utilization of the normal substrate. The phosphorylated derivative of TFT is a potent, irreversible inhibitor of thymidylate synthetase. Further phosphorylation to the di- or tri-phosphates and incorporation into the DNA of mammalian cells in culture have also been demonstrated.
- Research Organization:
- Univ. of California, Livermore
- OSTI ID:
- 5365608
- Journal Information:
- Mutat. Res.; (United States), Journal Name: Mutat. Res.; (United States) Vol. 60; ISSN MUREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550400 -- Genetics
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AZINES
BIOASSAY
CELL CULTURES
CELL DIVISION
CELL KILLING
DISEASES
DNA
HETEROCYCLIC COMPOUNDS
INHIBITION
LYMPHOMAS
MAMMALS
MICE
MUTAGENESIS
MUTANTS
NEOPLASMS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RIBOSIDES
RODENTS
THYMIDINE
TOXICITY
VERTEBRATES
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AZINES
BIOASSAY
CELL CULTURES
CELL DIVISION
CELL KILLING
DISEASES
DNA
HETEROCYCLIC COMPOUNDS
INHIBITION
LYMPHOMAS
MAMMALS
MICE
MUTAGENESIS
MUTANTS
NEOPLASMS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RIBOSIDES
RODENTS
THYMIDINE
TOXICITY
VERTEBRATES