Resistance to 5-fluorouracil associated with increased cytidine triphosphate levels in V79 Chinese hamster cells. 1984

E R Kaufman

Clones stably resistant to the toxic effects of 5-fluorouracil have been isolated from V79.5 Chinese hamster fibroblast cells by a single-step selection procedure. The 5-fluorouracil-resistant lines were found to (a) have an auxotrophic requirement when grown in dialyzed fetal calf serum that was satisfied by the addition of either thymidine, deoxyuridine, or deoxycytidine to the medium, (b) be cross-resistant to the toxic effects of 1-beta-D-arabinofuranosylcytosine and to high concentrations of thymidine, (c) have increased intracellular levels of cytidine 5'-triphosphate (CTP) and deoxycytidine 5'-triphosphate and decreased levels of uridine 5'-triphosphate, (d) also be resistant to 5-fluorouridine but not to 5-fluorodeoxyuridine, and (e) incorporate less 5-fluorouracil into RNA than do the wild-type cells. The primary lesion in these mutant appears to be an altered CTP synthetase activity which is no longer sensitive to negative regulation by CTP. The resulting increased CTP levels appear to be responsible for the various phenotypic characteristics of these mutants, including the resistance to 5-fluorouracil.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008025 Ligases A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6. Ligase,Synthetases,Synthetase
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D003570 Cytidine Triphosphate Cytidine 5'-(tetrahydrogen triphosphate). A cytosine nucleotide containing three phosphate groups esterified to the sugar moiety. CTP,CRPPP,Magnesium CTP,Mg CTP,Triphosphate, Cytidine
D003597 Cytosine Nucleotides A group of pyrimidine NUCLEOTIDES which contain CYTOSINE. Cytidine Phosphates,Nucleotides, Cytosine,Phosphates, Cytidine
D003854 Deoxyribonucleotides A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group. Deoxyribonucleotide
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005472 Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid. 5-FU,5-FU Lederle,5-FU Medac,5-Fluorouracil,5-Fluorouracil-Biosyn,5-HU Hexal,5FU,Adrucil,Carac,Efudex,Efudix,Fluoro-Uracile ICN,Fluoroplex,Fluorouracil Mononitrate,Fluorouracil Monopotassium Salt,Fluorouracil Monosodium Salt,Fluorouracil Potassium Salt,Fluorouracil-GRY,Fluorouracile Dakota,Fluorouracilo Ferrer Far,Fluoruracil,Fluracedyl,Flurodex,Haemato-FU,Neofluor,Onkofluor,Ribofluor,5 FU Lederle,5 FU Medac,5 Fluorouracil,5 Fluorouracil Biosyn,5 HU Hexal,Dakota, Fluorouracile,Fluoro Uracile ICN,Fluorouracil GRY,Haemato FU
Copied contents to your clipboard!