Clustered base substitutions in CTP synthetase conferring drug resistance in Chinese hamster ovary cells.
Dominantly acting mutations that eliminate the allosteric regulation of CTP synthetase confer a form of multidrug resistance and a mutator phenotype to cultured Chinese hamster ovary cells. Mutations responsible for this phenotype have been identified in 23 independent strains selected for resistance to arabinosyl cytosine and 5-fluorouracil. All these mutations were due to base substitutions at seven sites within a highly conserved region of the ctps gene. This clustering should make it feasible to assess the role of such mutations in the development of drug resistance encountered in the treatment of malignant disease.
Whelan
J
J
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, UK.
Phear
G
G
Yamauchi
M
M
Meuth
M
M
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D019731:Carbon-Nitrogen Ligases; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology*; D017931:DNA Primers; D018076:DNA, Complementary / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008025:Ligases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism
D017931:DNA Primers; D018076:DNA, Complementary; D011994:Recombinant Proteins; D003561:Cytarabine; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase; D005472:Fluorouracil