Gene amplification and drug resistance in cultured murine cells.

Resistance of mouse cells to the folate analog, methotrexate, results from selection of increasingly resistant cells on progressive increases of methotrexate in the culture medium. High-level resistance is associated with high rates of synthesis of dihydrofolate reductase and correspondingly high numbers of reductase genes. In some variants high resistance and gene copy number are stable in the absence of selection pressure, whereas in others they are unstable. Analogies are made to antibiotic and insecticide resistance wherein selection of organisms with increased capacity to counteract the drug effect results in emergence of resistance. Gene amplification may underlie many such resistance phenomena.

[1]  H. G. Boman,et al.  Resistance of Escherichia coli to Penicillins I. Genetic Study of Some Ampicillin-Resistant Mutants , 1965, Journal of bacteriology.

[2]  Fischer Ga.  Increased levels of folic acid reductase as a mechanism of resistance to amethopterin in leukemic cells. , 1961 .

[3]  R. Schimke,et al.  Synthesis and degradation of folate reductase in sensitive and methotrexate-resistant lines of S-180 cells. , 1976, The Journal of biological chemistry.

[4]  W. C. Werkheiser.  Specific Binding of 4-Amino Folic Acid Analogues by Folic Acid Reductase , 1961 .

[5]  L. Siminovitch,et al.  Isolation and partial characterization of three methotrexate-resistant phenotypes from Chinese hamster ovary cells , 1976, Somatic cell genetics.

[6]  M. Demerec.  Production of Staphylococcus Strains Resistant to Various Concentrations of Penicillin. , 1945, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Breeze,et al.  Trimethoprim-resistant mutants of E. coli K12: preliminary genetic mapping. , 1975, Genetical research.

[8]  G. A. Fischer.  Detective transport of amethopterin (methotrexate) as a mechanism of resistance to the antimetabolite in L5178Y leukemic cells. , 1962, Biochemical pharmacology.

[9]  H. Green,et al.  Alterations leading to increased ribonucleotide reductase in cells selected for resistance to deoxynucleosides. , 1974, Cell.

[10]  R. Rownd,et al.  Transition of R factor NR1 in Proteus mirabilis: molecular structure and replication of NR1 deoxyribonucleic acid , 1975, Journal of bacteriology.

[11]  J. King.  The Genetics of Resistance to DDT in Drosophila melanogaster. , 1954 .

[12]  M. Hakala,et al.  Relation of folic acid reductase to amethopterin resistance in cultured mammalian cells. , 1961, The Journal of biological chemistry.

[13]  R. L. Baldwin,et al.  Tandem genetic duplications in phage lambda. III. The frequency of duplication mutants in two derivatives of phage lambda is independent of known recombination systems. , 1975, Journal of molecular biology.

[14]  J. Littlefield,et al.  Altered regulation of the rate of synthesis of dihydrofolate reductase in methotrexate-resistant hamster cells. , 1976, The Journal of biological chemistry.

[15]  D. Hutchison,et al.  On the nature of a transport alteration determining resistance to amethopterin in the L1210 leukemia. , 1968, Cancer research.

[16]  G. Stark,et al.  Stable mutants of mammalian cells that overproduce the first three enzymes of pyrimidine nucleotide biosynthesis , 1976, Cell.

[17]  W. Folk,et al.  Duplication of the structural gene for glycyl-transfer RNA synthetase in Escherichia coli. , 1971, Journal of molecular biology.

[18]  M. Demerec.  Origin of Bacterial Resistance to Antibiotics , 1948, Journal of bacteriology.

[19]  J R Roth,et al.  Tandem duplications of the histidine operon observed following generalized transduction in Salmonella typhimurium. , 1976, Journal of molecular biology.

[20]  M. Sinensky.  Isolation of a mammalian cell mutant resistant to 25-hydroxy cholesterol. , 1977, Biochemical and biophysical research communications.

[21]  J. Bertino,et al.  Quantitation of dihydrofolate reductase in individual parental and methotrexate-resistant murine cells. Use of a fluorescence activated cell sorter. , 1978, The Journal of biological chemistry.

[22]  D. Hutchison,et al.  Two different species of dihydrofolate reductase in mammalian cells differentially resistant to amethopterin and methasquin. , 1972, Cancer research.

[23]  H. Moorefield,et al.  Resistance to DDT, DDT-Dehydrochlorinase, an Enzyme Found in DDT-Resistant Flies , 1954 .

[24]  F. Ruddle,et al.  Transfer of the human gene for hypoxanthine-guanine phosphoribosyltransferase via isolated human metaphase chromosomes into mouse L-cells. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J R Roth,et al.  Tandem genetic duplications in phage and bacteria. , 1977, Annual review of microbiology.

[26]  J. Littlefield.  Hybridization of hamster cells with high and low folate reductase activity. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[27]  J. Bertino,et al.  Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells. , 1978, The Journal of biological chemistry.

[28]  A. Goldin,et al.  The association of increased dihydrofolate reductase with amethopterin resistance in mouse leukemia. , 1962, Cancer research.

[29]  T. Grundström,et al.  Escherichia coli K-12 Mutants Hyperproducing Chromosomal Beta-Lactamase by Gene Repetitions , 1977, Journal of bacteriology.

[30]  B. Spengler,et al.  Metaphase chromosome anomaly: association with drug resistance and cell-specific products. , 1976, Science.

[31]  A. Sturtevant.  The Effects of Unequal Crossing over at the Bar Locus in Drosophila. , 1925, Genetics.

[32]  Stanley N Cohen.  Transposable genetic elements and plasmid evolution , 1976, Nature.

[33]  O. Mcbride,et al.  Transfer of genetic information by purified metaphase chromosomes. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[34]  L. C. Terriere.  Insecticide-Cytoplasmic Interactions in Insects and Vertebrates , 1968 .

[35]  M. Tsukamoto.  Biochemical genetics of insecticide resistance in the housefly. , 1969, Residue reviews.