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Genetic Variants of Cultured Animal Cells

  • Peter N. Ray
  • Louis Siminovitch
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 50)

Abstract

It has been clear for a number of years that the functional analysis of biological systems is highly dependent upon the availability of a large number of mutants of broad phenotypic classes. It was with this understanding that our laboratory undertook about ten years ago to develop methods for selection of mutants in somatic cells. Over this decade the field has developed extremely rapidly both in terms of methodological expertise and in the wide spectrum of mutants which can now be used for studies on gene function and regulation.

Keywords

Chinese Hamster Ovary Cell Chinese Hamster Ovary Thymidine Kinase Ribonucleotide Reductase Chinese Hamster Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    L. Siminovitch, On the origin of mutants of somatic cells, in “Eucaryotic Gene Regulation”, ICN-UCLA Symposia on Molecular and Cellular Biology, R. Axel, T. Maniatis, and C.F. Fox, eds., Academic Press, New York, pp.433–443 (1979).Google Scholar
  2. 2.
    L. Siminovitch, The Nature of Gene Variation and Gene Transfer in Somatic Cells, in “Genes, Chromosomes, and Neoplasia”, F.E. Arrighi, P.N. Rao, and E. Stubblefield, eds., Raven Press, New York (1981).Google Scholar
  3. 3.
    J. Hochstadt, H.L. Ozer and C. Shopsis, Genetic Alteration in Animal Cells in Culture, Current Topics, Microbiology and Immunology, W. Arber and H. Koprowsky, eds., Springer Verlag, Berlin, New York (in press).Google Scholar
  4. 4.
    P. Coffino, R. Baumal, R. Laskov and M.D. Scharff, Cloning of Mouse Myeloma Cells and Detection of Rare Variants, J. Cell Physiol. 79:429–440 (1971).Google Scholar
  5. 5.
    T.T. Puck and F.T. Kao, Genetics of somatic mammalian cells. V. Treatment with 5-bromodeoxyuridine and visible light for isolation of nutritionally deficient mutants. Proc. Natl. Acad. Sci. USA 58:1227–1234 (1967).PubMedGoogle Scholar
  6. 6.
    F.T. Kao and T.T. Puck, Genetics of somatic mammalian cells. VII. Induction and isolation of nutritional mutants in Chinese hamster cells, Proc. Natl. Acad. Sci. USA 60:1275–1281 (1968).PubMedGoogle Scholar
  7. 7.
    L.H. Thompson, R. Mankovitz, R.M. Baker, J.E. Till, L. Siminovitch and G.F. Whitmore, Isolation of temperature-sensitive mutants of L-cells, Proc. Natl. Acad. Sci. USA 66:377–384 (1970).PubMedGoogle Scholar
  8. 8.
    F.T. Kao and T.T. Puck, Genetics of somatic mammalian cells. IX. Quantitation of mutagenesis by physical and chemical agents, J. Cell. Physiol. 74:245–258 (1969).PubMedGoogle Scholar
  9. 9.
    F.T. Kao, L. Chasin and T.T. Puck, Genetics of somatic mammalian cells. X. Complementation analysis of glycine-requiring mutants, Proc. Natl. Acad. Sci. USA 64:1284–1291 (1969).PubMedGoogle Scholar
  10. 10.
    F.T. Kao and T.T. Puck, Genetics of Chinese hamster cell mutants with respect to the requirement for proline, Genetics 55:513–529 (1967).PubMedGoogle Scholar
  11. 11.
    D. Patterson, F.T. Kao and T.T. Puck, Genetics of somatic mammalian cells: Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism, Proc. Natl. Acad. Sci. USA 71:2057–2061 (1975).Google Scholar
  12. 12.
    D. Patterson, Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism: Biochemical analysis of eight mutants, Somat. Cell Genet. 1:91–110 (1975).PubMedGoogle Scholar
  13. 13.
    D. Patterson, Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism. III. Isolation and characterization of a mutant unable to convert IMP to AMP, Somat. Cell Genet. 2:41–53 (1976).Google Scholar
  14. 14.
    D. Patterson, Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism. IV. Isolation of a mutant which accumulates adenylosuccinic acid and succinylaminoimidazole carboxamide ribotide, Somat. Cell Genet. 2:189–203 (1976).PubMedGoogle Scholar
  15. 15.
    D.C. Oates and D. Patterson, Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism: Characterization of Chinese hamster cell mutants defective in phosphor ibosylpyrophosphate amidotransferase and phosphoribosylglycinamide synthetase and an examination of alternatives to the first step of purine biosynthesis, Somat. Cell Genet. 3:561–577 (1977).PubMedGoogle Scholar
  16. 16.
    E.H.Y. Chu, N.C. Sun and C.C. Chang, Induction of auxotrophic mutations by treatment of Chinese hamster cells with 5-bromodeoxyuridine and black light, Proc. Natl. Acad. Sci. USA 69:3459–3463 (1972).PubMedGoogle Scholar
  17. 17.
    R.K. Feldman and M.W. Taylor, Purine mutants of mammalian cell lines. II. Identification of a phosphoribosylpyrophosphate amidotransferase-deficient mutant of Chinese hamster lung cells, Biochem. Genet. 13:227–234 (1975).PubMedGoogle Scholar
  18. 18.
    R.K. Feldman and M.W. Taylor, Purine mutants of mammalian cell lines. I. Accumulation of formylglycinamide ribotide by purine mutants of Chinese hamster ovary cell, Biochem. Genet. 12:393–405 (1975).Google Scholar
  19. 19.
    E.W. Holmes, G.L. King, A. Layva and S.C. Singer, A purine auxotroph deficient in phosphoribosylpyrophosphate amidotransferase activities with normal activity of ribose-5-phosphate aminotransferase, Proc. Natl. Acad. Sci. USA 73:2458–2461 (1976).PubMedGoogle Scholar
  20. 20.
    R.T. Taylor and M.L. Hanna, Folate-dependent enzymes in cultured Chinese hamster cells: Folylpolyglutamate synthetase and its absence in mutants auxotrophic for glycine + adenosine + thymide, Arch. Biochem. Biophys. 181:331–344 (1977).PubMedGoogle Scholar
  21. 21.
    M. McBurney and G.F. Whitmore, Isolation and biochemical characterization of folate deficient mutants of Chinese hamster cells, Cell 2:173–182 (1974).PubMedGoogle Scholar
  22. 22.
    M. McBurney and G.F. Whitmore, Characterization of a Chinese hamster cell with a temperature-sensitive mutation in folate metabolism, Cell 2:183 (1974).PubMedGoogle Scholar
  23. 23.
    G. Urlaub and L.A. Chasin, Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity, Proc. Natl. Acad. Sci. USA 77:4216–4220 (1980).PubMedGoogle Scholar
  24. 24.
    M. Meuth, M. Trudel and L. Siminovitch, Selection of Chinese hamster cells auxotrophic for thymidine by 1-B-D-arbinofurano-syl cytosine, Somat. Cell Genet. 5:303–318 (1979).Google Scholar
  25. 25.
    D. Ayusawa, H. Koyama, K. Iwata and T. Seno, Single-step selection of mouse FM3A cell mutants defective in thymidylate synthetase, Somat. Cell Genet. 6:261–270 (1980).PubMedGoogle Scholar
  26. 26.
    D. Patterson and D.V. Carnright, Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells. I. Isolation of a mutant defective in the early steps of de novo pyrimidine synthesis, Somat. Cell Genet. 3:483–495 (1977).PubMedGoogle Scholar
  27. 27.
    J.N. Davidson, D.V. Carnright and D. Patterson, Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells. III. Association of carbamyl phosphate synthetase, aspartate transcarbamylase, and dihydroorotase in mutants of cultured Chinese hamster cells, Somat. Cell Genet. 5:176–191 (1979).Google Scholar
  28. 28.
    T. Kusano, M. Kato and I. Yamane, Isolation of uridine requiring variants in Chinese hamster cells. Cell Struct. and Funct. 1:393–396 (1976).Google Scholar
  29. 29.
    D. Patterson, Isolation and characterization of 5-fluoro-uracil-resistant mutants of Chinese hamster ovary cells deficient in the activities of orotate phosphoribosyltransferase and orotine 5′-monophosphate decarboxylase, Somat. Cell Genet. 6:101–114(1980).PubMedGoogle Scholar
  30. 30.
    B.B. Levinson, B. Ullman and D.W. Martin, Jr., Pyrimidine pathway variants of cultured mouse lymphoma cells with altered levels of both orotate phosphoribosyltransferase and orotidy-late decarboxylase, J. Biol. Chem. 254:4396–4404 (1979).PubMedGoogle Scholar
  31. 31.
    R.S. Krooth, W-L. Hsiao and B.W. Potvin, Resistance to 5-fluoroorotic acid and pyrimidine auxotrophy: A new bidirectional selective system for mammalian cells, Somat. Cell Genet. 5:551–569 (1979).PubMedGoogle Scholar
  32. 32.
    Y. Saito, S.M. Chou and D.F. Silbert, Animal cell mutants defective in sterol metabolism: A specific selection procedure and partial characterization of defects, Proc. Natl. Acad. Sci. USA 74:3730–3734 (1977).PubMedGoogle Scholar
  33. 33.
    T-Y. Chang and P.R. Vagelos, Isolation and characterization of an unsaturated fatty acid-requiring mutant of cultured mammalian cells, Proc. Natl. Acad. Sci. USA 73:24–28 (1976).PubMedGoogle Scholar
  34. 34.
    T-Y. Chang, C. Telakowski, W. Vanden Heuvel, A.W. Alberts and P.R. Vagelos, Isolation and partial characterization of a cholesterol-requiring mutant of Chinese hamster ovary cells, Proc. Natl. Acad. Sci. USA 74:832–836 (1977).PubMedGoogle Scholar
  35. 35.
    J.S. Limanek, J. Chn and T-Y. Chang, Mammalian cell mutant requiring cholesterol and unsaturated fatty acid for growth, Proc. Natl. Acad. Sci. USA 75:5452–5456 (1978).PubMedGoogle Scholar
  36. 36.
    K. Hidaka, S-I. Akiyama and M. Kuwano, Growth of amphotericin B-resistant hamster cell line requires exogenous cholesterol, Exper. Cell Res. 128:215–221 (1980).Google Scholar
  37. 37.
    C. Jones and T.T. Puck, Genetics of somatic mammalian cells. XVII. Induction and isolation of Chinese hamster cell mutants requiring serine, J. Cell Physiol. 81:299–304 (1973).PubMedGoogle Scholar
  38. 38.
    O. Hankinson, Mutants of the Chinese hamter ovary cell line requiring alanine and glutamate, Somat. Cell Genet. 2:497–507 (1976).Google Scholar
  39. 39.
    M.M.Y. Waye and C.P. Stanners, Isolation and characterization of CHO cell mutants with altered asparagine synthetase, Somat. Cell Genet. 5:625–639 (1979).PubMedGoogle Scholar
  40. 40.
    G. Ditta, K. Soderberg, F. Landy and I.E. Scheffler, The Selection of Chinese hamster cells deficient in oxidative energy metabolism, Somat. Cell Genet. 2:331–344 (1976).PubMedGoogle Scholar
  41. 41.
    L. DeFrancesco, D. Werntz and I.E. Scheffler, Conditionally lethal mutations in Chinese hamster cells. Characterization of a cell line with a possible defect in the Krebs cycle. J. Cell. Physiol. 85:293–306 (1975).PubMedGoogle Scholar
  42. 42.
    S.L. Naylor, L.L. Busby and R.J. Klebe, Biochemical selection systems for mammalian cells: The essential amino acids, Somat. Cell Genet. 2:93–111 (1976).PubMedGoogle Scholar
  43. 43.
    S.L. Naylor, J.K. Townsend and R.J. Klebe, Characterization of naturally occurring auxotrophic mammalian cells, Somat. Cell Genet. 5:271–277 (1979).PubMedGoogle Scholar
  44. 44.
    P.F. Coleman, D.P. Suttle and G.R. Stark, Purification from hamster cells of the multifunctional protein that initiates de novo synthesis of pyrimidine nucleotides, J. Biol. Chem. 252:6379–6385 (1977).PubMedGoogle Scholar
  45. 45.
    T. Kempe, E. Swyrd, M. Bruist and G. Stark, Stable mutants of mammalian cells that overproduce the first three enzymes of pyrimidine nucleotide biosynthesis, Cell 9:541–550 (1976).PubMedGoogle Scholar
  46. 46.
    R.A. Padgett, G.M. Wahl, P.F. Coleman and G.R. Stark, N-(phosphonacetyl)-L-aspartate-resistant hamster cells over-accumulate a single mRNA coding for the multifunctional protein that catalyzes the first step of UMP synthesis, J. Biol. Chem. 254:974–980 (1979).PubMedGoogle Scholar
  47. 47.
    L.A. Chasin, A. Feldman, M. Konstam and G. Urlaub, Reversion of a Chinese hamster cell auxotrophic mutant, Proc. Natl. Acad. Sci. USA 71:718 (1974).PubMedGoogle Scholar
  48. 48.
    D.C. Oates, D. Vannais and D. Patterson, A. mutant of CHO-K1 cells deficient in two-nonsequential steps of de novo purine biosynthesis, Cell 20:797–805 (1980).PubMedGoogle Scholar
  49. 49.
    D. Patterson, S. Graw and C. Jones, Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21, Proc. Natl. Acad. Sci. USA 78:405–409 (1981).PubMedGoogle Scholar
  50. 50.
    P.M. Naha, Temperature sensitive conditional mutants of monkey kidney cells, Nature 223:1380–1381 (1969).PubMedGoogle Scholar
  51. 51.
    B.J. Smith and N.M. Wigglesworth, A cell line which is temperature-sensitive for cytokinesis, J. Cell Physiol. 80:253–260 (1972).PubMedGoogle Scholar
  52. 52.
    H.K. Meiss and C. Basilico, Temperature-sensitive mutants of BHK 21 cells, Nature New Biol. 239:66–68 (1972).PubMedGoogle Scholar
  53. 53.
    C. Basilico, Temperature-sensitive mutations in animal cells, Adv. Can. Res. 24:223–266 (1977).Google Scholar
  54. 54.
    L.H. Thompson, J.L. Harkins and C.P. Stanners, A mammalian cell mutant with a temperature-sensitive leucyl-transfer RNA synthetase, Proc. Natl. Acad. Sci. USA 70:3094–3098 (1973).PubMedGoogle Scholar
  55. 55.
    L.H. Thompson, C.P. Stanners and L. Siminovitch, Selection by [3H] amino acids of CHO-cell mutants with altered leucyl and asparagyl-transfer RNA synthetases, Somat. Cell Genet. 1:187–208 (1975).PubMedGoogle Scholar
  56. 56.
    R.A. Farber and M.P. Deutscher, Physiological and biochemical properties of a temperature-sensitive leucyl-tRNA synthetase mutant (tsHI) and revertant from Chinese hamster cells, Somat. Cell Genet. 2:509–520 (1976).Google Scholar
  57. 57.
    L. Haars, A. Hampel and L.H. Thompson, Altered leucyl-transfer RNA synthetase from a mammalian cell culture mutant, Biochim. Biophys. Acta 454:493–503 (1976).PubMedGoogle Scholar
  58. 58.
    J.J. Wasmuth and C.T. Caskey, Selection of temperature-sensitive CHL asparagyl t-RNA synthetase mutants using the toxic lysine analog, S-2-aminoethyl-L-cysteine, Cell 9:655–662 (1976).PubMedGoogle Scholar
  59. 59.
    L.H. Thompson, D.J. Lofgren and G.M. Adair, CHO cell mutants for arginyl-, asparagyl-, glutaminyl-, histidyl-, and methionyl-transfer RNA synthetases: Identification and initial characteization, Cell 11:157–168 (1977).PubMedGoogle Scholar
  60. 60.
    L.H. Thompson, D.J. Lofgren and G.M. Adair, Evidence for structural gene alterations affecting aminoacyl-tRNA synthetases in CHO cell mutants and revertants, Somat. Cell Genet. 4:423–435 (1978).PubMedGoogle Scholar
  61. 61.
    G.M. Adiar, L.H. Thompson and P.A. Lindl, Six complementation classes of conditionally lethal protein synthesis mutants of CHO cells selected by 3H-amino acids, Somat. Cell Genet. 4:27–44 (1978).Google Scholar
  62. 62.
    I.L. Andrulis, G.S. Chiang, S.M. Arfin, T.A. Miner and G.W. Hatfield, Biochemical characterization of a mutant asparaginyl-tRNA synthetase from Chinese hamster ovary cells, J. Biol. Chem. 253:58–62 (1978).PubMedGoogle Scholar
  63. 63.
    C.R. Ashman, Mutations in the structural genes of CHO cell histidyl-, valyl-, and leucyl-tRNA synthetases, Somat. Cell Genet. 4:299–312 (1978).PubMedGoogle Scholar
  64. 64.
    C.P. Stanners, T.M. Wightman and J.L. Harkins, Effect of extreme amino acid starvation on the protein synthetic machinery of CHO cells, J. Cell Physiol. 95:125–138 (1978).PubMedGoogle Scholar
  65. 65.
    G.M. Adair, L.H. Thompson and S. Fond, [3H] Amino acid selection of aminoacyl-tRNA synthetase mutants of CHO cells: Evidence of homovs. hemizygosity at specific loci, Somat. Cell Genet. 5:329–344 (1979).Google Scholar
  66. 66.
    D. Toniolo, H.K. Meiss and C. Basilico, A temperature-sensitive mutation affecting 28S ribosomal RNA production in mammalian cells, Proc. Natl. Acad. Sci. USA 70:1273–1277 (1973).PubMedGoogle Scholar
  67. 67.
    D. Toniolo and C. Basilico, Processing of ribosomal RNA in a temperature sensitive mutant of BHK cells, Biochim. Biophys. Acta 425:409–418 (1976).PubMedGoogle Scholar
  68. 68.
    L.H. Thompson, R. Mankovitz, R.M. Baker, J.A. Wright, J.E. Till, L. Siminovitch and G.F. Whitmore, Selective and nonselective isolation of temperature sensitive mutants of mouse L-cells and their characterization, J. Cell Physiol. 78:431–439 (1971).PubMedGoogle Scholar
  69. 69.
    M.L. Slater and H.L. Ozer, Temperature-sensitive mutants of Balb/3T3 cells: Description of a mutant affected in cellular and polyoma virus DNA synthesis, Cell 7:289–295 (1976).PubMedGoogle Scholar
  70. 70.
    R. Sheinin, Preliminary characterization of the temperature-sensitive defect in DNA replication in a mutant mouse L cell, Cell 7:49–57 (1976).PubMedGoogle Scholar
  71. 71.
    K.K. Jha and H. Ozer, Genetic studies with a mutant mouse cell, ts-2 Balb/3T3 with a temperature-sensitive defect in DNA synthesis, Genetics (suppl.) 86:532–534 (1977).Google Scholar
  72. 72.
    D.J. Roufa, S.M. McGill and J.W. Mollenkamp, Ts mutant isolated from CHO cells-inhibition of DNA-replication at non-permissive temperature, Somat. Cell Genet. 5:97–115 (1979).PubMedGoogle Scholar
  73. 73.
    I.E. Scheffler and G. Buttin, Conditionally lethal mutations in Chinese hamster cells. I. Isolation of a temperature-sensitive line and its investigation by cell cycle studies, J. Cell Physiol. 81:199–216 (1973).PubMedGoogle Scholar
  74. 74.
    P.M. Naha, A.L. Meyer and K. Hewitt, Mapping of the G1 phase of mammalian cell cycle, Nature 258:49 (1975).PubMedGoogle Scholar
  75. 75.
    R.J. Wang, A novel temperature-sensitive mammalian cell line exhibiting defective prophase progression, Cell 8:257–261 (1976).PubMedGoogle Scholar
  76. 76.
    C. Basilico, Selective production of cell cycle specific ts mutants, J. Cell Physiol. 95:367–376 (1978).PubMedGoogle Scholar
  77. 77.
    N.B. Liskay and D.M. Prescott, Genetic analysis of the G1 period: Isolation of mutants (or variants) with a G1 period from a Chinese hamster cell line lacking G1, Proc. Natl. Acad. Sci. USA 75:2873–2877 (1978).PubMedGoogle Scholar
  78. 78.
    H.K. Meiss, A. Talavera and T. Nishimoto, A recurring temperature-sensitive mutant class of BHK-21 cells, Somat. Cell Genet. 4:125–130 (1978).PubMedGoogle Scholar
  79. 79.
    T. Nishimoto and C. Basilico, Analysis of a method for selecting temperature sensitive mutants of BHK-cells, Somat. Cell Genet. 4:323–340 (1978).PubMedGoogle Scholar
  80. 80.
    J. Melero, Isolation and cell cycle analysis of temperature-sensitive mutants from Chinese hamster cells, J. Cell Physiol. 98:17–30 (1979).PubMedGoogle Scholar
  81. 81.
    H.E. Schwartz, G.C. Moser, S. Holmes and H.K. Meiss, Assignment of temperature-sensitive mutations of BHK cells to the X chromosome, Somat. Cell Genet. 5:217–224 (1979).PubMedGoogle Scholar
  82. 82.
    P.M. Naha and R. Sorrentino, Biochemical controls of the G1 phase of a mammalian cell cycle. I. Analysis of chromatin proteins in temperature-sensitive variants, Cell Biol. International Reports 4:365–378 (1980).Google Scholar
  83. 83.
    T. Nishimoto, T. Takahashi and C. Basilico, A temperature-sensitive mutation affecting S-phase progression can lead to accumulation of cells with a G-2 DNA content, Somat. Cell Genet. 6:465–476 (1980).PubMedGoogle Scholar
  84. 84.
    R. Fenwick, Jr. and C. Caskey, Mutant Chinese hamster cells with a thermosensitive hypoxanthine-guanine phosphoribosyl-transferase, Cell 5:115–122 (1975).PubMedGoogle Scholar
  85. 85.
    R.G. Fenwick, Jr., T.H. Sawyer, G.D. Kruh, K.H. Astrin and C.T. Caskey, Forward and reverse mutations affecting the kinetics and apparent molecular weight of mammalian HGPRT, Cell 12:383–391 (1977).Google Scholar
  86. 86.
    C.J. Ingles, Temperature sensitive RNA polymerase II mutations in Chinese hamster ovary cells, Proc. Natl. Acad. Sci. USA 75:405–409 (1978).PubMedGoogle Scholar
  87. 87.
    M.M. Nakano, T. Sekiquicki and M. Hamada, A mammalian cell mutant with temperature-sensitive thymidine kinase, Somat. Cell Genet. 4:169–178 (1978).PubMedGoogle Scholar
  88. 88.
    K. Miyashita and T. Kakunaga, Isolation of heat and cold-sensitive mutants of Chinese hamster lung cells affected in their ability to express the transformed state, Cell 5:131–138 (1975).PubMedGoogle Scholar
  89. 89.
    R.A. Färber and P. Unrau, Isolation of cold-sensitive Chinese hamster cells, Molec. Genet. 138:233–242 (1975).Google Scholar
  90. 90.
    M.S.J. Crane and D.B. Thomas, Cell-cycle, cell-shape mutant with features of the G0 state, Nature 261:205–208 (1976).PubMedGoogle Scholar
  91. 91.
    B.M. Ohlsson-Wilhelm, J.F. Leary, M. Pacilio and T. Martin, Rapid, quantitative analysis of cell cycle stages of cold-sensitive derivatives of the Chinese hamster cell line CHO-K1, Somat. Cell Genet. 6:349–359 (1980).PubMedGoogle Scholar
  92. 92.
    V. Ling, A membrane-altered mutant cold-sensitive for growth, J. Cell Physiol. 91:209–224 (1977).PubMedGoogle Scholar
  93. 93.
    T-S. Chan, C. Long and H. Green, A human-mouse somatic hybrid line selected for human deoxycytidine deaminase, Somat. Cell Genet. 1:81–90 (1975).PubMedGoogle Scholar
  94. 94.
    B. Ullman, L.H. Gudas, S.M. Clift and D.W. Martin, Jr., Isolation and characterization of purine-nucleoside phosphorylase-deficient T-lymphoma cells and secondary mutants with altered ribonucleotide reductase: Genetic model for immunodeficiency disease, Proc. Natl. Acad. Sci. USA 76:1074–1078 (1979).PubMedGoogle Scholar
  95. 95.
    P. Hoffee, A method for the isolation of purine nucleoside phosphorylase-deficient variants of mammalian cell lines, Somat. Cell Genet. 5:319–328 (1979).Google Scholar
  96. 96.
    E.R. Giblett, A.J. Ammann, D.W. Wara, R. Sandman and L.K. Diamond, Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity, The Lancet 1:1010–1013 (1975).Google Scholar
  97. 97.
    R.L. Momparler, M.Y. Chu and G.A. Fischer, Studies on a new mechanism of resistance of L5178Y murine leukemia cells to cytosine arabinoside, Biochim. Biophys. Acta 161:481–493 (1968).PubMedGoogle Scholar
  98. 98.
    B.R. de Saint-Vincent and G. Buttin, Studies on l-β-D-Arbinofuranosyl-cytosine-resistant mutants of Chinese hamster fibroblasts, Eur. J. Biochem. 37:481–488 (1973).PubMedGoogle Scholar
  99. 99.
    M. Meuth and H. Green, Alterations leading to increased ribonucleotide reductase in cells selected for resistance to de-oxynucleosides, Cell 3:367–374 (1974).PubMedGoogle Scholar
  100. 100.
    M. Meuth, E. Aufreiter and P. Reichard, Deoxyribonucleotide pools in mouse-fibroblast cell lines with altered ribonucleotide reductase, Eur. J. Biochem. 71:39–43 (1976).PubMedGoogle Scholar
  101. 101.
    M. Meuth, N. L’Heureux-Huard and M. Trudel, Characterization of a mutator gene in Chinese hamster ovary cells, Proc. Natl. Acad. Sci. USA 76:6506–6509 (1979).Google Scholar
  102. 102.
    V.L. Chan and P. Juranka, Isolation and preliminary characterization of 9-β-D-arabinofuranosyladenine-resistant mutants of baby hamster cells, Somat. Cell Genet. 7:147–160 (1981).PubMedGoogle Scholar
  103. 103.
    W.F. Flintoff, S.V. Davidson and L. Siminovitch, Isolation and partial characterization of three methotrexate-resistant phenotypes from Chinese hamster ovary cells, Somat. Cell Genet. 2:245–261 (1976).PubMedGoogle Scholar
  104. 104.
    W.F. Flintoff, S.M. Spindler and L. Siminovitch, Genetic characterization of methotrexate-resistant Chinese hamster ovary cells, In Vitro 12:749–757 (1976).Google Scholar
  105. 105.
    F.W. Alt, R.E. Kellems and R.T. Schimke, Synthesis and degradation of folate reductase in sensitive and methotrexate-resistant lines of S-180 cells, J. Biol. Chem. 251:3063–3074 (1976).PubMedGoogle Scholar
  106. 106.
    R.S. Gupta, W.F. Flintoff and L. Siminovitch, Purification and properties of dihydrofolate reductase from methotrexate-sensitive and resistant Chinese hamster ovary cells, Canad. J. Biochem. 55:445–452 (1977).Google Scholar
  107. 107.
    R.T. Schimke, R.J. Kaufman, F.W. Alt and R.F. Kellems, Gene amplification and drug resistance in cultured murine cells, Science 202:1051–1055 (1978).PubMedGoogle Scholar
  108. 108.
    J.H. Nunberg, R.J. Kaufman, R.T. Schimke, G. Urlaub and L.A. Chasin, Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line, Proc. Natl. Acad. Sci. USA 75:5553–5556 (1978).PubMedGoogle Scholar
  109. 109.
    R.J. Kaufman, P.C. Brown and R.T. Schimke, Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes, Proc. Natl. Acad. Sci. USA 76:5669–5673 (1979).PubMedGoogle Scholar
  110. 110.
    R.E. Kellems, V.B. Morhenn, E.A. Pfendt, F.W. Alt and R.T. Schimke, Polyoma virus and cyclic AMP-mediated control of dihydrofolate reductase mRNA abundance in methotrexate-resistant mouse fibroblasts, J. Biol. Chem. 254:309–318 (1979).PubMedGoogle Scholar
  111. 111.
    B.J. Dolnick, R.J. Berenson, J.R. Bertino, R.J. Kaufman, J.H. Nunberg and R.T. Schimke, Correlation of dihydrofolate reductase elevation with gene amplification in a homogeneously staining chromosomal region in L5178Y cells, J. Cell Biol. 83:394–402 (1979).PubMedGoogle Scholar
  112. 112.
    W.H. Lewis, P.R. Srinivasan, N. Stokoe and L. Siminovitch, Parameters governing the transfer of the genes for thymidine kinase and dihydrofolate reductase into mouse cells using metaphase chromosomes of DNA, Somat. Cell Genet. 6:333–348 (1980).PubMedGoogle Scholar
  113. 113.
    M. Wigier, M. Perucho, D. Kurtz, S. Dana, A. Pellicer, R. Axel and S. Silverstein, Transformation of mammalian cells with an amplifiable dominant-acting gene, Proc. Natl. Acad. Sci. USA 77:3567–3570 (1980).Google Scholar
  114. 114.
    J.P. Thirion, D. Banville and H. Noel, Galactokinase mutants of Chinese hamster somatic cells resistant to 2-deoxyglucose, Genetics 83:137–147 (1976).PubMedGoogle Scholar
  115. 115.
    J.A. Wright and W.H. Lewis, Evidence for a common site of action for the antitumor agents hydroxyurea and guanazole, J. Cell Physiol. 83:437–440 (1974).PubMedGoogle Scholar
  116. 116.
    W.H. Lewis and J.A. Wright, Altered ribonucleotide reductase activity in mammalian tissue culture cells resistant to hydroxyurea, Biochem. Biophys. Res. Commun. 60:926–933.Google Scholar
  117. 117.
    W.H. Lewis and J.A. Wright, Genetic characterization of hydroxyurea-resistance in Chinese hamster ovary cells, J. Cell Physiol. 97:73–86 (1978).PubMedGoogle Scholar
  118. 118.
    W.H. Lewis and J.A. Wright, Isolation of hydroxyurea-resistant cells with altered levels of ribonucleotide reductase, Somat. Cell Genet. 5:83–96 (1979).PubMedGoogle Scholar
  119. 119.
    R.L. Davidson and E.R. Kaufman, Resistance to bromodeoxyuri-dine mutagenesis and toxicity in mammalian cells selected for resistance to hydroxyurea, Somat. Cell Genet. 5:873–885 (1979).PubMedGoogle Scholar
  120. 120.
    C-C. Chang, J.A. Boezi, S.T. Warren, C.L.K. Sabourin, P.K. Liu, L. Glatzer and J.E. Trosko, Isolation and characterization of a UV-sensitive hypermutable aphidicolin-resistant Chinese hamster cell line, Somat. Cell Genet. 7:235–253 (1981).PubMedGoogle Scholar
  121. 121.
    C.L.K. Sabourin, P.F. Bates, L. Glatzer, C-C. Chang, J.E. Trosko and J.A. Boezi, Selection of aphidicolin-resistant CHO cells with altered levels of ribonucleotide reductase, Somat. Cell Genet. 7:255–268 (1981).PubMedGoogle Scholar
  122. 122.
    M.W. McBurney and G.F. Whitmore, Mutants of Chinese hamster cells resistant to adenosine, J. Cell. Physiol. 85:87–100 (1975).PubMedGoogle Scholar
  123. 123.
    R.S. Gupta and L. Siminovitch, Genetic and biochemical studies with the adenosine analogs toyocamycin and tubercidin: Mutation at the adenosine kinase locus in Chinese hamster cells, Somat. Cell Genet. 4:715–736 (1978).PubMedGoogle Scholar
  124. 124.
    T-S. Chan, R.P. Creagan and M.P. Reardon, Adenosine kinase as a new selective marker in somatic cell genetics: Isolation of adenosine kinase-deficient mouse cell lines and human-mouse hybrid cell lines containing adenosine kinase, Somat. Cell Genet. 4:1–12 (1978).PubMedGoogle Scholar
  125. 125.
    M.S. Rabin and M.M. Gottesman, High frequency of mutation to tubercidin resistance in CHO cells, Somat. Cell Genet. 5:571–583 (1979).PubMedGoogle Scholar
  126. 126.
    W. Szbalski and M.J. Smith, Genetics of human cell lines. I. 8-azaguanine resistance, a selective “single-step” marker, Proc. Soc. Exp. Biol. Med. 101:662–666 (1959).Google Scholar
  127. 127.
    J.W. Littlefield, The inosinic acid pyrophosphorylase activity of mouse fibroblasts partially resistant to 8-azaguanine, Proc. Natl. Acad. Sci. USA 50:568–576 (1963).PubMedGoogle Scholar
  128. 128.
    E.H.Y. Chus, P. Brimer, K.B. Jacobsen and E. Merriam, Mammalian cell genetics. I. Selection and characterization of mutations auxotrophic for L-glutamine or resistant to 8-azaguanine in Chinese hamster cells in vitro, Genetics 62:359–377 (1969).Google Scholar
  129. 129.
    F.D. Gillin, D.J. Roufa, A.L. Beaudet and C.T. Caskey, 8-Azaguanine resistance in mammalian cells. I. Hypoxanthine-guanine phosphoribosyltransferase, Genetics 72:239–252 (1972).PubMedGoogle Scholar
  130. 130.
    J.D. Sharp, N.E. Capecchi and M.R. Capecchi, Altered enzymes in drug-resistant variants of mammalian tissue culture cells, Proc. Natl. Acad. Sci. USA 70:3145–3149 (1973).PubMedGoogle Scholar
  131. 131.
    L.A. Chasin, Mutations affecting adenine phosphoribosyl transferase activity in Chinese hamster cells, Cell 2:43–54 (1974).Google Scholar
  132. 132.
    G.E. Jones and P.A. Sargent, Mutants of cultured Chinese hamster cells deficient in adenine phosphoribosyl transferase, Cell 2:37–41 (1974).Google Scholar
  133. 133.
    M.W. Taylor, J.H. Pipkorn, M.K. Tokito and R.O. Pozzatti, Jr., Purine mutants of mammalian cells. III. Control of purine biosynthesis in adenine phosphoribosyl transferase mutants of CHO cells, Somat. Cell Genet. 3:195–206 (1977).PubMedGoogle Scholar
  134. 134.
    S. Kit, D.R. Dubbs, L.H. Piekarski and T.C. Hsu, Deletion of thymidine kinase activity from L cells resistant to bromode-oxyuridine, Exp. Cell Res. 31:297–312 (1963).PubMedGoogle Scholar
  135. 135.
    J.W. Littlefield, Studies on thymidine kinase in cultured mouse fibroblasts, Biochim. Biophys. Acta 95:14–22 (1965).PubMedGoogle Scholar
  136. 136.
    D. Clive, W.G. Flamm, M.R. Machesko and N.J. Berhneim, A mutational assay system using the thymidine kinase locus in mouse lymphoma cells, Mutat. Res. 16:77–87 (1972).PubMedGoogle Scholar
  137. 137.
    E.R. Kaufman and R.L. Davidson, Novel phenotypes arising from selection of hamster melanoma cells for resistance to BUdR, Exp. Cell Res. 107:15–24 (1977).PubMedGoogle Scholar
  138. 138.
    E.R. Kaufman and R.L. Davidson, Effects of thymidine analogs on Syrian hamster melanoma cells: Phenotypes arising from selection to analog resistance, Somat. Cell Genet. 3:649–661 (1977).PubMedGoogle Scholar
  139. 139.
    L. Medrano and H. Green, A uridine kinase-deficient mutant of 3T3 and a selective method for cells containing the enzyme, Cell 1:23–26 (1974).Google Scholar
  140. 140.
    M. Greenbert, D.E. Shumm and T.E. Weeb, Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine sensitive and resistant cell lines of the Novikoff Hepatoma, Biochem. J. 164:379–387 (1979).Google Scholar
  141. 141.
    G.M. Wahl, R.A. Padgett and G.R. Stark, Gene amplification causes overproduction of the first three enzymes of UMP synthesis in N-(Phosphonacetyl)-L-aspartate-resistant hamster cells, J. Biol. Chem. 254:8679–8689 (1979).PubMedGoogle Scholar
  142. 142.
    D.P. Suttle and G.R. Stark, Coordinate overproduction of orotate phosphoribosyltransferase and orotidine-5′-phosphate decarboxylase in hamster cells resistant to pyrazofurin and 6-azauridine, J. Biol. Chem. 254:4602–4607 (1979).PubMedGoogle Scholar
  143. 143.
    M. Wigier, S. Silverstein, L-S. Lee, A. Pellicer, Y-C. Cheng and R. Axel, Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells, Cell 11:223–232 (1977).Google Scholar
  144. 144.
    A.C. Minson, P. Wildy, A. Buchan and G. Darby, Introduction of the herpes simplex virus thymidine kinase gene into mouse cells using virus DNA or transformed cell DNA, Cell 13:581–587 (1978).PubMedGoogle Scholar
  145. 145.
    M. Wigier, A. Pellicer, S. Silverstein, R. Axel, G. Urlaub and L. Chasin, DNA-mediated transfer of the adenine phosphori-bosyltransferase locus into mammalian cells, Proc. Natl. Acad. Sci. USA 76:1373–1376 (1979).Google Scholar
  146. 146.
    M. Wigier, R. Sweet, G.K. Sim, B. Wold, A. Pellicer, E. Lacy, T. Maniatis, S. Silverstein and R. Axel, Transformation of mammalian cells with genes from procaryotes and eucaryotes, Cell 16:777–785 (1979).Google Scholar
  147. 147.
    L.H. Graf, Jr., G. Urlaub and L.A. Chasin, Transformation of the gene hypoxanthine phosphoribosyltransferase, Somat. Cell Genet. 5:1031–1044 (1979).Google Scholar
  148. 148.
    K. Willecke, M. Klomfass, R. Mierau and J. Dohmer, Intra-species transer via total cellular DNA of the gene for hypoxanthine phosphoribosyltransferase into cultured mouse cells, Mol. Gen. Genetics 179:179–185 (1979).Google Scholar
  149. 149.
    S.C. Lester, S.K. LeVan, C. Steglich and R. DeMars, Expression of human genes for adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase after genetic transformation of mouse cells with purified human DNA, Somat. Cell Genet. 6:241–259 (1980).PubMedGoogle Scholar
  150. 150.
    J.L. Peterson and O.W. McBride, Cotransfer of linked eukaryotic genes and efficient transfer of hypoxanthine phosphoribosyltransferase by DNA-mediated gene transfer, Proc. Natl. Acad. Sci. USA 77:1583–1587 (1980).PubMedGoogle Scholar
  151. 151.
    R.M. Liskay and R.J. Evans, Inactive X chromosome DNA does not function in DNA-mediated cell transformation for the hypoxanthine phosphoribosyltransferase gene, Proc. Natl. Acad. Sci. USA 77:4895–4898 (1980).PubMedGoogle Scholar
  152. 152.
    L.A. Chasin and G. Urlaub, Mutant alleles for hypoxanthine phosphoribosyl transferase: Codominant expression, complementation and segregation in hybrid Chinese hamster cells, Somat. Cell Genet. 2:453–467 (1976).Google Scholar
  153. 153.
    S.A. Farrell and R.G. Worton, Chromosome loss is responsible for segregation at the HPRT locus in Chinese hamster cell hybrids, Somat. Cell Genet. 3:539–551 (1977).Google Scholar
  154. 154.
    V. Ling, Drug resistance and membrane alteration in mutants of mammalian cells, Can. J. Genetics and Cytology 17:503–515 (1975).Google Scholar
  155. 155.
    R.L. Juliano and V. Link, A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants, Biochim. Biophys. Acta 455:152–162 (1976).PubMedGoogle Scholar
  156. 156.
    R.L. Juliano, J. Graves and V. Link, Drug-resistant mutants of Chinese hamster ovary cells possess an altered cell surface carbohydrate component, J. Supramolec. Struct. 4:521–526 (1976).Google Scholar
  157. 157.
    I.L. Andrulis and L. Siminovitch, DNA-mediated gene transfer of β-aspartylhydroxamate resistance into Chinese hamster ovary cells, Proc. Natl. Acad. Sci. USA 78:5724–5728 (1981).PubMedGoogle Scholar
  158. 158.
    I.L. Andrulis and L. Siminovitch, Isolation and characterization of CHO cells resistant to the amino acid analogue β-aspartyl hydroxamate (in preparation).Google Scholar
  159. 159.
    J. Choi and I.E. Scheffler, A mutant of Chinese hamster ovary cells resistant to α-methyl and or-difluoromethylornithine Somat. Cell Genet. 7:219–233 (1981).Google Scholar
  160. 160.
    M. Debatisse, M. Berry and G. Buttin, The potentiation of adenine toxicity to Chinese hamster cells by coformycin: suppression in mutants with altered regulation of purine biosynthesis or increased adenylate-deaminase activity, J. Cell Physiol. 106:1–11 (1981).PubMedGoogle Scholar
  161. 161.
    M. Sinensky, Isolation of a mammalian cell mutant resistant to 25-hydroxy cholesterol, Biochem. and Biophys. Res. Commun. 78:863–867 (1977).Google Scholar
  162. 162.
    W.J. Rigby, B.D. Burleigh, Jr. and B.S. Hartley, Gene duplication in experimental enzyme evolution, Nature 251:200–204 (1974).PubMedGoogle Scholar
  163. 163.
    J.A. Wright, Pleiotrophic changes in lines of Chinese hamster ovary cells resistant to concanavalin and phytohaemagglutinin, J. Cell Biol. 56:666–675 (1972).Google Scholar
  164. 164.
    C. Gottlieb, A.M. Skinner and S. Kornfeld, Isolation of a clone of Chinese hamster ovary cells deficient in plant lectin-binding sites, Proc. Natl. Acad. Sci. USA 72:1078–1082 (1974).Google Scholar
  165. 165.
    C. Gottlieb, J. Baenziger and S. Kornfeld, Deficient uridine diphosphate-N-acetylglucosamine: Glycoprotein N-acetyl-glycosaminyl-transferase activity in a clone of Chinese hamster ovary cells with altered surface glycoproteins, J. Biol. Chem. 250:3303–3309 (1975).PubMedGoogle Scholar
  166. 166.
    R.L. Juliano and P. Stanley, Altered cell surface glycoproteins phytohemagglutinin-resistant mutants of Chinese hamster ovary cells, Biochim. Biophys. Acta 389:401–406 (1975).PubMedGoogle Scholar
  167. 167.
    P. Stanley, V. Caillibot and L. Siminovitch, Stable alterations at the cell membrane of Chinese hamster ovary cells resistant to the cytotoxicity of phytohemagglutinin, Somat. Cell Genet. 1:3–26 (1975).PubMedGoogle Scholar
  168. 168.
    P. Stanley, V. Caillibot and L. Siminovitch, Selection and characterization of eight phenotypically-distinct lines of lectin-resistant Chinese hamster ovary cells, Cell 6:121–128 (1975).PubMedGoogle Scholar
  169. 169.
    P. Stanely, S. Narasimhan, L. Siminovitch and H. Schachter, Chinese hamster ovary cells selected for resistance to the cytotoxicity of phytohemagglutinin are deficient in a UBP-N-acetyl-glucosamine-glycoprotein-N-acetyl-glucosaminyl-transferase activity, Proc. Natl. Acad. Sci. USA 72:3323–3327 (1975).Google Scholar
  170. 170.
    P. Stanley and L. Siminovitch, Complementation between mutants of CHO cells resistant to a variety of plant lectins, Somat. Cell Genet. 3:391–405 (1977).PubMedGoogle Scholar
  171. 171.
    S.S. Krag, M. Cifone, P.W. Robbins and R.M. Baker, Reduced synthesis of [14C] mannosyl oligosaccharide-lipid by membranes prepared from concanavalin A-resistant Chinese hamster ovary cells, J. Biol. Chem. 252:3561–3564 (1977).PubMedGoogle Scholar
  172. 172.
    E.G. Briles, E. Li and S. Kornfeld, Isolation of wheat-germ agglutinin-resistant clones of CHO cells deficient in membrane sialic acid and galactose, J. Biol. Chem. 252:1107–1116 (1977).PubMedGoogle Scholar
  173. 173.
    P. Stanley, Surface carbohydrate alterations of mutant mammalian cells selected for resistance to plant lectins, in “Biochemistry of Glycoproteins and Proteoglycans,” W.J. Lennarz, ed., Plenum Publishing Corporation, pp. 161–189 (1980).Google Scholar
  174. 174.
    T. Sudo and K. Onodera, Isolation and characterization of Tunicamycin resistant mutants from Chinese hamster ovary cells, J. Cell Physiol. 101:149–156 (1979).PubMedGoogle Scholar
  175. 175.
    M. Taub and E. Englesberg, Isolation and characterization of 5-fluorotryptophan-resistant mutants with altered L-tryptophan transport, Somat. Cell Genet. 2:441–452 (1976).PubMedGoogle Scholar
  176. 176.
    M. Taub and E. Englesberg, 5-Fluorotryptophan resistant mutants affecting the A and L transport system in the mouse L cell line A9, J. Cell Physio. 97:477–486 (1978).Google Scholar
  177. 177.
    E. Gnglesberg, R. Bass and W. Heiser, Inhibition of the growth of mammalian cells in culture by amino acids and the isolation and characterization of L-phenylalanine-resistant mutants modifying L-phenylalanine transport, Somat. Cell Genet. 2:411–428 (1976).Google Scholar
  178. 178.
    M.C. Finkelstein, C.W. Slayman and E.A. Adelberg, Tritium suicide selection of mammalian cell mutants defective in the transport of neutral amino acids, Proc. Natl. Acad. Sci. USA 74:4549–4551 (1977).PubMedGoogle Scholar
  179. 179.
    C.E. Campbell, R.A. Gravel and R.G. Worton, Isolation and characterization of Chinese hamster cell mutants resistant to the cytotoxic effects of Chromate, Somat. Cell Genet. 7:535–546 (1981).PubMedGoogle Scholar
  180. 180.
    J. Mandel and W.I. Flintoff, Isolation of mutant mammalian cells altered in polyamine transport, J. Cell Physiol. 97:335–344 (1978).PubMedGoogle Scholar
  181. 181.
    V. Ling and L.H. Thompson, Reduced permeability in CHO cells as a mechanism of resistance to colchicine, J. Cell Physiol. 83:103–116 (1974).PubMedGoogle Scholar
  182. 182.
    N.T. Bech-Hansen, J.E. Till and V. Ling, Pleiotropic phenotype of colchicine-resistant CHO cells: Cross-resistance and collateral sensitivity, Jr. Cell Physiol. 88:23–39 (1976).Google Scholar
  183. 183.
    V. Ling and R.M. Baker, Dominance of colchicine resistance in hybrid CHO cells, Somat. Cell Genet. 6:193–200 (1978).Google Scholar
  184. 184.
    R.M. Baker, D.M. Brunette, R. Mankovitz, L.H. Thompson, G.F. Whitmore, L. Siminovitch and J.E. Till, Ouabain resistant mutants of mouse and hamster cells in culture, Cell 1:9–21 (1974).Google Scholar
  185. 185.
    C.H. Sibley and G.M. Tomkins, Isolation of lymphoma cell variant resistant to killing by glucocorticoids, Cell 2:213–220 (1974).PubMedGoogle Scholar
  186. 186.
    C.H. Sibley and G.M. Tomkins, Mechanisms of steroid resistance, Cell 2:221–227 (1974).PubMedGoogle Scholar
  187. 187.
    S. Bourgeois and R.F. Newby, Genetic analysis of glucocorticoid action on lymphoid cell lines, in “Hormones and Cancer,” S. Iacobelli et al., eds., Raven Press, New York, pp. 67–77 (1980).Google Scholar
  188. 188.
    T.J. Moehring and J.M. Moehring, Selection and characterization of cells resistant to diphtheria toxin and Pseudomonas exotoxin A: Presumptive translational mutants, Cell 11:447–454 (1977).PubMedGoogle Scholar
  189. 189.
    D. Pious, P. Hawley and G. Forrest, Isolation and characterization of HL-A variants in cultured human lymphoid cells, Proc. Natl. Acad. Sci. USA 70:1397–1400 (1973).PubMedGoogle Scholar
  190. 190.
    J.W. Dennis and R.S. Kerbel, Characterization of a deficiency in fucose metabolism in lectin-resistant variants of a murine tumor showing altered tumorigenic and metastatic capacities in vivo, Cancer Research 41:98–104 (1981).PubMedGoogle Scholar
  191. 191.
    J.W. Dennis, T.P. Donaghue and R.S. Kerbel, Membrane-associated alterations detected in poorly tumorigenic lectin-resistant variant sublines of a highly malignant and metastatic murine tumor, J. Natl. Cancer Inst. 66:129–139 (1981).PubMedGoogle Scholar
  192. 192.
    J. Dennis, T. Donaghue, M. Florian and R.S. Kerbel, Reversion of stable in vitro genetic markers detected in tumor cells from spontaneous metastases, Nature 292:242–245 (1981).PubMedGoogle Scholar
  193. 193.
    R.S. Gupta and L. Siminovitch, Isolation and preliminary characterization of mutants of CHO cells resistant to the protein synthesis inhibitor emetine, Cell 9:213–219 (1976).PubMedGoogle Scholar
  194. 194.
    R.S. Gupta and L. Siminovitch, The molecular basis of emetine resistance in Chinese hamster ovary cells: Alteration in the 40S subunit, Cell 10:61–66 (1977).PubMedGoogle Scholar
  195. 195.
    R.S. Gupta and L. Siminovitch, Mutants of CHO cells resistant to the protein synthesis inhibitors cryptopleurine and tylocrebrine: Genetic and biochemical evidence for common site of action of emetine, cryptopleurine, tylocrebrine and tubulosine, Biochem. 16:3209–3214 (1977).Google Scholar
  196. 196.
    R.S. Gupta and L. Siminovitch, Mutants of CHO cell resistant to the protein synthesis inhibitor emetine: Genetic and biochemical characterization of second step mutants, Somat. Cell Genet. 4:77–94 (1978).Google Scholar
  197. 197.
    R.S. Gupta and L. Siminovitch, An in vitro analysis of the dominance of emetine sensitivity in CHO cell hybrids, J. Biol. Chem. 253:3978–3982 (1978).PubMedGoogle Scholar
  198. 198.
    J.J. Wasmuth, J.M. Hill and L.S. Vock, Biochemical and genetic evidence for a new class of emetine-resistant Chinese hamster cells with alterations in the protein biosynthetic machinery, Somat. Cell Genet. 6:495–516 (1980).Google Scholar
  199. 199.
    R.S. Gupta and L. Siminovitch, Genetic and biochemical characterization of mutants of CHO cells resistant to the protein synthesis inhibitor trichodermin, Somat. Cell Genet. 4:355–375 (1978).PubMedGoogle Scholar
  200. 200.
    R.S. Gupta and L. Siminovitch, Diphtheria toxin resistant mutants of CHO cells defective in protein synthesis: A novel phenotype, Somat. Cell Genet. 4:553–571 (1978).PubMedGoogle Scholar
  201. 201.
    J.M. Moehring and T.J. Moehring, Characterization of the diphtheria toxin-resistance system in Chinese hamster ovary cells, Somat. Cell Genet. 5:453–468 (1979).PubMedGoogle Scholar
  202. 202.
    R.S. Gupta and L. Siminovitch, Diphtheria toxin resistance in Chinese hamster cells: Genetic and biochemical characteristics of the mutants affected in protein synthesis, Somat. Cell Genet. 6:361–379 (1980).Google Scholar
  203. 203.
    V. Chan, F.G. Whitmore and L. Siminovitch, Mammalian cells with altered forms of RNA polymerase II, Proc. Natl. Acad. Sci. USA 69:3119–3123 (1972).PubMedGoogle Scholar
  204. 204.
    P.E. Lobban and L. Siminovitch, α-Amanitin resistance: A dominant mutation in CHO cells, Cell 4:167–172 (1975).PubMedGoogle Scholar
  205. 205.
    P.E. Lobban and L. Siminovitch, The RNA polymerase II of an α-amanitin-resistant Chinese hamster ovary cell line, Cell 8:65–70 (1976).PubMedGoogle Scholar
  206. 206.
    C.J. Ingles, A. Guialis, J. Lam and L. Siminovitch, α-amanitin-resistance of RNA polymerase II in mutant Chinese hamster ovary cell lines, J. Biol. Chem. 251:2729–2734 (1976).PubMedGoogle Scholar
  207. 207.
    C.J. Ingles, M.L. Pearson, M. Buchwald, B.C. Beatty, M.M. Crerar, A. Guialis, P.E. Lobban, L. Siminovitch and D.C. Somers, α-Amanitin-resistant mutants of mammalian cells and the regulation of RNA polymerase II activity, in “RNA Polymerase,” M. Chamberlin and R. Losick, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., pp. 835–853 (1976).Google Scholar
  208. 208.
    R.S. Gupta, D.H.Y. Chan and L. Siminovitch, Evidence for variation in the number of functional gene copies at the AmaR locus in Chinese hamster cell lines, J. Cell Physiol. 97:461–468 (1978).PubMedGoogle Scholar
  209. 209.
    R.S. Gupta and L. Siminovitch, Pactamycin resistance in CHO cells: Morphological changes induced by the drug in wild type and mutant cells, J. Cell Physiol. 102:305–316 (1980).PubMedGoogle Scholar
  210. 210.
    R.S. Gupta, Diphtheria toxin resistance in human lymphoblast lines, Biochem. and Biophys. Res. Commun. 94:1303–1310 (1980).Google Scholar
  211. 211.
    R.S. Gupta and S. Goldstein, Diphtheria toxin resistance in human fibroblast cell strains from normal and cancer-prone individuals, Mutation Res. 73:331–338 (1980).PubMedGoogle Scholar
  212. 212.
    L.B. Jacoby, Canavine-resistant variants of human lymphoblasts, Somat. Cell Genet. 4:221–231 (1978).PubMedGoogle Scholar
  213. 213.
    S.J. Mento and L. Siminovitch, Isolation and preliminary characterization of sindbis virus-resistant Chinese hamster ovary cells, Virology (in press) (1981).Google Scholar
  214. 214.
    P. Coffino, H.R. Bourne, P.A. Insel, K.L. Melmon, G. Johnson and J. Vigne, Studies of cyclic AMP action using mutant tissue culture cells, InVitro 14:140–145 (1978).Google Scholar
  215. 215.
    T. Haga, E.M. Ross, H.J. Anderson and H.G. Gilman, Adenylate-cyclase uncoupled permanently from hormone receptors in a novel variant of S49 mouse lymphoma cells, Proc. Natl. Acad. Sci. USA 74:2016–2020 (1977).PubMedGoogle Scholar
  216. 216.
    H. Bourne, P. Coffino and G.M. Tomkins, Selection of a variant lymphoma cell deficient in adenylate cyclase, Science 187:750–751 (1975).PubMedGoogle Scholar
  217. 217.
    M.P. Shear, P. Insel, K. Mehnen and P. Coffino, Agonist specific refractoriness induced by isoproterenol, J. Biol. Chem. 251:7572–7576 (1976).PubMedGoogle Scholar
  218. 218.
    P.A. Insel, H.R. Bourne, P. Coffino and G.M. Tomkins, Cyclic AMP-dependent protein kinase-pivotal role in regulation of enzyme-induction and growth, Science 190:896–898 (1975).PubMedGoogle Scholar
  219. 219.
    J. Hochman, P.A. Insel, H.R. Bourne, P. Coffino and G.M. Tomkins, Structural gene mutations affecting regulatory sub-unit of cyclic AMP-dependent protein kinase in mouse lymphoma-cells, Proc. Natl. Acad. Sci. USA 72:5051–5055 (1976).Google Scholar
  220. 220.
    V. Friedrich and P. Coffino, Mutagenesis in S49 mouse lymphoma cells: induction of resistance to ouabain, 6-thioguanine, and dibutyl cyclic AMP, Proc. Natl. Acad. Sci. USA 74:679–683 (1977).PubMedGoogle Scholar
  221. 221.
    R.A. Steinberg, T. van Daalen Wetters and P. Coffino, Kinase negative mutants of S49 mouse lymphoma cells carrying a trans-dominant mutation affecting expression of cAMP-dependent protein kinase, Cell 15:1351–1361 (1978).PubMedGoogle Scholar
  222. 222.
    M.M. Gottesman, A. LeCam, M. Bukowski and I. Pastan, Isolation of multiple classes of mutants of CHO cells resistant to cyclic AMP, Somat. Cell Genet. 6:45–61 (1980).Google Scholar
  223. 223.
    I. Lemaire and P. Coffino, Cyclic AMP-induced cytolysis in S49 cells: Selection of an unresponsive deathless mutant, Cell 2:149–155 (1977).Google Scholar
  224. 224.
    V. Link, J.E. Aubin, A. Chan and F. Sarangi, Mutants of Chinese hamster ovary (CHO) cells with altered colcemid-binding affinity, Cell 18:423–430 (1979).Google Scholar
  225. 225.
    F. Cabrai, M.E. Sobel and M.M. Gottesman, CHO mutants resistant to colchicine, colcemid or griseofulvin have an altered β-tubulin, Cell 20:29–36 (1980).Google Scholar
  226. 226.
    R.A.B. Keates, F. Sarangi and V. Link, Structural and functional alterations in microtubule protein from Chinese hamster ovary cell mutants, Proc. Natl. Acad. Sci. USA 78:5638–5642 (1981).PubMedGoogle Scholar
  227. 227.
    A.E. Lagarde and L. Siminovitch, Studies on Chinese hamster ovary mutants showing multiple cross-resistance to oxidative phosphorylation inhibitors, Somat. Cell Genet. 5:84.7–871 (1979).Google Scholar
  228. 228.
    R.B. Wallace and K.B. Freeman, Selection of mammalian cells resistant to a chloramphenicol analog, J. Cell Biol. 65:492–498 (1975).PubMedGoogle Scholar
  229. 229.
    T. Lichtor and G.S. Getz, Cytoplasmic inheritance of rutamycin resistance in mouse fibroblasts, Proc. Natl. Acad. Sci. USA 75:324–328 (1978).PubMedGoogle Scholar
  230. 230.
    A. Wiseman and G. Attardi, Cytoplasmically inherited mutations of a human cell line resulting in deficient mitochondrial protein synthesis, Somat. Cell Genet. 5:241–262 (1979).PubMedGoogle Scholar
  231. 231.
    M. Harris, Cytoplasmic transfer of resistance to antimycin A in Chinese hamster cells, Proc. Natl. Acad. Sci. USA 75:5604–5608 (1978).PubMedGoogle Scholar
  232. 232.
    M. Rosenstraus and L.A. Chasin, Isolation of mammalian cell mutants deficient in glucose-6-phosphate dehydrogenase activity: Linkage to hypoxanthine phosphoribosyl transferase, Proc. Natl. Acad. Sci. USA 72:493–497 (1975).PubMedGoogle Scholar
  233. 233.
    A.R. Robbins, Isolation of lysosomal α-mannosidase mutants of Chinese hamster ovary cells, Proc. Natl. Acad. Sci. USA 76:1911–1915 (1979).PubMedGoogle Scholar
  234. 234.
    T.D. Stamato and D. Patterson, Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells. II. Isolation and characterization of a mutant of Chinese hamster ovary cells with defective dihydroorotate dehydrogenase (E.C . 1.3.3 .1) activity, J. Cell Physiol. 98:459–468 (1979).PubMedGoogle Scholar
  235. 235.
    J.D. Esko and C.R.H. Raetz, Replica plating and in situ enzymatic assay of animal cell colonies established on filter paper, Proc. Natl. Acad. Sci. USA 75:1190–1193 (1978).PubMedGoogle Scholar
  236. 236.
    J.D. Esko and C.R.H. Raetz, Autoradiographic detection of animal cell membrane mutants altered in phosphatidylcholine synthesis, Proc. Natl. Acad. Sci. USA 77:5192–5196 (1980).PubMedGoogle Scholar
  237. 237.
    T.D. Stamato and C.A. Waldren, Isolation of UV-sensitive variants of CHO-K1 by nylon cloth replica plating, Somat. Cell Genet. 3:431–440 (1977).PubMedGoogle Scholar
  238. 238.
    L.H. Thompson, J.S. Rubin, J.E. Cleaver, G.F. Whitmore and K. Brookman, A screening method for isolating DNA repair-deficient mutants of CHO cells, Somat. Cell Genet. 6:391–405 (1980).PubMedGoogle Scholar
  239. 239.
    D.B. Busch, J.E. Cleaver and D.A. Glaser, Large-scale isolation of UV-sensitive clones of CHO cells, Somat. Cell Genet. 6:407–418 (1980).PubMedGoogle Scholar
  240. 240.
    L. Siminovitch, On the nature of hereditable variation in cultured somatic cells, Cell 7:1–11 (1976).PubMedGoogle Scholar
  241. 241.
    R.S. Gupta, D.Y.H. Chan and L. Siminovitch, Evidence for functional hemizygosity at the Emt locus in CHO cells through segregation analysis, Cell 14:1007–1013 (1978).PubMedGoogle Scholar
  242. 242.
    E.M. Eves and R.A. Farber, Chromosome segregation is frequently associated with the expression of recessive mutations in mouse cells, Proc. Natl. Acad. Sci. USA 78:1768–1772 (1981).PubMedGoogle Scholar
  243. 243.
    C.H. Corsaro and M.L. Pearson, Competence for DNA transfer of ouabain resistance and thymidine kinase: Clonal variation in mouse L-cell recipients, Somat. Cell Genet. 7:617–630 (1981).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Peter N. Ray
    • 1
  • Louis Siminovitch
    • 1
  1. 1.Department of GeneticsHospital for Sick ChildrenTorontoCanada

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