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Somatic Cell and Molecular Genetics

, Volume 22, Issue 3, pp 177–189 | Cite as

Dominant genetic instability and sensitivity to DNA damaging agents in a mammalian cell line

  • Anderson J. Ryan
  • Robert T. Johnson
Article

Abstract

An SV40 transformed Indian muntjac cell line (SVM) has been shown to be hypersensitive to cell killing by a wide range of DNA damaging agents. Evidence points to defects in DNA replication and DNA recombination resulting in chromosome instability both spontaneously and following exposure to DNA damaging agents. We have generated proliferating hybrids between SVM and a spontaneously transformed Indian muntjac cell line (DM). Study of these hybrids indicates that the SVM phenotype acts in a genetically dominant manner and is associated with the expression of SV40 large T antigen. We propose that transformation and immortalization of Indian muntjac fibroblasts by SV40 virus can lead to a set of persistent changes in gene expression that result in chromosome instability and increased sensitivity to DNA damaging agents. Genes involved in these processes are likely to be of great importance as chromosome instability can play a central role in cancer development.

Keywords

Gene Expression Mammalian Cell Cell Killing Cancer Development Chromosome Instability 
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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Literature Cited

  1. 1.
    Friedberg, E.C., Walker, G.C., and Siede, W. (1995).DNA repair and mutagenesis, ASM Press, Washington, D.C.Google Scholar
  2. 2.
    Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D.A., Smith, S., Uziel, T., Sfez, S., Ashkenazi, M., Pecker, I., Frydman, M., Harnik, R., Patanjali, S.R., Simmons, A., Clines, G.A., Sartiel, A., Gatti, R.A., Chessa, L., Sanal, O., Lavin, M.F., Jaspers, N.G.J., Taylor, A.M.R., Crlett, C.F., Miki, T., Weissman, S.M., Lovett, M., Collins, F.S., and Shiloh, Y. (1995).Science 268:1749–1753.PubMedGoogle Scholar
  3. 3.
    Ellis, N.A., Groden, J., Ye, T-Z., Straughen, J., Lennon, D.J., Ciocci, S., Proytcheva, M., and German, J. (1995).Cell 83:655–666.CrossRefPubMedGoogle Scholar
  4. 4.
    Musk, S.R.R., Hatton, D.H., Bouffler, S.D., Margison, G.P., and Johnson, R.T. (1989).Carcinogenesis 10:1299–1306.PubMedGoogle Scholar
  5. 5.
    Ryan, A.J., Hall, M., Bouffler, S.D., Evans, A.E., Coates, J.A., and Johnson, R.T. (1992).Somatic Cell Mol. Genet. 18:529–541.PubMedGoogle Scholar
  6. 6.
    Pillidge, L., Downes, C.S., and Johnson, R.T. (1986).Int. J. Radiat. Biol. 50:119–136.Google Scholar
  7. 7.
    Pillidge, L., Musk, S.R.R., Johnson, R.T., and Waldren, C.A. (1986).Mutat. Res. 166:265–273.PubMedGoogle Scholar
  8. 8.
    Musk, S.R.R., Pillidge, L., Johnson, R.T., and Downes, C.S. (1990).Biochimica et Biophysica Acta 1052:53–62.PubMedGoogle Scholar
  9. 9.
    Hall, M. (1994).Ph.D. Thesis, University of Cambridge, U.K.Google Scholar
  10. 10.
    Bouffler, S.D., Godfrey, D.B., Musk, S.S.R., and Johnson, R.T. (1990).Somatic Cell Mol. Genet. 16:507–516.PubMedGoogle Scholar
  11. 11.
    Godfrey, D.B., Bouffler, S.D., Musk, S.R.R., Raman, M.J., and Johnson, R.T. (1992).Mutation Res. 274:225–235.PubMedGoogle Scholar
  12. 12.
    Southern, P.J., and Berg, P. (1982).J. Mol. Appl. Genet. 1:327–341.PubMedGoogle Scholar
  13. 13.
    Mulligan, R.C., and Berg, P. (1980).Science 209: 1422–1427.PubMedGoogle Scholar
  14. 14.
    Mulligan, R.C., and Berg, P. (1981).Proc. Natl. Acad. Sci. U.S.A. 78:2072–2076.PubMedGoogle Scholar
  15. 15.
    Feinberg, A.P. and Vogelstein, B. (1983).Anal. Biochem. 132:6–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989).MolecularCloning: A Laboratory Manual, 2nd Ed. Cold Spring Harbor, New York.Google Scholar
  17. 17.
    Rao, P.N., and Johnson, R.T. (1972). InMethods in Cell Physiology, D.M. Prescott (Ed.)5:76–126. Academic Press, London.Google Scholar
  18. 18.
    Ausubul, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., and Struhl, K. (1989).Short Protocols in Molecular Biology. John Wiley and Sons, New York.Google Scholar
  19. 19.
    Wurster, D.H., and Benirschke, K. (1970).Science 168:1364–1366.PubMedGoogle Scholar
  20. 20.
    Hadlaczky, G.Y., Went, M., and Ringertz, N.R. (1986).Exp. Cell Res. 167:1–15.CrossRefPubMedGoogle Scholar
  21. 21.
    Shulze, C. (1988).Ph.D. Thesis, The Free University of Berlin, Germany.Google Scholar
  22. 22.
    Somia, N.V. (1991).Ph.D. Thesis, University of Edinburgh, U.K.Google Scholar
  23. 23.
    Fainsod, A., Voss, R., Spann, P., Goitein, R., and Marcus, M. (1983).Cytogenet. Cell Genet. 35: 104–109.PubMedGoogle Scholar
  24. 24.
    Nichols, W.W. (1970).Ann. Rev. Microb. 24:479–500.PubMedGoogle Scholar
  25. 25.
    Sack, J.H. (1981).In Vitro 17:1–19.PubMedGoogle Scholar
  26. 26.
    Woods, C., LeFeuvre, C., Stewart, N., and Bacchetti, S. (1994).Oncogene 9:2943–2950.PubMedGoogle Scholar
  27. 27.
    Yamaguchi, N., and Huh, N. (1979).J. Gen. Virol. 42: 289–296.PubMedGoogle Scholar
  28. 28.
    Lee, J-Y., Koi, M., Stanbridge, E.J., Oshimura, M., Kumamoto, A.T., and Feinberg, A.P. (1994).Nature Genetics 7:29–33.CrossRefPubMedGoogle Scholar
  29. 29.
    Hori, T., Ayusawa, D., Shimizu, K., Koyama, H., and Seno, T. (1984).Cancer Res. 44:703–709.PubMedGoogle Scholar
  30. 30.
    Eki, T., Enomoto, T., Murakami, Y., Hanaoka, F., and Yamada, M. (1987).Cancer Res. 47:5162–5170.PubMedGoogle Scholar
  31. 31.
    Chatterjee, S., Hirschler, N.V., Petzold, S.J., Berger, S.J., and Berger, N.A. (1989).Exp. Cell Res. 184:1–15.CrossRefPubMedGoogle Scholar
  32. 32.
    Tsuji, H., Matsudo, Y., Tsuji, S., Hanaoka, F., Hyodo, M. and Hori, T. (1990).Somatic Cell Mol. Genet. 16:461–476.PubMedGoogle Scholar
  33. 33.
    Darroudi, F., and Natarajan, A.T. (1985).Mutation Res. 149:239–247.PubMedGoogle Scholar
  34. 34.
    Strathdee, C.A., Gavish, H., Shannon, W.R., and Buchwald, M. (1992).Nature 356:763–767.CrossRefPubMedGoogle Scholar
  35. 35.
    Debenham, P.G., and Webb, M.B.T. (1986).Somatic Cell Mol. Genet. 13:21–32.Google Scholar
  36. 36.
    Schreiber, V., Hunting, D., Trucco, C., Gowans, B., Grunwald, D., de Murcia, G., and de Murcia, J.M. (1995).Proc. Natl. Acad. Sci. U.S.A. 92:4753–4757.PubMedGoogle Scholar
  37. 37.
    Yarosh, D.B., Scudiero, D., Ziolkowski, C.H.J., Rhim, J.S., and Day, R.S. (1984).Carcinogenesis 5:627–633.PubMedGoogle Scholar
  38. 38.
    Fornace, A.J., Papathanasiou, M.A., Hollander, M.C., and Yarosh, D.B. (1990).Cancer Res. 50:7908–7911.PubMedGoogle Scholar
  39. 39.
    Strauss, B.S. (1990).Mutation Res. 233:139–150.PubMedGoogle Scholar
  40. 40.
    Costello, J.F., Futscher, B.W., Kroes, R.A., and Pieper, R.O. (1994).Mol. Cell. Biol. 14:6515–6521.PubMedGoogle Scholar
  41. 41.
    Von Wronski, M.A., and Brent, T.P. (1994).Carcinogenesis 15:577–582.Google Scholar
  42. 42.
    Fanning, E., and Knippers, R. (1992).Annu. Rev. Biochem. 61:55–85.CrossRefPubMedGoogle Scholar
  43. 43.
    Levitt, L.J., Boss, G.R., and Erbe, R.W. (1986).Cancer 57:764–768.PubMedGoogle Scholar
  44. 44.
    Sun, Y., Colburn, N.H., and Oberley, L.W. (1993).Carcinogenesis 14:1505–1510.PubMedGoogle Scholar
  45. 45.
    Saffer, J.D., Jackson, S.P., and Thurston, S.J. (1990).Genes Dev. 4:659–666.PubMedGoogle Scholar
  46. 46.
    Grouda, M.C., Zabolotny, J.M., Xiao, J.H., Davidson, I., and Alwine, J.C. (1993).Mol. Cell. Biol. 13: 961–969.Google Scholar
  47. 47.
    Farmer, G., Bargonetti, J., Zhu, H., Friedman, P., Prywes, R., and Prives, C. (1992).Nature 358:83–86.CrossRefPubMedGoogle Scholar
  48. 48.
    Bakalkin, G., Yakovleva, T., Selivanova, G., Magnusson, K.P., Szekely, L., Kiseleva, E., Klein, G., Terenius, L., and Wilman, K.G. (1994).Proc. Natl. Acad. Sci. U.S.A. 91:413–417.PubMedGoogle Scholar
  49. 49.
    Wang, X.W., Yeh, H., Schaeffer, L., Roy, R., Moncollin, V., Egly, J-M., Wang, Z., Friedberg, E.C., Evans, M.K., Taffe, B.G., Bohr, V.A., Weeda, G., Hoeijmakers, J.H.J., Forrester, K., and Harris, C.C. (1995).Nature Genetics 10:188–195.PubMedGoogle Scholar
  50. 50.
    Smith, M.L., Chen, I-T., Zhan, Q., O'Connor, P.M., and Fornace, A.J. (1995).Oncogene 10:1053–1059.PubMedGoogle Scholar
  51. 51.
    Ishizaki, K., Ejima, Y., Matsunaga, T., Hara, R., Sakamoto, A., Ikenaga, M., Ikawa, Y., and Aizawa, S. (1994).Int. J. Cancer 58:254–257.PubMedGoogle Scholar
  52. 52.
    Carr, A.M., Green, M.H.L., and Lehmann, A.R. (1992).Nature 359:486.CrossRefPubMedGoogle Scholar
  53. 53.
    Stacey, M., Thacker, S., and Taylor, A.M.R. (1989).Int. J. Radiat. Biol. 56:45–58.PubMedGoogle Scholar
  54. 54.
    Mezzina, M., Nocentini, S., Nardelli, J., Renault, G., Moustachi, E., and Sarasin, A. (1989).Molec. Carcinogenesis 2:179–183.Google Scholar
  55. 55.
    Bouffler, S.D., Jha, B., and Johnson, R.T. (1990).Somatic Cell Mol. Genet. 16:451–460.PubMedGoogle Scholar
  56. 56.
    Jha, B., Bouffler, S.D., Downes, C.S., and Johnson, R.T. (1991).Mutation Res. 254:13–25.PubMedGoogle Scholar
  57. 57.
    Musk, S.R.R., Downes, C.S., and Johnson, R.T. (1988).J. Cell Sci. 90:591–599.PubMedGoogle Scholar
  58. 58.
    Hartwell, L. (1992).Cell 71:543–546.CrossRefPubMedGoogle Scholar
  59. 59.
    Orth, K., Hung, J., Gazdar, A., Bowcock, A., Mathis, J.M., and Sambrook, J. (1994).Proc. Natl. Acad. Sci. U.S.A. 91:9495–9499.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Anderson J. Ryan
    • 1
  • Robert T. Johnson
    • 1
  1. 1.Cancer Research Campign Mammalian Cell DNA Repair Research Group, Department of ZoologyUniversity of CambridgeCambridgeUK

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