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Characterization of dominant hamster cell mutants resistant to oxygenated sterols

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Somatic Cell Genetics

Abstract

Stable mutants of Dede and CHO cells, resistant to suppression of cholesterogenesis by oxygenated sterols, have been isolated in a single step. Luria-Delbrück fluctuation analysis indicated a random occurrence of resistance at a rate of 1×10 −7 mutations/cell/generation. Cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and growth of the mutant cells were coordinately resistant to oxygenated sterols in the culture medium, and this resistance was expressed as a dominant traint in somatic cell hybrids of the wild-type and mutant cells. The dominant resistance was employed in the selection of various cell hybrids. There was complete additivity of reductase activities in mixed lysates of inhibited wild-type and uninhibited mutant cells, indicating that cytosolic (in)activation factors were not causative of this resistance. We suggest that oxygenated sterols are (co)repressors in suppression of the synthesis of the reductase and that the resistance mutant phenotypes result from altered regulatory loci.

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Literature cited

  1. Rodwell, V.W., McNamara, D.J., and Shapiro, D.J. (1973).Adv. Enzymol. Relat. Areas Mol. Biol. 38:373–412.

    Google Scholar 

  2. Kandutsch, A.A., and Saucier, S.E. (1969).Arch Biochem. Biophys. 135:201–208.

    PubMed  Google Scholar 

  3. Kandutsch, A.A., Heiniger, H.J., and Chen, H.W. (1977).Biochim. Biophys. Acta 486:260–272.

    PubMed  Google Scholar 

  4. Gaylor, J.L. (1963).Arch. Biochem. Biophys. 101:108–119.

    PubMed  Google Scholar 

  5. Chen, H.W., and Heiniger, H.J. (1974).Cancer Res. 34:1034–1307.

    Google Scholar 

  6. Chen, H.W., Kandutsch, A.A., Heiniger, H.J., and Meier, H. (1973).Cancer Res. 33:2774–2778.

    PubMed  Google Scholar 

  7. Siperstein, M.D., Gyde, A.M., and Morris, H.P. (1971).Proc. Natl. Acad. Sci. U.S.A. 68:315–317.

    PubMed  Google Scholar 

  8. Avigan, J., Williams, C.D., and Blass, J.P. (1970).Biochim. Biophys. Acta 218:381–384.

    Google Scholar 

  9. Brown, M.S., and Goldstein, J.L. (1974).J. Biol. Chem. 249:7306–7314.

    PubMed  Google Scholar 

  10. Kandutsch, A.A., and Chen, H.W. (1973).J. Biol. Chem. 248:8408–8417.

    PubMed  Google Scholar 

  11. Kandutsch, A.A., and Chen, H.W. (1974).J. Biol. Chem. 249:6057–6061.

    PubMed  Google Scholar 

  12. Erikson, S.K., Matsui, S.M., Shrewsbury, M.A., Cooper, A.D., and Gould, R.G. (1978).J. Biol. Chem. 253:4159–4164.

    PubMed  Google Scholar 

  13. Bell, J.J., Sargeant, T.E., and Watson, J.A. (1976).J. Biol. Chem. 251:1745–1758.

    PubMed  Google Scholar 

  14. Breslow, J.L., Lothrop, D.A., Spaulding, D.R. and Kandutsch, A.A. (1975).Biochim. Biophys. Acta 398:10–17.

    PubMed  Google Scholar 

  15. Gibbons, G.F., Pullinger, C.R., Chen, H.W., Cavenee, W.K., and Kandutsch, A.A. (1980).J. Biol. Chem. 255:395–400.

    PubMed  Google Scholar 

  16. Kandutsch, A.A., Chen, H.W., and Heiniger, H.J. (1978).Science 201:498–501.

    PubMed  Google Scholar 

  17. Cavenee, W.K., Gibbons, G.F., Chen, H.W., and Kandutsch, A.A. (1979).Biochim. Biophys. Acta 575:255–265.

    PubMed  Google Scholar 

  18. Chen, H.W., Cavenee, W.K., and Kandutsch, A.A. (1979).J. Biol. Chem. 254:715–720.

    PubMed  Google Scholar 

  19. Davidson, R.L., O'Malley, K.A., and Wheeler, J.B. (1976).Somat. Cell Genet. 2:271–278.

    PubMed  Google Scholar 

  20. Baker, R.M., Brunette, D.M., Mankovitz, R., Thompson, L.H., Whitmore, G.E., and Till, J.E. (1974).Cell 1:9–21.

    Google Scholar 

  21. Ling, V., and Baker, R.M. (1978).Somat. Cell Genet. 4:193–200.

    PubMed  Google Scholar 

  22. Chen, H.W., Kandutsch, A.A., and Waymouth, C. (1974).Nature 251:419–421.

    PubMed  Google Scholar 

  23. Luria, S.E., and Delbruck, M. (1943).Genetics 28:491–511.

    Google Scholar 

  24. Beg, Z.H., Stonik, J.A., and Brewer, H.B. (1978).Proc. Natl. Acad. Sci. U.S.A. 75:3678–3682.

    PubMed  Google Scholar 

  25. Gibson, D.M., and Ingebritsen, T.S. (1978).Life Sci. 23:2649–2664.

    PubMed  Google Scholar 

  26. Saucier, S.E., and Kandutsch, A.A. (1979).Biochim. Biophys. Acta 572:541–556.

    PubMed  Google Scholar 

  27. Thompson, L.H., and Baker, R.M. (1973). In (ed.), Prescott, D.Methods in Cell Biology, Vol. 7 (Academic Press, New York), pp. 209–281.

    Google Scholar 

  28. Kandutsch, A.A., Chen, H.W., and Shown, E.P. (1977).Proc. Natl. Acad. Sci. U.S.A. 74:2500–2503.

    PubMed  Google Scholar 

  29. Kandutsch, A.A., and Thompson, E.B., (1980).J. Biol. Chem. 255:10813–10826.

    PubMed  Google Scholar 

  30. Sinensky, M., and Mueller, G. (1981).Arch. Biochem. Biophys. 209:314–320.

    PubMed  Google Scholar 

  31. Alt, F.W., Kellens, R.E., Bertino, J.R., and Schimke, R.T. (1978).J. Biol. Chem. 253:1357–1370.

    PubMed  Google Scholar 

  32. Beirne, O.W., Heller, R.A., and Watson, J.A. (1977).J. Biol. Chem. 252:950–954.

    PubMed  Google Scholar 

  33. Cavenee, W.K., Chen, H.W., and Kandutsch, A.A. (1981).J. Biol. Chem. 256:2675–2681.

    PubMed  Google Scholar 

  34. Hardgrave, J.E., Heller, R.A., Herrera, M.G., and Scallen, T.J. (1979).Proc. Natl. Acad. Sci. U.S.A. 76:3834–3838.

    PubMed  Google Scholar 

  35. Higgins, M., and Rudney, H. (1976).Nature 246:60–61.

    Google Scholar 

  36. Tomkins, G.M., Geleherter, T., Granner, D., Martin, D., Samuels, H., and Thompson, E.B. (1969).Science 166:1474–1480.

    Google Scholar 

  37. Sinensky, M. (1977).Biochem. Biophys. Res. Commun. 78:863–867.

    PubMed  Google Scholar 

  38. Sinensky, M., Duwe, G., and Pinkerton, S. (1979).J. Biol. Chem. 254:4482–4486.

    PubMed  Google Scholar 

  39. Sinensky, M., Armagast, S., Mueller, G., and Torget, R. (1980).Proc. Natl. Acad. Sci. U.S.A. 77:6621–6623.

    PubMed  Google Scholar 

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Author notes

  1. Webster K. Cavenee

    Present address: Howard Hughes Medical Institute, University of Utah Medical School, 732 Wintrobe Building, 84132, Salt Lake City, Utah

  2. Raymond M. Baker

    Present address: Department of Experimental Therapeutics, Roswell Park Memorial Institute, 666 Elm St., 14263, Buffalo, New York

Authors and Affiliations

  1. Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, 02139, Cambridge, Massachusetts

    Webster K. Cavenee & Raymond M. Baker

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  1. Webster K. Cavenee
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  2. Raymond M. Baker
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Cavenee, W.K., Baker, R.M. Characterization of dominant hamster cell mutants resistant to oxygenated sterols. Somat Cell Mol Genet 8, 557–574 (1982). https://doi.org/10.1007/BF01542851

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  • DOI: https://doi.org/10.1007/BF01542851

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