Senescence pp 39-55 | Cite as

Comments about the Paper by Norwood et al. and an Idea Relating Somatic Cell Mutations to Cellular Senescence

  • Robert DeMars
Part of the Cellular Senescence and Somatic Cell Genetics book series (CSSCG, volume 2)


Cells, nuclei and cytoplasms from young, senescent and permanent line populations of human cells can be usefully combined as pairs in 30 different ways. Dr. Norwood, with his collaborators at Seattle, and others, have been attempting to create these combinations in order to answer three main questions: (i) Is the senescence phenotype dominant?; (ii) Can the senescence phenotype be imposed and maintained by the cytoplasm of a senescent cell or must the nucleus be present, too?; (iii) Is the senescence phenotype determined by primary, stable nuclear changes? Some of the possible combinations of cells and parts of cells have not been studied yet and the interpretation of the observations made so far must be tentative. Therefore, my main comments about Dr. Norwood’s presentation are an expression of admiration for what has been accomplished and a hope that the good work will continue.


Human Fibroblast Cellular Senescence Population Doubling Diploid Human Fibroblast Senescence Phenotype 
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  1. 1.
    Wright, W.E. and L. Hayflick. The regulation of cellular aging by nuclear events in cultured normal human fibroblasts (WI-38). Adv. Exp. Med. Biol. 61 (1975) 39–55.PubMedGoogle Scholar
  2. 2.
    Orgel, L.E. Ageing of clones of mammalian cells. Nature 243 (1973) 441–445.PubMedCrossRefGoogle Scholar
  3. 3.
    DeMars, R. and K. R. Held. The spontaneous azaguanineresistant mutants of diploid human fibroblasts. Humangenetik 16 (1972) 87–110.PubMedCrossRefGoogle Scholar
  4. 4.
    Rappaport, H. and R. DeMars. Diaminopurine-resistant mutants of cultured diploid human fibroblasts. Genetics 75 (1973) 335–345.PubMedGoogle Scholar
  5. 5.
    DeMars, R. Resistance of cultured human fibroblasts and other cells to purine and pyrimidine analogues in relation to mutagenesis detection. Mutation Res. 24 (1974) 335–364.PubMedCrossRefGoogle Scholar
  6. 6.
    Buchwald, M. and C.J. Ingles. Human diploid fibroblast mutants with altered RNA polymerase II. Somatic Cell Genet. 2 (1976) 225–233.PubMedCrossRefGoogle Scholar
  7. 7.
    Mankowitz, R., M. Buchwald and R. M. Baker. Isolation of ouabain-resistant human diploid fibroblasts. Cell 3 (1974) 221–226.CrossRefGoogle Scholar
  8. 8.
    Baker, R.M., et al. Ouabain-resistant mutants of mouse and hamster cells in culture. Cell 1 (1974) 9–21.CrossRefGoogle Scholar
  9. 9.
    Friedrich, U. and P. Coffino. Mutagenesis in S49 mouse lymphoma cells: induction of resistance to ouabain, 6-thioguanine and dibutyryl cyclic AMP. Proc. Nat. Acad. Sci. 74 (1977) 679–683.PubMedCrossRefGoogle Scholar
  10. 10.
    Chang, C.C., J.E. Trosko, and T. Akera. Characterization of UV-induced ouabain-resistant mutants in Chinese hamster cells. Submitted for publication in Mutation Research (1977).Google Scholar
  11. 11.
    Tartof, K.D. Redundant genes. Ann. Rev. Genet. 9 (1975) 355–385.PubMedCrossRefGoogle Scholar
  12. 12.
    Smith, J. R. and L. Hayflick. Variation in the life-span of clones derived from human diploid cell strains. J. Cell Blol. 62 (1974) 48–53.CrossRefGoogle Scholar
  13. 13.
    Medvedev, A. Z. Repetition of molecular-genetic information as a possible factor in evolutionary changes of life span. Exp. Gerontol. 7 (1972) 227–238.PubMedCrossRefGoogle Scholar
  14. 14.
    Cutler, R. G. Redundancy of information content in the genome of mammalian species as a protective mechanism determining aging rate. Mech. Aging and Develop. 2 (1973/1974) 381–408.CrossRefGoogle Scholar
  15. 15.
    Holliday, R. Growth and death of diploid and transformed human fibroblasts. Federation Proc. 34 (1975) 51–55.Google Scholar
  16. 16.
    Comfort, A, Aging, The Biology of Senescence. (Holt, Rinehart and Winston, New York, Publishers) (1964).Google Scholar
  17. 17.
    Hayflick, L. Biology of human aging. Am. J. Med. Sci. 265 (1973) 433–445.CrossRefGoogle Scholar
  18. 18.
    Holland, J.J., D. Kohne, and M. V. Doyle. Analysis of virus replication in ageing human fibroblast cultures. Nature 245 (1973) 316–318.PubMedCrossRefGoogle Scholar
  19. 19.
    Tompkins, G.A., E. J. Stanbridge and L. Hayflick. Viral probes of aging in the human diploid cell strain Wi-38. Proc. Soc. Exp. Blol. Med. 146 (1974) 385–390.Google Scholar
  20. 20.
    Pitha, J., E. Stark and E. Wimmer. Protein synthesis during aging of human cells in culture. Exptl. Cell Res. 94 (1975) 310–314.PubMedCrossRefGoogle Scholar
  21. 21.
    Stark, R.M. and J.W. Littlefield. Mutagenic effect of BUdr in diploid human fibroblasts. Mutation Res. 22 (1974) 281–286.PubMedCrossRefGoogle Scholar
  22. 22.
    Albertini, R.J. and R. DeMars. Somatic cell mutation: detection and quantification of X-ray-induced mutation in cultured, diploid human fibroblasts. Mutation Res. 18 (1973) 199–244.PubMedCrossRefGoogle Scholar
  23. 23.
    Thacker, J. and R. Cox. Mutation induction and inactivation in mammalian cells exposed to ionising radiation. Nature 258 (1975) 429–431.PubMedCrossRefGoogle Scholar
  24. 24.
    Cristofalo, V.J. Hydrocortisone as a modulator of cell division and population life span. Adv. Exp. Med. Biol. 61 (1975) 57–79.PubMedGoogle Scholar
  25. 25.
    Jacobs, L. and R. DeMars. Quantification of chemical mutagenesis in diploid human fibroblasts: induction of azaguanineresistant mutants by N-methyl-N′-nitro-N-nitrosoguanidine. Mutat. Res., in press (1977).Google Scholar
  26. 26.
    Hoehn, H., E.M. Bryant, P. Johnston, T. H. Norwood, and G.M. Martin. Non-selective isolation, stability and longevity of hybrids between normal human somatic cells. Nature 258 (1975) 608–610.PubMedCrossRefGoogle Scholar
  27. 27.
    McBride, O.W. and H.L. Ozer. Transfer of genetic information by purified metaphase chromosomes. Proc. Nat. Acad. Sci. USA 70 (1973) 1258–1262.PubMedCrossRefGoogle Scholar
  28. 28.
    Willecki, K. and Ruddle, F.H. Transfer of the human gene for hypoxanthine-guanine phosphoribosyltransferase via isolated human metaphase chromosomes in mouse L,-cells. Proc. Nat. Acad. Sci. USA 72 (1975) 1792–1796.CrossRefGoogle Scholar
  29. 29.
    Willecke, K., R. Lange, A. Kruger, and T. Reber. Cotransfer of two linked human genes into cultured mouse cells. Proc. Nat. Acad. Sci. USA 73 (1976) 1274–1278.PubMedCrossRefGoogle Scholar
  30. 30.
    Ege, T. and N.R. Ringertz. Preparation of micro cells by enucleation of micronucleate cells. Exptl. Cell Res. 87 (1974) 378–382.PubMedCrossRefGoogle Scholar
  31. 31.
    Schor, S.L., R. T. Johnson, and A.M. Mullinger, Perturbation of mammalian cell division. II. Studies on the isolation and characterization of human minisegregant cells. J. Cell Sci. 19 (1975) 281–303.PubMedGoogle Scholar
  32. 32.
    Fournier, R.E.K. and F.H. Ruddle. Microcell-mediated transfer of murine chromosomes into mouse, Chinese hamster, and human somatic cells. Proc. Nat. Acad. Sci. USA 74 (1977) 319–323.PubMedCrossRefGoogle Scholar
  33. 33.
    Hart, R.W. Role of DNA repair in cell aging. In “Aging, Carcinogenesis and Radiation Biology”. Editor, K.C. Smith, Plenum Press, New York (1976).Google Scholar
  34. 34.
    Reznikoff, C.A., J.S. Bertram, D.W. Brankow and C. Heidelberger. Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res. 33 (1973) 3239–3249.PubMedGoogle Scholar
  35. 35.
    Di Paolo, J.A., P.J. Donovan, and R.L. Nelson. Transformation of hamster cells in vitro by polycyclic hydrocarbons without cytotoxicity. Proc. Nat. Acad. Sci. USA 68 (1971) 2958–2961.CrossRefGoogle Scholar
  36. 36.
    Huberman, E. and Sachs, L. Cell susceptibility to transformation and cytotoxicity by the carcinogenic hydrocarbon benzo (A) pyrene. Proc. Nat. Acad. Sci. USA 56 (1966) 1123–1129.PubMedCrossRefGoogle Scholar
  37. 37.
    DeMars, R. and J. L. Jackson. Mutagenicity testing with human cells. J. Environ. Pathol. Toxicol., in press (1977).Google Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Robert DeMars
    • 1
  1. 1.Laboratory of GeneticsUniversity of WisconsinMadisonUSA

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