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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Jun;71(6):2231–2235. doi: 10.1073/pnas.71.6.2231

Dominance of the Senescent Phenotype in Heterokaryons Between Replicative and Post-Replicative Human Fibroblast-Like Cells

Thomas H Norwood 1, William R Pendergrass *, Curtis A Sprague 1, George M Martin 1
PMCID: PMC388425  PMID: 4366757

Abstract

In heterokaryons between senescent and young diploid fibroblast-like cells, dominance of the former with respect to nuclear DNA synthesis (incorporation of [3H]thymidine) was demonstrated. For identification of the respective partners, double-layer autoradiography was used after the old cells were labeled with [3H]methionine and the young cells were labeled with [14C]thymidine. Synchrony of nuclear labeling (i.e., all nuclei in a cell labeled with [3H]thymidine) was observed in the majority of di- and polykaryons during the second and third of three 24-hr periods of labeling with [3H]thymidine. The results are compatible with either terminal differentiation or error theories of clonal senescence.

Keywords: cell aging, cell fusion, cell division, fibroblast cultures

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Selected References

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  1. Cristofalo V. J., Sharf B. B. Cellular senescence and DNA synthesis. Thymidine incorporation as a measure of population age in human diploid cells. Exp Cell Res. 1973 Feb;76(2):419–427. doi: 10.1016/0014-4827(73)90394-7. [DOI] [PubMed] [Google Scholar]
  2. Ginsburg H., Lagunoff D. The in vitro differentiation of mast cells. Cultures of cells from immunized mouse lymph nodes and thoracic duct lymph on fibroblast monolayers. J Cell Biol. 1967 Dec;35(3):685–697. doi: 10.1083/jcb.35.3.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goldstein S. Lifespan of cultured cells in progeria. Lancet. 1969 Feb 22;1(7591):424–424. doi: 10.1016/s0140-6736(69)91404-4. [DOI] [PubMed] [Google Scholar]
  4. Goldstein S., Lin C. C. Rescue of senescent human fibroblasts by hybridization with hamster cells in vitro. Exp Cell Res. 1972 Feb;70(2):436–439. doi: 10.1016/0014-4827(72)90157-7. [DOI] [PubMed] [Google Scholar]
  5. Goldstein S., Littlefield J. W., Soeldner J. S. Diabetes mellitus and aging: diminished planting efficiency of cultured human fibroblasts. Proc Natl Acad Sci U S A. 1969 Sep;64(1):155–160. doi: 10.1073/pnas.64.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. HAYFLICK L. THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. Exp Cell Res. 1965 Mar;37:614–636. doi: 10.1016/0014-4827(65)90211-9. [DOI] [PubMed] [Google Scholar]
  7. Harris H., Sidebottom E., Grace D. M., Bramwell M. E. The expression of genetic information: a study with hybrid animal cells. J Cell Sci. 1969 Mar;4(2):499–525. doi: 10.1242/jcs.4.2.499. [DOI] [PubMed] [Google Scholar]
  8. Harris H. The reactivation of the red cell nucleus. J Cell Sci. 1967 Mar;2(1):23–32. doi: 10.1242/jcs.2.1.23. [DOI] [PubMed] [Google Scholar]
  9. Harris H., Watkins J. F., Ford C. E., Schoefl G. I. Artificial heterokaryons of animal cells from different species. J Cell Sci. 1966 Mar;1(1):1–30. doi: 10.1242/jcs.1.1.1. [DOI] [PubMed] [Google Scholar]
  10. Holliday R., Tarrant G. M. Altered enzymes in ageing human fibroblasts. Nature. 1972 Jul 7;238(5358):26–30. doi: 10.1038/238026a0. [DOI] [PubMed] [Google Scholar]
  11. Kenny G. E. Serological comparison of ten glycolytic Mycoplasma species. J Bacteriol. 1969 Jun;98(3):1044–1055. doi: 10.1128/jb.98.3.1044-1055.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lewis C. M., Tarrant G. M. Error theory and ageing in human diploid fibroblasts. Nature. 1972 Oct 6;239(5371):316–318. doi: 10.1038/239316a0. [DOI] [PubMed] [Google Scholar]
  13. Littlefield J. W. Attempted hybridizations with senescent human fibroblasts. J Cell Physiol. 1973 Aug;82(1):129–132. doi: 10.1002/jcp.1040820115. [DOI] [PubMed] [Google Scholar]
  14. Macieira-Coelho A., Pontén J., Philipson L. Inhibition of the division cycle in confluent cultures of human fibroblasts in vitro. Exp Cell Res. 1966 Aug;43(1):20–29. doi: 10.1016/0014-4827(66)90373-9. [DOI] [PubMed] [Google Scholar]
  15. Macieira-Coelho A., Pontén J., Philipson L. The division cycle and RNA-synthesis in diploid human cells at different passage levels in vitro. Exp Cell Res. 1966 Jun;42(3):673–684. doi: 10.1016/0014-4827(66)90280-1. [DOI] [PubMed] [Google Scholar]
  16. Martin G. M., Sprague C. A., Epstein C. J. Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype. Lab Invest. 1970 Jul;23(1):86–92. [PubMed] [Google Scholar]
  17. Martin G. M., Sprague C. A., Norwood T. H., Pendergrass W. R. Clonal selection, attenuation and differentiation in an in vitro model of hyperplasia. Am J Pathol. 1974 Jan;74(1):137–154. [PMC free article] [PubMed] [Google Scholar]
  18. Martin G. M., Sprague C. A. Symposium on in vitro studies related to atherogenesis. Life histories of hyperplastoid cell lines from aorta and skin. Exp Mol Pathol. 1973 Apr;18(2):125–141. doi: 10.1016/0014-4800(73)90012-9. [DOI] [PubMed] [Google Scholar]
  19. Muggleton A., Danielli J. F. Inheritance of the "life-spanning" phenomenon in Amoeba proteus. Exp Cell Res. 1968 Jan;49(1):116–120. doi: 10.1016/0014-4827(68)90524-7. [DOI] [PubMed] [Google Scholar]
  20. Neff J. M., Enders J. F. Poliovirus replication and cytopathogenicity in monolayer hamster cell cultures fused with beta propiolactone-inactivated Sendai virus. Proc Soc Exp Biol Med. 1968 Jan;127(1):260–267. doi: 10.3181/00379727-127-32668. [DOI] [PubMed] [Google Scholar]
  21. Orgel L. E. Ageing of clones of mammalian cells. Nature. 1973 Jun 22;243(5408):441–445. doi: 10.1038/243441a0. [DOI] [PubMed] [Google Scholar]
  22. Steel C. M. Non-identity of apparently similar chromosome aberrations in human lymphoblastoid cell lines. Nature. 1971 Oct 22;233(5321):555–556. doi: 10.1038/233555a0. [DOI] [PubMed] [Google Scholar]

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