Advertisement

The Histochemical Journal

, Volume 13, Issue 4, pp 681–692 | Cite as

Chromatin changes in apoptosis

  • A. H. Wyllie
  • G. J. Beattie
  • A. D. Hargreaves
Reviews and Papers

Summary

Murine lymphoid cell lines and rat thymocytes treatedin vitro with glucocorticoid hormones provide a convenient system for studying the nuclear changes in apoptosis. Morphologically the nucleolus disintegrates and chromatin undergoes an unusual, generalized condensation. This is associated with excision of most of the nuclear. DNA to short but well-organized chains of nucleosomes, apparently by an endogenous non-lysosomal nuclease. The process is dependent upon macromolecular synthesis and probably is mediated, at least remotely, by the classical steroid-receptor-gene activation pathway. A similar process of chromatin condensation and excision can be produced by the calcium-magnesium ionophore A23187. In other circumstances of programmed cell death', analogous chromatin condensation, excision and requirements for macromolecular synthesis have been documented.

Keywords

Cell Death Glucocorticoid Programme Cell Death Activation Pathway Lymphoid 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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Appleby, D. W. &Modak, S. P. (1977) DNA degradation in terminally differentiating lens fiber cells from chick embryos.Proc. natn. Acad. Sci., U.S.A. 74, 5579–83.Google Scholar
  2. Bachvaroff, R. J., Ayvazian, J. H., Skupp, S. K. &Rapaport, F. T. (1977) Specific restriction endonuclease degradation of DNA as a consequence of immunologically mediated cell damage.Transplanta. Proc. 9, 807–10.Google Scholar
  3. Ben-Ishay, Z. &Farber, E. (1975) Protective effects of an inhibitor of protein synthesis, cycloheximide, on bone marrow damage induced by cytosine arabinoside or nitrogen mustard.Lab. Invest. 33, 478–90.Google Scholar
  4. Berezney, R. (1979) Dynamic properties of the nuclear matrix. InThe Cell Nucleus, Vol. 7 (edited byBusch, H.), pp. 413–456. New York: Academic Press.Google Scholar
  5. Cho-Chung, Y. S. (1978) Antagonistic action between cyclic adenosine 3′∶5′-monophosphate and estrogen in rat mammary tumor growth control.Cancer Res. 38, 4071–5.Google Scholar
  6. Churchill, J. R., Urbanczyk, J. &Studzinski, G. P. (1973) Multiple deoxyribonuclease activities in nuclei of HeLa cells.Biochem biophys. Res. Commun. 53, 1009–16.Google Scholar
  7. Hewish, D. R. &Burgoyne, L. A. (1973) Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease.Biochem. biophys. Res. Commun. 52, 504–10.Google Scholar
  8. Higgins, S. J. &Gehring, H. (1978) Molecular mechanisms of steroid hormone action.Adv. Cancer Res. 28, 313–97.Google Scholar
  9. Ishida, R., Akiyoshi, H. &Takahasi, T. (1974) Isolation and purification of calcium and magnesium dependent endonuclease from rat liver nuclei.Biochem. biophys. Res. Commun. 56, 703–10.Google Scholar
  10. Kaiser, N. &Edelman, I. S. (1977) Calcium dependence of glucocorticoid-induced lymphocytolysis.Proc. natn. Acad. Sci., U.S.A. 74, 638–42.Google Scholar
  11. Kaiser, N. &Edelman, I. S. (1978) Further studies on the role of calcium in glucocorticoid-induced lymphocytolysis.Endocrinology 103, 936–42.Google Scholar
  12. Kerr, J. F. R. (1965) A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes.J. Path. Bact. 90, 419–35.Google Scholar
  13. Kerr, J. F. R. &Searle, J. (1972) The digestion of cellular fragments within phagolysosomes in carcinoma cells.J. Path. 108, 55–8.Google Scholar
  14. Kerr, J. F. R., Wyllie, A. H. &Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.Br. J. Cancer 26, 239–57.Google Scholar
  15. Kornberg, R. D. (1974) Chromatin structure: a repeating unit of histones and DNA.Science, N.Y. 184, 868–71.Google Scholar
  16. Krufger, R. C. (1978) A study of an endogenous nucleolytic reaction and of the action of micrococcal nuclease and DNase I on a salt-soluble, compact form of chromatin.Biochim. Biophys. Acta 520, 358–67.Google Scholar
  17. Kijo, M. T. &Hsu, T. C. (1978) Bleomycin causes release of nucleosomes from chromatin and chromosomes.Nature, Lond. 271, 83–4.Google Scholar
  18. Lieberman, M. W., Verbin, R. S., Landay, M., Liang, H., Farber, E., Lee, T.-N. &Starr, E. (1970) A probable role for protein synthesis in intestinal epithelial cell damage inducedin vivo by cytosine arabinoside, nitrogen mustard or x-irradiation.Cancer Res. 30, 942–51.Google Scholar
  19. Long, B., Huang, C.-Y. &Pogo, A. O. (1979) Isolation and characterization of the nuclear matrix in Friend erythroleukaemia cells: chromatin and hnRNA interactions with the nuclear matrix.Cell 18, 1079–90.Google Scholar
  20. Pratt, R. M. &Greene, R. M. (1976) Inhibition of palatal epithelial cell death by altered protein synthesis.Devl Biol. 54, 135–45.Google Scholar
  21. Searle, J., Collins, D. J., Harmon, B. &Kerr, J. F. R. (1973) The spontaneous occurrence of apoptosis in squamous carcinomas of the uterine cervix.Pathology 5, 163–9.Google Scholar
  22. Sierakowska, H. &Shugar, D. (1977) Mammalian nucleolytic enzymes.Progr. Nucleic Acid Res. 20, 59–130.Google Scholar
  23. Skalka, M., Matyášová, J. &Čejková, M. (1976) DNA in chromatin of irradiated lymphoid tissues degradesin vivo into regular fragments.FEBS Lett. 72, 271–4.Google Scholar
  24. Slor, H. &Lev, T. (1971) Acid deoxyribonuclease activity in purified calf thymus nuclei.Biochem. J. 123, 993–5.Google Scholar
  25. Suciu, D. (1979) Role of alkaline endonucleases in the release of soluble chromatin from thymus, spleen and liver nuclei of normal and irradiated mice.Int. J. Radiat. Biol. 35, 119–31.Google Scholar
  26. Tata, J. R. (1966) Requirement for RNA and protein synthesis for induced regression of tadpole tail in organ culture.Devl Biol. 13, 77–94.Google Scholar
  27. Trowell, D. A. (1966) Ultrastructural changes in lymphocytes exposed to noxious agentsin vitro.Q. Jl exp. Physiol. 51, 207–20.Google Scholar
  28. Waddell, A. W., Wyllie, A. H., Robertson, A. M. G., Mayne, K., Au, J. &Currie, A. R. (1979) Lethal and growth-inhibitory actions of glucocorticoids. InGlucocorticoid Action and Leukaemia (7th Tenovus Workshop) (edited byBell, P. A. andBorthwick, N. M.), pp. 75–83. Cardiff: Alpha Omega.Google Scholar
  29. Weser, R. (1965) Inhibitory effect of actinomycin D on tail atrophy inXenopus larvae at metamorphosis.Experimentia 21, 665–6.Google Scholar
  30. Williamson, R. (1970) Properties of rapidly labelled deoxyribonucleic acid fragments from the cytoplam of primary cultures of embryonic mouse liver.J. molec. Biol. 51, 157–68.Google Scholar
  31. Wyllie, A. H. (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation.Nature, Lond. 284, 555–6.Google Scholar
  32. Wyllie, A. H., Kerr, J. F. R. &Currie, A. R. (1981) Cell death: the significance of apoptosis.Int. Rev. Cytol. 68, 251–305.Google Scholar
  33. Zöilner, E. J., Reitz, M., Zahn, R. K., &Slor, H. (1979) Deoxyribonucleases in phytohaemagglutinin-stimulated lymphocytes.Expl Cell Res. 123, 365–9.Google Scholar

Copyright information

© Chapman and Hall Ltd. 1981

Authors and Affiliations

  • A. H. Wyllie
    • 1
  • G. J. Beattie
    • 1
  • A. D. Hargreaves
    • 1
  1. 1.Department of PathologyUniversity Medical SchoolEdinburghU.K.

Personalised recommendations