The Cell Cycle pp 263-269 | Cite as

Cell Proliferation as a Biomarker of Age and Development

  • M. H. Lu
  • S. F. Ali
  • D. S. He
  • A. Turturro
  • R. W. Hart
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Changes in the proliferative capacity of cells can serve as a biomarker of development, age, and carcinogenesis. Perturbation of the cell cycle is considered a toxic endpoint. A paucity of data is available on the cell cycle as a function of age. in order to understand the etiology of ontogenesis and carcinogenesis, it is essential that background information be established on cell proliferation. The brain is known to have a very high level of proliferation during the early stages of development which decreases with age. The present study was designed to establish background information on cell proliferation, by cell cycle analysis, in the brain of normal male rats during development. Brain tissues of Sprague-Dawley rats (newborn, 21 days, 6 months, and one year of age) were dissected to obtain the cerebrum, cerebellum, and brain stem. Cellular proliferation activity was determined by flow cytometry. The percentage of S-phase cells was used to establish the proliferative index (PI). Our results indicate that there are differences in proliferation among the three brain regions in all age groups except for the 6-month old animals. in all cases, cell proliferation was highest in newborn rats. Proliferation activity in the cerebrum of newborn and 21-day old rats was equivalent (17%); after 21 days of age, proliferative activity decreases and maintains the same low rate (about 6.5%) until at least one year of age. The proliferation activity of cerebellum (21% at birth) decreases in animals at day 21 (7%) and the decrease continues until 6 months of age at which time it remains constant (5%) for at least one year. The proliferative activity of brain stem decreases from 16% to 5% immediately after birth and maintains the same low rate from day 21 to one year of age.


Brain Stem Proliferative Activity Proliferative Index Cell Cycle Analysis External Granular Layer 
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  1. 1.
    J.W. Gray, F. Dolbeare, M.G. Pallavicini, W. Beisker, and F. Waldman, Cell cycle analysis using flow cytometry. Int. J. Radiat. Biol. 49: 237 (1986).CrossRefGoogle Scholar
  2. 2.
    P.D. Bowman. Aging and the cell cycle in vivo and in vitro, in: Handbook of cell biology and aging, V.J. Cristofolo, R.C. Adelman, and G.S. Roth, eds., CRC Press, Boca Raton, FL pp. 117 (1985).Google Scholar
  3. 3.
    M.H. Lu, W.G. Hinson, A. Turturro, J. Anson, and R.W. Hart, Cell cycle analysis in bone marrow and kidney tissues of dietary restricted rats. Mech. Ageing Devel. 59: 111 (1991).CrossRefGoogle Scholar
  4. 4.
    M.H. Lu, W.G. Hinson, A. Turturro, W.G. Sheldon, and R.W. Hart, Cell proliferation by cell cycle analysis in young and old dietary restricted mice. Mech. Ageing Devel. 68: 151 (1993).CrossRefGoogle Scholar
  5. 5.
    B. Barlogie, B. Drewinko, J. Schumann, and E.J. Freireich, Pulse cytophotometric analysis of cell cycle perturbation with bleomycin in vitro. Cancer Res. 36: 1182 (1976).PubMedGoogle Scholar
  6. 6.
    O. Sletvold and D. Laerum, Alterations of cell cycle distribution in the bone marrow of aging mice measured by flow cytometry. Exp. Gerontol. 23: 43 (1988).PubMedCrossRefGoogle Scholar
  7. 7.
    K. Yamada, M. Ohtsu, M. Sugano, and G. Kimura, Effects of butyrate on cell cycle progression and polyploidization of various types of mammalian cells. Biosti. Biotech. Biochem. 56: 126 (1992).Google Scholar
  8. 8.
    S. Remis and J.M. Goldman, The development of the brain: biological and functional perspectives, Charles C. Thomas Publisher, Springfield, IL pp. 123 (1980).Google Scholar
  9. 9.
    S.J. Rozovski and M. Wick, Nutrition and cellular growth, in: Nutrition: pre-and postnatal development, M. Winick, ed., Plenum Press, New York, pp. 61 (1979).Google Scholar
  10. 10.
    G.A. Dhopeshwarkar, Nutrition and brain development, Plenum Press, New York, pp. 13 (1983).Google Scholar
  11. 11.
    R. Balais, T. Jordan, P.D. Lewis, and A.J. Patel, Undernutrition and brain development, in: Human growth, vol. 3, Neurobiology and nutrition, F. Falkner and J.M. Tanner, eds., Plenum Press, New York, pp. 415 (1979).Google Scholar
  12. 12.
    H. Tuchmann-Duplessi, Drug effect on the fetus, AIDS Press, Sydney, pp. 63 (1975).Google Scholar
  13. 13.
    D.A. Karnofsky, Mechanisms of action of certain growth-inhibiting drugs, in: Teratology: principles and techniques, J.G. Wilson and J. Warkanay, eds., The University of Chicago Press, Chicago, IL pp. 185 (1965).Google Scholar
  14. 14.
    S.M. Cohen and L.B. Ellwein, Cell proliferation in carcinogenesis. Science 249: 1007 (1990).PubMedCrossRefGoogle Scholar
  15. 15.
    U.S. Interagency Staff Group on Carcinogens, Chemical carcinogenesis: a review of the science and its associated principles. Environ. Health Perspect. 67: 201 (1986).Google Scholar
  16. 16.
    J. Glowinski and L.L. Iversen, Regional studies of catecholamines in the rat brain, I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J. Neurochem. 13: 655 (1966).PubMedCrossRefGoogle Scholar
  17. 17.
    R.T. Robertson, J. Zimmer, and B.H. Gahwiler, Dissection procedures for preparation of slide cultures, in: A dissection and tissue culture manual of the nervous system, A. Schahar, J. de Vellis, A Vernadakis, and B. Haber, eds., Alan R. Liss, Inc., New York, pp. 1 (1989).Google Scholar
  18. 18.
    L.L. Vindelov, I.J. Christensen, and N.I. Nissen, A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3: 323 (1983).PubMedCrossRefGoogle Scholar
  19. 19.
    P.N. Dean, A simplified method of DNA distribution analysis. Cell Tissue Kinetics 13: 299 (1980).Google Scholar
  20. 20.
    S.L. Cohen, A.W. Rademaker, H.R. Salwen, W.A. Franklin, F. Gonzales-Crussi, S.T. Rosen, and K.D. Bauer, Analysis of DNA ploidy and proliferative activity in relation to histology and N-myc-amplification in neuroblastoma. Am. J. Pathol. 136: 1043 (1990).Google Scholar
  21. 21.
    I. Fish and M. Wick, Cellular growth in various regions of the developing rat brain. Pediatr. Res. 3: 407 (1969).PubMedCrossRefGoogle Scholar
  22. 22.
    P. Mandel, H. Rein, S. Harth-Edel, and R. Mardell, Distribution and metabolism of ribonucleic acid in the vertebrate central nervous system, in: Comparative neurochemistry, D. Richter, ed., Pergamon Press, London, pp. 153 (1964).Google Scholar
  23. 23.
    M. Wick and A Noble, Quantitative changes in DNA, RNA, and protein during prenatal and postnatal growth. Devel. Biol. 12: 451 (1965).CrossRefGoogle Scholar
  24. 24.
    M. Wimck, Normal cellular growth of the brain, in: Malnutrition and brain development, Chapter 2, Oxford University Press, New York, pp. 35 (1976).Google Scholar
  25. 25.
    J. Altman, Autoradiographic and histological studies of postnatal neurogenesis, III. Dating the time of production and onset of differentiation of cerebellar microsomes in rats. J. Comp. Neurol. 136: 26 (1969).CrossRefGoogle Scholar
  26. 26.
    M.G. Deo, V. Bijlani, and V. Ramalingaswami, Nutrition and cellular growth and differentiation, in: Growth and development of the brain: Nutrition, genetics, and environmental factors, M.A.B. Brazier, ed., Raven Press, New York, pp. 1 (1975).Google Scholar
  27. 27.
    G. Gopinath, V. Bijlani, and M.G. Deo, Undernutrition and developing cerebellar cortex in the rat. J. Neuropathol. Exp. Neuro. 35: 125 (1976).CrossRefGoogle Scholar
  28. 28.
    M. Winick, J.A. Brasel, and P. Rosso, Nutrition and cell growth, in: Nutrition and development, M. Winick, ed., John Wiley and Sons, New York, pp. 49 (1972).Google Scholar
  29. 29.
    A.M. Giuffrida, A. Hamberger, I. Serra, and E. Geremia, Effects of undernutrition on nucleic acid synthesis in neuronal and glial cells from different regions of developing rat brain. Nutr. Metab. 24: 189 (1980).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • M. H. Lu
    • 1
  • S. F. Ali
    • 1
  • D. S. He
    • 1
  • A. Turturro
    • 1
  • R. W. Hart
    • 1
  1. 1.National Center for Toxicological ResearchFood and Drug AdministrationJeffersonUSA

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