Cellular Growth: Brain, Liver, Muscle, and Lung

  • Jo Anne Brasel
  • Rhoda K. Gruen


The growth of tissues which are not self-renewing occurs by a combination of increase in the number and increase in the size of the component cells. Work in animals (Enesco and Leblond, 1962; Winick and Noble, 1965) in the last 15 years has shown that initially cell division and increase in number predominate; later the rate of cell division slows and increase in size begins. When cell division ceases, cells continue to grow in size causing further tissue enlargement until maturity is reached, when no further net increase in number or size occurs. These conclusions were based on the measurement of total tissue DNA and protein content. Since the DNA per diploid nucleus is constant within any one species and since essentially all cellular DNA is chromosomal (Boivin et al., 1948; Mirsky and Ris, 1949), the tissue DNA content is a reflection of growth in cell number. Such a biochemical measure of growth does not define which type of cell is increasing in number, and in tissues of multiple cell types its usefulness is limited in the absence of accompanying histologic information. In tissues where polyploidy or multinucleated cells develop during the growth process, total DNA content no longer reflects growth in cell number if a cell is to be strictly defined by membrane boundaries. It is, nonetheless, a reflection of the extent of DNA synthesis during growth and is an accurate reflection of the formation of “diploid cell units,” which, as discussed later, has some real biological significance.


Muscle Mass Cardiac Hypertrophy Human Heart Cellular Growth Postnatal Growth 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, R. D., and De Rueck, J., 1973, Metrics of muscle, in: Basic Research in Myology, Proceedings of the II International Congress on Muscle Diseases, Part I, pp. 3–11, Excerpta Medica, ICN Series #294, Amsterdam.Google Scholar
  2. Addis, T., 1928, Compensatory hypertrophy of the lung after unilateral pneumonectomy, J. Exp. Med. 47: 51.CrossRefGoogle Scholar
  3. Adler, C. P., and Hueck, C., 1971, DNA content in growing human hearts, Verh. Dtsch. Ges. Pathol. 55: 464.Google Scholar
  4. Alleyne, G. A. O., 1968, Studies on total body potassium in infantile malnutrition: The relation to body fluid spaces and urinary creatinine, Clin. Sci. (London) 34: 199.Google Scholar
  5. Angus, G. E., and Thurlbeck, W. M., 1972, Number of alveoli in the human lung, J. Appl. Physiol. 32: 483.Google Scholar
  6. Astorri, K., Chizzola, A., Visioli, O., Anversa, P., Olivetti, G., and Vitali-Mazza, L., 1971, Right ventricular hypertrophy—a cytometric study on 55 human hearts, J. Mol. Cell. Cardiol. 2: 99.CrossRefGoogle Scholar
  7. Beach, R. K., and Kostyo, J. L., 1968, Effect of growth hormone on the DNA content of muscles of young hypophysectomized rats, Endocrinology 82:882.CrossRefGoogle Scholar
  8. Bishop, S. P., 1971, Myocardial cell growth in the normal and hypertrophying neonatal heart, Circulation 44 (Suppl. 2): 142 (abstract).Google Scholar
  9. Boivin, A., Vendrely, R., and Vendrely, C., 1948, L’acide désoxyribonucléique du noyau cellulaire, dépositaire des caractères héréditaires; arguments d’ordre analytique, C.R. Acad. Sci. 226: 1061Google Scholar
  10. Bradley, K., McConnell-Bruel, S., and Crystal, R. G., 1975, Collagen in the human lung, J. Clin. Invest. 55: 543.CrossRefGoogle Scholar
  11. Brasel, J. A., and Cheek, D. B., 1968, The effect of growth hormone on the cellular mass of hypopituitary dwarfs, in: Growth Hormone ( A. Pecile and E. Muller, eds.), pp. 433–440, Excerpta Medica, Amsterdam.Google Scholar
  12. Buhain, W. J., and Brody, J. S., 1973, Compensatory growth of the lung following pneumonectomy, J. Appl. Physiol. 33: 898.Google Scholar
  13. Campiche, M. A., Gautier, A., Hernandez, E. I., and Reymond, A., 1963, An electron microscopic study of the fetal development of human lung, Pediatrics 32: 976.Google Scholar
  14. Charnock, E. L., and Doershuk, C. F., 1973, Developmental aspects of the human lung, Pediatr. Clin. North Am. 20: 275.Google Scholar
  15. Chase, H. P., Canosa, C. A., Dabiere, C. S., Welch, N. N., and O’Brien, D., 1974, Postnatal undernutrition and human brain development, J. Ment. Defic. Res. 18: 355.Google Scholar
  16. Cheek, D. B., 1968, Muscle cell growth in normal children, in: Human Growth ( D. B. Cheek, ed.), pp. 337–351, Lea and Febiger, Philadelphia.Google Scholar
  17. Cheek, D. B., 1973, Brain growth and nucleic acids: The effect of nutritional deprivation, in: Brain and Intelligence: Ecology of Child Human Development ( F. Richardson, ed.), pp. 237–256, National Educational Press, Hyattsville, Maryland.Google Scholar
  18. Cheek, D. B., 1974, Body composition, hormones, nutrition and adolescent growth, in: Control of Onset of Puberty ( M. M. Grumbach, G. D. Grave, and F. E. Mayer, eds.), pp. 426–447, John Wiley and Sons, New York.Google Scholar
  19. Cheek, D. B., 1975, The fetus, in: Fetal and Postnatal Cellular Growth ( D. B. Cheek, ed.), pp. 3–22, John Wiley and Sons, New York.Google Scholar
  20. Cheek, D. B., and Hill, D. E., 1970, Muscle and liver cell growth: Role of hormones and nutritional factors, Fed. Proc. 29: 1503.Google Scholar
  21. Cheek, D. B., Hill, D. E., Cordano, A., and Graham, G., 1970a, Malnutrition in infancy. Changes in muscle and adipose tissue before and after rehabilitation, Pediatr. Res. 4: 135.CrossRefGoogle Scholar
  22. Cheek, D. B., Schultz, R. B., Pana, A., and Reba, R. C., 1970b, Overgrowth of lean and adipose tissues in adolescent obesity, Pediatr. Res. 4: 268.CrossRefGoogle Scholar
  23. Cheek, D. B., Holt, A. B., Hill, D. E. and Talbert, J. L., 1971, Skeletal muscle cell mass and growth: The concept of the deoxyribonucleic acid unit, Pediatr. Res. 5: 312.CrossRefGoogle Scholar
  24. Dische, M. R., 1972, Observations on the morphological changes of the developing heart, Cardiovasc. Clin. 4: 175.Google Scholar
  25. Dobbing, J., 1970, Undernutrition and the developing brain: The relevance of animal models to the human problem, Am. J. Dis. Child. 120: 411.Google Scholar
  26. Dobbing, J., and Sands, J., 1970, Timing of neuroblast multiplication in developing human brain, Nature 226: 639.CrossRefGoogle Scholar
  27. Dobbing, J., and Sands, J., 1973, Quantitative growth and development of human brain, Arch. Dis. Child. 48: 757.CrossRefGoogle Scholar
  28. Enesco, M., and Leblond, C. P., 1962, Increase in cell number as a factor in the growth of the young male rat, J. Embryol. Exp. Morphol. 10: 530.Google Scholar
  29. Enesco, M., and Puddy, D., 1964, Increase in the number of nuclei and weights in skeletal muscle of rats of various ages, Am. J. Anat. 114: 235.CrossRefGoogle Scholar
  30. Epstein, C. J., 1967, Cell size, nuclear content, and the development of polyploidy in the mammalian liver, Proc. Natl. Acad. Sci. U.S.A. 57: 327.CrossRefGoogle Scholar
  31. Fisher, J. M., and Simnett, J. D., 1973, Morphogenetic and proliferative changes in the regenerating lung of the rat, Anat. Rec. 176: 389.CrossRefGoogle Scholar
  32. Forbes, G. B., 1964, Lean body mass and fat in obese children, Pediatrics 34: 308.Google Scholar
  33. Graham, G. D. C., Cordano, A., Blizzard, R., and Cheek, D. B., 1969, Infantile malnutrition: Changes in body composition during rehabilitation, Pediatr. Res. 3: 579.CrossRefGoogle Scholar
  34. Graystone, J. E., 1968, Creatinine excretion during growth, in: Human Growth ( D. B. Cheek, ed.), pp. 182–197, Lea and Febiger, Philadelphia.Google Scholar
  35. Grove, D., Nair, K. G., and Zak, R., 1969a, Biochemical correlates of cardiac hypertrophy III. Changes in DNA content; the relative contributions of polyploidy and mitotic activity, Circ. Res. 25: 463.CrossRefGoogle Scholar
  36. Grove, D., Zak, R., Nair, K. G., and Aschenbrenner, V., 1969b, Biochemical correlates of cardiac hypertrophy IV. Observations on the cellular organization of growth during myocardial hypertrophy in the rat, Circ. Res. 25: 473.CrossRefGoogle Scholar
  37. Howard, E., Granoff, D. M., and Bujnovszky, P., 1969, DNA, RNA and cholesterol increases in cerebrum and cerebellum during development of human fetus, Brain Res. 14: 697.CrossRefGoogle Scholar
  38. Inselman, L. S., Mellins, R. B., and Brasel, J. A., 1976, Effects of atelectasis on compensatory lung growth, Presented at the annual meeting of the American Thoracic Society, Am. Rev. Resp. Dis. 113: 41.Google Scholar
  39. Kapeller-Adler, R., and Hammad, W. A., 1972, A biochemical study on nucleic acids and protein synthesis in the human fetus and its correlation with relevant embryological data, J. Obstet. Gynaecol. Br. Commonw. 79: 924.CrossRefGoogle Scholar
  40. Kompmann, M., Paddags, I., and Sandritter, W., 1966, Feulgen cytophotometric DNA determinations on human hearts, Arch. Pathol. 82: 303.Google Scholar
  41. Leuchtenberger, C., Leuchtenberger, R., and Davis, A., 1954, A microspectrophotometric study of the desoxyribose nucleic acid (DNA) content in cells of normal and malignant human tissues, Am. J. Pathol. 30: 65.Google Scholar
  42. Levin, A. R., Brasel, J. A., Deely, W., Redo, S. F., Ogata, K., and Winick, M., 1975, The response of the right ventricle to experimentally induced pulmonary artery obstruction, Growth 39: 107.Google Scholar
  43. Mastaglia, F. L., 1974, The growth and development of skeletal muscles, in: Scientific Foundations of Paediatrics (J. A. Davis and J. Dobbing, eds.), pp. 348–375Google Scholar
  44. W. B. Saunders, Philadelphia. McDougall, J., and Smith, J. F., 1975, The development of the human type II pneumocyte, J. Pathol. 115: 245.CrossRefGoogle Scholar
  45. Mirsky, A. E., and Ris, H., 1949, Variable and constant components of chromosomes, Nature 163: 666.CrossRefGoogle Scholar
  46. Montgomery, R. D., 1992, Growth of human striated muscle, Nature 195: 194.CrossRefGoogle Scholar
  47. Morishita, T., Sasaki, R., and Yamagata, S., 1970, Studies on deoxyribonucleic acid content and cell count of human heart muscle, Jpn. Heart J. 11: 36.CrossRefGoogle Scholar
  48. Morkin, E., and Ashford, T. P., 1968, Myocardial DNA synthesis in experimental cardiac hypertrophy, Am. J. Physiol. 215: 1409.Google Scholar
  49. Moss, F. P., and Leblond, C. P., 1970, Nature of dividing nuclei in skeletal muscle of growing rats, J. Cell Biol. 44: 459.CrossRefGoogle Scholar
  50. Nattie, E. E., Wiley, C. W., and Bartlett, D., Jr., 1974, Adaptive growth of the lung following pneumonectomy in rats, J. Appl. Physiol. 37: 491.Google Scholar
  51. Neffgen, J. F., and Korecky, B., 1972, Cellular hyperplasia and hypertrophy in cardiomegalies induced by anemia in young and adult rats, Circ. Res. 30: 104.CrossRefGoogle Scholar
  52. Rabinowitz, M., and Zak, R., 1972, Biochemical and cellular changes in cardiac hypertrophy, Annu. Rev. Med. 23: 245.CrossRefGoogle Scholar
  53. Ranek, L., Keiding, N., and Jensen, S. T., 1975, A morphometric study of normal human liver cell nuclei, Acta Pathol. Microbiol. Scand. Sect. A 83: 467.Google Scholar
  54. Roberts, J. T., and Wearn, J. T., 1941, Quantitative changes in the capillary-muscle relationship in human hearts during normal growth and hypertrophy, Am. Heart J. 21: 617.CrossRefGoogle Scholar
  55. Romanova, L. K., Leikina, E. M., and Antipova, K. K., 1967, Nucleic acid synthesis and mitotic activity during development of compensatory hypertrophy of the lung in rats, Bull. Exp. Biol. Med. (U.S.S.R.) 63: 303.CrossRefGoogle Scholar
  56. Sandritter, W., and Adler, C. P., 1971, Numerical hyperplasia in human heart hypertrophy, Experientia 27: 1435.CrossRefGoogle Scholar
  57. Sasaki, R., Morishita, T., Ichikawa, S., and Yamagata, S., 1970, Autoradiographic studies and mitosis of heart muscle cells in experimental cardiac hypertrophy, Tohoku J. Exp. Med. 102: 159.CrossRefGoogle Scholar
  58. Swartz, F. J., 1956, The development in the human liver of multiple desoxyribose nucleic acid (DNA) classes and their relationship to the age of the individual, Chromosoma 8: 53.CrossRefGoogle Scholar
  59. Thurlbeck, W. M., 1975, Postnatal growth and development of the lung, Am. Rev. Resp. Dis. 111: 803.Google Scholar
  60. Weibel, E. R., 1974, A note on differentiation and divisibility of alveolar epithelial cells, Chest 65:19S (suppl.).CrossRefGoogle Scholar
  61. Widdowson, E. M., 1974, Changes in body proportions and composition during growth, in: Scientific Foundations of Paediatrics ( J. A. Davis and J. Dobbing, eds.), pp. 153–163, W. B. Saunders, Philadelphia.Google Scholar
  62. Widdowson, E. M., Crabb, D. E., and Milner, R. D. G., 1972, Cellular development of some human organs before birth, Arch. Dis. Child. 47: 652.CrossRefGoogle Scholar
  63. Winick, M., 1968, Changes in nucleic acid and protein content of the human brain during growth, Pediatr. Res. 2: 352.CrossRefGoogle Scholar
  64. Winick, M., and Noble, A., 1965, Quantitative changes in DNA, RNA, and protein during prenatal and postnatal growth in the rat, Dev. Biol. 12: 451.CrossRefGoogle Scholar
  65. Winick, M., and Noble, A., 1966, Cellular response in rats during malnutrition at various ages, J. Nutr. 89: 300.Google Scholar
  66. Winick, M., and Rosso, P., 1969, The effect of severe early malnutrition on cellular growth of human brain, Pediatr. Res. 3: 181.CrossRefGoogle Scholar
  67. Winick, M., Rosso, P., and Waterlow, J., 1970, Cellular growth of cerebrum, cerebellum, and brain stem in normal and marasmic children, Exp. Neurol. 26: 393.CrossRefGoogle Scholar
  68. Winick, M., Brasel, J. A., and Rosso, P., 1972, Nutrition and cell growth, in: Nutrition and Development ( M. Winick, ed.), pp. 49–97, John Wiley and Sons, New York.Google Scholar
  69. Zak, R., 1973, Cell proliferation during cardiac growth, Am. J. Cardiol. 31: 211.CrossRefGoogle Scholar
  70. Zak, R., 1974, Development and proliferative capacity of cardiac muscle cells, Circ. Res. Suppl. II: 17.Google Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • Jo Anne Brasel
    • 1
  • Rhoda K. Gruen
    • 1
  1. 1.Institute of Human Nutrition, Department of PediatricsColumbia University College of Physicians and SurgeonsNew YorkUSA

Personalised recommendations