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Human hepatocyte polyploidization kinetics in the course of life cycle

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Virchows Archiv B

Summary

The processes of polyploidization in normal human liver parenchyma from 155 individuals aged between 1 day and 92 years were investigated by Feulgen-DNA cytophotometry. It was shown that polyploid hepatocytes appear in individuals from 1 to 5 years old. Up to the age of 50 years the accumulation rate of binucleate and polyploid cells is very slow, but subsequently hepatocyte polyploidization is intensified, and in patients aged 86–92 years the relative number of cells with polyploid nuclei is about 27%. Only a few hepatocytes in the normal human liver reach 16C and 8C×2 ploidy levels for mononucleate and binucleate cells respectively. Using a mathematical modeling method, it was shown that during postnatal liver growth the polyploidization process in human liver is similar to that in the rat, and that polyploid cells are formed mainly from binucleate cells. As in rats, prior to an increase in ploidy level, diploid human hepatocytes can pass several times through the usual mitotic cycles maintaining their initial ploidy level. After birth, only one in ten hepatocytes starting DNA synthesis enters the polyploidization process. At maturity about 60% of 2C-hepatocytes starting DNA synthesis divide by conventional mitosis, the rest dividing by acytokinetic mitosis leading to the formation of binucleate cells. During ageing the probability of hepatocyte polyploidization increases and in this period there are two polyploid or binucleate cells for every diploid dividing by conventional mitosis.

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References

  • Adler CR, Ringlage WR, Böhm N (1981) DNA content and cell number in heart and liver of children. Pat Res Pract 172:25–41

    CAS  Google Scholar 

  • Altmann H-W, Loeschke K, Schenk K (1966) Über das Karyogramm der menschlichen Leber unter normalen und pathologischen Bedingungen. Virchows Arch [A] 341:85–101

    CAS  Google Scholar 

  • Ashworth CT, Reid HC (1947) Intralobular regeneration of liver cells in man. Am J Pathol 23:269–278

    Google Scholar 

  • Belov LN, Kogan ME, Leontjeva TA, Kostyrev OA, Cellarius YA (1975) Preparation of isolated cells by alkaline dissociation of formaldehyde fixed tissues (in Russian). Cytology 17:1332–1337

    CAS  Google Scholar 

  • Bluger AF, Kartashova OY (1977) Reparative processes under some liver deseases (in Russian). Sucsesses Hepatol 6:120–132

    Google Scholar 

  • Brodsky VY, Uryvaeva IV (1977) Cell polyploidy: its relation to tissue growth and function. Int Rev Cytol 50:275–332

    Article  PubMed  CAS  Google Scholar 

  • Brodsky VY, Uryvaeva IV (1985) Genome multiplication in growth and development. University Press, Cambridge

    Google Scholar 

  • Boyd E (1933) Normal variability in weight of the adult human liver and spleen. Arch Pathol 16:350–372

    Google Scholar 

  • Boyd E (1941) Outline of physical growth and development. Burgess, New York

    Google Scholar 

  • Carriere R, Patterson D (1962) The counting of mono- and binucleated cells in tissue section. Anat Rec 142:443–456

    Article  PubMed  CAS  Google Scholar 

  • Cavalli G (1960) Contenuto in acido dessiribonucleico e volume nucleare degli epatociti umani durante l'organogesi e nell'adulto. Z Mikr Anat Forsch 66:428–444

    PubMed  CAS  Google Scholar 

  • Epstein CJ (1967) Cell size, nuclear content and the development of polyploidy in the mammalian liver. Proc Natl Acad Sci 57:327–334

    Article  PubMed  Google Scholar 

  • Gahan PB, Middleton J (1984) Euploidization of human hepatocytes from donors of different ages and both sexes compared with those from cases of Werner's syndrome and progeria. Exp Gerontol 19:355–358

    Article  PubMed  CAS  Google Scholar 

  • Gerhard H, Schultze B, Maurer W (1971) Zellklassen und Ploidiestufen in isolierten Leberzellen der Maus. Exp Cell Res 69:223–226

    Article  PubMed  CAS  Google Scholar 

  • Grabner W, Pfitzer P (1974) Number of nuclei in isolated myocardial cells of pigs. Virchows Arch [B] 15:279–294

    CAS  Google Scholar 

  • Grisham JW (1969) Cellular proliferation in the liver. In: Fry RJM (ed) Normal and maligant cell growth. Springer, Berlin Heidelberg New York, pp 28–43

    Google Scholar 

  • Kanungo MS (1980) Biochemistry of ageing. Academic Press, London

    Google Scholar 

  • Kasten FH (1961) Auramine O-SO2, a highly fluorescent Schifftype reagent for DNA in the Feulgen reaction. J Histochem Cytochem 9:599

    Google Scholar 

  • Kitamura O, Hidaka T, Ashihara T, Takeoka O, Kagawa K, Okuda K, Takahashi T, Takino T (1979) Age-related changes in ploidy classes of liver cells in human and rats as studied by the Feulgen-DNA cytofluorometry. Jpn J Gastroenterol 76:223–230

    CAS  Google Scholar 

  • Koike Y, Suzuki Y, Nagata A, Furuta S, Nagata T (1982) Studies on DNA content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometry and radioautography. Histochemistry 73:549–562

    Article  PubMed  CAS  Google Scholar 

  • Korenchevsky V (1961) Physiological and pathological ageing. Karger, Basel

    Google Scholar 

  • Kudryavtsev BN, Kudryavtseva MV, Shalakhmetova TM, Zavadskaya EE, Ioffe VA, Barsky IY, Papayan GV (1979) Cytofluorometric determination of glycogen content in the rat liver cells of different ploidy (in Russian). Cytology 21:218–221

    CAS  Google Scholar 

  • Kudryavtsev BN, Kudryavtseva MV, Zavadskaya EE, Smirnova SA, Skorina AD (1982) Polyploidy in the human liver cells at the norm and in patients with chronical hepatitis (in Russian). Cytology 24:436–443

    Google Scholar 

  • Kudryavtsev BN, Rozanov YM (1974) Cytofluorometry. Main principles. In: Methods of developmental biology (in Russian). Nauka, Moscow, pp 497–500

    Google Scholar 

  • Kudryavtsev BN, Stein GI, Tereshin GG (1986) Analysis of cell polyploidization kinetics in the rat liver parenchyma (in Russian) Cytology 28:828–836

    Google Scholar 

  • Kudryavtseva MV, Zavadskaya EE, Skorina AD, Smirnova SA, Kudryavtsev BN (1983) A method for obtaining isolated human hepatocytes from puncture biopsies (in Russian). Lab Delo 9:21–22

    Google Scholar 

  • Leevy CM (1963) In vitro studies of hepatic DNA synthesis in percutaneous liver biopsy specimens. J Lab Clin Med 61:761–779

    CAS  Google Scholar 

  • Leevy CM (1967) Observations on hepatic regeneration in man. Adv Intern Med 13:97–126

    PubMed  CAS  Google Scholar 

  • Leuchtenberger C, Leuchtenberger R, Davis AM (1954) A microspectrophotometric study of the desoxyribose nucleic acid (DNA) content in cells of normal and maligant human tissues. Am J Pathol 30:65–80

    PubMed  CAS  Google Scholar 

  • Munzer FT (1923) Über die Zweikernigkeit der Leberzellen. Arch Mikr Anat 98:249–282

    Google Scholar 

  • Nadal C, Zaidela F (1966) Polyploïdie somatique dans le foie de rat. I. Le rôle des cellules binucléées dans la génese des cellules polyploïdes. Exp Cell Res 42:99–116

    Article  PubMed  CAS  Google Scholar 

  • Nagl W (1978) Endopolyploidy and polyteny in differentiation and evolution. Towards and understanding of quantitative and qualitative variation of nuclear DNA on ontogeny and phylogeny. North-Holland, Amsterdam

    Google Scholar 

  • Polischuk AM (1983) Peculiarities of the hepatocytes polyploidization in the growing and regenerating liver (in Russian) Sucsess Mod Biol 96:451–465

    Google Scholar 

  • Ranek L (1976) Cytophotometric studies of the DNA, nucleic acid and ptotein content of human liver cell nuclei. Acta Cytol 20:151–157

    PubMed  CAS  Google Scholar 

  • Ranek L, Keiding N, Jensen ST (1975) A morphometric study of normal human liver cell nuclei. Acta Pathol Microbiol Scand 83:467–476

    CAS  Google Scholar 

  • Schultze B, Kellerer AM, Grossman C, Maurer W (1978) Growth fraction and cycle duration of hepatocytes in three-week-old rat. Cell Tiss Kinet 11:241–249

    CAS  Google Scholar 

  • Seglen PO (1976) Preparation of isolated rat liver cells. Methods Cell Biol 13:29–83

    Article  PubMed  CAS  Google Scholar 

  • Stein GI, Kudryavtsev BN (1992) A method for investigating hepatocyte polyploidization kinetics during postnatal development in mammals. J Theor Biol 156:349–363

    Article  PubMed  CAS  Google Scholar 

  • Swartz FJ (1956) The development in the human liver of multiple desoxyribose nucleic acid (DNA) classes and their relationship to the age of the individual. Chromosoma 8:53–72

    Article  PubMed  CAS  Google Scholar 

  • Takehara K (1975) Studies on nucleic acid metabolism in diseasen livers with special references to different responces of each tissue constituent of the liver. I. Investigation of human livers of patients with various liver diseases. Jpn J Gastroenterol 72:527–536

    CAS  Google Scholar 

  • Tauchi H (1961) On the fundamental morphology of the senile changes. Nagoya J Med Sci 24:97–132

    PubMed  CAS  Google Scholar 

  • Tauchi H, Morikava T (1954) On the nature of senile atrophy of liver and spleen in comparison with non-senile atrophy. Nagoya Med J 2:1–12

    Google Scholar 

  • Tauchi H, Sato T (1978) Hepatic cells of the aged. In: Liver and ageing. Elsevier, Amsterdam, pp 3–20

    Google Scholar 

  • Uryvaeva IV, Faktor VM (1974) The delay of the mitotic cycle processes in mice proliferating hepatocytes under stress effect (in Russian). Cytology 16:1100–1105

    CAS  Google Scholar 

  • Uryvaeva IV, Marschak TL (1969) Analysis of proliferation of diploid and polyploid cells in the regenerating liver of mouse (in Russian). Cytology 10:1252–1258

    Google Scholar 

  • Watanabe M (1970) DNA synthesis in polyploid and binucleate hepatic cells in the regenerating rat liver of different ages. J Med Sci 33:1–11

    CAS  Google Scholar 

  • Watanabe T, Shimada H, Tanaka Y (1978) Human hepatocytes and ageing: a cytophotometrical analysis in 35 suddendeath cases. Virchows Arch [B] 27:307–316

    CAS  Google Scholar 

  • Wheatley DN (1972) Binucleation in mammalian liver. Exp Cell Res 74:455–465

    Article  PubMed  CAS  Google Scholar 

  • Zavarzin AA (1967) The DNA synthesis and the cell populations kinetics in mammalian ontogenesis (in Russian). Nauka, Leningrad

    Google Scholar 

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Kudryavtsev, B.N., Kudryavtseva, M.V., Sakuta, G.A. et al. Human hepatocyte polyploidization kinetics in the course of life cycle. Virchows Archiv B Cell Pathol 64, 387–393 (1993). https://doi.org/10.1007/BF02915139

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  • DOI: https://doi.org/10.1007/BF02915139

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