Reconstitution of liver mass via cellular hypertrophy in the rat

Authors

  • Peter Nagy,

    1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, Hungary
    2. Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Tadahisa Teramoto,

    1. Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Valentina M. Factor,

    1. Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Aranzazu Sanchez,

    1. Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Janos Schnur,

    1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, Hungary
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  • Sandor Paku,

    1. Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis University of Medicine, Budapest, Hungary
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  • Snorri S. Thorgeirsson Dr.

    Corresponding author
    1. Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD
    • National Cancer Institute, Bldg. 37, Room 3C28, 37 Convent Drive MSC4255, Bethesda, MD 20892-4255. fax: 301-496-0734.
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Abstract

The liver has an extremely effective regenerative capacity. When 70% of a rat liver is removed by surgery, the liver mass regrows in 7 to 10 days by the compensatory hyperplasia of the remnant part. In case of damage to the surviving hepatocytes, the facultative stem-cell compartment is activated and the liver regenerates by means of oval-cell proliferation/differentiation. In the present study, we demonstrate that when both hepatocyte proliferation and stem-cell activation were prevented by dexamethasone (Dex) administration, the liver mass was restored in the absence of DNA synthesis. The restoration of the liver was accomplished by the preferential enlargement/hypertrophy of the periportal hepatocytes. A similar response was observed when cell proliferation was arrested by 5-fluorouracil (FU) following partial hepatectomy. Therefore, the hepatocytic hypertrophy appears to provide an alternative mechanism of liver-mass restoration. This hypertrophic condition of the liver is not stable, because following the withdrawal of Dex, the enlarged hepatocytes entered in the cell cycle and the normal liver structure and DNA content was re-established.

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