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Related Experiment Videos

Induction of replicative competence ("priming") in normal liver.

J E Mead1, L Braun, D A Martin

  • 1Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912.

Cancer Research
|November 1, 1990
PubMed
Summary

Liver cells can be primed for replication through nutritional manipulation. Protein-deprived rats show enhanced DNA synthesis and mitosis upon refeeding, indicating a preparatory stage for cell proliferation.

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Area of Science:

  • Hepatocyte biology
  • Cellular and Molecular Physiology
  • Nutritional Science

Background:

  • Hepatocytes, the main cells of the liver, possess regenerative capacity.
  • Understanding the triggers and stages of liver cell replication is crucial for regenerative medicine and disease treatment.
  • Previous studies suggest that specific conditions can induce liver regeneration, but the priming mechanisms remain unclear.

Purpose of the Study:

  • To investigate if hepatocytes can be primed for replication in vivo using nutritional manipulation.
  • To determine the changes in protooncogene expression during this priming process.
  • To compare the response of primed hepatocytes to normal hepatocytes in vitro.

Main Methods:

  • Nutritional manipulation in rats: protein deprivation followed by amino acid refeeding.

Related Experiment Videos

  • Analysis of protooncogene (c-jun, c-myc, p53, c-fos, c-ras) mRNA expression in liver tissue.
  • Assessment of hepatic DNA synthesis and mitosis.
  • In vitro culture of hepatocytes from normal and protein-deprived rats.
  • Stimulation of DNA synthesis using growth factors (transforming growth factor alpha and epidermal growth factor).

    • Main Results:

    • Protein deprivation followed by amino acid refeeding induced hepatic DNA synthesis and mitosis in rats.
    • Protooncogenes c-jun, c-myc, and p53 mRNA levels were elevated in protein-deprived rat livers.
    • Amino acid administration to protein-deprived rats accelerated DNA synthesis and induced p53 and c-ras expression.
    • Hepatocytes from protein-deprived rats showed higher c-myc mRNA, faster morphological changes, and earlier peak DNA synthesis rates in culture.
    • Transforming growth factor alpha was more effective than epidermal growth factor in stimulating DNA synthesis in both normal and primed hepatocytes.

    Conclusions:

    • Hepatocytes undergo a priming stage before proliferation.
    • Replicative competence, without immediate DNA synthesis, can be induced in normal liver hepatocytes.
    • Nutritional manipulation provides a model for studying hepatocyte priming and replication.