Control of Liver Growth by Growth Inhibitors (Chalones)
Chalones are auto-inhibitory factors which control tissue growth by reducing cell multiplication. To belong to this class of factors, a product extracted from blood or organs has to meet the following conditions: (1) It acts specifically on one type of cells, (2) the same cells produce the factor and are sensitive to it, and (3) the factor is truly involved in the physiological regulation of cell multiplication.
Various methods have been used to detect chalone-like factors affecting hepatic cells.
In vivo methods. Factors are assayed on synchronized or semisynchronized hepatocyte multiplication induced by mitogenic stimulus, i.e. (1) Partial hepatectomy in adult rats or weanlings, and (2) irritating stress in 10-day-old rats.
In vitro methods. Factors are assayed on in vitro cell multiplication or DNA synthesis.
Cultivation of liver cells has not been widely used because hepatocytes grow poorly and dedifferentiate.
Hepatoma cells are easier to manage but have probably lost some of the normal cell’s physiological regulatory mechanisms.
Liver slices were prepared during the period of maximum DNA synthesis after partial hepatectomy and used to detect factors reducing this synthesis.
Origin: liver extracts, blood serum or plasma.
Time of action in the cell cycle: at the initiation of the cell cycle or early G1, in late G1 or at the G1-S transition, in the S phase, in G2 or at the G2-M transition.
Molecular weight: factors of about 2,000 daltons or proteins of more than 40,000.
The present article raises several questions: Are there really several factors or only one with different characteristics, depending on the methodologies used for extraction, purfication and assay? Are these factors really involved in physiological regulation, and are they auto-inhibitory?
Precise answers will depend on the purification of the starting products and on the use of more sensitive methods for physiological investigations.
Key wordsHepatocytes Proliferation Inhibitors Cell cycle Chalones
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