ABSTRACT
A 12 kD protein (IHP-12) was isolated from the cytosol of liver cells; IHP-12 inhibited proliferation of the liver cells by 50% when injected at 2.5 mg/100 g animal weight. Repeated injections of IHP-12 induced resistance of the liver cells to its anti-proliferative effect. After intraperitoneal injection, IHP-12 is localized in the cytosol and to a lesser extent, in cell nuclei. IHP-12 is degraded in the cytosol but in nuclei it retained its native structure for at least 8 h. The mechanism of induced resistance to IHP-12 was not related to a change in cell binding of IHP-12, its distribution in cellular compartments, and intracellular metabolism. The induced resistance may be associated with a change in the direction of IHP-12 activity, i.e., change in its function in the animal.
Subject(s)
Growth Inhibitors/pharmacology , Proteins/pharmacology , Animals , Cell Division/drug effects , Cell Nucleus/metabolism , Cytosol/metabolism , DNA/metabolism , Drug Resistance , Growth Inhibitors/isolation & purification , Growth Inhibitors/metabolism , Liver/chemistry , Liver/cytology , Liver/drug effects , Liver Regeneration , Proteins/isolation & purification , Proteins/metabolism , RNA/metabolism , Rats , Rats, WistarABSTRACT
The duration and reversibility of the liver chalone-containing fraction on DNA synthesis in regenerating liver cells have been studied. It has been shown that administration of the [14C] chalone-containing fraction results in a rapid specific binding of the label to liver cells in which the label is retained for no less than 12 hours. The specific radioactivity of DNA in regenerating liver cells decreases 3-4-fold irrespective of the time of administration of the [14C] chalone-containing fraction. After repeated injections of the fraction under study, the hepatocytes loss their sensitivity towards this fraction. It is suggested that chalones exclude some part of the hepatocytes from the cell cycle which, in turn, leads to the asynchronous involvement in the cell cycle of a new hepatocyte population which is resistant to the chalone action.
Subject(s)
Growth Inhibitors/physiology , Liver Regeneration/physiology , S Phase/physiology , Animals , DNA Replication/physiology , Liver/cytology , Liver/metabolism , Rats , Rats, WistarABSTRACT
The age dynamics of albino rat kidney cell proliferation in conditions of compensatory hypertrophy and influence of endogenous inhibitors on this process have been studied. The lack of influence of repeated injection of inhibitors on kidneys cell division of 1-month old rats has been shown, while the level of kidney proliferation of 3-month old rat and 12-month old rat decreased of about 50% and of 24-month old rat decreased of about 34%.
