Effect of triiodothyronine or etiroxate on DNA synthesis in intact and regenerating liver

An increase in liver DNA synthesis (p less than 0.01) was found in rats with an intact liver 24 h after the administration of a single dose of triiodothyronine (200 micrograms/kg i.g.) Statistically significant stimulation of DNA synthesis was also found in rats given triiodothyronine (p less than 0.01) or etiroxate (p less than 0.05) for 3 days at 24-hour intervals. When a single dose of triiodothyronine was administered immediately after partial hepatectomy (65-70% resection of the liver), increased stimulation of DNA synthesis (p less than 0.01) was found 24 h after the operation. Etiroxate partly inhibited DNA synthesis (p less than 0.05). In rats given triiodothyronine at 24-h intervals, starting at the time of partial hepatectomy, DNA synthesis 72 h after the operation was double the value in the control group. Marked stimulation of DNA synthesis by triiodothyronine (p less than 0.01) and an increase in the total DNA content of the liver (p less than 0.05) were likewise found 48 h after partial hepatectomy if the hormone was administered once, 24 h after the operation. The increase in the two indicators after the administration of etiroxate was not statistically significant.     

Effect of realimentation after several days' pure carbohydrate intake on DNA synthesis in regenerating rat liver

The authors studied the effect of realimentation after several days' isolated glucose or fructose intake on DNA synthesis in liver regenerating after partial hepatectomy (PH) (65-70%) or after carbon tetrachloride (CCl4) poisoning 1.5 ml/kg. Two days before PH or the administration of CCl4 and two days after, the experimental rats were given glucose (50% solution) of fructose (50% solution) as the only source of energy. Rats with PH were then fed for one day on a standard laboratory diet (25 cal% protein) or a high protein diet (81 cal% protein). Rats with CCl4 liver damage were fed for one day on the standard laboratory diet only. In the rats given glucose, liver DNA synthesis and the total amount of these nucleic acids in the liver 48 hours after CCl4 administration was lower than in the controls or the rats given fructose. In all the experimental groups (PH and CCl4), stimulation of liver DNA synthesis was observed after one day's realimentation. The total DNA content of the liver of rats with PH rose markedly during realimentation. The experiments indicate that the regenerative activity of damaged liver can be influenced by the nutritional regimen.     

Effect of realimentation after several days' isolated glucose or fructose intake on DNA synthesis in rat liver.

Marked stimulation of liver DNA synthesis was observed in rats given an isolated glucose or fructose diet for 4 days and theen refed one day on diets with different protein contents. The strongest stimulatn effect was found in rats refed, after an isolated glucose intake, with a high protein diet (81 cal%). The stimulant effect of refeeding on liver DNA synthesis was far less pronounced in rats subjected to several days' starvation before realimentation than in rats given a carbohydrate diet. The stimulant effect of realimentation after an isolated glucose intake was distinctly enhanced if triiodothyronine (50 microgram/100 g b.w., i.g.) was administered just before the change to a high protein diet. The increase in liver DNA synthesis in rats fed three days on fructose before undergoing partial hepatectomy was the same as in the controls. In rats given glucose prior to partial hepatectomy, the post-operative increase in DNA synthesis was partly inhibited.     

Effect of colchicine and vincristine on DNA synthesis in regenerating rat liver

The increases in the activities of hepatic thymidylate synthetase and thymidine kinase were significantly suppressed at 24 h after 70% partial hepatectomy in rats which had been administered a microtubule disrupter, colchicine or vincristine. The decrease of these enzymic activities was accompanied by a reduction of DNA content in 24 h regenerating liver. The immunoblotting assay showed that the depression of the thymidylate synthetase activity by the injection of colchicine or vincristine was due to the decrease of the enzyme protein. These results indicate that colchicine and vincristine inhibit the DNA synthesis during liver regeneration by inhibiting the induction of the key enzyme in DNA synthesis.     

Effect of triiodothyronine and hydrocortisone on aldolase metabolism in the rat liver

The biosynthesis, spontaneous breakdown and lifetime of rat liver aldolase after a single injection of thyroid adreno-cortical hormones were studied. Triiodothyronine and hydrocortisone were shown to have a pronounced effect on the enzyme metabolism.     

Effect of triiodothyronine on rat liver chromatin protein kinase.

1. Injection of triiodothyronine to rats stimulates protein kinase activity in liver chromatin nonhistone proteins. A significant increase was found after two daily injections. A 4-fold increase was observed with the purified enzyme after eight daily injections of the hormone. No variations were observed in cytosol protein kinase activity. Electrophoretic pattern, effect of heat denaturation, effect of p-hydroxymercuribenzoate seem to indicate that the enzyme present in treated rats is not identical to the enzyme in control animals, which suggests that thyroid hormone has induced nuclear protein kinase. Diiodothyronine, 3, 3', 5'-triiodothyronine have no effect on protein kinase. 2. Chromatin non-histone proteins isolated from rats injected with triiodothyronine incorporated more 32P when incubated with [gamma-32P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32P incorporation. It is suggested that some of the biological activity of thyroid hormone could be mediated through its effect on chromatin non-histone proteins.     

Effect of urethan on polyamine and DNA synthesis in the regenerating rat liver

When a single dose of urethan was injected into the peritoneal cavity of rats immediately after partial hepatectomy, DNA synthesis was delayed by 12 h. The induction of ornithine decarboxylase which was induced biphasically following partial hepatectomy was also reduced and delayed by 14–15 h by the administration of urethan. S-Adenosylmethionine decarboxylase activity in urethan-treated rat liver at 20 h and 29 h after operation was significantly lower than that of untreated animals. This enzyme activity was shown to increase thereafter, reaching a higher level than in untreated rats at 37–42 h. Hepatic spermidine content changed biphasically in a manner similar to DNA synthesis. These results suggest that the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase may correlate with DNA synthesis and that an increase of spermidine concentration is necessary to DNA synthesis.     

Effect of human fetal liver cells on the rate of DNA and nRNA synthesis in regenerating rat liver

The model of partial hepatectomy was utilized to investigate the influence of human fetal liver cells (FLCs) and of human embryo tissue (PCF) postnuclear cytoplasm fraction injection on the rate of DNA and nRNA synthesis in regenerating rat liver cells. Single infusion of FLCs and PCF into the spleen pulp of rats has been shown to increase the DNA synthesis 24 hours after the operation in 2.5 +/- 0.4 and 3.2 +/- 0.5 times respectively. A group of rats has been identified with no influence of the infusion on the DNA synthesis 24 hours after partial hepatectomy, this process having been even retarding in 48 hours after the operation. Meanwhile the FLCs and PCF infusion enhanced the intensity of nRNA synthesis in 72 hours after the operation in all the animal groups. The effect demonstrated is probably caused by the biologically active substances contained in the fetal tissues.     

Effect of triiodothyronine on the content of phospholipids in the rat liver nuclei.

The aim of the present study was to examine the effect of triiodothyronine (T3) on the content of phospholipids and on the incorporation of blood-borne palmitic acid into the phospholipid moieties in the nuclei of the rat liver. T3 was administered daily for 7 days, 10 microg x 100 g(-1). The control rats were treated with saline. Each rat received 14C-palmitic acid, intravenously suspended in serum. 30 min after administration of the label, samples of the liver were taken. The nuclei were isolated in sucrose gradient. Phospholipids were extracted from the nuclei fraction and from the liver homogenate. They were separated into the following fractions: sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine and cardiolipin. The content and radioactivity of each fraction was measured. It was found that treatment with T3 reduced the content of phosphatidylinositol and increased the content of cardiolipin in the nuclear fraction. In the liver homogenate, the content of phosphatidylinositol decreased and the content of phosphatidylethanolamine and cardiolipin increased after treatment with T3. The total content of phospholipids after treatment with T3 remained unchanged, both in the nuclear fraction and in the liver homogenate. T3 reduced the specific activity of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and cardiolipin and had no effect on the specific activity of sphingomyelin and phosphatidylinositol both in the fraction of the nuclei and the liver homogenate. It is concluded that excess of triiodothyronine affects the content of phospholipids in the nuclei. The changes in the content of phospholipids in the nuclei largely reflect changes in their content in the liver.     

Effect of an exogenous energy source and amino acids on DNA synthesis in regenerating rat liver

Rats on a protein-free diet synthesized less DNA after partial hepatectomy than rats on a normal diet. In regenerating livers of animals on the protein-free diet, induction of several enzymes involved in the DNA precursor synthetic pathway, and especially ribonucleotide reductase, were depressed. When young rats were maintained solely by parenteral nutrition after partial hepatectomy, exogenous amino acids were more important than the exogenous energy source for induction of enzymes involved in synthesis of DNA and its pyrimidine nucleotide precursors. In particular, induction of ribonucleotide reductase appeared to be controlled by exogenous amino acids. Tryptophan, methionine, phenylalanine, leucine, valine, isoleucine and threonine seemed to stimulate the induction of this enzyme most after partial hepatectomy.     

Tumor necrosis factor stimulates DNA synthesis in the liver of intact rats

TNF is cytotoxic to tumor cell lines but enhances growth of some nontransformed cells. Because animals administered TNF have an increase in liver size, we studied the [3H]thymidine incorporation into DNA in the liver of intact rats. A significant increase in [3H]thymidine incorporation is seen 20 hours following TNF administration and peaks at 24 hours. The lowest dose of TNF that increases DNA synthesis is 10 micrograms/200 g rat with a maximal increase occurring with 25 micrograms/200 g, considerably less than the dose required for maximally increasing plasma triglycerides. The increase in [3H]thymidine incorporation was shown to be due to an increase in DNA polymerase alpha activity (associated with the replication of DNA) rather than DNA polymerases beta (associated with DNA repair) plus gamma activity. These results indicate that TNF administration stimulates DNA replication in the liver of intact animals.