Factors within the body determining the glycogen reserves in the tissues of rats with transplantable tumours.

Attempts have been made to determine the reason for the depletion of glycogen reserves in tumour-bearing rats. The possible roles of anorexia, competition for glucose by the tumour, and lack of hormonal control of glycogen biosynthesis have been investigated. The glycogen content of the liver, skeletal muscle, and brain, and the levels of glucose and the hormones corticosterone, insulin, and glucagon were determined in healthy rats which had been starved for various periods and in tumour-bearing rats carrying the fast-growing Zajdela ascites hepatoma or the slow-growing solid hepatoma 27. It was found that towards the terminal stages of tumour development there was an increase in the content of corticosterone and glucagon in the blood serum and also an increase in the glycogen reserves in skeletal muscle and brain despite the presence of hypoglycaemia and hypo-insulinaemia. There was at this time a sharp fall in the level of liver glycogen. It is shown that neither anorexia nor excessive competition for glucose by the tumour were the main reasons for liver glycogen depletion and hypoglycaemia. A strong correlation was observed, however, between the occurrence of anaemia and the loss of liver glycogen, which suggests that the former may be an important factor in the changes in host tissue observed in response to tumour growth.

Intracellular factors determining the deposition of glycogen. The role of gluconeogenesis.

The interrelationship between glycogen biosynthesis and do novo glucose formation in rats was studied by determining the oxaloacetic acid, ATP, and glycogen levels in the tissues of healthy starved rats and during the growth of transplantable hepatomas with different rates of growth. From the results obtained it was proposed that glycogen biosynthesis and de novo glucose formation are mutually enhanced and coupled processes. The validity of this conclusion was confirmed by in vitro model experiments involving the use of isolated-liver perfusion. Results of a multiple regression analysis indicated that the efficiency of gluconeogenesis and glycogen deposition is determined by the supply of oxygen to the liver, by the oxaloacetic acid content of this organ, and also by the degree of reduction of the glucose precursor. It was also shown that the ability of glucocorticoids and glucagon to enhance gluconeogenesis is dependent on the supply of oxygen to the liver. From the results of this in vivo and in vitro comparative study it is concluded that deposition of glycogen in the liver and possibly also in the brain is determined by the efficiency of gluconeogenesis.

Effect of putrescine on carbohydrate and lipid metabolism in rats.

Administration of putrescine (tetramethylenediamine) to healthy rats induced rapid and significant changes in carbohydrate and lipid metabolism. On the basis of changes in the stores of glycogen in the liver and muscles, and the concentration of glucose, nonesterified fatty acids, and total lipids in the blood, it appears that the sites of action of putrescine are the liver, muscle, and probably adipose tissue. A low dose of putrescine [30 mumol (100 g)-1 body weight] produced effects similar to those induced by glucagon and adrenaline. The increase in glycogen reserves and the sharp reduction in the levels of nonesterified fatty acids and total lipids seen after administration of high doses of putrescine [60-120 mumol (100 g)-1 body weight] are similar to the combined effects of insulin and glucocorticoids. The induction of hypoglycaemia, the reduction in the levels of nonesterified fatty acids and total lipids, and the increased reserves of glycogen in muscle that were seen with the higher doses occurred alongside a fall in blood insulin level. It is suggested that increased levels of polyamines in the blood might produce disturbances in the link between carbohydrate and lipid metabolism in cancer patients and tumour-bearing animals.

[Changes in gene expression in the brain of rats with Zajdela's ascitic hepatoma]. / Izmeneniia ékspressii nekotorykh genov v golovnom mozge krys s perevivaemoi astsitnoi gepatomoi Zaidela.

Expression of some genes in the brain of ascitic hepatoma of Zajdela bearing rats was compared with that of control animals using Northern blot hybridization technique. The differences revealed were: an increased expression of actin gene and decreased expression of hsp70 gene in the brain of tumor-bearing animals.

[Change in tissue glycogen reserves in tumor bearers as a reflection of a hypoglycemic stress syndrome]. / Izmenenie zapasov glikogena v tkaniakh organizma-opukholenositelia kak otrazhenie gipoglikemicheskogo stress-sindroma.

Glycogen content in the brain, liver and skeletal muscles of rats bearing ascite Zajdela hepatoma (AZH) and solid 27 hepatoma (27-H) has been studied. Serum glucose levels directly correlated with liver glycogen reserves. In the terminal stage of tumor growth depletion of liver glycogen was observed, while the stores of muscle glycogen did not diminish. Within 1-4 days (AZH) and 15-30 days (27-H) after implantation the stores even exceeded those of control healthy rats. In the terminal stage, in spite of hypoglycaemia development, the content of brain glycogen was significantly elevated in both groups of animals.

[Glucocorticoid-mediated degradation of DNA in thymocytes of rats with transplantable Zajdela ascites hepatoma]. / Oposredovannyi gliukokortikoidami raspad DNK v timotsitakh krys s perevivaemoi astsitnoi gepatomoi Zaidela.

Tumour growth was shown to be associated with DNA breakdown in thymocytes of rats bearing Zajdela ascites hepatomas. The tumour action on the thymus is mediated through adrenal glands since bilateral adrenalectomy completely prevents DNA breakdown in thymocytes. Using Southern hybridization of DNA genome with probes for histone, ribosomal and heat shock gene (hsp 70), it was shown that the degradation products of specific DNA sequences are as heterogenous as those of total DNA, although marked differences in appearance of nucleosomal ladder were seen. These data were interpreted to indicate different patterns of DNA breakdown in dying thymocytes. DNA breakdown in thymocytes in vivo and in isolated rat liver nuclei in vitro seems to proceed by similar mechanisms.

[Activation of lipolysis and ketogenesis in tumor-bearing animals as a reflection of chronic stress states]. / Aktivatsiia lipoliza i ketogeneza v opukholevom organizme kak otrazhenie khronicheskogo stressornogo sostoianiia.

In order to elucidate the peculiarities of brain metabolism in tumour-bearing organisms, the arterio-venous (A-V) content of glucose, acetoacetate (Ac-Ac), beta-hydroxybutyrate (beta-HB) and non-esterified fatty acids (NEFA) in growing Zajdela ascite hepatoma (ZAH) and solid hepatoma 27 (H-27) was compared. Analysis of metabolic patterns of healthy, starving and fed recipients (ZAH and H-27) revealed the inadequacy of the concepts on anorexia as being the cause of carbohydrate-lipid metabolic disturbances. In tumour-bearing organisms lipolysis and ketogenesis reflect the tumour-induced chronic stress. Absorption of beta-HB and release of Ac-Ac by brain were observed at all stages of malignant growth. This is probably due to a partial switch-over of brain metabolism to non-carbohydrate energy sources. Besides, certain stages of tumour growth are associated with active assimilation of NEFA by brain. A correlation between the A-V difference with respect to glucose and Ac-Ac as well as between the glucose and NEFA contents was established. It was assumed that the A-V difference in glucose is the main regulator of ketone body metabolism.

[Relation between disorders of glucose metabolism, secretion of somatotropic hormone, thyroxine, thyrotropin and hematocrit indices in rats with transplanted hepatomas]. / Vzaimosviaz' narushenii obmena gliukozy i sekretsii somatotropnogo gormona, tiroksina, tirotropina, pokazatelia gematokrita u krys s perevivnymi gepatomami.

The levels of growth hormone (GH) in the blood of rats with ascite Zajdela hepatoma and hepatoma 27 (H-27) are shown to increase during the tumour growth. Stimulation of the GH secretion is a result of the hypoglycaemic stress. An increase in the blood GH secretion is also observed in the fasting rats. To reveal the predominance of catabolic GH effects over the anabolic ones in the tumour host determination of the molar insulin/GH ratio in the blood is suggested. A direct correlation is found between reduction of this index, glycaemia and the content of liver glycogen. A short-term induced hyperglycaemia evokes a paradoxical reaction in terms of GH secretion. In contrast to control fasting rats, in tumour-bearing animals no correlation between thyrotropin and thyroxine blood concentration could be observed. Anaemia increasing progressively in the course of the tumour growth may be the cause of the above phenomenon.

[Characteristics of disorders of water-electrolyte homeostasis in rats with transplantable hepatomas]. / Osobennosti narushenii vodno-élektrolitnogo gomeostaza u krys s perevivivymi gepatomami.

The growth of ascitic Zajdela and solid 27 hepatomas in vivo is accompanied by significant changes in parathyroid hormones, calcitonin and aldosterone blood levels. In periods close to terminal ones, their level decreases presumably as a result of energy deficiency in the endocrine glands. The arising hormonal shifts are a result of a "metabolic stress" caused by the growing tumour.

[Role of supranucleosomal structures of chromatin in the uneven distribution of DNA-bound 7,12-dimethylbenz(a)anthracene metabolites formed in vivo or in the perfused rat liver]. / Rol' nadnukleosomnoi struktury khromatina v neravnomernom raspredelenii sviazannykh s DNK metabolitov 7,12-dimetilbenz(a)antratsena, obrazuiushchikhsia in vivo ili v perfuziruemoi pecheni krys.

It was demonstrated that the DNA closely associated with the nuclear matrix preferentially binds 7,12-dimethylbenz(a)anthracene (DMBA) metabolites. In experiments with perfused rat liver, it was found that the kinetic curves for adduct formation in all DNA fractions of DNP have maxima, the largest differences in the rate of metabolite binding in the DNA fractions being observed at the initial moment of perfusion. There is evidence that the preferential binding of DMBA metabolites to matrix DNA is due to the increased accessibility of the DNA to the metabolites rather than to its proximity to the nuclear membrane. This accessibility, in its turn, is due to the peculiarities of the supranucleosomal structure of transcriptionally active DNP fragments associated with the nuclear matrix.