The relation of the phenomenon of nuclear achromasia to cell activation for proliferation

As it has been shown earlier, the cells of experimental tumours as well as some normal cells of the thymus, spleen and testes show the phenomenon of nuclear achromasia (low affinity for ionic dyes) in cytological preparations. Possible connection between the phenomenon and activation for proliferation was the subject of the study presented. A reliable increase in the number of cells displaying the nuclear achromasia when staining with methylene blue after treatment with phytohaemagglutinin for 30 min as well as appearance of such cells in rat liver regenerates 1 h after partial hepatectomy was substantiated to be a result of the cell activation as tested by the enhanced acridine orange intercalation into their DNA.     

The origin of 5 S DNA from tumor ascitic fluid

Certain properties of DNA from chromatin mononucleosomes of the normal rat liver were compared with those of 5 S DNA from the ascitic fluids of human and animal tumours. Both DNA proved to be identical by their electrophoretic mobility in 8% PAAG and by characteristic violet tinge when stained with methylene blue. Thermal and alkaline denaturation causes less degradation of mononuclesome DNA than 5 S DNA. It is shown that 5 S DNA of ascitic fluid of Ehrlich ascite tumour of mice hybridizes with a higher amount of mouse genome DNA restricts. An assumption is advanced that 5 S DNA is either a product of chromatin decay to mononucleosomes or a product of extracopial synthesis and is delivered to ascitic fluid surrounding the tumour cells as a result of activation of Ca, Mg-dependent endonuclease of the latter.     

Appearance of new transplantation antigens in tumor cells treated with RNA

Immunization of mice with the Wistar rat liver tissue increased their resistance to the subsequent intramuscular transplantation of Krebs-2 tumour cells preincubated with the rat liver RNA and did not affect the transplantability and growth of the same untreated tumour cells. The growth of the tumour cells pretreated with allogenic RNA did not differ from the growth of the untreated tumour cells when the mice were immunized with material genotypically different from the RNA tissue-source. When the immunizing tissue and RNA source were genotypically identical, the mass of the tumours growing in three tested mice strains (A/He, CC57BR, BALB/c) was 40-50% less than that of untreated tumours and the enhancement effect was observed in C3Hf mice. It is suggested that RNA preparations induce the appearance of the transplant antigens in tumour cells similar to those of RNA donors tissues. The effect of RNA preparations was abolished by RNAse incubation.     

Characteristics of the epidermal growth factor receptors in the epithelium of the gastrointestinal tract of rats and in intestinal tumors induced by 1,2-dimethylhydrazine

Using the Scatchard analysis of 125J-EGF binding it was shown that plasma membranes of gastric and small intestinal epithelial cells contain approximately 20 times less EGF-receptors (EGF-R) than liver cells. Investigation of the phosphorylation activity of EGF-R-kinase was performed in vitro on plasma membranes from intestine, intestinal tumours and liver cells. The main protein phosphorylated at tyrosine in the tumours was p34 but the intensity of EGF-R autophosphorylation and its total protein-tyrosine kinase activity were reduced (as compared with small-intestinal and liver cell membranes). In the tumours of the colon induced by DMH an increased binding of 125J-EGF has been observed as compared with normal colonic enterocytes and increased number of EGF-R was clearly demonstrated. Phosphorylation of p34 in the intestinal membranes proceeds much more intensively than that of EGF-R.     

Changes in the epidermal growth factor receptors in the liver cells of rats in N-nitrosodiethylamine-induced hepatic carcinogenesis

A sharp decrease in the number of epidermal growth factor receptors (EGF-R) in the rat liver plasma membranes had been found at different stages of diethylnitrosamine-induced carcinogenesis. The complete loss of high-affinity binding sites for EGF did not prevent EGF-dependent autophosphorylation of EGF-R. Hepatocytes from the rat liver tumors in the primary culture had two classes of EGF-R: high and low affinity ones, though their number had been twice less than in the normal hepatocytes. The dynamics of internalization and down-regulation of EGF-R was very similar in the primary culture of transformed and normal hepatocytes. It testifies that there are some factors of microenvironment in the liver during carcinogenesis which cause the loss of EGF-R (down-regulation) and a decrease of their affinity (activation of protein kinase C). A possible autocrine or paracrine nature of these factors is discussed.     

Carcinogenic hazard of small doses of nitrite in connection with the endogenous synthesis of nitroso compounds

Carcinogenic risk of small doses of precursors of nitroso compounds, i.e. sodium nitrite (total dose in 0.2-2.0 g/mouse in drinking water) and morpholine (total dose is 0.23 g/mouse in bread) was studied in 520 CBA and 290 C57Bl mice during 96 weeks. It is shown that under these conditions the carcinogenic effect was more pronounced in CBA mice: there was a significant increase in general incidence of tumours, particularly liver tumours and hemoblastoses in CBA females and malignant liver tumours in CBA males.     

Effect of immunization with tularemia vaccine on 3,4-benz[a]pyrene-induced blastomogenesis and mutagenesis in rats

The living tularemia vaccine is studied for its effect on rat tumours and chromosome aberrations in bone marrow cells during 3,4-benz(a)pyrene injection (BP). It is established that a single epicutaneous vaccination of rats decreases the incidence of BP-induced tumours, prolongs the latent period and reduces the mean weight of tumours as well as lowers the number of myelocaryocytes with chromosome aberrations when BP is administered 15 days after immunization. 125 days after a single subcutaneous injection of BP in a dose of 4 mg the tumours appeared in 57% of animals and in 35% of preliminarily immunized animals. 24 h after intraperitoneal administration of 4 mg of BP the immunized rats revealed a 35% decrease in the amount of chromosome aberrations in myelocaryocytes as compared to the nonimmunized rats.     

Specific growth rate and macrophagal infiltration of experimental tumors

The relationship between the macrophage infiltration and the specific growth rate of tumours was studied by the technique of spontaneous migration of lymphoreticular cells from tissue fragments. In the case of dimethylnitrosamine-induced rat kidney tumours and Ehrlich solid tumour in mice the increased migration of activated macrophages was associated with the average specific growth rate. The macrophage infiltration of tumours and systemic immune reactivity to tumour-associated antigens depend probably on tumour cell kinetics.     

Dynamics of levels of 3-OAK antigens and ascorbic acid in the liver of rats and mice during hepatocarcinogenesis

Dynamics of the content of 3-OAK-A in the liver, blood and urine as well as of free and bound AK in the liver of rats and mice was traced by the quantitative precipitation reaction and oxidimetric method of ascorbic acid (AA) determination. It was shown that an increase in the content of 3-OAK-A in the liver during carcinogenesis initiation and progression is accompanied by a decrease in the AA content in this organ. One of the possible mechanisms inhibiting the formation of 3-OAK-A is "interception" of the proteins involved in the formation of 3-OAK-A.     

Carcinogenic effect of N-nitrosodimethylamine after application to rat skin

A pronounced carcinogenic action was detected after ten-fold application of nitrosodimethylamine in 3 doses (calculated doses equal 10.0; 5.0; 1.0 mg per rat). The tumour incidence in groups is equal to 93.3%, 20.0%, 6.6% and 3.3% (in control). No morphological changes were found in the place of application. Induced tumours localized in the liver, lungs and kidneys.     

Polyamine levels and diamine oxidase activity in the rat liver and kidneys during hepatocarcinogenesis induced by N-nitrosodiethylamine

Changes in the polyamine metabolism in the liver and kidneys have been studied in rats with N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis and under diethylamine administration. It is found that the intracellular content of polyamines rises and the diaminooxidase activity falls in the liver (but not in the kidneys) of rats who were given NDEA in drinking water. These changes are most pronounced during the first month of carcinogenesis and in the induced tumours. It is a typical (though not specific) biochemical peculiarity of hepatocarcinogenesis.     

Changes in the proteolytic activity and components of the blood kallikrein-kinin system during the growth and metastasis of experimental neoplasms

Changes in the total blood proteolytic activity, prekallikrein level, serum kallikrein inhibitors and other proteinases were studied during the growth and metastatic spreading of different experimental tumours. It has been established that the dissemination and metastatic spreading of Guérin carcinoma inoculated intratesticularly to rats is accompanied by a decrease in the content of prekallikrein and serum kallikrein inhibitors, which shows the activation of blood kinins. Changes in the total proteolysis and in prekallikrein content in mice with carcinoma 3LL and melanoma B-16 are of two-phase character: at the first stage after tumour inoculation there occurs an increase in the proteolytic activity and in prekallikrein content. At the second stage (14 to 28 days) characterized by the appearance of lung metastases, quite a pronounced and stable inhibition of the total proteolysis and of prekallikrein level was observed together with an increased level of proteinase inhibitors. The data obtained show that disturbances in the reactions of limited proteolysis, in particular shifts of the blood kallikrein-kinin system, play a definite role in the development of the metastatic process.     

1,2-dimethylhydrazine induction of epithelial tumors of the kidneys in CBA strain mice

The results of experiments on the 1,2-dimethylhydrazine (DMH) induction of epithelial renal tumours in CBA male mice are presented. The dose-response study shows a sharp increase (from 5 to 75%) of the epithelial renal tumour incidence in the range of 2, 4 and 8 injections of DMH. Higher doses induce a decrease of the tumour incidence due to the early death caused by other tumours. DMH is shown to be the most powerful renal carcinogen in mice. Serial sacrifice of mice after 5 injections of DMH is a convenient model for the study of renal carcinogenesis in mice. Main histological types of epithelial renal tumours are illustrated.     

A comparative study of graph-based, eikonal, and monodomain simulations for the estimation of cardiac activation times

The bidomain and monodomain equations are well established as the standard set of equations for the simulation of cardiac electrophysiological behavior. However, the computational cost of detailed bidomain/monodomain simulations limits their applicability in scenarios where a large number of simulations needs to be performed (e.g., parameter estimation). In this study, we present a graph-based method, which relies on point-to-point path finding to estimate activation times for single points in cardiac tissue with minimal computational costs. To validate our approach, activation times are compared to monodomain simulation results for an anatomically based rabbit ventricular model, incorporating realistic fiber orientation and conduction heterogeneities. Differences in activation times between the graph-based method and monodomain results are less than 10% of the total activation time, and computational performance is orders of magnitude faster with the proposed method when calculating activation times at single points. These results suggest that the graph-based method is well suited for estimating activation times when the need for fast performance justifies a limited loss of accuracy.     

Agonist-like activity of antibodies directed against the second extracellular loop of the human cardiac serotonin 5-HT4(e) receptor in transfected COS-7 cells

We have previously reported that antipeptide antibodies directed against the second extracellular loop of the cardiac h5-HT4 receptor could block the activation of the L-type Ca channel in human atrial cardiomyocytes. In this paper we investigate the immunological and physiological activity of these antibodies, in a cell system expressing a larger amount of receptors than the atrial cells. The recombinant receptor was expressed at the surface of COS-7 cells under an active form (serotonin, EC50 = 1.81 x 10(-7) M), at a high level (375 +/- 25 fmol receptor/mg total protein) and was able to bind a specific ligand (GR113808) with a high affinity (Kd = 0.28 +/- 0.05 nM). In this system, the same anti-peptide antibodies used for the cardiac cells induced an "agonist-like" effect on the recombinant h5-HT4 receptor. These results are in line with those shown for others G-protein coupled receptors, as adrenoreceptors. In addition, this work showed that the effect of the antibodies is not only dependent on the epitopic region recognised but also on the molecular density and/or the cellular environment of the target receptors. Finally, our results support the hypothesis that the h5-HT4 receptor could be a new target for autoantibodies in patients with atrial arrhythmia.     

Effect of the epidermal growth factor on 1,2-dimethylhydrazine-induced carcinogenesis in the rat intestinal mucosa

The radioimmunological and radioreceptor methods have been used to show that sialadenectomy leads to the stable decrease of the epidermal growth factor (EGF) concentration in saliva and blood serum. The mean number of colon tumours per rat was significantly lower among the rats which had been sialadenectomized before injections of the carcinogen, than in the control. But a sharp stimulation of carcinogenesis in the duodenal mucosa was observed after sialadenectomy. The production of the alpha-transforming growth factor with the EGF-competing activity for the EGF-receptors was found in the chemically-induced rat colon tumours.     

Effect of correcting liver function on the development of DMBA-induced mammary gland tumors and the metabolism of sex steroid hormones in rats

The tumours of mammary glands in Wistar rat females were induced by threefold intravenous administration of 7,12-dimethylbenz (a) anthracene (DMBA). The application of pharmacological preparations contributing to the liver function correction (PCLF) in the process of carcinogenesis and during the surgical treatment of mammary tumours leads to prolongation of the first tumour latent period after DMBA administration and of recurrent tumours after the operation. The lowering of the frequency, multiplicity and the rate of mammary tumours growth were also observed. The use of PCLF exerted a normalizing effect on the level of sex steroid hormones in rats.     

大鼠肝脏热损伤的光散射研究

利用连续波 (6 5 0nm)透射测量技术 ,对不同温度 (5 5～ 95℃ )作用下大鼠肝脏组织的热损伤过程进行了动态监测。薄样品的采用 ,使得通过透射测量直接得到散射系数的变化量随时间及温度的变化关系成为可能。结果表明 ,热作用过程中 ,散射系数的变化量随时间的变化关系可用于描述生物组织的热损伤过程 ;利用所得结果推导出了大鼠肝脏组织的热损伤参数 (其反应的活化能为 135 2 (kJ mol) ,熵为 116 7(J K·mol) ) ;在此基础上对组织的热损伤情况进行了探讨。     

Variability and inheritability of the "level of endogenous SH groups" trait in cell and clone populations of transplantable rat tumors

Heterogeneity of cell and clone populations in various histogenesis of rat tumours has been studied by the content of the endogenic SH-groups. The distribution of the ovary tumour cells and their clone lines, as well as lung clones of the sublines of rat rhabdomyosarcoma RA-2 as to the content of endogenic SH-groups is of persistent and monopeak character. Modal classes are well expressed, in several clone lines variability of the cell composition is higher than in the initial population. In this case the distribution of cells as to the SH-group content differs from the normal (asymmetrically). The level of SH-groups in the RA-2 rat subclone in 71 lung clones positively correlates with the level in hypodermic transplants. So, the heterogeneity of the clone populations as to the amount of SH-groups depends on both the genetic interclonal differences and fluctuations of the environmental factors.     

Phospholipid composition of tumors and homologous tissues of rats exposed to dimethylnitrosamine

Quantitative changes in phospholipid spectra of blood serum, liver, kidneys and tumour tissues were determined at different stages of carcinogenesis induced by nitrosodimethylamine in rats. It was established that tissue of kidney tumours differs from homologous tissue only in the total amount of phospholipids as well as of cardiolipin phosphatidylethanolamine, phosphatidylserine and sphingomyelin. Essential changes were revealed in the phospholipid spectrum of blood serum and liver of tumour-bearing rats. The inverse correlation was found in phosphatidylethanolamine and phosphatidylserine amount in these tissues.