[Cell death in Jurkat cells induced by oxygen/nitrogen stress].

The maintenance of balance between lymphocyte proliferation and lymphocyte death is extremely important for normal functioning of the immune system. Considering essential role of nitrogen and oxygen radicals in functioning of immune competent cells, we studied the mechanisms of cell death induced by nitrogen/oxygen stress on the model of Jurkat cell line. We have observed that hyperproduction of reactive oxygen in Jurkat cells incubated with hydrogen peroxide contributes to the activation of membrane peroxidation, to a decrease in the intensity of apoptosis and its replacement by more severe mechanism of cell death - necrosis, which is obviously conditioned by a dramatic decrease in the intensity of energogenesis in mitochondria. In cells incubated with sodium nitroprusside moderate NO-induced inhibition of electron transport in oxidative chain and mitochondrial energogenesis and intensification of oxidative stress in Jurkat cells is accompanied with the activation of the cell death mechanisms- both apoptosis and necrosis.

[Alterations of tissue blood supply of experimental animals at malignant tumor growth].

The aim of the research was to study tissue blood flow in the dynamics of malignant tumor growth (Ehrlich carcinoma of 80 mice, sarcoma--37-80 rats, 30 rabbit--Brown-Pirs carcinoma) in functionally different organs of experimental animals (mice, rats, rabbits): skeletal muscles, liver, ear, mammary gland and ciliary body of eye. The study was conducted using H clearance method. Deformability of erythrocytes was studied using filtration-photometry method. Blood surface tension was studied by Rebinder bubble maximal pressure method. Obtained data were analyzed by Student's t criterion. The investigation showed that intensity of local hemocirculation and erythrocytes deformability in "intact" organs and tissues of experimental animals in the dynamics of malignant tumor growth progressively decreases while, blood surface tension increases. It was revealed that paraneoplastic disorders of local hemocirculation were stereotyped, universal and common phenomenon for malignant tumor growth. It was concluded that alterations of blood rheology decreased deformability of erythrocytes and increased blood surface tension play one of the leading roles in the mechanism of paraneoplastic disorders of local hemocirculation.

[Mechanisms of gamma-inducible death of Jurkat cells line].

Mechanisms of radio-inducible death of Jurkat cells were investigated. Human lymphoblastoid T-cell line Jurkat is widely established model for studying apoptosis mechanisms. The cell was radiated by "Teragam" (Czech Republic) by dose 2 g during 1 minute. After radiation cells were incubated at standard conditions during 24 hours. After gamma radiation in cell population amount of cells in gaplois (apoptotic G 0) stage was increased 8,2 folds, in diplois (G 0/G1) stage - by 17%, in synthetic (S) stage decreased by 35% and tetraploid (G2/M) stage by 73% in comparison to control group. It was revealed intensive production of free radicals of oxygen and nitric oxide and decreasing activity of antioxidant enzymes (superoxidismutasa, catalasa and glutathione peroxidase). Revealed dependence between intensification of apoptosis and radiation-induced arrest of cell cycle G2/M phase may be determined by excess amount of free oxygen and nitrogen radicals generated in Jurkat cells as a result of nondirect effects of low doses of gamma radiation.

Changes in the prooxidant and antioxidant status of tissues during paraneoplastic processes.

Electron paramagnetic resonance was used to identify paramagnetic centers in the blood and liver of laboratory rats with S-45 sarcoma and mice with Ehrlich carcinoma. Paraneoplastic changes in prooxidant and antioxidant activity of the blood and liver tissue, mitochondrial respiration, and NO metabolism and inhibition of antioxidant processes contribute to impairment of cell membrane structures, erythrocyte hemolysis, and hypoxia. An important role of these processes in the pathogenesis of paraneoplastic anemia is confirmed by the positive effect of antioxidant and membrane-stabilizing therapy.

[Role of peroxidation processes and nitric oxide in mechanisms of paraneoplastic alterations of hemocirculation].

The present work was aimed to study mechanisms of paraneoplastic alterations of tissue redox-status, intensity of local blood flow in liver and their possible interrelations in case of malignant tumor growth. It has been investigated the electronic paramagnetic centres of blood and liver using the electronic paramagnetic resonance (EPR) method and intensity of local hemocirculation with the use of H(+) clearance polarography method. Experiments have been carried out on adult white rats of mixed population with carcinoma Walker and mice -- with carcinoma Ehrlich. It has been shown that malignant tumor growth displays conditions that lead to exaggerated lipid peroxidation (production of POL promoters -- Fe(2+), Mn(2+), NO, ubiquinone) and suppression of antioxidant protection of organism (reduction of total ceruloplasmin concentration in blood and increased concentration of oxidized ceruloplasmin). It has been suggested that in case of malignant tumor growth sharp paraneoplastic alterations of redox-status plays essential role in mechanisms of paraneoplastic disorders of tissues blood supply. All of these interrelated processes result in generalized paraneoplastic hypoxia in organs and tissues.