Search

The dynamics of the production of nitric oxide (NO) metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs.

The endogenous formation of metabolites of NO - nitrite (NI), nitrates (NA) and volatile nitrosamines in the body, tumor tissue and by abdominal cavity by macrophages for dynamics was investigated in mice F1(C57BlxCBA), Balb/c and BDF with subcutaneous transplanted tumors (Erlich carcinoma - EC and metastatic Lewis lung carcinoma - LLC). It was shown that growth of EC was accompanied by a statistically significant increase in the concentrations of NI and NA in tumor tissue to (7.3±4.67)'10-6 - (7.8±2.57)'10-5 (mol/kg) for the first three weeks and a sharp increase in urinary excretion of NI and NA. The maximum total concentration of NI and NA - (3.,6±0.46)'10-5 in tissue LLC was registered during the early stage of the tumor growth (7 days); it later declined, negatively correlating with the mass of the tumor. NI secretion by abdominal cavity macrophages demonstrated statistically significantly decrease at the stage of intensive growth LLC (14, 21 days). The tissue of EC contained varied concentration of cancerogenic N-nitrosodimethylamine and N-nitrosodiethylamine at all investigated time points. Thus, the ability of different gistogenesis tumor tissue to synthesize metabolites NO depended on time parameters and was more pronounced for EC, than LLC.V issledovaniiakh na myshakh F1(C57BlxCBA), Balb/c i BDF s podkozhno perevitymi opukholiami (kartsinoma Érlikha – KÉ i metastaziruiushchaia kartsinoma legkikh L'iuisa – KL) izuchena dinamika éndogennogo obrazovaniia metabolitov NO – nitritov (NI), nitratov (NA), letuchikh nitrozaminov v organizme, v opukholevoĭ tkani i peritoneal'nymi makrofagami. Pokazano, chto rost KÉ v techenie pervykh trekh nedel' soprovozhdaetsia statisticheski znachimym uvelicheniem summarnoĭ kontsentratsii NI+NA v opukholevoĭ tkani do urovneĭ (7,3±4,67)´10-6 – (7,8±2,57)´10-5 (mol'/kg), a takzhe rezkogo uvelicheniia vydeleniia NI+NA s mochoĭ. V to zhe vremia, v opukholevoĭ tkani KL maksimal'nyĭ uroven' kontsentratsii NI+NA (3,6±0,46kh10-5) registrirovali na 7-e sutki, v dal'neĭshem on snizhalsia, otritsatel'no korreliruia s massoĭ opukholi. Na étape intensivnogo rosta KL (14, 21 sutki) obnaruzheno dostovernoe podavlenie sekretsii NI peritoneal'nymi makrofagami. Na vsekh kontroliruemykh srokakh razvitiia opukholevaia tkan' KÉ soderzhala kantserogennye N-nitrozodimetilamin i N-nitrozodiétilamin, kontsentratsiia kotorykh sushchestvenno var'irovala. Takim obrazom, sposobnost' opukholevoĭ tkani sintezirovat' metabolity NO bolee vyrazhena u KÉ, po sravneniiu s KL i zavisit ot vremennykh parametrov rosta opukholeĭ.

Twenty-four rosettes (proliferative epidermal units) in epithelial tissue are united into morphofunctional zones, where cambial cells proliferate with the formation of maternal and daughter cells and these latter ones differentiate under the influence of electrical field generated by 12 maternal cells. The number of cambial cells in morphofunctional zone of a malignant tumor is reduced at least 2-fold. Hence, the number of maternal cells is reduced to 6, which is insufficient for electric field generation and stimulation of daughter cells differentiation. The percentage of cambial cells in a benign tumor decreases 1.5 times. Daughter cells are differentiated in an electric field whose strength is below optimal, but above the threshold value at which cells do not differentiate; hence, differentiation is incomplete.

The basal layer of mouse skin epidermis consists of special structures - rosettes functionally arranged in zones including about 20 rosettes. The rosette contains a central cambial cell; after division of this cell the mother cell remains in the center of the rosette and the daughter cell migrated to the center of a free rosette. The mother and daughter cells are dipole cells (sources of electric field). If the disposition of mother cells is unidirectional and they predominate over daughter cells, the latter cells transform into other cells, i. e. are differentiated.

Studies of mouse ear epidermis showed that proliferative activity of basal epidermal cells has two active and two passive phases throughout 24 h. Active phases consist of two subphases: long (proliferation of cambial cell descendants) and very short (cambial cell proliferation). Cambial cells proliferate at the boundary between active and passive phases; this results in an increase in the counts of epidermal melanocytes and Langerhans cells resultant from division of epidermal cambial cells. The count of Langerhans cells almost 2-fold surpasses melanocyte count, because melanocytes gradually transform into epidermal basal cells.

Epidermis and dermis form an integral morphofunctional area, where cambial cells proliferate and their first-division daughter cells differentiate. An important feature of this area is different rates of the development of daughter cells (fibroblasts) in the dermis and epidermis, which is greater in the epidermis. This asymmetry results in the prevalence of first epidermal daughter cells and, hence, their effect on cambial cells, and then of stromal daughter cells and their effects on cambial cells. The regulator factors of epidermal daughter cells promote unblocking of the major polarity axis of cambial (mother) cell, while stromal cells (fibroblasts) induce their polarization along the major axis and the onset of mitosis. In the dermis and epidermis, division of cambial cells is asymmetric; a prominent role in the formation of mother and daughter cells is given to the basal membrane as an elastic support. Mother and daughter cells form ring-like structures generating electric field that can promote differentiation of the daughter cells.