Experimental Carcinogenesis with 7,12-Dimethylbenz(a)Anthrazene (DMBA) and Its Inhibition with Extra Virgin Olive Oil and a Diet of Mature Olives (Picual Variety)

7,12-Dimethylbenz(a)anthrazene (DMBA) is a carcinogen that induces carcinomas within a few weeks of application. Forty-four male hamsters were divided into four groups: DMBA dissolved in paraffin oil (DMBA-PO), DMBA dissolved in olive oil (DMBA-OO), paraffin oil and olive oil. Their mouths were swabbed daily with paraffin oil or extra virgin olive oil alternatively for the first two weeks, during the biweekly application of DMBA at 0.5% diluted in paraffin oil or olive oil for five weeks and daily until the twentieth week. The animals in the DMBA-OO and olive oil groups received an additional diet of mature Picual olives. The DMBA-PO carcinogen effect (35 carcinomas) is 100% and the inhibitory effect 0. The use of olive oil as DMBA solvent and the ad libitum diet with Picual olive has an inhibitory effect of 80%, with only three intraepithelial carcinomas and four verrucous carcinomas occurring and no invasive carcinoma.

FEATURES OF RAT THYMUS MORPHOLOGY AT THE INDUCTION OF THE BREAST CANCER BY N-METHYL-N-NITROSOUREA

The immune system as a whole plays a leading role in the formation of an adequate immune response during the onset and development of tumors. The aim of the study was to reveal the features of the change in the morphology and level of biogenic amines of the thymus of rats during experimental carcinogenesis of breast cancer by the injection of N-methyl-N-nitrosourea. In the work used luminescence-histochemical, general histological and immunohistochemical methods, which made it possible to obtain important information about the functional activity of the cellular elements of the thymus, the quantitative composition of macrophages, dendritic cells, lymphocytes and the qualitative characteristics of mast cells. The experiment was carried out on 85 white nonlinear female rats, which were injected with the carcinogen N-methyl-N-nitrosourea, which induces a breast tumor. Animals were divided into two groups: intact (n=30) and rats injected with a carcinogen (n=45). The thymus structure was examined 1, 2, and 3 months after the end of the injections. During the study, changes in the morphometric parameters of the organ are noted. A month after the injection of the drug, the area of the medulla of the thymus and the thickness of the cortex substance of the organ increases, which decrease with an increase in the study period. Replacement of the thymus parenchyma with adipose and connective tissue begins after 2 months and progresses with an increase in the study period. A tendency to wavelike changes in biogenic amines was revealed, after 1 month there is a significant increase in the level of histamine and a decrease in serotonin and catecholamines, after 2 months an increase in all biogenic amines, especially histamine (1.5 times or more) in premedullary and mast cells, thymocytes of the cortex. After 3 months, on the contrary, there is a decrease in histamine and an increase in the level of monoamines. The ratio (serotonin+histamine)/catecholamines after 1 month indicate a decrease in the functional activity of the thymus, and after 3 months - about its increase. At all stages of the study, degranulated forms of mast cells predominate. In the dynamics of the experiment, an increase in the number of dendritic cells, lymphocytes, and twice the number of macrophages and Bcl-2+cells was revealed. The data obtained in the course of the study suggested that the introduction of N-methyl-N-nitrosourea and the subsequent development of a breast tumor is reflected in the change in the morphofunctional state of the thymus. In this case, the greatest changes were observed 2 months after the end of the administration of the carcinogen, even before the formation of a breast tumor. The data obtained can have a certain value in determining the immune status in models of experimental carcinogenesis.

THE MORPHOLOGY OF THE ACCIDENTAL INVOLUTION OF THE THYMUS AT THE EXPERIMENTAL CANCEROGENESIS

The development of tumors in the body is a powerful factor in the dysfunction of the immune system. The features of involution processes in the thymus in experimental carcinogenesis are due to impaired metabolism in the body as a whole and the production of lymphoid cells with altered functions. The purpose of the study is to summarize data from modern scientific literature and own research on the accidental transformation of the thymus and the reaction of its cellular structures against the background of experimental carcinogenesis with the development of a mammary gland tumor, stress and the combined effect of these factors. Based on the analysis, it was found that dendritic and mast cells of the thymus respond most actively to tumor growth and stress. Morphometric parameters and changes in organ's cytoarchitecture correspond to the phases of the development of accidental involution, which is most pronounced with the combined effect of two factors. A significant role in these processes belongs to biogenic amines and hormones. The introduction of carcinogens leads to a structural reorganization of the gland: the lobules become more elongated, the interlobular spaces increase, the thickness of the cortical and the area of the medulla increase. There is a decrease in the number of S-100+-cells, an increase in the number of mast cells with a predominance of degranulated and completely devastated forms. The level of histamine in the cells of the pre-medullar area decreases in 1,3 times, in the thymocytes of the cortex and medulla in 1,7 times. Along with the change in the level of biogenic amines, there is a decrease in the ratio of their ratio, which indicates an increase in the functional activity of cells. Against the background of stress, as an additional factor that depresses the immune system, there is a pronounced disorganization of the thymus lobes: a decrease in the thickness of the cortical and the area of the medulla, expansion and filling of the interlobular connective tissue septa with adipose tissue. The number of dendritic cells also decreases and the content of degranulated and completely devastated forms of mast cells increases, the level of histamine significantly decreases in all structures. Thus, data from the literature and our own research indicate that the combined effect of carcinogenesis and stress leads to more pronounced changes in the structure of the thymus in the process of accidental involution and the structural specificity of its manifestations.