АIR POLLUTION EMISSIONS ARE ASSOCIATED WITH INCIDENCE AND PREVALENCE OF BREAST CANCER IN THE AKTOBE REGION OF WESTERN KAZAKHSTAN.

Purpose - to establish a relationship between the incidence and the prevalence of breast cancer and air emissions of pollutants in the Aktobe region of the Republic of Kazakhstan.A retrospective study of the database was carried out on the territory of the Aktobe region of Western Kazakhstan. The data were obtained from the Register of Oncological Diseases of the Aktobe Regional Cancer Center. Data on air emissions for 2014-2019 were obtained from the Annual Statistical Bulletin "Environmental statistics. On the state of protection of atmospheric air in Kazakhstan" of the Committee on Statistics of the Republic of Kazakhstan.Breast cancer ranks is first among the malignant oncological pathology of women in the Aktobe region in 2019 and is 20.5% (95% CI 19.6-21.4) of all cancer cases. The analysis shows that the incidence and prevalence of breast cancer in 2014-2019 continues to grow: incidents from 37.3 (2014) to 56.0 (2019) per 100,000 population, the growth rate is 8.3%; prevalence: from 274.0 (2014) to 344.8 (2019) per 100,000 population, the growth rate is 4.7%. Spearman's rank correlation analysis showed a strong direct relationship between benzene emissions and the incidence (r=0.8, p=0.027). A direct strong relationship was found between the prevalence of breast cancer and the amount of emissions into the atmosphere (r=0.8, p=0.027), carbon monoxide (r=0.9, p=0.037), nitrogen oxides (r=0.9, p=0.037), lead (r=0.8, p=0.021), hexavalent chromium (r=0.6, p=0.048), xylene (r=0.7, p=0.047), toluene (r=0.8, p=0.034), methanol (r=0.8, p=0.040), butyl acetate (r=0.7, p=0.046).The unfavorable environmental situation in the Aktobe region associated with the release of chemical pollutants and heavy metals can contribute to the development of cancer. The revealed correlation between the prevalence of breast cancer and the release of chemical elements into the atmosphere requires further study to determine risk factors for breast cancer in the region of Western Kazakhstan.

[MODERN ISSUES OF PUBLIC HEALTH:THE REVIEW].

The purpose of this review is the study of literature for the development of effective public health programs. The overall health of the population depends on complex of social and biological factors of the environment, which is measured by demographic indices, physical development, morbidity, disability and socioeconomic characteristics. Key health data, socioeconomic and demographic statistics of the region are presented. The complex tools necessary to answer the public health requirements of residents in a certain area are recommended. Monitoring of health and demographic situation is urgent, because it makes it possible to adjust the basis of social, ecological and economic processes in the given area.

[The effect of thyroid hormones and 5-azacytidine on the gene transcription of malic enzyme and 6-phosphogluconate dehydrogenase]. / Vliianie tireoidnykh gormonov i 5-azatsitidina na transkriptsiiu genov malik-fermenta i 6-fosfogliukonatdegidrogenazy.

The effect of thyroid hormones and the methylation inhibitor 5-azacytidine on the level of expression of thyroid hormone-responsive genes (malic enzyme and 6-phosphogluconate dehydrogenase genes) has been studied. DNA-RNA hybridization has shown there is an inverse correlation between the level of DNA methylation and gene expression of malic enzyme and 6-phosphogluconate dehydrogenase. Thus it suggests that the regulation of thyroid hormone gene expression can take place via DNA methylation blocking and that DNA demethylation is part of structural changes essential to the binding of thyroid hormones with DNA elements recognized by thyroid hormone receptors and to further induction of synthesis of specific mRNA.

[The regulation of the nuclear RNA polymerase activity of the liver and brain in rats of different ages by a cytoplasmic modulator of thyroxine action]. / Reguliatsiia aktivnosti RNK-polimerazy iader pecheni i golovnogo mozga krys razlichnogo vozrasta tsitoplazmaticheskim moduliatorom deistviia tiroksina.

The effect of physiological, concentration of thyroxine and cytoplasm thyroxine-binding protein (thyroxine action modulator, TAM4) on the RNA-polymerase activity in rat liver and bain cells in ontogenesis was studied. The physiological doses of the hormone were shown not to effect the RNA-polymerase of isolated liver and brain nuclei, while TAM4 caused the stimulation of enzymatic activity in these organs. ++TAM4 stimulating effect in liver correlated with increasing animal age, while the maximum RNA-polymerase activation by tAM was discovered in young rats under one month-At later stage the RNA-polymerase activity was same as in the controls. In is suggested that the cytoplasmic hormone-binding proteins take part in the formation of liver and brain sensitivity to the action of the thyroid gland hormones.

[Liver nuclear phospholipids of rats with varying thyroid status]. / Fosfolipidy iader pecheni krys s razlichnym tireoidnym statusom.

Thin-layer chromatography was used for fractionation of rat liver nuclear phospholipids after in vivo administration of 14C-sodium acetate. The administration of T3 to thyroidectomized rats caused a sharp increase in the incorporation of the label in all phospholipids of the nuclear fraction. The action of sphingomyelin and sphingomyelase on RNA-polymerase of nuclei isolated from the liver of thyroidectomized rats was tested. Sphingomyelin was shown to cause stimulation of RNA nuclear synthesis; parallel incubation with sphingomyelinase eliminated a stimulating effect of this phospholipid.

[Changes in the chromatin structure of the thyroid cells related to the expression of the thyroglobulin gene]. / Izmeneniia struktury khromatina tireoidnykh kletok, sviazannye s ékspressiei gena tireoglobulina.

A highly purified thyroglobulin mRNA was isolated from human nodal euthyroid goiter. A full-length cDNA was synthesized from 33S RNA by using reverse transcriptase in the presence of human placenta ribonuclease inhibitor. A DNA complementary to human Tg mRNA was used in liquid hybridization experiments to quantify Tg mRNA. The amount of Tg mRNA in euthyroid nodal and congenital goiter was reduced. In thyroid cancer Tg specific mRNA was absent. Direct correlation between Tg gene expression in thyroid cells and DNAase-I hypersensitivity of chromatin from the thyroid gland nucleus was revealed.

[The effect of thyroid hormones on structural-functional relations in rat liver chromatin]. / Vliianie tireoidnykh gormonov na strukturno-funktsional'nye vzaimootnosheniia v khromatine pecheni krys.

The effects of thyroid hormones on chromatin structure at different levels of its functional activity were investigated. No differences in the sensitivity of hepatocyte nuclei to DNAase I were found, presumably due to the restriction of acceptor sites for thyroid hormones on DNA.

[The nature of thyroid hormone receptors. Intracellular functions of thyroxine-binding prealbumin]. / O prirode retseptorov tireoidnykh gormonov. Vnutrikletochnye funktsii tiroksinsviazyvaiushchego preal'bumina.

The effect of tyroxin-binding prealbumin (TBPA) of blood serum on the template activity of chromatin was studied. It was found that the values of binding constants of TBPA for T3 and T4 are 2 X 10(-11) M and 5 X 10(-10) M, respectively. The receptors isolated from 0.4 M KCl extract of chromatin and mitochondria as well as hormone-bound TBPA cause similar effects on the template activity of chromatin. Based on experimental results and the previously published comparative data on the structure of TBPA, nuclear, cytoplasmic and mitochondrial receptors of thyroid hormones as well as on translocation across the plasma membrane and intracellular transport of TBPA, a conclusion was drawn, which suggested that TBPA is the "core" of the true thyroid hormone receptor. It was shown that T3-bound TBPA caused histone H1-dependent conformational changes in chromatin. Based on the studies with the interaction of the TBPA-T3 complex with spin-labeled chromatin, a scheme of functioning of the thyroid hormone nuclear receptor was proposed.

[The nature of thyroid hormone receptors. Intracellular transport and compartmentalization of chromatin receptors and thyroid hormones]. / O prirode retseptorov tireoidnykh gormonov. Vnutrikletochnyi transport i kompartmentalizatsiia khromatinovogo retseptora tireoidnykh gormonov.

It is well established that in vivo administered labelled TBPA penetrates into liver, brain and lung cells, is translocated from cytosol into the nucleus and is accepted by chromatin without being affected by modifications touching upon the antigenic determinants of this protein. Electron microscopic autoradiography demonstrated that 125I-TBPA translocated from cytosol into the nucleus is localized on the border between hetero- and euchromatin. The data obtained may serve as an additional proof of the universal structure of intracellular thyroid hormone receptors and suggest that TBPA participate in manifestation of genetic effects of thyroid hormones.

[The nature of thyroid hormone receptors. Thyroxine- and triiodothyronine-binding proteins of mitochondria]. / O prirode retseptorov tireoidnykh gormonov. Tiroksin- i triiodtironinsviazyvaiushchie belki mitokhondrii.

T4- and T3-binding proteins of rat liver were studied. It was found that the external mitochondrial membranes and matrix contain a protein whose electrophoretic mobility is similar to that of thyroxine-binding blood serum prealbumin (TBPA) and which binds either T4 or T3. This protein is precipitated by monospecific antibodies against TBPA. The internal mitochondrial membrane has two proteins able to bind thyroid hormones, one of which is localized in the cathode part of the gel and binds only T3, while the second one capable of binding T4 rather than T3 and possessing the electrophoretic mobility similar to that of TBPA. Radioimmunoprecipitation with monospecific antibodies against TBPA revealed that this protein also the antigenic determinants common with those of TBPA. The in vivo translocation of 125I-TBPA into submitochondrial fractions was studied. The analysis of densitograms of submitochondrial protein fraction showed that both TBPA and hormones are localized in the same protein fractions. Electron microscopic autoradiography demonstrated that 125I-TBPA enters the cytoplasm through the external membrane and is localized on the internal mitochondrial membrane and matrix.

[The nature of thyroid hormone receptors. Translocation of thyroid hormones through plasma membranes]. / O prirode retseptorov tireoidnykh gormonov. Translokatsiia tireoidnykh gormonov cherez plazmaticheskuiu membranu.

The in vivo translocation of thyroxine-binding blood serum prealbumin (TBPA) was studied. It was found that the TBPA-hormone complex penetrates-through the plasma membrane into the cytoplasm of target cells. Electron microscopic autoradiography revealed that blood serum TBPA is localized in ribosomes of target cells as well as in mitochondria, lipid droplets and Golgi complex. Negligible amounts of the translocated TBPA is localized in lysosomes of the cells insensitive to thyroid hormones (spleen macrophages). Study of T4- and T3-binding proteins from rat liver cytoplasm demonstrated that one of them has the antigenic determinants common with those of TBPA. It was shown autoimmunoradiographically that the structure of TBPA is not altered during its translocation.