FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.

The aim of the research was to study the frequency of VKROC1 and CYP2C9 genes different alleles for healthy donors and for patients with thrombosis, in Abkhazian population and to reveal the interdependence of the studied genes products in the treatment of thrombosis with warfarin. Warfarin is an anticoagulant, causing the inactivation of the VKORC1 gene product, which is one of the clotting factors. The protein product of CYP2C9 gene is involved in the metabolism of warfarin. Genotyping of blood samples for studied genes alleles was carried out using a tube scanner (ESE Quant Tube Scaner), allowing to identify SNPs. With the highest frequency in the studied group of healthy donors of Abkhazian population, by VKROC1 gene found Heterozygous (AG genotype) (74,5 %). The distribution of homozygous of "wild" (GG) and mutant genotype (AA) accounted for 13,5% and 11,8%, respectively. In the group of patients with Thrombosis, wild-type homozygotes accounted for 32.5%, which is significantly high compared to the control group. The percentage of heterozygotes was significantly lower than in the control group and accounted 56,25%. as for the homozygous mutant genotype, it was practically the same as in control group (11,2%). Regarding the rate of polymorphic variants of the CYP2C9 gene, quite large differences between diseased and healthy individuals were detected according to some of them. CYP2C9 *1/*1 genotype (wild- type homozygote) was observed in 32.9% of healthy individuals, while the same genotype was detected in only 14.5% of patients with thrombosis. The percentage of CYP2C9 *1/*2 genotype was slightly different between healthy and thrombotic subjects and corresponded to 27.5% in healthy individuals and 30.4% in thrombotic patients. CYP2C9 *1/*3 genotype accounted for 16.1% in healthy individuals. The mentioned indicator was significantly different from the similar indicator of patients with thrombosis, which corresponded to 24.1%. The largest difference between the percentages was observed according to the CYP2C9 *2/*3 (mutant heterozygote) genotype. In healthy individuals, this rate corresponded to 40.3%, and in thrombotic individuals - 11.4%. The CYP2C9 *2/*2 genotype was not observed in any of the study groups, while the percentage of CYP2C9 *3/*3 (mutant homozygous) individuals did not differ and amounted to 1.6% (in healthy individuals) and 1.2% (in thrombotic patients). VKORC1 and / or CYP2C9 genes polymorphisms are presented in a number of clinical dosing algorithms and in prospective clinical trials. In conclusion, it should be noted that the present work revealed a significant variability of genotypes between the groups of patients with thrombosis and healthy individuals, in Abkhazian population. The results obtained in determining the polymorphic variants of the VKORC1 and CYP2C9 genes, studied by us, should be taken into account when using algorithms to determine the optimal dosage for warfarin treatment in thrombotic individuals of the Abkhazian population, both during treatment and for the prevention of thrombosis.

EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON THE "OLD" CHROMATIN.

In the present study, on the one hand, the epigenetic modification of condensed "old" chromatin was determined, and on the other hand, the influence of peptide bioregulators (Ala-Glu-Asp-Gly-Epitalon; Lys-Glu-Asp-Ala-Livagen; Ala-Glu-Asp-Pro - Cortagen and Lys-Glu - Vilon) on condensed chromatin in lymphocytes from old individuals. Were used molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks-NORs; polymorphism of structural pericentromeric C-heterochromatin; variability of the facultative heterochromatin (sister chromatid exchanges - SCE) in the culture of lymphocytes from 75-88-year-old individuals. The analysis of results shows the chromosome progressive heterochromatinization (condensation of eu - and heterochromatin regions) occur in aging. Epigenetics process - heterochromatinization can deactivate many previously functioning active genes. It blocks certain stages of normal metabolic processes in the cell, which inhibits many specific enzymes and leads to aging pathologies. We show that peptide bioregulators induced unrolling deheterochromatinization (decondensation) of total heterochromatin, deheterochromatinization of satellite stalks of acrocentric chromosome, activating synthetic processes of ribosomal genes, does not cause deheterochromatinized of pericentromeric structural heterochromatin. This data also indicates that each of the studied peptide bioregulators (Ala-Glu-Asp-Gly; Lys-Glu-Asp-Ala; Ala-Glu-Asp-Pro and Lys-Glu) has a selective effect on definite regions of chromosomes. Thus, short peptide bioregulators induce selective heterochromatinization and deheterochromatinization of chromosome regions (remodeling of facultative heterochromatin) in individuals 75-88 years old that opens up new opportunities in the treatment of aging diseases.

[GENOMIC VARIABILITY DURING PREGNANCY TRIMESTERS].

The article presents data on the genome status of pregnant women in different trimesters of pregnancy, during the normal course of pregnancy. The variability of ribosomal cystone activation as well as the variability of genome stability (frequencies of chromosomal aberrations and fragile sites) in different trimesters of pregnancy have been studied to detect genome-specific functional variability for each trimester.It was found that the level of genome stability determined by the frequency of chromosomal structural disorders and fragile sites in all three trimesters of pregnancy did not differ significantly from similar rates for non-pregnant healthy women. The exception was the frequency of fragile sites in the first trimester of pregnancy, which was statistically significantly higher than the control rate, which may be a specific feature (characteristic) for this trimester of pregnancy.At the same time, specific variability in genomic parameters was identified. In particular, deheterochromatization of pericentromeric heterochromatin and heterochromatinization of the medial region and pretelomeric heterochromatin.Based on data on the activation of Nucleolar organizing regions of acrocentric chromosomes and changes in the frequency of acrocentric chromosome associations, which are statistically significantly higher than the control level, a conclusion is made about increased activity of protein-synthesizing apparatus of the cell in all three trimesters of pregnancy. A statistically significant increase in the associative activity of the 15 acrocentric chromosome in the third trimester of pregnancy has been identified, which may also indicate possible specific modification variability on this chromosome and be characteristic of a given trimester of pregnancy.

EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON "AGED" HETEROCHROMATIN.

Following the completion of the Human Genome Project, the strategic direction of modern genetics has moved toward functional genomics, to explore the functions of non-coding regions of DNA. These non-coding regions are localized in heterochromatin. The functions of heterochromatin largely remain unclear. Facultative heterochromatin occurs in aging. The effect of synthetic peptide bioregulators (tetrapeptides: Ala-Glu-Asp-Gly; Lys-Glu-Asp-Ala; Ala-Glu-Asp-Pro and dipeptide - Lys-Glu) on total heterochromatin, constitutive (structural) and facultative heterochromatin in cultured lymphocytes of individuals aged 75-88 and 20 - 40 years have been studied. We used a molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks - NORs; C-heterochromatin; sister chromatid exchanges (SCE). The results showed that peptide bioregulators: 1. induce unrolling - deheterochromatinization of total heterochromatin, constitutive (pericentromeric, telomeric, and nucleolar organizer regions (NOR)) and facultative heterochromatin; 2. induce higher level of SCEs (deheterochromatinization), were registered in telomeric heterochromatin and decreased (heterochromatinization) SCEs level in the medial regions of chromosome arms; 3. each peptide bioregulator selectively deheterochromatinizes a specific region of chromosomes releasing inactive (once active) genes, which, apparently, can contribute to the targeted treatment of aging diseases. The proposed genetic mechanism responsible for the remodeling of constitutive and facultative heterochromatin emphasizes the importance of external and internal factors in the development of diseases and may lead to the development of a strategy for the therapeutic treatment of senile pathology.

[FREQUENCY OF POLYMORPHIC VARIANTS OF GSTT1 AND GSTM1 GENES IN PATIENTS WITH PULMONARY TUBERCULOSIS IN GEORGIAN POPULATION].

A study was made for determining the frequencies of polymorphic variants of GST genes - GSTM1 and GSTT1, both among healthy individuals of the Georgian population (the Tbilisi population, populations of Eastern and Western Georgia), and among patients with tuberculosis; was also conducted a study on the relationship of certain genotypes with hepatotoxicity in patients taking anti Pulmonary Tuberculosis (PT) treatment. As a result of the analysis, it turned out that the general population indicator for healthy individuals for GSTT1 and GSTM1 positive variants of GST genes was 82%; for GSTT1 (-) / GSTM1 (+) variant was 13%; The GSTT1 (+) / GSTM1 (-) genotype was observed in 2%; as for the double null genotype - GSTT1 (-) / GSTM1 (-), the total population indicator was 3%. As for individuals suffering pulmonary tuberculosis, it turned out that 79% of studied patients revealed positive genotypes by the studied genes - GSTT1 (+)/GSTM1 (+); 3% have the GSTT1(-)/GSTM1(+) genotype; the genotype GSTT1(+)/GSTM1(-) was observed in 6% of investigated individuals, and the double null genotype - GSTT1 (-) / GSTM1 (-) - in 12%, which significantly exceeds the general population indicator for healthy individuals. The results of the studies also showed that there is a relationship between the double null genotypes of GSTM1 and GSTT1 genes and drug induced liver injury in patients with pulmonary tuberculosis, in Georgian population. It has been suggested that it is possible to recommend a preliminary analysis of the polymorphism of GSTM1 and GSTT1 genes in patients with pulmonary tuberculosis, before starting antituberculotic treatment, for preventive measures in the case of detection of double null genotypes. It should be noted, that this study has been conducted in Georgia first time.

COMPARATIVE ANALYSIS OF WHOLE CARTILAGE TISSUE THERMOSTABILITY IN DISEASED PATIENTS VERSUS INJURED PATIENTS.

We conducted comparative thermodynamic analysis of femoral cartilages tissue of injured (healthy) patients and patients with congenital hip dislocation. It is shown, that temperature which corresponds to maximum of heat absorption peak of femoral cartilages tissue of diseased patient is on 6.4oC lower than heat absorption peak of femoral cartilages tissue of healthy patient. Heat absorbed during denaturation process in all these cases are close to each other with experimental error accuracy and corresponds to 52±2.6, 51±2.6 and 50±2.5 J/g of dried biomass accordingly. Analysis of the published data makes it possible to assert that the dominant heat absorption stage on DSC curves of tested fresh tissues samples is associated with melting of collagen fibers, hence the thermal stability of the collagen fibers in the patient's tissue is reduced relative to norm.

[EVALUATION OF GENOMIC PARAMETERS IN DUCTAL BREAST CANCER PATIENTS AND THE ABILITY OF IT'S CORRECTION].

The level of DNA single strand breaks, chromosomal abnormalities and sister chromatid exchanges and the possibility of its normalization with oligopeptide bioregulator Livagen and cobalt ions in the lymphocyte culture from patients with breast cancer have been studied. The results show that the genome of ductal breast cancer patients is characterized by the high density of DNA single strand breaks, high frequency of chromosomal abnormalities and increased levels of chromatin condensation. The usage of Livagen and cobalt in the form of modifying agents has a protective effect by all studied parameters. The obtained results allow us to conclude that research of lymphocytes of ductal breast cancer patients using the analysis conducted by us, can be useful in assessing the therapeutic effect in the treatment of breast cancer patients.

[GENOMIC VARIABILITY IN PATIENTS WITH DUCTAL FORM OF BREAST CANCER AND THE POSSIBILITY OF CORRECTION THE PEPTIDE BIOREGULATOR AND METAL IONS].

Level of genome stability (structural aberrations, aneuploidy and fragile sites) was studied in cells of the lymphocyte culture of ductal breast cancer patients (DBC). Was studied the correctional influence of separate and combinative action of peptide bioregulator (Ala-Glu-Asp-Gly) and heavy metal - nickel. It is shown that DBC patients are characterized by high level of genome instability, which is the result of the chromatin changing state. The used tests makes it possible to conclude that in the case of this form of cancer subordinates to specific epigenetic variation as a hetero- also euchromatic regions of genome. The agents - peptide bioregulator (Ala-Glu-Asp-Gly) and nickel ions, used in cell culture of ductal breast cancer patients, revealed the protective effect what indicates the prospects to further study for their involving purpose in combined therapy of this form of cancer.

[FREQUENCY OF POLYMORPHISM OF VKORC1 AND CYP2C9 GENES IN TWO REGIONS OF GEORGIA].

The aim of the research was to study the frequency of VKROC1 and CYP2C9 genes different alleles for healthy donors and for patients with thrombosis, in two regions of Georgia - in Samegrelo and in Tbilisi and to reveal the interdependence of the studied genes products in the treatment of thrombosis with warfarin. Warfarin is an anticoagulant, causing the inactivation of the VKORC1 gene product, which is one of the clotting factors. The protein product of CYP2C9 gene is involved in the metabolism of warfarin. Genotyping of blood samples for studied genes alleles was carried out using a tube scanner (ESE Quant Tube Scaner), allowing to identify SNPs. In the studied group of patients with thrombosis from Samegrelo region the wild-type homozygotes by the gene VKORC1 were - 90%; heterozygotes - 10%; mutant homozygotes have not met at all. In the studied group of patients with thrombosis from Tbilisi, also predominated homozygous wild type (60%); heterozygotes were - 40%; mutant homozygotes were not met. The genotypes of healthy donors fromTbilisi does not differed from the same indicator of of Samegrelo (homozygous "wild" AA - 37%; genotype AB - 47%; and mutant genotype - BB - 16%). In patients with thrombosis, from Samegrelo, wild-tipe homozygotes and heterozygotes by CYP2C9 gene were almost the same rate (51% and 49% -, respectively); mutant homozygotes were not revealed. In patients from Tbilisi, the frequency of wild-type homozygotes was 70%, heterozygotes and mutant homozygotes was 20% and 10% - respectively. The ratio of the frequencies of CYP2C9 gene alleles in healthy donors from Tbilisi and Samegrelo is not different - wild-type homozygotes - 77%; heterozygotes - 23%; mutant homozygotes in both regions were not met. VKORC1 and / or CYP2C9 genes polymorphisms are presented in a number of clinical dosing algorithms and in prospective clinical trials. It is revealed the significant variation of genotypes in patients with thrombosis (in both studied regions), which indicates the importance of as in treatment process, as well as for the prevention of thrombosis.

[Genomic instability in atherosclerosis].

A comparative study of the level of genomic instability, parameters of quantitative and structural mutations of chromosomes (aberration, aneuploidy, polyploidy) in lymphocyte cultures from patients with atherosclerosis of age 80 years and older (control group - 30-35 years old) was conducted. The possibility of correction of disturbed genomic indicators by peptide bioregulators - Livagen (Lys-Glu-Asp-Ala) and cobalt ions with separate application or in combination was also studied. Control was lymphocyte culture of two healthy respective age groups. It was also shown that patients with atherosclerosis exhibit high level of genomic instability in all studied parameters, regardless of age, which may suggest that there is marked increase in chromatin condensation in atherosclerosis. It was also shown that Livagen (characterized by modifying influence on chromatin) separately and in combination with cobalt ions, promotes normalization of altered genomic indicators of atherosclerosis in both age groups. The results show that Livagen separately and in combination with cobalt ions has impact on chromatin of patients with atherosclerosis. The identified protective action of Livagen proves its efficacy in prevention of atherosclerosis.

[Genome instability in pulmonary tuberculosis before and after treatment].

Pulmonary tuberculosis is classified as a disease with a genetic predisposition, and therefore, as with other pathologies related to this group of diseases, by pulmonary tuberculosis, special importance is given to finding those markers that enable early identification of risk groups, such as skrinnig in general population and relatives of patients with tuberculosis, which in turn can provide the basis for preventive measures. One of this markers is the level of genome stability. The aim of this study was a comparative evaluation of the functional parameters of the genome variability in patients with sensitive form of pulmonary tuberculosis before and after treatment, and the possibility of its correction with anti-stress peptide bioregulator - epitalon. The studies were conducted using short-term mitoge -stimulated cell cultures of TB patients, before and after treatment. As an indicator of genome stability has been studied the frequency of structural and numerical chromosome aberrations and fragile sites. It is shown, that in intact cultures from patients with pulmonary tuberculosis, before treatment was significantly higher level of frequency of cells with structural chromosome aberrations, that still retained after the treatment. As for epithalon, it appears that was shown a pronounced protective effect after treatment, on the test of chromosome aberrations, by reducing both overall mean frequency aberrant cells and indicators for all individuals. In the study of fragility of chromosomes in patients with primary tuberculosis was found, that in intact cultures, the proportion of cells with chromosomal fragile sites was higher than in control group of healthy individuals, befor and after treatment. High frequency of chromosome fragility persisted by treatment with peptide bioregulator in both cases - before and after treatment. It is suggested that the identified patterns can be correlated with a high incidence of re- TB.

[Deheterochromatinization of the chromatin in old age induced by oligopeptide bioregulator (Lys-Glu-Asp-Pro)].

In this work is presented the data on the variability of the functional characteristics of the chromosomes in the cells exposed by oligopeptide bioregulator - Prostamax from old individuals (75-86 years). Evaluated: the frequency of sister chromatid exchanges (SCE); Ag-positive NORs (in associations and nonassociations), as well as the variability of the structural C-pericentromeric heterochromatin. Prostamax changed the chromosomal parameters: 1) increased the frequency of SCE to 12,0±0,28 exchange in per cell (in intact cells - 5,9±0,2); 2) increased the frequency of Ag-positive NORs to 2.5 per cell (in intact cells - 0.95) 3) reduced in the frequency of large segments of the options from the pericentromeric heterochromatin for the 1st and 9th chromosomes. Comparison of the results indicates the ability of Prostamax to decondensation, deheterchromatinization the chromatin during aging, and thus release by heterochromatinization repressed genes. On the other hand, the data obtained in this work suggest that the basis for the protective action of Prostamax its modifying effect on chromatin.

Extracellular matrix thermostability of breast gland carcinoma.

Thermostability of epithelial cell matrix in composition of normal and breast ductal carcinoma tissues at various stages of the disease has been studied in the temperature range 40-90°C with help of differential scanning calorimeter (DSC). It has been shown that the denaturation process has three stages of transition in both cases. The temperatures corresponding to maxima of these structural transitions (Td) in case of normal and ductal carcinoma tissues equals to 55 , 66,78 C and 48, 55, 60, 85°C, respectively. Denaturation enthalpy (∆Hd) reflects contribution of hydrogen bonds, electrostatic and hydrophobic interactions in stability of native structures of biomacromolecules; in case of normal tissues, it equals 68,5±6.0 J/g dry biomass and decreases up to 52.5±6.0 J/g dry biomass in stage III of the disease. On the basis of presented and published experimental data, it is affirmed that the dominant transitions with Td around 66 and 60°C in case of norm and carcinoma, accordingly, correspond to denaturation of collagen IV fibers--the main component of microenvironment of duct epithelial cells (ECM)--and weakly expressed transition stages at 55, 78, 85°C correspond to denaturation of cytoplasmatic proteins. It is supposed that the observed significant differences in thermostability, in particular, 6° decrease of the ECM main component collagen, 7° increase of cytoplasmic proteins, and a significant decrease of total ∆Hd in case of ductal carcinoma compared to norm may be used as a new express test together with other existed tests for diagnosis of breast cancer at early stage of disease using some mg quantities of biopsy tissue.

Influence of tetrapeptide on chromatin thermostability.

It is known that short peptides are capable to interact with DNA, as a result of changes in particular gene expression. In the given work, influence of Ala-Asp-Glu-Leu peptide on thermostability of white rat liver chromatin, in which H1 histone and non-histone proteins are depleted, have been studied. It was shown that in 10 nm chromatin filaments, in which nucleosomas do not interact, the tetrapeptide unfolds the nucleosomal nucleus (core) and this causes release of about 15% of core DNA that melts in the melting temperature range of internucleosomal linker DNA. Thus, the studied tetrapeptide can increase accessibility of DNA for transcription.

Effect of the peptide bronchogen (Ala-Asp-Glu-Leu) on DNA thermostability.

Thermodynamic parameters of DNA melting in the presence of a peptide bronchogen in various concentrations were estimated on a differential scanning microcalorimeter. Bronchogen was shown to serve as a DNA-stabilizing agent. Bronchogen increased the melting temperature of DNA from calf thymus and mouse liver by 3.1°C in a narrow range of r (molar ratio of bronchogen/DNA b.p., 0.01-0.055). A further increase in r was not accompanied by changes in the melting temperature. The complex melting enthalpy (ΔH(melt)) remained unchanged in this range of r (0.01-1.0). ΔH(melt) for DNA from the thymus and mouse liver was 11.4 and 12.7 cal/g, respectively. Our results indicate that bronchogen is not an adenine-thymine-specific or guanine-cytosine-specific ligand. The type of binding is considered as strong and occasional. The binding occurs with both strands of DNA (mainly with nitrogen bases).

Impact of unfounded vaccine safety concerns on the nationwide measles-rubella immunization campaign, Georgia, 2008.

Vaccine safety fears following media reports of adverse events led to low (50.3%) coverage in a supplementary measles-rubella immunization campaign in Georgia in 2008. Review of adverse events associated with the campaign identified 432 reports (<0.1% of ∼ 493,000 vaccinees) including 338 (78.2%) cases of syncope. There were no deaths. Causality assessment was performed for 79 cases perceived by providers as severe and with clinical details available. Conditions likely caused by the vaccine were identified in 13 (16.5%) cases (allergic and local reactions, thrombocytopenia). Thirty-seven (46.8%) cases had symptoms consistent with syncope or anxiety attack; 36 (97.3%) of them were initially misdiagnosed as anaphylactic shock/allergies/"postvaccinal reactions". Twenty-nine (36.7%) cases had coincidental illnesses. Safety fears were unfounded and exaggerated by media reports and providers' difficulties in recognizing syncope/anxiety attacks. Risk communication strategies to address perceived vaccine safety concerns are urgently needed to ensure that the goal of measles and rubella elimination in the European Region of the World Health Organization is met.

Microcalorimetric study of human blood lymphocytes culture at presence of copper, cadmium and prostamax.

Research goal was study of separate and joint influence of bioregulator prostamax and Cu(II) and Cd(II) ions on the chromatin structure in situ. The thermal characteristics of the denaturation process of blood lymphocytes culture of aging people in the presence of some microg quantities of Cu(II) and Cd(II) ions have been determined. It has been shown that Cu(II) and Cd(II) ions at these low concentrations don't influence on the temperature stability of membrane, nuclear and cytoplasm proteins. It has been shown that Cu(II) ions cause an additional condensation of the heterochromatin, and Cd(II) ions cause decondensation of heterochromatin and its partial denaturation.

Mathematical model for satellite associations of human acrocentric chromosomes.

Short arms, satellite stalks and satellites of human acrocentric chromosomes (13, 14, 15, 21 and 22) represent heterochromatic regions. Enforced by mutual attraction of heterochromatic regions, the short arms of acrocentric chromosomes come close to each other and compose associations. The associations of human acrocentric chromosomes cause nucleolus formation, undergo age-related changes, account for elevated incidence of chromosome rearrangements and, consequently, can cause chromosome diseases. Most acrocentric chromosome associations are formed by chromatid satellite stalks. This work contains results of acrocentric association rates assessed with use of newly designed mathematical model, which is based on two parameters: the probability of formation and the association intensity for different acrocentric chromosome pairs. For middle-aged individuals the following values were defined: S(0) = 0.558, lambda(V) = 0.2706, lambda(V) = 0.4768 and lambda(W) = 0.0960. The new mathematical model for satellite associations makes it possible to compare two cells not only by the total number of acrocentric chromosome associations, but also by the type and character of each association.

[Variability of C-structural heterochromatin in cells derived from the patients with cardiomiopathy and from their relatives].

Variability of C-structural heterochromatin segments in chromosome 1,9 and 16 has been studied in lymphocyte cultures of peripheral blood taken from the patients with the hypertrophy (HC) and dilatate (DC) forms of cardiomiopathy and their 1st degree relatives (32 individuals, in total). 10 healthy individuals composed the control group. C-segments were sorted according to Patil and Lubs: a<0.5 x 16p; b>0.5-1 x 16p; c>1.5 x 16p; d>1.5-2 x 16p; e>2 x 16p. The total amount of C-heterochromatin in all the studied chromosomes was tended to increase for DC patients and the relatives of the patients with the two forms of cardiomiopathy. Individual specificity within the group was found when the c-variants were assessed in chromosomes. In particular, the results obtained in cells of HC patients and their relatives did not differ from the control values, while the distribution pattern of C-segments within the group of DC patients and their relatives underwent changing. The elevated induces of pericentromeric inversion were found in all the patients with both forms of the disease and their relatives indicating C-structural heterochromatin polymorphism in the tested individuals.

[The effect of heavy metal ions and peptide bioregulators on the expression of chromosome fragile sites in the individuals of different age groups and breast cancer patients].

Expression rates of chromosome fragile sites in peripheral blood lymphocytes have been studied in clinically healthy individuals of different age groups (20-38 yrs and 75-86 yrs) and breast cancer patients (8 cases). In individuals with a normal check-up of different age groups the heavy metal (nickel, zinc and cobalt) ions were also examined on their influence on the expression of the fragile sites and the peptide bioregulators (Livagen and Epithalon) were tested on their ability to correct the pattern of expression. Short-term lymphocyte cultures were used as tested material. The analysis showed that the chromosomes of people from young and old age groups differ from each other by the expression pattern of fragile sites - the chromosomes of young individuals were found to be more active by spontaneous formation of fragile sites. They were also sensitive to their induction by heavy metals. Both tested bioregulators lessen heavy metals effect that was statistically reliable only for the young people group. As for the patients with breast cancer general elevated fragility of chromosomes and specific distribution of the fragile sites along the chromosomes were revealed.