[The changing of cell-free DNA properties of peripheral blood and TCR-mutant cell frequency in individuals exposed to ionizing radiation].

Some properties of the cell-free DNA (cfDNA) of peripheral blood plasma were assessed in 153 employees of atomic industry enterprises. The contents of ribosomal repeat (rDNA) and its concentration in plasma increased in cfDNA of the group of persons in comparison with non-irradiated individuals. The contents of satellite III in cfDNA of donors and of irradiated persons do not differ and less than in DNA nucleus.

[The DNA fragments obtained from the culture media exposed to adaptive doses of the ionizing radiation as factors of stress signaling between lymphocytes and bystander cells].

At the initial stages of an adaptive response the transposition of the homologous chromosome loci from the peripheral parts of the nucleus and their approach happens. It is necessary for the repair of DNA double strand breaks in the process of the homologous recombination. Was shown that the chromosome loci transposition and accompanied by the nucleolus activities took place first in the irradiated (X-rays, 10 cGy) G0-lymphocytes, and then in the intact (bystander) cells incubated in the growth medium of irradiated lymphocytes.

Blood serum DNA in patients with rheumatoid arthritis is considerably enriched with fragments of ribosomal repeats containing immunostimulatory CpG-motifs.

We previously hypothesized that the sequence of transcribed region of human ribosomal repeats is selectively accumulated in circulating extracellular DNA due to its increased resistance to double-strand breaks caused by accumulation of single-chain breaks produced by nucleases. The contents of rDNA in blood serum DNA and in DNA from leukocytic nuclei both in healthy donors and in patients with rheumatoid arthritis were compared using dot hybridization method. By the content of non-methylated CpG-repeats, transcribed region of rDNA is identical to bacterial DNA, which is characterized by potent immunostimulatory effect.

Stimulatory effect of fragments from transcribed region of ribosomal repeat on human peripheral blood lymphocytes.

Fragments from the transcribed region of the ribosomal repeat include considerable amounts of unmethylated CpG DNA motifs. These motifs activate immune cells via the interaction with Toll receptors. In vitro experiments confirmed the stimulatory effect of transcribed region of ribosomal repeat on human lymphocytes.

[Transposition of chromosome loci in bystander cells upon exposure to an adaptive dose of ionizing radiation].

During the process of the realization of the bystander effect the trans of the Signal from irradiated cells to the intact cell (bystander cells) happens. So both type of cells (irradiated and intact cells) have the same damages and reactions. There are new data about bystander effect as the transduction mechanism of the adaptive response and we have investigated this phenomenon.

[The structural reorganization of chromatin as a process of its self-organization in eukaryotic cells and DNA repair problem].

Below were demonstrated the differences in the cell reaction of the chromosome loci transference induced by adaptive doses X-radiation in the cells nucleus in norm cells and in cells with repair process defect of the oncological patients and patients with hereditary disease. It was supposed that the transference of the homologous chromosome loci is necessary for the realization of the correct DNA's double strand repair. The chromosome loci transference in normal cells could be induced by different factors such as X-radiation, RNA-polymerize II repression by alpha-amanitin and possible by other factors.

[Early and late responses to oxidative stress in human dermal fibroblasts of healthy donors and rheumatoid arthritis patients. Relationship between the cell death rate and the genomic dosage of active ribosomal genes].

A study was made of the effect of the oxidizing agent potassium chromate (K2CrO4, PC) on cultured dermal fibroblasts of a healthy donor and three patients with rheumatoid arthritis (RA). Characteristics of the rRNA gene (RG) complex-RG copy number, active RG (ARG) dosage, and 18S rRNA content--were determined for each cell line. In cells of the healthy donor, oxidative stress caused by low doses of PC (2-4 microM, 1-4 h) induced an early response, including a 50-80% increase in total RNA and rRNA.

[Expression of p16INK4a in various cancer cells].

The p16INK4a protein was detected by means of monoclonal antibodies to this protein in the cells of some carcinomas: that of the lungs (17 samples), urinary bladder (6 samples) and mammary gland (4 samples) as well as in the cells of three cell lines from of human uterine cervix carcinoma: SiHa (containing high risk HPV genome), C33A and HT3 (both HPV-negative but have RB mutations in RB gene). Lung carcinoma samples were very heterogenous by the part of cells expressing p16INK4a. High content of this protein was found in all 6 samples of transient cell urinary bladder carcinoma and in 1 sample of mammary gland ductal carcinoma.

[Activation of total and ribosomal RNA transcription under adapting doses of ionizing radiation inducing displacement of chromosome loci in human G0-lymphocyte].

As we demonstrated earlier, the adapting X-ray doses (3 and 10 cGy) induced movement of chromosome centromeric loci in G0-lymphocyte nuclei. In the present study we investigated the influence of X-rays with 3 and 10 cGy doses on the content of total, 18S and 45S rRNA in human G0-lymphocytes because it is known that the transcription products participate in nucleus organization. It was shown that 3 h after irradiation the content of both total and 18S RNA was significantly increased.

[The 3H-thymidine incorporation into G0 human lymphocytes induced by low doses of UVC radiation].

The 3H-thymidine incorporation in human lymphocytes of healthy donors induced by UVC radiation under doses 0.0008-60 J/m2 was investigated. It was shown that the incorporation of 3H-thymidine increases under doses in interval 0.

[Structural and functional changing induced by exposure to adaptive doses of X-rays in the human lymphocytes both normal and defective by reparation of DNA double strands breaks].

In the present work it is shown that the phenomenon of interphase chromosome centromeric region displacement, earlier revealed by the authors, is not realized in G0-lymphocytes with heterozygous BRCA1/2 gene mutations. The role of these genes in DNA double strand break (DSB) reparation is known. It is concluded that chromosome locus displacement is necessary for DSB repair, at least in the process of homologous recombination.

[Expression of the protein marker p16INK4a in the cervix uteri cancer].

Immunohistochemical study was carried out of 18 cervical carcinomas (13 squamous and 5 adenomatous) and of 3 cases of cervical intraepithelial dysplasia. Formalin-fixed paraffin-embedded tissue samples from biopsies as well as from surgical material were used. Staining was performed with monoclonal antibodies to protein p16INK4a.

[Theoretical and experimental approach to the problem of changes in functional capability of cells under the effects of adaptive doses of ionizing radiation].

It is concluded that a dose range from background dose to several cGy may be separated into two parts: a) first--the interval of small doses limited from above by D* which is determined from (1 g (D*/Doc)) < -0.51 g (n/2)), where Dse is an average dose of a single event, n--quantity of irradiated cells; in this interval only one track intersects a sensitive volume; b) second--the interval of low doses, in which in average one track intersects the volume and which is ranged from top D* to bottom Dse. Because events in this region qualitatively are similar to background events, cells in the dose range b) may be adapted to the influence of radiation.

[Potential relationship between mutation process induced by low doses of ionizing radiation, and positional dynamics of chromosomes in nuclei of eukaryotic cells].

The mutation process has many stages. The information presented in this article suggest that a cell exposed to low LET radiation in the low-dose range (up to 1 cGy) must almost completely repair all spontaneous and radiation-induced DNA lesions. But reparation of DNA double-stranded breaks (DSB), which are the basis of genome instability has peculiarity.

[Elements of structural organization of the transcribed area of the ribosomal repeat (rDNA) in human peripheral blood lymphocytes].

The rDNA transcribed region (TR) was tested for accessibility to RsaI recognizing 15 TR sites, DNase I, and photoinducible arylazide (N-(4-azido-2-hydroxybenzoyl)-N,N'-diaminoheptane acetate) in isolated nuclei and, with arylazide, in intact cells. Arylazide entered cells well and did not appreciably affect the chromatin structure. Its photolysis products efficiently modified DNA in accessible sites.

[The accumulation of single-stranded breaks does not lead to paired DNA damage--the characteristic of the transcribing fragment of the human ribosomal operon that allows its being detected in biological fluids at the death of different body cells].

It was shown by blot-hybridization with corresponding DNA probes after electrophoretic separation of control and experimental samples of human genome DNA that accumulation of single-strand breaks in the chains of double-strand fragment of transcribing range of ribosomal gene (TRrDNA) does not result in double-strand breaks. That differs from the other studied DNA sequences (cluster of histon genes, Alu-repetition, telomeric repetition and satellite III). Single-strand breaks and double-strand breaks were induced by endonucleases and by gamma-radiation.

[Lymphocyte subpopulation of human peripheral blood responds to the low doses of ionizing radiation,interleukin-2 and to both factors].

Increasing of 3H-thymidine incorporation in lymphocytes of human peripheral blood which depends non-linearly on X-ray dose (3 cGy max) and interleukin-2 (IL-2) concentration (17.5 Units/ml) is shown. However addition of IL-2 (17.

[Novel biophysical and biological aspects of mechanisms of effects of low doses of ionizing radiation (low LET) on eukaryotic cells].

Novel biophysical and biological aspects of eukaryotic cell response to low doses of low-LET radiation are considered in the present paper. The model of universal nuclear target in eukaryotic cells is proposed. The target is considered as a spherical volume homogeneously filled of DNA with adjacent water layer.

[Biophysical modeling of radiation damage in DNA and chromatin induced by radiation of varying quality].

DNA double strand breaks in chromatin induced by high LET ionizing radiation are analysed on the basis of biophysical modelling and computer simulation. Theoretical and experimental data are presented arguing in favour of nonrandom clustered distribution of DNA double strand breaks in chromatin.

[Changes induced by low doses of ionizing radiation in the accessibility to DNA restriction enzymes of the ribosomal gene system of human lymphocytes].

Human lymphocytes were X-irradiated at doses 0-10(-2) Gy and allowed to repair for some time. Nuclei were prepared and digested with restriction endonuclease Rsa I to selectively release 28S RNA gene fragment fraction, containing the DNA-binding protein, Hpa II digestion of nuclei was used to investigate the methylation of the 28S RNA gene fragment. There was a differential enrichment of 28S RNA gene binding protein for different X-ray doses with maximum enrichment for dose 2-3 x 10(-2) Gy with following diminish to 10 x 10(-2).

[Radiobiological constant in irradiation stimulation of cells for the subsequent adaptive response].

It was shown that the maximum adaptive response to damaging irradiation dose would be achieved after preirradiation when for latter the product of the dose by the dose rate (i. e. D*D/t) is equal to constant value.