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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. If there is a bystander effect the quantity of irradiated cells may be three order less than the bystander cells that affirms the great capacity of stress-signalization system. Moreover, the DNA fragments (the factors of stress signaling) were obtained from the growth medium supernatant of the irradiated and of the intact lymphocytes. In other independent experiments they were inoculated into the growth medium of recipient cells. Was demonstrated that there is loci transposition of homologous chromosomes loci and of nucleus activity after introducing the DNA fragments of irradiated cells. After introducing the DNA fragments of non-irradiated cells the both effects were not observed. In the work the characteristics of the obtained factors and the possible ways of stress signaling between the irradiated and the bystander lymphocytes were discussed.

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. In accordance with our data, some feature (pericentromeric cluster disintegration and displacement, the nucleus size increasing) characteristic for S- and G0-lymphocytes are observed in normal G0-lymphocytes treated with 3 and 10 cGy. However, the size of nucleus in G0-lymphocytes is restored through 6 hours after irradiation in opposite to the process in dividing cells. It was proposed that some typical for resting cell functions of G0-lymphocytes after inducing by adaptive doze of radiation are stopped as similarly as after stimulation of cells. Interestingly, that the process of the induced chromosome loci displacement is correlated with the decreasing of DNA reparation possibilities under UV-irradiation. The induced apoptosis level also decreases when chromosome loci are displaced. The possible mechanisms of the revealed phenomenon are discussed. This research supported by RFBR grant (No. 01-04-49180).

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. In spite of higher chemical modification of TRrDNA by arylazide and dimethylsulfate (because of high content of GC-pairs), under the following fragmentation TRrDNA was found to be more resistant to double-strand breaks than other studied DNA sequences. At the same time in the range of non-transcribing spacer (NTS) of ribosomal gene, the section with higher sensitivity to double-strand breaks was found. Higher resistance of TRrDNA to double breaks makes it possible to identify these fragments in cell material from different tissue after death or in DNA samples after prolonged storage. Resistance of TRrDNA to formation of double-strand breaks can be used for its detection in biological fluids after cell death, including the death initiated by ionizing radiation.

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.

The model predicting quantitatively a dose response for genetic lesions in low dose range is presented. The model is based on the concept of programmed initiation of the genetic damage in the subpopulation of specific cells of "evolutionary reserve" (CER). It is demonstrated that complex shape of dose-response curve results from superposition of processes in different subpopulations within exposed cell population, mainly in CER. The model allows us to explain the minimum observed in the dose-response curve at doses corresponding to one (on the average) event of energy deposition per CER with spontaneous aberrations. The equation for dose-response function for dicentrics describes satisfactory experimental observations. Advantage of proposed equation is that it does not deal with free parameters to fit the data. They are determined independently by using known physical and biological characteristics. The data described allow us to suggest that sensitive body for CER is a cell as a whole. Probably, programmed initiation of genetic lesions in CER requires both two hits at cell membrane and radiation effect on cell nucleus.

The dependence of UV-induced unscheduled DNA synthesis (UDS) in the unstimulated lymphocytes of human peripheral blood on the ionic strength (mu) of the culture medium has been shown. In the level of mu lower or higher than the physiological (mu ph) one, UDS significantly decreases. The effect of modification of mu due to the changes of ionic strength is absent in the lymphocytes of the classic form of xeroderma pigmentosum. The phenomenon may become useful in the development of a new test for revealing cells with a genetically or physiologically changed system of UV-induced DNA repair. The mechanisms of investigated phenomenon, particularly their dependence on the structure of chromatin, as well as the influence of ionic strength on binding of the repair enzymes with DNA are discussed.

The dependence of UV-induced unscheduled DNA synthesis (UDS) in non-stimulated lymphocytes of human peripheral blood on the ionic strength (mu) of the culture medium has been shown. With the level of mu lower or higher than physiological (mu ph) the UDS significantly decreases. The effect of modification of mu due to changes in ionic strength is absent in the lymphocytes of patients with the classic form of xeroderma pigmentosum. This phenomenon may become useful for development of a new test revealing cells with genetically or physiologically changed system of UV-induced DNA repair. Mechanisms of investigated phenomenon, particularly their dependence on the chromatin structure, as well as the influence of ionic strength on binding the repair enzymes with DNA are discussed.

The distribution of single-strand DNA breaks induced by various N-methyl-N-nitrosourea concentrations in S-phase of the cell cycle has been studied in Djungarian hamster fibroblast culture in the isolated samples of fractions of metaphase chromosomes of varying size. For the first time, a dose-effect relationship between the molecular mass of single-stranded DNA fragments isolated in an alkaline sucrose gradient from small chromosomes and the lack of the effect on DNA in large chromosomes has been established. The phenomenon detected is being discussed in terms of structural heterogeneity of interphase nuclear chromatin, i.e. irregular distribution of eu- and heterochromatin in small and large chromosomes. Another possible explanation is the storage of various damaged chromosome fragments in small chromosomes. The data obtained, apart from their significance for chromatin structure analysis, can serve as an experimental basis for the detection of, otherwise undetectable, postreparative molecular DNA damages.