[Biophysical modeling of dose response for γ-ray induced complex chromosomal aberrations].

Experiments with FISH painting of chromosomes, including full-color mFISH, have revealed unexpectedly high yields of complex chromosomal aberrations (CA). The ratio of complex and simple aberrations observed in the 1st postirradiation mitosis has proved to depend on the cell line, LET and time after irradiation in a complicated way. According to the widely accepted viewpoint, interchanges are formed as a result of interaction between either contacting lesions or those having come into contact on a boundary between chromosome territories. However, the theoretical analysis has shown that the mechanism of CA formation at the boundary between chromosome territories is insufficient to explain the high ratio of complex/simple aberrations induced by γ-rays in human lymphocytes at different doses. In the present work, the origin of high yields of complex CA is investigated by means of biophysical modeling. The hypothesis that CA are formed on nuclear centers is able to explain quantitatively the dose response relationships for both simple and complex interchanges observed by mFISH technique after low-LET irradiation.

[Radiation induced chromosomal instability: dose response study based on biophysical modeling].

The increased level of non-clonal chromosomal aberrations in the progeny of irradiated cells is recognized as the manifestation of radiation induced chromosomal instability (CI). The shape of the CI dose-response is different from that in the first post-irradiation mitosis; however, the origin of this difference is not established at present experimentally. In the present work, CI dose-response for unstable chromosomal aberrations is studied on the basis of the biophysical model of CI, taking into account formation of delayed dicentrics at different times after irradiation. The model based on the CI data analysis for low-LET radiation allows us to assess the contribution of the proposed mechanisms of CI, such as replication dependent generation of persistent DNA breakage in the descendents of irradiated cells, chromosome breakage-fusion cycle, etc.

[Mechanistic modelling allows to assess pathways of DNA lesion interactions underlying chromosome aberration formation].

The knowledge of radiation-induced chromosomal aberration (CA) mechanisms is required in many fields of radiation genetics, radiation biology, biodosimetry, etc. However, these mechanisms are yet to be quantitatively characterised. One of the reasons is that the relationships between primary lesions of DNA/chromatin/chromosomes and dose-response curves for CA are unknown because the pathways of lesion interactions in an interphase nucleus are currently inaccessible for direct experimental observation. This article aims for the comparative analysis of two principally different scenarios of formation of simple and complex interchromosomal exchange aberrations: by lesion interactions at chromosome territories' surface vs. in the whole space of the nucleus. The analysis was based on quantitative mechanistic modelling of different levels of structures and processes involved in CA formation: chromosome structure in an interphase nucleus, induction, repair and interactions of DNA lesions. It was shown that the restricted diffusion of chromosomal loci, predicted by computational modelling of chromosome organization, results in lesion interactions in the whole space of the nucleus being impossible. At the same time, predicted features of subchromosomal dynamics agrees well with in vivo observations and does not contradict the mechanism of CA formation at the surface of chromosome territories. On the other hand, the "surface mechanism" of CA formation, despite having certain qualities, proved to be insufficient to explain high frequency of complex exchange aberrations observed by mFISH technique. The alternative mechanism, CA formation on nuclear centres is expected to be sufficient to explain frequent complex exchanges.

[Children's physical and mental development in the Moscow North-Western Administrative District].

The paper gives development quotients in 5-6-year-old children from the North-Western Administrative District of Moscow, which were obtained from the survey made in 2005. Only 41.9% of the boys and 30.7% of the girls were ascertained to have no physical developmental deviations. The major problem of childhood development is the underdevelopment of the functional parameters of the locomotor apparatus and respiratory system. The physical development is significantly worse in the girls than that in the boys in the majority of integral indices.

[Micronuclear test evaluating cytogenetic effects of occupational radiation in low doses].

The authors compared cytogenetic injuries level among "Radon" staffers subjected and not subjected to occupational radiation. Both groups compared demonstrated no reliable differences in spontaneous frequency of micronuclear cells. Micronuclear analysis showed no dependence of the injuried cells level on duration of work with radioactive substances and on doses of occupational radiation. Finding was significant increase in lymphocytes radiosensitivity in individuals subjected to occupational radiation. This group appeared to contain the staffers with micronuclear cells share more than 2 times exceeding average values.

[Retention of tumorigenicity in radioresistant progeny of cells surviving exposure to high doses of gamma irradiation]. / Sokhranenie tumorogennosti u radiorezistentnykh potomkov kletok, vyzhivshikh posle vozdeistviia gamma-izlucheniia v bol'shikh dozakh.

The cell tumorigenic ability and the cell clonogenicity in semi-solid medium of highly radioresistant variant cell line, PIC-20 (the progeny of djungarian hamster fibroblast cell line DX-TK- surviving acute exposure to 20 Gy of gamma-irradiation), were examined. In the absence of additional radiation, no differences between tested features of non-irradiated PIC-20 cells and parental DX-TK- cells were observed. On the contrary, after gamma-irradiation with high doses the essential differences in the properties of the examined cell lines were revealed. After exposure to 10 Gy the surviving fraction of PIC-20 cells was 20 times higher than that of the parental cells. Both irradiated and non-irradiated PIC-20 cells produced colonies of similar size. It is revealed that even after irradiation with doses of 5, 10 or 15 Gy, the PIC-20 cells kept their tumorigenicity as high as non-irradiated ones. In all these cases the 90-100% of animals had the tumour, with the average latent period of tumour appearance after inoculation being the same both for irradiated and non-irradiated PIC-20 cells. After irradiation of parental DX-TK- cells with the highest dose of 15 Gy, the amount animals with tumour decreased by 70% and the average latent period of tumour appearance increased fivefold as compared with that for non-irradiated DX-TK- cells. The data obtained indicate that PIC-20 is highly radioresistant cells, which are able to proliferate both in semi-solid medium and in an animal organism even after radiation exposure to high doses.

[Small doses of ionizing radiation as radiation modifying factor]. / Malye dozy ioniziruiushchego izlucheniia kak radiomodifitsiruiushchii faktor.

To investigate the biological effects of small dose ionizing radiation has been acquiring greater importance. The awareness of how and in what direction it show its modifying effects in small doses is an essential scientific basis for developing standards, living conditions under specific environmental conditions. Cultured Hela cells and DEF 4/21 fibroblasts were used to evaluate the biological effects of small-dose ionizing radiation, by examining the conditions under which it showed its modifying effect in small doses (0.1 Gy) in particular. Preexposure to small-dose radiation was shown to alter cell responses to subsequent radiation in large doses. The modifying effects of small-dose radiation turned out to depend on the interval of exposure to small and large doses. Sensitization was recorded at an interval of 2-3 min; an adaptive response was achieved when the interval increased up to 3-5 hours. Upon exposure, intercellular contacts contribute to the modifying effects of small-dose radiation. There was neither effect of sensitization nor adaptive response if single cells were exposed to radiation.

[The appearance of a fracture of radioresistant cells in a fibroblast population irradiated at high doses]. / Vozniknovenie fraktsii radiorezistentnykh kletok v obluchennoi bol'shimi dozami populiatsii fibroblastov.

Two sublines of Djungarian DEF 4/21 hamster cells survived after gamma irradiation with the doses of 10 and 20 Gy were obtained. The survived cell posterity (SCP) of both cell lines are considerably more clonogenic. They show a higher proliferative activity and a shorter period of generation than the control cells. The sublines are several times more radioresistant as compared to the original cells. After exposure to high doses of radiation, the cell culture of the SCP exhibits a 17 to 20% high-resistant fraction. Supposedly, the cells of this fraction are responsible for repopulation after exposure to lethal doses of gamma irradiation.