[Comparative analysis of cytogenetic examination of control groups of subjects carried out in different Russian laboratories].

The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated control subjects was analyzed using cytogenetic data obtained from 9 cytogenetic laboratories located in Moscow, St.-Petersburg, Obninsk, and Dubna (Russia). The objective of this study was to estimate the level and spectrum of spontaneous chromosome aberrations in human lymphocytes. 1140 blood samples were taken from 1112 subjects (594 men and 546 women) aged 1 to 72. The total metaphase number was 466795. The uniform Giemsa method for peripheral blood lymphocyte cultures was used. After counting 466795 metaphases, 4288 chromosomal aberrations of various types were classified. The most frequent types of aberrations were acentrics and chromatid deletions. They made up 90% of the total number of aberrations. The remaining 10% were exchange aberrations. The number of chromosome exchanges (dicentrics and centric rings) was twice the number of chromatid exchanges. Overall, the portion ofcells with chromosomal or (and) chromatid aberrations was 0.89 +/- 0.01%; the frequency of acentrics was 0.29 +/- 0.01; the frequency of dicentrics was 0.046 +/- 0.003; the frequency of unstable chromosome aberrations was 0.35 +/- 0.01; and the frequency of chromatid aberrations was 0.57 +/- 0.01 per 100 cells.

Chromosome instability of HPRT-mutant subclones induced by ionising radiation of various LET.

The induction of HPRT-mutations and survival of Chinese hamster cells (line B11ii-FAF28, clone 431) were studied after irradiation by 4He and 12C-ions of various LET (20-360 keV/micrometers), produced by the U-200 heavy ion accelerator. The RBE increases with LET up to the maximum at 100-200 keV/micrometers and then decreases. Cytogenetic analysis was performed on the HPRT-mutant subclones selected from unirradiated Chinese hamster V-79 cells and from HPRT-mutant subclones that arose after exposure to gamma-rays, 1 GeV protons and 14N-ions (LET-77 keV/micrometers), produced by the synchrophasotron and the U-400M heavy ion accelerator. Slow growing mutant subclones were observed. The cytogenetic properties of individual clones were highly heterogeneous and chromosome instability was observed in both spontaneous and radiation-induced mutants. Chromosome instability was highest among spontaneous mutants and decreased with increasing LET.

Exchange aberrations among 11 chromosomes of human lymphocytes induced by gamma-rays.

PURPOSE: To detect the frequencies of interchanges among 11 chromosomes in lymphocytes irradiated with gamma-rays and to find out whether these frequencies reflect the proximity of some of these chromosomes within the interphase nucleus. MATERIAL AND METHODS: Exchange aberrations were detected in the first mitosis after irradiation of human lymphocytes with 3 and 5 Gy gamma-rays of 60Co. Two-colour repeated FISH with two differently chemically modified probes in each hybridization was applied. The microscope stage positions of each mitosis were recorded after the first hybridization and used for the automatic scanning of images after all successive experiments. Five images were obtained for each mitosis differing in visualized pairs of chromosomes. Comparing these images, exchanges among 10 chromosomes could be detected. Painting of the p arm of chromosome 21 with the painting probe for chromosome 22 also made it possible to detect exchanges of this chromosome with other chromosomes of the selected group. RESULTS: Frequencies of exchange aberrations induced in chromosomes of the selected group as well as interchanges between many pairs of chromosomes of this group were roughly proportional to the DNA content of chromosomes. Higher frequencies of interchanges than expected according to the model of linear proportionality were found between several chromosomes involved in translocations frequent in different subtypes of leukaemia. CONCLUSIONS: Frequencies of interchanges among 11 chromosomes of human lymphocytes induced by gamma-rays do not indicate as clearly as fast neutrons the non-random arrangement of chromosomes in the cell nucleus. The interaction of a large number of chromosomes in exchange aberrations suggests that the chromatin in the territory of one chromosome is accessible for several other chromosomes.

[Cytogenetic damage and mutagenesis in mammalian and human cells induced by ionizing radiation with varying LET]. / Tsitogeneticheskie narusheniia i mutagenez v kletkakh mlekopitaiushchikh i cheloveka, industirovannye ioniziruiushchimi izlucheniiami s razlichnoi LPE.

Base oneself on analysis of literature and proper data the conclusion was inferred about essential role of structural chromosomal (and gene) damages for radiation-induced mutagenesis of mammalian and human cells (for example HPRT loci). The evidences are adduced of their increase role in mutagenesis after influence of ionizing radiations with high LET. The consequences of HPRT-gene damages have been examined hypothetically.

Distribution of ABL and BCR genes in cell nuclei of normal and irradiated lymphocytes.

Using dual-color fluorescence in situ hybridization (FISH) combined with two-dimensional (2D) image analysis, the locations of ABL and BCR genes in cell nuclei were studied. The center of nucleus-to-gene and mutual distances of ABL and BCR genes in interphase nuclei of nonstimulated and stimulated lymphocytes as well as in lymphocytes stimulated after irradiation were determined. We found that, after stimulation, the ABL and BCR genes move towards the membrane, their mutual distances increase, and the shortest distance between heterologous ABL and BCR genes increases. The distribution of the shortest distances between ABL and BCR genes in the G0 phase of lymphocytes corresponds to the theoretical distribution calculated by the Monte-Carlo simulation. Interestingly, the shortest ABL-BCR distances in G1 and S(G2) nuclei are greater in experiment as compared with theory. This result suggests the existence of a certain regularity in the gene arrangement in the G1 and S(G2) nuclei that keeps ABL and BCR genes at longer than random distances. On the other hand, in about 2% to 8% of lymphocytes, the ABL and BCR genes are very close to each other (the distance is less than approximately 0.2 to 0.3 microm). For comparison, we studied another pair of genes, c-MYC and IgH, that are critical for the induction of t(8;14) translocation that occurs in the Burkitt's lymphoma. We found that in about 8% of lymphocytes, c-MYC and IgH are very close to each other. Similar results were obtained for human fibroblasts. gamma-Radiation leads to substantial changes in the chromatin structure of stimulated lymphocytes: ABL and BCR genes are shifted to the nuclear center, and mutual ABL-BCR distances become much shorter in the G1 and S(G2) nuclei. Therefore, we hypothesize that the changes of chromatin structure in the irradiated lymphocytes might increase the probability of a translocation during G1 and S(G2) stages of the cell cycle. The fact that the genes involved in the t(8;14) translocation are also located close together in a certain fraction of cells substantiates the hypothesis that physical distance plays an important role in the processes leading to the translocations that are responsible for oncogenic transformation of cells.

[The lethal and mutagenic actions of radiations with different LETs on mammalian cells]. / Letal'noe i mutagennoe deistvie izluchenii s raznoi LPE na kletki mlekopitaiushchikh.

Inactivation and induction of mutations in the HGPRT locus in Chinese hamster cells after irradiation with accelerated heavy ions in the LET range of 20 to 367 keV/micron were studied. In both cases, inactivation and induction of mutations, the LET dependence of RBE is described by a curve with a local maximum in the range of 80 to 100 keV/micron. The maximum RBE value for the mutagenic action is almost twice as high as that for inactivation. However, the RBE coefficients of the mutation induction criterion for a certain level of cell-survival is lower significantly and tend to decrease with an increase in inactivation. The obtained data show that the mutagenic effects, induction of chromosome aberrations, and deaths have their origins in the same kind of primary damages, i.e., double-strand breaks of DNA.

[Stable and unstable chromosome aberrations in human blood lymphocytes in vitro after gamma irradiation]. / Stabil'nye i nestabil'nye khromosomnye aberratsii v limfotsitakh krovi cheloveka in vitro posle gamma-oblucheniia.

Radiation-induced (137Cs-gamma-rays) aberrations in the first chromosome in human peripheral lymphocytes were investigated using FISH technique. It was shown that the most of detectable aberrations were translocations (about one half) often appearing with deletions: about 1/3 of the number of translocations were dicentrics; rings and insertions were rare.

[The mutagenic action of gamma radiation on Chinese hamster cells. The cytogenetic characteristics of the mutants at the HPRT locus]. / Mutagennoe deistvie gamma-izlucheniia na kletki kitaiskogo khomiachka. Tsitogeneticheskaia kharakteristika mutantov po lokusu HPRT.

The peculiarities of mutation induction and cytogenetic characteristics of spontaneous and radiation-induced HPRT mutant clones have been studied. The linear-quadratic dependence of the mutation induction on radiation dose has been found. High heterogeneity of cytogenetic parameters (aneuploidy and chromosome aberration frequency) has been shown in the mutants.

[Lethal action of accelerated heavy ions on mammalian cells as affected by inhibitors of DNA synthesis. A theoretical analysis]. / Letal'noe deistvie uskorennykh tiazhelykh ionov na kletki mlekopitaiushchikh v usloviiakh vliianiia ingibitorov sinteza DNK. Teoreticheskii analiz.

Günter-Schulz's model and the authors' own model were used to study the dependence of radiosensitivity (D0(-1)) of Chinese hamster cells on linear energy transfer (LET) upon irradiation in standard conditions and in the presence of DNA synthesis inhibitors, arabinosylcytosine and hydroxyurea. A better agreement of the experimental and theoretical results was obtained using Kozubek-Krasavin's model than the model of Günter and Schulz.

[Lethal action of accelerated heavy ions on mammalian cells as affected by inhibitors of DNA synthesis. Results of experimental research]. / Letal'noe deistvie uskorennykh tiazhelykh ionov na kletki mlekopitaiushchikh v usloviiakh vliianiia ingibitorov sinteza DNK. Rezul'taty éksperimental'nykh issledovanii.

Radiosensitivity of Chinese hamster cells exposed to 137Cs-gamma-radiation and accelerated heavy ions of 4He (L = 22 and 60 keV/micron), 12C (L = 231 keV/micron), and 20Ne (L = 690 keV/micron) was studied in standard conditions and in the presence of arabinosylcytosine and hydroxyurea. These agents were shown to exert a radiosensitizing effect in the case of gamma-radiation. The effect was less pronounced with 4He ion-radiation and was absent upon irradiation with 12C and 20Ne ions. The radiosensitivity was maximum upon irradiation with 4He ions at L = 60 keV/micron. The RBE coefficients of heavy ions under study decreased in the presence of DNA synthesis inhibitors.

[Effect of inhibitors of DNA synthesis on the sensitivity of mammalian cells to radiation with different levels of linear energy transfer]. / Vliianie ingibitorov sinteza DNK na chuvstvitel'nost' kletok mlekopitaiushchikh k deistviiu izluchenii s raznoi lineinoi peredachei énergii.

Radiosensitivity of Chinese hamster cells increased by 1.71 times in the presence of arabinoside cytosine and hydroxyurea after gamma-irradiation, and no sensitization occurred after irradiation with carbon ions of 6.6 MeV/nuclon (LET, 227 keV/micron). Under a standard set of conditions, the RBE coefficient of carbon ions decreased from 3.09 to 1.78 in the presence of DNA synthesis inhibitors. The possible mechanism of this phenomenon is discussed.

[Effect of elevated temperatures on human lymphocyte chromosomes]. / Vliianie povyshennykh temperatur na khromosomy limfotsitov cheloveka.

The influence of elevated temperatures (38-41 degrees C) on chromosomes of human lymphocytes on different phases of the cell cycle was studied. A high thermosensitivity of chromosomes was demonstrated during (S + G2)-phases of the cell cycle. There was a significant increase in the number of aberrant cells at t greater than 38.5%. The main types of chromosome aberrations were chromatid and chromosome deletions. Cells with 3-5 aberrations and induction of chromosome aberrations due to breaks in the centromere region were noticed at high temperatures (40-41 degrees).

[Cytogenetic effects in exposure to high-energy charged particles]. / Issledovanie tsitogeneticheskikh éffektov pri vozdeistvii vysokoénergicheskikh zariazhennykh chastits.

The cytogenetic effects of irradiation were investigated in the bone marrow and corneal epithelium of mice, human white blood cells, and Stamm V79-4 cells of Chinese hamsters exposed to protons with E=9.2 GeV, deutons and helium ions with E=4.6 GeV/nuclon. It was demonstrated that with an increase in the irradiation dose the number of aberrant cells and chromosome aberrations grew. A high yield of exchange type aberrations was found. The proliferative activity of cells of bone marrow decreased and its depletion occurred. The RBE coefficients of high-energy particles varied from 1.3 to 2.7 in relation to the cell type and parameters measured.