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The association between polymorphisms in genes COMT, HFE that takes part in oxidative stress regulation, and chromosome aberration frequency in lymphocytes was assessed in 278 female residents of radiation polluted regions of Central Russia: Bryansk (322 kBk/m2) and Tula Districts (137Cs - 171 kBk/m2). The C187G, G845A genotyping of HFE and G1947A (H/L) of COMT was done by means of polymerase chain reaction-restriction fragment length polymorphism. Studied population was divided into 3 subgroups by level of chromosome aberrations per cell (0-2, 3-4, >5). There was shown statistically significant difference in distribution of COMTand HFE genotypes between the groups. The high frequency of chromosome aberrations (> or = 5%) was associated with homozygotes of the high activity COMT G/G and HFE CC. Heterozygotes for G1947A COMT and C187G HFE reveal negative association with the high frequency of chromosome aberrations and correspond to "resistance factors".

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The analysis of chromosome lesions in peripheral blood lymphocytes of Hodgkin's lymphoma (HL) patients after chemotherapy and chemotherapy with the subsequent course of radiation therapy is carried out. Is shown, that the mean aberration frequency was significantly higher in HL patients after chemotherapy (7.20 +/- 0.58 per 100 metaphases) than in non-treated HL patients (4.80 +/- 0.54, p < 0.01). The subsequent carrying out of radiation therapy enlarges number of chromosome aberrations on 100 metaphases up to 46.7 +/- 10.7 (p < 0.05), of which chromosome-type aberrations (43.2 +/- 10.3 on 100 metaphases) averaged 92.5%. In lymphocytes of 37 out of 43 HL antitumoral treatment patients, we found, in addition to ordinary aberrant cells, a large number of multiaberrant (MA-cells) cells, i.e. metaphases carrying multiple (at least four) chromosome-type exchange aberrations. In 30 non-treated HL patients only one MA-cell was found. From 171 MA-cells which were in 43 HL patients after antitumoral treatment, 114 MA-cells were found at inspection of 9766 diploid metaphases, and the remaining 57 MA-cells were found at inspection of 196 polyploid metaphases. The carrying out after chemotherapy of radiation therapy enlarges in lymphocytes frequency of appearance of MA-cells. The analysis of MA-cells in diploid and polyploid metaphases shown, that the MA-cells could be formed both in vivo, and in vitro in absence of influence of clastogenic factors, and could survive at least two rounds of in vitro replication.

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The lymphocytes of healthy donors were exposed to 60Co gamma-rays in doses ranging 0.5 to 6.0 Gy, and were incubated with PHA and 5-bromodeoxyuridine at 37 degrees C for 72 h. In the course of five consecutive in vitro divisions of cultured lymphocytes, the frequency of polyploid metaphases were determined, and chromosome structural aberrations in polyploid and diploid metaphases were analyzed. Dose dependence of polyploid formation was investigated, and patterns of polyploid cells were analyzed at various DNA replication cycles post exposure and 5-bromodeoxyuridine addition. Radiation is most effective induces of polyploid metaphase of the second and of the third mitotic divisions. In metaphases of the fourth mitotic divisions radiation does not enlarge authentically frequency of polyploid cells. In metaphases of the fifth divisions was not retrieved of polyploid cells. Was shown, that 84.8% of polyploid metaphases compound of tetraploids, while of octoploids and the cells with endoreduplicated chromosomes compound, accordingly, 8.4 and 6.8%. The analysis of chromosome aberrations have shown that the percentage of aberrant cells was higher in polyploid metaphases than in diploids, which indicated that chromosome lesions were involved in formation of polyploid metaphases.

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The aim of the study was assessment of bronchial capacity in the treatment with ACE inhibitors. 92 patients with essential hypertension stage I-II (mean age 52 years), ischemic heart disease and bronchial asthma (a mild, moderate and severe course) in a relative remission were treated for arterial hypertension with ACE inhibitors enalapril and diroton. Enalapril improved cough indices by 38.3%, diroton--by 13.3%. This was accompanied by a rise in the level of natural antibodies to bradikinin.

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Peripheral blood samples from seven healthy donors were exposed to 2 Gy of (60)Co gamma rays. Lymphocyte cultures were prepared from the samples and stimulated to proliferate either immediately after the exposure or after 1, 2 or 4 h. No significant differences were found between the frequencies of chromosome aberrations (breaks or exchange) observed in lymphocytes stimulated after different postirradiation periods. We conclude that unstimulated lymphocytes do not undergo significant levels of recovery from potentially lethal damage at the chromosomal level.

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Human lymphocytes from 16 healthy donors were exposed in vitro to an adapting dose of gamma-rays (0.05 Gy) at G0, or G1, or G1/S stage of the cell cycle and subsequently to a challenging dose of gamma-rays at G1, or G1/S, or S (1 Gy), or G2 (0.5 Gy) stage. Frequencies and distributions of the induced chromosome aberrations were analyzed in first-division metaphases. The data averaged over the donors revealed the protective action of the adapting exposure under the irradiation schemes with the challenging dose delivered at S or G2 stage. The majority of aberrations induced at these stages belonged to the chromatid type, and their yield was significantly higher in G2-exposed cells than in S-exposed cells. However, the relative reduction of the challenging dose effect (about 34%) in the adapted cells did not depend on the magnitude of this effect, and its value remained the same (within the experimental error) if aberrations were subdivided into chromosome and chromatid types or grouped as total deletions and total fragments. The adaptive response was not revealed under the schemes with the challenging dose delivered at G1 or G1/S stage. Analysis of the individual results showed that, in one and the same donor, the adaptive response could be observed under one irradiation scheme and not observed under other schemes, the most effective schemes being those with the challenging dose delivered at G2 stage. Four donors, however, did not show the adaptive response even under such schemes. Data on aberration distributions suggested that different repair processes, rather than a unique one, may underlie the adaptive response.

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The purpose of this study was to elucidate whether an enhanced skin radiation reaction correlated with an enhanced chromosome radiation response. Twelve patients with late radiation skin ulcers formed after courses of radiation therapy were chosen as a group of individuals with elevated skin radiosensitivity. Half of the venous blood samples from each donor were irradiated with 2 Gy gamma-rays; the other half remained unexposed. Using standard cytogenetic technique, lymphocyte cultures were prepared with all samples. On the metaphase preparations, all chromosome aberrations detectable without karyotype identification were scored. The frequency of various aberrations in each patient were compared with relevant mean values in healthy unexposed donors. In several patients, the frequency of one aberration type or another exceeded the control value significantly. Comparison of aberration patterns in irradiated and nonirradiated cultures and consideration of elapsed time after therapeutic exposures suggested that the observed increased aberration levels reflected individual features of the patients' radiosensitivity, rather than lesions induced by previous in vivo exposures. Therefore, the question of a correlation between skin and chromosome radiosensitivity can be answered positively. Analysis of the peculiarities of cellular distribution of aberrations and of the relative contribution of different aberration types in patients and healthy donors indicates that the investigation of in vitro-induced aberrations is more suitable for the assessment of individual radiosensitivity than the study of aberrations observed in unexposed cultures.

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Formation of single-stranded DNA regions was investigated during the presynthetic stage of human lymphocyte cell cycle. Two peaks of single-stranded region production were found in about the middle and near the end of the G1 stage. Both the peaks appeared some hours earlier in gamma-irradiated cells than in control. Experiments showed that the periods of the peak formation coincided with the terms when time-effect dependence for gamma-induced chromosomal aberrations changed its character. The interpretation of the results supposes existence of inherent for the G1 stage process of genetic material correction.

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Formation of SCE was studied in lymphocytes irradiated by 60Co gamma-rays at the G1 stage of the first or second mitotic cycles. The yield of SCEs induced by irradiation in the presence of 5-bromodeoxyuridine (BrdU) proved to be significantly higher than that obtained in the absence of BrdU. The enhancing influence of BrdU on SCE induction depends on neither replication cycle nor the molecular constitution of chromosomes under irradiation. Direct modification of chromosomal radiosensitivity by BrdU is excluded. The results obtained suggest the interference of free BrdU present in culture medium with processes of DNA reparation at the G1 stage.

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The onset of 3H-thymidine incorporation in DNA precedes a short-term activation of cell respiration. gamma-Irradiation (5 Gy, 0.1 Gy/s) significantly inhibits oxygen consumption by human peripheral blood lymphocytes. It should be noted that time dependence maxima of oxygen consumption are shifted towards later times of cultivation.

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The formation of SCE was studied in human lymphocytes irradiated at the presynthetic stage of the cell cycle in the presence or absence of 5-bromodeoxyuridine. The results obtained showed that 5-bromodeoxyuridine present in the culture medium at the time of exposure or during the postirradiation period increased the yield of SCE. It is suggested that 5-bromodeoxyuridine exerts its effect through interfering with DNA repair.

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Single-stranded DNA regions in the nuclei of human lymphocytes were detected by means of fluorescent antibody technique. The frequency of fluorescent nuclei increased with the onset of the S stage, as expected. Also, a clear peak of the fluorescent nuclei amount was observed in about the middle of the G1 stage. The appearance of this peak correlated with some regularities of production of structural mutations by radiation. The suggestion is made that the maximum discovered might reflect the beginning of the recombinational repair of double-stranded breaks.

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