Cytogenetic studies in 12 patients with itai-itai disease.

Among 12 Itai-Itai disease patients examined, 8 patients showed a remarkably high frequency of chromatid aberrations, whereas the other 4 patients showed a much lower frequency of such aberrations, although a significant number of stable type aberrations was observed also in the latter patients. The frequencies of aneuploid cells of all 12 patients were significantly higher than those of the controls. The abnormalities were found in 50-hour and 72-hour cultures, from which it can be concluded that the aberrations occurred in the blood stem cell of the patients. In addition to these structural and numerical aberrations, satellite associations of the D and G group chromosomes were often observed.     

The protective effect of newly synthesized compounds against the action of UV-C irradiation on human lymphocytes in vitro

In this work we present our data about the protective effect of the newly synthesized compound 1-(4-fluorphenyltioureido)-4-methyl-piperazyne (FTMP) against high doses UV-C irradiation using human lymphocytes in vitro as a model system. The endpoint used was chromosome aberrations. The genotoxic effect of different UV-C doses in the range from 10 J/m2 to 200 J/m2 was evaluated. Studying the protective effect of FTMP, it was obtained that a low, adaptive concentration (10(-6) mol/l) applied before harmful doses of UV-C irradiation (100 J/M2 and 150 J/M2) induces the yield of chromosome aberrations lower than theoretical, estimated as a sum of single effects of both agents. A tendency for reducing the damage effect of UV-C irradiation was established. The effect is the most clear when a 4-hour interval between the treatments was used. The mitotic index was not affected. These results pointed out the ability of FTMP to decrease the damaging effect of UV-C irradiation in this type of cells and possess the potential to induce the adaptive response against the damaging effect of UV-C irradiation.     

Frequency of chromosome aberrations induced in human peripheral lymphocytes by in vitro 60Co gamma quanta at doses of 1 to 5 Gr. in an analysis of the 1st-division cells at different fixation times

The quantitative analysis of chromosomal aberrations in the first division cells of 50-, 54-, 58-, 52- and 66-hour peripheral blood lymphocytes cultures of healthy donors was performed after irradiation in vitro with 60Co gamma-quantums at doses 1--5 Gy. Cells of the first division were identified by a differential staining of sister chromatid method using 5-bromdeoxyuridine. No significant differences in frequencies of aberrant cells and aberrations of chromosomal type were found between cultures fixed at different times. The distribution of dicentrics in cells did not differ from the Poisson distribution regardless of fixation times and doses. On the basis of these findings it is concluded that chromosomes of human peripheral blood lymphocytes passing the cell cycle at different rates have approximately equal radiosensitivity.     

A 24-HOUR AMBULATORY ECG MONITORING IN ASSESSMENT OF QT INTERVAL DURATION AND DISPERSION IN ROWERS WITH PHYSIOLOGICAL MYOCARDIAL HYPERTROPHY

Myocardial hypertrophy (MH) due to cardiac pathology is characterized by an increase in QT interval duration and dispersion, while the findings for exercise-induced myocardial hypertrophy are contradictory. The majority of published research findings have not explored this relationship, but there have only been a few conducted studies using 24-hour ECG monitoring. The aim of the study was to determine the QT interval duration and dispersion in short-term and 24-hour ECG in endurance athletes with myocardial hypertrophy and without it. Methods: A total of 26 well-trained rowers underwent a resting 12-lead ECG, 24-hour ECG monitoring and echocardiography. Results: Athletes with MH (n = 7) at rest did not show any increase in QTc interval duration and dispersion, or mean and maximal QTc duration in Holter monitoring compared to athletes without MH (n = 19). Left ventricular mass was not significantly correlated with any QTc characteristics. Furthermore, athletes with MH had significantly longer mean QT (P = 0.01) and maximal QT (P = 0.018) intervals in Holter monitoring and higher 24-hour heart rate variability indexes due to stronger vagal effects. Conclusions: The present study demonstrated that athlete''s heart syndrome with myocardial hypertrophy as a benign phenomenon does not lead to an increase in QT interval duration, or increases in maximal and mean duration in a 24-hour ECG. An increase in QT interval duration in athletes may have an autonomic nature.     

The distribution of chromosome aberrations after gamma and neutron irradiation among cells in various stages of the mitotic cycle in a human lymphocyte culture

Distribution of chromosome aberrations among cells depending on radiation dose, stage of mitotic cycle of human lymphocyte culture, time of cell fixation under the effect of 6 MeV neutrons and their combination with postirradiation hyperthermia has been investigated. The regularities in the distribution of aberrations within cells are similar with both neutron- and gamma-radiation. In experiments with both types of radiation delivered at the S stage and fixation 52 h after the onset of incubation, distribution of aberrations follows Poisson formula whereas with 62-hour fixation, the correlation is disturbed. This is due to the presence of cells dividing for the second time after irradiation which makes the data obtained with delayed fixation scantily informative. Additional hyperthermia does not affect substantially the structure of cell population with both radiation types.     

Relation of the frequency of chromosome aberrations in mouse bone marrow cells to the concentration (dose) of benzene administered by various routes

Experiments on mice were made to study the rate of bone marrow cells with chromosome aberrations after continuous inhalation of benzene for 7 days at the concentrations 13.9, 36.8 and 73.7 mg/m3 and after a 10-fold intragastric administration of benzene at the doses 5,20 and 80 mg/kg, the interval between administrations being 24 hours. The rate of cells with chromosome aberrations increased as the benzene level was raised (upon both administration routes) and was satisfactorily depicted by linear equations. The doses 36.8 and 20 mg/kg appeared the least effective.     

Transferrin C2 and radiation-induced chromosomal damage

Radiation-induced chromosomal damage (after exposure to 1 Gy) in lymphocytes was studied in relation to transferrin C subtype (C1 vs. C2). In 72-hour lymphocyte cultures a significantly increased frequency of cells with radiation induced aberrations was observed in individuals with the transferrin type C2. Thus the results lend some support to the hypothesis that transferrin C2 may act as an enhancer of chromosomal damage.     

X-ray-induced chromosome aberrations in mouse dictyate oocytes. I. Time and dose relationships.

Structural chromosome aberrations were analyzed in superovulated metaphase-I oocytes of the mouse, Mus musculus, at various times after a single acute dose of 200 R of X-rays. The aberrations seen were of the chromatid type, i.e., chromatid interchanges, isochromatid deletions and chromatid deletions. The aberration frequency was low during the interval 24 h to 5 days between irradiation and ovulation; peak frequency was reached when irradiation was given 14 days prior to ovulation. A dose-response study was made 14 days prior to ovulation at doses of 50, 100, 200, 300 and 400 R. A curve of these data indicated that a significant two-track component was present for both interchanges and deletions. Centromere staining revealed that symmetrical and asymmetrical interchanges occurred at approximately equal frequency and also that the asymmetrical equivalent of crossing-over was induced at a measurable frequency.     

Numerical relationship between cells with radiation-induced chromosome aberrations and cells lethally injured by radiation

Summary The numerical relationship between radiation-induced chromosome aberrations in humanG ₀ lymphocytes and reproductive lethality of human bone-marrow lymphocytes is analysed within a large LET interval. The comparison is based upon the evaluation of the coefficient of the linear component of the corresponding dose-effect-relation for the frequency of cells without aberrations and for the frequency of surviving cells respectively. The good correlation between these coefficients over a large LET interval supports the hypothesis that structural chromosome aberrations and reproductive cell death both result from the same gross chromatin damage.This work was supported by the Bundesministerium des Innern, Bonn     

Remote effects at cell and subcell level in the hemopoietic system after chronic radiation exposure in man

The parameters characterizing the state of hemopoietic cells obtained from chronically exposed residents of the Techa riverside villages studied at late time after the exposure included: the level of somatic mutations in the TCR gene, the level of chromosome aberrations, the intensity of peripheral blood lymphocyte apoptosis. Exposed versus unexposed subjects (controls) showed an increased frequency of CD3-CD4+ T-lymphocytes, chromosome aberrations of stable type (translocations) and unstable type (dicentrics, rings), and also increased intensity of lymphocyte apoptosis. The findings of tests using a standard additional gamma-irradiation (1 Gy) accompanied by 24-hour incubation indicated that the rate of apoptosis of lymphocytes was significantly higher in exposed individuals in comparison with unexposed ones. It was suggested basing on the obtained data that at late time the chronic (for over 50 years) exposure at RBM doses from 0.01 to 3.22 Sv was a factor inducing the damage to the genetic apparatus of hemopoietic cells. Evidently, the initial chronic low-intensity irradiation in the above-indicated dose range activates adaptive processes at the cellular level in hemopoietic cells. Late time after the onset of exposure the adaptation reserves are depleted in chronically exposed persons which brings about its failure in the case of a challenge by additional external exposures.     

Cytogenetic analysis of chromosome segments containing radiosensitivity genes in Drosophila. Radiation mutagenesis in the 44-45 region of chromosome 2 of Drosophila melanogaster

The first step of cytogenetic analysis of Drosophila melanogaster chromosome 2 44F-45D containing the radiosensitivity gene rad(2)201 is described. Using various mutation selection systems as well as lines of different origin and two kinds of ionizing radiation--gamma-rays and neutrons--the mutagenesis in the region of interest is characterized at the cytogenetic level. 85 gamma-induced mutations affecting viability were isolated in the 44F 2-4; 45C6-7 interval, 27% of mutations being chromosomal aberrations. 15 radiation-induced aberrations were obtained by selecting mutations at the white gene inserted into the 45D region by P-mediated transformation. The 44F-45D region is characterized by relatively low frequency of deficiency formation and by significant predomination of heterochromatic aberrations in the spectrum of rearrangements. In these regions, the existence of hot spots for heterochromatic aberrations was discovered. As low deletion frequency is not connected with the presence of haplolethal and haplosterile loci in the region studied, the unusual character of radiation mutagenesis reflects possibly the peculiarities in sequence organization of the chromosomal region mentioned or the packaging in the sperm nuclei.     

Size and specific radioactivity of the [h]thymidine triphosphate pool and DNA synthesis in the radicles of germinating cotton

By relating the specific radioactivity, size, and turnover of the labeled thymidine triphosphate pool to DNA synthesis, it was shown that the 32- to 38-hour interval of cotton seedling (Gossypium barbadense L.) germination was the peak period of DNA synthesis within the radicle tip during a total germination time of 48 hours at 35 C.     

Kinetics of reparation of sublethal radiation damage in early hematopoietic precursors

The authors studied the ability of the CFU-S, forming colonies on the 8th and 11th days after bone marrow cells transplantation, to repair the sublethal radiation damages (SRD), according to Elkind's model. Special attention was given to the kinetics fo reparation for SRD for two subpopulations of CFU (8th- and 11th-days' CFU-S). the 1-6 hour intervals between two equivalent doses of irradiation were made. The ability to repair the SRD of the 11th-days' CFU-S was lower than that of the 8th-days' CFU-S at all time intervals. The maximum reparation of the 8th-days' CFU-S was observed at 5-hour period; and that was twice as high as the maximum reparation of the 11th-days' CFU-S, which was determined at 3-hour interval between the two irradiation doses.     

Hormonal and inflammatory responses to different types of sprint interval training

We evaluated the effect of different types of sprint interval sessions on the balance between anabolic and catabolic hormones and circulating inflammatory cytokines. Twelve healthy elite junior handball players (17-25 years) participated in the study. Exercise consisted of increasing distance (100 m, 200 m, 300 m, 400 m) and decreasing distance (400 m, 300 m, 200 m, 100 m) sprint interval runs on a treadmill (at random order), at a constant work rate of 80% of the personal maximal speed (calculated from the maximal speed of a 100 m run). The total rest period between the runs in the different interval sessions were similar. Blood samples were collected before, after each run, and after 1-hour recovery. Both types of sprint interval trainings led to a significant (p < 0.05) increase in lactate and the anabolic factors growth hormone, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and testosterone levels. Both types of sprint interval sessions led to a significant (p < 0.05) increase in the circulating pro- and anti-inflammatory mediators IL-1, IL-6, and IL1ra. IL-6 remained elevated in both sessions after 1-hour recovery. Area under the curve was significantly greater (p < 0.05) for lactate and growth hormone (GH) in the decreasing distance session. In contrast, rate of perceived exertion was higher in the increasing distance session, but this difference was not statistically significant (p = 0.07). Changes in anabolic-catabolic hormones and inflammatory mediators can be used to gauge the training intensity of anaerobic-type exercise. Changes in the GH-IGF-I axis and testosterone level suggest exercise-related anabolic adaptations. Increases in inflammatory mediators may indicate their important role in muscle tissue repair after anaerobic exercise. The decreasing distance interval was associated with a greater metabolic (lactate) and anabolic (GH) response but not with a higher rate of perceived exertion. Coaches and athletes should be aware of these differences, and as a result, of a need for specific recovery adaptations after different interval training protocols.     

Paternally transmitted chromosomal aberrations in mouse zygotes determine their embryonic fate

The developmental consequences of chromosomal aberrations in embryos include spontaneous abortions, morphological defects, inborn abnormalities, and genetic/chromosomal diseases. Six germ-cell mutagens with different modes of action and spermatogenic stage sensitivities were used to investigate the relationship between the types of cytogenetic damage in zygotes with their subsequent risk of postimplantation death and of birth as a translocation carrier. Independent of the mutagen used, over 98% of paternally transmitted aberrations were chromosome type, rather than chromatid type, indicating that they were formed during the period between exposure of male germ cells and initiation of the first S phase after fertilization. There were consistent one-to-one agreements between the proportions of a) zygotes with unstable aberrations and the frequencies of dead embryos after implantation (slope = 0.87, confidence interval [CI]: 0.74, 1.16) and b) zygotes with reciprocal translocations and the frequency of translocation carriers at birth (slope = 0.74, CI: 0.48, 2.11). These findings suggest that chromosomal aberrations in zygotes are highly predictive of subsequent abnormal embryonic development and that development appears to proceed to implantation regardless of the presence of chromosomal abnormalities. Our findings support the hypothesis that, for paternally transmitted chromosomal aberrations, the fate of the embryo is already set by the end of G1 of the first cell cycle of development.     

Antimutagenic effect of chemosignals from isolated female house mouse on male germ cells (Mus musculus L.)

The influence of chemosignals from isolated mature females of the CBA strain on level of spontaneous and radiation-induced meiotic disturbances in spermatocytes I of males of the same strain was studied. Using an ana-telophase method, 24-hour exposure of males to soiled bedding containing isolated females’ chemosignals was shown to lead to a significantly lower frequency of chromosomal aberrations and other meiotic disturbances in spermatocytes I as compared to males kept on clean bedding. The same effect of female chemosignals was found in the germ cells of irradiated males (4 Gr). The mechanisms and importance of the revealed antimutagenic effect of mouse female chemosignals on the male reproductive cells in the reproduction process are discussed.     

Chromosomes of human sperm: Variability among normal individuals

Summary The chromosomal constitution of 2468 human sperm cells been investigated by fusion of human sperm with hamster eggs. The overall frequency of cells with structural aberrations was 7.7%, ranging from 1.9% to 15.8%, and varying significantly among individuals. The highest frequency occurred in sperm from the oldest donor (49 years), who also had had a vasectomy reversal three years prior to sampling. The overall aneuploidy frequency was 1.7%, ranging from 0.6% to 3.1%. In nine out of ten donors from whom blood samples were available the frequency of sperm cells with structural aberrations was higher than that for lymphocytes. Two previously reported donors (Brandriff et al. 1984) were resampled after an interval of 14 and 16 months respectively, and were each found to have similar frequencies of sperm chromosome abnormalities at both sampling times. A father-son pair included in the study had several chromosome breakpoints in common, although no more frequently than unrelated individuals.     

Relationship of DNA repair to chromosome aberrations, sister-chromatid exchanges and survival during liquid-holding recovery in X-irradiated mammalian cells

The repair of X-ray induced DNA single strand breaks and DNA—protein cross-links was investigated in stationary phase, contact-inhibited mouse cells by the alkaline-elution technique. Approx. 90% of X-ray induced single strand breaks were rejoined during the first hour of repair, whereas most of the remaining breaks were rejoined more slowly during the next 5 h. At early repair times, the number of residual non-rejoined sungle strand breaks was approx. proportional to the X-ray dose. DNA—protein cross-links were removed at a slower rate (T1/2 approx. 10–12 h). Cells were held in stationary growth for various periods of time after irradiation before subculture at low density to score for colony survival (potentially lethal damage repair), chromosome aberrations in the first mitosis, and sister-chromatid exchanges in the second mitosis. Both cell killing and the frequency of chromosome aberrations decreased during the first several hours of recovery, reaching a minimum level by 6 h; this decrease correlated temporally with the repair of the slowly rejoining DNA-strand breaks. Relatively few sister-chromatid exchanges were observed when the cells were subcultured immediately after X-ray. The exchange frequency rose to maximum levels after a 4-h recovery interval, and returned to control levels after 12 h of recovery. The possible relationship of DNA repair to these changes in survival, chromosome aberrations, and sister-chromatid exchanges during liquid-holding recovery is discussed.     

C-MYC Aberrations as Prognostic Factors in Diffuse Large B-cell Lymphoma: A Meta-Analysis of Epidemiological Studies

Objectives

Various studies have investigated the prognostic value of C-MYC aberrations in diffuse large B-cell lymphoma (DLBCL). However, the role of C-MYC as an independent prognostic factor in clinical practice remains controversial. A systematic review and meta-analysis were performed to clarify the clinical significance of C-MYC aberrations in DLBCL patients.

Methods

The pooled hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS) were calculated as the main effect size estimates. The procedure was conducted according to the Cochrane handbook and PRISMA guidelines, including the use of a heterogeneity test, publication bias assessment, and meta-regression, as well as subgroup analyses.

Results

Twenty-four eligible studies enrolling 4662 patients were included in this meta-analysis. According to the nature of C-MYC aberrations (gene, protein, and mRNA), studies were divided into several subgroups. For DLBCL patients with C-MYC gene abnormalities, the combined HR was 2.22 (95% confidence interval, 1.89 to 2.61) for OS and 2.29 (95% confidence interval, 1.81 to 2.90) for EFS, compared to patients without C-MYC gene abnormalities. For DLBCL patients with overexpression of C-MYC protein and C-MYC mRNA, pooled HRs for OS were 2.13 and 1.62, respectively. C-MYC aberrations appeared to play an independent role among other well-known prognostic factors in DLBCL. Addition of rituximab could not overcome the inferior prognosis conferred by C-MYC.

Conclusion

The present systematic review and meta-analysis confirm the prognostic value of C-MYC aberrations. Screening of C-MYC should have definite prognostic meaning for DLBCL stratification, thus guaranteeing a more tailored therapy.