Chromosomal instability in in vivo radiation exposed subjects (original) (raw)
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Scientific reports, 2017
The mechanisms behind the transmission of chromosomal aberrations (CA) remain unclear, despite a large body of work and major technological advances in chromosome identification. We reevaluated the transmission of CA to second- and third-division cells by telomere and centromere (TC) staining followed by M-FISH. We scored CA in lymphocytes of healthy donors after in vitro irradiation and those of cancer patients treated by radiation therapy more than 12 years before. Our data demonstrate, for the first time, that dicentric chromosomes (DCs) decreased by approximately 50% per division. DCs with two centromeres in close proximity were more efficiently transmitted, representing 70% of persistent DCs in ≥M3 cells. Only 1/3 of acentric chromosomes (ACs), ACs with four telomeres, and interstitial ACs, were paired in M2 cells and associated with specific DCs configurations. In lymphocytes of cancer patients, 82% of detected DCs were characterized by these specific configurations. Our findi...
Clinical Biochemistry, 2011
Objective: Studies indicate that ionizing radiation can induce persistent genetic instability in a high proportion of exposed cells. It has also been reported that exposure of radiotherapy workers to ionizing radiation causes chromosomal damages. Some of the damaged cells show a large number of aberrations such as dicentrics, polycentrics, rings, and numerous acentric fragments.To determine, whether chromosomal damages can be used as a biomarker of possible radiation in occupational exposure in a hospital setting. Methodology: In this study, chromosome abnormalities were evaluated in peripheral blood lymphocytes from fifty medical radiotherapy workers who handled ionizing radiation for an average of twelve years, and forty three control individuals who did not knowingly come in contact with any radiation source. Chromosome aberrations were evaluated by the conventional solid stain technique. Results: Dicentrics, fragments, followed by ring chromosomes, as well as total chromosome aberrations were elevated in the experimental group. We did not observe any aneuploidy chromosome in the present study. Although the level of exposure was below the annual permissible limit of twenty mSv/y recommended by the International Commission for Radiation Protection for whole body exposure, the mean frequencies of different chromosomal aberrations were higher in radiotherapy workers compared with controls (P=0.041). Although the mean frequencies of chromosomal aberrations in the female workers (3.5±1.42) was slightly higher than in males (3.28±0.95), there was no significant differences (P=0.74) in the frequency of chromosome aberration between males and females of ionizing radiotherapy workers.
Cancer Letters, 2000
The new method of chemical-induced premature chromosome condensation combined with¯uorescence in situ hybridization was used to analyze chromosomal damage in peripheral blood mononuclear lymphocytes of patients undergoing radiation treatment for esophageal cancer with high-energy X-rays or accelerated carbon ions at the National Institute of Radiological Sciences (Chiba, Japan). Total number of aberrant cells correlated with radiation ®eld size, but no correlation was found with acute toxicity. A high frequency of complex-type exchanges were also recorded. This aberration type presented a high individual variability, and correlated well with the acute morbidity. Cytogenetic analysis by interphase chromosome painting is proposed as a useful tool for monitoring normal tissue effects during radiotherapy. q
Lack of recovery from radiation induced chromosome damage in G0 human lymphocytes
Experimental Cell Research, 1972
Human peripheral blood lymphocyte cultures were irradiated with a dose of X-rays split in two equal fractions. The first fraction of dose was given shortly after culture initiation and the second one at 0, 2, 4, 18, 20, 22 and 24 h thereafter. Dicentric and ring chromosomes were scored at 54 h of cultivation. The aberration yields were essentially the same regardless of whether the radiation was given in a single burst or in two fractions separated by intervals of up to 20 h. The results unexpectedly revealed that no rejoining took place during this period. A drop in aberration yield occurred when the interval between exposures increased to 24 h, suggesting that at this time the system responsible for the rejoining of broken chromosome ends becomes operative. It was also noticed that no rejoining took place in small non-stimulated lymphocytes incubated at 37°C for 6 h prior to cultivation. These findings may explain the production of two-hit aberrations in peripheral blood lymphocytes of persons chronically exposed to small doses and very small dose rates of ionizing radiations.
We report the occurrence of chromosome instability in human T lymphocytes irradiated in vitro with γ-rays and cultured for several generations before analysis. The delayed effects of γ-radiation have been evaluated by conventional and molecular (chromosome painting) cytogenetics in preparations obtained from long-term bulk cultures or clonal cultures. The results indicate that the cell progeny of γ irradiated human T lymphocytes can be characterized by a higher rate of chromosome damage, but this effect depends on the individual donor response to ionizing radiation. Evidence has been collected about a differential involvement of chromosomes 7, 9 and 19 in the induced chromosome rearrangements, and this effect is equally visible as an immediate or delayed response of human T lymphocytes to ionizing radiation.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1985
The quantitative analysis of the chromosome rearrangements detected in 2128 R-banded metaphases, obtained from T-irradiated human lymphocytes after 48 to 96 h in culture is reported. Depending on the culture time, and possibly on the dose of radiation (from 1 to 3 Gy), the most frequent type of rearrangement was either dicentrics or reciprocal translocations. In first generation mitoses, the frequency of cells without rearrangement ranged from 0.66 to 0.18, and the mean number of rearranged chromosomes per cell from 0.79 to 3.28. The dose-response curve follows a quadratic function for dicentric aberration yields, but not for other rearrangements.
Radiation-induced Chromosome Instability: The Role of Dose and Dose Rate
Genome Integrity, 2019
Nontargeted effects include radiation-induced genomic instability (RIGI) which is observed in the progeny of cells exposed to ionizing radiation and can be manifested in different ways, including chromosomal instability and micronucleus (MN) formation. Since genomic instability is commonly observed in tumors and has a role in tumor progression, RIGI has the potential of being an important mechanism for radiation-induced cancer. The work presented explores the role of dose and dose rate on RIGI, determined using a MN assay, in normal primary human fibroblast (HF19) cells exposed to either 0.1 Gy or 1 Gy of X-rays delivered either as an acute (0.42 Gy/min) or protracted (0.0031 Gy/min) exposure. While the expected increase in MN was observed following the first mitosis of the irradiated cells compared to unirradiated controls, the results also demonstrate a significant increase in MN yields in the progeny of these cells at 10 and 20 population doublings following irradiation. Minimal ...
Mutagenesis
We report the occurrence of chromosome instability in human T lymphocytes irradiated in vitro with gamma-rays and cultured for several generations before analysis. The delayed effects of gamma-radiation have been evaluated by conventional and molecular (chromosome painting) cytogenetics in preparations obtained from long-term bulk cultures or clonal cultures. The results indicate that the cell progeny of gamma irradiated human T lymphocytes can be characterized by a higher rate of chromosome damage, but this effect depends on the individual donor response to ionizing radiation. Evidence has been collected about a differential involvement of chromosomes 7, 9 and 19 in the induced chromosome rearrangements, and this effect is equally visible as an immediate or delayed response of human T lymphocytes to ionizing radiation.