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Sample records for chromosome aberration analysis

  1. DETECTION OF CHROMOSOME ABERRATIONS IN TWELVE PRIMARY GASTRIC CANCERS BY DIRECT CHROMOSOME ANALYSIS AND FISH

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Direct chromosome analysis and FISH were performed on twelve primary gastric carcinomas. Two of them had simple chromosome changes: 48,XX, +8, +20, and 49, XY, +2, +8, +9, and the others had complicated chromosome changes, which includes much more numerical and structural chromosome aberrations. Frequent structural changes in the complicated types involved chromosome 7, 3, 1, 5 and 12 etc. The del 7q was noted in eight cases. The del (3p) and del (1p) were noted in six and five cases, respectively. The results provide some important clues for isolation of the genes related to gastric cancer.

  2. Analysis of chromosome aberration data by hybrid-scale models

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    Indrawati, Iwiq [Research and Development on Radiation and Nuclear Biomedical Center, National Nuclear Energy Agency (Indonesia); Kumazawa, Shigeru [Nuclear Technology and Education Center, Japan Atomic Energy Research Institute, Honkomagome, Tokyo (Japan)

    2000-02-01

    This paper presents a new methodology for analyzing data of chromosome aberrations, which is useful to understand the characteristics of dose-response relationships and to construct the calibration curves for the biological dosimetry. The hybrid scale of linear and logarithmic scales brings a particular plotting paper, where the normal section paper, two types of semi-log papers and the log-log paper are continuously connected. The hybrid-hybrid plotting paper may contain nine kinds of linear relationships, and these are conveniently called hybrid scale models. One can systematically select the best-fit model among the nine models by among the conditions for a straight line of data points. A biological interpretation is possible with some hybrid-scale models. In this report, the hybrid scale models were applied to separately reported data on chromosome aberrations in human lymphocytes as well as on chromosome breaks in Tradescantia. The results proved that the proposed models fit the data better than the linear-quadratic model, despite the demerit of the increased number of model parameters. We showed that the hybrid-hybrid model (both variables of dose and response using the hybrid scale) provides the best-fit straight lines to be used as the reliable and readable calibration curves of chromosome aberrations. (author)

  3. mBAND Analysis of Late Chromosome Aberrations in Human Lymphocytes Induced by Gamma Rays and Fe Ions

    Science.gov (United States)

    Sunagawa, Mayumi; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2014-01-01

    Chromosomal translocations and inversions are considered stable, and cells containing these types of chromosome aberrations can survive multiple cell divisions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. Detailed analysis of chromosome break ends participating in exchanges revealed a greater fraction of break ends involved in intrachromosome aberrations in the 7- and 14-day samples in comparison to the fraction at first mitosis. In particular, simple inversions were found at 7 and 14 days, but not at the first mitosis, suggesting that some of the aberrations might be formed days post irradiation. In contrast, at the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Comparison between low and high doses of Fe ion irradiation in the induction of late damages will also be discussed.

  4. [Familial, structural aberration of the Y chromosome with fertility disorders].

    Science.gov (United States)

    Gall, H; Schmid, M; Schmidtke, J; Schempp, W; Weber, L

    1985-11-01

    Cytogenetic studies on a patient with Klinefelter's syndrome revealed an inherited, structural aberration of the Y-chromosome which has not been described before. The aberrant Y-chromosome was characterized by eight different banding methods. The value of individual staining techniques in studies on Y-heterochromatin aberrations is emphasized. Analysis of the cytogenetic studies (banding methods, restriction endonuclease of DNA, and measurement of the length of the Y-chromosome) permits an interpretation to be made on how the aberrant Y-chromosome originated. The functions of the Y-chromosome are discussed. The decrease in fertility (cryptozoospermia) in the two brothers with the same aberrant Y-chromosome was striking.

  5. Comparative analysis of clastogen-induced chromosome aberrations observed with light microscopy and by means of atomic force microscopy.

    Science.gov (United States)

    Koleva, Vanya Petrova; Dragoeva, Asya Pencheva; Andreeva, Andreana Ivanova; Burova, Marina Todorova; Georgiev, Sevdalin; Enchev, Dobromir Dimitrov

    2013-04-30

    Different types of chromosome aberration were observed in mouse bone-marrow cells after treatment with 4-bromo-N,N-diethyl-5,5-dimethyl-2,5-dihydro-1,2-oxaphosphol-2-amine 2-oxide (Br-oxaphosphole, Br-oxph) in a previous study. The aim of the present study is to perform a comparative analysis of these chromosomal damages observed with light microscopy (LM) and by means of atomic force microscopy (AFM). The kinds of aberrations scored by LM were substantially corrected by images at the ultrastructural level. The AFM analysis excluded 29.0% of gaps and 33.3% of fusion-type aberrations. On the other hand, AFM revealed the presence of aberrations that were not visible under the LM. This indicates that only AFM images would provide precise information about the real nature of chromosomal damages. The results of our study revealed that the 'real gaps' represented about 50% of all the gaps visible under LM. Excluded 'false gaps' were detected via AFM as breaks or decondensed chromosome regions. These results would support the statement that gaps must be included when testing genotoxicity. The ultrastructural analysis also confirmed the validity of using LM in the mouse bone-marrow chromosome aberration test, as a tool for detecting genotoxicity of chemicals in routine studies. When there is a need for precise evaluation of chromosome damage, only AFM images can provide information on specific genotoxic effects.

  6. Characterization of a new aberration of the human Y chromosome by banding methods and DNA restriction endonuclease analysis.

    Science.gov (United States)

    Schmid, M; Gall, H; Schempp, W; Weber, L; Schmidtke, J

    1981-01-01

    Comparative cytogenetic analyses were performed with ten different banding methods on a previously undescribed, inherited structural aberration of a Y chromosome, and the results compared with those of normal Y chromosomes occurring in the same family. The value of the individual staining techniques in investigations of Y chromosomal aberrations is emphasized. The aberrant Y chromosome analyzed can be formally derived from an isodicentric Y chromosome for the short arm with a very terminal long-arm breakpoint, in which the centromere, an entire short arm, and the proximal region on one long arm was lost. This interpretation was confirmed by determining the amount of the two Y-specific DNA sequences (2.1 and 3.4 kb in length) by means of Hae III restriction endonuclease analysis. The karyotype-phenotype correlations in the men with this aberrant Y chromosome, especially the fertility dysfunctions (oligoasthenoteratozoospermia, cryptozoospermia), are discussed. The possibility of the existence of fertility factors involved in the control of spermatogenesis within the quinacrine-bright heterochromatic region of the Y long arm is presented.

  7. Chromosome Aberrations in Human Epithelial Cells Exposed Los Alamos High-Energy Secondary Neutrons: M-BAND Analysis

    Science.gov (United States)

    Hada, M.; Saganti, P. B.; Gersey, B.; Wilkins, R.; Cucinotta, F. A.; Wu, H.

    2007-01-01

    High-energy secondary neutrons, produced by the interaction of galactic cosmic rays (GCR) with the atmosphere, spacecraft structure and planetary surfaces, contribute a significant fraction to the dose equivalent radiation measurement in crew members and passengers of commercial aviation travel as well as astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility's 30L beam line (4FP30L-A/ICE House) is known to generate neutrons that simulate the secondary neutron spectrum of the Earth's atmosphere at high altitude. The neutron spectrum is also similar to that measured onboard spacecrafts like the MIR and the International Space Station (ISS). To evaluate the biological damage, we exposed human epithelial cells in vitro to the LANSCE neutron beams with an entrance dose rate of 2.5 cGy/hr, and studied the induction of chromosome aberrations that were identified with multicolor-banding in situ hybridization (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of inter-chromosomal aberrations (translocation to unpainted chromosomes) and intra-chromosomal aberrations (inversions and deletions within a single painted chromosome). Compared to our previous results with gamma-rays and 600 MeV/nucleon Fe ions of high dose rate at NSRL (NASA Space Radiation Laboratory at Brookhaven National Laboratory), the neutron data from the LANSCE experiments showed significantly higher frequency of chromosome aberrations. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intrachromosomal aberrations but few inversions were accompanied by interchromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both

  8. Chromosome aberrations induced by zebularine in triticale.

    Science.gov (United States)

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  9. Analysis of the Ambient Particulate Matter-induced Chromosomal Aberrations Using an In Vitro System.

    Science.gov (United States)

    Miousse, Isabelle R; Koturbash, Igor; Chalbot, Marie-Cécile; Hauer-Jensen, Martin; Kavouras, Ilias; Pathak, Rupak

    2016-12-21

    Exposure to particulate matter (PM) is a major world health concern, which may damage various cellular components, including the nuclear genetic material. To assess the impact of PM on nuclear genetic integrity, structural chromosomal aberrations are scored in the metaphase spreads of mouse RAW264.7 macrophage cells. PM is collected from ambient air with a high volume total suspended particles sampler. The collected material is solubilized and filtered to retain the water-soluble, fine portion. The particles are characterized for chemical composition by nuclear magnetic resonance (NMR) spectroscopy. Different concentrations of particle suspension are added onto an in vitro culture of RAW264.7 mouse macrophages for a total exposure time of 72 hr, along with untreated control cells. At the end of exposure, the culture is treated with colcemid to arrest cells in metaphase. Cells are then harvested, treated with hypotonic solution, fixed in acetomethanol, dropped onto glass slides and finally stained with Giemsa solution. Slides are examined to assess the structural chromosomal aberrations (CAs) in metaphase spreads at 1,000X magnification using a bright-field microscope. 50 to 100 metaphase spread are scored for each treatment group. This technique is adapted for the detection of structural chromosomal aberrations (CAs), such as chromatid-type breaks, chromatid-type exchanges, acentric fragments, dicentric and ring chromosomes, double minutes, endoreduplication, and Robertsonian translocations in vitro after exposure to PM. It is a powerful method to associate a well-established cytogenetic endpoint to epigenetic alterations.

  10. Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

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    Hada, M.; Huff, J. L.; Patel, Z.; Pluth, J. M.; George, K. A.; Cucinotta, F. A.

    2009-01-01

    A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome

  11. A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease.

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    Bae, Joon Seol; Koh, InSong; Cheong, Hyun Sub; Seo, Jeong-Meen; Kim, Dae-Yeon; Oh, Jung-Tak; Kim, Hyun-Young; Jung, Kyuwhan; Sul, Jae Hoon; Park, Woong-Yang; Kim, Jeong-Hyun; Shin, Hyoung Doo

    2016-11-01

    Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. Although the RET proto-oncogene is considered to be the main risk factor for HSCR, only about 30% of the HSCR cases can be explained by variations in previously known genes including RET. Recently, copy number variation (CNV) and loss of heterozygosity (LOH) have emerged as new ways to understand human genomic variation. The goal of this present study is to identify new HSCR genetic factors related to CNV in Korean patients. In the genome-wide genotyping, using Illumina's HumanOmni1-Quad BeadChip (1,140,419 markers), of 123 HSCR patients and 432 unaffected subjects (total n = 555), a total of 8,188 CNVs (1 kb ∼ 1 mb) were identified by CNVpartition. As a result, 16 CNV regions and 13 LOH regions were identified as associated with HSCR (minimum P = 0.0005). Two top CNV regions (deletions at chr6:32675155-32680480 and chr22:20733495-21607293) were successfully validated by additional real-time quantitative polymerase chain reaction analysis. In addition, 2 CNV regions (6p21.32 and 22q11.21) and 2 LOH regions (3p22.2 and 14q23.3) were discovered to be unique to the HSCR patients group. Regarding the large-scale chromosomal aberrations (>1 mb), 11 large aberrations in the HSCR patients group were identified, which suggests that they may be a risk factor for HSCR. Although further replication in a larger cohort is needed, our findings may contribute to the understanding of the etiology of HSCR.

  12. Chromosome aberration assays in Allium

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    Grant, W.F.

    1982-01-01

    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  13. Analysis of Unstable Chromosome Aberrations for Partial Body Exposures with Gamma Rays

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    Syaifudin, Mukh [Center for Technology of Radiation Safety and Metrology, National Nuclear Energy Agency, Jakarta (Indonesia); Yun, Hyun Jin; Kim, Eun Ju; Kang, Chang Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-04-15

    Scoring of unstable chromosome aberrations (dicentrics, rings and fragments) in circulating lymphocytes are the most extensively studied biological means for estimating individual exposure to ionizing radiation. The effects of radiation, however, can be significantly different when only portions of the body or an individual organ system are irradiated, such as might occur during the use of radiation for medical treatment, where some problems can arise especially to quantify the fraction of body irradiated. After partial-body exposure, peripheral blood samples contain a mixture of exposed and unexposed lymphocytes, which render the interpretation of the overall aberration frequencies more difficult. In this experiment, peripheral blood samples from four volunteers (two Indonesian and two Korean) were irradiated with 2.0 Gy of gamma rays for simulation of partial-body exposure by mixing irradiated and non-irradiated blood from the same volunteers in proportions of 10-100%. Dose estimates are crucial for risk assessment as well as for clinical planning of treatment of highly exposed victims. The results presented in this experiment concluded that the scoring of chromosome aberration is reliable methodology for investigating exposure to ionizing irradiation, such as partial-body ones. This study constitutes a preliminary step in our process of defining the possibilities of cytological technique for biological dosimetry expertise. Because of the limitations of a number of cases, no clear conclusion could be reached.

  14. Flow cytometric detection of aberrant chromosomes

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    Gray, J.W.; Lucas, J.; Yu, L.C.; Langlois, R.

    1983-05-11

    This report describes the quantification of chromosomal aberrations by flow cytometry. Both homogeneously and heterogeneously occurring chromosome aberrations were studied. Homogeneously occurring aberrations were noted in chromosomes isolated from human colon carcinoma (LoVo) cells, stained with Hoechst 33258 and chromomycin A3 and analyzed using dual beam flow cytometry. The resulting bivariate flow karyotype showed a homogeneously occurring marker chromosome of intermediate size. Heterogeneously occurring aberrations were quantified by slit-scan flow cytometry in chromosomes isolated from control and irradiated Chinese hamster cells and stained with propidium iodide. Heterogeneously occurring dicentric chromosomes were detected by their shapes (two centrometers). The frequencies of such chromosomes estimated by slit-scan flow cytometry correlated well with the frequencies determined by visual microscopy.

  15. Chromosomal aberrations in ISS crew members

    Science.gov (United States)

    Johannes, Christian; Goedecke, Wolfgang; Antonopoulos, Alexandra

    2012-07-01

    High energy radiation is a major risk factor in manned space missions. Astronauts and cosmonauts are exposed to ionising radiations of cosmic and solar origin, while on the Earth's surface people are well protected by the atmosphere and a deflecting magnetic field. There are now data available describing the dose and the quality of ionising radiation on-board of the International Space Station (ISS). Nonetheless, the effect of increased radiation dose on mutation rates of ISS crew members are hard to predict. Therefore, direct measurements of mutation rates are required in order to better estimate the radiation risk for longer duration missions. The analysis of chromosomal aberrations in peripheral blood lymphocytes is a well established method to measure radiation-induced mutations. We present data of chromosome aberration analyses from lymphocyte metaphase spreads of ISS crew members participating in short term (10-14 days) or long term (around 6 months) missions. From each subject we received two blood samples. The first sample was drawn about 10 days before launch and a second one within 3 days after return from flight. From lymphocyte cultures metaphase plates were prepared on glass slides. Giemsa stained and in situ hybridised metaphases were scored for chromosome changes in pre-flight and post-flight blood samples and the mutation rates were compared. Results obtained in chromosomal studies on long-term flight crew members showed pronounced inter-individual differences in the response to elevated radiation levels. Overall slight but significant elevations of typical radiation induced aberrations, i.e., dicentric chromosomes and reciprocal translocations have been observed. Our data indicate no elevation of mutation rates due to short term stays on-board the ISS.

  16. Genetic Alterations in Pesticide Exposed Bolivian Farmers: An evaluation by analysis of chromosomal aberrations and the comet assay

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    Erik Jørs

    2007-01-01

    Full Text Available Background: Pesticides are of concern in Bolivia because of increasing use. Frequent intoxications have been demonstrated due to use of very toxic pesticides, insufficient control of distribution and sale and little knowledge among farmers of protective measures and hygienic procedures.Method: Questionnaires were applied and blood tests taken from 81 volunteers from La Paz County, of whom 48 were pesticide exposed farmers and 33 non-exposed controls. Sixty males and 21 females participated with a mean age of 37.3 years (range 17–76. Data of exposure and possible genetic damage were collected and evaluated by well known statistical methods, controlling for relevant confounders. To measure genetic damage chromosomal aberrations and the comet assay analysis were performed.Results: Pesticide exposed farmers had a higher degree of genetic damage compared to the control group. The number of chromosomal aberrations increased with the intensity of pesticide exposure. Females had a lower number of chromosomal aberrations than males, and people living at altitudes above 2500 metres seemed to exhibit more DNA damage measured by the comet assay.Conclusions: Bolivian farmers showed signs of genotoxic damage, probably related to exposure to pesticides. Due to the potentially negative long term health effects of genetic damage on reproduction and the development of cancer, preventive measures are recommended. Effective control with imports and sales, banning of the most toxic pesticides, education and information are possible measures, which could help preventing the negative effects of pesticides on human health and the environment.

  17. Radiotherapeutical chromosomal aberrations in laryngeal cancer patients

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    Stošić-Divjak Svetlana L.

    2009-01-01

    Full Text Available Introduction. The authors present the results of cytogenetic analysis of 21 patients with laryngeal carcinomas diagnosed and treated in the period 1995-2000 at the Institute of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia and Clinical Center of Novi Sad. Material and methods. The patients were specially monitored and the material was analyzed at the Institute of Human Genetics of the School of Medicine in Belgrade as well as in the Laboratory for Radiological Protection of the Institute of Occupational and Radiological Health 'Dr Dragomir Karajovic' in Belgrade. Results. The incidence of chromosomal aberrations and incidence of exchange of material between sister chromatids were observed in the preparation of the metaphasic lymphocyte chromosomes of the peripheral blood obtained in the culture. Structural aberrations were found on the chromosomes in the form of breakups, rings, translocations and dicentrics as early as after a single exposure of patients to tumor radiation dose of 2 Gy in the field sized 5x7. Out of the total number of 35 cultivated blood samples obtained from 13 patients, 21 were successfully cultivated and they were proved to contain chromosomal aberrations. Some of the peripheral blood samples failed to show cell growth in vitro due to the lethal cell damages in vivo. Discussion.. We have consluded that the number of structural aberrations cannot be used as a biological measure of the absorbed ionizing radiation dose. The presence of aberrations per se is indicative of the mutagenic effect of the ionizing radiation, which was also confirmed in our series on the original model by cultivation of the peripheral blood lymphocytes in the culture of the cells of the volunteer donors upon in vitro radiation. Using the method of bromdeoxyuridylreductase, the increased incidence of SCE as a mutagenic effect was registered. Conclusion. It has been concluded that the increase of absorbed radiation dose in

  18. Fast-FISH Detection and Semi-Automated Image Analysis of Numerical Chromosome Aberrations in Hematological Malignancies

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    Arif Esa

    1998-01-01

    Full Text Available A new fluorescence in situ hybridization (FISH technique called Fast-FISH in combination with semi-automated image analysis was applied to detect numerical aberrations of chromosomes 8 and 12 in interphase nuclei of peripheral blood lymphocytes and bone marrow cells from patients with acute myelogenous leukemia (AML and chronic lymphocytic leukemia (CLL. Commercially available α-satellite DNA probes specific for the centromere regions of chromosome 8 and chromosome 12, respectively, were used. After application of the Fast-FISH protocol, the microscopic images of the fluorescence-labelled cell nuclei were recorded by the true color CCD camera Kappa CF 15 MC and evaluated quantitatively by computer analysis on a PC. These results were compared to results obtained from the same type of specimens using the same analysis system but with a standard FISH protocol. In addition, automated spot counting after both FISH techniques was compared to visual spot counting after standard FISH. A total number of about 3,000 cell nuclei was evaluated. For quantitative brightness parameters, a good correlation between standard FISH labelling and Fast-FISH was found. Automated spot counting after Fast-FISH coincided within a few percent to automated and visual spot counting after standard FISH. The examples shown indicate the reliability and reproducibility of Fast-FISH and its potential for automatized interphase cell diagnostics of numerical chromosome aberrations. Since the Fast-FISH technique requires a hybridization time as low as 1/20 of established standard FISH techniques, omitting most of the time consuming working steps in the protocol, it may contribute considerably to clinical diagnostics. This may especially be interesting in cases where an accurate result is required within a few hours.

  19. DNA Repair Defects and Chromosomal Aberrations

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    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  20. Chromosome aberration analysis in persons exposed to low-level radiation from the JCO criticality accident in Tokai-mura.

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    Sasaki, M S; Hayata, I; Kamada, N; Kodama, Y; Kodama, S

    2001-09-01

    Chromosome aberrations were studied in peripheral blood lymphocytes of 43 persons who were exposed to low-level radiation of mixed neutrons and gamma-rays resulting from the JCO criticality accident. When the age-adjusted frequencies of dicentric and ring chromosomes were compared with the dose calibration curve established in vitro for 60Co gamma-rays as a reference radiation, a significant correlation was observed between the chromosomally estimated doses and the documented doses evaluated by physical means. The regression coefficient of the chromosomal doses against the documented doses, 1.47 +/- 0.33, indicates that the relative biological effectiveness of fission neutrons at low doses is considerably higher than that currently adopted in the radiation protection standard.

  1. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

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    Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

    2013-07-08

    The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.

  2. Effect of therapeutic hypothermia on chromosomal aberration in perinatal asphyxia

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    Bahubali D Gane

    2016-01-01

    Full Text Available Introduction: Perinatal asphyxia is a major cause for neonatal mortality and morbidity around the world. The reduction of O2results in the generation of reactive oxygen species which interact with nucleic acid and make alteration in the structure and functioning of the genome. We studied the effect of therapeutic hypothermia on chromosomes with karyotyping. Subjects and Methods: Babies in the hypothermia group were cooled for the first 72 h, using gel packs. Rectal temperature of 33–34°C was maintained. Blood sample was collected after completion of therapeutic hypothermia for Chromosomal analysis. It was done with IKAROS Karyotyping system, Metasystems, based on recommendations of International system of human cytogenetic nomenclature. Results: The median chromosomal aberration was lower in hypothermia [2(0-5] than control group [4(1-7] and chromatid breakage was commonest aberration seen. Chromosomal aberration was significantly higher in severe encephalopathy group than moderate encephalopathy group. Conclusion: We conclude that the TH significantly reduces DNA damage in perinatal asphyxia.

  3. Incidence of chromosomal aberrations and micronuclei in cave tour guides.

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    Bilban, M; Bilban-Jakopin, C; Vrhovec, S

    2001-01-01

    An analysis of structural chromosomal aberrations (SCA) and micronucleus tests (MN) were performed in 38 subjects, cave tour guides and in appropriate control group. The dominant type of chromosomal aberrations in tourist guides were chromosomal breaks (0.013 per cell) and acentric fragments (0.011 per cell). In the control group, these aberrations were present up to 0.008 on cells. Considering the analysed cells of the guides in total (33,556), the incidence of dicentric and rings range is below 0.0008 on cells, even though three dicentric and ring chromosoms were found already in the first 1000 in vitro metaphases of some guides. Only 0.0003 dicentrics and neither other translocations were found in control group (ambiental exposure). The incidence of micronuclei in cytokinesis blocked lymphocytes ranged from 12-32 per 500 CB cells in the cave tour guides and from 4-11 per 500 CB cells in control group. Measurements of radon and its daughters were performed at different locations in the cave. Annual doses from 40-60 mSv were estimated per 2000 work hours for cave guides. The changes found in the genome of somatic cells may be related to the exposure doses of radon and its daughters, although smoking should not be ignored.

  4. Biological dosimetry of ionizing radiation by chromosomal aberration analysis; Dosimetria biologica de las radiaciones ionizantes mediante el analisis de aberraciones cromosomicas

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Castano, S.; Silva, A.; Navlet, J.

    1990-07-01

    Biological dosimetry consists of estimating absorbed doses for people exposed to radiation by mean biological methods. Several indicators used are based in haematological, biochemical, and cytogenetic data, although nowadays without doubt, the cytogenetic method is considered to be the most reliable. In this case, the study ol chromosomal aberrations, normally dicentric chromosomes, in peripheral lymphocytes can be related to absorbed dose through an experimental calibration curve. An experimental dose-response curve, using dicentric chromosomes analysis, X-rays at 300 kVp, 114 rad/min and temperature 37 degree celsius has been produced. Experimental data is fitted to model Y ={alpha} + {beta}{sub 1}D + {beta}{sub 2}D 2 , where Y is the number of dicentrics per cell and D the dose. The curve is compared with those produced elsewhere. (Author) 14 refs.

  5. Morphological images analysis and chromosomic aberrations classification based on fuzzy logic; Analise morfologica de imagens e classificacao de aberracoes cromossomicas por meio de logica fuzzy

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Leonardo Peres

    2011-07-01

    This work has implemented a methodology for automation of images analysis of chromosomes of human cells irradiated at IEA-R1 nuclear reactor (located at IPEN, Sao Paulo, Brazil), and therefore subject to morphological aberrations. This methodology intends to be a tool for helping cytogeneticists on identification, characterization and classification of chromosomal metaphasic analysis. The methodology development has included the creation of a software application based on artificial intelligence techniques using Fuzzy Logic combined with image processing techniques. The developed application was named CHRIMAN and is composed of modules that contain the methodological steps which are important requirements in order to achieve an automated analysis. The first step is the standardization of the bi-dimensional digital image acquisition procedure through coupling a simple digital camera to the ocular of the conventional metaphasic analysis microscope. Second step is related to the image treatment achieved through digital filters application; storing and organization of information obtained both from image content itself, and from selected extracted features, for further use on pattern recognition algorithms. The third step consists on characterizing, counting and classification of stored digital images and extracted features information. The accuracy in the recognition of chromosome images is 93.9%. This classification is based on classical standards obtained at Buckton [1973], and enables support to geneticist on chromosomic analysis procedure, decreasing analysis time, and creating conditions to include this method on a broader evaluation system on human cell damage due to ionizing radiation exposure. (author)

  6. Considerations for comparing radiation-induced chromosome aberration data with predictions from biophysical models

    Science.gov (United States)

    Wu, H.; Furusawa, Y.; George, K.; Kawata, T.; Cucinotta, F.

    Biophysical models addressing the formation of radiation-induced chromosome aberrations are usually based on the assumption that chromosome aberrations are formed by DNA double strand break (DSB) misrejoining, via either the homologous or the non-homologous repair pathway. However, comparing chromosome aberration data with model predictions is not always straightforward. In this paper we discuss some of the aspects that must be considered to make these comparisons meaningful. Firstly, biophysical models are usually applied to DSB rejoining and misrejoining in the G0/G1 phase of the cell cycle, while most chromosome aberration data reported in the literature are analyzed in metaphase. Since cells must progress through the cell cycle check points in order to reach mitosis, model predictions that differ from the metaphase chromosome analysis may actually agree with the aberration data in chromosomes collected in interphase. Secondly, high- LET radiation generally produces more complex aberrations involving exchanges between three or more DSB. While some models have successfully provided quantitative predictions of high-LET radiation induced complex aberrations in human lymphocytes, applying such models to other cell types requires special considerations due to the lack of geometric symmetry of the nucleus. Chromosome aberration data for non-spherical human fibroblast cells bombarded from various directions by high-LET charged particles will be presented, and their implication on physical modeling will be discussed.

  7. Pattern of Chromosomal Aberrations in Patients from North East Iran

    Directory of Open Access Journals (Sweden)

    Saeedeh Ghazaey

    2013-01-01

    Full Text Available Objective: Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques.Materials and Methods: In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in Khorasan province. Karyotyping was performed on 3728 patients suspected of having chromosomal abnormalities.Results: The frequencies of the different types of chromosomal abnormalities were determined, and the relative frequencies were calculated in each group. Among these patients, 83.3% had normal karyotypes with no aberrations. The overall incidences of chromosomal abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of those, 75.1 % showed autosomal chromosomal aberrations. Down syndrome (DS was the most prevalent autosomal aberration in the patients (77.1%. Pericentric inversion of chromosome 9 was seen in 5% of patients. This inversion was prevalent in patients with recurrent spontaneous abortion (RSA. Sex chromosomal aberrations were observed in 24.9% of abnormal patients of which 61% had Turner’s syndrome and 33.5% had Klinefelter’s syndrome.Conclusion: According to the current study, the pattern of chromosomal aberrations in North East of Iran demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. These findings provide a reason for preparing a local cytogenetic data bank to enhance genetic counseling of families who require this service.

  8. Chromosomal aberrations in ovine lymphocytes exposed in vitro to tolylfluanid.

    Science.gov (United States)

    Sutiaková, Irena; Kovalkovičová, Natália; Sutiak, Václav

    2012-01-01

    Chromosomal aberrations have been used as important cytogenetic biomarkers to study the mutagenic effects of different chemicals in vivo and in vitro. Chromosomal aberrations were evaluated in cultures of sheep lymphocytes in vitro exposed to the fungicide tolylfluanid. Lymphocyte cultures from three donors were exposed to four different concentrations of fungicide (1.10(-4) M(.)L; 1.10(-5) M(.)L; 1.10(-6) M(.)L; 1 × 10(-7) M(.)L). Chromosomal analysis showed a significant (P = 0.018 and 0.038 respectively, Anova test, P Tukey test) increase in the frequency of aberrant cells (ABC) in cultures treated with the highest negative experimental concentrations of tolylfluanid (1.10(-4) M(.)L; 1.10(-5) M(.)L) compared to control. Significantly increased numbers of chromatid breaks (7.67 ± 0.58% against 1.67 ± 2.08%, P = 0.009, Anova test, P Tukey test) and chromatid gaps (7.67 ± 1.15% against 2.67 ± 0.58%, P = 0.003, Anova test, P Tukey test) were observed in ovine cultures treated with the highest experimental concentration of tolylfluanid (1.10(-4) M(.)L). Tolylfluanid induced also chromosomal exchanges (P = 0.038, and 0.016 respectively, Anova test, P Tukey test) in ovine cultures treated with the highest experimental concentrations of tolylfluanid (1.10(-4) M(.)L; 1.10(-5) M(.)L). The mitotic index has not shown any statistical differences between the various treatments and control groups. Our results suggest a significant genotoxic effect of tolylfluanid only at the highest concentration in sheep peripheral lymphocytes in vitro.

  9. Micronuclei versus Chromosomal Aberrations Induced by X-Ray in Radiosensitive Mammalian Cells.

    Directory of Open Access Journals (Sweden)

    Cristina Plamadeala

    2015-03-01

    Full Text Available An experimental study was accomplished to compare estimation methods of ionizing radiations genotoxicity in mammalian cell cultures by means of two cytogenetic parameters with focus on aberrant cells characterized by multiple chromosomal damages.In vitro study was carried out on the genotoxicity of low-medium doses of 190 kV X-rays absorbed in Chinese hamster ovary cell cultures. Micronuclei and ten types of chromosomal aberrations were identified with Giemsa dying and optical microscope screening.The first parameter consisting in micronuclei relative frequency has led to higher linear correlation coefficient than the second one consistent with chromosomal aberrations relative frequency. However, the latter parameter estimated as the sum of all chromosomal aberrations appeared to be more sensitive to radiation dose increasing in the studied dose range, from 0 to 3 Gy. The number of micronuclei occurring simultaneously in a single cell was not higher than 3, while the number of chromosomal aberrations observed in the same cell reached the value of 5 for doses over 1 Gy.Polynomial dose-response curves were evidenced for cells with Ni micronuclei (i=1,3 while non-monotonic curves were evidenced through detailed analysis of aberrant cells with Ni chromosomal changes [Formula: see text] - in concordance with in vitro studies from literature. The investigation could be important for public health issues where micronucleus screening is routinely applied but also for research purposes where various chromosomal aberrations could be of particular interest.

  10. Chromosome aberrations in solid tumors have a stochastic nature

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Mauro A.A. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil) and Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil) and Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil) and Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil)]. E-mail: mauro@ufrgs.br; Onsten, Tor G.H. [Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil); Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil); Moreira, Jose C.F. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil); Almeida, Rita M.C. de [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil)

    2006-08-30

    An important question nowadays is whether chromosome aberrations are random events or arise from an internal deterministic mechanism, which leads to the delicate task of quantifying the degree of randomness. For this purpose, we have defined several Shannon information functions to evaluate disorder inside a tumor and between tumors of the same kind. We have considered 79 different kinds of solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also obtained for each solid tumor type in order to correlate data with tumor malignance. The results here show that aberration spread is specific for each tumor type, with high degree of diversity for those tumor types with worst survival indices. Those tumor types with preferential variants (e.g. high proportion of a given karyotype) have shown better survival statistics, indicating that aberration recurrence is a good prognosis. Indeed, global spread of both numerical and structural abnormalities demonstrates the stochastic nature of chromosome aberrations by setting a signature of randomness associated to the production of disorder. These results also indicate that tumor malignancy correlates not only with karyotypic diversity taken from different tumor types but also taken from single tumors. Therefore, by quantifying aberration spread, we could confront diverse models and verify which of them points to the most likely outcome. Our results suggest that the generating process of chromosome aberrations is neither deterministic nor totally random, but produces variations that are distributed between these two boundaries.

  11. M-BAND Analysis of Chromosome Aberration Induced by Fe-Ions in Human Epithelial Cells Cultured in 3-Dimensional Matrices

    Science.gov (United States)

    Hada, M.; Cucinotta, F. A.; Wu, H.

    2008-01-01

    Energetic heavy ions pose a great health risk to astronauts in extended ISS and future lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D cellular environment in vitro can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelia cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultued at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference of the chromosome aberration yield between 2D and 3D cell cultures for gamma exposures, but not for Fe ion exposures

  12. M-BAND analysis of chromosome aberration induced by Fe-ions in human epithelial cells cultured in 3-dimensional matrices

    Science.gov (United States)

    Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    Energetic heavy ions pose a great health risk to astronauts in extended ISS and future lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied lowand high-LET radiationinduced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D cellular environment in vitro can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelial cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137 Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultured at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference of the chromosome aberration yield between 2D and 3D cell cultures for gamma exposures, but not for Fe ion exposures

  13. Chromosome aberrations in workers of ignalina nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Griciene, B.; Januskeviciute, I.; Mierauskiene, J.; Slapsyte, G. [Vilnius Univ. (Lithuania)

    2006-07-01

    individual for the presence of chromosome aberrations. Chromosome aberration analysis revealed no differences between the two groups of radiation workers, or between the radiation workers and controls. The mean total chromosome aberration frequencies were: 1,32 {+-} 0,27 CA/100 cells (group A), 1,56{+-}0,39 CA/100 cells (group B), and 1,65{+-}0,15 CA/100 cells (group C). The average yield of dicentric chromosomes per 100 cells in A and B radiation groups was 0,10{+-}0.06 and 0,05{+-}0,04, respectively, and 0,08{+-}0,02 in controls. Thus, the results of the present study indicate no increase in chromosome aberration frequencies in I.N.P.P. workers exposed to doses close to permissible annual dose limits. The next blood sampling of I.N.P.P. workers will be performed in October 2005. The Lithuanian Bio ethics Committee approved the study. (authors)

  14. Mathematical Modeling of Carcinogenesis Based on Chromosome Aberration Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-bo Li

    2009-01-01

    Objective: The progression of human cancer is characterized by the accumulation of genetic instability. An increasing number of experimental genetic molecular techniques have been used to detect chromosome aberrations. Previous studies on chromosome abnormalities often focused on identifying the frequent loci of chromosome alterations, but rarely addressed the issue of interrelationship of chromosomal abnormalities. In the last few years, several mathematical models have been employed to construct models of carcinogenesis, in an attempt to identify the time order and cause-and-effect relationship of chromosome aberrations. The principles and applications of these models are reviewed and compared in this paper. Mathematical modeling of carcinogenesis can contribute to our understanding of the molecular genetics of tumor development, and identification of cancer related genes, thus leading to improved clinical practice of cancer.

  15. Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs).

    Science.gov (United States)

    Kim, Taehyun; Bershteyn, Marina; Wynshaw-Boris, Anthony

    2014-01-01

    The fusion of the short (p) and long (q) arms of a chromosome is referred to as a "ring chromosome." Ring chromosome disorders occur in approximately 1 in 50,000-100,000 patients. Ring chromosomes can result in birth defects, mental disabilities, and growth retardation if additional genes are deleted during the formation of the ring. Due to the severity of these large-scale aberrations affecting multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have so far been proposed. Our recent study (Bershteyn et al.) using patient-derived fibroblast lines containing ring chromosomes, found that cellular reprogramming of these fibroblasts into induced pluripotent stem cells (iPSCs) resulted in the cell-autonomous correction of the ring chromosomal aberration via compensatory uniparental disomy (UPD). These observations have important implications for studying the mechanism of chromosomal number control and may lead to the development of effective therapies for other, more common, chromosomal aberrations.

  16. Antimutagenic potential of curcumin on chromosomal aberrations in Allium cepa

    Institute of Scientific and Technical Information of China (English)

    RAGUNATHAN Irulappan; PANNEERSELVAM Natarajan

    2007-01-01

    Turmeric has long been used as a spice and food colouring agent in Asia. In the present investigation, the antimutagenic potential of curcumin was evaluated in Allium cepa root meristem cells. So far there is no report on the biological properties of curcumin in plant test systems. The root tip cells were treated with sodium azide at 200 and 300 μg/ml for 3 h and curcumin was given at 5, 10 and 20 μg/ml for 16 h, prior to sodium azide treatment. The tips were squashed after colchicine treatment and the cells were analyzed for chromosome aberration and mitotic index. Curcumin induces chromosomal aberration in Allium cepa root tip cells in an insignificant manner, when compared with untreated control. Sodium azide alone induces chromosomal aberrations significantly with increasing concentrations. The total number of aberrations was significantly reduced in root tip cells pretreated with curcumin. The study reveals that curcumin has antimutagenic potential against sodium azide induced chromosomal aberrations in Allium cepa root meristem cells. In addition, it showed mild cytotoxicity by reducing the percentage of mitotic index in all curcumin treated groups, but the mechanism of action remains unknown. The antimutagenic potential of curcumin is effective at 5 μg/ml in Allium cepa root meristem cells.

  17. Chromosome aberrations as biomarkers of radiation exposure: Modelling basic mechanisms

    Science.gov (United States)

    Ballarini, F.; Ottolenghi, A.

    The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).

  18. mBAND analysis of chromosome aberrations in human epithelial cells induced by gamma-rays and secondary neutrons of low dose rate.

    Science.gov (United States)

    Hada, M; Gersey, B; Saganti, P B; Wilkins, R; Cucinotta, F A; Wu, H

    2010-08-14

    Human risks from chronic exposures to both low- and high-LET radiation are of intensive research interest in recent years. In the present study, human epithelial cells were exposed in vitro to gamma-rays at a dose rate of 17 mGy/h or secondary neutrons of 25 mGy/h. The secondary neutrons have a broad energy spectrum that simulates the Earth's atmosphere at high altitude, as well as the environment inside spacecrafts like the Russian MIR station and the International Space Station (ISS). Chromosome aberrations in the exposed cells were analyzed using the multicolor banding in situ hybridization (mBAND) technique with chromosome 3 painted in 23 colored bands that allows identification of both inter- and intrachromosome exchanges including inversions. Comparison of present dose responses between gamma-rays and neutron irradiations for the fraction of cells with damaged chromosome 3 yielded a relative biological effectiveness (RBE) value of 26+/-4 for the secondary neutrons. Our results also revealed that secondary neutrons of low dose rate induced a higher fraction of intrachromosome exchanges than gamma-rays, but the fractions of inversions observed between these two radiation types were indistinguishable. Similar to the previous findings after acute radiation exposures, most of the inversions observed in the present study were accompanied by other aberrations. The fractions of complex type aberrations and of unrejoined chromosomal breakages were also found to be higher in the neutron-exposed cells than after gamma-rays. We further analyzed the location of the breaks involved in chromosome aberrations along chromosome 3, and observed hot spots after gamma-ray, but not neutron, exposures.

  19. M-BAND Study of Radiation-Induced Chromosome Aberrations in Human Epithelial Cells: Radiation Quality and Dose Rate Effects

    Science.gov (United States)

    Hada, Megumi; Cucinotta, Francis; Wu, Honglu

    2009-01-01

    The advantage of the multicolor banding in situ hybridization (mBAND) technique is its ability to identify both inter- (translocation to unpainted chromosomes) and intra- (inversions and deletions within a single painted chromosome) chromosome aberrations simultaneously. To study the detailed rearrangement of low- and high-LET radiation induced chromosome aberrations in human epithelial cells (CH184B5F5/M10) in vitro, we performed a series of experiments with Cs-137 gamma rays of both low and high dose rates, neutrons of low dose rate and 600 MeV/u Fe ions of high dose rate, with chromosome 3 painted with multi-binding colors. We also compared the chromosome aberrations in both 2- and 3-dimensional cell cultures. Results of these experiments revealed the highest chromosome aberration frequencies after low dose rate neutron exposures. However, detailed analysis of the radiation induced inversions revealed that all three radiation types induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intra-chromosomal aberrations but few inversions were accompanied by inter-chromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosomal exchanges. The location of the breaks involved in chromosome exchanges was analyzed along the painted chromosome. The breakpoint distribution was found to be randomly localized on chromosome 3 after neutron or Fe ion exposure, whereas non-random distribution with clustering breakpoints was observed after -ray exposure. Our comparison of chromosome aberration yields between 2- and 3-dimensional cell cultures indicated a significant difference for gamma exposures, but not for Fe ion exposures. These experimental results indicated that the track structure of the radiation and the cellular/chromosome structure can both affect radiation-induced chromosome

  20. Induction of chromosomal aberrations in human lymphocytes by fission neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcia Augusta da; Coelho, Paulo Rogerio Pinto; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br

    2009-07-01

    Chromosome aberrations induced by sparsely ionizing radiation (low-LET) are well known and cytogenetic analyses of irradiated human lymphocytes have been widely applied to biological dosimetry. However, much less is known about chromosome aberrations induced by densely ionizing radiation (high LET), such as that of alpha particles or neutrons. Such particles induce DNA strand breaks, as well as chromosome breakage and rearrangements of high complexity. This damage is more localized and less efficiently repaired than after X- or {gamma}-ray irradiation. This preferential production of complex aberrations by densely ionizing radiation is related to the unique energy deposition patterns, which produces highly localized multiple DNA damage at the chromosomal level. A better knowledge of the interactions between different types of radiation and cellular DNA is of importance, not only from the radiobiological viewpoint but also for dosimetric and therapeutic purposes. The objective of the present study was to analyse the cytogenetic effects of fission neutrons on peripheral blood lymphocytes in order to evaluate structural and numerical aberrations and number of cells in the different mitotic cycles. So, blood samples from five healthy donors, 22-25 years old, of both sexes, were irradiated in the Research Reactor IEA-R1 of our Institute (IPEN/CNEN-SP) with thermal and fast neutrons at doses of 0.2; 0.3; 0.5 and 1.0 Gy. The {gamma} contribution to the total absorbed dose was about 30%. These doses were monitored by thermoluminescent dosemeters: LiF-600 (for neutrons) and LiF-700 (for {gamma}-rays). The data concerning structural aberrations were evaluated with regard to three parameters: percentage of cells with aberrations, number of aberrations/cell and number of dicentric/cell. The cytogenetic results showed an increase in the three parameters after irradiation with neutrons, as a function of radiation dose. Apparently, there was no influence of neutrons on the

  1. Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays

    Directory of Open Access Journals (Sweden)

    Y. Lusiyanti

    2013-12-01

    Full Text Available Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + αD + βD2. The result showed that α and β values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validated.

  2. Chromosome aberrations frequency in peripheral blood lymphocytes in young tobacco smoking and non-smoking people

    Directory of Open Access Journals (Sweden)

    Anja Haverić

    2016-10-01

    Full Text Available Introduction: Cigarette smoking is associated with severe health problems, especially cancers. In addition, cigarette smoking causes different genotoxic effects. Chromosome aberrations are one of well-known intermediate end points in carcinogenesis. The aim of this study was to compare frequencies of chromosome aberrations in peripheral blood lymphocytes between young smokers and non-smokes groups.Methods: The study was conducted with 30 smokers (average age 26.93 years and 30 non-smokers (average age 26.96 years, and included the analysis of 100 metaphases per each blood sample. Differences in the arithmetic means of determined frequencies of chromosome aberrations were tested by two-tailed t-test for independent samples with the significance level of p < 0.05.Results: The results showed a significant increase in the frequencies of chromatid-type aberrations and total structural chromosome aberrations in smoker group. Frequencies of numerical aberrations did not differ significantly between two groups.Conclusions: This study confirmed genotoxicity of cigarette smoking and provided new evidence about its clastogenic activity.

  3. Chromosome Aberrations in Human Lymphocytes Irradiated with Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    The purpose of the present experiment was to provide data on the dose-dependent production of chromosome aberrations such as dicentrics, centric rings, and excess acentrics. Radiation is one of the more dangerous clastogens in the environment. Ionizing radiation causes chromosome breakages and various cytogenetic aberrations in exposed cells. In an investigation into radiation emergencies, it is important to estimate the dose to exposed persons for several reasons. Physical dosimeters (e. g., film badges) may misrepresent the actual radiation dose and may not be available in a radiological accident or terrorism incident. Biological dosimetry is suitable for estimating the radiation dose during such accidents. The dicentric chromosome assay is very sensitive and a reliable bio-indicator in cases of accidental overexposure.

  4. Chromosomal Aberrations in Humans Induced by Urban Air Pollution

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, Hannu; Gamborg, Michael O.

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes...... that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  5. Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana

    NARCIS (Netherlands)

    Ji, X.

    2014-01-01

    Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. I studied numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. The large genomic changes are important for

  6. Chromosome Analysis

    Science.gov (United States)

    1998-01-01

    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  7. Karyotype evolution in apomictic Boechera and the origin of the aberrant chromosomes.

    Science.gov (United States)

    Mandáková, Terezie; Schranz, M Eric; Sharbel, Timothy F; de Jong, Hans; Lysak, Martin A

    2015-06-01

    Chromosome rearrangements may result in both decrease and increase of chromosome numbers. Here we have used comparative chromosome painting (CCP) to reconstruct the pathways of descending and ascending dysploidy in the genus Boechera (tribe Boechereae, Brassicaceae). We describe the origin and structure of three Boechera genomes and establish the origin of the previously described aberrant Het and Del chromosomes found in Boechera apomicts with euploid (2n = 14) and aneuploid (2n = 15) chromosome number. CCP analysis allowed us to reconstruct the origin of seven chromosomes in sexual B. stricta and apomictic B. divaricarpa from the ancestral karyotype (n = 8) of Brassicaceae lineage I. Whereas three chromosomes (BS4, BS6, and BS7) retained their ancestral structure, five chromosomes were reshuffled by reciprocal translocations to form chromosomes BS1-BS3 and BS5. The reduction of the chromosome number (from x = 8 to x = 7) was accomplished through the inactivation of a paleocentromere on chromosome BS5. In apomictic 2n = 14 plants, CCP identifies the largely heterochromatic chromosome (Het) being one of the BS1 homologues with the expansion of pericentromeric heterochromatin. In apomictic B. polyantha (2n = 15), the Het has undergone a centric fission resulting in two smaller chromosomes - the submetacentric Het' and telocentric Del. Here we show that new chromosomes can be formed by a centric fission and can be fixed in populations due to the apomictic mode of reproduction.

  8. Aberrations of chromosome 8 in myelodysplastic syndromes: Clinical and biological significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2006-01-01

    Full Text Available Introduction: Rearrangements of any single chromosome in human karyotype have been reported in patients with pMDS. Objective: To examine the role of aberrations of chromosome 8 in pathogenesis, clinical presentation and progression of myelodysplastic syndromes. Method: Cytogenetic analysis of bone marrow cells was carried out by direct method and by means of 24- and/or 48-hour unstimulated cell culture. Chromosomes were obtained by modified method of HG-bands. Results: On presentation, 109 out of 271 successfully karyotyped patients (40,2% had abnormal karyotypes. Among them, 22 patients (10.9% had aberrations of chromosome 8. Ten patients had trisomy 8 as "simple" aberration whilst additional three cases had trisomy 8 included in "complex" karyotypes (≥3 chromosomes. Cases with constitutional trisomy 8 mosaicism (CT8M were excluded using the chromosome analyses of PHA-stimulated blood cultures. On the contrary, monosomy (seven patients or deletion of chromosome 8 (two patients were exclusively found in "complex" karyotypes. During prolonged cytogenetic follow-up, trisomy 8 was not recorded in evolving karyotypes. In contrast, trisomy 8 disappeared in two cases during subsequent cytogenetic studies, i.e. 23 and 72 months from diagnosis, accompanied in one patient with complete hematological remission. No difference regarding age, sex, cytopenia, blood and marrow blast count or response to treatment was found between patients with trisomy 8 as the sole aberration compared to those with normal cytogenetics. Median survival of patients with trisomy 8 as the sole aberration was 27 months, as compared to 32 months in patients with normal cytogenetics (p=0.468, whilst median survival of patients with aberrations of chromosome 8 included in "complex" karyotypes was only 4 months. Conclusion: Aberrations of chromosome 8 are common in patients with pMDS. The presence of a clone with trisomy 8 is not always the sign of disease progression or poor

  9. Chromosome aberrations and cell death by ionizing radiation: Evolution of a biophysical model

    Science.gov (United States)

    Ballarini, Francesca; Carante, Mario P.

    2016-11-01

    The manuscript summarizes and discusses the various versions of a radiation damage biophysical model, implemented as a Monte Carlo simulation code, originally developed for chromosome aberrations and subsequently extended to cell death. This extended version has been called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations). According to the basic assumptions, complex double-strand breaks (called ;Cluster Lesions;, or CLs) produce independent chromosome free-ends, mis-rejoining within a threshold distance d (or un-rejoining) leads to chromosome aberrations, and ;lethal aberrations; (i.e., dicentrics plus rings plus large deletions) lead to clonogenic cell death. The mean number of CLs per Gy and per cell is an adjustable parameter. While in BIANCA the threshold distance d was the second parameter, in a subsequent version, called BIANCA II, d has been fixed as the mean distance between two adjacent interphase chromosome territories, and a new parameter, f, has been introduced to represent the chromosome free-end un-rejoining probability. Simulated dose-response curves for chromosome aberrations and cell survival obtained by the various model versions were compared with literature experimental data. Such comparisons provided indications on some open questions, including the role of energy deposition clustering at the nm and the μm level, the probability for a chromosome free-end to remain un-rejoined, and the relationship between chromosome aberrations and cell death. Although both BIANCA and BIANCA II provided cell survival curves in general agreement with human and hamster fibroblast survival data, BIANCA II allowed for a better reproduction of dicentrics, rings and deletions considered separately. Furthermore, the approach adopted in BIANCA II for d is more consistent with estimates reported in the literature. After testing against aberration and survival data, BIANCA II was applied to investigate the depth-dependence of the radiation

  10. Chromosomal aberrations induced by alpha particles; Aberraciones cromosomicas inducidas por particulas {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C.; Brena V, M. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: cgc@nuclear.inin.mx

    2005-07-01

    The chromosomal aberrations produced by the ionizing radiation are commonly used when it is necessary to establish the exposure dose of an individual, it is a study that is used like complement of the traditional physical systems and its application is only in cases in that there is doubt about what indicates the conventional dosimetry. The biological dosimetry is based on the frequency of aberrations in the chromosomes of the lymphocytes of the individual in study and the dose is calculated taking like reference to the dose-response curves previously generated In vitro. A case of apparent over-exposure to alpha particles to which is practiced analysis of chromosomal aberrations to settle down if in fact there was exposure and as much as possible, to determine the presumed dose is presented. (Author)

  11. Chromosome aberrations in ataxia telangiectasia cells exposed to heavy ions

    Science.gov (United States)

    Kawata, T.; Cucinotta, F.; George, K.; Wu, H.; Shigematsu, N.; Furusawa, Y.; Uno, T.; Isobe, K.; Ito, H.

    Understanding of biological effects of heavy ions is important to assess healt h risk in space. One of the most important issues may be to take into account individual susceptibility. Ataxia telangiectasia (A-T) cells are known to exhibit abnormal responses to radiations but the mechanism of hyper radiosensitivity of A-T still remains unknown. We report chromosome aberrations in normal human fibroblasts and AT fibroblasts exposed to low- and high-LET radiations. A chemical-induced premature chromosome condensation (PCC) technique combined with chromosome- painting technique was applied to score chromosome aberrations in G2/M-phase cells. Following gamma irradiation, GM02052 cells were approximately 5 times more sensitive to g-rays than AG1522 cells. GM02052 cells had a much higher frequency of deletions and misrejoining than AG1522 cells. When the frequency of complex type aberrations was compared, GM02052 cells showed more than 10 times higher frequency than AG1522 cells. The results will be compared with those obtained from high-LET irradiations.

  12. FISH and array-CGH analysis of a complex chromosome 3 aberration suggests that loss of CNTN4 and CRBN contributes to mental retardation in 3pter deletions.

    Science.gov (United States)

    Dijkhuizen, Trijnie; van Essen, Ton; van der Vlies, Pieter; Verheij, Joke B G M; Sikkema-Raddatz, Birgit; van der Veen, Anneke Y; Gerssen-Schoorl, Klasien B J; Buys, Charles H C M; Kok, Klaas

    2006-11-15

    Imbalances of 3p telomeric sequences cause 3p- and trisomy 3p syndrome, respectively, showing distinct, but also shared clinical features. No causative genes have been identified in trisomy 3p patients, but for the 3p- syndrome, there is growing evidence that monosomy for one or more of four genes at 3pter, CHL1, CNTN4, CRBN, and MEGAP/srGAP3, may play a causative role. We describe here an analysis of a complex chromosome 3p aberration in a severely mentally retarded patient that revealed two adjacent segments with different copy number gains and a distal deletion. The deletion in this patient included the loci for CHL1, CNTN4, and CRBN, and narrowed the critical segment associated with the 3p- syndrome to 1.5 Mb, including the loci for CNTN4 and CRBN. We speculate that the deletion contributes more to this patient's phenotype than the gains that were observed. We suggest that 3p- syndrome associated features are primarily caused by loss of CNTN4 and CRBN, with loss of CHL1 probably having an additional detrimental effect on the cognitive functioning of the present patient.

  13. Dose Assessment using Chromosome Aberration Analyses in Human Peripheral Blood Lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin-Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    The healthy five donors were recruited to establish the dose-response calibration curve for chromosomal aberrations by ionizing radiation exposure. Our cytogenetic results revealed that the mean frequency of chromosome aberration increased with increasing radiation dose. In this study, dicentric assay and CBMN assay were compared considering the sensitivity and accuracy of dose estimation. Therefore, these chromosome aberration analyses will be the foundation for biological dosimetric analysis with additional research methods such as translocation and PCC assay. The conventional analysis of dicentric chromosomes in HPBL was suggested by Bender and Gooch in 1962. This assay has been for many years, the golden standard and the most specific method for ionizing radiation damage. The dicentric assay technique in HPBL has been shown as the most sensitive biological method and reliable bio-indicator of quantifying the radiation dose. In contrast, the micronucleus assay has advantages over the dicentric assay since it is rapid and requires less specialized expertise, and accordingly it can be applied to monitor a big population. The cytokinesis-block micronucleus (CBMN) assay is a suitable method for micronuceli measurement in cultured human as well as mammalian cells. The aim of our study was to establish the dose response curve of radiation-induced chromosome aberrations in HPBL by analyzing the frequency of dicentrics and micronuclei.

  14. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2008-01-01

    Full Text Available Background/Aim. Intrauterine growth retardation (IUGR is a pathological condition of pregnancy characterised by birth weight below the 10th centile. A number of fetal, placental and maternal causes can lead to IUGR; although, in most cases no specific causes can be identified. The aim of this study was to determine the part of chromosomal abnormalities in IUGR etiology. Methods. Fetal blood karyotype taken by cordocentesis from 168 fetuses with diagnosed IUGR was analyzed. Results. Chromosomal rearrangements both numerical and structural were detected in 14 cases (12.2%. Two cases were triploid. Patau syndrome, Edwards syndrome and Down syndrome were found in two cases each. There was one case of trisomy 7 (47, XY, +7 and one case of trisomy 16 (47, XX, +16; one translocation, 46, XY, t (2; 14(q23; q32 and a deletion 46, XYdel (12 (p12 as well as two cases of sex chromosomes abnormalities, 45, X (Turner syndrome and 47, XYY. Conclusion. These findings suggest that a consistent number of symmetrical IUGR cases (about 12% can be associated with chromosomal rearrangements. Chromosomal aberrations that cause IUGR are heterogeneous, aberration of autosomes, mostly autosomal trisomies, being the most common.

  15. [Aluminum induces chromosome aberrations in wheat root meristem cells].

    Science.gov (United States)

    Bulanova, N V; Synzynys, B I; Koz'min, G V

    2001-12-01

    The yield and pattern of chromosome structure aberrations in wheat seedlings treated with aluminum nitrate and aluminum sulfate at various concentrations have been determined by the anaphase method. Aluminum has a genotoxic effect causing genome, chromatid, and chromosome aberrations in apical root meristem cells. The relationship between the total yield of structural mutations and the aluminum concentration follows a bell-shaped curve. The mutagenic activity of aluminum nitrate peaks at 10(-3) mg/ml, which is twice as high as the permissible concentration limit (PCL) of aluminum in potable water. The maximum of the mutagenic activity of aluminum sulfate is observed at 5 x 10(-4) mg/ml, i.e., one PCL. Tap water boiled for 2 h in an aluminum vessel has virtually no genotoxic effect on wheat cells.

  16. [239Pu and chromosomal aberrations in human peripheral blood lymphocytes].

    Science.gov (United States)

    Okladnikova, N D; Osovets, S V; Kudriavtseva, T I

    2009-01-01

    The genome status in somatic cells was assessed using the chromosomal aberration (CA) test in peripheral blood lymphocytes from 194 plutonium workers exposed to occupational radiation mainly from low-transportable compounds of airborne 230Pu. Pu body burden at the time of cytogenetic study varied from values close to the method sensitivity to values multiply exceeding the permissible level. Standard (routine) methods of peripheral blood lymphocytes cultivation were applied. Chromatid- and chromosomal-type structural changes were estimated. Aberrations were estimated per 100 examined metaphase cells. The quantitative relationship between the CA frequency and Pu body burden and the absorbed dose to the lung was found. Mathematical processing of results was carried out based on the phenomenological model. The results were shown as theoretical and experimental curves. The threshold of the CA yield was 0.43 +/- 0.03 kBq (Pu body burden) and 6.12 +/- 1.20 cGy (absorbed dose to the lung).

  17. Chromosomic aberrations in female workers exposed to pesticides

    OpenAIRE

    Cuenca, Patricia; Ramírez, Vanessa

    2014-01-01

    The purpose of this work was to determine if the occupational exposure to those pesticides used at banana plantations’ packaging plants produces genetic damage to somatic cells of female workers. Chromosomal aberrations were scored in lymphocytes of 20 women, 10 female exposed workers and 10 female controls. Workers were recruited from independent farms from two locations in Costa Rica, during January through June in 1996 and 1997. These females had a minimum of three months of work, had neve...

  18. Chromosomal aberrations related to metastasis of human solid tumors

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin

    2002-01-01

    The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic alterations.So does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor genes.During the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have occurred.There is still controversial with the association

  19. Increased risk of cancer in radon-exposed miners with elevated frequency of chromosomal aberrations.

    Science.gov (United States)

    Smerhovsky, Zdenek; Landa, Karel; Rössner, Pavel; Juzova, Dagmar; Brabec, Marek; Zudova, Zdena; Hola, Nora; Zarska, Hana; Nevsimalova, Emilie

    2002-02-15

    In spite of the extensive use of cytogenetic analysis of human peripheral blood lymphocytes in the biomonitoring of exposure to various mutagens and carcinogens, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 1323 cytogenetic assays and 225 subjects examined because of occupational exposures to radon (range of exposure from 1.7 to 662.3 working level month (WLM)). Seventy-five subjects were non-smokers. We found 36 cases of cancer in this cohort. Chromatid breaks were the most frequently observed type of aberrations (mean frequency 1.2 per 100 cells), which statistically significantly correlated with radon exposure (Spearman's correlation coefficient R=0.22, P<0.001). Also, the frequency of aberrant cells (median of 2.5%) correlated with radon exposure (Spearman's correlation coefficient R=0.16, P<0.02). Smoking and silicosis were not associated with results of cytogenetic analyses. The Cox regression models, which accounted for the age at time of first cytogenetic assay, radon exposure, and smoking showed strong and statistically significant associations between cancer incidence and frequency of chromatid breaks and frequency of aberrant cells, respectively. A 1% increase in the frequency of aberrant cells was paralleled by a 62% increase in risk of cancer (P<0.000). An increase in frequency of chromatid breaks by 1 per 100 cells was followed by a 99% increase in risk of cancer (P<0.000). We obtained similar results when we analyzed the incidence of lung cancer and the incidence other than lung cancer separately. Contrary to frequency of chromatid breaks and frequency of aberrant cells, the frequency of chromatid exchanges, and chromosome-type aberrations were not predictive of cancer.

  20. Frequencies of complex chromosome exchange aberrations induced by 238Pu alpha-particles and detected by fluorescence in situ hybridization using single chromosome-specific probes.

    Science.gov (United States)

    Griffin, C S; Marsden, S J; Stevens, D L; Simpson, P; Savage, J R

    1995-04-01

    We undertook an analysis of chromosome-type exchange aberrations induced by alpha-particles using fluorescence in situ hybridization (FISH) with whole chromosome-specific probes for human chromosomes 1 or 4, together with a pan-centromeric probe. Contact-inhibited primary human fibroblasts (in G1) were irradiated with 0.41-1.00 Gy 238Pu alpha-particles and aberrations were analysed at the next mitosis following a single chromosome paint. Exchange and aberration painting patterns were classified according to Savage and Simpson (1994a). Of exchange aberrations, 38-47% were found to be complex derived, i.e. resulting from three or more breaks in two or more chromosomes, and the variation with dose was minimal. The class of complex aberrations most frequently observed were insertions, derived from a minimum of three breaks in two chromosomes. There was also an elevated frequency of rings. The high level of complex aberrations observed after alpha-particle irradiation indicates that, when chromosome domains are traversed by high linear energy transfer alpha-particle tracks, there is an enhanced probability of production of multiple localized double-strand breaks leading to more complicated interactions.

  1. Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis

    DEFF Research Database (Denmark)

    Bardi, G; Pandis, N; Fenger, C;

    1993-01-01

    Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural...... rearrangements were found that led to loss of genetic material from 1p. In three of the cases, the deletion was restricted to the 1p36 band; the rest had lost larger 1p segments. The rearrangement of chromosome 1 was the sole karyotypic anomaly in three adenomas, all with mild or moderate dysplasia......- as the sole change showed only mild or moderate dysplasia and that the del(1p) was found also in the hyperplastic polyp suggests that this aberration is more related to the induction of hyperproliferation than to differentiation disturbances in the intestinal mucosa....

  2. Comparative study of chromosome aberrations yield induced by cesium and cobalt sources in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Mariana E.; Mendonca, Julyanne C.G.; Souza, Priscilla L.G.; Santos, Neide; Lima, Fabiana F., E-mail: mendes_sb@hotmail.com [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2013-07-01

    Analysis of chromosome aberrations is the most developed method for biological monitoring. From the frequency of these aberrations it is possible to evaluate the absorbed dose. This technique can ve used to support physical dosimetry or when it is impossible to achieve it. The aim of this research is to compare frequencies of unstable chromosome alterations induce by a gamma beam with two different sources: {sup 137}Cs and {sup 60}Co. The first sample was exposed to {sup 137}Cs resulting in absorbed dose 0.45 Gy, 0.726 Gy and 1.375 Gy and the second one was exposed to {sup 60}Co (Gammacel 220) resulting in absorbed doses 0.51 Gy, 0.77 Gy and 1.5 Gy. Mitotic metaphase cells were obtained by Iymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. Among the unstable chromosome aberrations were analyzed dicentrics, ring centric and acentric. These results showed a statistical similarity in the frequencies of dicentrics and acentric per cell, except the frequencies of acentric when irradiated with the lowest dose. However, the dose rate of {sup 137}Cs source is lower than the dose rate of {sup 60}Co source (30.78 mGy/h and 3.277 Gy/h, respectively). This would be a factor to be considered in the analysis of unstable chromosome aberrations once prolonged irradiation time reduces the number of produced aberrations by low LET radiation doses, however further studies with other absorbed doses are necessary in the search for more reliable results for that statement. (author)

  3. Analysis of the frequency of unstable chromosome aberrations in human lymphocytes irradiated with {sup 60}Co; Analise da frequencia de alteracoes cromossomicas instaveis em linfocitos humanos irradiados com {sup 60}Co

    Energy Technology Data Exchange (ETDEWEB)

    Mendonca, Julyanne C.G.; Mendes, Mariana E.; Lima, Fabiana F., E-mail: july_cgm@hotmail.com, E-mail: mendes_sb@hotmail.com [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Santos, Neide, E-mail: santos_neide@yahoo.com.br [Universidade Federal de Pernambuco (CCB/UFPE), Recife, PE (Brazil). Departamento de Genetica

    2013-07-01

    The aim of this study was to analyze the frequency of unstable chromosomal aberrations induced by gamma radiation from a {sup 60}Co source at two different doses. Samples were obtained from a healthy donor and exposed to {sup 60}Co source (Gammacel 220 ) located in the Department of Nuclear Energy of Pernambuco Federal University (DEN/UFPe/Brazil) with a rate of air Kerma to 3,277 Gy/h. Exposures resulted in absorbed dose 0.51 Gy and 0.77 Gy. Mitotic metaphases were obtained by culturing lymphocytes for chromosome analysis and the slides were stained with 5% Giemsa. Among the unstable chromosomal aberrations the dicentric chromosomes, ring chromosomes and acentric fragments were analyzed. To calculate the significance level the chi - square test was used, considering relevant differences between the frequencies when the value of p < 0.05. To calculate the significance level of the chi - square test was used, considering relevant differences between the frequencies when the value of p < 0.05. The results showed that there was significant difference of the frequencies of dicentric chromosomes (from 0.18 to 0.51 to 0.37 Gy to 0.77 Gy), however there was no statistically significant difference between the frequencies of acentric fragments ( 0.054 to 0, 51 Gy to 0.063 to 0.77 Gy) and ring chromosomes (0.001 to 0.51 Gy to 0.003 to 0.77 Gy). The low number of rings is found justified, considering that in irradiated human lymphocytes, its appearance is rare relative to dicentrics. The results confirm that dicentrics are the most reliable biomarkers in estimating dose after exposure to gamma radiation. These two points will make the calibration curve dose-response being built for Biological Dosimetry Laboratory of CRCN-NE/CNEN.

  4. Propranolol induced chromosomal aberrations in Chinese hamster ovary cell line

    Directory of Open Access Journals (Sweden)

    Mozhgan Sedigh-Ardekani

    2013-03-01

    Full Text Available Propranolol (PL, a non-selective beta-blocker, is a cardiovascular drug widely used to treat hypertension. The present study was concerned with assessing the cytogenetic effects of this drug on Chinese hamster ovary (CHO cell line. MTT assay was then carried out to determine the cytotoxicity index (IC50 of the drug. The IC50 value of PL was 0.43±0.02 mM. To investigate the clastogenic effects of the drug, chromatid and chromosome breaks and polyploidy in metaphases were analyzed. CHO cells were exposed to different concentrations of the drug (0.1, 0.2, 0.3, 0.4 mM for 24 hours. Considering that PL has liver metabolism, experiments were carried out in the presence and absence of the metabolic activation system (S9 mix. Mitomycin-C and sodium arsenite were used as positive controls. It was observed that in cells treated with different PL concentrations as 0.1, 0.2 and 0.3 mM, the frequency of chromatid and chromosome breaks as well as polyploidy increased when compared with untreated CHO cells. The addition of S9 mix significantly decreased the chromatid breaks, chromosome breaks and polyploidy compared to the treatment of PL alone. It is concluded that, PL causes chromatid and chromosome aberrations in CHO cell line and the metabolic activation system (S9 mix, playing an important role in drug cytotoxicity reduction.

  5. Dicentric chromosome aberration analysis using giemsa and centromere specific fluorescence in-situ hybridization for biological dosimetry: An inter- and intra-laboratory comparison in Indian laboratories.

    Science.gov (United States)

    Bhavani, M; Tamizh Selvan, G; Kaur, Harpreet; Adhikari, J S; Vijayalakshmi, J; Venkatachalam, P; Chaudhury, N K

    2014-09-01

    To facilitate efficient handling of large samples, an attempt towards networking of laboratories in India for biological dosimetry was carried out. Human peripheral blood samples were exposed to (60)Co γ-radiation for ten different doses (0-5Gy) at a dose rate of 0.7 and 2Gy/min. The chromosomal aberrations (CA) were scored in Giemsa-stained and fluorescence in-situ hybridization with centromere-specific probes. No significant difference (p>0.05) was observed in the CA yield for given doses except 4 and 5Gy, between the laboratories, among the scorers and also staining methods adapted suggest the reliability and validates the inter-lab comparisons exercise for triage applications.

  6. Relationship between radiation induced dicentric chromosome aberrations and micronucleus formation in human lymphocytes.

    Science.gov (United States)

    Hatayoglu, S E; Orta, T

    2007-06-01

    Chromosome damage measured by the chromosome aberration technique is a reliable method to assess the radiation dose absorbed by cells. However, this technique has some disadvantages. Scoring is difficult and requires skill and experience which of these lead low number of cell counts. The micronucleus (MN) technique which also measures chromosome losses has easy scoring criteria leading high numbers of cell counts and therefore holds more statistical power. In this study, the relationship between the results of the micronucleus technique and those obtained by the chromosome aberration technique was investigated after radiation doses of 1Gy, 2Gy, 3Gy and 4Gy to peripheral blood lymphocytes of 3 healthy individuals. Increases in the chromosome damage after radiation were observed in both techniques. When the dicentric aberration frequencies that were measured in the chromosome aberration technique and the micronucleus frequencies were compared, no difference (p > 0.05) between these two independent measures of radiation damage was reported. The relationship between the micronuclei and the free acentric chromosome aberrations measured in the chromosome aberration technique was not significant as well as that between the dicentrics and micronuclei. On the basis of the relationship between the dicentric aberrations and the micronucleus frequencies, the micronucleus technique with an easy and short-term application and with an easy scoring can be used as an alternative to the chromosome aberration technique.

  7. Anti-topoisomerase drugs as potent inducers of chromosomal aberrations

    Directory of Open Access Journals (Sweden)

    Loredana Bassi

    2000-12-01

    Full Text Available DNA topoisomerases catalyze topological changes in DNA that are essential for normal cell cycle progression and therefore they are a preferential target for the development of anticancer drugs. Anti-topoisomerase drugs can be divided into two main classes: "cleavable complex" poisons and catalytic inhibitors. The "cleavable complex" poisons are very effective as anticancer drugs but are also potent inducers of chromosome aberrations so they can cause secondary malignancies. Catalytic inhibitors are cytotoxic but they do not induce chromosome aberrations. Knowledge about the mechanism of action of topoisomerase inhibitors is important to determine the best anti-topoisomerase combinations, with a reduced risk of induction of secondary malignancies.As topoisomerases de DNA catalisam alterações topológicas no DNA que são essenciais para a progressão do ciclo celular normal e, portanto, são um alvo preferencial para o desenvolvimento de drogas anticâncer. Drogas anti-topoisomerases podem ser divididas em duas classes principais: drogas anti-"complexos cliváveis" e inibidores catalíticos. As drogas anti-"complexos cliváveis" são muito eficazes como drogas anticancerígenas, mas são também potentes indutores de aberrações cromossômicas, podendo causar neoplasias malignas secundárias. Inibidores catalíticos são citotóxicos mas não induzem aberrações cromossômicas. Conhecimento a respeito do mecanismo de ação de inibidores de topoisomerases é importante para determinar as melhores combinações anti-topoisomerases, com um reduzido risco de indução de neoplasias malignas secundárias.

  8. Pig chromosome aberrations after vaccination against classical swine fever in field trials.

    Science.gov (United States)

    Genghini, Rosa; Tiranti, Iván; Wittouck, Patricia

    2002-07-26

    Chromosomal aberrations were observed after vaccination against classical swine fever (CSF) in a previous study done on experimental pigs. To determine if the same effect occurs in farm animals, field trials were done with immunized pigs. The cytogenetic analysis was made from lymphocyte cultures of pigs sampled in three farms of Río Cuarto region on six different periods: one, pre-vaccination (control) and in five post-vaccination (days 3, 7, 10, 15 and 22). Vaccine inoculation induced significant increase of cell frequency with chromosomal aberrations from days 3 to 10, when maximal frequencies of 6.78, 10.36 and 7.21% were observed in farms A, B and C, respectively. Afterwards, a decrease was recorded, reaching values not significantly different from controls. Mean frequencies of cells with chromosomal aberrations were 2.8+/-0.3, 5.9+/-0.4, 3.1+/-0.3%, for A, B and C farms, respectively. Cytogenetic effect was clastogenic, being chromosome breaks the first type of alteration to increase from the day 3 post-vaccination onwards, followed by chromatid exchanges and cells with multiple abnormalities. Chromosome pulverization was the last type to show increment, reaching a top value on day 10, after that it started to diminish gradually. There was no difference in the frequency of polyploid cells among sampling dates meaning that this type of alteration would not be induced by vaccination. Results of this field study confirm the mutagenic capacity of live virus vaccines against CSF and indicate that the evolution of chromosome alterations on the five evaluated post-vaccination periods was similar at different environments.

  9. Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.

    Science.gov (United States)

    Jakab, Z; Balogh, E; Kiss, C; Pajor, L; Oláh, E

    1999-01-01

    Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.

  10. Maternal age, reproduction and chromosomal aberrations in Wistar derived rats.

    Science.gov (United States)

    Niggeschulze, A; Kast, A

    1994-01-01

    The fertility of rats ranges from one to 18 months. In standard teratogenicity testing young, mature females are used which may not reflect the situation in women above 35 years old. Reproduction among different age groups of Wistar ats (strain Chbb: THOM) was compared at 3, 6, 9, 12, 15 and 18 months. At least 20 virgin females were inseminated per age group. The copulation rate did not differ between the groups. From the maternal age of 12 months, the pregnancy rate was significantly decreased, from the age of 9 months, the litter values were significantly lowered and the resorption rates were increased. Maternal age did not influence the incidence of fetal variations and malformations. Additionally, the chromosomal aberration rate in the bone marrow was evaluated in male and female rats. Twelve animals of each sex were scheduled per group, and studied at the age of 1, 3, 6, 12, 15, 18, 21 or 24 months. In males, the aberration rate increased continuously from 0.18 through 3%, while in females the increase continued from 0.33 to 2.29% at 15 months old when a plateau was reached. When testing new compounds for embryotoxicity or genotoxicity in female rats, the animals should be of comparable age to man in order to avoid a misinterpretation of spontaneous abnormalities. From these studies, however, it was concluded that the use of higher age groups of female rats in teratogenicity studies would not improve the risk assessment.

  11. Impact of various parameters in detecting chromosomal aberrations by FISH to describe radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Keller, U.; Mueller, E.; Grabenbauer, G.; Sauer, R.; Distel, L. [Div. of Radiobiology, Dept. of Radiotherapy, Erlangen (Germany); Kuechler, A. [Div. of Radiotherapy, Dept. of Radiology, Jena (Germany); Inst. for Human Genetics and Anthropology, Jena (Germany); Liehr, T. [Inst. for Human Genetics and Anthropology, Jena (Germany)

    2004-05-01

    Background and purpose: analysis of radiation-induced chromosomal aberrations is regarded as the ''gold standard'' for classifying individual radiosensitivity. A variety of different parameters can be used. The crucial question, however, is to explore which parameter is suited best to describe the differences between patients with increased radiosensitivity and healthy individuals. Patients and methods: in this study, five patients with severe radiation-induced late effects of at least grade 3, classified according to the Radiation Therapy Oncology Group (RTOG), and eleven healthy individuals were examined retrospectively. Peripheral blood lymphocytes were irradiated in vitro with 0.7 Gy and 2.0 Gy prior to cultivation and stained by means of three-color fluorescence in situ hybridization (FISH). The detailed analysis was focused on the number of breaks per metaphase, on breaks from complex chromosomal rearrangements per metaphase, as well as on the percentage of translocations, dicentric chromosomes, breaks, and excess acentric fragments - each in comparison with the total number of mitoses analyzed. Results: using the number of breaks from complex chromosomal rearrangements after 2.0 Gy, radiosensitive patients as endpoint were clearly to be distinguished (p = 0.001) from healthy individuals. Translocations (p = 0.001) as well as breaks per metaphase (p = 0.002) were also suitable indicators for detecting differences between patients and healthy individuals. The parameters ''percentage of dicentric chromosomes'', ''breaks'', and ''excess acentric fragments'' in comparison to the total number of mitoses analyzed could neither serve as meaningful nor as significant criteria, since they showed a strong interindividual variability. Conclusion: to detect a difference in chromosomal aberrations between healthy and radiosensitive individuals, the parameters ''frequency of breaks

  12. Chromosomal aberrations and SCEs as biomarkers of cancer risk

    DEFF Research Database (Denmark)

    Norppa, H; Bonassi, S; Hansteen, I-L

    2006-01-01

    between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid...... species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool...

  13. ANTIMUTAGENIC EFFECT OF TRIPHALA ON CHROMOSOMAL ABERRATIONS IN SWISS ALBINO MICE

    Directory of Open Access Journals (Sweden)

    Thomas Amrutha Merin

    2012-10-01

    Full Text Available Triphala is a herbal formula used in the ancient Science of Ayurveda. Triphala, a composite mixture of Terminalia bellerica, Terminalia chebula and Emblica officinalis, has been used in traditional system of medicine for the treatment of many malaises such as heart ailment and hepatic disease. The present set of investigation is designed to evaluate the antimutagenic potential of aqueous extract of Triphala using in vivo chromosomal aberration assay in Swiss albino mice. Cyclophosphamide(CP, a well known mutagen was given by intraperitoneal injection at a dose of 40mg/kg body weight. Triphala was given at the dose of 125,250 and 500mg/kg body weight orally for seven consecutive days prior to Cyclophosphamide treatment. The animals were sacrificed at the sampling time of 24hrs after treatment and their bone marrow tissues were analysed for chromosomal damage and mitotic index. In Cyclophosphamide treated animals, a significant induction of chromosomal aberration was recorded with decrease in mitotic index. However, in Triphala supplemented animals, no significant induction in chromosomal damage or change in mitotic index was recorded. In different Triphala supplemented groups, a dose dependent significant decrease in Cyclophosphsmide induced clastogenicity was recorded. The incidence of aberrant cell was found to be reduced by the doses of Triphala when compared to Cyclophosphamide treated group. The study revealed the antimutagenic potential of Triphala against Cyclophosphamide induced chromosomal mutations. Analysis of the individual constituents of Triphala is shown to be rich in tannins as well as other chemical agents like carbohydrates, saponins, gallic acid, ellagic acids. Presence of these active principles in Triphala is likely to make it an effective antimutagenic agent.

  14. [FREQUENCIES OF FETAL CHROMOSOMAL ABERRATIONS DETECTED BY AMNIOCENTESIS: OUR 15-YEARS EXPERIENCE].

    Science.gov (United States)

    Stoyanova, V; Ivanov, H; Linev, A; Vachev, T

    2015-01-01

    Amniocentesis is the most common and reliable prenatal diagnostic method for chromosomopathies. The purpose of the present study is to retrospectively evaluate our 15-year experience with prenatal cytogenetic diagnosis by amniocentesis, focusing on the indications and rates of chromosome abnormalities. The current study involve prenatal cytogenetic analysis from 564 amniocentesis performed at the Department of Medical Genetics, St. George University Hospital, Plovdiv between January 2000 and December 2014. Among clinical indications, abnormal maternal serum screening results (54.96%; 310/564) have been the most common indication for amniocentesis. Chromosomal abnormalities were detected in 5.5% (31/546) of cases. Structural rearrangements were the most common abnormality found (16/3 1;51,61%) with prevalence of balanced aberrations--11 cases. The highest detection rate of chromosome aberrations was in cases undergoing amniocentesis due to known family history of chromosomal abnormality (15.1%), followed by abnormal fetal ultrasound finding group (7.69%), increasing-risk maternal prenatal screening results (4.52%), and advanced maternal age (3.28%). This study provides important information for prenatal genetic counseling of families at risk with aim of prenatal care and prevention during pregnancies.

  15. Chromosomal Aberrations and DNA Repair Gene Variants in a Radon-exposed Population

    Energy Technology Data Exchange (ETDEWEB)

    Kiuru, A.; Lindholm, C.; Koivistoinen, A.; Salomaa, S.

    2004-07-01

    Polymorphisms of XRCC1 (X-ray repair cross-complementing group 1), XRCC3 (X-ray repair cross-complementing group 3), and hOGG1 (the human homologue of the yeast OGG1 gene) DNA repair genes have been associated with altered DNA repair capacity and risk of various cancers. In the present study our goal was to clarify the influence of various DNA repair gene variants on the frequency of chromosomal aberrations (CA) in subjects exposed to residential radon. The study group of 84 non-smoking, healthy individuals exposed to domestic radon were analysed using the fluorescence in-situ hybridization (FISH) technique. No association between radon concentration and CA frequencies was observed. However, a significant increase with age was shown as well as a large variability in translocation frequencies between individuals within the same age group. In order to investigate the role of individual susceptibility to this variation genotypes of DNA repair genes XRCC1 (codons 194, 280 and 399), XRCC3 (codon 241) and hOGG1 (codon 326) were determined from leukocyte DNA using methods based on polymerase chain reaction. Multiple regression analysis was applied to evaluate the effect of the polymorphisms and the other confounding factors (age, exposure to randon etc) to the frequency of CA. The preliminary statistical analyses showed that the different gene appeared not to be related to a pronounced increase in chromosome aberration frequencies observed by FISH painting. However, the analysis indicated that the homozygous variant of XRCC3 codon 241 was associated (P<0.05) with two-ways translocations in conjunction with age. Larger studies, both with regard to the cohort and the number of gene variants are needed to elucidate the influence of other DNA repair variants to the yield of chromosomal aberrations. The results indicate that the chromosomal translocations accumulated by age (spontaneous background) may be partly explained by defects in homologous recombination repair. (Author

  16. Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2017-01-01

    Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative

  17. Nuclear anomalies, chromosomal aberrations and proliferation rates in cultured lymphocytes of head and neck cancer patients.

    Science.gov (United States)

    George, Alex; Dey, Rupraj; Bhuria, Vikas; Banerjee, Shouvik; Ethirajan, Sivakumar; Siluvaimuthu, Ashok; Saraswathy, Radha

    2014-01-01

    Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANEUP) in patients (CSAs, 0.0294±0.0038; CTAs, 0.0925±0.0060; DICs, 0.0213±0.0028; and CANEUPs, 0.0308±0.0035) compared to controls (CSAs, 0.0005±0.0003; CTAs, 0.0058±0.0015; DICs, 0.0005±0.0003; and CANEUPs, 0.0052±0.0013) where pnuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, 0.01867±0.00108; NPBs, 0.01561±0.00234; NBUDs, 0.00658±0.00068) compared with controls (MNi, 0.00027±0.00009; NPBs, 0.00002±0.00002; NBUDs, 0.00011±0.00007).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients (1.525±0.005552) compared to healthy subjects (1.686±0.009520 ) (pproliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.

  18. Heavy ion-induced chromosomal aberrations analyzed by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Durante, M.; Gialanella, G.; Grossi, G.; Pugliese, M. [Univ. ``Federico II``, Naples (Italy). Dept. of Physics]|[INFN, Naples (Italy); Cella, L.; Greco, O. [Univ. ``Federico II``, Naples (Italy). Dept. of Physics; Furusawa, Y. [NIRS, Chiba (Japan); George, K.; Yang, T.C. [NASA Lyndon B. Johnson Space Center, Houston, TX (United States)

    1997-09-01

    We have investigated the effectiveness of heavy ions in the induction of chromosomal aberrations in mammalian cells by the recent technique of fluorescence in situ hybridization (FISH) with whole-chromosome probes. FISH-painting was used both in metaphase and interphase (prematurely condensed) chromosomes. The purpose of our experiments was to address the following problems: (a) the ratio of different types of aberrations as a function of radiation quality (search for biomarkers); (b) the ratio between aberrations scored in interphase and metaphase as a function of radiation quality (role of apoptosis); (c) differences between cytogenetic effects produced by different ions at the same LET (role of track structure). (orig./MG)

  19. Research on spontaneously emerged chromosomal aberrations in the periphery blood lymphocytes in cattle ('Busa' breed).

    Science.gov (United States)

    Hasanbasić, Danica; Rukavina, Dunja; Hodzić, Aida; Brka, Muhamed; Vegara, Mensur; Hamamdzić, Muhidin

    2007-11-01

    Knowledge of spontaneous aberrations, namely, of their frequency in non-irradiated cells is of paramount importance not only in cytogenetic research, but also in contemporary animal production. The paper deals with research on spontaneously emerged chromosomal aberrations in the peripheral blood lymphocytes in the cattle of 'Busa' breed. To obtain metaphase chromosomes the conventional method of lymphocyte cultivation was used, albeit slightly modified and adapted to the examined animals and the laboratory conditions. The research findings indicate that a certain percent of spontaneously emerged chromosomal aberrations of chromatid type (gap and break) have been found in the peripheral blood lymphocytes in the cattle of 'Busa' breed.

  20. Chromatin Folding, Fragile Sites, and Chromosome Aberrations Induced by Low- and High- LET Radiation

    Science.gov (United States)

    Zhang, Ye; Cox, Bradley; Asaithamby, Aroumougame; Chen, David J.; Wu, Honglu

    2013-01-01

    We previously demonstrated non-random distributions of breaks involved in chromosome aberrations induced by low- and high-LET radiation. To investigate the factors contributing to the break point distribution in radiation-induced chromosome aberrations, human epithelial cells were fixed in G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome in separate colors. After the images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multimega base pair scale. Specific locations of the chromosome, in interphase, were also analyzed with bacterial artificial chromosome (BAC) probes. Both mBAND and BAC studies revealed non-random folding of chromatin in interphase, and suggested association of interphase chromatin folding to the radiation-induced chromosome aberration hotspots. We further investigated the distribution of genes, as well as the distribution of breaks found in tumor cells. Comparisons of these distributions to the radiation hotspots showed that some of the radiation hotspots coincide with the frequent breaks found in solid tumors and with the fragile sites for other environmental toxins. Our results suggest that multiple factors, including the chromatin structure and the gene distribution, can contribute to radiation-induced chromosome aberrations.

  1. Chromosome-specific segmentation revealed by structural analysis of individually isolated chromosomes.

    Science.gov (United States)

    Kitada, Kunio; Taima, Akira; Ogasawara, Kiyomoto; Metsugi, Shouichi; Aikawa, Satoko

    2011-04-01

    Analysis of structural rearrangements at the individual chromosomal level is still technologically challenging. Here we optimized a chromosome isolation method using fluorescent marker-assisted laser-capture and laser-beam microdissection and applied it to structural analysis of two aberrant chromosomes found in a lung cancer cell line. A high-density array-comparative genomic hybridization (array-CGH) analysis of DNA samples prepared from each of the chromosomes revealed that these two chromosomes contained 296 and 263 segments, respectively, ranging from 1.5 kb to 784.3 kb in size, derived from different portions of chromosome 8. Among these segments, 242 were common in both aberrant chromosomes, but 75 were found to be chromosome-specific. Sequences of 263 junction sites connecting the ends of segments were determined using a PCR/Sanger-sequencing procedure. Overlapping microhomologies were found at 169 junction sites. Junction partners came from various portions of chromosome 8 and no biased pattern in the positional distribution of junction partners was detected. These structural characteristics suggested the occurrence of random fragmentation of the entire chromosome 8 followed by random rejoining of these fragments. Based on that, we proposed a model to explain how these aberrant chromosomes are formed. Through these structural analyses, it was demonstrated that the optimized chromosome isolation method described here can provide high-quality chromosomal DNA for high resolution array-CGH analysis and probably for massively parallel sequencing analysis.

  2. ANALYSES OF CHROMOSOME ABERRATIONS IN LYMPHOCYTES AND BONE MARROW CELLS INDUCED BY RADIATION OR BENZENE

    Institute of Scientific and Technical Information of China (English)

    张鸿源; 王兰金; 等

    1995-01-01

    The chromosomoe and chromatid type aberration can be induced by benzene and the dicentric and ring ones were not observed in vitro experiment but observed in vivo one.In vitro experiment a good linear reression can be given between benzene concentrations and total aberration cells while power regression for radiation dose.The chromosome aberrations induced by benzene combined with radiation in rabbit blood lymphocytes are higher than in bone marryow cells.

  3. Chromosomal aberrations in bone marrow cells of rats irradiated with different gamma-doses and protected with adeturone

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, B.; Mileva, M.; Bulanova, M.; Pantev, T. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1982-01-01

    Sexually mature wistor rats were irradiated on cesium gamma source ''IGUR-1'' with emissive power 3.25 mA/kg. The animals were divided in five groups of 10 rats each. They were irradiated respectively with 0.0129 C/kg, O, 0.0258 C/kg, 0.0516 C/kg, 0.1032 C/kg and control group. Five animals of each group received 300 meg/g weight Adeturone 15 minutes before exposure. The animals were sacrifices 20 hours after irradiation and preparations made from bone-marrow cells for chromosomal analysis. The number of structural chromosomal aberrations, aberrant cells and total number of aberrations in protected and in nonprotected cells were read under high-power microscope. The results were statistically processed by variation and regression analysis. It was found that Adeturone displays strong protective effect on the hereditary cell structures in all animals exposed to doses higher than 0.0129 C/kg, with the exception of chromatid fragments at a dose of 0.0258 C/kg. Mathematical models of the curves of the yields of chromatid and chromosomal fragments, aberrant cells and total number of aberrations in protected and nonprotected animals were described.

  4. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    Genomic instability, induced by various metabolic, genetic, and environmental factors, is the driving force of tumorigenesis. Radiation exposure from different types of radiation sources induces different types of DNA damages, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo experiments. The cell survival rates and frequency of chromosome aberrations depend on the genetic background and radiation sources. To further understand genomic instability induced by charged particles, we exposed human lymphocytes ex vivo, human fibroblast cells, human mammary epithelial cells, and bone marrow cells isolated from CBA/CaH and C57BL/6 mice to high energy protons and Fe ions, and collected chromosomes at different generations after exposure. Chromosome aberrations were analyzed with fluorescent in situ hybridization with whole chromosome specific probes.

  5. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.;

    2015-01-01

    karyotype have demonstrated the presence of prognostic driver aberrations (that is, NPM1, FLT3-ITD and FLT3-TKD) in committed HPCs but not in multipotent HSCs. However, the HSC populations lacking the prognostic driver aberrations contained preleukemic clones harboring a series of recurrent molecular...... aberrations that were present in the fully transformed committed HPCs together with the prognostic driver aberration. Adding to this vast heterogeneity and complexity of AML genomes and their clonal evolution, a recent study of a murine AML model demonstrated that t(9;11) AML originating from HSCs responded...

  6. Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy.

    Science.gov (United States)

    Itoh, Satoru; Hattori, Chiharu; Nagata, Mayumi; Sanbuissho, Atsushi

    2012-08-30

    The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89-98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8-10 days after PH.

  7. Low doses of UVB or UVA induce chromosomal aberrations in cultured human skin cells

    NARCIS (Netherlands)

    Emri, G.; Wenczl, E.; Erp, P. van; Jans, J.; Roza, L.; Horkay, I.; Schothorst, A.A.

    2000-01-01

    Chromosomal defects are frequently present in malignant and premalignant skin disorders; however, it is not known whether ultraviolet radiation from sunlight plays a role in their induction. To obtain information on the ability of ultraviolet A and ultraviolet B to induce chromosomal aberrations, cu

  8. Comparison of chromosome aberrations in peripheral blood lymphocytes from people occupationally exposed to ionizing and radiofrequency radiation.

    Directory of Open Access Journals (Sweden)

    Lalić H

    2001-04-01

    Full Text Available The genotoxic effects of occupational exposure to ionizing and non-ionizing radiation were investigated in 25 physicians and nurses working in hospitals and in 20 individuals working at radio-relay stations. Examination was conducted by chromosome aberration analysis of peripheral blood lymphocytes. The data showed that total number of chromosome aberrations in people exposed to ionizing and radio-frequency radiation (4.08 +/- 0.37 and 4.35 +/- 0.5 on 200 scored metaphases, respectively were almost equally higher than those of non-irradiated subjects. The increase was in proportion to the number of individuals having more that 5-aberration/200 metaphases. Acentric fragments comprised the most frequently seen type of aberration. The average numbers in examined groups (11.8 x 10(-3 and 14.8 x 10(-3 per cell, respectively, were significantly higher than 4.2 x 10(-3, which was observed in controls, unexposed individuals. Dicentric fragments were also frequent (4.8 x 10(-3 and 6.25 x 10(-3, respectively, vs. 0.52 x 10(-3 in control. In contrast, the frequency of chromatid breaks increased only after ionizing radiation (3.8 x 10(-3 vs. 0.26 x 10(-3 in control. A positive correlation between the total number of chromosome aberrations and cumulative 6-years dosage was also found. The data emphasized the dangerous effects of prolonged exposure to both types of radiation and indicated that chromosomal aberration analysis should be obligatory for individuals working at radio-relay stations.

  9. [The dependence of the level of chromosome aberrations in human lymphocytes on the duration of their cultivation under ultraviolet irradiation].

    Science.gov (United States)

    Rushkovskiĭ, S R; Bezrukov, V F; Bariliak, I R

    1998-01-01

    The effect of duration of cultivation of lymphocytes of human UV-irradiated peripheral blood on the chromosomal aberration rate was studied. Under prolonged cultivation the more irradiated blood samples revealed higher level of chromosomal aberrations. The existence of UV-induced delayed chromosomal instability is supposed that may be found under prolonged cultivation. The mechanisms of this phenomenon are discussed.

  10. Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2.

    Directory of Open Access Journals (Sweden)

    Thorsten Klampfl

    Full Text Available Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs. Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%. Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013. One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized.

  11. Chromosomal aberrations induced by Glycidol in Allium cepa L root meristem cells

    Directory of Open Access Journals (Sweden)

    N.Panneerselvam

    2012-02-01

    Full Text Available Glycidol is used as a stabilizer in the manufacture of vinyl polymers and natural oils and as an intermediate in the synthesis of glycerol, glycidyl ethers, and amines. It is also used as an alkylating agent,demulsifier, and dye-leveling agent and for sterilizing milk of magnesia. Glycidol is an alkylating agent which reacts readily with glutathione; it causes a decrease in glutathione content in rat liver, probably reflecting its binding to glutathione. It is a suspected reproductive toxicant and exposure to it has the potential to negatively affect the human reproductive system. The study investigated the cytotoxic effects of glycidol in Allium cepa L root meristem cells. Different concentrations of glycidol ranging 10, 20, 40 and 50μg/ml for 1, 2, 3 and 5h were treated with root meristem cells of Allium cepa L. Fuelgen squash technique was used to determine the aberrations in root tip cells. For each concentration 3000 well-spread cells were scored and cytological abnormalities such as break, gap, exchange, multiple breaks and chromosome fragments were observed. One way analysis of variance was used the study the significant different control and treatment exposed root tip cells.Significant difference between control and glycidol exposed cells were observed. Increasing concentrations increased the number of chromosomal aberrations.

  12. 江西省某铀矿工人周围血淋巴细胞染色体畸变分析%Analysis on chromosome aberration in peripheral blood lymphocytes among workers in a uranium mine of Jiangxi province

    Institute of Scientific and Technical Information of China (English)

    李小亮; 吕玉民; 韩林; 阮健磊; 陈以水; 孙全富; 刘建香

    2015-01-01

    .05 )% in the miner group while ( 0.12 ±0.05 )% in the control group.A negative binominal regression analysis was performed after adjusting the factors of gender, age, length of service, smoking and alcohol drinking.The“dic+r” rate in the miner group was 5.76 times as much as that in the control group ( Z=2.28, P=0.023) .Conclusion The unstable chromosome aberration level in peripheral blood lymphocytes among uranium miners was found to be high.The prevention and control measures for occupational radiation disease among the uranium miners should be strengthened.

  13. [Spontaneous chromosome aberrations in the oogenesis of laboratory rats].

    Science.gov (United States)

    Dyban, A P; Chebotar', N A

    1975-08-01

    Cytological preparations were made by Tarkovsky's method from 2335 rat oocytes obtained after an induced superodulation. The chromosomes could be counted exactly in 861 oocytes. In 797 oocytes (92.7%) euploidy (metaphase II with 21 chromosomes) and in 64 oocytes (7.5%) aneuploidy was found. 60 oocytes were hypoploid, but only 4 oocytes (0.4%) were hyperploid (with 22 chromosomes). Hypoploidy can often be due to the presence of artefacts. Probably the rate of spontaneous aneuploidy in rat oogenesis is about 0.8%, this being significantly lower than the rate of spontaneous aneuploidy in mice oogenesis.

  14. Lanthanum nitrate genotoxicity evaluation: Ames test, mouse micronucleus assay, and chromosome aberration test.

    Science.gov (United States)

    Yang, Hui; Zhang, Xiaopeng; Liu, Haibo; Cui, Wenming; Zhang, Qiannan; Li, Yongning; Yu, Zhou; Jia, Xudong

    2016-11-01

    The increasing use of rare-earth elements (REE) and their compounds has led to their accumulation in the environment and has raised concern about their safety. The toxic effects of REE such as lanthanum are largely unknown; genotoxicity studies have been limited and results are controversial. We evaluated the genotoxicity of lanthanum nitrate (La(NO3)3) in several in vitro and in vivo tests, including bacterial reverse mutation assay (Ames test), mouse bone marrow micronucleus assay, and chromosome aberration assay. La(NO3)3 was not mutagenic in the Ames test. La(NO3)3 did not increase the frequencies of bone marrow micronuclei or chromosome aberration in the mouse after repeated treatments at oral doses up to 735 (females) and 855mg/kg (males). The compound did not increase the frequency of chromosome aberrations in CHO cells in vitro. These results indicate that lanthanum is not a genotoxic hazard.

  15. Influence of DMSO on Carbon K ultrasoft X-rays induced chromosome aberrations in V79 Chinese hamster cells

    Energy Technology Data Exchange (ETDEWEB)

    Natarajan, Adayapalam T., E-mail: natarajan@live.nl [University of Tuscia, Viterbo (Italy); Palitti, Fabrizio [University of Tuscia, Viterbo (Italy); Hill, Mark A. [CRUK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom); MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD (United Kingdom); Stevens, David L. [MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD (United Kingdom); Ahnstroem, Gunnar [Department of Microbiology and Genetic Toxicology, Stockholm University, Stockholm (Sweden)

    2010-09-10

    Ultrasoft X-rays have been shown to be very efficient in inducing chromosomal aberrations in mammalian cells. The present study was aimed to evaluate the modifying effects of DMSO (a potent scavenger of free radicals) on the frequencies of chromosome aberrations induced by soft X-rays. Confluent held G1 Chinese hamster cells (V79) were irradiated with Carbon K ultrasoft X-rays in the presence and absence of 1 M DMSO and frequencies of chromosome aberrations in the first division cells were determined. DMSO reduced the frequencies of exchange types of aberrations (dicentrics and centric rings) by a factor of 2.1-3.5. The results indicate that free radicals induced by ultrasoft X-rays contribute to a great extent to the induction of chromosome aberrations. The possible implications of these results in interpreting the mechanisms involved in the high efficiency of ultrasoft X-rays in the induction of chromosome aberrations are discussed.

  16. Antimutagenic effects of piperine on cyclophosphamide-induced chromosome aberrations in rat bone marrow cells.

    Science.gov (United States)

    Wongpa, Sareeya; Himakoun, Lakana; Soontornchai, Sarisak; Temcharoen, Punya

    2007-01-01

    Piperine is a major pungent substance and active component of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). Both plants are used worldwide as household spices and condiments. They are also used as important ingredients in folklore medicine in many Asian countries. Therefore, it is of interest to study antimutagenic effects of piperine. In this study, its influence on chromosomes was investigated in rat bone marrow cells. Male Wistar rats were orally administered piperine at the doses of 100, 400 and 800 mg/kg body weight for 24 hours then challenged with cyclophosphamide at a dose of 50 mg/kg body weight by intraperitoneal injection. Twenty-four hours thereafter, all animals were sacrificed and bone marrow samples were collected for chromosomal analysis. The results demonstrated that piperine at a dose of 100 mg/kg body weight gave a statistically significant reduction in cyclophosphamide-induced chromosomal aberrations. In conclusion, piperine may have antimutagenic potential. The underlying molecular mechanisms now require attention.

  17. Particle-induced chromosome aberrations and mutations: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, S. [Gesellschaft fuer Schwerionenforschung, Darmstadt (Germany)

    1997-09-01

    This overview will focus on progress in chromosome and mutation studies achieved by the application of new techniques. Furthermore, recent relevant data on longterm genetic effects of densely ionizing radiation will be summarized. (orig./MG)

  18. Dose-response calibration curves of {sup 137}Cs gamma rays for dicentric chromosome aberrations in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Wol Soon; Oh, Su Jung; Jeong, Soo Kyun; Yang, Kwang Mo [Dept. of Research center, Dong Nam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Jeong, Min Ho [Dept. of Microbiology, Dong A University College of Medicine, Busan (Korea, Republic of)

    2012-11-15

    Recently, the increased threat of radiologically industrial accident such as radiation nondestructive inspection or destruction of nuclear accident by natural disaster such as Fukushima accident requires a greater capacity for cytogenetic biodosimetry, which is critical for clinical triage of potentially thousands of radiation-exposed individuals. Dicentric chromosome aberration analysis is the conventional means of assessing radiation exposure. Dose–response calibration curves for {sup 13}'7Cs gamma rays have been established for unstable chromosome aberrations in human peripheral blood lymphocytes in many laboratories of international biodosimetry network. In this study, therefore, we established dose– response calibration curves of our laboratory for {sup 137}Cs gamma raysaccording to the IAEA protocols for conducting the dicentric chromosome assay We established in vitro dose–response calibration curves for dicentric chromosome aberrations in human lymphocytes for{sup 13}'7Cs gamma rays in the 0 to 5 Gy range, using the maximum likelihood linear-quadratic model, Y = c+αD+βD2. The estimated coefficients of the fitted curves were within the 95% confidence intervals (CIs) and the curve fitting of dose–effect relationship data indicated a good fit to the linear-quadratic model. Hence, meaningful dose estimation from unknown sample can be determined accurately by using our laboratory’s calibration curve according to standard protocol.

  19. Impact of types of lymphocyte chromosomal aberrations on human cancer risk

    DEFF Research Database (Denmark)

    Hagmar, Lars; Strömberg, Ulf; Bonassi, Stefano

    2004-01-01

    The frequency of cells with structural chromosomal aberrations (CAs) in peripheral blood lymphocytes is the first genotoxicity biomarker that has shown an association with cancer risk. CAs are usually divided into chromosome-type (CSAs) and chromatid-type aberrations (CTAs), with different...... blood lymphocytes, using Nordic (1981 subjects with CA data, 1871 subjects with CSA/CTA data) and Italian (1573 subjects with CA data, 877 subjects with CTA/CSA data) cohorts, with a median follow-up of 17 years. High levels of CAs at test were clearly associated with increased total cancer incidence...

  20. Aberrations in the Chromosomes of Cirrhinus mrigala (Hamilton upon Exposure to Butachlor

    Directory of Open Access Journals (Sweden)

    Abhay Singh Yadav

    2016-07-01

    Full Text Available Background: Cirrhinus mrigala, one of the important fish widely consumed in India, was used for karyological observations and to evaluate the toxic effect of butachlor, an extensively used herbicide in rice fields in terms of chromosomal aberration test. Methods: Fishes were collected from “National Fish Seed Farm” Jyotisar with mean body weight of 20-50g. The experimental fishes were kept in two treatments each with replicate of two. There were 15 fish each in the control group (T1 without exposure to butachlor and in T2 where fishes were exposed to butachlor. Results: Karyotype revealed the 2n=50 chromosome from the somatic cell. Chromosomal aberrations were reported after 24 hrs, 48 hrs, 72 hrs, and 96 hrs from kidney cell preparation in fishes exposed to 1.0 ppm, sublethal concentration of butachlor. Frequencies of chromosomal aberration revealed a significant (P<0.05 time-dependent response. Stickiness and clumping appeared at 24 and 48 hrs of exposure, end to end joining appeared after 72 hrs and chromosomal fragmentations were observed after exposure for 96 hrs. Conclusion: These studies clearly revealed the genotoxic potential of butachlor even at low dose level (1.0 ppm and suggest that butachlor interferes with cellular activities in fishes at genetic level, inducing chromosomal aberrations. Therefore, the results of these investigations suggest a serious concern towards the potential danger of butachlor for aquatic organisms and the environment suggesting judicious and careful use of this pesticide in agricultural area. These aberrations in chromosome from kidney cell preparation illustrate the risk that butachlor possesses.

  1. Induction of Chromosomal Aberrations by Propoxur in Mouse Bone Marrow Ceils

    Institute of Scientific and Technical Information of China (English)

    R. C. AGRAWAL

    1999-01-01

    Propoxur is a widely used dithiocarbamate insecticide. In this study, the clastogenic effect of propoxur has been evaluated using chromosomal aberration assay in mouse bone marrow cells. Singlei. p. administration of propoxur, at 25 nag/kg b.wt., a maximum tolerated dose (MTD) and 12.5mg/kg b.wt (50% of MTD) have significantly induced different types of aberrations after 24 h of treatment. The aberrations were dose and time dependent and reached a maximum after 24 h of exposure. The sresult suggest a genotoxic potential of propoxur.

  2. Induction of chromosomal aberrations by propoxur in mouse bone marrow cells.

    Science.gov (United States)

    Agrawal, R C

    1999-12-01

    Propoxur is a widely used dithiocarbamate insecticide. In this study, the clastogenic effect of propoxur has been evaluated using chromosomal aberration assay in mouse bone marrow cells. Single i.p. administration of propoxur, at 25 mg/kg b.wt., a maximum tolerated dose (MTD) and 12.5 mg/kg b.wt (50% of MTD) have significantly induced different types of aberrations after 24 h of treatment. The aberrations were dose and time dependent and reached a maximum after 24 h of exposure. The results suggest a genotoxic potential of propoxur.

  3. The effects of biological and life-style factors on baseline frequencies of chromosome aberrations in human lymphocytes

    Directory of Open Access Journals (Sweden)

    Hilada Nefic

    2014-01-01

    Full Text Available Objective: This study investigated the influence of sex and ageing on chromosomal damage and the role of life-style habits on the frequency of chromosomal aberrations (CAs in peripheral blood lymphocytes (PBLs of healthy Bosnian subjects. Materials and Methods: Peripheral blood samples were obtained from 100 healthy, unrelated individuals in Bosnia and Herzegovina during 2010 and 2011. Chromosome preparations were made by dropping and air drying and slides were stained with 10% Giemsa solution (pH 6.8. The cytogenetic analysis was carried out in a cytogenetic laboratory in the Department of Biology of the Faculty of Science in Sarajevo. The category of total structural CAs was sub classified as chromosome-type aberrations (CSAs and chromatid-type aberrations (CTAs while the category of total numerical CAs was sub classified as aneuploid and polyploid mitoses. All statistical analyses were carried out using Microsoft Excel 2010 (Microsoft Corporation and the Windows Kwikstat Winks SDA 7.0.2 statistical software package (Texa Soft Cedar Hill, Texas. Results: Cytogenetic analysis revealed the average number of structural CAs was 2.84 and of numerical CAs was 9.56. There was a significant increase in the frequency of chromosome-type aberrations (1.92 compared with chromatid-type aberrations (CTAs (0.92 and a significant increase in the frequency of aneuploid (8.83 compared with polyploid (0.73 mitoses. Significant positive correlations between age and CTAs in human PBLs were also demonstrated. Additional statistical analysis showed that ageing increase number of numerical CAs in lymphocytes of drinkers. The frequency of structural CAs of females exposed to radiation was significantly greater than in males. Analysis indicates the presence of a positive association between CAs and smoking in younger subjects but a negative correlation between aberrant cells frequencies and alcohol in older drinkers. Conclusion: The results of the study support the

  4. Detection of chromosome aberrations in interphase nuclei using fluorescence in situ hybridization technique.

    OpenAIRE

    1993-01-01

    We report here several experiences of interphase cytogenetics, using fluorescence in situ hybridization (FISH) technique, for the detection of chromosome aberrations. FISH, using alpha satellite specific probes of 18, X, Y chromosomes, was done in interphase nuclei from peripheral blood of patients with Edwards' syndrome, Klinefelter's syndrome and Turner's syndrome with healthy male and female controls, respectively. The distributions of fluorescent signals in 100 interphase nuclei were well...

  5. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Castanos-Velez Esmeralda

    2006-09-01

    Full Text Available Abstract Background Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression. Results We investigated genome-wide gene expression in colorectal carcinoma (CRC and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC. Conclusion An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.

  6. Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Arianna Aricò

    Full Text Available Canine Diffuse Large B-cell Lymphoma (cDLBCL is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs by high-resolution array comparative genomic hybridization (aCGH in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30% were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%. In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL.

  7. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation

    Science.gov (United States)

    Lu, Tao; Wu, Honglu; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Bowler, Deborah

    2016-07-01

    DNA damages induced by space radiation, consisting of protons and high-LET charged particles, can be complex in nature, which are often left unrepaired and cause chromosomal aberrations. Increased level of genomic instability is attributed to tumorigenesis and increased cancer risks. To investigate genomic instability induced by charged particles, human lymphocytes ex vivo, human fibroblasts, and human mammary epithelial cells, as well as mouse bone marrow stem cells isolated from CBA/CaH and C57BL/6 strains were exposed to high energy protons and Fe ions. Metaphase chromosome spreads at different cell divisions after radiation exposure were collected and, chromosome aberrations were analyzed with fluorescence in situ hybridization with whole chromosome-specific probes for human cells. With proton irradiation, levels of chromosome aberrations decreased by about 50% in both lymphocytes and epithelial cells after multiple cell divisions, compared to initial chromosome aberrations at 48 hours post irradiation in both cell types. With Fe ion irradiation, however, the frequency of chromosome aberrations in lymphocytes after multiple cell divisions was significantly lower than that in epithelial cells at comparable cell divisions, while their initial chromosome aberrations were at similar levels. Similar to the human cells, after Fe ion irradiation, the frequency of late chromosome aberrations was similar to that of the early damages for radio-sensitive CBA cells, but different for radio-resistant C57 cells. Our results suggest that relative biological effectiveness (RBE) values are dependent not only on radiation sources, but also on cell types and cell divisions.

  8. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    DNA damages induced by space radiation, consisting of protons and high-LET charged particles, can be complex in nature, which are often left unrepaired and cause chromosomal aberrations. Increased level of genomic instability is attributed to tumorigenesis and increased cancer risks. To investigate genomic instability induced by charged particles, human lymphocytes ex vivo, human fibroblasts, and human mammary epithelial cells, as well as mouse bone marrow stem cells isolated from CBA/CaH and C57BL/6 strains were exposed to high energy protons and Fe ions. Metaphase chromosome spreads at different cell divisions after radiation exposure were collected and, chromosome aberrations were analyzed with fluorescence in situ hybridization with whole chromosome-specific probes for human cells. With proton irradiation, levels of chromosome aberrations decreased by about 50% in both lymphocytes and epithelial cells after multiple cell divisions, compared to initial chromosome aberrations at 48 hours post irradiation in both cell types. With Fe ion irradiation, however, the frequency of chromosome aberrations in lymphocytes after multiple cell divisions was significantly lower than that in epithelial cells at comparable cell divisions, while their initial chromosome aberrations were at similar levels. Similar to the human cells, after Fe ion irradiation, the frequency of late chromosome aberrations was similar to that of the early damages for radio-sensitive CBA cells, but different for radio-resistant C57 cells. Our results suggest that relative biological effectiveness (RBE) values are dependent not only on radiation sources, but also on cell types and cell divisions.

  9. 40 CFR 799.9537 - TSCA in vitro mammalian chromosome aberration test.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA in vitro mammalian chromosome aberration test. 799.9537 Section 799.9537 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....g., heparin) or separated lymphocytes obtained from healthy subjects are added to culture...

  10. 40 CFR 799.9538 - TSCA mammalian bone marrow chromosomal aberration test.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA mammalian bone marrow chromosomal aberration test. 799.9538 Section 799.9538 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... be used. Commonly used laboratory strains of young healthy adult animals should be employed. At...

  11. Chromosome Aberrations of East Asian Bullfrog (Hoplobatrachus rugulosus around a Gold Mine Area with Arsenic Contamination

    Directory of Open Access Journals (Sweden)

    Atidtaya Suttichaiya

    2016-01-01

    Full Text Available The objectives of this study are to investigate the chromosome aberrations of the East Asian Bullfrog (Hoplobatrachus rugulosus in the gold mine area compared to an unaffected area. Three H. rugulosus were collected, and chromosome aberrations were studied using bone marrow. The level of arsenic was measured in water, sediment and H. rugulosus samples. The average concentrations of arsenic in the water and sediment samples from the gold mine and unaffected areas were 0.03 ± 0.003 mg/l and not detected in water as well as 351.59 ± 5.73 and 1.37 ± 1.07 mg/kg in sediment, respectively. The gold mine values were higher than the permissible limit of the water and soil quality standards, but the arsenic concentrations in the samples from the unaffected area were within prescribed limit. The average concentrations of arsenic in H. rugulosus samples from the gold mine and unaffected areas were 0.39 ± 0.30 and 0.07 ± 0.01 mg/kg, respectively, which were both lower than the standard of arsenic contamination in food. The diploid chromosome number of H. rugulosus in both areas was 2n=26, and the percentage of chromosome breakages of H. rugulosus in the gold mine area were higher than the unaffected area. There were eight types of chromosome aberrations, including a single chromatid gap, isochromatid gap, single chromatid break, isochromatid break, centric fragmentation, deletion, fragmentation and translocation. The most common chromosome aberration in the samples from the affected area was deletion. The difference in the percentage of chromosome breakages in H. rugulosus from both areas was statistically significant (p<0.05.

  12. Chromosome aberration yields and apoptosis in human lymphocytes irradiated with Fe-ions of differing LET

    Science.gov (United States)

    Lee, R.; Nasonova, E.; Ritter, S.

    In the present paper the relationship between cell cycle delays induced by Fe-ions of differing LET and the aberration yield observable in human lymphocytes at mitosis was examined. Cells of the same donor were irradiated with 990 MeV/n Fe-ions (LET = 155 keV/μm), 200 MeV/n Fe-ions (LET = 440 keV/μm) and X-rays and aberrations were measured in first cycle mitoses harvested at different times after 48 84 h in culture and in prematurely condensed G2-cells (PCCs) collected at 48 h using calyculin A. Analysis of the time-course of chromosomal damage in first cycle metaphases revealed that the aberration frequency was similar after X-ray irradiation, but increased two and seven fold after exposure to 990 and 200 MeV/n Fe-ions, respectively. Consequently, RBEs derived from late sampling times were significantly higher than those obtained at early times. The PCC-data suggest that the delayed entry of heavily damaged cells into mitosis results especially from a prolonged arrest in G2. Preliminary data obtained for 4.1 MeV/n Cr-ions (LET = 3160 keV/μm) revealed, that these delays are even more pronounced for low energy Fe-like particles. Additionally, for the different radiation qualities, BrdU-labeling indices and apoptotic indices were determined at several time-points. Only the exposure to low energy Fe-like particles affected the entry of lymphocytes into S-phase and generated a significant apoptotic response indicating that under this particular exposure condition a large proportion of heavily damaged cells is rapidly eliminated from the cell population. The significance of this observation for the estimation of the health risk associated with space radiation remains to be elucidated.

  13. Cell survival and chromosomal aberrations in CHO-K1 cells irradiated by carbon ions.

    Science.gov (United States)

    Czub, J; Banaś, D; Błaszczyk, A; Braziewicz, J; Buraczewska, I; Choiński, J; Górak, U; Jaskóła, M; Korman, A; Lankoff, A; Lisowska, H; Łukaszek, A; Szefliński, Z; Wójcik, A

    2009-03-01

    Chinese hamster ovary CHO-K1 cells were exposed to high LET (12)C-beam (LET: 830 keV/microm) in the dose range of 0-6 Gy and to (60)Co irradiation and the RBE value was obtained. Effects of (12)C-beam exposure on cell survival and chromosomal aberrations were calculated. The chromosomal aberration data were fitted with linear equation. The distribution of aberration in cells was examined with a standard u-test and used to evaluate the data according to Poisson probabilities. The variance to the mean ratio sigma(2)/Y and the dispersion index (u) were determined. Overdispersion was significant (p<0.05) when the value of u exceeded 1.96.

  14. [Estimation of efficiency of seed irradiation by thermal neutrons for inducing chromosomal aberration in M2 of cotton Gossipium hirsutum L].

    Science.gov (United States)

    Rakhmatullina, E M; Sanam'ian, M F

    2007-05-01

    Cytogenetic analysis of M2 plants after irradiation of cotton by thermal neutrons was performed in 56 families. In 40 plants of 27 M2 families, different abnormalities of chromosome pairing were found. These abnormalities were caused by primary monosomy, chromosomal interchange, and desynapsis. The presence of chromosome aberrations in some cases decreased meiotic index and pollen fertility. Comparison of the results of cytogenetics analysis, performed in M1 and M2 after irradiation, showed a nearly two-fold decrease in the number of plants with chromosomal aberrations in M2, as well as narrowing of the spectrum of these aberrations. The latter result is explained by the fact that some mutations are impossible to detect in subsequent generations because of complete or partial sterility of aberrant M1 plants. It was established that the most efficient radiation doses for inducing chromosomal aberrations in the present study were 15 and 25 Gy, since they affected survival and fertility of altered plant to a lesser extent.

  15. Chromosome Aberration in Human Blood Lymphocytes Exposed to Energetic Protons

    Science.gov (United States)

    Hada, M.; George, Kerry A.; Cucinotta, F. A.

    2008-01-01

    During space flight, astronauts are exposed to a space radiation consisting of high-energy protons, high charge and energy (HZE) nuclei, as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary particles have a higher LET value than primary protons and therefore expected to have a higher relative biological effectiveness (RBE). To investigate this theory, we exposed human peripheral blood lymphocytes to protons with energies of 250 MeV, 800MeV, 2 GeV, or 2.5 GeV. LET values for these protons ranged from 0.4 to 0.2 keV/micrometer. and doses ranged from 0.2 to 3 Gy. Over this energy the probability of nuclear reaction leading to secondary radiation, and the multiplicity of reaction produces such as neutrons and mesons increases substantially. The effect of aluminum and polyethylene shielding was also assessed using the 2 GeV and 2.5GeV proton beams. After exposure lymphocytes were stimulated to divide and chromosomes were collected from cells in the first G2 and metaphase cell cycle after exposure using a chemical induced premature chromosome condensation (PCC) technique. Dose response data for chromosome damage was analyzed using the fluorescence in situ hybridization (FISH) chromosome painting technique. Selected samples were also analyzed with multicolor FISH (mFISH) and multicolor banding FISH (mBAND) techniques. Data indicates that the dose response for simple-type exchanges is similar for proton and gamma exposure, whereas protons induce higher yields of complex exchanges that are LET dependent. RBE values will be presented for each proton energy, and the effects of shielding and possible cytogenetic signatures of proton exposure will be discussed.

  16. Chromosome aberrations in human blood lymphocytes exposed to energetic protons

    Science.gov (United States)

    Hada, Megumi; George, Ms Kerry; Cucinotta, Francis A.

    During space flight, astronauts are exposed to space radiation consisting of high-energy protons, high charge and energy (HZE) nuclei, as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary particles have a higher LET value than primary protons and are therefore expected to have a higher relative biological effectiveness (RBE). To investigate this theory, we exposed human peripheral blood lymphocytes to protons with energies of 250 MeV, 800MeV, 2 GeV, or 2.5 GeV. LET values for these protons ranged from 0.4 to 0.2 keV/µm. and doses ranged from 0.2 to 3 Gy. Over this energy range the probability of nuclear reaction leading to secondary radiation, and the multiplicity of reaction products such as neutrons and mesons increases substantially. The effect of aluminum and polyethylene shielding was also assessed using the 2 GeV and 2.5GeV proton beams. After exposure lymphocytes were stimulated to divide and chromosomes were collected from cells in the first G2 and metaphase cell cycle after exposure using a chemical induced premature chromosome condensation (PCC) technique. Dose response data for chromosome damage was analyzed using the fluorescence in situ hybridization (FISH) chromosome painting technique. Selected samples were also analyzed with multicolor FISH (mFISH) and multicolor banding FISH (mBAND) techniques. Data indicates that the dose response for simple-type exchanges is similar for proton and gamma exposure, whereas protons induce higher yields of complex exchanges that are energy dependent. RBE values will be presented for each proton energy, and the effects of shielding and possible cytogenetic signatures of proton exposure will be discussed.

  17. Kinetics of DSB rejoining and formation of simple chromosome exchange aberrations

    Science.gov (United States)

    Cucinotta, F. A.; Nikjoo, H.; O'Neill, P.; Goodhead, D. T.

    2000-01-01

    PURPOSE: To investigate the role of kinetics in the processing of DNA double strand breaks (DSB), and the formation of simple chromosome exchange aberrations following X-ray exposures to mammalian cells based on an enzymatic approach. METHODS: Using computer simulations based on a biochemical approach, rate-equations that describe the processing of DSB through the formation of a DNA-enzyme complex were formulated. A second model that allows for competition between two processing pathways was also formulated. The formation of simple exchange aberrations was modelled as misrepair during the recombination of single DSB with undamaged DNA. Non-linear coupled differential equations corresponding to biochemical pathways were solved numerically by fitting to experimental data. RESULTS: When mediated by a DSB repair enzyme complex, the processing of single DSB showed a complex behaviour that gives the appearance of fast and slow components of rejoining. This is due to the time-delay caused by the action time of enzymes in biomolecular reactions. It is shown that the kinetic- and dose-responses of simple chromosome exchange aberrations are well described by a recombination model of DSB interacting with undamaged DNA when aberration formation increases with linear dose-dependence. Competition between two or more recombination processes is shown to lead to the formation of simple exchange aberrations with a dose-dependence similar to that of a linear quadratic model. CONCLUSIONS: Using a minimal number of assumptions, the kinetics and dose response observed experimentally for DSB rejoining and the formation of simple chromosome exchange aberrations are shown to be consistent with kinetic models based on enzymatic reaction approaches. A non-linear dose response for simple exchange aberrations is possible in a model of recombination of DNA containing a DSB with undamaged DNA when two or more pathways compete for DSB repair.

  18. Chromosomal Aberrations in Human Peripheral Blood Lymphocytes after Exposure to Ionizing Radiation

    Science.gov (United States)

    Ryu, Tae Ho; Kim, Jin-Hong; Kim, Jin Kyu

    2016-01-01

    Biological dosimetry using chromosome aberration analyses in human peripheral blood lymphocytes is suitable and useful tool for estimating the dose when a nuclear or radiological emergency is investigated. Blood samples from five healthy donors were obtained to establish dose-response calibration curves for chromosomal aberrations after exposure to ionizing radiation. In this work, dicentric assay and CBMN assay were compared considering the sensitivity and accuracy of dose estimation. In a total of 21,688 analyzed metaphase spreads, 10,969 dicentric chromosomes, 563 centric rings and 11,364 acentric chromosomes were found. The number of metaphase cells decreased with increasing radiation dose. The centric rings were not found in the non-irradiated control. There was no relationship between radiation dose and acentric ring induction. The frequency of total MN increased in a dose-dependent manner. In comparison with the control value, MN increased about 9, 32, 75, 87, and 52 fold higher after treatment with 1, 2, 3, 4, and 5 Gy, respectively. The results revealed that the mean frequency of chromosomal aberrations, both in dicentric and in micronuclei analyses increased with increasing radiation dose. PMID:28217281

  19. MICRONUCLEI PROFILE: AN INDEX OF CHROMOSOMAL ABERRATIONS IN FRESHWATER FISHES (SYNODONTIS CLARIAS AND TILAPIA NILOTICA

    Directory of Open Access Journals (Sweden)

    J.C. OKONKWO

    2011-01-01

    Full Text Available Incidence of chromosomal aberrations in Synodontis clarias and Tilapia nilotica (Linnaeus 1757 were measured using the conventional micronucleus assay in fish erythrocytes. The species showed varying degree of micronuclei frequencies in their respective genomes of sampled gill and kidney blood. Cytological examinations showed bi-nucleated cells, deformed nuclei including the main aberrations, micronucleus formations in various genomes of the fish from different locations considered in this study. Comparison of the micronucleus rates in peripheral and kidney blood of the two species revealed no statistical difference (P> 0.05. On species occurrence of the measured chromosomal aberrations, averages of micronucleus frequencies recorded in Synodontis clarias showed visible variation and to be 2.2 folds higher than the values obtained in the corresponding Tilapia sp. but there was no statistical difference (P>0.01 among the two breeds. The work recommends that micronuclei tests in fish erythrocytes be carried out at various times, thus making it possible to follow-up the changing micronuclei frequencies and concludes that gills and kidney erythrocytes can be used in studies concerning chromosomal aberrations since the sampling of the peripheral blood is appropriate as it allows collecting several samples from the same individuals, without having to sacrifice it.

  20. Chromosome aberrations determined by sFISH and G-banding in lymphocytes from workers with internal deposits of plutonium

    Science.gov (United States)

    Tawn, E. Janet; Curwen, Gillian B.; Jonas, Patricia; Riddell, Anthony E.; Hodgson, Leanne

    2016-01-01

    Abstract Purpose: To examine the influence of α-particle radiation exposure from internally deposited plutonium on chromosome aberration frequencies in peripheral blood lymphocytes of workers from the Sellafield nuclear facility, UK. Materials and methods: Chromosome aberration data from historical single colour fluorescence in situ hybridization (sFISH) and Giemsa banding (G-banding) analyses, together with more recent sFISH results, were assessed using common aberration analysis criteria and revised radiation dosimetry. The combined sFISH group comprised 29 men with a mean internal red bone marrow dose of 21.0 mGy and a mean external γ-ray dose of 541 mGy. The G-banding group comprised 23 men with a mean internal red bone marrow dose of 23.0 mGy and a mean external γ-ray dose of 315 mGy. Results: Observed translocation frequencies corresponded to expectations based on age and external γ-ray dose with no need to postulate a contribution from α-particle irradiation of the red bone marrow by internally deposited plutonium. Frequencies of stable cells with complex aberrations, including insertions, were similar to those in a group of controls and a group of workers with external radiation exposure only, who were studied concurrently. In a similar comparison there is some suggestion of an increase in cells with unstable complex aberrations and this may reflect recent direct exposure to circulating lymphocytes. Conclusions: Reference to in vitro dose response data for the induction of stable aberrant cells by α-particle irradiation indicates that the low red bone marrow α-particle radiation doses received by the Sellafield workers would not result in a discernible increase in translocations, thus supporting the in vivo findings. Therefore, the greater risk from occupational radiation exposure of the bone marrow resulting in viable chromosomally aberrant cells comes from, in general, much larger γ-ray exposure in comparison to α-particle exposure from plutonium

  1. Disruption of Maternal DNA Repair Increases Sperm-DerivedChromosomal Aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Essers, Jeroun; Kanaar, Roland; Wyrobek,Andrew J.

    2007-02-07

    The final weeks of male germ cell differentiation occur in aDNA repair-deficient environment and normal development depends on theability of the egg to repair DNA damage in the fertilizing sperm. Geneticdisruption of maternal DNA double-strand break repair pathways in micesignificantly increased the frequency of zygotes with chromosomalstructural aberrations after paternal exposure to ionizing radiation.These findings demonstrate that radiation-induced DNA sperm lesions arerepaired after fertilization by maternal factors and suggest that geneticvariation in maternal DNA repair can modulate the risk of early pregnancylosses and of children with chromosomal aberrations of paternalorigin.

  2. Functional Analysis and Treatment of Aberrant Behavior.

    Science.gov (United States)

    Mace, F. Charles; And Others

    1991-01-01

    This article reviews general classes of variables which help to maintain aberrant behavior including attention seeking, sensory and perceptual consequences, and access to materials or activities. Suggestions for a methodology providing a comprehensive functional analysis are offered which include descriptive analysis, hypothesis forming,…

  3. Chromosomal aberrations in peripheral lymphocytes from male native miners working in the Peruvian Andes

    Directory of Open Access Journals (Sweden)

    Sergio R. Santa Maria

    2007-01-01

    Full Text Available We analyzed the frequency of chromosomal aberrations in peripheral lymphocytes from underground miners from the Casapalca (n = 8, mean age = 45 y, range = 36 y to 55 y and Bellavista (n = 8, mean age = 28 y, range 23 y to 34 y high-altitude mining camps in the Peruvian Andes. This population was occupationally exposed to heavy metals such as lead and zinc as well as diesel emission particles, organic solvents and mine dust. The control groups consisted of individuals from a high altitude farming community in the Peruvian village of Tinco (n = 8, mean age = 37 y, range = 25 y to 52 y and the sea level city of Lima (n = 14, mean age = 26 y, range = 20 y to 35 y. All individuals were male native Peruvians. A significantly higher incidence (1.88%, p < 0.05 of chromosomal aberrations (chromatid deletions and breaks, chromosome breaks and acentric fragments were detected in lymphocytes from miners at the Casapalca camp as compared to miners from the Bellavista camp (0.5%, chromatid deletions and acentric fragments only and the Lima sea level (0.07%, chromatid deletions only and Tinco high altitude (no aberrations controls. These results suggest that male native Peruvians occupationally exposed to underground mining activity have an increased frequency of chromosomal aberrations, which could be related to both age and exposure time. The increased chromosomal damage observed in the mining populations studied may be attributable to the complex mixture of genotoxic agents to which the miners may have been exposed.

  4. The use of unstable chromosome aberrations and micronuclei in the individual biomonitoring: a comparative study; Emprego das aberracoes cromossomicas instaveis e micronucleos no biomonitoramento individual: estudo comparativo

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Thiago de Salazar e

    2005-02-15

    Biodosimetry is based on the investigation of radioinduced biological effects in order to correlate them with the absorbed dose. The quantification of unstable chromosome aberrations and micronuclei, in peripheral blood lymphocytes, are two methods commonly used in biodosimetry. In this context, the aim of this research was to compare these methods in the biomonitoring of health care professionals occupationally exposed to ionizing radiation. In parallel, the technique of C-banding was evaluated for quality control of unstable chromosome aberrations analyses. Thus, samples of peripheral blood from health care professionals of three hospitals from Recife (Brazil) were collected, and the lymphocytes cultures were carried out based on the cytogenetic classical technique. It was pointed out that analysis of micronuclei is faster than the unstable chromosome aberrations ones, which suggests the use of the former in preliminary evaluation in cases of suspected accidental exposure. C-banding technique was efficient, as confirmatory test, in the identification of dicentrics and rings during the analyses of unstable chromosome aberrations, being able to be applied in the quality control in biodosimetry. The comparison between the individual work conditions with the frequencies of unstable aberrations and micronuclei obtained from cytogenetic analysis, resulted in the change of behavior of the professionals involved in this research, with a better observance of the radioprotection standards. (author)

  5. Analysis on chromosomal aberrations of peripheral blood lymphocytes in radiological workers in Shenzhen City%深圳市放射工作人员周围血淋巴细胞染色体畸变分析

    Institute of Scientific and Technical Information of China (English)

    刘征宇; 杨学琴; 惠长野; 高朝贤; 李丽梅; 陈郁筠; 曹建伟

    2013-01-01

    [Objective] To analyze the occupational health damage in radiological worker in Shenzhen City,provide the data for assessing the effect of radiation protection.[Methods] 825 radiological workers received the radiation hygienic monitoring from 2008-2011 in Shenzhen City were chosen as the objectives,and the chromosomal aberrations of peripheral blood lymphocytes were detected.The types of chromosomal aberrations were compared between different year,different working year,different gender,and different work type of workers.[Results] During 2008-2011,the annual rates of chromosomal aberration in radiological workers were significantly higher than that in the control group (all P < 0.05).The annual rate of chromosomal aberration from high to low was in 2008,2009,2011and 2010.There was no significant difference between males and females (P > 0.05).The rates of chromosomal aberrations increased with radiation exposure age,and the highest rate was observed in workers with more than 30 years of service,which was significantly higher than groups (P < 0.05).The rate of chromosomal aberrations in industrial radiological workers was significantly higher than that in medical radiological workers,and the rate in both two groups were significantly higher than that in the control group (P < 0.05).The incidence rate of acentric aberrations (acentric fragment,minute and acentric ring)was significantly higher than that of dicentric (dic) and ring (r) chromosomes.[Conclusion] Long-term exposure to low dose of ionizing radiation may cause the increasing chromosomal aberrations of peripheral blood lymphocyte in radiological workers,so it is necessary to strengthen the radiation protection to reduce the ionizing radiation injury.%目的 分析深圳市放射工作人员的职业健康损害情况,为评价放射卫生防护工作提供依据.方法 对该市2008-2011年4年间接受放射卫生监护健康检查的825名放射工作人员进行周围血淋巴细胞染色体畸

  6. Somatic pairing, endomitosis and chromosome aberrations in snakes (Viperidae and Colubridae

    Directory of Open Access Journals (Sweden)

    Beçak Maria Luiza

    2003-01-01

    Full Text Available The positioning of macrochromosomes of Bothrops jararaca and Bothrops insularis (Viperidae was studied in undistorted radial metaphases of uncultured cells (spermatogonia and oogonia not subjected to spindle inhibitors. Colchicinized metaphases from uncultured (spleen and intestine and cultured tissues (blood were also analyzed. We report two antagonic non-random chromosome arrangements in untreated premeiotic cells: the parallel configuration with homologue chromosomes associated side by side in the metaphase plate and the antiparallel configuration having homologue chromosomes with antipolar distribution in the metaphase ring. The antiparallel aspect also appeared in colchicinized cells. The spatial chromosome arrangement in both configurations is groupal size-dependent and maintained through meiosis. We also describe, in untreated gonia cells, endomitosis followed by reductional mitosis which restores the diploid number. In B. jararaca males we observed that some gonad regions present changes in the meiotic mechanism. In this case, endoreduplicated cells segregate the diplochromosomes to opposite poles forming directly endoreduplicated second metaphases of meiosis with the suppression of first meiosis. By a successive division, these cells form nuclei with one set of chromosomes. Chromosome doubling in oogonia is known in hybrid species and in parthenogenetic salamanders and lizards. This species also presented chromosome rearrangements leading to aneuploidies in mitosis and meiosis. It is suggested that somatic pairing, endomitosis, meiotic alterations, and chromosomal aberrations can be correlated processes. Similar aspects of nuclei configurations, endomitosis and reductional mitosis were found in other Viperidae and Colubridae species.

  7. Chromosomal aberrations suggestive of mutagen-related leukemia after 21 years of therapeutic radon exposure

    Energy Technology Data Exchange (ETDEWEB)

    Rechavi, G.; Berkowicz, M.; Rosner, E.; Neuman, Y.; Ben-Bassat, I.; Ramot, B. (Tel-Aviv Univ. (Israel))

    1990-08-01

    A 68-year-old woman with acute myelomonocytic leukemia, who was treated annually for 21 consecutive years by therapeutic low-dose radon gas radiation because of spondyloarthritis, is described. The karyotype of the malignant clone was 45,XX, -17, -18,del(5)(q15q33), +t(17;18)(q11.2q23). In 45% of the metaphases, the modal number was between hyperdiploid to near tetraploid. Double minute chromosomes were demonstrated in 60% of the cells. These chromosomal aberrations are suggestive of mutagen-related leukemia.

  8. Microarray Technology for the Diagnosis of Fetal Chromosomal Aberrations: Which Platform Should We Use?

    Directory of Open Access Journals (Sweden)

    Evangelia Karampetsou

    2014-06-01

    Full Text Available The advantage of microarray (array over conventional karyotype for the diagnosis of fetal pathogenic chromosomal anomalies has prompted the use of microarrays in prenatal diagnostics. In this review we compare the performance of different array platforms (BAC, oligonucleotide CGH, SNP and designs (targeted, whole genome, whole genome, and targeted, custom and discuss their advantages and disadvantages in relation to prenatal testing. We also discuss the factors to consider when implementing a microarray testing service for the diagnosis of fetal chromosomal aberrations.

  9. Chromosome aberrations induced in patients treated with telecobalt therapy for mammary carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Antoine, J.L. (CEN/SCK, Mol, Belgium); Gerber, G.B.; Leonard, A.; Richard, F.; Wambersie, A.

    1981-04-01

    The yields of dicentric and ring chromosomes were recorded during telecobalt therapy for mammary carcinoma. The data were fitted to a power or a quadratic function and were compared with those obtained in patients treated for ankylosing spondylitis and nuclear dockyard workers as well as with the results of an in vitro blood irradiation. As expected, the aberration yield for the same absorbed dose level is much greater after irradiation of ankylosing spondylitis than after irradiation for mammary carcinoma; lymphocytes exposed in vitro display the highest rate of aberration. A deviation of the aberrations observed in cells of the mammary carcinoma patients from the theoretical Poisson distribution also indicates that not all lymphocytes in the body has been exposed under these conditions.

  10. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J

    1983-01-01

    The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...... with women without elevated risk. Spontaneous abortion rate and prematurity rate did not differ from rates expected without amniocentesis. It is concluded that current indications may be characterized as a mixture of evident high risk factors and factors with only a minor influence on risk. Indications...

  11. [Chromosome aberrations in human lymphocytes at a various duration of cultivation after irradiation].

    Science.gov (United States)

    Riabchenko, N I; Antoshchina, M M; Nasonova, V A; Fesenko, E V; Gotlib, V Ia

    2004-01-01

    Human peripheral blood lymphocytes were exposed to 60Co gamma-rays (a dose of 3 Gy) and cultivated during seven days in the presence of PHA and BrdU. It was shown that the metaphases of the first and second mitosises occurred during cultivation of the irradiated and unirradiated lymphocytes, being evidence about of irregularity of the coming into division of various fractions of lymphocytes. The time of cultivation did not influence a rate of aberrations in metaphases of the first and second mitosises of the irradiated lymphocytes. During the first and the subsequent mitosises the number of exchange chromosome aberrations decreased and reached a control level in metaphases of the fourth and fifth mitosises. The number of paired fragments at second and third mitosises increased a little and started to decrease only in metaphases of the fourth and fifth mitosises. The decrease in chromosome aberrations with prolongation of the cultivation of lymphocytes after irradiating is a consequence of elimination of cells with chromosome damages during sequential mitotic divisions.

  12. Bleomycin-induced chromosome aberrations in head and neck cancer patients analyzed by classical cytogenetics and FISH.

    Science.gov (United States)

    Zych, M; Schlade-Bartusiak, K; Chorostkowska, A; Stembalska, A; Krêcicki, T; Sasiadek, M

    2000-05-01

    Individual sensitivity to mutagens has been considered to play an important role in head-and-neck squamous cells carcinoma (HNSCC) development. The bleomycin test was introduced for establishing constitutional susceptibility to mutagens (T.C. Hsu, D.A. Johnston, L.M. Cherry, D. Ramkisson, S.P. Schantz, J.M. Jessup, R.J. Winn, L. Shirley, C. Furlong, Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis, Int. J. Cancer 43 (1989) 403-409). Its criteria are based on scoring of chromosome aberrations (CAs, mainly breaks) in Giemsa-stained chromosomes. Fluorescence in situ hybridization (FISH) offers an easy method for analysis of translocations, acentric fragments and dicentrics. In the present study FISH was applied in the analysis of bleomycin-induced CAs of the HNSCC patients and controls. The results proved that FISH is a complementary method to the classical staining in monitoring of bleomycin-induced CAs.

  13. The Level and Distribution of Chromosomal Aberration of Tomato Seeds at Different Penetration Depths of Carbon Ions

    Institute of Scientific and Technical Information of China (English)

    WANG Jufang; LI Wenjian; ZHANG Ying

    2008-01-01

    The relationship between the penetration depth and the level and distribution of chromosomal aberration of the root tip cells were investigated by exposure of the superposed tomato seeds to 80 MeV/u carbon ions. The results showed that on the entrance of the beam the chromosomal aberration level was low. Damage such as breaks and gaps were dominant. At the Bragg peak, the chromosomal aberration level was high. The yields of dicentrics, rings and disintegrated small chromosomes increased but the yields of breaks and gaps decreased. These results are consistent with the distribution of the physical depth dose profile of carbon ions. It is effective to deposit the Bragg peak on the seeds to induce hereditary aberration in the mutation breeding with heavy ions.

  14. Simple numerical chromosome aberrations in two pituitary adenomas

    DEFF Research Database (Denmark)

    Dietrich, C U; Pandis, N; Bjerre, P

    1993-01-01

    Cytogenetic analysis of short-term cultures of one non-secreting and one prolactin-producing pituitary adenoma revealed simple clonal numerical abnormalities in both tumors. The karyotype of the non-secreting adenoma was 48,XX, +4, +9[42]/49,XX, +4, +9, +20[2]/46,XX[6]. In the prolactin-secreting...

  15. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer

    DEFF Research Database (Denmark)

    Bonassi, Stefano; Norppa, Hannu; Ceppi, Marcello

    2008-01-01

    studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer...... for stomach cancer [RR(medium) = 1.17 (95% CI = 0.37-3.70), RR(high) = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information...

  16. Nonhomologous DNA end joining and chromosome aberrations in human embryonic lung fibroblasts treated with environmental pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Rossner, Pavel, E-mail: prossner@biomed.cas.cz; Rossnerova, Andrea; Beskid, Olena; Tabashidze, Nana; Libalova, Helena; Uhlirova, Katerina; Topinka, Jan; Sram, Radim J.

    2014-05-15

    Highlights: • We analyzed the effect of air pollutants on NHEJ and chromosome aberrations. • In HEL12469 cells B[a]P and extractable organic matter induced DSBs. • The compounds induced XRCC4 expression and a weak Ku70/80 response. • We found increased frequency of aberrations of chromosomes 1, 2, 4, 5, 7 and 17. • The tested compounds preferentially affected chromosome 7. - Abstract: In order to evaluate the ability of a representative polycyclic aromatic hydrocarbon (PAH) and PAH-containing complex mixtures to induce double strand DNA breaks (DSBs) and repair of damaged DNA in human embryonic lung fibroblasts (HEL12469 cells), we investigated the effect of benzo[a]pyrene (B[a]P) and extractable organic matter (EOM) from ambient air particles <2.5 μm (PM2.5) on nonhomologous DNA end joining (NHEJ) and induction of stable chromosome aberrations (CAs). PM2.5 was collected in winter and summer 2011 in two Czech cities differing in levels and sources of air pollutants. The cells were treated for 24 h with the following concentrations of tested chemicals: B[a]P: 1 μM, 10 μM, 25 μM; EOMs: 1 μg/ml, 10 μg/ml, 25 μg/ml. We tested several endpoints representing key steps leading from DSBs to the formation of CAs including histone H2AX phosphorylation, levels of proteins Ku70, Ku80 and XRCC4 participating in NHEJ, in vitro ligation activity of nuclear extracts of the HEL12469 cells and the frequency of stable CAs assessed by whole chromosome painting of chromosomes 1, 2, 4, 5, 7 and 17 using fluorescence in situ hybridization. Our results show that 25 μM of B[a]P and most of the tested doses of EOMs induced DSBs as indicated by H2AX phosphorylation. DNA damage was accompanied by induction of XRCC4 expression and an increased frequency of CAs. Translocations most frequently affected chromosome 7. We observed only a weak induction of Ku70/80 expression as well as ligation activity of nuclear extracts. In summary, our data suggest the induction of DSBs and

  17. High-LET Radiation Induced Chromosome Aberrations in Normal and Ataxia Telangiectasia Fibroblast Cells

    Science.gov (United States)

    Kawata, Tetsuya; George, Ms Kerry; Cucinotta, Francis A.; Shigematsu, Naoyuki; Ito, Hisao; Furusawa, Yoshiya; Uno, Takashi

    We investigated the effects of heavy ions beams on chromosomal aberrations in normal and AT cells. Normal and AT fibroblast cells arrested at G0/G1 phase were irradiated with 2 Gy of X-rays, 490 MeV/u Silicon (LET 55 keV/micron), 500 MeV/u Iron (LET 185 keV/micron) and 200 MeV/u Iron (LET 440 keV/micron) particles, and then cells were allowed to repair for 24 hours at 37 degrees before subculture. Calyculin-A induced PCC method was employed to collect G2/M chromosomes and whole DNA probes 1 and 3 were used to analyze chromosomal aberrations such as color-junctions, deletions, simple exchanges (incomplete and reciprocal exchanges) and complex-type exchanges. The percentages of aberrant cells were higher when normal and AT cells were exposed to heavy ions compared to X-rays, and had a tendency to increase with increasing LET up to 185 keV/micron and then decreased at 440 keV/micron. When the frequency of color-junctions per cell was compared after X-ray exposure, AT cells had around three times higher frequency of color-junctions (mis-rejoining) than normal cells. However, at 185 keV/micron there was no difference in the frequency of color-junctions between two cell lines. It was also found that the frequency of simple exchanges per cell was almost constant in AT cells regardless LET levels, but it was LET dependent for normal cells. Interestingly, the frequency of simple exchanges was higher for normal fibroblast cells when it was compared at 185 keV/micron, but AT cells had more complex-type exchanges at the same LET levels. Heavy ions are more efficient in inducing chromosome aberrations in normal and AT cells compared to X-rays, and the aberration types between normal and AT fibroblast appeared different probably due to difference in the ATM gene function.

  18. Evaluation of genotoxicity of Trois through Ames and in vitro chromosomal aberration tests

    Institute of Scientific and Technical Information of China (English)

    Manu Chaudhary; Anurag Payasi

    2013-01-01

    Objective: To investigate the mutagenic potential of Trois using the bacterial reverse mutation assay (Ames test) and in vitro chromosomal aberration test.Methods:typhimurium (TA 98, TA100, TA1535 and TA1537) and Escherichia coli (WP2 uvrA) with and without metabolic activation system (S9 mix) at the dose range of 313 to 5000 µg/plate. Chromosomal aberrations were evaluated in Chinese hamster lung (CHL) cell line at the dose levels of 15, 7.5, 3.7, 1.9 and 0.9 mg/mL in the absence and presence of S9 mix.Results:The ability of Trois to induce reverse mutations was evaluated in Salmonella Trois used in the study with and without S9 mix in all tester strains. Trois did not produce any structural aberration in CHL cells in the presence or absence of S9 mix. There were no increases in the number of revertant colonies at any concentrations of Conclusions: Results of this study suggest that Trois is non-mutagenic.

  19. Drinking beer reduces radiation-induced chromosome aberrations in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Monobe, Manami [Chiba Univ. (Japan). Graduate School of Science and Technology; Ando, Koichi [National Inst. of Radiological Sciences, Chiba (Japan)

    2002-09-01

    We here investigated and reported the effects of beer drinking on radiation-induced chromosome aberrations in blood lymphocytes. Human blood that was collected either before or after drinking a 700 ml beer was in vitro irradiated with 200 kVp X rays or 50 keV/{mu}m carbon ions. The relation between the radiation dose and the aberration frequencies (fragments and dicentrics) was significantly (P<0.05) lower for lymphocytes collected 3 h after beer drinking than those before drinking. Fitting the dose response to a linear quadratic model showed that the alpha term of carbon ions was significantly (P<0.05) decreased by beer drinking. A decrease of dicentric formation was detected as early as 0.5 h after beer drinking, and lasted not shorter than 4.5 h. The mitotic index of lymphocytes was higher after beer drinking than before, indicating that a division delay would not be responsible for the low aberrations induced by beer drinking. An in vitro treatment of normal lymphocytes with 0.1 M ethanol, which corresponded to a concentration of 6-times higher than the maximum ethanol concentration in the blood after beer drinking, reduced the dicentric formation caused by X-ray irradiation, but not by carbon-ion irradiation. The beer-induced reduction of dicentric formation was not affected by serum. It is concluded that beer could contain non-ethanol elements that reduce the chromosome damage of lymphocytes induced by high-LET radiation. (author)

  20. Development of a two-parameter slit-scan flow cytometer for screening of normal and aberrant chromosomes: application to a karyotype of Sus scrofa domestica (pig)

    Science.gov (United States)

    Hausmann, Michael; Doelle, Juergen; Arnold, Armin; Stepanow, Boris; Wickert, Burkhard; Boscher, Jeannine; Popescu, Paul C.; Cremer, Christoph

    1992-07-01

    Laser fluorescence activated slit-scan flow cytometry offers an approach to a fast, quantitative characterization of chromosomes due to morphological features. It can be applied for screening of chromosomal abnormalities. We give a preliminary report on the development of the Heidelberg slit-scan flow cytometer. Time-resolved measurement of the fluorescence intensity along the chromosome axis can be registered simultaneously for two parameters when the chromosome axis can be registered simultaneously for two parameters when the chromosome passes perpendicularly through a narrowly focused laser beam combined by a detection slit in the image plane. So far automated data analysis has been performed off-line on a PC. In its final performance, the Heidelberg slit-scan flow cytometer will achieve on-line data analysis that allows an electro-acoustical sorting of chromosomes of interest. Interest is high in the agriculture field to study chromosome aberrations that influence the size of litters in pig (Sus scrofa domestica) breeding. Slit-scan measurements have been performed to characterize chromosomes of pigs; we present results for chromosome 1 and a translocation chromosome 6/15.

  1. Dependence of Early and Late Chromosomal Aberrations on Radiation Quality and Cell Types

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Rohde, Larry; Wu, Honglu

    2017-01-01

    Exposure to radiation induces different types of DNA damage, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo. The susceptibility of cells to radiation depends on genetic background and growth condition of cells, as well as types of radiation. Mammalian cells of different tissue types and with different genetic background are known to have different survival rate and different mutation rate after cytogenetic insults. Genomic instability, induced by various genetic, metabolic, and environmental factors including radiation, is the driving force of tumorigenesis. Accurate measurements of the relative biological effectiveness (RBE) is important for estimating radiation-related risks. To further understand genomic instability induced by charged particles and their RBE, we exposed human lymphocytes ex vivo, human fibroblast AG1522, human mammary epithelial cells (CH184B5F5/M10), and bone marrow cells isolated from CBA/CaH(CBA) and C57BL/6 (C57) mice to high energy protons and Fe ions. Normal human fibroblasts AG1522 have apparently normal DNA damage response and repair mechanisms, while mammary epithelial cells (M10) are deficient in the repair of DNA DSBs. Mouse strain CBA is radio-sensitive while C57 is radio-resistant. Metaphase chromosomes at different cell divisions after radiation exposure were collected and chromosome aberrations were analyzed as RBE for different cell lines exposed to different radiations at various time points up to one month post irradiation.

  2. A recurrent pattern of chromosomal aberrations and immunophenotypic appearance defines anal squamous cell carcinomas.

    Science.gov (United States)

    Heselmeyer, K; du Manoir, S; Blegen, H; Friberg, B; Svensson, C; Schröck, E; Veldman, T; Shah, K; Auer, G; Ried, T

    1997-01-01

    Squamous cell carcinomas of the anus are rare neoplasias that account for about 3% of large bowel tumours. Infections with human papillomaviruses are frequently detected in these cancers, suggesting that pathogenic pathways in anal carcinomas and in carcinomas of the uterine cervix are similar. Little is known regarding recurrent chromosomal aberrations in this subgroup of squamous cell carcinomas. We have applied comparative genomic hybridization to identify chromosomal gains and losses in 23 cases of anal carcinomas. A non-random copy number increase of chromosomes 17 and 19, and chromosome arm 3q was observed. Consistent losses were mapped to chromosome arms 4p, 11q, 13q and 18q. A majority of the tumours were aneuploid, and most of them showed increased proliferative activity as determined by staining for Ki-67 antigen. p53 expression was low or undetectable, and expression of p21/WAF-1 was increased in most tumours. Sixteen cancers were satisfactorily tested for the presence of HPV by consensus L1-primer polymerase chain reaction; nine were HPV positive, of which eight were positive for HPV 16.

  3. The effects of exposure to different clastogens on the pattern of chromosomal aberrations detected by FISH whole chromosome painting in occupationally exposed individuals

    Energy Technology Data Exchange (ETDEWEB)

    Beskid, O. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Dusek, Z. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Solansky, I. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Sram, R.J. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic)]. E-mail: sram@biomed.cas.cz

    2006-02-22

    The pattern of chromosomal aberrations (CA) was studied by fluorescence in situ hybridization (FISH) technique (whole chromosomes 1 and 4 painting) in workers occupationally exposed to any of the four following conditions: acrylonitrile (ACN), ethyl benzene (EB), carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), and irradiation in nuclear power plants (NPP), respectively. Decrease in the relative frequency of translocations was observed in EB group, and an increase in reciprocal translocations in ACN and NPP-exposed groups. An increase in a relative number of insertions was registered under all four conditions (significant at ACN, EB, c-PAHs, quasisignificant at NPP-exposed groups). Significant differences in the percentage of lymphocytes with aberrations on chromosome 1 (58.8 {+-} 32.7%, versus 73.8 {+-} 33.6% in the controls, P < 0.05), and chromosome 4 (47.0 {+-} 34.1%, versus 29.4 {+-} 32.2%, P < 0.01) were found in workers exposed to ACN. Similarly, a decrease in the proportion of cells with aberration on chromosome 1 (61.0 {+-} 24.0%, versus 73.8 {+-} 33.6%, P < 0.05) and an increase on chromosome 4 (45.6 {+-} 24.6%, versus 29.4 {+-} 32.2%, P < 0.05) were observed in workers exposed to EB. Frequency of aberrant cells (%AB.C.) as well as genomic frequency of translocations (F {sub G}/100) increased with age (P < 0.001). Aging also increased the percentage of translocations and reciprocal translocations (P < 0.05), but decreased the relative number of acentric fragments (P < 0.01). Smoking led to significantly increased F {sub G}/100 (P < 0.05), but did not affect the pattern of chromosomal aberrations. Our results seem to indicate that different carcinogens may induce a different pattern of chromosomal aberrations.

  4. Brahmarasayana protects against Ethyl methanesulfonate or Methyl methanesulfonate induced chromosomal aberrations in mouse bone marrow cells

    Directory of Open Access Journals (Sweden)

    Guruprasad Kanive

    2012-08-01

    Full Text Available Abstract Background Ayurveda, the traditional Indian system of medicine has given great emphasis to the promotion of health. Rasayana is one of the eight branches of Ayurveda which refers to rejuvenant therapy. It has been reported that rasayanas have immuno-modulatory, antioxidant and antitumor functions, however, the genotoxic potential and modulation of DNA repair of many rasayanas have not been evaluated. Methods The present study assessed the role of Brahmarasayana (BR on Ethyl methanesulfonate (EMS-and Methyl methanesulfonate (MMS-induced genotoxicity and DNA repair in in vivo mouse test system. The mice were orally fed with BR (5 g or 8 mg / day for two months and 24 h later EMS or MMS was given intraperitoneally. The genotoxicity was analyzed by chromosomal aberrations, sperm count, and sperm abnormalities. Results The results have revealed that BR did not induce significant chromosomal aberrations when compared to that of the control animals (p >0.05. On the other hand, the frequencies of chromosomal aberrations induced by EMS (240 mg / kg body weight or MMS (125 mg / kg body weight were significantly higher (p Conclusion The effect of BR, as it relates to antioxidant activity was not evident in liver tissue however rasayana treatment was observed to increase constitutive DNA base excision repair and reduce clastogenicity. Whilst, the molecular mechanisms of such repair need further exploration, this is the first report to demonstrate these effects and provides further evidence for the role of brahmarasayana in the possible improvement of quality of life.

  5. Radiation induced chromosome aberrations in somatic and germ cells of the male marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Brewen, J. G.; Preston, R. J.

    1977-01-01

    The induction of chromosome aberrations by low LET radiations was studied in peripheral lymphocytes and spermatogonial stem cells of the male marmoset. The data showed that there was no significant difference in the sensitivity of the lymphocytes whether they were irradiated in vitro or in vivo, but the frequency of heritable translocations recovered in the primary spermatocytes was considerably lower than that calculated to occur in the lymphocytes. The data are used to make estimates of human genetic risk from radiation based on limited interspecific comparisons.

  6. Radiation-induced chromosome aberrations in somatic and germ cells of the male marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Brewen, J.G.; Preston, R.J.

    1978-01-01

    The induction of chromosome aberrations by low LET radiations was studied in peripheral lymphocytes and spermatogonial stem cells of the male marmoset. The data showed that there was not significant difference in the sensitivity of the lymphocytes whether they were irradiated in vitro or in vivo, but the frequency of heritable translocations recovered in the primary spermatocytes were considerably lower than that calculated to occur in the lymphocytes. The data are used to make estimates of human genetic risk from radiation based on limited interspecific comparisons.

  7. Genotoxicity evaluation of dimethoate to experimental mice by micronucleus, chromosome aberration tests, and comet assay.

    Science.gov (United States)

    Ayed-Boussema, Imen; Rjiba, Karima; Mnasri, Nourhène; Moussa, Amal; Bacha, Hassen

    2012-01-01

    Dimethoate (DM) is an organophosphate insecticide with numerous uses on field and agricultural crops and ornamentals. Data concerning DM-acute genotoxicity are controversial and knowledge on its delayed effect is limited. For this reason, we aimed to further explore DM genotoxicity resulting from subchronic intoxication of experimental mice. Thus, DM was administered to mice at doses ranging from 1 to 30 mg/kg body weight for a period of 30 consecutive days. There was a significant increase (P < .05) in the frequency of micronucleated bone marrow cells following DM administration. Furthermore, the chromosome aberration assay revealed a significant increase in the percentage of chromosome abnormalities in a dose-dependent manner. Dimethoate was also found to induce significant DNA damage in mouse bone marrow cells as assessed by the comet assay. Altogether, our results showed that, after a subchronic exposure, DM was a genotoxic compound in experimental mice.

  8. 七例疑似受照的医疗工作人员染色体畸变分析%Analysis of chromosomal aberration in seven medical staffs suspected with exposure to ionizing radiation

    Institute of Scientific and Technical Information of China (English)

    韩林; 赵风玲; 王喜爱; 王平; 姜峰; 吕玉民

    2012-01-01

    目的 通过对怀疑受到电离辐射照射的医疗工作人员进行外周血淋巴细胞染色体畸变分析,探讨可能的受影响因素.方法 某医院检验科工作人员7名,男性1名,女性6名.他们工作室的楼下是医院CT室,工作室和CT室间的楼板为厚度约6 cm的普通预制板.采用常规法,对7名人员外周血淋巴细胞染色体畸变进行分析.结果 4例女性工作人员外周血中检测到双着丝粒体(dic),dic率为0.40% ~ 1.60%,明显高于dic的自发率(0.03%,x2=36.79,P<0.05);在所有工作人员中均检测到易位畸变,易位率在0.33%~1.20%之间,明显高于易位的自发率(0.01%,X2=42.90,P<0.05).结论 推测这些工作人员受到过量电离辐射照射.%Objective To investigate the chromosomal aberrations in seven medical staffs suspected with exposure to ionizing radiation and to speculate its possible causation.Methods The hospital staffs,including 6 females and 1 male,worked in a clinical laboratory where a CT room was located downstairs.The thickness of precast slab between these two rooms was 6 cm.Peripheral blood lymphocytes of seven staffs were examined for conventional chromosomal aberrations.Results The frequencies of dicentrics in the peripheral lymphocytes of 4 females were from 0.40% to 1.60% that was significantly higher than the spontaneous frequency of dicentrics (0.03%,x2 =36.79,P < 0.05).The translocation was observed in the lymphocytes from all subjects with frequencies from 0.33% to 1.20%,obviously higher than its spontaneous frequency of 0.01% (x2 =42.90,P < 0.05).Conclusion These staffs suffer from ionizing radiation.

  9. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira

    2016-01-01

    An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

  10. Cells bearing chromosome aberrations lacking one telomere are selectively blocked at the G2/M checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Pilar [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Barquinero, Joan Francesc [Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Duran, Assumpta [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Caballin, Maria Rosa [Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Ribas, Montserrat [Servei de Radiofisica i Radioproteccio de l' Hospital de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Barrios, Leonardo, E-mail: Lleonard.Barrios@uab.cat [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain)

    2009-11-02

    Cell cycle checkpoints are part of the cellular mechanisms to maintain genomic integrity. After ionizing radiation exposure, the cells can show delay or arrest in their progression through the cell cycle, as well as an activation of the DNA repair machinery in order to reduce the damage. The G2/M checkpoint prevents G2 cells entering mitosis until the DNA damage has been reduced. The present study evaluates which G0 radiation-induced chromosome aberrations are negatively selected in the G2/M checkpoint. For this purpose, peripheral blood samples were irradiated at 1 and 3 Gy of {gamma}-rays, and lymphocytes were cultured for 48 h. Calyculin-A and Colcemid were used to analyze, in the same slide, cells in G2 and M. Chromosome spreads were consecutively analyzed by solid stain, pancentromeric and pantelomeric FISH and mFISH. The results show that the frequency of incomplete chromosome elements, those lacking a telomeric signal at one end, decreases abruptly from G2 to M. This indicates that cells with incomplete chromosome elements can progress from G0 to G2, but at the G2/M checkpoint suffer a strong negative selection.

  11. Detection of Inter-chromosomal Stable Aberrations by Multiple Fluorescence In Situ Hybridization (mFISH) and Spectral Karyotyping (SKY) in Irradiated Mice.

    Science.gov (United States)

    Pathak, Rupak; Koturbash, Igor; Hauer-Jensen, Martin

    2017-01-11

    Ionizing radiation (IR) induces numerous stable and unstable chromosomal aberrations. Unstable aberrations, where chromosome morphology is substantially compromised, can easily be identified by conventional chromosome staining techniques. However, detection of stable aberrations, which involve exchange or translocation of genetic materials without considerable modification in the chromosome morphology, requires sophisticated chromosome painting techniques that rely on in situ hybridization of fluorescently labeled DNA probes, a chromosome painting technique popularly known as fluorescence in situ hybridization (FISH). FISH probes can be specific for whole chromosome/s or precise sub-region on chromosome/s. The method not only allows visualization of stable aberrations, but it can also allow detection of the chromosome/s or specific DNA sequence/s involved in a particular aberration formation. A variety of chromosome painting techniques are available in cytogenetics; here two highly sensitive methods, multiple fluorescence in situ hybridization (mFISH) and spectral karyotyping (SKY), are discussed to identify inter-chromosomal stable aberrations that form in the bone marrow cells of mice after exposure to total body irradiation. Although both techniques rely on fluorescent labeled DNA probes, the method of detection and the process of image acquisition of the fluorescent signals are different. These two techniques have been used in various research areas, such as radiation biology, cancer cytogenetics, retrospective radiation biodosimetry, clinical cytogenetics, evolutionary cytogenetics, and comparative cytogenetics.

  12. Chromosome aberrations, micronucleus and sperm head abnormalities in mice treated with natamycin, [corrected] a food preservative.

    Science.gov (United States)

    Rasgele, Pinar Goc; Kaymak, Fisun

    2010-03-01

    Natamycin [corrected] is used as preservative in foods. The genotoxic effects of the food preservative natamycin [corrected] were evaluated using chromosome aberrations and micronucleus test in bone marrow cells and sperm head abnormality assays in mice. Blood samples were taken from mice and levels of total testosterone in serum were also determined. Natamycin [corrected] was intraperitoneally (ip) injected at 200, 400 and 800 mg/kg. Natamycin [corrected] did not induce chromosome aberrations but significantly increased the number of micronucleated polychromatic erythrocytes in bone marrow and sperm head abnormalities at all concentrations and treatment periods. It also decreased MI at all concentrations for 6, 12 and 24h treatment periods. Natamycin [corrected] decreased PCE/NCE ratio at all concentrations for 48h in female mice, for 24 and 48h treatment periods in male mice. At the 800 mg/kg concentration, natamycin [corrected] decreased PCE/NCE ratio for 24 and 72h in female mice. A dose dependent increase was observed in the percentage of sperm head abnormalities. The levels of serum testosterone decreased dose-dependently. The obtained results indicate that natamycin [corrected] is not clastogenic, but it is aneugenic in mice bone marrow and it is a potential germ cell mutagen in sperm cells.

  13. Genotoxicity evaluation of dental restoration nanocomposite using comet assay and chromosome aberration test

    Science.gov (United States)

    Musa, Marahaini; Thirumulu Ponnuraj, Kannan; Mohamad, Dasmawati; Rahman, Ismail Ab

    2013-01-01

    Nanocomposite is used as a dental filling to restore the affected tooth, especially in dental caries. The dental nanocomposite (KelFil) for tooth restoration used in this study was produced by the School of Dental Sciences, Universiti Sains Malaysia, Malaysia and is incorporated with monodispersed, spherical nanosilica fillers. The aim of the study was to determine the genotoxic effect of KelFil using in vitro genotoxicity tests. The cytotoxicity and genotoxicity of KelFil was evaluated using MTT assay, comet assay and chromosome aberration tests with or without the addition of a metabolic activation system (S9 mix), using the human lung fibroblast cell line (MRC-5). Concurrent negative and positive controls were included. In the comet assay, no comet formation was found in the KelFil groups. There was a significant difference in tail moment between KelFil groups and positive control (p < 0.05). Similarly, no significant aberrations in chromosomes were noticed in KelFil groups. The mitotic indices of treatment groups and negative control were significantly different from positive controls. Hence, it can be concluded that the locally produced dental restoration nanocomposite (KelFil) is non-genotoxic under the present test conditions.

  14. Effect of aspirin on chromosome aberration and DNA damage induced by X-rays in mice

    Science.gov (United States)

    Niikawa, M.; Chuuriki, K.; Shibuya, K.; Seo, M.; Nagase, H.

    In order to reveal the anticlastogenic potency of aspirin, we evaluated the suppressive ability of aspirin on chromosome aberrations induced by X-ray. Aspirin at doses of 0.5, 5 and 50 mg/kg was administrated intraperitoneally or orally at 0.5 h after or before the X-ray irradiation. The anticlastogenic activity of aspirin on chromosome aberrations induced by X-ray was determined in the mouse micronucleus test and alkaline single cell gel electrophoresis (SCG) assay in vivo. The frequency by polychromatic erythrocytes with micronuclei (MNPCEs) was decreased by about 19-61% at 0.5 h after and about 23-62% at 0.5 h before the X-ray irradiation. DNA damage by X-ray was significantly decreased by oral administration of aspirin at 0.5 h after or before the X-ray irradiation for the SCG assay. We consider aspirin can be used as preventive agents against exposure of X-ray.

  15. Recurrent chromosomal aberrations in intravenous leiomyomatosis of the uterus: high-resolution array comparative genomic hybridization study.

    Science.gov (United States)

    Buza, Natalia; Xu, Fang; Wu, Weiqing; Carr, Ryan J; Li, Peining; Hui, Pei

    2014-09-01

    Uterine intravenous leiomyomatosis (IVL) is a distinct smooth muscle neoplasm with a potential of clinical aggressiveness due to its ability to extend into intrauterine and extrauterine vasculature. In this study, chromosomal alterations analyzed by oligonucleotide array comparative genomic hybridization were performed in 9 cases of IVL. The analysis was informative in all cases with multiple copy number losses and/or gains observed in each tumor. The most frequent recurrent loss of 22q12.3-q13.1 was observed in 6 tumors (66.7%), followed by losses of 22q11.23-q13.31, 1p36.13-p33, 2p25.3-p23.3, and 2q24.2-q32.2 and gains of 6p22.2, 2q37.3 and 10q22.2-q22.3, in decreasing order of frequency. Copy number variants were identified at 14q11.2, 15q11.1-q11.2, and 15q26.2. Genes mapping to the regions of loss include CHEK2, EWS, NF2, PDGFB, and MAP3K7IP1 on chromosome 22q, HEI10 on chromosome 14q, and succinate dehydrogenase subunit B, E2F2, ARID1A KPNA6, EIF3S2 , PTCH2, and PIK3R3 on chromosome 1p. Regional losses on chromosomes 22q and 1p and gains on chromosomes 12q showed overlaps with those previously observed in uterine leiomyosarcomas. In addition, presence of multiple chromosomal aberrations implies a higher level of genetic instability. Follow-up polymerase chain reaction (PCR) sequencing analysis of MED12 gene revealed absence of G> A transition at nucleotides c.130 or c.131 in all 9 cases, a frequent mutation found in uterine leiomyoma and its variants. In conclusion, this is the first report of high-resolution, genome-wide investigation of IVL by oligonucleotide array comparative genomic hybridization. The presence of high frequencies of recurrent regional loss involving several chromosomes is an important finding and likely related to the pathogenesis of the disease.

  16. A model for interphase chromosomes and evaluation of radiation-induced aberrations

    Science.gov (United States)

    Holley, W. R.; Mian, I. S.; Park, S. J.; Rydberg, B.; Chatterjee, A.

    2002-01-01

    We have developed a theoretical model for evaluating radiation-induced chromosomal exchanges by explicitly taking into account interphase (G(0)/G(1)) chromosome structure, nuclear organization of chromosomes, the production of double-strand breaks (DSBs), and the subsequent rejoinings in a faithful or unfaithful manner. Each of the 46 chromosomes for human lymphocytes (40 chromosomes for mouse lymphocytes) is modeled as a random polymer inside a spherical volume. The chromosome spheres are packed randomly inside a spherical nucleus with an allowed overlap controlled by a parameter Omega. The rejoining of DSBs is determined by a Monte Carlo procedure using a Gaussian proximity function with an interaction range parameter sigma. Values of Omega and sigma have been found which yield calculated results of interchromosomal aberration frequencies that agree with a wide range of experimental data. Our preferred solution is one with an interaction range of 0.5 microm coupled with a relatively small overlap parameter of 0.675 microm, which more or less confirms previous estimates. We have used our model with these parameter values and with resolution or detectability limits to calculate yields of translocations and dicentrics for human lymphocytes exposed to low-LET radiation that agree with experiments in the dose range 0.09 to 4 Gy. Five different experimental data sets have been compared with the theoretical results. Essentially all of the experimental data fall between theoretical curves corresponding to resolution limits of 1 Mbp and 20 Mbp, which may reflect the fact that different investigators use different limits for sensitivity or detectability. Translocation yields for mouse lymphocytes have also been calculated and are in good agreement with experimental data from 1 cGy to 10 cGy. There is also good agreement with recent data on complex aberrations. Our model is expected to be applicable to both low- and high-LET radiation, and we include a sample prediction of

  17. Evaluation of radiosensitivity of human tumor cells after irradiation of γ-rays based on G2-chromosome aberrations

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The aim of the present investigation is to determine initial G2-chromosome aberrations and to validate whether the G2-chromosome aberrations can predict the cellular clonogenic survival in human tumor cell lines. Cell lines of human ovary carcinoma cells (HO8910) and human hepatoma cells (HepG2) were irradiated with a range of doses and assessed both for initial G2-chromosome aberrations and for cell survival after γ-irradiation. The initial G2-chromosome aberrations were measured by counting the number of G2-chromatid breaks after irradiation, detected by the premature chromosome condensation technique, and the G2-assay method. Cell survival was documented by a colony formation assay. A linear-quadratic survival curve was observed in both cell lines. The dose-response results show that the numbers of G2-chromatid breaks increase with the increase in dose in the two cell lines. At higher doses (higher than 4 Gy) of irradiation, the number of G2-chromatid breaks for the G2-assay method cannot be determined because too few cells reach mitosis, and hence their detection is difficult. A good correlation is found between the clonogenic survival and the radiation-induced initial G2-chromatid breaks per cell (r=0.9616). The present results suggest that the premature chromosome condensation technique may be useful for determining chromatid breaks in G2 cells, and the number of initial G2-chromatid breaks holds promise for predicting the radiosensitivity of tumor cells.

  18. Chromosomes in the flow to simplify genome analysis.

    Science.gov (United States)

    Doležel, Jaroslav; Vrána, Jan; Safář, Jan; Bartoš, Jan; Kubaláková, Marie; Simková, Hana

    2012-08-01

    Nuclear genomes of human, animals, and plants are organized into subunits called chromosomes. When isolated into aqueous suspension, mitotic chromosomes can be classified using flow cytometry according to light scatter and fluorescence parameters. Chromosomes of interest can be purified by flow sorting if they can be resolved from other chromosomes in a karyotype. The analysis and sorting are carried out at rates of 10(2)-10(4) chromosomes per second, and for complex genomes such as wheat the flow sorting technology has been ground-breaking in reducing genome complexity for genome sequencing. The high sample rate provides an attractive approach for karyotype analysis (flow karyotyping) and the purification of chromosomes in large numbers. In characterizing the chromosome complement of an organism, the high number that can be studied using flow cytometry allows for a statistically accurate analysis. Chromosome sorting plays a particularly important role in the analysis of nuclear genome structure and the analysis of particular and aberrant chromosomes. Other attractive but not well-explored features include the analysis of chromosomal proteins, chromosome ultrastructure, and high-resolution mapping using FISH. Recent results demonstrate that chromosome flow sorting can be coupled seamlessly with DNA array and next-generation sequencing technologies for high-throughput analyses. The main advantages are targeting the analysis to a genome region of interest and a significant reduction in sample complexity. As flow sorters can also sort single copies of chromosomes, shotgun sequencing DNA amplified from them enables the production of haplotype-resolved genome sequences. This review explains the principles of flow cytometric chromosome analysis and sorting (flow cytogenetics), discusses the major uses of this technology in genome analysis, and outlines future directions.

  19. High- and low-LET Radiation-induced Chromosome Aberrations in Human Epithelial Cells Cultured in 3-dimensional Matrices

    Science.gov (United States)

    Hada, M.; George K.; Cucinotta, F. A.; Wu, H.

    2008-01-01

    Energetic heavy ions pose a great health risk to astronauts who participate in extended ISS missions and will be an even greater concern for future manned lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D in vitro cellular environment can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelial cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultured at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected in the first cell cycle after irradiation using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference in the

  20. Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction.

    Science.gov (United States)

    Shamsi, Monis B; Kumar, Rajeev; Malhotra, Neena; Singh, Nita; Mittal, Suneeta; Upadhyay, Ashish D; Dada, Rima

    2012-09-01

    Male infertility is a multi-factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non-azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males.

  1. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  2. DNA methylation signature in peripheral blood reveals distinct characteristics of human X chromosome numerical aberrations

    OpenAIRE

    2015-01-01

    Background Abnormal sex chromosome numbers in humans are observed in Turner (45,X) and Klinefelter (47,XXY) syndromes. Both syndromes are associated with several clinical phenotypes, whose molecular mechanisms are obscure, and show a range of inter-individual penetrance. In order to understand the effect of abnormal numbers of X chromosome on the methylome and its correlation to the variable clinical phenotype, we performed a genome-wide methylation analysis using MeDIP and Illumina’s Infiniu...

  3. Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH)

    DEFF Research Database (Denmark)

    Hagmar, L; Bonassi, S; Strömberg, U;

    1998-01-01

    Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased...... cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hypothesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a pooled analysis of updated data for 3541 subjects...... examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variation, the results for the various cytogenetic end points were trichotomized on the basis of the absolute value distribution within each laboratory as "low" (1-33 percentile), "medium" (34-66 percentile), or "high" (67...

  4. Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

    Science.gov (United States)

    Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

    2011-01-01

    Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

  5. Comparison of RBE values of high- LET α-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death

    Directory of Open Access Journals (Sweden)

    Aten Jacob

    2011-06-01

    Full Text Available Abstract Background Various types of radiation effects in mammalian cells have been studied with the aim to predict the radiosensitivity of tumours and normal tissues, e.g. DNA double strand breaks (DSB, chromosome aberrations and cell reproductive inactivation. However, variation in correlations with clinical results has reduced general application. An additional type of information is required for the increasing application of high-LET radiation in cancer therapy: the Relative Biological Effectiveness (RBE for effects in tumours and normal tissues. Relevant information on RBE values might be derived from studies on cells in culture. Methods To evaluate relationships between DNA-DSB, chromosome aberrations and the clinically most relevant effect of cell reproductive death, for ionizing radiations of different LET, dose-effect relationships were determined for the induction of these effects in cultured SW-1573 cells irradiated with gamma-rays from a Cs-137 source or with α-particles from an Am-241 source. RBE values were derived for these effects. Ionizing radiation induced foci (IRIF of DNA repair related proteins, indicative of DSB, were assessed by counting gamma-H2AX foci. Chromosome aberration frequencies were determined by scoring fragments and translocations using premature chromosome condensation. Cell survival was measured by colony formation assay. Analysis of dose-effect relations was based on the linear-quadratic model. Results Our results show that, although both investigated radiation types induce similar numbers of IRIF per absorbed dose, only a small fraction of the DSB induced by the low-LET gamma-rays result in chromosome rearrangements and cell reproductive death, while this fraction is considerably enhanced for the high-LET alpha-radiation. Calculated RBE values derived for the linear components of dose-effect relations for gamma-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0 ± 0.3, 14

  6. Persistence of unstable and stable chromosome aberrations in lymphocytes of cancer patients treated with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Di Giorgio, M.; Vallerga, M.B.; Taja, M.R. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Sardi, M. [Hospital Italiano - Mevaterapia, Buenos Aires (Argentina)

    2006-07-01

    Background: Radiation-induced DNA damage in human lymphocytes has equal probability of producing both stable or unstable chromosome aberrations (C.A.). Reports of its in vivo persistence show considerable variations. The quantification of unstable C.A. (dicentrics) in peripheral blood lymphocytes (P.B.L.) is the most reliable biological method for estimating whole-body doses of recent overexposures to ionizing radiation. Given that during the division of T cell precursors, proliferative death of cells containing dicentrics reduces the number of such lymphocytes in peripheral blood, dicentric methodology should be modified to account for past exposures. Micronuclei (M.N.) in cytokinesis-blocked human P.B.L. are well established bio markers for assessing radiation damage in vivo. However, persistence of radiation induced M.N. is limited. Unlike dicentrics and M.N., stable C.A. (translocations) identified at present by the FISH technique, seem to be an adequate indicator for the dosimetric evaluation of past exposures, since translocations are not selected against during mitotic division in the haematopoietic stem cells compartment. Nevertheless, for partial -body exposures with high dose there is some evidence that the decline with time of dicentrics causes some reduction in the yield of translocations. Purpose: To assess the persistence along time of dicentrics, M.N. and translocations in lymphocytes of cancer patients after radiotherapy in order to model changes in C.A. frequencies with partial-body exposures. Materials and methods: 22 cancer patients with different tumor sites, treated with radiotherapy, were evaluated through dicentric chromosome, M.N. and FISH techniques with a follow-up time of up to 90 months after the end of radiotherapy. Regression analysis were performed: 1) for dicentric and for M.N. frequencies in relation to time after the end of radiotherapy and total tumor dose; 2) for the percentage of uns table cells in relation to time after the end

  7. Chromosomal aberrations in the bone marrow cells of mice induced by accelerated {sup 12}C{sup 6+} ions

    Energy Technology Data Exchange (ETDEWEB)

    Ma Xiaofei [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang Hong, E-mail: zhangh@impac.ac.cn [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Wang Zhenhua; Min Xianhua; Liu Yang; Wu Zhenhua [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Sun Chao [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Hu Bitao [School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000 (China)

    2011-11-01

    Highlights: {yields} 220 MeV/u {sup 12}C{sup 6+} ions is 1.5 times more effective than X-rays in inducing chromosomal aberration in bone marrow cell. {yields} The ratio of dose averaged liner energy transfer is approach the RBE. {yields} {sup 12}C{sup 6+} ions could induce severe mitosis delay. {yields} The cell cycle is not recovered 72 h following irradiation. - Abstract: The whole bodies of 6-week-old male Kun-Ming mice were exposed to different doses of {sup 12}C{sup 6+} ions or X-rays. Chromosomal aberrations of the bone marrow (gaps, terminal deletions and breaks, fragments, inter-chromosomal fusions and sister-chromatid union) were scored in metaphase 9 h after exposure, corresponding to cells exposed in the G{sub 2}-phase of the first mitosis cycle. Dose-response relationships for the frequency of chromosomal aberrations were plotted both by linear and linear-quadratic equations. The data showed that there was a dose-related increase in the frequency of chromosomal aberrations in all treated groups compared to controls. Linear-quadratic equations were a good fit for both radiation types. The compound theory of dual radiation action was applied to decipher the bigger curvature (D{sup 2}) of the dose-response curves of X-rays compared to those of {sup 12}C{sup 6+} ions. Different distributions of the five types of aberrations and different degrees of homogeneity were found between {sup 12}C{sup 6+} ion and X-ray irradiation and the possible underlying mechanism for these phenomena were analyzed according to the differences in the spatial energy deposition of both types of radiation.

  8. Effects of chronic restraint-induced stress on radiation-induced chromosomal aberrations in mouse splenocytes.

    Science.gov (United States)

    Katsube, Takanori; Wang, Bing; Tanaka, Kaoru; Ninomiya, Yasuharu; Varès, Guillaume; Kawagoshi, Taiki; Shiomi, Naoko; Kubota, Yoshihisa; Liu, Qiang; Morita, Akinori; Nakajima, Tetsuo; Nenoi, Mitsuru

    2017-01-01

    Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53(+/-)) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53(+/+)) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53(+/+) C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR.

  9. Structural chromosomal aberrations in bone-marrow cells of single and fractionally irradiated adeturone-protected rats

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, B.; Bulanova, M.; Pantev, T.; Mileva, M (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1981-01-01

    Single irradiation with doses of 0.0516 K/kg and 0.1032 K/kg and fractionated twice with a dose of 0.0516 K/kg at intervals between the two irradiations of 3, 6 and 17 hours were performed in sexually mature wistar rats, using cesium gamma-source ''IGUR-1''. Single and fractionated irradiation was associated with the radiomodifying effect of the protector adeturone, which was administered before the first and second irradiation to elucidate its effect and the mechanism of its protective action. Bone-marrow cell preparation for chromosomal analysis was made from irradiated and protected animals 20 hours after irradiation. The quantitative results were statistically analyzed, showing that adeturone has a potent peotective effect on single-irradiated animals. In animals exposed to fractionated irradiation with adeturone applied before the first and second irradiation procedure at 3 and 6 hours between the two fractions. There was a statistically lower yield of chromosomal aberrations, than after a single irradiation. A marked protective effect of adeturone was noticed also between a fractionated irradiation and a fractionated with protection one, when the protector was administered before the first or second irradiation with 3 and 6 hours between them. No such effect has been observed at a 17 hour interval between the two irradiations. These data show that adeturone intensifies the repair process in irradiated cells. The semi restoration period in protected animals was twice as low.

  10. Frequencies of chromosomal aberrations and sister chromatid exchanges in the benthic worm Neanthes arenaceodentata exposed to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, F.L.; Rice, D.W. Jr., Moore, D.H.

    1984-07-01

    Traditional bioassays are unsuitable for assessing sublethal effects from ocean disposal of low-level radioactive waste because mortality and phenotypic responses are not anticipated. We compared the usefulness of chromosomal aberration and sister chromatid exchange (SCE) induction as measures of low-level radiation effects in a sediment-dwelling marine worm, Neanthes arenaceodentata. The SCEs, in contrast to chromosomal aberrations, do not alter the overall chromosome morphology and in mammalian cells appear to be a more sensitive indicator of DNA alterations caused by environmental mutagens. Newly hatched larvae were exposed to two radiation-exposure regimes of either x rays at a high dose rate of 0.7 Gy (70 rad)/min for as long as 5.5 min or to /sup 60/Co gamma rays at a low dose rate of from 4.8 x 10/sup -5/ to 1.2 x 10/sup -1/ Gy (0.0048 to 12 rad)/h for 24 h. After irradiation, the larvae were exposed to 3 x 10/sup -5/M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h (/sup 60/Co-irradiated larvae). Larval cells were examined for the proportion of cells in first, second, and third or greater division. Frequencies of chromosomal aberrations and SCEs were determined in first and second division cells, respectively. Results from x-ray irradiation indicated that dose-related increases occur in chromosome and chromatid deletions, but a dose of equal or greater 2 Gy (equal to or greater than 200 rad) was required to observe a significant increase. Worm larvae receiving /sup 60/Co irradiation showed elevated SCE frequencies with a significant increase of 0.6 Gy (60 rad). We suggest that both SCEs and chromosomal aberrations may be useful for measuring effects on genetic material induced by radiation. 56 references, 7 figures, 9 tables.

  11. Status of human chromosome aberrations as a biological radiation dosimeter in the nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Bender, M.A.

    1978-01-01

    It seems that the determination of peripheral lymphocyte chriomosome aberration levels is now firmly established as a means of biological dosimetry of great value in many phases of the nuclear industry. In the case of large external exposure it can provide valuable quantitative estimates, as well as information on dose distribution and radiation quality. In the case of routine occupational exposures the technique is more qualitative, but is of value particularly in resolving uncertainties as to whether suspected overexposures did in fact occur. Where workers accumulate burdens of internal emitters, aberration analysis provides a valuable, though at present quite qualitative indicator. In spite of the expense of cytogenetic analyses, they are of sufficient value to justify much more widespread application, particularly in high risk situations.

  12. Is 24-color FISH detection of in-vitro radiation-induced chromosomal aberrations suited to determine individual intrinsic radiosensitivity?

    Energy Technology Data Exchange (ETDEWEB)

    Kuechler, A.; Wendt, T.G. [Clinic of Radiology, Jena (Germany). Dept. of Radiotherapy; Neubauer, S.; Grabenbauer, G.G.; Sauer, R. [Erlangen Univ. (Germany). Dept. of Radiotherapy; Claussen, U.; Liehr, T. [Jena Univ. (Germany). Inst. of Human Genetics and Anthropology

    2002-04-01

    Background: Reliable determination of intrinsic radiosensitivity in individual patients is a serious need in radiation oncology. Chromosomal aberrations are sensitive indicators of a previous exposure to ionizing irradiation. Former molecular cytogenetic studies showed that such aberrations as an equivalent of intrinsic radiosensitivity can be detected by fluorescence in-situ hybridization (FISH) techniques using whole chromosome painting (wcp) probes. However, only one up to three randomly chosen wcp probes have been applied for such approaches until now. As a random distribution of chromosomal rearrangements along the chromosomes is up to now still controversial, the power of the 24-color FISH approach should be elucidated in the present study. Methods and Material: Lymphocytes derived from lymphoblastoid cell lines of one patient with Nijmegen breakage syndrome (NBS homozygote) and of two NBS heterozygotes and peripheral blood lymphocytes of two controls were analyzed. Samples of each patient/control were irradiated in vitro with 0.0 Gy, 0.7 Gy or 2.0 Gy prior to cultivation. Chromosomal aberrations were analyzed in detail and quantified by means of 24-color FISH as an expression of the individual intrinsic radiosensitivity. Results: 24-color FISH analyses were done in a total of 1,674 metaphases. After in-vitro irradiation, 21% (0.7 Gy) or 57% (2.0 Gy) of the controls' cells, 15% (0.7 Gy) or 53% (2.0 Gy) of the heterozygotes' cells and 54% (0.7 Gy) or 79% (2.0 Gy) of the homozygote's cells contained aberrations. The highest average rates of breaks per mitosis [B/M] (0.7 Gy: 1.80 B/M, 2.0 Gy: 4.03 B/M) and complex chromosomal rearrangements [CCR] (0.7 Gy: 0.20 CCR/M, 2.0 Gy: 0.47 CCR/M) were observed in the NBS patient. Moreover, the proportion of different aberration types after irradiation showed a distinct increase in the rate of CCR combined with a decrease in dicentrics in the NBS homozygote. Conclusion: To come to a more complete picture of

  13. The Induction of Chromosome Aberrations and Micronuclei in Human Peripheral Blood Lymphocytes at Low Doses of Radiation

    CERN Document Server

    Shmakova, N L; Krasavin, E A; Melnikova, L A; Fadeeva, T A

    2003-01-01

    The chromosome damage induced by the low doses of gamma-irradiation with ^{60}Co and X-rays in peripheral blood lymphocytes has been studied using different cytogenetic assays. Isolated lymphocytes were exposed to 0.01-1.0 Gy, simulated by PHA, and analysed for chromosome aberrations by the metaphase and the anaphase methods, by the micronucleus assay. Despite the quantitative differences in the amount of chromosome damage revealed by different methods, all of them demonstrated complex nonlinear dose dependence of the frequency of aberrant cells and aberrations. At the dose range of 0.01-0.05 Gy the cells showed the highest radiosensitivity; at 0.05-0.5 Gy the dose-independent induction of chromosome damage was revealed. At the doses of 0.5-1.0 Gy the dose-effect curves became linear with the decreased slope compared with the initial one (by a factor of 5 to 10 for different criteria) reflecting a higher radioresistance of the cells. These data confirm the idea that the direct linear extrapolation of high-dos...

  14. Effect of low-dose radiation on frequencies of chromosome aberrations and micronucleus-containing cells of occupationally exposed individuals: a Meta analysis%低剂量电离辐射对职业暴露人群染色体畸变率和微核细胞率影响的Meta分析

    Institute of Scientific and Technical Information of China (English)

    姜晶; 高露; 黄波; 周平坤; 让蔚清

    2014-01-01

    目的 用Meta分析的方法综合定量分析电离辐射对职业暴露人群染色体畸变率和微核细胞率的影响.方法 全面检索国内外中英文相关文献,按预先设定的纳入排除标准进行严格筛选后,最终纳入21篇文献,总研究细胞数1 970 626个.用Stata 12.0进行Meta分析,异质性检验用Q检验和I2统计量,发表偏倚用漏斗图法、Begg秩相关法和Egger线性回归法3种方法识别.结果 放射工作人员发生染色体型畸变、双着丝粒体+环状染色体畸变、易位、微核细胞的危险性要高于非放射工作人员,其比值比及95%的可信区间分别为3.03 (2.59,3.56)、4.12 (2.99,5.67)、2.73 (1.67,4.46)、1.70 (1.40,2.06).结论 长期暴露在低剂量电离辐射下会显著增加外周血淋巴细胞染色体畸变率和微核细胞率,应加强放射工作人员的辐射防护.%Objective To quantitatively investigate the effect of low-dose ionizing radiation on the frequencies of chromosome aberrations and micronucleus-containing cells of radiation workers.Methods Nine electronic databases were systematically searched on the basis of the published studies evaluating the effects of low-dose ionizing radiation on the frequencies of chromosome aberrations and micronucleuscontaining cells.Of the 195 studies searched,21 studies were identified with a total of 1 970 626 cells under studying.Cochrane' s Q and I2 statistics were used to evaluate heterogeneity among studies and pooling odds ratio (OR) with 95% confidence intervals (CI) were calculated using random-effect models or fixed-effect models,and publication bias were also calculated.Meta-analysis was performed using Stata 12.0.Results The pooling OR of chromosome-type aberrations [OR =3.03 (2.59,3.56)],dicentric plus centric rings [OR =4.12 (2.99,5.67)],translocations [OR =2.73 (1.67,4.46)],micronucleuscontaining cells [OR =1.70 (1.40-2.06)] were higher for radiation workers when compared with control group

  15. Changes in metal levels and chromosome aberrations in the peripheral blood of patients after metal-on-metal hip arthroplasty.

    Science.gov (United States)

    Ladon, Dariusz; Doherty, Ann; Newson, Roger; Turner, Justine; Bhamra, Manjit; Case, C Patrick

    2004-12-01

    A prospective study was performed to investigate changes in metal levels and chromosome aberrations in patients within 2 years of receiving metal-on-metal hip arthroplasties. There was a statistically significant increase of cobalt and chromium concentrations, with a small increase in molybdenum, in whole blood at 6, 12, and 24 months after surgery. There was also a statistically significant increase of both chromosome translocations and aneuploidy in peripheral blood lymphocytes at 6, 12, and 24 months after surgery. The changes were generally progressive with time, but the change in aneuploidy was much greater than in chromosome translocations. No statistically significant correlations were found in secondary analyses between chromosome translocation indices and cobalt or chromium concentration in whole blood. Although the clinical consequences of these changes, if any, are unknown, future epidemiological studies could usefully include direct comparisons of patients with implants of different composition.

  16. [A modification factor of spontaneous chromosomal aberrations in miner's towns and settlements].

    Science.gov (United States)

    Volkov, A V; Golovina, T A; Minina, V I; Mokrushina, N V; Druzhinin, V G; Glushkov, A N; Shabaldin, A V

    2006-01-01

    The level and qualitative spectrum of spontaneous chromosomal aberrations (CA) were comparatively analyzed in the lymphocytes of 655 children and adolescents from the Kemerovo Region. The presented sample was divided into 3 groups according to the type of an inhabited locality: 1) small miner's towns; 2) large industrial towns; and 3) rural localities. The maximum frequency of CA (3.77 +/- 0.22%) was noted in a group of dwellers in the miner's towns; its minimum frequency (2.68 +/- 0.17%) among the rural inhabitants. The significant clastogenic effects (including the markers of radiation exposure) were detected in the miner's towns located in the southern part of the region, which represented mountain and submountain areas. At the same time, in the northern and western parts of the Kemerovo Region, the average frequencies of CA in children and adolescents did not exceed the control background values. Thus, the residence in the inhabited localities specializing in mining is not a factor of absolute toxicogenetic risk.

  17. Sensitivity of Bidens laevis L. to mutagenic compounds. Use of chromosomal aberrations as biomarkers of genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Perez, D.J. [Laboratorio de Genetica, Estacion Experimental Agropecuaria Balcarce (INTA), Facultad de Ciencias Agrarias, UNMdP, CC 276, 7620 Balcarce (Argentina); Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina); Lukaszewicz, G. [Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Menone, M.L., E-mail: lujanm@mdp.edu.a [Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina); Camadro, E.L. [Laboratorio de Genetica, Estacion Experimental Agropecuaria Balcarce (INTA), Facultad de Ciencias Agrarias, UNMdP, CC 276, 7620 Balcarce (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina)

    2011-01-15

    The wetland macrophyte Bidens laevis possesses suitable cytological characteristics for genotoxicity testing. To test its sensitivity as compared to terrestrial plants species currently in use in standardized assays, Methyl Methanesulfonate (MMS), N-ethyl-N-nitrosourea (ENU) and Maleic Hydrazide (HM) were used. On the other hand, the insecticide Endosulfan (ES) - an environmentally relevant contaminant - was assayed in seeds and two-month old plants. Mitotic Index (MI), frequency of Chromosome Aberrations in Anaphase-Telophase (CAAT) and frequency of Abnormal Metaphases (AM) were analyzed. MH, MMS and ENU caused a significant decrease of the MI. MMS was aneugenic whereas MH and ENU were both aneugenic and clastogenic. ES caused a significant concentration-dependent increase of total- and aneugenic-CAAT in roots and a significant high frequency of AM at high concentrations. Because of its sensitivity to mutagenic substances, B. laevis can be regarded as a reliable and convenient species for genotoxicity assays especially if aquatic contaminants are evaluated. - The wetland macrophyte Bidens laevis is sensitive to genotoxic compounds similarly to terrestrial standardized species.

  18. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  19. Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding

    Science.gov (United States)

    George, K.; Willingham, V.; Wu, H.; Gridley, D.; Nelson, G.; Cucinotta, F. A.

    2002-01-01

    Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  20. Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

    Directory of Open Access Journals (Sweden)

    Eilers Paul HC

    2008-10-01

    Full Text Available Abstract Background Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes. Methods We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry. Results Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF. The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss. Conclusion On basis of integrative analysis this study identified one well known CRC gene (SMAD2 and several other genes (EFNA1, BOP1, TGIF2 and STMN3 that possibly could be used for rectal cancer characterization.

  1. Chromosomal aberrations in persons occupationally exposed to annual x-irradiation doses lower than 25 mSv

    Energy Technology Data Exchange (ETDEWEB)

    Kubelka, D.; Garaj-Vrhovac, V.; Horvat, D. (Zagreb Univ. (Yugoslavia). Inst. for Medical Research and Occupational Health)

    1992-03-01

    The authors applied chromosomal aberration counting to determine possible changes in the cell genome of subjects occupationally exposed to x-radiation. Subjects were restricted to those exposed to annual radiation levels no higher than 25 mSv as determined by regular dosimetry monitoring in the previous two years. Results indicate the possibility of a cumulative effect of ionising radiation and point to the need for more frequent and controlled health surveillance of occupationally exposed subjects. (UK).

  2. Dose assessment by quantification of chromosome aberrations and micronuclei in peripheral blood lymphocytes from patients exposed to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Silva-Barbosa, Isvania; Pereira-MagnataI, Simey; Amaral, Ademir [Pernambuco Univ., Recife, PE (Brazil). Dept. de Energia Nuclear. Grupo de Estudos em Radioprotecao e Radioecologia - GERAR; Sotero, Graca [Fundacao de Hematologia e Hemoterapia, Recife, PE (Brazil); Melo, Homero Cavalcanti [Hospital do Cancer, Recife, PE (Brazil). Centro de Radioterapia de Pernambuco]. E-mail: isvania@uol.com.br

    2005-07-15

    Scoring of unstable chromosome aberrations (dicentrics, rings and fragments) and micronuclei in circulating lymphocytes are the most extensively studied biological means for estimating individual exposure to ionizing radiation (IR), which can be used as complementary methods to physical dosimetry or when the latter cannot be performed. In this work, the quantification of the frequencies of chromosome aberrations and micronuclei were carried out based on cytogenetic analyses of peripheral blood samples from 5 patients with cervical uterine cancer following radiotherapy in order to evaluate the absorbed dose as a result of partial-body exposure to 60Co source. Blood samples were collected from each patient in three phases of the treatment: before irradiation, 24 h after receiving 0.08 Gy and 1.8 Gy, respectively. The results presented in this report emphasize biological dosimetry, employing the quantification of chromosome aberrations and micronuclei in lymphocytes from peripheral blood, as an important methodology of dose assessment for either whole or partial-body exposure to IR.

  3. Genotoxic and antigenotoxic effects of Fucus vesiculosus extract on cultured human lymphocytes using the chromosome aberration and Comet assays

    Directory of Open Access Journals (Sweden)

    Cleide Leite-Silva

    2007-01-01

    Full Text Available The brown seaweed Fucus vesiculosus (Fucales, Fucaceae was screened for its protective activity using doxorubicin-induced DNA damage in human lymphocytes. In this study, we assessed the genotoxic and antigenotoxic potential of three different concentrations (0.25, 0.5 and 1.0 mg mL-1 of F. vesiculosus aqueous extract using the chromosome aberration and Comet assays. Treatment of human lymphocyte cultures with 0.25, 0.5 and 1.0 mg mL-1 F. vesiculosus aqueous extract had no effect on the chromosome aberration frequency or on the extent of DNA damage detected by the Comet assay. The antigenotoxic effects of the extract were tested in human lymphocyte cultures treated with 15 µg mL-1 of doxorubicin, either alone or combined with the different concentrations of the extract, which was added to the cultures before, simultaneously with or after the doxorubicin. Only when lymphocytes were pre-treated with extract there was a reduction in doxorubicin-induced chromosome aberrations and DNA damage as detected by the Comet assay. These results demonstrate that F. vesiculosus aqueous extract is not genotoxic in cultured human lymphocytes and indicate that when added to lymphocyte cultures before doxorubicin it has antigenotoxic activity against doxorubicin-induced DNA damage.

  4. Chromosome aberrations in human lymphocytes from the plateau region of the Bragg curve for a carbon-ion beam

    Science.gov (United States)

    Manti, L.; Durante, M.; Grossi, G.; Pugliese, M.; Scampoli, P.; Gialanella, G.

    2007-06-01

    Radiotherapy with high-energy carbon ion beams can be more advantageous compared to photons because of better physical dose distribution and higher biological efficiency in tumour cell sterilization. Despite enhanced normal tissue sparing, damage incurred by normal cells at the beam entrance is unavoidable and may affect the progeny of surviving cells in the form of inheritable cytogenetic alterations. Furthermore, the quality of the beam along the Bragg curve is modified by nuclear fragmentation of projectile and target nuclei in the body. We present an experimental approach based on the use of a polymethylmethacrylate (PMMA) phantom that allows the simultaneous exposure to a particle beam of several biological samples positioned at various depths along the beam path. The device was used to measure the biological effectiveness of a 60 MeV/amu carbon-ion beam at inducing chromosomal aberrations in G0-human peripheral blood lymphocytes. Chromosome spreads were obtained from prematurely condensed cells and all structural aberration types were scored in Fluorescence in situ Hybridization (FISH)-painted chromosomes 1 and 2. Our results show a marked increase with depth in the aberration frequency prior to the Bragg peak, which is consistent with a linear energy transfer (LET)-dependent increase in biological effectiveness.

  5. Evaluation of chromosome 5 aberrations in complex karyotypes of patients with myeloid disorders reveals their contribution to dicentric and tricentric chromosomes, resulting in the loss of critical 5q regions.

    Science.gov (United States)

    Herry, Angèle; Douet-Guilbert, Nathalie; Morel, Frédéric; Le Bris, Marie-Josée; Morice, Patrick; Abgrall, Jean François; Berthou, Christian; De Braekeleer, Marc

    2007-06-01

    Dicentric chromosomes have often been observed in complex karyotypes in previously reported studies of therapy-related myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Fluorescence in situ hybridization (FISH) has now made the characterization of these rearrangements much easier. Dicentric and tricentric chromosomes were identified in 21 patients (9 MDS and 12 AML) among the 133 consecutive MDS/AML patients (17%) who had a structural or numerical aberration of chromosome 5 using conventional cytogenetic analysis. One third (7/21) of the patients had received alkylating drugs for a previously diagnosed cancer or chronic myeloproliferative disease. Loss of 5q material was identified in all 21 patients. One copy of the EGR1 (5q31) or the CSF1R (5q33 approximately q34) genes was lost in 20 of the 21 patients. Dicentric and tricentric chromosomes involving chromosome 5 are frequently observed in complex karyotypes among patients with de novo or therapy-related MDS/AML. They lead to deletions of various parts of the long arm of chromosome 5.

  6. Direct ChromOSOme Analysis and FISH Detection of Primary Gastric cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate chromosome aberrations and their role in the genesis and development of primary gastric cancer. Methods: An improved, direct chromosome preparation from solid tumors was adopted for G-banding analysis followed by FISH on decolored G-banding chromosomes so that chromosome aberrations could be confirmed at DNA level. Results: A total of 28 primary gastric cancer specimens were studies. Case 1 and case 2 had simple chromosome numerical changes: 49, XY, +2, +8, +9 and 48, +8, +20, respectively. All but case 1 and 2 had complicated chromosome abnormalities. Chromosome structural of frequent occurrence involved del(7q)(21/26), del(3p)(14/26), del(lp)(l1/26) and del(17p)(10/26). The chromosome abnormalities could be simple and complicated. In former, numerical changes involving 1 to 3 chromosome could be observed. Trisomies 8 and 9 might represent a cytogenetic subgroup of primary gastric cancer. In the later, the del(7q) was the most consistent aberration. 7q32-qter was the commonly lost segment. Conclusion: Numerical and structural alterations of chromosomes are present in primary gastric cancer. Del(7q) is one of the structural change characteristic of primary gastric cancer. In the 7q32-qter fragment, a tumor suppressor gene probably exists and it may have close relation to the genesis and progression of gastric cancer.

  7. Chromosome aberrations and micronucleus in continuously irradiated mice for a low dose rate of {sup 137}Cs {gamma}-rays

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Jun; Yanai, Takanori; Shirata, Katsutoshi; Tanaka, Kimio; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    2002-07-01

    Delayed chromosomal instability is developed by radiation after several cell divisions in cultured rodent and human cells. The genetic instability might be related to cancer development and it has been mainly found in cultured rodent and human cells irradiated at high dose rate. It has not been well studied whether the genetic instability is induced by prolonged irradiation with low dose rate in vivo or not. Mice irradiated with 20 mGy/day for 5-8 Gy were analyzed by FISH to estimate the chromosome aberration rate and micronucleus incidence in spleen and bone marrow cells. Spleen cells in mice exposed to 8 Gy have higher incidence of monosomy and trisomy than non-exposed mice. The number of cells with 2-4 micronuclei in 10,000 scored spleen cells is also higher in 5-8 Gy exposed mice. These numerical chromosome aberrations are not induced directly by radiation exposure. These results indicate that prolonged {sup 137}Cs {gamma} ray-irradiation with low dose rates of 20 mGy/day induces delayed chromosome instability in mice. (author)

  8. Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration

    Directory of Open Access Journals (Sweden)

    Ana P. Berbegall

    2014-06-01

    Full Text Available Neuroblastoma (NB is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked (ATRX protein expression, and the presence of tumor-associated inflammatory cells. Thirty-one NB patients older than 10 years who were included in the Spanish NB Registry were considered for the current study; seven young and middle-aged adult patients (range 18-60 years formed part of the cohort. We performed single nucleotide polymorphism arrays, immunohistochemistry for immune markers (CD4, CD8, CD20, CD11b, CD11c, and CD68, and ATRX protein expression. Assorted genetic profiles were found with a predominant presence of a segmental chromosome aberration (SCA profile. Preadolescent and adolescent NB tumors showed a higher number of SCA, including 17q gain and 11q deletion. There was also a marked infiltration of immune cells, mainly high and heterogeneous, in young and middle-aged adult tumors. ATRX negative expression was present in the tumors. The characteristics of preadolescent, adolescent, young adult, and middle-aged adult NB tumors are different, not only from childhood NB tumors but also from each other. Similar examinations of a larger number of such tumor tissues from cooperative groups should lead to a better older age–dependent tumor pattern and to innovative, individual risk-adapted therapeutic approaches for these patients.

  9. Identification of the origin of chromosomal aberrations by laser microdissection: Double minutes observed in two cases derive from different chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Rajcan-Separovic, E. [Univ. of Ottawa (Canada); Wang, H.S.; Janes, L. [Children`s Hospital of Eastern Ontario, Ottawa (Canada)

    1994-09-01

    Single copies of tiny chromosome fragments appearing as double minutes were observed in high frequency in amniotic fluid cultures of two mothers who underwent prenatal testing because of advanced age. In case 1, the minutes were C band and NOR negative, while in case 2 they were C band positive, NOR negative. In both cases centromeric DNA sequences were detected on double minutes by fluorescence in situ hybridization (FISH) using all human centromeric probe (ONCOR). We applied the laser microdissection method to diagnose the origin of double minutes. The diagnostic procedures consisted of microdissection of double minutes from single cells, polymerase chain reaction (PCR) amplification of the dissected DNA and subsequent FISH using PCR products as a probe pool on metaphase chromosomes from the patient`s amniocytes and fibroblasts from a karyotypically normal newborn. Using this strategy we observed strong FISH signals on double minutes and centromeres of a D and G group chromosome in case 1 amniocyytes, while in case 2 the signal was present on double minutes and a C group chromosome centromere. Hybridization of amniocyte chromosome spreads with centromeric {alpha}-satellite probes for the candidate chromosomes 13/21 and 14/22 (ONCOR) in case 1 revealed FISH signals on double minutes only with the 13/21 probe. In case 2, {alpha}-satellite probes for candidate chromosomes 10 and 12 (ONCOR) were used, and only the probe for chromosome 12 hybridized to double minutes. With the laser microdissection method we were thus able to diagnose and confirm that the double minutes observed in human amniocytes derived from centromeres of chromosomes 13/21 in case 1, and from centomeres of chromosome 12 in case 2. This demonstrates the utility of laser microdissection for identification of chromosomal abnormalities of unknown origin.

  10. Theoretical and experimental tests of a chromosomal fingerprint for densely ionizing radiation based on F ratios calculated from stable and unstable chromosome aberrations

    Science.gov (United States)

    Lucas, J. N.; Deng, W.; Oram, S. W.; Hill, F. S.; Durante, M.; George, K.; Wu, H.; Owens, C. L.; Yang, T.

    1999-01-01

    In the present study, F ratios for both stable chromosome aberrations, i.e. ratios of translocations to pericentric inversions, and unstable aberrations, i.e. dicentrics and centric rings, were measured using fluorescence in situ hybridization. F ratios for stable aberrations measured after exposure to low (2.89 Gy 60Co gamma rays) and high-LET (0.25 Gy 56Fe ions; 1.25 Gy 56Fe ions; 3.0 Gy 12C ions) radiation were 6.5 +/- 1.5, 4.7 +/- 1.6, 9.3 +/- 2.5 and 10.4 +/- 3.0, respectively. F ratios for unstable aberrations measured after low (2.89 Gy 60Co gamma rays) and high-LET (0.25 Gy 56Fe ions; 3.0 Gy 12C ions) radiations were 6.5 +/- 1.6, 6.3 +/- 2.3 and 11.1 +/- 3.7, respectively. No significant difference between the F ratios for low- and high-LET radiation was found. Further tests on the models for calculation of the F ratio proposed by Brenner and Sachs (Radiat. Res. 140, 134-142, 1994) showed that the F ratio may not be straightforward as a practical fingerprint for densely ionizing radiation.

  11. Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea [Institute of Pathology, Ruhr-University Bochum (Germany); Wieczorek, Stefan; Epplen, Joerg Thomas [Department of Human Genetics, Ruhr-University Bochum (Germany); Tilkorn, Daniel [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Steinstraesser, Lars, E-mail: lars.steinstraesser@rub.de [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany)

    2013-07-15

    Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations.

  12. Chromosomal aberrations in lymphocytes of employees in transformer and generator production exposed to electromagnetic fields and mineral oil.

    Science.gov (United States)

    Skyberg, K; Hansteen, I L; Vistnes, A I

    2001-04-01

    The objective was to study the risk of cytogenetic damage among high voltage laboratory workers exposed to electromagnetic fields and mineral oil. This is a cross sectional study of 24 exposed and 24 matched controls in a Norwegian transformer factory. The exposure group included employees in the high voltage laboratory and in the generator soldering department. Electric and magnetic fields and oil mist and vapor were measured. Blood samples were analyzed for chromosomal aberrations in cultured lymphocytes. In addition to conventional cultures, the lymphocytes were also treated with hydroxyurea and caffeine. This procedure inhibits DNA synthesis and repair in vitro, revealing in vivo genotoxic lesions that are repaired during conventional culturing. In conventional cultures, the exposure group and the controls showed similar values for all cytogenetic parameters. In the DNA synthesis- and repair-inhibited cultures, generator welders showed no differences compared to controls. Among high voltage laboratory testers, compared to the controls, the median number of chromatid breaks was doubled (5 vs. 2.5 per 50 cells; P0.05) and the median number of aberrant cells was 5 vs. 3.5 (Poil exposure may produce chromosomal aberrations.

  13. Dynamic Investigation on Chromosome Aberration of a Human Retinoblastoma Cell Line SO-Rb_(50)

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    G-banding and karyotype analyses of cells in seventeen passages of SO-Rb_(50) during a long period of culture for about four years were performed. Three chromosome markers 13q14~-, 1p36~+ and 12p13~+ were found. Cells possessed 13q14~- reduced to zero after the 200th passage while 1p~+ and 12p~+ cells increased to 100% after 30 and 200 passages respectively. Abnormal chromosomes, ring chromosomes, chromosome radiuses and double minutes were also observed. These chromosomal changes were more often seen b...

  14. Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage

    DEFF Research Database (Denmark)

    Hagmar, L; Brøgger, A; Hansteen, I L;

    1994-01-01

    Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target...... tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange.......0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk....

  15. Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster (CHO) Cells With and Without Metabolic Activation. Test Article. Diethylene triamine trinitrate (DETN)

    Science.gov (United States)

    2010-02-25

    chromatid interchanges between chromosomes leading to four-armed configurations. This could be asymmetrical with formation of a dicentric and an acentric...fragment which may be misaligned and a shortened monocentric chromosome , and where there is no sister chromatid union. Dicentric - an asymmetrical...Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster Ovary (CHO) Cells With and Without Metabolic Activation Test

  16. Chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with sodium metabisulfite, a food preservative.

    Science.gov (United States)

    Rencüzogullari, E; Ila, H B; Kayraldiz, A; Topaktaş, M

    2001-02-20

    The aim of this study was to investigate the ability of sodium metabisulfite (SMB) which is used as an antimicrobial substance in food, to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in human lymphocytes. SMB-induced CAs and SCEs at all concentrations (75, 150 and 300 microg/ml) and treatment periods (24 and 48h) dose-dependently. However, SMB decreased the replication index (RI) and the mitotic index (MI) at the concentrations of 150 and 300 microg/ml for 24 and 48h treatment periods. This decrease was dose-dependent as well.

  17. Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster Ovary (CHO) Cells with and without Metabolic Activation, Test Article: 3-Nitro-1,2,4-Triazol-5-one (NTO)

    Science.gov (United States)

    2008-10-30

    3110 Dicentric - an asymmetrical exchange between two chromosomes resulting in a chromosome with two centromeres with or without an accompanying...chromatid union. Dicentric - an asymmetrical exchange between two chromosomes resulting in a chromosome with two centromeres with or without an...Test for Chemical fuduction of Chromosome Aberrations in Cultured Chinese Hamster Ovary (CHO) Cells With and Without Metabolic Activation Test

  18. Heterogeneous Chromosomal Aberrations in Intraductal Breast Lesions Adjacent to Invasive Carcinoma

    Directory of Open Access Journals (Sweden)

    Michaela Aubele

    2000-01-01

    Full Text Available There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH and ductal carcinoma in situ (DCIS. In this study we applied comparative genomic hybridization (CGH to formalin‐fixed, paraffin‐embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC, to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser‐microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP‐PCR and further processed for CGH analysis.

  19. Higher frequencies of chromosomal aberrations in lymphocytes of children with acute lymphoblastic leukemia after in vitro gamma irradiation

    Directory of Open Access Journals (Sweden)

    A Ramyar

    2012-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood, characterized by excess lymphoblasts, and immature white blood cells that are continuously multiplying and overproducing in the bone marrow. The aim of this investigation was to measure the sensitivity of lymphocytes against gamma irradiation in patients with acute lymphoblastic leukemia, and also find out the effect of such irradiations in causing chromosomal abnormalities.Methods: In this investigation performed between April 2010 and July 2011, at the Department of Genetics, Cancer Institute of Iran, we studied the effects of gamma irradiation on the lymphocytes of 20 children with acute lymphoblastic leukemia. The lymphocytes of 30 healthy donors were used to establish as a normal response to gamma irradiation and seven age-matched ataxia telangiectasia patients were recruited as positive control. The chromosomal radiosensitivity was assessed with the G2- and the G0-assay. We compared the mean number of chromosomal abnormalities such as chromosome and chromatid breakages, chromosome and chromatid gaps, and chromatid exchanges in one-hundred metaphases of patients and control groups.Results: The frequency of chromosomal aberrations was statistically higher among patients with acute lymphoblastic leukemia than the normal controls (P<0.01. In total, 65% of the patients were sensitive to gamma irradiation, but the remaining 35% were similar to the normal controls. Patients with ataxia telangiectasia showed the highest sensitivity to gamma irradiation (P=0.001.Conclusion: Our results showed that a high percentage of patients with acute lymphoblastic leukemia were sensitive to irradiation, meaning that maximum care should be taken during their treatment to avoid unnecessary X-rays or radiotherapies.

  20. Pan-cancer analysis of ROS1 genomic aberrations

    OpenAIRE

    Wang, Yidan; 王奕丹

    2015-01-01

    The ROS proto-oncogene 1 (ROS1) encodes the ROS1 receptor kinase. ROS1 rearrangements are known to be oncogenic in glioblastoma, non–small-cell lung carcinoma (NSCLC) and cholangiocarcinoma. The clinical relevance of ROS1 genomic aberrations in other human cancers is largely unexamined. Here, we performed a pan-cancer analysis of ROS1 genomic aberrations across 20 cancer sites by interrogating the whole-exome sequencing data of the Cancer Genome Atlas (TCGA) via the cBioportal (www.cbioportal...

  1. 七例产前诊断的标记染色体及复杂染色体畸变的光谱核型分析%Spectral karyotyping of seven prenatally detected marker chromosomes and complex chromosome aberrations

    Institute of Scientific and Technical Information of China (English)

    宋花蕾; 陈宝江; 方群; 谢英俊; 林少宾; 吴坚柱

    2012-01-01

    Objective To perform spectral karyotyping (SKY),fluorescence in situ hybridization (FISH) and conventional karyotyping on prenatally detected marker chromosomes and complex chromosomal aberrations.Methods Five marker chromosomes and 2 complex chromosome aberrations diagnosed by G banding were collected.SKY was performed to verify the composition of marker chromosomes.FISH was used to confirm the diagnosis when necessary.In certain cases,C or N banding technique was employed to verify the composition of chromosomes.Results of ultrasonography and pregnancy outcome were reviewed.Results Among the 5 marker chromosomes,2 were large and 3 were medium in size,4 were de novo and one was inherited from the father.By SKY analysis,2 marker chromosomes have originated from non-acrocentric chromosomes (4 and 9),whilst the other two have originated from acrocentric chromosomes (21 and 22).The remainder was derived from X chromosome.The SKY results were confirmed by FISH in 3 cases.Four cases have chosen to terminate the pregnancy after genetic counseling.A fetus with inherited paternal marker chromosome was delivered at term,and showed normal development during the first year of life. As for the other 2 cases with complex chromosome aberrations, by SKY examination, one had duplication in chromosome 8 and the other had chromosome rearrangements derived from translocation between chromosomes 2 and 6.In the latter case the fetus was delivered at term but showed developmental retardation at 6 months. Conclusion SKY in combination with FISH can facilitate identification of the origins of marker chromosomes as well as complex chromosomal aberrations.With combined information from ultrasonography,SKY and FISH,effective counseling may be offered to the patients.%目的 探讨光谱核型分析( spectral karyotyping,SKY)结合荧光原位杂交(fluorescence in situ hybridization,FISH)及传统核型分析技术在产前诊断标记染色体及复杂染色体畸变中的应用.方法

  2. Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.

    Science.gov (United States)

    Nakano, M; Kodama, Y; Ohtaki, K; Itoh, M; Awa, A A; Cologne, J; Kusunoki, Y; Nakamura, N

    2004-03-01

    Quantifying the proliferative capacity of long-term hematopoietic stem cells in humans is important for bone marrow transplantation and gene therapy. Obtaining appropriate data is difficult, however, because the experimental tools are limited. We hypothesized that tracking clonal descendants originating from hematopoietic stem cells would be possible if we used clonal chromosome aberrations as unique tags of individual hematopoietic stem cells in vivo. Using FISH, we screened 500 blood T lymphocytes from each of 513 atomic bomb survivors and detected 96 clones composed of at least three cells with identical aberrations. The number of clones was inversely related to their population size, which we interpreted to mean that the progenitor cells were heterogeneous in the number of progeny that they could produce. The absolute number of progenitor cells contributing to the formation of the observed clones was estimated as about two in an unexposed individual. Further, scrutiny of ten clones revealed that lymphocyte clones could originate roughly equally from hematopoietic stem cells or from mature T lymphocytes, thereby suggesting that the estimated two progenitor cells are shared as one hematopoietic stem cell and one mature T cell. Our model predicts that one out of ten people bears a non- aberrant clone comprising >10% of the total lymphocytes, which indicates that clonal expansions are common and probably are not health-threatening.

  3. G-banding chromosomal aberration assay of lymphocyte after radiation%辐射后淋巴细胞的G显带染色体畸变分析

    Institute of Scientific and Technical Information of China (English)

    赵明刚; 施常备; 赵华; 袁勇; 姚俊涛; 陆建荣; 袁彬; 陈葳; 王翔

    2011-01-01

    目的:通过染色体G显带技术研究辐射后染色体的结构畸变情况.方法:4MV的X线辐射离体入血,淋巴细胞培养后,应用染色体G显带技术,分析辐射后染色体的结构畸变情况,包括双着丝粒、缺失、易位、环状染色体、染色体片段,等.结果:辐射后观察分散良好、形态清晰的细胞核型100个,染色体畸变总数为428,其中双着丝粒、缺失、易位、环状染色体、染色体片段的发生数分别为 86、41、111、9、181.分析各号染色体辐射后畸变情况,未见明显差异.结论:染色体G带分析可以提供较丰富的染色体结构畸变信息.%Objective : To validate the value of G - banding chromosomal aberration of lymphocyte after radiation. Methods : The blood was irradiated by 4 MV X - ray and was cultured 3 days. The G - banding chromosomal aherration was assayed including dicentrics, deletions, translocations, rings, and fragments chromosomal aberration. Results:There were 100 good karyotypes observed. The total of chromosomal aberration was 428. The dicentric, deletion, translocation, ring, and fragment chromosomal aberration were 86, 41 , 111 , 9, and 181 respectively. There was no significant difference in chromosomal aherration after radiation in every NO. chromosome. Conclusion : The G - banding chromosomal aberration assay should be paid more attention in radiation biology.

  4. 精子大头多尾畸形与性染色体异常%Malformed macrocephalous sperm with polytails and chromosomal aberrance

    Institute of Scientific and Technical Information of China (English)

    范立青; 朱文兵; 谭跃球; 罗克莉; 卢光王秀; 曾庆善

    2001-01-01

    目的 探讨精子畸形与精子染色体异常的关系,了解畸形精子的病理学改变。方法 应用光学和电子显微镜、性染色体特异性探针荧光原位杂交(FISH)技术研究罕见的大头多尾畸形精子。结果 巴氏染色后观察的精子畸形率达98.75%(油镜下测量头部畸形达100%),精子多尾率达60.25%(最多达8尾);电镜观察证实,精子头部表面凹凸不平、核型极不规则、有大量细胞质结构,尾部除数量异常外, 尚有中心粒、线粒体和鞭毛结构的异常;FISH结果证实,性染色体多体率为61.4%,与精子多尾的组成比有大致的平行关系。结论 尽管体细胞染色体正常,畸形精子仍可伴有严重染色体异常。%Objective To investigate the relationship between sperm anomalies and chromosomal aberrance and to further understand the pathological changes of anomalous spermatozoa.Methods Light and electronic (SEM or TEM) microscopes were used for morphological analysis. Fluorescence in situ hybridization(FISH) with chromosome X-,Y-specific probes were used for aneuploidy detection in sperms of the patient. Results Ninety eight point seven five per cent of the Papanicolaou stained sperms were observed to be abnormal; 100% of the sperm heads were abnormal, measured under oil objective (1000×); 60.25% of the sperms had two or more tails (the maximum being eight tails). SEM and TEM demonstrated that the heads contained a large amount of cytoplasmic structure, the surfaces of heads were uneven, the nuclei were of much irregular shape; besides aberrance in quantity, anomalies occurred with centromeres, mitochondria and flagella in the tails. The results of FISH showed that the aneuploidy rate of sex chromosomes was 61.41% which was parallel to the rate of polytails.Conclusion Even though the chromosomes in somatic cells are normal, the chromosomes in anomalous sperms may be abnormal.

  5. Analysis of the Aberration in Directly-writing Atom Lithography

    Institute of Scientific and Technical Information of China (English)

    LI Chuanwen; CAI Weiquan; WANG Yuzhu

    2000-01-01

    After deriving the approximation solution which describes the motion of neutral atoms in an optical standing wave field with large detuning, the spherical aberration and the chromatic aberration are analyzed and possible methods to reduce these aberrations are discussed.

  6. Unstable chromosome aberrations do not accumulate in normal human fibroblast after fractionated x-irradiation.

    Directory of Open Access Journals (Sweden)

    Mitsuaki Ojima

    Full Text Available We determined the frequencies of dicentric chromosomes per cell in non-dividing confluent normal human fibroblasts (MRC-5 irradiated with a single 1 Gy dose or a fractionated 1 Gy dose (10X0.1 Gy, 5X0.2 Gy, and 2X0.5 Gy. The interval between fractions was between 1 min to 1440 min. After the completion of X-irradiation, the cells were incubated for 24 hours before re-plating at a low density. Then, demecolcine was administrated at 6 hours, and the first mitotic cells were collected for 42 hours. Our study demonstrated that frequencies of dicentric chromosomes in cells irradiated with a 1 Gy dose at different fractions were significantly reduced if the fraction interval was increased from 1 min to 5 min (p<0.05, χ2-test. Further increasing the fraction interval from 5 up to 1440 min did not significantly affect the frequency of dicentric chromosomes. Since misrejoining of two independent chromosome breaks introduced in close proximity gives rise to dicentric chromosome, our results indicated that such circumstances might be quite infrequent in cells exposed to fractionated X-irradiation with prolonged fraction intervals. Our findings should contribute to improve current estimation of cancer risk from chronic low-dose-rate exposure, or intermittent exposure of low-dose radiation by medical exposure.

  7. Chromosome analysis of arsenic affected cattle

    Directory of Open Access Journals (Sweden)

    S. Shekhar

    2014-10-01

    Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.

  8. Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

    NARCIS (Netherlands)

    Franssen, M. T. M.; Korevaar, J. C.; Tjoa, W. M.; Leschot, N. J.; Bossuyt, P. M. M.; Knegt, A. C.; Suykerbuyk, R. F.; Hochstenbach, R.; van der Veen, F.; Goddijn, M.

    2008-01-01

    Objective To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis. Methods From the databases of three centres for clinical genetics in the Netherlands, all cases of inherited unbalanced structural chromosome abnorma

  9. Analysis of plant meiotic chromosomes by chromosome painting.

    Science.gov (United States)

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  10. 小儿恶性肿瘤患者染色体畸变的观察%Significance of the Chromosome Aberration in Children With Malignant Tumor

    Institute of Scientific and Technical Information of China (English)

    高解春; 倪祖德; 金百祥

    1995-01-01

    The chromosome aberration in 10 children with malignant tumor was observed and compared with normal children. These patients commonly had chromosome fragmentation . gap or dicentric chromosome. Six of them had chromosome deletion at distal end. The chromosome aberration rate in children with malignant tumor (2. 13%) was remarkably higher than that in normal children (0. 5%). The significance of chromosome aberration on tumor pathogenesis, gene mutation and genetic research is discussed.%观察10例小儿恶性肘,瘤患者染色体畸变情况,并与正常儿童对照.恶性肿瘤患者常见染色体断裂、裂隙或双着丝粒染色体,并有6例10个染色体有远端断缺失.恶性肿瘤患者染色体畸变率(2.13%)显著高于正常儿童(0.52%).探讨染色体畸变对肿瘤发病机理、基因突变、遗传研究的意义.

  11. Inhaled ozone as a mutagen. II - Effect on the frequency of chromosome aberrations observed in irradiated Chinese hamsters.

    Science.gov (United States)

    Zelac, R. E.; Cromroy, H. L.; Bolch, W. E., Jr.; Dunavant, B. G.; Bevis, H. A.

    1971-01-01

    Exposure-adjusted break frequencies for chromosome aberrations produced in Chinese hamster circulating blood lymphocytes were the quantitative indicator of damage from 5 hrs of exposure to X-radiation and/or to ozone. Radiation produced 5.51 x 0.0001 breaks/cell rad for cells withdrawn 2 weeks after exposure, a reasonable value when compared with data from in vivo exposure of human lymphocytes and Chinese hamster bone marrow cells. Animals exposed to the two agents simultaneously exhibited more than 70% of the total breaks anticipated assuming the expected equal contributions to be additive. Extending to humans, at presently permitted levels, exposure to ozone would be much more detrimental than exposure to radiati*n.

  12. Calibration of chromosomal aberrations in the National Institute of Nuclear Research; Calibracion de aberraciones cromosomicas en el ININ

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C.; Arceo M, C.; Brena V, M. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)]. e-mail: cgc@nuclear.inin.mx

    2008-07-01

    In the laboratory of biological dosimetry of the National Institute of Nuclear Research one carried out a calibration of chromosomal aberrations. The result obtained by the different participants does not mark to significant differences between the readings of the cells and the considered one of dose for each one of the cases. The biological material for this intercomparison was prepared in the Republic of Argentina like part of the activities of the Project Regional OIEA-RLA/9/054 {sup S}trengthening of the National Systems for the Preparation and Answer in Radiological and Nuclear Emergencies{sup .} In this regional project participates seven countries of the area and in October of this year will be presented the results of each one of them. Part of the objectives of this project is the one to conform a network of mutual aid in case of radiological accidents for which the participants must unify criteria. (Author)

  13. Research on automatic human chromosome image analysis

    Science.gov (United States)

    Ming, Delie; Tian, Jinwen; Liu, Jian

    2007-11-01

    Human chromosome karyotyping is one of the essential tasks in cytogenetics, especially in genetic syndrome diagnoses. In this thesis, an automatic procedure is introduced for human chromosome image analysis. According to different status of touching and overlapping chromosomes, several segmentation methods are proposed to achieve the best results. Medial axis is extracted by the middle point algorithm. Chromosome band is enhanced by the algorithm based on multiscale B-spline wavelets, extracted by average gray profile, gradient profile and shape profile, and calculated by the WDD (Weighted Density Distribution) descriptors. The multilayer classifier is used in classification. Experiment results demonstrate that the algorithms perform well.

  14. Transvitreal Retinochoroidal Biopsy Provides a Representative Sample From Choroidal Melanoma for Detection of Chromosome 3 Aberrations

    DEFF Research Database (Denmark)

    Bagger, Mette; Andersen, Morten T.; Heegaard, Steffen

    2015-01-01

    PURPOSE: To compare the status of chromosomes 3 and 8 in 25-gauge transvitreal retinochoroidal (TVRC) biopsy specimens and enucleated eyes in order to evaluate for genetic heterogeneity and the utility of TVRC biopsy to obtain an adequate sampling of the tumor. METHODS: Genetic heterogeneity...

  15. Cytotoxicity and chromosome aberrations in normal human oral keratinocytes induced by chemical carcinogens: Comparison of inter-individual variations.

    Science.gov (United States)

    Tsutsui, T; Kawamoto, Y; Suzuki, N; Gladen, B C; Barrett, J C

    1991-01-01

    Normal human keratinocytes from the oral cavity were cultured in vitro in serum-free medium. Cultures from different individuals were established, and the responses of the cells to different chemicals were compared. The cells, grown at clonal densities, were treated separately with an alkylating agent (N-methyl-N'-nitro-N-nitrosoguanidine; MNNG), two arsenical salts (sodium arsenate or sodium arsenite), sodium fluoride or two polyaromatic hydrocarbons (benzo[a]pyrene or 7,12-dimethylbenz[a]-anthracene). There were no significant differences in the colony-forming efficiencies (22.8 +/- 4.2%) of control (untreated) cells from five different individuals. At selected doses, each of the chemicals reduced the colony-forming efficiencies of the treated cells. The cytotoxicity of most of the chemicals did not differ significantly among cells derived from different individuals, with the exception of sodium arsenate at two doses and sodium fluoride at the highest dose tested. Induction of chromosome aberrations by MNNG, sodium arsenite, sodium arsenate and sodium flouride was analysed with cells derived from up to nine individuals. There was little difference in the inducibilities of chromosome aberrations among cultured keratinocytes from different donors. Treatment of cells from nine donors with one dose of sodium fluoride revealed a statistically significant inter-individual variation. These findings provide a model system to study the effects of carcinogens on the target cells for oral cancers. The results can be compared with findings for cells from other epithelial tissues, since the culture conditions support the growth of keratinocytes regardless of origin. Little inter-individual variation was observed in the response of oral keratinocytes to the chemicals examined.

  16. Influence of age and gender in response to {gamma}-radiation in Portuguese individuals using chromosomal aberration assay - Preliminary findings

    Energy Technology Data Exchange (ETDEWEB)

    Martins, V.; Antunes, A.C. [Instituto Tecnologico e Nuclear, Unidade de Proteccao e Seguranca Radiologica, Dosimetry and Radiobiology Group, E.N. 10, Apartado 21, 2686-953 Sacavem (Portugal); Cardoso, J.; Santos, L. [Instituto Tecnologico e Nuclear, Unidade de Proteccao e Seguranca Radiologica, Metrology Laboratory of Ionizing Radiation, E.N. 10, Apartado 21, 2686-953 Sacavem (Portugal); Gil, O. Monteiro, E-mail: octavia.gil@itn.pt [Instituto Tecnologico e Nuclear, Unidade de Proteccao e Seguranca Radiologica, Dosimetry and Radiobiology Group, E.N. 10, Apartado 21, 2686-953 Sacavem (Portugal)

    2011-09-15

    Cytogenetic indicators are widely used in radiobiology to evaluate effects of ionizing radiation since dicentric chromosomes (Dic) are almost exclusively induced by ionizing radiation, and spontaneous frequency of Dic is very low in the healthy general population (about one Dic per 1000 cells). A particular interest of biodosimetry has been not only to obtain absorbed dose estimates using adequate calibration curves, under the assumption that all individuals respond equally to radiation-induced chromosome aberrations, but also to find a way to demonstrate inter-individual radiosensitivity and a possible correlation with age and gender. Thus, the objective of this preliminary work was the evaluation of the influence of age and gender on the outcome of cytogenetic biomarkers after {gamma}-irradiation. Samples of peripheral blood lymphocytes from six healthy, non-smoker, donors from both genders (three men and three women), in the range of 20 to 49 years, were irradiated with doses from 0 Gy to 3 Gy air kerma, using a {sup 60}Co gamma rays source with a dose rate from 170-180 mGy/min. A clear dose-dependent increase in terms of aberrant cells excluding gaps (ACEG) and Dic was observed for all donors. Our preliminary results suggest, in the higher dose level evaluated (3 Gy), a larger intervariability among individuals for Dic, with females apparently more sensitive than males (P<0.05). Considering the different age groups, male donors showed a decrease, with age, for Dic and ACEG at the higher dose and also, for the background level, in case of ACEG. Future work will consider the study of more individuals, from both genders and different ages, in order to verify if this tendency persists and to enable the implementation of a dose-response calibration curve at Instituto Tecnologico e Nuclear for the Portuguese population, to quantify the biological dose in case of a radiological accident or emergency.

  17. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.

    Science.gov (United States)

    Svobodova, Karla; Zemanova, Zuzana; Lhotska, Halka; Novakova, Milena; Podskalska, Lucie; Belickova, Monika; Brezinova, Jana; Sarova, Iveta; Izakova, Silvia; Lizcova, Libuse; Berkova, Adela; Siskova, Magda; Jonasova, Anna; Cermak, Jaroslav; Michalova, Kyra

    2016-03-01

    Complex karyotypes are seen in approximately 20% of patients with myelodysplastic syndromes (MDS) and are associated with a high risk of transformation to acute myeloid leukemia and poor outcomes in patients. Copy number neutral loss of heterozygosity (CN-LOH, i.e., both copies of a chromosomal pair or their parts originate from one parent) might contribute to increased genomic instability in the bone-marrow cells of patients with MDS. The pathological potential of CN-LOH, which arises as a clonal aberration in a proportion of somatic cells, consists of tumor suppressor gene and oncogene homozygous mutations. The aim of our study was to evaluate the frequency of CN-LOH at 17p in bone-marrow cells of newly diagnosed MDS patients with complex chromosomal aberrations and to assess its correlation with mutations in the TP53 gene (17p13.1). CN-LOH was detected in 40 chromosomal regions in 21 (29%) of 72 patients analyzed. The changes in 27 of the 40 regions identified were sporadic. The most common finding was CN-LOH of the short arm of chromosome 17, which was detected in 13 (18%) of 72 patients. A mutational analysis confirmed the homozygous mutation of TP53 in all CN-LOH 17p patients, among which two frameshift mutations are not registered in the International Agency for Research on Cancer TP53 Database. CN-LOH 17p correlated with aggressive disease (median overall survival 4 months) and was strongly associated with a complex karyotype in the cohort studied, which might cause rapid disease progression in high-risk MDS. No other CN-LOH region previously recorded in MDS or AML patients (1p, 4q, 7q, 11q, 13q, 19q, 21q) was detected in our cohort of patients with complex karyotype examined at the diagnosis of MDS. The LOH region appeared to be balanced (i.e., with no DNA copy number change) when examined with conventional and molecular cytogenetic methods. Therefore, a microarray that detects single-nucleotide polymorphisms is an ideal method with which to identify and

  18. Comparison of RBE values of high-LET α-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death

    NARCIS (Netherlands)

    Franken, N.A.P.; ten Cate, R.; Krawczyk, P.M.; Stap, J.; Haveman, J.; Aten, J.; Barendsen, G.W.

    2011-01-01

    Various types of radiation effects in mammalian cells have been studied with the aim to predict the radiosensitivity of tumours and normal tissues, e.g. DNA double strand breaks (DSB), chromosome aberrations and cell reproductive inactivation. However, variation in correlations with clinical results

  19. Chromosomal aberrations, sister-chromatid exchanges, cells with high frequency of SCE, micronuclei and comet assay parameters in 1, 3-butadiene-exposed workers.

    Science.gov (United States)

    Srám, R J; Rössner, P; Peltonen, K; Podrazilová, K; Mracková, G; Demopoulos, N A; Stephanou, G; Vlachodimitropoulos, D; Darroudi, F; Tates, A D

    1998-11-09

    The association of occupational exposure to 1,3-butadiene (BD) and induction of cytogenetic damage in peripheral lymphocytes was studied in 19 male workers from a monomer production unit and 19 control subjects from a heat production unit. The exposure to BD was measured by passive personal monitors. The following biomarkers were used: chromosomal aberrations (CA), sister chromatid exchanges (SCE), cells with a high frequency of SCE (HFC), micronuclei, comet assay parameters like tail length (TL) and percentage of DNA in tail [T (%)] and polymorphisms of GSTM1 and GSTT1 genotypes. BD exposure with a median value of 0.53 mg/m3 (range: 0.024-23.0) significantly increased (a) the percentage of cells with chromosomal aberrations in exposed vs. control groups (3.11% vs. 2.03%, P<0.01), (b) the frequency of SCE per cell (6.96 vs. 4.87, P<0.001), and (c) the percentage of HFC (19.9% vs. 4.1%, P<0.001). BD exposure had no significant effects on formation of micronuclei and on comet assay parameters. Effect of smoking was observed only for HFC in BD-exposed group. GSTM1 genotype affected chromosomal aberrations in exposed group, while GSTT1 genotype affected chromosomal aberrations in controls. No effect of GSTM1 or GSTT1 genotypes was observed on any other biomarkers used.

  20. Radiochemical and radioecological studies on Brazilian areas of high natural background. Progress report, October 30, 1974--October 30, 1975. [Etiology of radioinduced chromosomal aberrations in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Costa-Ribeiro, C.; Penna-Franca, E.; Rocha-Nogueira, A.; Christian-Pfeiffer, W.

    1975-11-01

    The absorption of /sup 212/Pb and/or /sup 212/Bi by ertythrocytes was investigated in an attempt to explain the in vivo genesis of somatic chromosomal aberrations of the type detected in peripheral blood lymphocytes of workers professionally exposed to /sup 220/Rn and its decay products, as well as in dwellers of Brazilian areas of high natural radioactivity. (auth)

  1. Unstable chromosome aberrations on peripheral blood lymphocytes from patients with cervical uterine cancer following radiotherapy; Aberracoes cromossomicas instaveis em linfocitos de pacientes com cancer de colo de utero

    Energy Technology Data Exchange (ETDEWEB)

    Magnata, Simey de Souza Leao Pereira

    2002-09-01

    Absorbed dose determination is an important step for risk assessment related to an exposure to ionizing radiation. However, physical dosimetry cannot be always performed, principally in the case of retrospective estimates. In this context, the use of bioindicators (biological effects) has been proposed, which defines the so-called biological dosimetry. In particular, scoring of unstable chromosomes aberrations (dicentrics, centric rings and fragments) of peripheral blood lymphocytes, while is the most reliable biological method for estimating individual exposure to ionizing radiation. In this work, blood samples from 5 patients, with cervical uterine cancer, were evaluated after partial-body radiotherapy with a source of {sup 69} Co. For this, conventional cytogenetic method was employed, based on Giemsa coloration and fluorescence in situ hybridization, in order to correlate the frequency of unstable chromosome aberrations of blood lymphocytes with absorbed dose, as a result of the radiotherapy. A good agreement was observed between the frequency of chromosome aberrations scored and the values of dose previously calculated by physical dosimetry during patient's radiotherapy. The results presented in this work point out the importance of concerning analyses of unstable chromosome aberrations as biological dosimeter in the investigation of partial-body exposure to ionizing radiation. (author)

  2. X-ray-induced chromosome aberrations in the leukocytes of mouse and man

    Energy Technology Data Exchange (ETDEWEB)

    Preston, R.J.; Brewen, J.G.

    1977-01-01

    In our earlier studies we showed that the frequency of dicentrics induced by x-rays in human leukocytes was about twice that induced in mouse leukocytes. The frequencies of deletions were similar in both species. However, the mouse cultures were fixed at 60 hrs and the human cultures at 54 hrs. In both cases it was likely that some of the cells analyzed were in their second post-treatment mitosis. Further studies were carried out using fixation times of 48 hrs for both human and mouse cultures. The same relationships held here, namely twice as many dicentrics in human, and similar deletion frequencies in both. The aberration frequencies observed were corrected to take account of second division cells, by assuming cells containing a dicentric without an accompanying fragment were in their second division. There were more such cells with the mouse. To further increase reliance on the conclusions, cultures were fixed at the earliest times that 300 cells per dose could be obtained--36 hrs for the mouse, 42 hrs for human. The frequencies of dicentrics were increased in both, and a relationship of about 2:1 for human to mouse was obtained. Deletion frequencies were similar in both. Three different human donors were used. Since no dicentrics without fragments were obtained, it appeared that aberration frequencies in first division cells only were being compared.

  3. Chromosomal aberrations in human hepatocellular carcinomas associated with hepatitis C virus infection detected by comparative genomic hybridization

    Science.gov (United States)

    Sakakura, C; Hagiwara, A; Taniguchi, H; Yamaguchi, T; Yamagishi, H; Takahashi, T; Koyama, K; Nakamura, Y; Abe, T; Inazawa, J

    1999-01-01

    Thirty-five hepatocellular carcinomas (HCCs) associated with hepatitis C virus (HCV) were analysed by comparative genomic hybridization (CGH), to screen for changes in copy-number of DNA sequences. Chromosomal losses were noted in 1p34–36 (37%), 4q12–21 (48%), 5q13–21 (35%), 6q13–16 (23%), 8p21–23 (28%), 13q (20%), 16q (33%) and 17p13 (37%). Gains were noted in 1q (46%), 6p (20%), 8q21–24 (31%) and 17q (43%). High level gains indicative of gene amplifications were found in 7q31 (3%), 11q13 (3%), 14q12 (6%) and 17q12 (3%); amplification at 14q12 may be characteristic for HCCs. No significant difference in chromosomal aberrations was noted between carcinomas associated with HCV-infection in our study and those reported earlier in HCCs infected with hepatitis B virus (HBV), indicating that both HBV- and HCV-related carcinomas may progress through a similar cascade of molecular events. © 1999 Cancer Research Campaign PMID:10471057

  4. Chromosomal aberrations in humans induced by urban air pollution: influence of DNA repair and polymorphisms of glutathione S-transferase M1 and N-acetyltransferase 2

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, H; Gamborg, M O

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes...... that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  5. Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm.

    Science.gov (United States)

    Rumi, Elisa; Harutyunyan, Ashot; Elena, Chiara; Pietra, Daniela; Klampfl, Thorsten; Bagienski, Klaudia; Berg, Tiina; Casetti, Ilaria; Pascutto, Cristiana; Passamonti, Francesco; Kralovics, Robert; Cazzola, Mario

    2011-12-01

    Myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These disorders may undergo phenotypic shifts, and may specifically evolve into secondary myelofibrosis (MF) or acute myeloid leukemia (AML). We studied genomic changes associated with these transformations in 29 patients who had serial samples collected in different phases of disease. Genomic DNA from granulocytes, i.e., the myeloproliferative genome, was processed and hybridized to genome-wide human SNP 6.0 arrays. Most patients in chronic phase had chromosomal regions with uniparental disomy (UPD) and/or copy number changes. Disease progression to secondary MF or AML was associated with the acquisition of additional chromosomal aberrations in granulocytes (P = 0.002). A close relationship was observed between aberrations of chromosome 9p (UPD and/or gain) and progression from PV to post-PV MF (P = 0.002). The acquisition of one or more aberrations involving chromosome 5, 7, or 17p was specifically associated with progression to AML (OR 5.9, 95% CI 1.2-27.7, P = 0.006), and significantly affected overall survival (HR 18, 95% CI 1.9-164, P = 0.01). These observations indicate that disease progression from chronic-phase MPN to secondary MF or AML is associated with specific chromosomal aberrations that can be detected by means of high-resolution SNP array analysis of granulocyte DNA.

  6. Chromosomal aberration frequencies determined by conventional methods: Parallel increases over time in the region of a petrochemical industry and throughout the Czech Republic.

    Science.gov (United States)

    Sram, Radim J; Rössner, Pavel; Beskid, Olena; Bavorova, Hana; Ocadlikova, Dana; Solansky, Ivo; Albertini, Richard J

    2007-03-20

    The rationale for cytogenetic monitoring to determine if safe maximum allowable concentrations (MAC) of genotoxic chemicals are being maintained in a workplace is that exposure levels that do not increase chromosomal aberration frequencies are without harmful effects. Such monitoring, widely used in occupational health programs in the Czech Republic (CR), includes workers exposed to 1,3-butadiene (BD) or other chemicals. Studies of BD exposed workers in the years 1992, 1993, 1994, 1998, and 2004 compared mean frequencies of cells carrying chromosomal aberrations (frequency of aberrant cells=%AB.C.) in exposed workers with those in non-exposed matched controls in the same plant or in other individuals living in the region of the same petrochemical industry. Workers potentially exposed to acrylonitrile at this site were also evaluated in 2000, along with another unexposed matched control group. The %AB.C. values of exposed workers and their controls were also compared with reference values determined for normal individuals (ages 20-59 years) throughout the CR. Substantial discrepancies were noted between subjects in the region of the petrochemical industry (exposed workers and controls) for the years 2000 and 2004 and the reference CR-wide normal values that had been determined during an earlier time period. The matched non-exposed controls at the petrochemical industry site showed a mean %AB.C. value of 1.56+/-1.23% (N=25) in 1998; this rose to a mean of 2.65+/-2.29% (N=33) in 2000. In 2004, values for non-exposed matched controls at the industry site were 2.64+/-1.75% for males (N=25) and 2.38+/-1.74% (N=26) for females. However, the earlier determined CR-wide %AB.C. mean reference values for normal individuals were 1.77+/-1.16% (N=1305) for the interval 1977-1988 and 1.45+/-1.17% (N=2140) for the interval 1991-1999. As both reference values are substantially lower than those determined in 2000 and 2004 for the non-exposed matched controls at the petrochemical

  7. Spherical aberration and other higher-order aberrations in the human eye : from summary wave-front analysis data to optical variables relevant to visual perception

    NARCIS (Netherlands)

    Jansonius, Nomdo M.

    2010-01-01

    Wave-front analysis data from the human eye are commonly presented using the aberration coefficient c(4)(0) (primary spherical aberration) together with an overall measure of all higher-order aberrations. If groups of subjects are compared, however, the relevance of an observed difference cannot eas

  8. Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Benkhaled, L.; Xuncla, M.; Caballin, M.R. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain); Barrios, L. [Universitat Autonoma de Barcelona, Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia (Spain); Barquinero, J.F. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain)], E-mail: Francesc.Barquinero@uab.es

    2008-01-01

    Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation ({approx}0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.

  9. [Retrospective Cytogenetic Dose Evaluation. I. Chromosome Aberration Levels in Remote Periods after Acute External Exposure in Different Situations].

    Science.gov (United States)

    Nugs, V Yu; Khvostunov, I K; Goloub, E V; Kozlova, M G; Nadejina, N M; Galstian, I A

    2015-01-01

    Cytogenetic analysis of peripheral blood lymphocyte cultures of 22 persons was performed in remote terms after acute external γ-, γ-β- or γ-neutron irradiation as a result of various accidents using the classical me- thod. The initial dose estimates were obtained using physical calculations, the method of measuring the EPR signal in tooth enamel, according to haematological and/or cytogenetic parameters. The purpose of this study was to obtain evidence about the state of the lymphocyte chromosome apparatus of people approxi- mately 17-50 years after an accidental radiation exposure. In general, elevated levels of chromosome aberra- tions were detected. An average correlation was observed between the atypical chromosome frequency and absorbed dose. It is proposed to use the obtained results in the future to explore the possibility of retrospective dose evaluation on the basis of a special computer program.

  10. Induction of chromosomal aberrations in rat bone marrow cells and mutations in Salmonella typhimurium by benz[a]anthracene derivatives.

    Science.gov (United States)

    Ito, Y; Ueda, N; Maeda, S; Murao, S; Sugiyama, T; Lee, H; Harvey, R G

    1988-09-01

    Benz[a]anthracene (BA) and its derivatives containing methyl and/or ethyl groups in the 7 and/or 12 positions were tested for their ability to induce chromosome aberrations (CA) in rat bone marrow cells and for their mutagenicity to Salmonella typhimurium TA100 or TA98. The incidence of aberrant cells induced by the BA derivatives, given in lipid emulsion as a single-pulse dose of 50 mg/kg body weight into the caudal vein, was in the order: DMBA greater than EMBA greater than MEBA greater than other BA derivatives = control. The alkyl groups, at least 1 methyl group, at the 7 and 12 positions of BA seemed to be necessary to induce CA, although DEBA having ethyl groups at both the 7 and 12 positions of BA did not induce CA. DMBA or EMBA induced not only gaps and breaks but also exchanges and multiple CA, while the CA induced by other BA derivatives consisted of only gaps and breaks. 7MBA and 12MBA which exhibit carcinogenic activity intermediate between that of DMBA and BA induced few CA in the present system. However, the correlation coefficient between the logarithm incidence of aberrant cells and the carcinogenicity index calculated from the data of 9 BA derivatives including both 7MBA and 12MBA was 0.792. The relative mutagenicities of the BA derivatives with TA100 in the presence of hepatic S9 from polychlorinated biphenyl (PCB)-treated rats were in the order: BA greater than 7MBA greater than DMBA greater than 12MBA greater than 7EBA greater than EMBA greater than MEBA greater than 12EBA = DEBA = control. The results with TA98 were essentially the same as those with TA100. The results with TA100 in the presence of hepatic S9 from phenobarbital (PB)-treated rats were in the order: DMBA greater than 12MBA greater than 7MBA greater than 7EBA greater than BA greater than EMBA = MEBA greater than 12EBA = DEBA = control. These findings reveal no obvious relation between the mutagenic activities of the BA derivatives with the PCB-S9 or PB-S9 activating systems and

  11. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  12. High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts

    Science.gov (United States)

    Kawata, T.; Gotoh, E.; Durante, M.; Wu, H.; George, K.; Furusawa, Y.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

    2000-01-01

    PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

  13. mBAND Analysis of Early and Late Damages in the Chromosome of Human Lymphocytes after Exposures to Gamma Rays and Fe Ions

    Science.gov (United States)

    Sunagawa, Mayumi; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2013-01-01

    Stable type chromosome aberrations that survive multiple generations of cell division include translocation and inversions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. At the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Detailed analysis of breaks participating in total chromosome exchanges within the first cell cycle post irradiation revealed a common hotspot located in the 3p21 region, which is a known fragile site corresponding to the band 6 in the mBand analysis. The breakpoint distribution in chromosomes collected at 7 days, but not at 14 days, post irradiation appeared similar to the distribution in cells collected within the first cell cycle post irradiation. The breakpoint distribution for human lymphocytes after radiation exposure was different from the previously published distribution for human

  14. Evaluation of chromosome aberration frequency instable in individual groups residents at the municipality of Monte Alegre, Para, Brazil, exposed to radon; Avaliacao da frequencia de aberracoes cromossomicas instaveis em grupos de individuos residentes no municipio de Monte Alegre - PA expostos diferencialmente ao radonio

    Energy Technology Data Exchange (ETDEWEB)

    Yunes, Samira Nogarol

    2010-07-01

    The municipality of Monte Alegre is a region that presents natural radiation high due to the presence of the radionuclide uranium ({sup 238}U) in its soil, which through its decay gives rise to element Rn, a gas. The radioactivity of the rocks has become a problem for the population of Monte Alegre, from the moment when the radioactive material began to be used in the construction of houses and paving of streets. Among all bio markers related to environmental exposures and its biological effects, the chromosomal aberrations are considered good bio markers as predictors of the risk of cancer. Studies suggest that the frequency of chromosomal aberrations may be related to the genetic instability individual and/or exposure to ionizing radiation. Our work aimed to evaluate the frequency of chromosomal aberrations in individuals in the region of high natural radioactivity in Monte Alegre-PA. As well as to correlate the cytogenetic analysis made in this study with the results of analysis of frequency of polymorphisms of genes of DNA repair carried out in another study that resulted in other dissertation. In accordance with the distribution of the data obtained in characterizing environmental radiological and in the calculation of dose, were chosen residents of homes with more and less exposure to radiation. The samples of peripheral blood of 85 individuals of the resident population of the region of Monte Alegre - PA were collected and examine provided two slides for individual was performed to verify the quality of the sample. Through this evaluation we decide that 33% of the material collected, or is, samples of 28 individuals were in suitable conditions for analysis of the frequency of chromosomal aberrations. After the collections lymphocytes present in the sample were cultivated in accordance with the methodology proposed for obtaining of cells in metaphase. were analyzed 6,177 metaphases of 28 individuals among which were found dicentric chromosomes 4 and 19

  15. Influence of retinol on carcinogen-induced sister chromatid exchangers and chromosome aberrations in V79 cells

    Energy Technology Data Exchange (ETDEWEB)

    Qin, S.; Batt, T.; Huang, C.C.

    1985-01-01

    The influence of retinol (Rol) on sister chromatid exchangers (SCE) in V79 cells induced by six indirect and two direct carcinogens, and on chromosome aberration (CA) in V79 cells induced by four indirect carcinogens were studied. The indirect carcinogens used were aflatoxin B/sub 1/ (AFB), cyclophosphamide (CPP), benzo(a)anthracene (BA), benzo(a)pyrene (BP), 9,10-dimethyl-1,2-benz(a)anthracene (DMBA), and 3-methylcholanthrene (MCA). The two direct carcinogens were ethyl methane sulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rol effectively inhibited SCE and CA induced by AFB and CPP in a dose-dependent manner, but it had no effect on SCE induced by BA, BP, DMBA, MCA, EMS, and MNNG. To the contrary, Rol had an enhancing effect on CA induced by BP and DMBA. The possibility that Rol exerts its anticarcinogenic effects by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of precarcinogens, such as AFB and CPP but not those enzymes required by BA, BP, DMBA, and MCA, is discussed.

  16. Examination of the potential genotoxicity of pure capsaicin in bacterial mutation, chromosome aberration, and rodent micronucleus tests.

    Science.gov (United States)

    Proudlock, Raymond; Thompson, Crista; Longstaff, Eric

    2004-01-01

    There is widespread dietary exposure to capsaicin in the form of chili peppers, while capsaicin's analgesic qualities have led to increased use of a topical herbal remedy in various impure forms. Most recently, injection of pure capsaicin has been proposed as a means of relieving a variety of debilitating diseases, in which case tissues would receive relatively high and direct exposure. The purpose of the present study, where a series of standard assays were performed in accordance with the Organisation for Economic Cooperation and Development guidance, was to clarify earlier conflicting reports concerning potential genotoxicity of capsaicin prior to administering it to patients in an injectable form. The results confirm the absence of genotoxic activity of high-purity capsaicin in the bacterial mutation and chromosome aberration tests. In addition, no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow micronucleus test, where systemic exposure to pure capsaicin was achieved using the subcutaneous route and a rising dose toleration protocol. It is concluded that pure capsaicin is not active in the standard battery of genotoxicity assays recommended by the International Conference on Harmonisation for evaluation of new medicines; earlier reported in vitro genotoxic activity is probably associated with mutagenic impurities in commercial grades of the material.

  17. Simulations of DSB Yields and Radiation-induced Chromosomal Aberrations in Human Cells Based on the Stochastic Track Structure iIduced by HZE Particles

    Science.gov (United States)

    Ponomarev, Artem; Plante, Ianik; George, Kerry; Wu, Honglu

    2014-01-01

    The formation of double-strand breaks (DSBs) and chromosomal aberrations (CAs) is of great importance in radiation research and, specifically, in space applications. We are presenting a new particle track and DNA damage model, in which the particle stochastic track structure is combined with the random walk (RW) structure of chromosomes in a cell nucleus. The motivation for this effort stems from the fact that the model with the RW chromosomes, NASARTI (NASA radiation track image) previously relied on amorphous track structure, while the stochastic track structure model RITRACKS (Relativistic Ion Tracks) was focused on more microscopic targets than the entire genome. We have combined chromosomes simulated by RWs with stochastic track structure, which uses nanoscopic dose calculations performed with the Monte-Carlo simulation by RITRACKS in a voxelized space. The new simulations produce the number of DSBs as function of dose and particle fluence for high-energy particles, including iron, carbon and protons, using voxels of 20 nm dimension. The combined model also calculates yields of radiation-induced CAs and unrejoined chromosome breaks in normal and repair deficient cells. The joined computational model is calibrated using the relative frequencies and distributions of chromosomal aberrations reported in the literature. The model considers fractionated deposition of energy to approximate dose rates of the space flight environment. The joined model also predicts of the yields and sizes of translocations, dicentrics, rings, and more complex-type aberrations formed in the G0/G1 cell cycle phase during the first cell division after irradiation. We found that the main advantage of the joined model is our ability to simulate small doses: 0.05-0.5 Gy. At such low doses, the stochastic track structure proved to be indispensable, as the action of individual delta-rays becomes more important.

  18. Simulations of DSB Yields and Radiation-induced Chromosomal Aberrations in Human Cells Based on the Stochastic Track Structure Induced by HZE Particles

    Science.gov (United States)

    Ponomarev, Artem; Plante, Ianik; George, Kerry; Wu, Honglu

    2014-01-01

    The formation of double-strand breaks (DSBs) and chromosomal aberrations (CAs) is of great importance in radiation research and, specifically, in space applications. We are presenting a new particle track and DNA damage model, in which the particle stochastic track structure is combined with the random walk (RW) structure of chromosomes in a cell nucleus. The motivation for this effort stems from the fact that the model with the RW chromosomes, NASARTI (NASA radiation track image) previously relied on amorphous track structure, while the stochastic track structure model RITRACKS (Relativistic Ion Tracks) was focused on more microscopic targets than the entire genome. We have combined chromosomes simulated by RWs with stochastic track structure, which uses nanoscopic dose calculations performed with the Monte-Carlo simulation by RITRACKS in a voxelized space. The new simulations produce the number of DSBs as function of dose and particle fluence for high-energy particles, including iron, carbon and protons, using voxels of 20 nm dimension. The combined model also calculates yields of radiation-induced CAs and unrejoined chromosome breaks in normal and repair deficient cells. The joined computational model is calibrated using the relative frequencies and distributions of chromosomal aberrations reported in the literature. The model considers fractionated deposition of energy to approximate dose rates of the space flight environment. The joined model also predicts of the yields and sizes of translocations, dicentrics, rings, and more complex-type aberrations formed in the G0/G1 cell cycle phase during the first cell division after irradiation. We found that the main advantage of the joined model is our ability to simulate small doses: 0.05-0.5 Gy. At such low doses, the stochastic track structure proved to be indispensable, as the action of individual delta-rays becomes more important.

  19. 35. Detection of numerical chromosome aberrations in sperm of workers exposed to benzene series by two-color fluorescence in situ hybridization

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To study the frequency of numerical chromosome aberrations in sperm of workers exposed to benzene series, the aneuploidy frequencies of 9 and 18 chromosomes were detected in sperm of workers by two color fluorescence in situ hybridization with digoxingenin labeled 9 chromosome probe (D9zl) and biotin labeled 18 chromosome probe (D18zl). The timeweight average air concentration (TWA ) of benzene in the workplace was 86.49 mg/m3, it was two fold higher than the national maximum allowable concentration. The concentration of urinary trans,trans-muconic acid (ttMA) in exposed group was significantly higher than that of control group. The sperms counted in 14 exposed workers and 16 control workers were 136 401 and 156 955 respectively. The results showed that the disomy frequencies of sperm for chromosome 9, 18 in (0.168%±0.063% and 0.055%±0.031% respectively) and the frequency of diploidy sperm (0.073%±0.045%) were statistically increased over that of the control group(0.050%±0.030%; 0.033%±0.025% and 0.040%±0.036%, respectively). The nullisomic frequencies of 9,18 chromosome in the exposed group (0.206%±0.047%, 0.068%±0.044%) were statistically increased over that of the control group too (0.067%±0.037%, 0.048%±0.034%). The frequency of overall numerical chromosome aberrations in the exposed group was 0.570%±0.144%, when this value was compared with that of control (0.218%±0.071%), a statistically significance was presented. Our experiments showed that exposed to benzene at higher concentration may induce increase in aneuploidy frequency of sperm autosomal chromosome in exposed workers.

  20. Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, Megumi; George, Kerry A.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.

  1. Chromosome aberrations induced in human lymphocytes by U-235 fission neutrons: I. Irradiation of human blood samples in the "dry cell" of the TRIGA Mark II nuclear reactor.

    Science.gov (United States)

    Fajgelj, A; Lakoski, A; Horvat, D; Remec, I; Skrk, J; Stegnar, P

    1991-11-01

    A set-up for irradiation of biological samples in the TRIGA Mark II research reactor in Ljubljana is described. Threshold activation detectors were used for characterisation of the neutron flux, and the accompanying gamma dose was measured by TLDs. Human peripheral blood samples were irradiated "in vitro" and biological effects evaluated according to the unstable chromosomal aberrations induced. Biological effects of two types of cultivation of irradiated blood samples, the first immediately after irradiation and the second after 96 h storage, were studied. A significant difference in the incidence of chromosomal aberrations between these two types of samples was obtained, while our dose-response curve fitting coefficients alpha 1 = (7.71 +/- 0.09) x 10(-2) Gy-1 (immediate cultivation) and alpha 2 = (11.03 +/- 0.08) x 10(-2) Gy-1 (96 h delayed cultivation) are in both cases lower than could be found in the literature.

  2. Automation of the in vitro micronucleus and chromosome aberration assay for the assessment of the genotoxicity of the particulate and gas-vapor phase of cigarette smoke.

    Science.gov (United States)

    Roemer, Ewald; Zenzen, Volker; Conroy, Lynda L; Luedemann, Kathrin; Dempsey, Ruth; Schunck, Christian; Sticken, Edgar Trelles

    2015-01-01

    Total particulate matter (TPM) and the gas-vapor phase (GVP) of mainstream smoke from the Reference Cigarette 3R4F were assayed in the cytokinesis-block in vitro micronucleus (MN) assay and the in vitro chromosome aberration (CA) assay, both using V79-4 Chinese hamster lung fibroblasts exposed for up to 24 h. The Metafer image analysis platform was adapted resulting in a fully automated evaluation system of the MN assay for the detection, identification and reporting of cells with micronuclei together with the determination of the cytokinesis-block proliferation index (CBPI) to quantify the treatment-related cytotoxicity. In the CA assay, the same platform was used to identify, map and retrieve metaphases for a subsequent CA evaluation by a trained evaluator. In both the assays, TPM and GVP provoked a significant genotoxic effect: up to 6-fold more micronucleated target cells than in the negative control and up to 10-fold increases in aberrant metaphases. Data variability was lower in the automated version of the MN assay than in the non-automated. It can be estimated that two test substances that differ in their genotoxicity by approximately 30% can statistically be distinguished in the automated MN and CA assays. Time savings, based on man hours, due to the automation were approximately 70% in the MN and 25% in the CA assays. The turn-around time of the evaluation phase could be shortened by 35 and 50%, respectively. Although only cigarette smoke-derived test material has been applied, the technical improvements should be of value for other test substances.

  3. Influence of DNA repair gene polymorphisms of hOGG1, XRCC1, XRCC3, ERCC2 and the folate metabolism gene MTHFR on chromosomal aberration frequencies.

    Science.gov (United States)

    Skjelbred, Camilla Furu; Svendsen, Marit; Haugan, Vera; Eek, Anette Kildal; Clausen, Kjell Oskar; Svendsen, Martin Veel; Hansteen, Inger-Lise

    2006-12-01

    We have studied the effect of genetic polymorphisms in the DNA repair genes hOGG1, XRCC1, XRCC3, ERCC2 and the MTHFR gene in the folate metabolism on the frequencies of cells with chromosomal aberrations (CA), chromosome-type aberrations (CSA), chromatid-type aberrations (CTA), chromatid breaks (CTB) and chromatid gaps (CTG) scored in peripheral blood lymphocytes from 651 Norwegian subjects of Caucasian descendant. DNA was extracted from fixed cell suspensions. The log-linear Poisson regression model was used for the combined data which included age, smoking, occupational exposure and genotype for 449 subjects. Our results suggest that individuals carrying the hOGG1 326Cys or the XRCC1 399Gln allele have an increased risk of chromosomal damage, while individuals carrying the XRCC1 194Trp or the ERCC2 751Gln allele have a reduced risk regardless of smoking habits and age. Individuals carrying the XRCC1 280His allele had an increased risk of CSA which was only apparent in non-smokers. This was independent of age. A protective effect of the XRCC3 241Met allele was only found in the older age group in non-smokers for CA, CSA and CTA, and in smokers for CSA. In the youngest age group, the opposite effect was found, with an increased risk for CA, CTA and CTG in smokers. Carrying the MTHFR 222Val allele gave an increased risk for chromosome and chromatid-type aberrations for both non-smokers and smokers, especially for individuals in the older age group, and with variable results in the youngest age group. The variables included in the different regression models accounted, however, for only 4-10% of the variation. The frequency ratio for CTG was significantly higher than for CTA and CTB for only 7 of the 43 comparisons performed. Some of the gap frequencies diverge from the trend in the CA, CSA, CTA and CTB results.

  4. [The effect of mixed cultivation of lymphocytes irradiated at a dose of 1 Gy and non-irradiated lymphocytes on the frequency of chromosomal aberration].

    Science.gov (United States)

    Kolesnikova, I S

    2012-01-01

    The mutual influence of irradiated (1 Gy) and non-irradiated cells was demonstrated on the model of the mixed culture oflymphocytes from opposite gender donors using chromosome aberrations (ChA) as an endpoint. The number of ChA in non-irradiated lymphocytes in mixed cultures with irradiated ones increased as compared to the corresponding monocultures. At the same time, the number of induced ChA decreased in the irradiated lymphocytes cultivated with non-irradiated ones.

  5. The antigenotoxic activities of cactus (Opuntia ficus-indica) cladodes against the mycotoxin zearalenone in Balb/c mice: prevention of micronuclei, chromosome aberrations and DNA fragmentation.

    Science.gov (United States)

    Zorgui, Lazhar; Ayed-Boussema, Imen; Ayed, Yosra; Bacha, Hassen; Hassen, Wafa

    2009-03-01

    Zearalenone (ZEN) is a potent estrogenic metabolite. Evidence of its cytotoxicity and genotoxicity has recently emerged from several reports. This study was conducted to evaluate the ability of cactus (Opuntia ficus-indica) cladodes to protect Balb/c mice against ZEN induced genotoxicity. To this end, the effect of a single dose of ZEN (40 mg/kg b.w.) alone and with extract of cactus cladodes (25, 50 and 100 mg/kg b.w.) was monitored by measuring: (i) micronuclei induction in bone marrow cells, (ii) chromosome aberrations mainly breaks and gaps in bone marrow cells also and finally and (iii) DNA fragmentation in liver and kidney. Our results clearly show that ZEN is genotoxic to Balb/c mice. It induces DNA damage as indicated by DNA fragmentation, micronuclei and chromosomal aberrations in bone marrow cells. It is of note that cactus cladodes extract assayed alone at high dose (100 mg/kg b.w.) was found completely safe and did not induce any genotoxic effects. The simultaneous administration of cactus cladodes extract with ZEN resulted in an efficient prevention of micronuclei (the number of PCE MN decreased from 71.3+/-6.1 for animals treated with Zen to 32.6+/-15.5 for animals treated with cactus cladodes), chromosomal aberrations frequency (the % of chromosomal aberrations decreased from 38.3+/-3.0 to 18.6+/-1.1) in bone marrow cells and of DNA fragmentation compared to the group treated with ZEN alone. It could be concluded that cactus cladodes extract was effective in the protection against ZEN genotoxicity. This could be relevant, particularly with the emergent demand for natural products which may neutralize the genotoxic effects of the multiple food contaminants.

  6. Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud’s phenomenon

    Directory of Open Access Journals (Sweden)

    L. Migliore

    2011-09-01

    Full Text Available Objective: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud’s phenomenon (RP, by means of molecular cytogenetic analysis. Methods: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH analysis using a pancentromeric DNA probe was also performed. Results: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39±15.2 vs 10±2.1 and 9.8±3.5 respectively p<0.0001. Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44±8.1 as compared to subjects with different antibody pattern (26±7.1. Conclusions: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP.

  7. Particle trajectories in seeds of Lactuca sativa and chromosome aberrations after exposure to cosmic heavy ions on cosmos biosatellites 8 and 9

    Science.gov (United States)

    Facius, R.; Scherer, K.; Reitz, G.; Bücker, H.; Nevzgodina, L. V.; Maximova, E. N.

    1994-10-01

    The potentially specific importance of the heavy ions of the galactic cosmic radiation for radiation protection in manned spaceflight continues to stimulate in situ, i.e., spaceflight experiments to investigate their radiobiological properties. Chromosome aberrations as an expression of a direct assault on the genome are of particular interest in view of cancerogenesis being the primary radiation risk for man in space. In such investigations the establishment of the geometrical correlation between heavy ions' trajectories and the location of radiation sensitive biological substructures is an essential task. The overall qualitative and quantitative precision achieved for the identification of particle trajectories in the order of 2~10 μm as well as the contributing sources of uncertainties are discussed. We describe how this was achieved for seeds of Lactuca sativa as biological test organisms, whose location and orientation had to be derived from contact photographies displaying their outlines and those of the holder plates only. The incidence of chromosome aberrations in cells exposed during the COSMOS 1887 (Biosatellite 8) and the COSMOS 2044 (Biosatellite 9) mission was determined for seeds hit by cosmic heavy ions. In those seeds the incidence of both single and multiple chromosome aberrations was enhanced. The results of the Biosatellite 9 experiment, however, are confounded by spaceflight effects unrelated to the passage of heavy ions.

  8. In vitro Antigenotoxicity of Ulva rigida C.Agardh (Chlorophyceae) Extract against Induction of Chromosome Aberration,Sister Chromatid Exchange and Micronuclei by Mutagenic Agent MMC

    Institute of Scientific and Technical Information of China (English)

    SERAP CELIKLER; GAMZE YILDIZ; OZGUR VATAN; RAHMI BILALOGLU

    2008-01-01

    To determine the in vitro possible clastogenic and cytotoxic activities of Uh,a rigida crude extracts (UP,E),and identify their antigenotoxic and protective effects on chemotherapeutic agent mitomycine-C (MMC).Methods Anti-clastogenic and anti-genotoxic activities of Ulva rigida crude extracts (URE) were studied using chromosome aberration (CA),sister chromatid exchange (SCE),and micronuclei (MN) tests in human lymphocytes cultured in vitro.Results The chromosome aberration,sister chromatid exchange or micronuclei tests showed that URE at concentrations of 10,20,and 40 μg/mL had no clastogenic activity in human lymphocyte cell culture.Three doses of URE significantly decreased the number of chromosomal aberrations and the frequencies of SCE and MN when compared with the culture treated with MMC (P<0.0001).Conclusion Although URE itself is not a clastogenic or cytotoxic substance,it possesses strong antigenotoxic,anti-clastogenic,and protective effects on MMC in vitro.

  9. Test for Chemical Induction of Chromosome Aberration in Cultured Chinese Hamster Ovary (CHO) Cells With and Without Metabolic Activation. Test Article: N,N,N’,N’-tetramethyl Ethanediamine (TMEDA)

    Science.gov (United States)

    2008-06-13

    union. d Dicentric - an asymmetrical exchange between two chromosomes resulting in a chromosome with two centromeres with or without an accompanying...Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster Ovary (CHO) Cells With and Without Metabolic Activation Test...number. 1. REPORT DATE 26 JUN 2008 2. REPORT TYPE 3. DATES COVERED 4. TITLE AND SUBTITLE Test for Chemical Induction of Chromosome

  10. Chromatin dynamics during cell cycle mediate conversion of DNA damage into chromatid breaks and affect formation of chromosomal aberrations: Biological and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Terzoudi, Georgia I.; Hatzi, Vasiliki I. [Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' Demokritos' , 15310 Ag. Paraskevi Attikis, Athens (Greece); Donta-Bakoyianni, Catherine [Oral Diagnosis and Radiology, University of Athens Dental School, Athens (Greece); Pantelias, Gabriel E., E-mail: gabriel@ipta.demokritos.gr [Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' Demokritos' , 15310 Ag. Paraskevi Attikis, Athens (Greece)

    2011-06-03

    The formation of diverse chromosomal aberrations following irradiation and the variability in radiosensitivity at different cell-cycle stages remain a long standing controversy, probably because most of the studies have focused on elucidating the enzymatic mechanisms involved using simple DNA substrates. Yet, recognition, processing and repair of DNA damage occur within the nucleoprotein complex of chromatin which is dynamic in nature, capable of rapid unfolding, disassembling, assembling and refolding. The present work reviews experimental work designed to investigate the impact of chromatin dynamics and chromosome conformation changes during cell-cycle in the formation of chromosomal aberrations. Using conventional cytogenetics and premature chromosome condensation to visualize interphase chromatin, the data presented support the hypothesis that chromatin dynamic changes during cell-cycle are important determinants in the conversion of sub-microscopic DNA lesions into chromatid breaks. Consequently, the type and yield of radiation-induced chromosomal aberrations at a given cell-cycle-stage depends on the combined effect of DNA repair processes and chromatin dynamics, which is cell-cycle-regulated and subject to up- or down-regulation following radiation exposure or genetic alterations. This new hypothesis is used to explain the variability in radiosensitivity observed at various cell-cycle-stages, among mutant cells and cells of different origin, or among different individuals, and to revisit unresolved issues and unanswered questions. In addition, it is used to better understand hypersensitivity of AT cells and to provide an improved predictive G2-assay for evaluating radiosensitivity at individual level. Finally, experimental data at single cell level obtained using hybrid cells suggest that the proposed hypothesis applies only to the irradiated component of the hybrid.

  11. From amplification to gene in thyroid cancer: A high-resolution mapped bacterial-artificial-chromosome resource for cancer chromosome aberrations guides gene discovery after comparative genome hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X.N.; Gonsky, R.; Korenberg, J.R. [UCLA School of Medicine, Los Angeles, CA (United States). Cedars-Sinai Research Inst.; Knauf, J.A.; Fagin, J.A. [Univ. of Cincinnati, OH (United States). Div. of Endocrinology/Metabolism; Wang, M.; Lai, E.H. [Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Pharmacology; Chissoe, S. [Washington Univ. School of Medicine, St. Louis, MO (United States). Genome Sequencing

    1998-08-01

    Chromosome rearrangements associated with neoplasms provide a rich resource for definition of the pathways of tumorigenesis. The power of comparative genome hybridization (CGH) to identify novel genes depends on the existence of suitable markers, which are lacking throughout most of the genome. The authors now report a general approach that translates CGH data into higher-resolution genomic-clone data that are then used to define the genes located in aneuploid regions. They used CGH to study 33 thyroid-tumor DNAs and two tumor-cell-line DNAs. The results revealed amplifications of chromosome band 2p21, with less-intense amplification on 2p13, 19q13.1, and 1p36 and with least-intense amplification on 1p34, 1q42, 5q31, 5q33-34, 9q32-34, and 14q32. To define the 2p21 region amplified, a dense array of 373 FISH-mapped chromosome 2 bacterial artificial chromosomes (BACs) was constructed, and 87 of these were hybridized to a tumor-cell line. Four BACs carried genomic DNA that was amplified in these cells. The maximum amplified region was narrowed to 3--6 Mb by multicolor FISH with the flanking BACs, and the minimum amplicon size was defined by a contig of 420 kb. Sequence analysis of the amplified BAC 1D9 revealed a fragment of the gene, encoding protein kinase C epsilon (PKC{epsilon}), that was then shown to be amplified and rearranged in tumor cells. In summary, CGH combined with a dense mapped resource of BACs and large-scale sequencing has led directly to the definition of PKC{epsilon} as a previously unmapped candidate gene involved in thyroid tumorigenesis.

  12. Chromosome analysis and sorting using flow cytometry.

    Science.gov (United States)

    Doležel, Jaroslav; Kubaláková, Marie; Cíhalíková, Jarmila; Suchánková, Pavla; Simková, Hana

    2011-01-01

    Chromosome analysis and sorting using flow cytometry (flow cytogenetics) is an attractive tool for fractionating plant genomes to small parts. The reduction of complexity greatly simplifies genetics and genomics in plant species with large genomes. However, as flow cytometry requires liquid suspensions of particles, the lack of suitable protocols for preparation of solutions of intact chromosomes delayed the application of flow cytogenetics in plants. This chapter outlines a high-yielding procedure for preparation of solutions of intact mitotic chromosomes from root tips of young seedlings and for their analysis using flow cytometry and sorting. Root tips accumulated at metaphase are mildly fixed with formaldehyde, and solutions of intact chromosomes are prepared by mechanical homogenization. The advantages of the present approach include the use of seedlings, which are easy to handle, and the karyological stability of root meristems, which can be induced to high degree of metaphase synchrony. Chromosomes isolated according to this protocol have well-preserved morphology, withstand shearing forces during sorting, and their DNA is intact and suitable for a range of applications.

  13. Focal chromosomal copy number aberrations identify CMTM8 and GPR177 as new candidate driver genes in osteosarcoma.

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    Joeri Both

    Full Text Available Osteosarcoma is an aggressive bone tumor that preferentially develops in adolescents. The tumor is characterized by an abundance of genomic aberrations, which hampers the identification of the driver genes involved in osteosarcoma tumorigenesis. Our study aims to identify these genes by the investigation of focal copy number aberrations (CNAs, <3 Mb. For this purpose, we subjected 26 primary tumors of osteosarcoma patients to high-resolution single nucleotide polymorphism array analyses and identified 139 somatic focal CNAs. Of these, 72 had at least one gene located within or overlapping the focal CNA, with a total of 94 genes. For 84 of these genes, the expression status in 31 osteosarcoma samples was determined by expression microarray analysis. This enabled us to identify the genes of which the over- or underexpression was in more than 35% of cases in accordance to their copy number status (gain or loss. These candidate genes were subsequently validated in an independent set and furthermore corroborated as driver genes by verifying their role in other tumor types. We identified CMTM8 as a new candidate tumor suppressor gene and GPR177 as a new candidate oncogene in osteosarcoma. In osteosarcoma, CMTM8 has been shown to suppress EGFR signaling. In other tumor types, CMTM8 is known to suppress the activity of the oncogenic protein c-Met and GPR177 is known as an overexpressed upstream regulator of the Wnt-pathway. Further studies are needed to determine whether these proteins also exert the latter functions in osteosarcoma tumorigenesis.

  14. The frequency of chromosomal aberrations in sheep from the area contaminated by depleted uranium during NATO air strikes in 1999

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    Fišter Svetlana L.

    2014-01-01

    Full Text Available This paper presents the results of cytogenetic studies in sheep from the region of Bujanovac that was contaminated by depleted uranium during the NATO air strikes in 1999. The study was conducted on sheep blood lymphocytes, in order to determine the frequency of chromosomal aberrations and to assess the presence of genetic risk as a result of the possible impact of depleted uranium. Blood samples for lymphocyte cultures were taken at random from the 20 animals of the households in the village of Borovac, near Bujanovac. The animals were chosen because they were pastured, fed, and watered in the NATO bombing area. With the purpose of comparing the results two control groups were cytogenetically analyzed, each consisted of 20 sheep from Zemun and Ovča, two northern localities that were not contaminated with depleted uranium. The established structural chromosomal changes were of breaks and gap types, and their frequencies in sheep of all surveyed localities were within the range of basic level values that are commonly found in the sheep lymphocyte cultures analyses. Significant differences are apparent between the values defined in the sheep from Bujanovac compared to those obtained in the sheep from the northern locality (Zemun, probably as a result of breeding of animals in the farm conditions and their being less exposed to the impact of environmental agents. There were neither elevated values of polyploid and aneuploid cells nor significant differences between the sites. According to earlier known data, depleted uranium was below the detection limit of the method applied both in the soil and feed given to cytogenetically analyzed animals. Based on the low-level changes that are in the range of the basic level changes, commonly observed in sheep lymphocytes control cultures, it cannot be said with certainty that it was depleted uranium that caused the changes, or that it is wide-spread in the region of Bujanovac. [Projekat Ministarstva nauke

  15. Analysis of chromosome translocation frequency after a single CT scan in adults.

    Science.gov (United States)

    Abe, Yu; Miura, Tomisato; Yoshida, Mitsuaki A; Ujiie, Risa; Kurosu, Yumiko; Kato, Nagisa; Katafuchi, Atsushi; Tsuyama, Naohiro; Kawamura, Fumihiko; Ohba, Takashi; Inamasu, Tomoko; Shishido, Fumio; Noji, Hideyoshi; Ogawa, Kazuei; Yokouchi, Hiroshi; Kanazawa, Kenya; Ishida, Takashi; Muto, Satoshi; Ohsugi, Jun; Suzuki, Hiroyuki; Ishikawa, Tetsuo; Kamiya, Kenji; Sakai, Akira

    2016-06-01

    We recently reported an increase in dicentric chromosome (DIC) formation after a single computed tomography (CT) scan (5.78-60.27 mSv: mean 24.24 mSv) and we recommended analysis of 2000 metaphase cells stained with Giemsa and centromere-FISH for dicentric chromosome assay (DCA) in cases of low-dose radiation exposure. In the present study, we analyzed the frequency of chromosome translocations using stored Carnoy's-fixed lymphocyte specimens from the previous study; these specimens were from 12 patients who were subject to chromosome painting of Chromosomes 1, 2 and 4. Chromosomes 1, 2 and 4 were analyzed in ∼5000 cells, which is equivalent to the whole-genome analysis of almost 2000 cells. The frequency of chromosome translocation was higher than the number of DICs formed, both before and after CT scanning. The frequency of chromosome translocations tended to be higher, but not significantly higher, in patients with a treatment history compared with patients without such a history. However, in contrast to the results for DIC formation, the frequency of translocations detected before and after the CT scan did not differ significantly. Therefore, analysis of chromosome translocation may not be a suitable assay for detecting chromosome aberrations in cases of low-dose radiation exposure from a CT scan. A significant increase in the frequency of chromosome translocations was not likely to be detected due to the high baseline before the CT scan; the high and variable frequency of translocations was probably due to multiple confounding factors in adults.

  16. Prenatal diagnosis and molecular cytogenetic analysis of a de novo isodicentric chromosome 18

    Science.gov (United States)

    Zhang, Yanliang; Dai, Yong; Ren, Jinghui; Wang, Linqian

    2010-01-01

    Isodicentric chromosome 18 [idic(18)] is rare structural aberration. We report on a prenatal case described by conventional and molecular cytogenetic analyses. The sonography at 24 weeks of gestation revealed multiple fetal anomalies; radial aplasia and ventricular septal defect were significant features. Routine karyotyping showed a derivative chromosome replacing one normal chromosome 18. The parental karyotypes were normal, indicating that the derivative chromosome was de novo. Array comparative genomic hybridization (array-CGH) revealed 18p11.21→qter duplication and 18p11.21→pter deletion for genomic DNA of the fetus. The breakpoint was located at 18p11.21 (between 12104527 bp and 12145199 bp from the telomere of 18p). Thus, the derivative chromosome was ascertained as idic(18)(qter→p11.21::p11.21→qter). Fluorescent in situ hybridization (FISH) confirmed that the derivative chromosome was idic(18). Our report describes a rare isodicentric chromosome 18 and demonstrates that array-CGH is a useful complementary tool to cytogenetic analysis for reliable identifying derivative chromosome. PMID:20864786

  17. Induction of chromosome aberration in human lymphocytes and its dependence on X ray energy

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero-Carbajal, C.; Edwards, A.A.; Lloyd, D.C

    2003-07-01

    The variations of dose response with X ray energy observed with the human lymphocyte dicentric assay is examined. In order to determine reliably the initial slopes (RBE{sub m}) many cells need to be analysed at low doses. Insufficient analysis may explain some reported interlaboratory differences in fitted dose-response coefficients. One such discrepancy at 150 kV{sub p}, E(mean) = 70 keV is examined. Data are also presented for an X ray spectrum of 80 kV{sub p}, E(mean) = 58 keV. Over the photon energy range 20 keV X rays to 1.25 MeV gamma rays RBE{sub m} varies by about a factor of 5, with the lower energies being more effective. This is consistent with microdosimetric theory. By contrast, in radiological protection a radiation weighting factor of 1.0 is assumed for all photons when assessing the risk of inducing cancer at low doses. The measured variations of biological effect with photon energy have led to suggestions that the lower energies, as used for some diagnostic radiology, carry a greater risk per unit dose than is normally assumed by those involved in radiological protection. Interpretation of the data reported in this paper does not support this view. (author)

  18. The association between DNA copy number aberrations at chromosome 5q22 and gastric cancer.

    Directory of Open Access Journals (Sweden)

    Pei-Chien Tsai

    Full Text Available BACKGROUND: Gastric cancer is common cancer. Discovering novel genetic biomarkers might help to identify high-risk individuals. Copy number variation (CNV has recently been shown to influence risk for several cancers. The aim of the present study was sought to test the association between copy number at a variant region and GC. METHODS: A total of 110 gastric cancer patients and 325 healthy volunteers were enrolled in this study. We searched for a CNV and found a CNV (Variation 7468 containing part of the APC gene, the SRP19 gene and the REEP5 gene. We chose four probes targeting at APC-intron8, APC-exon9, SRP19 and REEP5 to interrogate this CNV. Specific Taqman probes labeled by different reporter fluorophores were used in a real-time PCR platform to obtain copy number. Both the original non-integer data and transformed integer data on copy number were used for analyses. RESULTS: Gastric caner patients had a lower non-integer copy number than controls for the APC-exon9 probe (Adjusted p = 0.026 and SRP19 probe (Adjusted p = 0.002. The analysis of integer copy number yielded a similar pattern although less significant (Adjusted p = 0.07 for APC-exon9 probe and Adjusted p = 0.02 for SRP19 probe. CONCLUSIONS: Losses of a CNV at 5q22, especially in the DNA region surrounding APC-exon 9, may be associated with a higher risk of gastric cancer.

  19. The type and yield of ionising radiation induced chromosomal aberrations depend on the efficiency of different DSB repair pathways in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Natarajan, Adayapalam T.; Berni, Andrea; Marimuthu, Kodumudi M. [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo (Italy); Palitti, Fabrizio [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo (Italy)], E-mail: palitti@unitus.it

    2008-07-03

    In order to evaluate the relative role of two major DNA double strand break repair pathways, i.e., non-homologous end joining (NHEJ) and homologous recombination repair (HRR), CHO mutants deficient in these two pathways and the parental cells (AA8) were X-irradiated with various doses. The cells were harvested at different times after irradiation, representing G{sub 2}, S and G{sub 1} phase at the time of irradiation, The mutant cell lines used were V33 (NHEJ deficient), Irs1SF, 51-D1 (HRR deficient). In addition to parental cell line (AA8), a revertant of V33, namely V33-155 was employed. Both types of mutant cells responded with increased frequencies of chromosomal aberrations at all recovery times in comparison to the parental and revertant cells. Mutant cells deficient in NHEJ were more sensitive in all cell stages in comparison to HRR deficient mutant cells, indicating NHEJ is the major repair pathway for DSB repair through out the cell cycle. Both chromosome and chromatid types of exchange aberrations were observed following G{sub 1} irradiation (16 and 24 h recovery). Interestingly, configurations involving both chromosome (dicentrics) and chromatid exchanges were encountered in G{sub 1} irradiated V33 cells. This may indicate that unrepaired DSBs accumulate in G{sub 1} in these mutant cells and carried over to S phase, where they are repaired by HRR or other pathways such as B-NHEJ (back up NHEJ), which appear to be highly error prone. Both NHEJ and HRR, which share some of the same proteins in their pathways, are involved in the repair of DSBs leading to chromosomal aberrations, but with a major role of NHEJ in all stages of cell cycle.

  20. In Vitro genotoxic and antigenotoxic studies of Thai Noni fruit juice by chromosomal aberration and sister chromatid exchange assays in human lymphocytes

    Directory of Open Access Journals (Sweden)

    Treetip Ratanavalachai

    2008-09-01

    Full Text Available The genotoxic and antigenotoxic effects of Noni fruit juice produced in Thailand have been studied in human lymphocytes for chromosome aberration assay and sister chromatid exchange (SCE assay in vitro. Treatment of Noni fruit juice(3.1-50 mg/ml alone for 3 h did not significantly induce chromosomal aberration or SCE (p<0.05. Noni fruit juice at 6.2 mg/ml is the optimum dose for cell survival and cell replication as demonstrated by the highest value of mitotic index and proliferation index (P.I.. Interestingly, pretreatment of Noni fruit juice at the same concentration of 6.2 mg/ml for 2 hfollowed by mitomycin C treatment at 3 μg/ml for 2 h significantly reduced SCE level induced by mitomycin C (p<0.05. However, these treatments did not show significant decrease in chromatid-type aberrations. Our data indicate that Thai Noni fruit juice is not genotoxic against human lymphocytes in vitro. In addition, pretreatment of Noni fruit juice at 6.2 mg/ml demonstrated no anticlastogenic effect while had some antigenotoxic effects as demonstrated by significant decrease in the SCE level induced by mitomycin C (p<0.05. Therefore, the optimum dose of Noni fruit juice used as a traditional medicine is required and needs to be studied further for the benefit of human health.

  1. Chromosomal aberrations in in-vitro matured oocytes influence implantation and ongoing pregnancy rates in a mouse model undergoing intracytoplasmic sperm injection.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available Implantation failure and early pregnancy loss have been reported to be closely related to the quality of mammalian oocytes; however, the pregnant outcome of embryos from in-vitro matured (IVM oocytes remains unknown. In this study we examined spindle assembly and chromosome segregation during differentiation, and the duration of IVM of mouse oocytes. The resulting implantation and pregnancy outcomes were analyzed to clarify the relationship between the spindle and chromosomes of IVM oocytes and implantation and early pregnancy. Cumulus-enclosed germinal vesicle oocytes were collected and randomly cultured in IVM medium with different IVM durations. One part of IVM oocytes were analyzed the spindle and chromosome morphology by immunofluorescence method, and the other part of them were fertilized by intracytoplasmic sperm injection. The resulting embryos were transferred into pseudo-pregnant female mice, and the post-implantation and full term development was observed. The chromosome aberrations and incorrect spindle assembly seems not affect the early development and blastocyst cell number derived from IVM oocytes, however the development potential of the resulting embryos after implantation were significant decreased with the ratio increasing of chromosome aberrations and incorrect spindle assembly. Accordingly, the full-term development was also decreased. In conclusion, the present study showed the spindle assembly of in vitro-matured oocytes was one of the most important factors that affected the implantation and ongoing pregnancy rates of IVM oocytes, and the improvement by an appropriate duration of maturation in vitro will enhance the post-implantation development potential of the resulting embryos, and decrease implantation failure and early pregnancy loss.

  2. Chromosomal aberrations in in-vitro matured oocytes influence implantation and ongoing pregnancy rates in a mouse model undergoing intracytoplasmic sperm injection.

    Science.gov (United States)

    Li, Min; Zhao, Hong-Cui; Li, Rong; Yu, Yang; Qiao, Jie

    2014-01-01

    Implantation failure and early pregnancy loss have been reported to be closely related to the quality of mammalian oocytes; however, the pregnant outcome of embryos from in-vitro matured (IVM) oocytes remains unknown. In this study we examined spindle assembly and chromosome segregation during differentiation, and the duration of IVM of mouse oocytes. The resulting implantation and pregnancy outcomes were analyzed to clarify the relationship between the spindle and chromosomes of IVM oocytes and implantation and early pregnancy. Cumulus-enclosed germinal vesicle oocytes were collected and randomly cultured in IVM medium with different IVM durations. One part of IVM oocytes were analyzed the spindle and chromosome morphology by immunofluorescence method, and the other part of them were fertilized by intracytoplasmic sperm injection. The resulting embryos were transferred into pseudo-pregnant female mice, and the post-implantation and full term development was observed. The chromosome aberrations and incorrect spindle assembly seems not affect the early development and blastocyst cell number derived from IVM oocytes, however the development potential of the resulting embryos after implantation were significant decreased with the ratio increasing of chromosome aberrations and incorrect spindle assembly. Accordingly, the full-term development was also decreased. In conclusion, the present study showed the spindle assembly of in vitro-matured oocytes was one of the most important factors that affected the implantation and ongoing pregnancy rates of IVM oocytes, and the improvement by an appropriate duration of maturation in vitro will enhance the post-implantation development potential of the resulting embryos, and decrease implantation failure and early pregnancy loss.

  3. Mutagenic studies on the effect of Aldicarb "Temik" and vitamin C as antioxidant agent on the white rat:(Chromosomal aberrations and Micronucleus tests

    Directory of Open Access Journals (Sweden)

    Fatma M. Hamam* and Ihab H. Foda

    2004-12-01

    Full Text Available Widespread contamination of the environment due to increased and frequently indiscriminate usage of insecticides during the last two decades has aroused much concern over the possibility of their radiominetic effect. Evidence accumulating over the years emphasized the indisputable link between certain insecticides, chromosomal damage and possibility of gene mutation. There is a wide variety of insecticides, among which the carbamates. Their chemical relationship to ethyl carbamate makes them worthy of study for their possible deleterious effect on biological system. The main object of the present study is to evaluate the mutagenic effect of a carbamate insecticide" Aldicarb" alone and in combination of vitamin C as an antioxidant agent to decrease their mutagenicity. Male albino rats were tested orally for 48 hours , two doses of aldicarb were used in absence and in the presence of viamin C (1/4 and 1/10 LD50. The obtained data showed highly significant increase in the micronucleus (PCEM and in chromosomal aberrations in rat bone marrow cells at the two doses of aldicarb compared to control group. (P< 0.0001. The frequency of chromosomal aberrations and micronucleus decreased in rats treated with aldicarb and vitamin C than in aldicarb treated group. From these results we concluded that cytogenetic effect of aldicarb might be decreased by the usage of vitamin as an antioxidant agent.

  4. Development of EST-PCR Markers for the Chromosome 4VofHaynaldia villosaand Their Application in Identification of 4V Chromosome Structural Aberrants

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ren-hui; WANG Hai-yan; JIA Qi; XIAO Jin; YUAN Chun-xia; ZHANG Ya-jun; HU Qing-shan; WANG Xiu-e

    2014-01-01

    EST-PCR based molecular markers speciifc for alien chromosomes are not only useful for the detection of the introgressed alien chromatin in the wheat background, but also provide evidence of the syntenic relationship between homoeologous chromosomes. In the present study, in order to develop high density and evenly distributed molecular markers on chromosome 4V ofHaynaldia villosa, a total of 607 primer pairs were designed according to the EST sequences, which were previously located in 23 different bins of wheat chromosomes 4A, 4B and 4D. By using theTriticum durum-H. villosaamphiploid and T. aestivum-H. villosa alien chromosome lines involving chromosome 4V, it was found that 9.23% of the tested primers could amplify speciifc bands for chromosome 4V. Thirty and twenty-six speciifc markers could be assigned to chromosome arms 4VS and 4VL, respectively. These 4V speciifc markers provided efifcient tools for the characterization of structural variation involving the chromosome 4V as well as for the selection of useful genes located on chromosome 4V in breeding programs.

  5. Determination of genotoxic effects of Imazethapyr herbicide in Allium cepa root cells by mitotic activity, chromosome aberration, and comet assay.

    Science.gov (United States)

    Liman, Recep; Ciğerci, İbrahim Hakkı; Öztürk, Nur Serap

    2015-02-01

    Imazethapyr (IM) is an imidazolinone herbicide that is currently used for broad-spectrum weed control in soybean and other legume crops. In this study, cytotoxic and genotoxic effects of IM were investigated by using mitotic index (MI), mitotic phases, chromosomal abnormalities (CAs) and DNA damage on the root meristem cells of Allium cepa. In Allium root growth inhibition test, EC50 value was determined as 20 ppm, and 0.5xEC50, EC50 and 2xEC50 concentrations of IM herbicide were introduced to onion tuber roots. Distilled water and methyl methane sulfonate (MMS, 10 mg/L) were used as a negative and positive control, respectively. As A. cepa cell cycle is 24 hours, so, application process was carried out for 24, 48, 72 and 96 hours. All the applied doses decreased MIs compared to control group and these declines were found to be statistically meaningful. Analysis of the chromosomes showed that 10 ppm IM except for 48 h induced CAs but 40 ppm IM except for 72 h decreased CAs. DNA damage was found significantly higher in 20 and 40 ppm of IM compared to the control in comet assay. These results indicated that IM herbicide exhibits cytotoxic activity but not genotoxic activity (except 10 ppm) and induced DNA damage in a dose dependent manner in A. cepa root meristematic cells.

  6. Mutagenic effects of tributyltin and inorganic lead (Pb II on the fish H. malabaricus as evaluated using the comet assay and the piscine micronucleus and chromosome aberration tests

    Directory of Open Access Journals (Sweden)

    Marcos Vinícius M. Ferraro

    2004-01-01

    Full Text Available Genotoxicity studies on toxic metals and their organic compounds are very important, especially so in the investigation of the effects of these compounds on the aquatic environments where they tend to accumulate. The use of endemic aquatic organisms as biological sentinels has proved useful to environmental monitoring. We assessed the mutagenic potential of tributyltin (TBT and inorganic lead (PbII using samples of the fish Hoplias malabaricus (commonly called traíra using the comet assay and the piscine micronucleus and chromosome aberration tests. Eighteen H. malabaricus were acclimatized in three individual aquariums, each containing six fish, six fish being exposed to 0.3 mg/g of body weight (bw of TBT, six to 21 mg/g bw of PbII and six being used as controls. Exposure to TBT and PbII was achieved by feeding the fish every five days with Astyanax (a small fish that is part of the normal diet of H. malabaricus which had been injected with solutions of TBT, PbII or with water (the control group. After two months the H. malabaricus were sacrificed and their peripheral blood collected and subjected to the comet and micronucleus assays, the chromosome aberration assay being conducted using kidney-tissue. Although the comet assay showed now mutagenic effects at the lead concentrations used but encountered results with TBT, the micronucleus and chromosome aberrations assays both indicated that TBT and PbII are potentially mutagenic (p < 0.01, the micronucleus assay showing morphological alterations of the nucleus.

  7. Nicotine derived genotoxic effects in human primary parotid gland cells as assessed in vitro by comet assay, cytokinesis-block micronucleus test and chromosome aberrations test.

    Science.gov (United States)

    Ginzkey, Christian; Steussloff, Gudrun; Koehler, Christian; Burghartz, Marc; Scherzed, Agmal; Hackenberg, Stephan; Hagen, Rudolf; Kleinsasser, Norbert H

    2014-08-01

    Genotoxic effects of nicotine were described in different human cells including salivary gland cells. Based on the high nicotine concentration in saliva of smokers or patients using therapeutic nicotine patches, the current study was performed to evaluate the genotoxic potential of nicotine in human salivary gland cells. Therefore, primary salivary gland cells from 10 patients undergoing parotid gland surgery were exposed to nicotine concentrations between 1 μM and 1000 μM for 1 h in the absence of exogenous metabolic activation. The acinar phenotype was proven by immunofluorescent staining of alpha-amylase. Genotoxic effects were evaluated using the Comet assay, the micronucleus test and the chromosome aberration test. Cytotoxicity and apoptosis were determined by trypan blue exclusion test and Caspase-3 assay. Nicotine was able to induce genotoxic effects in all three assays. The chromosome aberration test was the most sensitive and increases in numerical and structural (chromatid-type and chromosome-type) aberrations were seen at ≥1 μM, whereas increases in micronuclei frequency were detected at 10 μM and DNA damage as measured in the Comet assay was noted at >100 μM. No cytotoxic damage or influence of apoptosis could be demonstrated. Nicotine as a possible risk factor for tumor initiation in salivary glands is still discussed controversially. Our results demonstrated the potential of nicotine to induce genotoxic effects in salivary gland cells. These results were observed at saliva nicotine levels similar to those found after oral or transdermal exposure to nicotine and suggest the necessity of careful monitoring of the use of nicotine in humans.

  8. Switching the centromeres on and off: epigenetic chromatin alterations provide plasticity in centromere activity stabilizing aberrant dicentric chromosomes.

    Science.gov (United States)

    Sato, Hiroshi; Saitoh, Shigeaki

    2013-12-01

    The kinetochore, which forms on a specific chromosomal locus called the centromere, mediates interactions between the chromosome and the spindle during mitosis and meiosis. Abnormal chromosome rearrangements and/or neocentromere formation can cause the presence of multiple centromeres on a single chromosome, which results in chromosome breakage or cell cycle arrest. Analyses of artificial dicentric chromosomes suggested that the activity of the centromere is regulated epigenetically; on some stably maintained dicentric chromosomes, one of the centromeres no longer functions as a platform for kinetochore formation, although the DNA sequence remains intact. Such epigenetic centromere inactivation occurs in cells of various eukaryotes harbouring 'regional centromeres', such as those of maize, fission yeast and humans, suggesting that the position of the active centromere is determined by epigenetic markers on a chromosome rather than the nucleotide sequence. Our recent findings in fission yeast revealed that epigenetic centromere inactivation consists of two steps: disassembly of the kinetochore initiates inactivation and subsequent heterochromatinization prevents revival of the inactivated centromere. Kinetochore disassembly followed by heterochromatinization is also observed in normal senescent human cells. Thus epigenetic centromere inactivation may not only stabilize abnormally generated dicentric chromosomes, but also be part of an intrinsic mechanism regulating cell proliferation.

  9. Clastogenic effects of known and suspect spindle poisons studied by chromosome analysis in mouse bone marrow cells.

    Science.gov (United States)

    Xu, W; Adler, I D

    1990-07-01

    The present study was performed within the project 'Genomic Mutations' (sponsored by the Commission of the European Communities) in order to gather all possible experimental information on 10 chemicals selected on the basis of their possible capacity to induce aneuploidy. An analysis of chromosomal aberrations was carried out in bone marrow cells of mice with the first five chemicals: colchicine (COL), econazole (EZ), chloralhydrate (CH), hydroquinone (HQ) and diazepam (DIAZ). The experiments were performed in parallel to micronucleus tests with the objective to distinguish a positive micronucleus response due to chromosomal breakage from that obtained by lagging chromosomes. The results of the micronucleus tests will be reported elsewhere. COL, CH, EZ and DIAZ showed no clastogenic effects in mouse bone marrow cells after single intraperitoneal injection. Polyploid cells were significantly more frequent after COL treatment. HQ showed a dose-dependent induction of chromosomal aberrations at 6 and 24 h after treatment. After 24 h, cells with multiple aberrations up to complete chromosome fragmentation were frequently observed. They indicate that a small fraction of the cell population, probably related to a specific stage of the cell cycle, was particularly sensitive to HQ. A sex difference in clastogenic response to HQ was not observed. It is concluded that of the five chemicals tested only HQ was clastogenic in mouse bone marrow cells under the present experimental conditions.

  10. Late-occurring chromosome aberrations and global DNA methylation in hematopoietic stem/progenitor cells of CBA/CaJ mice exposed to silicon ({sup 28}Si) ions

    Energy Technology Data Exchange (ETDEWEB)

    Rithidech, Kanokporn Noy, E-mail: kanokporn.rithidech@stonybrookmedicine.edu [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Honikel, Louise M. [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Reungpathanaphong, Paiboon [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Applied Radiation and Isotopes, Faculty of Sciences, Kasetsart University, Chatuchuck, Bangkok 10900 (Thailand); Tungjai, Montree [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Radiologic Technology, Faculty of Associated Medical Sciences, Center of Excellence for Molecular Imaging, Chiang Mai University, Chiang Mai 50200 (Thailand); Jangiam, Witawat [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Chemical Engineering, Faculty of Engineering, Burapha University, Chonburi 20131 (Thailand); Whorton, Elbert B. [StatCom, PO Box 3041, Galveston, TX 77551 (United States)

    2015-11-15

    Highlights: • Late-occurring chromosome aberrations were found in HSPCs of exposed CBA/CaJ mice. • A dose-dependent reduction in the level of global 5hmC was detected in HSPCs. • There is a link between reduced global 5hmC levels and genomic instability in vivo. • The level of global 5hmC is a better marker of radiation exposure than that of 5mC. - Abstract: Although myeloid leukemia (ML) is one of the major health concerns from exposure to space radiation, the risk prediction for developing ML is unsatisfactory. To increase the reliability of predicting ML risk, a much improved understanding of space radiation-induced changes in the target cells, i.e. hematopoietic stem/progenitor cells (HSPCs), is important. We focused on the in vivo induction of late-occurring damage in HSPCs of mice exposed to {sup 28}Si ions since such damage is associated with radiation-induced genomic instability (a key event of carcinogenesis). We gave adult male CBA/CaJ mice, known to be sensitive to radiation-induced ML, a whole-body exposure (2 fractionated exposures, 15 days apart, that totaled each selected dose, delivered at the dose-rate of 1 cGy/min) to various doses of 300 MeV/n {sup 28}Si ions, i.e. 0 (sham controls), 0.1, 0.25, or 0.5 Gy. At 6 months post-irradiation, we collected bone marrow cells from each mouse (five mice per treatment-group) for obtaining the myeloid-lineage of HSPC-derived clones for analyses. We measured the frequencies of late-occurring chromosome aberrations (CAs), using the genome-wide multicolor fluorescence in situ hybridization method. The measurement of CAs was coupled with the characterization of the global DNA methylation patterns, i.e. 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). A dose-dependent increase in the frequencies of CAs was detected (Analysis of Variance or ANOVA, p < 0.01), indicating the induction of genomic instability after exposure of mice to 300 MeV/n {sup 28}Si ions. Slight increases in the levels of 5m

  11. Chromosome

    Science.gov (United States)

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  12. Influence of GSTM1, GSTT1, GSTP1, NAT1, NAT2, EPHX1, MTR and MTHFR polymorphism on chromosomal aberration frequencies in human lymphocytes.

    Science.gov (United States)

    Skjelbred, Camilla Furu; Svendsen, Marit; Haugan, Vera; Eek, Anette Kildal; Clausen, Kjell Oskar; Kure, Elin H; Tuimala, Jarno T; Svendsen, Martin Veel; Norppa, Hannu; Hansteen, Inger-Lise

    2011-03-01

    We have studied the influence of genetic polymorphisms in the xenobiotic-metabolizing genes GSTM1, GSTP1, GSTT1, EPHX1, NAT1 and NAT2 and the folate-metabolizing genes MTR and MTHFR on the frequencies of cells with chromosomal aberrations (CAs) in peripheral lymphocytes of Norwegian men. Log-linear Poisson regression models were applied on 357 subjects of whom data on all the polymorphisms examined were available. Total CAs and chromosome-type aberrations (CSAs) were significantly increased by higher age alone, whereas chromatid-type aberrations (CTAs) were elevated by the GSTT1-null genotype and MTHFR codon 222 variant allele and chromatid gaps (CTGs) by EPHX1 high activity genotype and occupational exposure. Stratification by smoking and age (<40 and ≥40 years) showed that the effect of the GSTT1 null and EPHX1 high activity genotypes only concerned (older) smokers, in agreement with the roles of the respective enzymes in detoxification and metabolic activation. The MTHFR codon 222 variant allele was associated with high CTGs in smokers, the MTR codon 919 variant allele with high CTAs in older smokers and the NAT2 fast acetylator genotype with high CTGs in older subjects. Among younger nonsmokers, however, carriers of the MTHFR codon 222 and MTR codon 919 variant alleles showed a decrease in the level of CTGs and total CAs, respectively. In conclusion, polymorphisms of GSTT1, EPHX1, MTHFR, MTR and NAT2 differentially affect the frequency of CTAs, CSAs and CTGs, showing interaction with smoking and age. It appears that CA subtypes rather than total CAs should be considered in this type of studies.

  13. BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1

    Directory of Open Access Journals (Sweden)

    Estivill Xavier

    2009-12-01

    Full Text Available Abstract Background Microdeletion of the chromosome 22q11.2 region is the most common genetic aberration among patients with velocardiofacial syndrome (VCFS but a subset of subjects do not show alterations of this chromosome region. Methods We analyzed 18 patients with VCFS-like features by comparative genomic hybridisation (aCGH array and performed a face-to-face slide hybridization with two different arrays: a whole genome and a chromosome 22-specific BAC array. Putative rearrangements were confirmed by FISH and MLPA assays. Results One patient carried a combination of rearrangements on 1q21.1, consisting in a microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously reported in patients with variable phenotypes, including mental retardation, congenital heart defects (CHD and schizophrenia. While 326 control samples were negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212-kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected four copy number variants (CNVs inherited from one parent (a 744-kb duplication on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a gain of 140 kb on 22q13.2, not present in control subjects, raising the potential role of these CNVs in the VCFS-like phenotype. Conclusions Our results confirmed aCGH as a successful strategy in order to characterize additional submicroscopic aberrations in patients with VCF-like features that fail to show alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1, detected in two patients, which may contribute to CHD.

  14. Induction of chromosome aberrations in the Allium cepa test system caused by the exposure of cells to benzo(a) pyrene.

    Science.gov (United States)

    Cabaravdic, Mirsad

    2010-01-01

    Higher plants have been proposed as test organisms for the detection of genotoxic substances in the environment. Several plant test systems are already in use and are found to be as sensitive and reliable as other short-term tests. Allium cepa is one of these plants, which has been used in different studies to detect chromosome aberrations induced by chemicals. The use of non-animal test methods, including in vitro studies, provides importent tools to enhance our understanding of hazardous effect of chemicals, and for predicting these effects in humans. In vitro systems are used principally for screening purposes, and for generating toxicological profiles. Numerous chemicals can generate the breakage or interchange of DNA segments between chromosomal structures. Allium test is used as a screening method for genotoxicity evaluation of different chemical substances, including polycyclic aromatic hydrocarbons (PAHs). Benzo(a)pyrene (BaP), as representative member of PAHs, were investigated of genotoxicity by using Allium roote chromosomes assay. The treatment with different series of concentrations of BaP, ranging from 1.0-50.0 microg/ml respectively. Used BaP caused decreased in the Mitotic index (MI) and increase frequency of abnormal mitosis when compared with the control.

  15. Heterogeneity of chromosome damage in [beta]-thalassaemia traits. An evaluation of spontaneous and [gamma]-ray-induced micronuclei and chromosome aberrations in lymphocytes in vitro after G[sub 0] and G[sub 2] phase irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaja, A.P.; Sharma, N.K. (Bhabha Atomic Research Centre, Bombay (India). Molecular Biology and Agriculture Div.)

    1994-07-01

    This study is an attempt to evaluate the chromosomal radiosensitivity of [beta]-thalassaemia traits compared with healthy individuals from the general population, necessitated by the fact that [beta]-thalassaemia trait is present in 1-17% of different population groups in India and the chances of encountering them in radiation and chemical related industries do exist. Spontaneous chromosome aberration frequencies in peripheral blood lymphocytes from [beta]-thalassaemia traits were found to be in the normal range, whereas significantly higher frequencies of micronuclei (MN) were observed in thalassaemia traits. Based on MN frequency at 2 Gy, [beta]-thalassaemia traits fall into two distinct categories. A hypersensitive group with significant increase in radiation-induced MN over the control group, and a second group with MN frequency slightly above normal individuals. Even when compared with the fitted data at 2 Gy obtained from the pooled results of extensive dose-response investigations from 0.5-5 Gy [gamma]-rays with normal donors for MN, dicentrics and total aberrations, the difference between the means of MN frequencies in [beta]-thalassaemia traits and normals is significant. (author).

  16. The impact of homologous recombination repair deficiency on depleted uranium clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from chromosome aberrations, but increases chromosome fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Maine Center for Toxicology and Environmental Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth Street, P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Joyce, Kellie [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Maine Center for Toxicology and Environmental Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Xie, Hong [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Maine Center for Toxicology and Environmental Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth Street, P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Falank, Carolyne [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); Maine Center for Toxicology and Environmental Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States of America (United States); and others

    2014-04-15

    Highlights: • The role of homologous recombination repair in DU-induced toxicity was examined. • Loss of RAD51D did not affect DU-induced cytotoxicity or genotoxicity. • XRCC3 protects cell from DU-induced chromosome breaks and fusions. • XRCC3 plays a role in DU-induced chromosome fragmentation of the X chromosome. - Abstract: Depleted uranium (DU) is extensively used in both industry and military applications. The potential for civilian and military personnel exposure to DU is rising, but there are limited data on the potential health hazards of DU exposure. Previous laboratory research indicates DU is a potential carcinogen, but epidemiological studies remain inconclusive. DU is genotoxic, inducing DNA double strand breaks, chromosome damage and mutations, but the mechanisms of genotoxicity or repair pathways involved in protecting cells against DU-induced damage remain unknown. The purpose of this study was to investigate the effects of homologous recombination repair deficiency on DU-induced genotoxicity using RAD51D and XRCC3-deficient Chinese hamster ovary (CHO) cell lines. Cells deficient in XRCC3 (irs1SF) exhibited similar cytotoxicity after DU exposure compared to wild-type (AA8) and XRCC3-complemented (1SFwt8) cells, but DU induced more break-type and fusion-type lesions in XRCC3-deficient cells compared to wild-type and XRCC3-complemented cells. Surprisingly, loss of RAD51D did not affect DU-induced cytotoxicity or genotoxicity. DU induced selective X-chromosome fragmentation irrespective of RAD51D status, but loss of XRCC3 nearly eliminated fragmentation observed after DU exposure in wild-type and XRCC3-complemented cells. Thus, XRCC3, but not RAD51D, protects cells from DU-induced breaks and fusions and also plays a role in DU-induced chromosome fragmentation.

  17. Computerized prototypes of DAPI-stained chromosomes for FISH analysis

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, A.; Smith, L.C.; Knapp, R.D. [Baylor College of Medicine, Houston, TX (United States)

    1994-09-01

    DAPI is fluorescent dye widely used in chromosome counterstaining for fluorescence in situ hybridization (FISH) experiments. It produces a Q-banding pattern that allows chromosomes to be identified and permits molecular probes to be assigned to specific cytogenetic bands. Using a statistical procedure based on eigenanalysis, we have extracted features from digital images of DAPI-stained chromosomes and constructed prototypes of each of the 24 human chromosomes. The features of prototypes are directly proportional, in intensity profile and band location, to those of real chromosomes. The prototype`s intensity profile can be translated into cytogenetic bands to provide a computer-based strategy for chromosome mapping and analysis amenable to automation. Data have been obtained using images from the 24 human chromosomes and mouse X chromosome. Moreover, the same procedure is general and can be used for the analysis of chromosomes from other species, as well as with banding techniques other than those using DAPI. Images of hybridization patterns produced by complex probes are also suitable for this analysis. The speed and flexibility of the procedure opens the way to application so far unexplored, such as computer-assisted chromosome band assignment of probe; combined analysis of multiple, geometrically distorted chromosomes; and the direct comparison of raw data from different experiments. The applications will not be limited to mapping experiments but will include analysis of chromosome structure, variability and analysis of the pattern of chromosome distribution of repetitive sequences. The results from such analysis is suitable for objective statistical evaluation and, eventually, for autonomous machine interpretation.

  18. Chromosome analysis of three species of Myoxidae

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Civitelli

    1995-05-01

    Full Text Available Abstract Karyotype analysis was carried out on three species of dormice: Myoxus glis, 4 populations from Northern and Southern Italy and from Turkey; Dryomys nitedula, 4 populations from Northern and Southern Italy, from Israel and from Turkey; Myomimus roachi, 1 specimen from Turkey. Myoxus glis shows 2n=62; comparison of our specimens from different localities shows complete correspondence between karyotypes, both for the autosomes and the heterochromosomes. Dryomys nitedula shows 2n=48. All populations we studied, show the same karyotypic pattern, except for the NOR-bearing chromosomes. Myomimus roachi, here studied for the first time, shows 2n=44. All the autosomes are biarmed of decreasing size. The X-chromosome is a medium size metacentric, while the Y-chromosome is the smallest one. All the three species we studied, show one pair of NOR-bearing chromosomes, Ag-NORs always correspond to the secondary constriction. Differences in the fundamental number and in heterochromosome morphology, have been observed by other authors, in different European populations. This variability is analysed and discussed. Riassunto Analisi cromosomica in tre specie di Myoxidae - L'analisi cromosomica è stata condotta su popolazioni europee di tre specie di Myoxidae: Myoxus glis, 4 popolazioni provenienti dal Nord e Sud Italia, e dalla Turchia; Dryomys nitedula, 4 popolazioni provenienti dal Nord e Sud Italia, da Israele e dalla Turchia; Myomimus roachi, 1 esemplare, proveniente dalla Turchia. Myoxus glis presenta 2n=62. Gli esemplari, provenienti dalle diverse popolazioni, mostrano corrispondenza nella morfologia sia degli autosomi che degli eterocromosomi. Dryomys nitedula presenta 2n=48. La morfologia dei cromosomi nei cariotipi appare corrispondente mentre diversa è la localizzazione degli Ag-NOR.

  19. Focal chromosomal copy number aberrations identify CMTM8 and GPR177 as new candidate driver genes in osteosarcoma.

    Science.gov (United States)

    Both, Joeri; Krijgsman, Oscar; Bras, Johannes; Schaap, Gerard R; Baas, Frank; Ylstra, Bauke; Hulsebos, Theo J M

    2014-01-01

    Osteosarcoma is an aggressive bone tumor that preferentially develops in adolescents. The tumor is characterized by an abundance of genomic aberrations, which hampers the identification of the driver genes involved in osteosarcoma tumorigenesis. Our study aims to identify these genes by the investigation of focal copy number aberrations (CNAs, GPR177 as a new candidate oncogene in osteosarcoma. In osteosarcoma, CMTM8 has been shown to suppress EGFR signaling. In other tumor types, CMTM8 is known to suppress the activity of the oncogenic protein c-Met and GPR177 is known as an overexpressed upstream regulator of the Wnt-pathway. Further studies are needed to determine whether these proteins also exert the latter functions in osteosarcoma tumorigenesis.

  20. Clinical Omics Analysis of Colorectal Cancer Incorporating Copy Number Aberrations and Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Yoshida

    2010-07-01

    Full Text Available Background: Colorectal cancer (CRC is one of the most frequently occurring cancers in Japan, and thus a wide range of methods have been deployed to study the molecular mechanisms of CRC. In this study, we performed a comprehensive analysis of CRC, incorporating copy number aberration (CRC and gene expression data. For the last four years, we have been collecting data from CRC cases and organizing the information as an “omics” study by integrating many kinds of analysis into a single comprehensive investigation. In our previous studies, we had experienced difficulty in finding genes related to CRC, as we observed higher noise levels in the expression data than in the data for other cancers. Because chromosomal aberrations are often observed in CRC, here, we have performed a combination of CNA analysis and expression analysis in order to identify some new genes responsible for CRC. This study was performed as part of the Clinical Omics Database Project at Tokyo Medical and Dental University. The purpose of this study was to investigate the mechanism of genetic instability in CRC by this combination of expression analysis and CNA, and to establish a new method for the diagnosis and treatment of CRC. Materials and methods: Comprehensive gene expression analysis was performed on 79 CRC cases using an Affymetrix Gene Chip, and comprehensive CNA analysis was performed using an Affymetrix DNA Sty array. To avoid the contamination of cancer tissue with normal cells, laser micro-dissection was performed before DNA/RNA extraction. Data analysis was performed using original software written in the R language. Result: We observed a high percentage of CNA in colorectal cancer, including copy number gains at 7, 8q, 13 and 20q, and copy number losses at 8p, 17p and 18. Gene expression analysis provided many candidates for CRC-related genes, but their association with CRC did not reach the level of statistical significance. The combination of CNA and gene

  1. Cytogenetic analysis of chromosomal abnormalities in Sri Lankan children

    Institute of Scientific and Technical Information of China (English)

    Colombo; Sri Lanka

    2015-01-01

    Background: Cytogenetic analysis is a valuable investigation in the diagnostic work up of children with suspected chromosomal disorders. The objective of this study was to describe the prevalence of various types of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis. Methods: Cytogenetic reports of 1554 consecutive children with suspected chromosomal disorders who underwent karyotyping in two genetic centers in Sri Lanka from January 2006 to December 2011 were reviewed retrospectively. Results: A total of 1548 children were successfully karyotyped. Abnormal karyotypes were found in 783 (50.6%) children. Numerical and structural abnormalities accounted for 90.8% and 9.2%, respectively. Down syndrome was the commonest aneuploidy identifi ed. Other various autosomal and sex chromosomal aneuploidies as well as micro-deletion syndromes were also detected. Conclusions: The prevalence of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis for suspected chromosomal disorders was relatively higher than that in Caucasian and other Asian populations.

  2. Uniparental disomy analysis in carriers of balanced chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    May, K.M.; Pettay, D.; Muralidharan, K. [Emory Univ. School of Medicine, Atlanta, GA (United States)] [and others

    1994-09-01

    Although most individuals who carry a balanced familial chromosome rearrangement are phenotypically normal, those who are clinically abnormal raise the question of whether or not the rearrangement plays a causative role. One possible mechanism involves meiotic segregation of a normal homolog along with the rearranged chromosome(s) such that a trisomic conception occurs. Subsequent loss by mitotic nondisjunction of the structurally normal chromosome contributed by the non-carrier parent would then result in uniparental disomy (UPD) in a conceptus carrying a balanced rearrangement. UPD for chromosomes 14 and 15 has been demonstrated in several clinically abnormal individuals who carry a familial Robertsonian translocation. We have extended this type of analysis to include other forms of balanced chromosome rearrangements. We report the results of UPD analysis of 14 families who have a phenotypically abnormal child with an apparently balanced rearrangement. The series includes 4 reciprocal translocations, 4 Robertsonian translocations, 2 X;autosome translocations, and 4 inversions. High resolution chromosomes were used to compare breakpoints between parent and offspring to exclude the possibility of further rearrangements. Parental origin of the chromosome(s) involved was determined by DNA polymorphism analysis using PCR or Southern blotting techniques. We found no evidence of UPD in any of the 14 cases. Our data suggest that UPD is not a common explanation for phenotypically abnormal carriers of balanced chromosome rearrangements.

  3. Cytogenetic Analysis for Suspected Chromosomal Abnormalities; A Five Years Experience

    Science.gov (United States)

    Karra, Vijay Kumar; Jindal, Ankur; Puppala, Madhavi; Singh, Pratiksha; Rawat, Kanchan; Kapoor, Seema

    2016-01-01

    Introduction Chromosomal abnormalities are the results of alterations in the number or structure of chromosomes causing significant human morbidity and mortality. They are responsible for a large proportion of miscarriages, developmental delay, disorders of sexual development, congenital malformations and mental retardation. Aim The aim of this study was to describe the prevalence of different chromosomal abnormalities in North Indian patients referred for cytogenetic analysis. Materials and Methods Total of 859 patients ranging from newborn to 37 years of age were referred to the division of genetics, Department of Paediatrics between 2010 and 2015, with a variety of clinical disorders; Down syndrome (DS), Turner’s syndrome (TS) and Klinefelter syndrome; amenorrhea; ambiguous sex and multiple congenital malformations. Chromosomal analysis was performed on lymphocyte culture according to standard methods. Results Of the 859 cases studied, 371 (43.1%) had chromosomal abnormalities. The most common autosomal abnormalities were DS 302 (81.4%) and sex chromosomal abnormalities were TS 51 (13.7%). Numerical abnormalities were accounted for 353 (41.0%) and structural abnormalities 18 (2.0%), respectively. Various other chromosomal anomalies were also reported. Conclusion We have reviewed the incidence and distribution of chromosomal abnormalities and found higher rate of chromosomal abnormalities 43.1% in the referred cases. Our data suggest that chromosomal analysis is important tool in the evaluation of genetic disorders and helps clinicians to provide accurate diagnosis and proper genetic counselling. PMID:27790464

  4. The quantitative radiation dose of 32P by chromosomal aberration%染色体畸变率估算32P的辐射剂量

    Institute of Scientific and Technical Information of China (English)

    施常备; 许建林; 袁勇; 陆建荣; 袁彬; 赵明刚; 王翔; 陈葳; 邓敬兰

    2012-01-01

    Objective To quantify the radiation dose of32P by the G-banding chromosomal aberration rate.Methods The human blood was irradiated by 4 MV X-ray of 0.5,1,2,4 Gy respectively.The doseresponse curve between the radiation dose and the dicentrics aberration rate was assayed.74 kBq 32p colloid was put into culture solution and,after 72 h,the dicentrics aberration rate was observed.The radiation dose of 32p was assayed by the dose-response curve.Results The dose-response curve between the radiation dose and the dicentrics aberration rate was y=24.05x-13.34 (R2=0.975).The dicentrics aberration rate of 74 kBq 32p was 18% and the radiation dose of 32p in 5 ml culture solution during 72 h was 1.3 Gy.Conclusion The radiation dose of radionuclide can be estimated by chromosomal aberration rate.%目的 应用G显带的染色体双着丝粒畸变率评估32p的辐射剂量.方法 应用4 MV的X射线对离体人血液进行0.5 Gy、1 Gy、2 Gy和4 Gy的照射,建立染色体双着丝粒畸变率和X射线的辐射剂量的剂量-效应曲线.将74 kBq的32p胶体加入淋巴细胞的培养液后72 h,进行G显带染色体分析,通过X射线的辐射剂量和染色体双着丝粒畸变率的剂量-效应曲线来评估32p的辐射剂量.结果 4 MV的X射线的辐射剂量和染色体的双着丝粒畸变率呈线性正相关,剂量-效应曲线为y=24.05x- 13.34 (R2=0.975).74 kBq的32P胶体产生的染色体双着丝粒畸变率为18%,即74 kBq的32p胶体在5 ml淋巴细胞培养液中72 h约产生1.3 Gy的辐射剂量.结论 应用染色体畸变率可以有效地评估放射性核素的内照射剂量.

  5. Chromosome abnormalities in colorectal adenomas: two cytogenetic subgroups characterized by deletion of 1p and numerical aberrations

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N

    1996-01-01

    changes were +20, +13, and monosomy 18, found in six, five, and two adenomas, respectively. Rearrangement of chromosome 1 was the most common structural change. Abnormalities involving 1p were seen in six adenomas, leading to visible loss of material in three. One adenoma had one clone with a large...

  6. VEGF siRNA致中国仓鼠肺细胞染色体畸变的研究%Research of chromosome aberration in Chinese hamster lung fibroblast induced by VEGF siRNA

    Institute of Scientific and Technical Information of China (English)

    荆春霞; 张洹; 杨光; 吴赤蓬; 何林

    2011-01-01

    Objective To explore the effects of VECF siRNA on chromosome aberration in Chinese hamster lung fibroblasts (CHL). Methods The chromosome aberrations were observed after CHL were transfected with VECF siRNA for 24 hours and 48h. Results There were a questionable positive in 100nmol/L VEGF siRNA after VECF siRNA were transfected for 24h and the chromosome aberration rate was 6 percentages. Both 50nmol/L VEGF siRNA and 100nmol/L VECF siRNA caused the questionable positive after VEGF siRNAs were transfected for 48h, and the chromosome aberration rates was 6 percentages and 10 percentages separately. There were no the chromosome aberration in 25nmol/L VEGF siRNA. The types of chromosomal aberration induced by VEGF siRNAs included break, Dicentric grain, polyploid, gap, and three trajectories. Conclusion lOOnmol/L VEGF siRNA might cause CHL chromosome aberration.%目的 研究VEGF siRNA对中国仓鼠肺细胞(CHL)的染色体畸变作用.方法 采用25、50和100nmol/L的VEGF siRNA转染中国仓鼠的肺细胞,分别观察24h、48h后的染色体畸变情况.结果 在VEGFsiRNA转染24小时,仅100nmol/L VEGF siRNA产生可疑阳性反应,其染色体的畸变率为6%;在VEGFsiRNA转染48小时后,50nmol/L的VEGF siRNA和100nmol/L的VEGF siRNA均产生可疑阳性反应,染色体的畸变率分别为6%和10%.而25nmol/L的VEGF siRNA无论是在转染后24h还是48h,均未产生染色体的畸变作用.VEGF siRNA产生的染色体畸变类型有断裂、双着丝粒、多倍体、裂隙、三射体.结论 100nmol/L的VEGFsiRNA分子可引起CHL细胞产生染色体畸变.

  7. Antioxidants in aqueous extract of Myristica fragrans (Houtt.) suppress mitosis and cyclophosphamide-induced chromosomal aberrations in Allium cepa L. cells.

    Science.gov (United States)

    Akinboro, Akeem; Mohamed, Kamaruzaman Bin; Asmawi, Mohd Zaini; Sulaiman, Shaida Fariza; Sofiman, Othman Ahmad

    2011-11-01

    In this study, freeze-dried water extract from the leaves of Myristica fragrans (Houtt.) was tested for mutagenic and antimutagenic potentials using the Allium cepa assay. Freeze-dried water extract alone and its combination with cyclophosphamide (CP) (50 mg/kg) were separately dissolved in tap water at 500, 1000, 2000, and 4000 mg/kg. Onions (A. cepa) were suspended in the solutions and controls for 48 h in the dark. Root tips were prepared for microscopic evaluation. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radicals' scavenging power of the extract was tested using butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as standards. Water extract of Myristica fragrans scavenged free radicals better than BHA, but worse than BHT. The extract alone, as well as in combination with CP suppressed cell division, and induced chromosomal aberrations that were insignificantly different from the negative control (P ≤ 0.05). However, cytotoxic and mutagenic actions of CP were considerably suppressed. The observed effects on cell division and chromosomes of A. cepa may be principally connected to the antioxidant properties of the extract. The obtained results suggest mitodepressive and antimutagenic potentials of water extract of the leaves of M. fragrans as desirable properties of a promising anticancer agent.

  8. Antioxidants in aqueous extract of Myristicafragrans (Houtt.) suppress mitosis and cyclophosphamide-induced chromosomal aberrations in Allium cepa L.cells

    Institute of Scientific and Technical Information of China (English)

    Akeem AKINBORO; Kamaruzaman Bin MOHAMED; Mohd Zaini ASMAWI; Shaida Fariza SULAIMAN; Othman Ahmad SOFIMAN

    2011-01-01

    In this study,freeze-dried water extract from the leaves of Myristica fragrans (Houtt.) was tested for mutagenic and antimutagenic potentials using the Allium cepa assay.Freeze-dried water extract alone and its combination with cyclophosphamide (CP) (50 mg/kg) were separately dissolved in tap water at 500,1000,2000,and 4000 mg/kg.Onions (A.cepa) were suspended in the solutions and controls for 48 h in the dark.Root tips were prepared for microscopic evaluation.2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radicals' scavenging power of the extract was tested using butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as standards.Water extract of Myristica fragrans scavenged free radicals better than BHA,but worse than BHT.The extract alone,as well as in combination with CP suppressed cell division,and induced chromosomal aberrations that were insignificantly different from the negative control (P≤0.05).However,cytotoxic and mutagenic actions of CP were considerably suppressed.The observed effects on cell division and chromosomes of A.cepa may be principally connected to the antioxidant properties of the extract.The obtained results suggest mitodepressive and antimutagenic potentials of water extract of the leaves of M.fragrans as desirable properties of a promising anticancer agent.

  9. Interspecific comparisons of the sensitivity to chromosome aberration production by x rays. [Comparative in vitro radiosensitivity of leukocyte chromosomes from mice to man

    Energy Technology Data Exchange (ETDEWEB)

    Brewen, J.G.

    1978-01-01

    It is concluded that arm number probably plays a minor role, if any, in the relative radiosensitivity of a species. Instead the reported differences are probably a reflection of inherent basic biological mechanisms of repair that vary from one order of mammals to the next. It should be added, however, that the ultimate goal of all of these studies is to make a reasonable risk estimate for man. In that context the best approach is that of conservatism and the current data on mouse and man suggest that man has 1.5 to 2.0 times the risk of mice for chromosome rearrangement induction by x rays.

  10. Factor Analysis of the Aberrant Behavior Checklist in Individuals with Autism Spectrum Disorders

    Science.gov (United States)

    Brinkley, Jason; Nations, Laura; Abramson, Ruth K.; Hall, Alicia; Wright, Harry H.; Gabriels, Robin; Gilbert, John R.; Pericak-Vance, Margaret A. O.; Cuccaro, Michael L.

    2007-01-01

    Exploratory factor analysis (varimax and promax rotations) of the aberrant behavior checklist-community version (ABC) in 275 individuals with Autism spectrum disorder (ASD) identified four- and five-factor solutions which accounted for greater than 70% of the variance. Confirmatory factor analysis (Lisrel 8.7) revealed indices of moderate fit for…

  11. Clinical utility of chromosomal microarray analysis of DNA from buccal cells: detection of mosaicism in three patients.

    Science.gov (United States)

    Sdano, Mallory R; Vanzo, Rena J; Martin, Megan M; Baldwin, Erin E; South, Sarah T; Rope, Alan F; Allen, William P; Kearney, Hutton

    2014-12-01

    Mosaic chromosomal abnormalities are relatively common. However, mosaicism may be missed due to multiple factors including failure to recognize clinical indications and order appropriate testing, technical limitations of diagnostic assays, or sampling tissue (s) in which mosaicism is either not present, or present at very low levels. Blood leukocytes have long been the "gold standard" sample for cytogenetic analysis; however, the culturing process for routine chromosome analysis can complicate detection of mosaicism since the normal cell line may have a growth advantage in culture, or may not be present in the cells that produce metaphases (the lymphocytes). Buccal cells are becoming increasingly utilized for clinical analyses and are proving to have many advantages. Buccal swabs allow for simple and noninvasive DNA collection. When coupled with a chromosomal microarray that contains single nucleotide polymorphic probes, analysis of buccal cells can maximize a clinician's opportunity to detect cytogenetic mosaicism. We present three cases of improved diagnosis of mosaic aberrations using buccal specimens for chromosomal microarray analysis. In each case, the aberration was either undetectable in blood or present at such a low level it likely could have gone undetected. These cases highlight the limitations of certain laboratory methodologies for identifying mosaicism. We also present practice implications for genetic counselors, including clinic workflow changes and counseling approaches based on increasing use of buccal samples.

  12. WE-D-BRE-05: Prediction of Late Radiation-Induced Proctitis in Prostate Cancer Patients Using Chromosome Aberration and Cell Proliferation Rate

    Energy Technology Data Exchange (ETDEWEB)

    Oh, J; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

    Purpose: Chromosome damage and cell proliferation rate have been investigated as potential biomarkers for the early prediction of late radiationinduced toxicity. Incorporating these endpoints, we explored the predictive power for late radiation proctitis using a machine learning method. Methods: Recently, Beaton et al. showed that chromosome aberration and cell proliferation rate could be used as biomarkers to predict late radiation proctitis (Beaton et al. (2013) Int J Rad Onc Biol Phys, 85:1346–1352). For the identification of radiosensitive biomarkers, blood samples were collected from 10 patients with grade 3 late proctitis along with 20 control patients with grade 0 proctitis. After irradiation at 6 Gy, statistically significant difference was observed between the two groups, using the number of dicentrics and excess fragments, and the number of cells in metaphase 2 (M2). However, Beaton et al. did not show the usefulness of combining these endpoints. We reanalyzed the dataset to investigate whether incorporating these endpoints can increase the predictive power of radiation proctitis, using a support vector machine (SVM). Results: Using the SVM method with the number of fragments and M2 endpoints, perfect classification was achieved. In addition, to avoid biased estimate of the classification method, leave-one-out cross-validation (LOO-CV) was performed. The best performance was achieved when all three endpoints were used with 87% accuracy, 90% sensitivity, 85% specificity, and 0.85 AUC (the area under the receiver operating characteristic (ROC) curve). The most significant endpoint was the number of fragments that obtained 83% accuracy, 70% sensitivity, 90% specificity, and 0.82 AUC. Conclusion: We demonstrated that chromosome damage and cell proliferation rate could be significant biomarkers to predict late radiation proctitis. When these endpoints were used together in conjunction with a machine learning method, the better performance was obtained

  13. [Biological effects in natural populations of small rodents in radiation-polluted territories. Dynamics of chromosome aberration frequency in a number of generations of European bank vole (Clethrionomys glareolus, Schreber)].

    Science.gov (United States)

    Goncharova, R I; Riabokon', N I

    1998-01-01

    The dynamics of chromosome aberration frequency in bone marrow cells of many generations (14) of bank vole living in the radioactive trace of the Chernobyl catastrophe (1986-1992) has been analysed. The study revealed that the chromosome aberration frequency in voles in the areas with radio-contamination density 220 and 1526 kBq/m2 (for 137Cs) significantly exceeds the control level 3-7 times over the whole period under investigation. The dynamics of the frequency of structural chromosome injuries from 1986 to 1991-1992 is characterised by the tendency to increase in all populations inhabiting the areas with various radio-contamination density (8-1526 kBq/m2).

  14. [Comparison of the frequency of chromosomal disorders in populations of in vitro-matured and ovulating rat oocytes].

    Science.gov (United States)

    Kitaev, E M; Pimenova, M N

    1980-12-01

    The rat oocytes extracted from the rat ovaries and cultivated for 42-46 hours were compared with ovulated oocytes by the chromosomal aberration rate. The chromosomal aberration rate in the population of "follicular" oocytes was 8.2% on the average whereas in ovulated oocytes, it did not exceed 1.8%. Analysis of the chromosomal aberrations depending on the phase of the estral cycle suggests that the main portion of chromosomal aberrations in cultivated oocytes occurs during the physiological process of follicular atresia.

  15. The DNA sequence, annotation and analysis of human chromosome 3

    DEFF Research Database (Denmark)

    Muzny, Donna M; Scherer, Steven E; Kaul, Rajinder

    2006-01-01

    After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chr...

  16. Should the indications for prenatal chromosome analysis be changed?

    DEFF Research Database (Denmark)

    Philip, J; Bang, J; Madsen, Mette

    1977-01-01

    Amniocentesis for chromosome analysis was performed in 1086 pergnant women, 739 of whom had an increased risk of giving birth to a child with chromosome abnormalities. Such abnormalities were found in almost identical proportions among the fetuses with an increased risk (1.2%) and among those...

  17. Identification of chromosome aberrations in sporadic microsatellite stable and unstable colorectal cancers using array comparative genomic hybridization

    DEFF Research Database (Denmark)

    Jensen, Thomas Dyrsø; Li, Jian; Wang, Kai;

    2011-01-01

    Colorectal cancer (CRC) is one of the most common cancers in Denmark and in the western world in general, and the prognosis is generally poor. According to the traditional molecular classification of sporadic colorectal cancer, microsatellite stable (MSS)/chromosome unstable (CIN) colorectal...... cancers constitute approximately 85% of sporadic cases, whereas microsatellite unstable (MSI) cases constitute the remaining 15%. In this study, we used array comparative genomic hybridization (aCGH) to identify genomic hotspot regions that harbor recurrent copy number changes. The study material...

  18. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...... show that high expression of 5q14 genes and low levels of TNFR2 pathway genes were associated with poor survival in basal-like cancers. Furthermore, low expression of 5q33 genes and interleukin-12 pathway genes were associated with poor outcome exclusively in ERBB2-like tumors. Conclusion...

  19. Molecular cytogenetic analysis of dicentric chromosomes in acute myeloid leukemia.

    Science.gov (United States)

    Sarova, Iveta; Brezinova, Jana; Zemanova, Zuzana; Ransdorfova, Sarka; Izakova, Silvia; Svobodova, Karla; Pavlistova, Lenka; Berkova, Adela; Cermak, Jaroslav; Jonasova, Anna; Siskova, Magda; Michalova, Kyra

    2016-04-01

    Dicentric chromosomes (DCs) have been described in many hematological diseases, including acute myeloid leukemia (AML). They are markers of cancer and induce chromosomal instability, leading to the formation of other chromosomal aberrations and the clonal evolution of pathological cells. Our knowledge of the roles and behavior of human DCs is often derived from studies of induced DCs and cell lines. It is difficult to identify all the DCs in the karyotypes of patients because of the limitations of metaphase cytogenetic methods. The aim of this study was to revise the karyotypes of 20 AML patients in whom DCs were found with conventional G-banding or multicolor fluorescence in situ hybridization (mFISH) with (multi)centromeric probes and to characterize the DCs at the molecular cytogenetic level. FISH analyses confirmed 23 of the 29 expected DCs in 18 of 20 patients and identified 13 others that had not been detected cytogenetically. Fourteen DCs were altered by other chromosomal changes. In conclusion, karyotypes with DCs are usually very complex, and we have shown that they often contain more than one DC, which can be missed with conventional or mFISH methods. Our study indicates an association between number of DCs in karyotype and very short survival of patients.

  20. Flow karyotyping and sorting of human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Peters, D.; Pinkel, D.; Trask, B.; van den Engh, G.; Van Dilla, M.A.

    1986-07-16

    Flow cytometry and sorting are becoming increasingly useful as tools for chromosome classfication and for the detection of numerical and structural chromosome aberrations. Chromosomes of a single type can be purified with these tools to facilitate gene mapping or production of chromosome specific recombinant DNA libraries. For analysis of chromosomes with flow cytometry, the chromosomes are extracted from mitotic cells, stained with one or more fluorescent dyes and classified one-by-one according to their dye content(s). Thus, the flow approach is fundamentally different than conventional karyotyping where chromosomes are classified within the context of a metaphase spread. Flow sorting allows purification of chromosomes that can be distinguished flow cytometrically. The authors describe the basic principles of flow cytometric chromosome classification i.e. flow karyotyping, and chromosome sorting and describe several applications. 30 refs., 8 figs.

  1. Quickscan dicentric chromosome analysis for radiation biodosimetry.

    Science.gov (United States)

    Flegal, F N; Devantier, Y; McNamee, J P; Wilkins, R C

    2010-02-01

    The dicentric chromosome assay (DCA) is the gold-standard assay for accurately estimating unknown radiological doses to individuals following radiological or nuclear accidents. However in a mass-casualty scenario, this assay is not well suited for providing timely dose estimates due to its time- and expertise-intensive nature. In Canada, two approaches are being developed in an attempt to increase triage-quality biological dosimetry throughput. These are 1) increasing the number of trained personnel capable of conducting the DCA, and 2) evaluating alternative biodosimetry approaches or DCA variations. In a recent exercise, a new scoring technique (termed DCA QuickScan) was evaluated as an alternative rapid-scoring approach. Triage-quality conventional DCA and DCA QuickScan analysis were based upon scoring a minimum of 50 metaphase cells or 30 dicentrics by 9-15 scorers across four laboratories. Dose estimates for the conventional DCA were found to be within 0.5 Gy of the actual dose for 83% of the unknown samples, while DCA QuickScan dose estimates were within 0.5 Gy for 80% of the samples. Of the dose estimates falling 0.5 Gy or more outside the actual dose, the majority were dose over-estimates. It was concluded that the DCA QuickScan approach can provide critical dose information at a much faster rate than the conventional DCA without sacrificing accuracy. Future studies will further evaluate the accuracy of the DCA QuickScan method.

  2. High-resolution microarray analysis unravels complex Xq28 aberrations in patients and carriers affected by X-linked blue cone monochromacy.

    Science.gov (United States)

    Yatsenko, S A; Bakos, H A; Vitullo, K; Kedrov, M; Kishore, A; Jennings, B J; Surti, U; Wood-Trageser, M A; Cercone, S; Yatsenko, A N; Rajkovic, A; Iannaccone, A

    2016-01-01

    The human X chromosome contains ∼ 1600 genes, about 15% of which have been associated with a specific genetic condition, mainly affecting males. Blue cone monochromacy (BCM) is an X-linked condition caused by a loss-of-function of both the OPN1LW and OPN1MW opsin genes. The cone opsin gene cluster is composed of 2-9 paralogs with 99.8% sequence homology and is susceptible to deletions, duplications, and mutations. Current diagnostic tests employ polymerase chain reaction (PCR)-based technologies; however, alterations remain undetermined in 10% of patients. Furthermore, carrier testing in females is limited or unavailable. High-resolution X chromosome-targeted CGH microarray was applied to test for rearrangements in males with BCM and female carriers from three unrelated families. Pathogenic alterations were revealed in all probands, characterized by sequencing of the breakpoint junctions and quantitative real-time PCR. In two families, we identified a novel founder mutation that consisted of a complex 3-kb deletion that embraced the cis-regulatory locus control region and insertion of an additional aberrant OPN1MW gene. The application of high-resolution X-chromosome microarray in clinical diagnosis brings significant advantages in detection of small aberrations that are beyond the resolution of clinically available aCGH analysis and which can improve molecular diagnosis of the known conditions and unravel previously unrecognized X-linked diseases.

  3. Yeast X-chromosome-associated protein 5 (Xap5) functions with H2A.Z to suppress aberrant transcripts.

    Science.gov (United States)

    Anver, Shajahan; Roguev, Assen; Zofall, Martin; Krogan, Nevan J; Grewal, Shiv I S; Harmer, Stacey L

    2014-08-01

    Chromatin regulatory proteins affect diverse developmental and environmental response pathways via their influence on nuclear processes such as the regulation of gene expression. Through a genome-wide genetic screen, we implicate a novel protein called X-chromosome-associated protein 5 (Xap5) in chromatin regulation. We show that Xap5 is a chromatin-associated protein acting in a similar manner as the histone variant H2A.Z to suppress expression of antisense and repeat element transcripts throughout the fission yeast genome. Xap5 is highly conserved across eukaryotes, and a plant homolog rescues xap5 mutant yeast. We propose that Xap5 likely functions as a chromatin regulator in diverse organisms.

  4. Study of radiation-induced chromosomal aberrations; Untersuchung strahleninduzierter Chromosomenaberrationen. Bestrahlung der Brustdruesenepithelzelllinie MCF-12A mit Roentgenstrahlung aus konventionellen Roentgenroehren und Bestimmung der Dosis-Effekt-Kurve. Studienarbeit

    Energy Technology Data Exchange (ETDEWEB)

    Wolfring, E. [Technische Univ. Bergakademie Freiberg (Germany). Interdisziplinaeres Oekologisches Zentrum

    2004-06-01

    A method for determining chromosomal aberrations was established for the purpose of examining the relative biological effectiveness (RBE) of photon radiation with respect to mammary epithelium cells. Cells were exposed to 25 kV X-radiation and to 200 kV X-radiation for comparison and the resulting concentrations of chromosomal aberrations were compared. The RBE{sub M} value for radiation-induced fragmentation was found to be 4.2 {+-} 2.4, while the RBE{sub M} value for radiation-induced generation of dicentric chromosomes was found to be 0.5 {+-} 0.5. In addition to the evaluation of chromosomal aberrations the number of cell cycles undergone by the cells was monitored by means of BrDU staining. As expected, the proportion of cells which underwent more than one cell cycle following exposure to 5 Gy was very low in both cases, amounting to 1.9% (25 kV) and 3.2 (200 kV). Non-radiated cells yielded control values of 26.0% and 12.6%, suggesting variations in external conditions from day to day.

  5. Effect of Ginsenoside Rd on Chromosome Aberration in Chinese Hamster Lung Cells%人参皂苷Rd对中国仓鼠肺细胞染色体畸变作用

    Institute of Scientific and Technical Information of China (English)

    高梅; 曹冲; 朱春花; 曲保恩

    2013-01-01

    目的 研究人参皂苷Rd致中国仓鼠肺细胞(Chinese hamster lung cells,CHL)染色体畸变的作用.方法 细胞计数法测定人参皂苷Rd对CHL细胞的半数抑制浓度(IC50),根据IC50设立不同剂量组,进行染色体畸变试验,分别观察人参皂苷Rd染毒6、24h及加S9后染毒6h CHL细胞染色体的数目及结构变化,进行染色体畸变分析.结果 人参皂苷Rd染毒6、24h及加S.后染毒6h CHL细胞染色体畸变为阴性.结论 在本试验条件下,人参皂苷Rd不能引起CHL细胞染色体产生畸变.%Objective To explore the effect of ginsenoside Rd on chromosome aberration in Chinese hamster lung cells(CHL). Methods We used the method of cell counting to determine the IC50, of ginsenoside Rd on CHL cells,then to establish the range of doses according to the IC50 and to do the cell chromosome aberration experiment. When the CHL cells were exposured to ginsenoside Rd at 6h and 24h and plused S9 mixture at 6h respectively, we observed the changes of chromosome number and structure, then to judge the chromosome aberration results. Results Negative response was found at 6h and 24h after the treatment with ginsenoside Rd and at 6h after the addition of S9 mixture. Conclusion Under the condition of this experiment, ginsenoside Rd does not induce chromosome aberration in CHL cells.

  6. Measurements of metaphase and interphase chromosome aberrations transmitted through early cell replication rounds in human lymphocytes exposed to low-LET protons and high-LET {sup 12}C ions

    Energy Technology Data Exchange (ETDEWEB)

    Manti, Lorenzo [Radiation Biophysics Laboratory, Department of Physical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Naples (Italy) and Istituto Nazionale di Fisica Nucleare (INFN), Naples (Italy)]. E-mail: manti@na.infn.it; Durante, Marco [Radiation Biophysics Laboratory, Department of Physical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Naples (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Naples (Italy); Grossi, Gianfranco [Radiation Biophysics Laboratory, Department of Physical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Naples (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Naples (Italy); Ortenzia, Ornella [Radiation Biophysics Laboratory, Department of Physical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Naples (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Naples (Italy); Pugliese, Mariagabriella [Radiation Biophysics Laboratory, Department of Physical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Naples (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Naples (Italy); Scampoli, Paola [Radiation Biophysics Laboratory, Department of Physical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Naples (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Naples (Italy); Gialanella, Giancarlo [Radiation Biophysics Laboratory, Department of Physical Sciences, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Naples (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Naples (Italy)

    2006-04-11

    Inheritable chromosome aberrations (CA) are of concern because cytogenetic damage may trigger the carcinogenic process. Moreover, stability of radiation-induced CA is a prerequisite for meaningful biological dosimetry. CA inheritability arguably depends on the aberration structure, with symmetrical exchanges being favoured over asymmetrical rearrangements, but it is also affected by radiation quality. CA induced by low-LET protons and high-LET {sup 12}C ions in G peripheral blood lymphocytes were measured in first- , second- and third-generation by combined FISH/harlequin staining of metaphase as well as prematurely condensed interphase chromosomes 1 and 2. As expected, the frequency of non-transmissible (NT) aberrations declined through replication rounds. A radiation-induced arrest occurred prior to first post-irradiation mitosis that prevalently affected aberrant cells. Aberrant cells incurred cycle delays also at subsequent cycles following proton-irradiation but not {sup 12}C ion-irradiation. As expected, the frequency of reciprocal translocations remained fairly stable while that of dicentrics was halved at each mitotic round. A significant fraction of complex-type exchanges was found in third-generation cells following both irradiations and appeared to be transmitted relatively more efficiently after protons than {sup 12}C ions. A low but stably transmitted frequency of transmissible (T)-type insertions were detected after {sup 12}C ions but not after low LET-irradiation. Our data support a differential ability by aberrant cells to progress through post-irradiation mitoses that is influenced by the aberration burden and radiation quality.

  7. Comparison of the micronucleus and chromosome aberration techniques for the documentation of cytogenetic damage in radiochemotherapy-treated patients with rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, Henrik Andreas; Hennies, Steffen; Herrmann, Markus Karl Alfred [Goettingen Univ. Medicine (DE). Dept. of Radiotherapy and Radiooncology] (and others)

    2011-01-15

    Purpose: The goal of the interdisciplinary Clinical Research Unit KFO179 (Biological Basis of Individual Tumor Response in Patients with Rectal Cancer) is to develop an individual Response and Toxicity Score for patients with locally advanced rectal cancer treated with neoadjuvant radiochemotherapy. The aim of the present study was to find a reliable and sensitive method with easy scoring criteria and high numbers of cell counts in a short period of time in order to analyze DNA damage in peripheral blood lymphocytes. Thus, the cytokinesis-block micronucleus (CBMN) assay and the chromosome aberration technique (CAT) were tested. Materials and Methods: Peripheral blood lymphocytes obtained from 22 patients with rectal cancer before (0 Gy), during (21.6 Gy), and after (50.4 Gy) radiochemotherapy were stimulated in vitro by phytohemagglutinin (PHA); the cultures were then processed for the CBMN assay and the CAT to compare the two methods. Results: A significant increase of chromosomal damage was observed in the course of radiochemotherapy parallel to increasing radiation doses, but independent of the chemotherapy applied. The equivalence of both methods was shown by Westlake's equivalence test. Conclusion: The results show that the CBMN assay and the CAT are equivalent. For further investigations, we prefer the CBMN assay, because it is simpler through easy scoring criteria, allows high numbers of cell counts in less time, is reliable, sensitive, and has higher statistical power. In the future, we plan to integrate cytogenetic damage during radiochemotherapy into the planned Response and Toxicity Score within our interdisciplinary Clinical Research Unit. (orig.)

  8. 辐射诱导染色体畸变的快速FISH方法的建立%Establishment of a rapid FISH method to analyze chromosome aberrations induced by Establishment of a rapid FISH method to analyze chromosome aberrations induced by irradiation irradiation

    Institute of Scientific and Technical Information of China (English)

    李爽; 陆雪; 赵骅; 封江彬; 刘青杰

    2014-01-01

    目的:建立一种检测辐射诱导染色体畸变的快速荧光原位杂交(FISH)方法。方法:两步简并引物PCR法扩增人α-卫60星DNA,制备荧光基团直接标记的泛着丝粒探针;对 Coγ射线照射后的人外周血淋巴细胞染色体标本进行FISH分析,荧光显微镜下检测着丝粒及染色体形态。结果:直接标记泛着丝粒探针杂交后显示所有染色体着丝粒均有较强的信号;应用制备的FISH探针检测到γ射线照射诱导的双着丝粒、着丝粒环和易位染色体畸变,37℃杂交5-12 h后经过简单的洗涤即可在荧光显微镜下检测到较好的信号。结论:本研究制备的直接标记泛着丝粒探针,可用于FISH快速检测辐射诱导的染色体双着丝粒体、着丝粒环和易位畸变。目的:建立一种检测辐射诱导染色体畸变的快速荧光原位杂交(FISH)方法。方法:两步简并引物PCR法扩增人α-卫60星DNA,制备荧光基团直接标记的泛着丝粒探针;对 Coγ射线照射后的人外周血淋巴细胞染色体标本进行FISH分析,荧光显微镜下检测着丝粒及染色体形态。结果:直接标记泛着丝粒探针杂交后显示所有染色体着丝粒均有较强的信号;应用制备的FISH探针检测到γ射线照射诱导的双着丝粒、着丝粒环和易位染色体畸变,37℃杂交5-12 h后经过简单的洗涤即可在荧光显微镜下检测到较好的信号。结论:本研究制备的直接标记泛着丝粒探针,可用于FISH快速检测辐射诱导的染色体双着丝粒体、着丝粒环和易位畸变。%OBJECTIVE: To establish a rapid fluorescence in situ hybridization (FISH) method and to analyze the chromosome aberrations induced by irradiation.METHODS:Human centromeric alpha satellite DNA was amplified and directly labeled with Cy3-dUTP or Fluorescein-12-dUTP by degenerate oligonucleotide priming-PCR (DOP-PCR) to prepare two pan-centromeric probes. Chromosome

  9. Induced chromosome aberrations analyzed by fluorescence in situ hybridization. Eight years follow up of the Goiania radiation accident victims

    Energy Technology Data Exchange (ETDEWEB)

    Natarajan, A.T.; Santos, S.J.; Darroudi, F.; Hadjidikova, V.; Vermeulen, S.; Chatterjee, S.; Van de Berg, M.; Grigorova, M. [Leiden University Medical Centrum LUMC, Department of Radiation Genetics and Chemical Mutagenesis, Wassenaarseweg 72, 2333 AL Leiden (Netherlands); Sakamoto-Hojo, E.T. [Department of Biology, Faculty of Philosophy, Sciences and Letters of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto (Brazil); Granath, F. [Department of Mathematical Statistics, Stockholm University, Stockholm (Sweden); Ramalho, A.T. [Institute of Radioprotection and Dosimetry, National Commission of Nuclear Energy, Rio de Janeiro (Brazil); Curado, M.P. [Foundation Leide das Neves Ferreira, Goiania (Brazil)

    1998-05-25

    The radiation accident in focus here occurred in a section of Goiania (Brazil) where more than a hundred individuals were contaminated with on September 1987. In order to estimate the absorbed radiation doses, initial frequencies of dicentrics and rings were determined in 129 victims [A.T. Ramalho, PhD Thesis, Subsidios a tecnica de dosimetria citogenetica gerados a partir da analise de resultados obtidos com o acidente radiologico de Goiania, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 1992]. We have followed some of these victims cytogenetically over the years seeking for parameters that could be used as basis for retrospective radiation dosimetry. Our data on translocation frequencies obtained by fluorescence in situ hybridization (FISH) could be directly compared to the baseline frequencies of dicentrics available for those same victims. Our results provided valuable information on how precise these estimates are. The frequencies of translocations observed years after the radiation exposure were two to three times lower than the initial dicentrics frequencies, the differences being larger at higher doses (>1 Gy). The accuracy of such dose estimates might be increased by scoring sufficient amount of cells. However, factors such as the persistence of translocation carrying lymphocytes, translocation levels not proportional to chromosome size, and inter-individual variation reduce the precision of these estimates

  10. Chromosomal instability in meningiomas.

    Science.gov (United States)

    van Tilborg, Angela A G; Al Allak, Bushra; Velthuizen, Sandra C J M; de Vries, Annie; Kros, Johan M; Avezaat, Cees J J; de Klein, Annelies; Beverloo, H Berna; Zwarthoff, Ellen C

    2005-04-01

    Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumor suppressor gene on chromosome 22. No causative gene is known for the remaining 40%. Cytogenetic analysis shows that meningiomas caused by inactivation of the NF2 gene can be divided into tumors that show monosomy 22 as the sole abnormality and tumors with a more complex karyotype. Meningiomas not caused by the NF2 gene usually have a diploid karyotype. Here we report that, besides the clonal chromosomal aberrations, the chromosome numbers in many meningiomas varied from one metaphase spread to the other, a feature that is indicative of chromosomal instability. Unexpectedly and regardless of genotype, a subgroup of tumors was observed with an average number of 44.9 chromosomes and little variation in the number of chromosomes per metaphase spread. In addition, a second subgroup was recognized with a hyperdiploid number of chromosomes (average 48.5) and considerable variation in numbers per metaphase. However, this numerical instability resulted in a clonal karyotype with chromosomal gains and losses in addition to loss of chromosome 22 only in meningiomas caused by inactivation of the NF2 gene. In cultured cells of all tumor groups, bi- and multinucleated cells were seen, as well as anaphase bridges, residual chromatid strings, multiple spindle poles, and unseparated chromatids, suggesting defects in the mitotic apparatus or kinetochore. Thus, we conclude that even a benign and slow-growing tumor like a meningioma displays chromosomal instability.

  11. Implementation of a dose-response curve for γ-radiation in the Portuguese population by use of the chromosomal aberration assay.

    Science.gov (United States)

    Martins, V; Antunes, A C; Monteiro Gil, O

    2013-01-20

    An in vitro dose-response curve following exposure to γ-radiation was determined at the IST/ITN, by use of the chromosomal aberration assay. This is the first study of this kind carried out among the Portuguese population. Un-irradiated and γ-irradiated peripheral blood lymphocytes from 16 healthy donors were cultured. A total of 22,395 metaphases were analyzed for frequency and distribution of dicentrics and centric rings, as a function of the radiation dose. The dose-response data for dicentrics and dicentrics plus centric rings were fitted by use of a linear-quadratic model: Y(dic)=(0.0011±0.0006)+(0.0105±0.0035)D+(0.0480±0.0019)D(2) and Y(dic+rings)=(0.0011±0.0006)+(0.0095±0.0036)D+(0.0536±0.0020)D(2). Also, calibration curves related to age and gender were determined, but no significant differences were found. Following the establishment of the dose-response curves, a validation experiment was carried out with three individuals. Real and estimated doses, obtained with the dose-response curves, were in agreement. These results give us confidence to apply both dose-response calibration curves in future biological dosimetry requirements.

  12. Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster (CHO) Cells With and Without Metabolic Activation, Test Acticle: Ethylenediamine Dinitrate (EDDN)

    Science.gov (United States)

    2010-02-25

    chromosomes leading to four-armed configurations. This could be asymmetrical with formation of a dicentric and an acentric chromatid, ifunion is complete, or...a shortened monocentric chromosome , and where there is no sister chromatid union. Dicentric - an asymmetrical exchange between two chromosomes ...a shortened monocentric chromosome , and where there is no sister chromatid union. Dicentric - an asymmetrical exchange between two chromosomes

  13. Analysis of chromosomal alterations induced by asbestos and ceramic fibers.

    Science.gov (United States)

    Dopp, E; Schiffmann, D

    1998-08-01

    Asbestos and other mineral fibers have long been known as carcinogenic agents. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We have investigated mitotic disturbances caused by amosite, crocidolite, and chrysotile in Syrian hamster embryo (SHE) fibroblasts. We also analyzed micronucleus formation as a result of mitotic disturbances, and carried out a characterization of the induced micronucleus population by kinetochore staining. In addition, the spindle fiber morphology was examined. Supravital UV-microscopy was used to analyze changes in chromatin structure, impaired chromatid separation and blocked cytokinesis. All three fiber types induced micronuclei in SHE cells with a high frequency (up to 200 MN/2000 cells; dose range: 0.1-5.0 microg/cm2) in a dose-dependent manner with a maximum between 48 and 66 h. Kinetochore staining revealed that 48% of fiber-induced micronuclei reacted positively. Furthermore, spindle deformation was observed in cells with disturbed meta- and anaphases while the spindle fiber morphology appeared unchanged. Our results show that asbestos fibers may cause both loss as well as breakage of chromosomes in the absence of direct interaction with spindle fibers. In addition, we analyzed the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic fluid cells (AFC) in vitro by amosite, chrysotile and crocidolite asbestos and ceramic fibers. The response of human (AFC) and rodent (SHE) cells to fiber treatment was compared using the micronucleus assay. AFC were much less susceptible than SHE cells to the induction of micronuclei by mineral fibers. The application of fluorescence in situ hybridization (FISH) with tandem DNA probes yielded more detailed informations about specific structural chromosome aberrations in the 1(cen-q12) and 9(cen-q12) regions and about abnormal numbers of chromosomes in interphase AFC. Using this FISH approach we found a statistically significant

  14. Comparative genomic hybridization analysis of genetic aberrations associated with development of esophageal squamous cell carcinoma in Henan, China

    Institute of Scientific and Technical Information of China (English)

    Yan-Ru Qin; Li-Dong Wang; Zong-Min Fan; Dora Kwong; Xin-Yuan Guan

    2008-01-01

    AIM: To characterize cytogenetic alterations in esophageal squamous cell carcinoma (ESCC) and its metastasis.METHODS: A total of 37 cases of primary ESCC and 15 pairs of primary ESCC tumors and their matched metastatic lymph nodes cases were enrolled from Linzhou, the high incidence area for ESCC in Henan, northern China. The comparative genomic hybridization (CGH) was applied to determine the chromosomal aberrations on the DNA extracted from the frozen ESCC and metastatic lymph node samples from these patients.RESULTS: CGH showed chromosomal aberrations in all the cases. In 37 cases of primary ESCC, chromosomal profile of DNA copy number was characterized by frequently detected gains at 8q (29/37, 78%), 3q (24/37, 65%), 5p (19/37, 51%); and frequently detected losses at 3p (21/37, 57%), 8p and 9q (14/37, 38%). In 15 pairs of primary ESCC tumors and their matched metastatic lymph node cases, the majority of the chromosomal aberrations in both primary tumor and metastatic lymph node lesions were consistent with the primary ESCC cases, but new candidate regions of interest were also detected. The most significant finding is the gains of chromosome 6p with a minimum high-level amplification region at 6pl2-6ql2 in 7 metastatic lymph nodes but only in 2 corresponding primary tumors (P = 0.05) and 20p with a minimum high-level amplification region at 20pl2 in 11 metastatic lymph nodes but only in 5 corresponding primary tumors (P < 0.05). Another interesting finding is the loss of chromosome 10p and 10q in 8 and 7 metastatic lymph nodes but only in 2 corresponding primary tumors (P < 0.05).CONCLUSION: Using the CGH technique to detect chromosomal aberrations in both the primary tumor and its metastatic lymph nodes of ESCC, gains of 8q, 3q and 5p and loss of 3p, 8p, 9q and 13q were specifically implicated in ESCC in Linzhou population. Gains of 6p and 20p and loss of 10pq may contribute to the lymph node metastasis of ESCC. These findings suggest that the gains and losses

  15. Chromosome analysis of nuclear power plant workers using fluorescence in situ hybridization and Giemsa assay.

    Science.gov (United States)

    Hristova, Rositsa; Hadjidekova, Valeria; Grigorova, Mira; Nikolova, Teodora; Bulanova, Minka; Popova, Ljubomira; Staynova, Albena; Benova, Donka

    2013-09-01

    The aim of this study was to evaluate the genotoxic effects of ionizing radiation in vivo in exposed Bulgarian nuclear power plant workers by using classical cytogenetic and molecular cytogenetic analyses of peripheral lymphocytes. Chromosome analysis using fluorescence in situ hybrydization (FISH) and Giemsa techniques was undertaken on 63 workers and 45 administrative staff controls from the Bulgarian Nuclear Power Plant. Using the Giemsa method, the frequencies of cells studied with chromosome aberrations, dicentrics plus rings and chromosome fragments in the radiation workers were significantly higher compared with the control group (P = 0.044, P = 0.014, and P = 0.033, respectively). A significant association between frequencies of dicentrics plus rings and accumulated doses was registered (P < 0.01). In the present study, a FISH cocktail of whole chromosome paints for chromosomes 1, 4 and 11 was used. A significant association between frequency of translocations and accumulated doses was also observed (P < 0.001). Within the control group, a correlation was found between age and the spontaneous frequency of translocations. No correlation was found between smoking status and frequency of translocations. When compared with the control group, workers with accumulated doses up to 100 mSv showed no increase in genome translocation frequency, whereas workers with accumulated doses from 101 to 200 mSv showed a statistically significant doubling of genome translocation frequency (P = 0.009). Thus, in cases of chronic exposure and for purposes of retrospective dosimetry, the genome frequency of translocations is a more useful marker for evaluation of genotoxic effects than dicentric frequency.

  16. Chromosome analysis of nuclear power plant workers using fluorescence in situ hybridization and Giemsa assay

    Science.gov (United States)

    Hristova, Rositsa; Hadjidekova, Valeria; Grigorova, Mira; Nikolova, Teodora; Bulanova, Minka; Popova, Ljubomira; Staynova, Albena; Benova, Donka

    2013-01-01

    The aim of this study was to evaluate the genotoxic effects of ionizing radiation in vivo in exposed Bulgarian nuclear power plant workers by using classical cytogenetic and molecular cytogenetic analyses of peripheral lymphocytes. Chromosome analysis using fluorescence in situ hybrydization (FISH) and Giemsa techniques was undertaken on 63 workers and 45 administrative staff controls from the Bulgarian Nuclear Power Plant. Using the Giemsa method, the frequencies of cells studied with chromosome aberrations, dicentrics plus rings and chromosome fragments in the radiation workers were significantly higher compared with the control group (P = 0.044, P = 0.014, and P = 0.033, respectively). A significant association between frequencies of dicentrics plus rings and accumulated doses was registered (P < 0.01). In the present study, a FISH cocktail of whole chromosome paints for chromosomes 1, 4 and 11 was used. A significant association between frequency of translocations and accumulated doses was also observed (P < 0.001). Within the control group, a correlation was found between age and the spontaneous frequency of translocations. No correlation was found between smoking status and frequency of translocations. When compared with the control group, workers with accumulated doses up to 100 mSv showed no increase in genome translocation frequency, whereas workers with accumulated doses from 101 to 200 mSv showed a statistically significant doubling of genome translocation frequency (P = 0.009). Thus, in cases of chronic exposure and for purposes of retrospective dosimetry, the genome frequency of translocations is a more useful marker for evaluation of genotoxic effects than dicentric frequency. PMID:23536543

  17. Ocular higher-order aberrations features analysis after corneal refractive surgery

    Institute of Scientific and Technical Information of China (English)

    WANG Yan; ZHAO Kan-xing; HE Ji-chang; JIN Ying; ZUO Tong

    2007-01-01

    Background The recent studies have shown that visual performance might be affected by the ocular aberration after the corneal refractive surgery, and try to minimize it. This study was to investigate the effects of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) on the higher order of wavefront aberration and analysis of their characteristics.Method This prospective study involved 32 eyes with similar refractive powers (-5.0 D to -6.0 D preoperatively). LASIK and PRK were performed with the same parameters of 6 mm diameter optical zone and 7 mm diameter transition zone ablation. Wavefront aberrations were tested using a ray tracing technique preoperatively and 3 months postoperatively.Three measurements were obtained for each condition; the root mean squared wavefront error (RMS), values for overall wavefront aberrations and each order of the Zernike aberrations were analyzed using the Matlab software. The 2-tailed t test was used for statistical analysis.Results Overall higher order aberrations were increased from (0.55±0.26) μm preoperatively to (0.93±0.37) μm for PRK and (0.79±0.38) μm for LASIK postoperatively. This was a 1.69 fold increase in the PRK group (t=3.95, P<0.001)and a 1.43 fold increase in the LASIK group (t=2.60, P<0.05). At 3 months, the mean RMS value for higher-order (3rd to 6th) were significantly increased compared with the corresponding preoperative values (P<0.05). The fourth order aberrations, spherical like aberration, were dominant by a 2.64 fold in PRK and a 2.31 fold in LASIK. Different influences of the PRK group and LASIK group were shown in the various zernike components. The statistically significant differences were seen in C40, C4+4, C5+1, C5+3, C5+5 and C6+2 of the PRK group and C3-3, C40, C5-5, C5+5, C6-2 of the LASIK group, which represents a 7.42, 3.58, 9.21, 2.72 and 5.3 fold increases in PRK group, and 6.40, 10.80, 11.06, 3.47 and 6.09 fold increases in LASIK group, respectively. C3

  18. Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men

    Directory of Open Access Journals (Sweden)

    Dinić Jelena

    2007-01-01

    Full Text Available Background/Aim. Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene. Methods. This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE method. Results. Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions. Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations. Conclusion. This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine diagnostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recommended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and

  19. Not para-, not peri-, but centric inversion of chromosome 12

    DEFF Research Database (Denmark)

    Silahtaroglu, A N; Hacihanefioglu, S; Güven, G S;

    1998-01-01

    A 39 year old male with primary infertility was diagnosed as having Klinefelter syndrome by conventional cytogenetic analysis, which also showed an abnormal chromosome 12. Fluorescence in situ hybridisation (FISH) analysis of the aberrant chromosome using a 12 specific centromeric probe showed...

  20. Detection of chromosomal aberrations of bladder carcinoma by fluorescence in situ hybridization%荧光原位杂交技术检测膀胱癌染色体畸变的研究

    Institute of Scientific and Technical Information of China (English)

    李晓娟; 符生苗; 刘元晓; 邓立群

    2012-01-01

    Objective To detect the common chromosomal aberrations from (he bladder transitional cell carcinoma by using M-FISH. Methods 50 urine samples were detected by FISH with centromeric probes of chromosome 17,7,3 and band probe of 9p2 l,and then the results were analyzed. Results There were four chromosomes showing a high distortion in 50 cases of bladder carcinoma group,showing significant association between chromosome 17,7,3,9p2 1 aberrations and pathological stage,grade (P<0.01). Conclusion Fluorescence in situ hybridization is an effective way for detection of chromosomal aberrations of urothelial tumors, as well as the early diagnosis of urothelial cancer.%目的 用多色荧光原位杂交(M-FISH)检测膀胱移行细胞癌中常见的染色体畸变. 方法 50例尿液标本采用FISH技术检测9p21区带及17、7、3号染色体的畸变情况,并对结果进行相应的统计学分析. 结果 50例膀胱癌病人组中,4个染色体均显示较高的畸变率.9p21以及17、7和3号染色体畸变率与病理分期、分级均有显著相关性(P<0.01).结论 用荧光原位杂交技术是检测尿路上皮肿瘤染色体畸变的有效方法,可作为早期诊断尿路上皮肿瘤的重要途径.

  1. Human oocyte chromosome analysis: complicated cases and major pitfalls

    Indian Academy of Sciences (India)

    Bernd Rosenbusch; Michael Schneider; Hans Wilhelm Michelmann

    2008-08-01

    Human oocytes that remained unfertilized in programmes of assisted reproduction have been analysed cytogenetically for more than 20 years to assess the incidence of aneuploidy in female gametes. However, the results obtained so far are not indisputable as a consequence of difficulties in evaluating oocyte chromosome preparations. Because of the lack of guidelines, we decided to summarize for the first time, the possible pitfalls in human oocyte chromosome analysis. Therefore, we screened the material from our previous studies and compiled representative, complicated cases with recommendations for their cytogenetic classification. We point out that maturity and size of the oocyte are important parameters and that fixation artefacts, as well as the particular structure of oocyte chromosomes, may predispose one to misinterpretations. Moreover, phenomena related to oocyte activation and fertilization are illustrated and explained. This compilation may help to avoid major problems in future studies and contribute to a more precise, and uniform assessment of human oocyte chromosomes.

  2. Mitochondrial-associated cell death mechanisms are reset to an embryonic-like state in aged donor-derived iPS cells harboring chromosomal aberrations.

    Science.gov (United States)

    Prigione, Alessandro; Hossini, Amir M; Lichtner, Björn; Serin, Akdes; Fauler, Beatrix; Megges, Matthias; Lurz, Rudi; Lehrach, Hans; Makrantonaki, Eugenia; Zouboulis, Christos C; Adjaye, James

    2011-01-01

    Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs) acquire features of human embryonic stem cells (hESCs) and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. However, reprogrammed cell lines have been found to harbor various genomic alterations. In addition, we recently discovered that the mitochondrial DNA of human fibroblasts also undergoes random mutational events upon reprogramming. Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the oncogenic potential of reprogrammed cells due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. Here, we investigated whether aged reprogrammed cells harboring chromosomal abnormalities show resistance to apoptotic cell death or mitochondrial-associated oxidative stress, both hallmarks of cancer transformation. Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. Despite the presence of karyotype aberrations, all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence of genomic

  3. Mitochondrial-associated cell death mechanisms are reset to an embryonic-like state in aged donor-derived iPS cells harboring chromosomal aberrations.

    Directory of Open Access Journals (Sweden)

    Alessandro Prigione

    Full Text Available Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs acquire features of human embryonic stem cells (hESCs and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. However, reprogrammed cell lines have been found to harbor various genomic alterations. In addition, we recently discovered that the mitochondrial DNA of human fibroblasts also undergoes random mutational events upon reprogramming. Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the oncogenic potential of reprogrammed cells due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. Here, we investigated whether aged reprogrammed cells harboring chromosomal abnormalities show resistance to apoptotic cell death or mitochondrial-associated oxidative stress, both hallmarks of cancer transformation. Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. Despite the presence of karyotype aberrations, all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence

  4. Genotoxic effects of a particular mixture of acetamiprid and alpha-cypermethrin on chromosome aberration, sister chromatid exchange, and micronucleus formation in human peripheral blood lymphocytes.

    Science.gov (United States)

    Kocaman, Ayşe Yavuz; Topaktaş, Mehmet

    2010-04-01

    The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and alpha-cypermethrin (alpha-cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 microg/mL of Acm+alpha-cyp, respectively, for 24 and 48 h. The mixture of Acm+alpha-cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration-dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, microg/mL of Acm+alpha-cyp when compared with both controls although these increases were not concentration-dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 microg/mL) for both the 24- and 48-h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration-dependent at 48-h treatment period. In general, Acm+alpha-cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+alpha-cyp were compared with the results of single effects of Acm or alpha-cyp (Kocaman and Topaktas,2007,2009, respectively). In conclusion, the particular mixture of Acm+alpha-cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes.

  5. Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster Ovary (CHO) Cells With and Without Metabolic Activation. Test Article: Dimethylamine-2-2ethyl azide (DMAZ)

    Science.gov (United States)

    2008-07-26

    chromosomes leading to four-armed configurations. This could be asymmetrical with formation of a dicentric and an acentric chromatid, ifunion is complete...chromatid union. Dicentric - an asymmetrical exchange between two chromosomes resulting in a chromosome with two centromeres with or without an...no sister chromatid union. ’ d - Dicentric - an asymmetrical exchange between two chromosomes resulting, r dm in a chromosome with two centromeres

  6. CHROMOSOMAL ABNORMALITIES IN A REFERRED POPULATION: A REPORT OF 383 IRANIAN CASES

    Directory of Open Access Journals (Sweden)

    M. T. Akbari.

    1998-07-01

    Full Text Available This report presents the cytogenetic findings (G -banded chromosomal analysis} in 383 cases referred for suspected chromosomal abnormalities because of abnormal clinical features. Chromosomal aberrations were found in 63 116.5% of these cases, free trisomy 21 (7% being the most common abnormality , followed by 47, XXYkaryotype (4%. The breakdown figures for each group is discussed in the text.

  7. Analysis of chromosome damage for biodosimetry using imaging flow cytometry.

    Science.gov (United States)

    Beaton, L A; Ferrarotto, C; Kutzner, B C; McNamee, J P; Bellier, P V; Wilkins, R C

    2013-08-30

    The dicentric chromosome assay (DCA), which involves counting the frequency of dicentric chromosomes in mitotic lymphocytes and converting it to a dose-estimation for ionizing radiation exposure, is considered to be the gold standard for radiation biodosimetry. Furthermore, for emergency response, the DCA has been adapted for triage by simplifying the scoring method [1]. With the development of new technologies such as the imaging flow cytometer, it may now be possible to adapt this microscope-based method to an automated cytometry method. This technology allows the sensitivity of microscopy to be maintained while adding the increased throughput of flow cytometry. A new protocol is being developed to adapt the DCA to the imaging cytometer in order to further increase the rapid determination of a biological dose. Peripheral blood mononuclear cells (PBMC) were isolated from ex vivo irradiated whole blood samples using a density gradient separation method and cultured with PHA and Colcemid. After 48h incubation, the chromosomes were isolated, stained for DNA content with propidium iodide (PI) and labelled with a centromere marker. Stained chromosomes were then analyzed on the ImageStream(×) (EMD-Millipore, Billerica, MA). Preliminary results indicate that individual chromosomes can be identified and mono- and dicentric chromosomes can be differentiated by imaging cytometry. A dose response curve was generated using this technology. The details of the method and the dose response curve are presented and compared to traditional microscope scoring. Imaging cytometry is a new technology which enables the rapid, automated analysis of fluorescently labelled chromosomes. Adapting the dicentric assay to this technology has the potential for high throughput analysis for mass casualty events.

  8. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

  9. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  10. Differential algebraic method for arbitrary order curvilinear-axis combined geometric-chromatic aberration analysis

    CERN Document Server

    Cheng Min; Lu Yi Long; Yao Zhen Hua

    2003-01-01

    The principle of differential algebra is applied to analyse and calculate arbitrary order curvilinear-axis combined geometric-chromatic aberrations of electron optical systems. Expressions of differential algebraic form of high order combined aberrations are obtained and arbitrary order combined aberrations can be calculated numerically. As an example, a typical wide electron beam focusing system with curved optical axes named magnetic immersion lens has been studied. All the second-order and third-order combined geometric-chromatic aberrations of the lens have been calculated, and the patterns of the corresponding geometric aberrations and combined aberrations have been given as well.

  11. Genomic analysis of plant chromosomes based on meiotic pairing

    Directory of Open Access Journals (Sweden)

    Lisete Chamma Davide

    2007-12-01

    Full Text Available This review presents the principles and applications of classical genomic analysis, with emphasis on plant breeding. The main mathematical models used to estimate the preferential chromosome pairing in diploid or polyploid, interspecific or intergenera hybrids are presented and discussed, with special reference to the applications and studies for the definition of genome relationships among species of the Poaceae family.

  12. Effects of hepatitis B virus infection on human sperm chromosomes

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Huang; Tian-Hua Huang; Huan-Ying Qiu; Xiao-Wu Fang; Tian-Gang Zhuang; Hong-Xi Liu; Yong-Hua Wang; Li-Zhi Deng; Jie-Wen Qiu

    2003-01-01

    AIM: To evaluate the level of sperm chromosome aberrations in male patients with hepatitis B, and to directly detect whether there are HBV DNA integrations in sperm chromosomes of hepatitis B patients.METHODS: Sperm chromosomes of 14 tested subjects (5healthy controls, 9 patients with HBV infection, including 1with acute hepatitis B, 2 with chronic active hepatitis B, 4with chronic persistent hepatitis B, 2 chronic HBsAg carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free golden hamster ova and human spermatozoa, and the frequencies of aberration spermatozoa were compared between subjects of HBV infection and controls. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes.RESULTS: The total frequency of sperm chromosome aberrations in HBV infection group (14.8%, 33/223) was significantly higher than that in the control group (4.3%,5/116). Moreover, the sperm chromosomes in HBV infection patients commonly presented stickiness, clumping, failure to staining, etc, which would affect the analysis of sperm chromosomes. Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis. In 9 (9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots, others presented 2 to 4signals. There was significant difference of fluorescence intensity among the signal spots. The distribution of signal sites among chromosomes was random.CONCLUSION: HBV infection can bring about mutagenic effects on sperm chromosomes. Integrations of viral DNA into sperm chromosomes which are multisites and nonspecific, can further increase the instability of sperm chromosomes. This study suggested that HBV infection can create extensively hereditary effects by alteration genetic constituent and

  13. Chromosomal Analysis of Couples with Repeated Spontaneous Abortions in Northeastern Iran

    Directory of Open Access Journals (Sweden)

    Saeedeh Ghazaey

    2015-04-01

    Full Text Available Background: Cytogenetic study of reproductive wastage is an important aspect in determining the genetic background of early embryogenesis. Approximately 15 to 20% of all pregnancies in humans are terminated as recurrent spontaneous abortions (RSAs. The aim of this study was to detect chromosome abnormalities in couples with RSAs and to compare our results with those reported previously. Materials and Methods: In this retrospective study, the pattern of chromosomal aberrations was evaluated during a six-year period from 2005 to 2011. The population under study was 728 couples who attended genetic counseling services for their RSAs at Pardis Clinical and Genetics Laboratory, Mashhad, Iran. Results: In this study, about 11.7% of couples were carriers of chromosomal aberrations. The majority of abnormalities were found in couples with history of abortion, without stillbirth or livebirth. Balanced reciprocal translocations, Robertsonian translocations, inversions and sex chromosome aneuploidy were seen in these cases. Balanced reciprocal translocations were the most frequent chromosomal anomalies (62.7% detected in current study. Conclusion: These findings suggest that chromosomal abnormalities can be one of the important causes of RSAs. In addition, cytogenetic study of families who experienced RSAs may prevent unnecessary treatment if RSA are caused by chromosomal abnormalities. The results of cytogenetic studies of RSA cases will provide a standard protocol for the genetic counselors in order to follow up and to help these families.

  14. Chromosome aberrations in Japanese fishermen exposed to fallout radiation 420-1200 km distant from the nuclear explosion test site at Bikini Atoll: report 60 years after the incident.

    Science.gov (United States)

    Tanaka, Kimio; Ohtaki, Megu; Hoshi, Masaharu

    2016-08-01

    During the period from March to May, 1954, the USA conducted six nuclear weapon tests at the "Bravo" detonation sites at the Bikini and Enewetak Atolls, Marshall Islands. At that time, the crew of tuna fishing boats and cargo ships that were operating approximately 150-1200 km away from the test sites were exposed to radioactive fallout. The crew of the fishing boats and those on cargo ships except the "5th Fukuryu-maru" did not undergo any health examinations at the time of the incident. In the present study, chromosome aberrations in peripheral blood lymphocytes were examined in detail by the G-banding method in 17 crew members from 8 fishing boats and 2 from one cargo ship, 60 years after the tests. None of the subjects examined had suffered from cancer. The percentages of both stable-type aberrations such as translocation, inversion and deletion, and unstable-type aberrations such as dicentric and centric ring in the study group were significantly higher (1.4- and 2.3-fold, respectively) than those in nine age-matched controls. In the exposed and control groups, the percentages of stable-type aberrations were 3.35 % and 2.45 %, respectively, and the numbers of dicentric and centric ring chromosomes per 100 cells were 0.35 and 0.15, respectively. Small clones were observed in three members of the exposed group. These results suggest that the crews were exposed to slightly higher levels of fallout than had hitherto been assumed.

  15. Genetic toxicity assessment: employing the best science for human safety evaluation. Part II: Performances of the in vitro micronucleus test compared to the mouse lymphoma assay and the in vitro chromosome aberration assay.

    Science.gov (United States)

    Lorge, Elisabeth; Lambert, Carine; Gervais, Véronique; Becourt-Lhote, Nathalie; Delongeas, Jean-Luc; Claude, Nancy

    2007-04-01

    The in vitro micronucleus test is commonly used in the early stages of pharmaceutical development as a predictive tool for the regulatory mouse lymphoma assay or in vitro chromosome aberration test. The accumulated data from this assay leads to the suggestion that it could be used as an alternative to the chromosome aberration test or the mouse lymphoma assay in the regulatory genotoxicity battery. In this paper, we present the results of the in vitro micronucleus test on L5178Y mouse lymphoma cells with 25 compounds from Servier research and have compared these results to those obtained in the genotoxicity regulatory battery. All the negative compounds were also negative in the in vitro micronucleus assay. Among the 14 positive compounds, two of them, positive in the mouse lymphoma assay, were found negative in the in vitro micronucleus test. However, this apparent discordance was likely to be due to cytotoxicity- or high concentration-related false positive responses in the mouse lymphoma assay. In addition, we confirmed that the in vitro micronucleus assay is useful for detecting aneugens, especially, when cells in metaphasis and multinucleated cells are also scored and when cells are allowed to recover after the long treatment. On this series of compounds, the in vitro micronucleus assay showed high sensitivity and possibly a better specificity than the mouse lymphoma assay. Thus, the in vitro micronucleus assay was shown to be at least as adequate as the mouse lymphoma assay or the in vitro chromosome aberration test to be used in the standard genotoxicity battery.

  16. Effects of shunshuang nourishing anti-dandruff shampoo on chromosome aberration of CHL cell in vitro%顺爽滋养去屑型洗发露CHL细胞体外染色体畸变试验

    Institute of Scientific and Technical Information of China (English)

    方选; 李昇刚

    2012-01-01

    Objective:To assess whether shunshuang nourishing anti — dandruff shampoo causes the chromosome aberration. Methods: At the concentrations of 0.5 mg/ml, 0.25 mg/ml, 0.125 mg/ml,the mutagenicity of shunshuang nourishing anti - dandruff shampoo on Chinese hamster lung cell in the presence and absence of the liver ho-mogenate fraction(S9mix) in vitro was evaluated. Results; Shunshuang shampoo achieved a chromosome aberration of less than 5% in the presence and absence of S9mix. Conclusion; Shunshuang nourishing anti — dandruff shampoo has not demonstrated effects on chromosome aberration.%目的:检测顺爽滋养去屑型洗发露对CHL细胞染色体致畸变作用.方法:用体外方法检测顺爽洗发露在0.5 mg/ml、0.25 mg/ml、0.125 mg/ml时,代谢活化组(含S9mix)及非活化组(不含S9mix)CHL细胞的染色体畸变率.结果:顺爽洗发露代谢活化组(含S9mix)及非活化组(不含S9mix)的染色体畸变率均低于5%.结论:在本实验条件下顺爽滋养去屑型洗发露未诱发CHL细胞染色体畸变率增加.

  17. 包钢选矿厂含钍粉尘作业工人外周血淋巴细胞适应性反应的研究%Adaptive responses on chromosome aberration and DNA breakage of peripheral lymphocytes from workers exposed to thorium and rare earth mixed dust in Baotou Steel Plant

    Institute of Scientific and Technical Information of China (English)

    刘青杰; 封江彬; 陆雪; 陈德清; 刘玉飞; 贾柯君; 吕慧敏; 苏旭

    2008-01-01

    Objective To explore if the occupational exposure to low dose thorium could induce adaptive response in peripheral lymphocytes.Methods 40 individuals.who exposed to thorium and rare earth mixed dust(exposure group) or control in Baotou Steel Plant, were selected, and chromosome aberrations were analyzed.Then the peripheral blood samples were irradiated in vitro with 2 Gy60Co γ-rays,and unstable chromosome aberration or DNA stand breakage analysis using single cell gel electrophoresis was performed. Results The dicentrics before 2 Gy exposure in exposure group was higher than that in control(P>0.05). But the dicentries after 2 Gy exposure in exposure group was lower than that in control,but not significantly (P>0.05).The tricentrics in exposure group was significantly lower than that in control(U=3.1622, 0.0ol0.05),三着丝粒畸变在两组间差异具有统计学意义(u=3.1622,0.001

  18. Biological dose assessment by the analyses of chromosomal aberrations in 2 subjects accidentally exposed to ionizing radiation%2例电离辐射意外照射事件受检者染色体畸变分析和生物剂量估计

    Institute of Scientific and Technical Information of China (English)

    王金合; 姜峰; 韩林; 王平; 王喜爱; 吕玉民

    2011-01-01

    Objective: To investigate biological dose assessment by the analyses of chromosomal aberrations in 2 subjects accidentally exposed to ionizing radiation. Methods: Biological doses were estimated by the analysis of conventional chromosomal aberration from peripheral blood lymphocyte of the subjects. Results:The frequencies of dicentrics and translocation in 2 subjects were significantly higher than spontaneous frequency, and the equivalent whole body doses for the 2 subjects were estimated to be 0.21Gy (A) and 0.17Gy ( B) respectively. Conclusion:2 subjects suffered from over - exposure of ionizing radiation.%目的:对2例电离辐射意外照射事件受检人员进行外周血染色体畸变分析和生物剂量估计.方法:常规法分析受检者外周血淋巴细胞染色体畸变并估计受照剂量.结果:2例受检者的双着丝粒体和易位率均明显高于自发畸变率,估计的全身平均吸收剂量分别为0.21Gy(A)和0.17Gy(B).结论:2例受检者受到过量照射.

  19. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

    Science.gov (United States)

    Zavattari, P; Deidda, E; Whalen, M; Lampis, R; Mulargia, A; Loddo, M; Eaves, I; Mastio, G; Todd, J A; Cucca, F

    2000-12-12

    Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

  20. Early and Late Chromosome Damages in Human Lymphocytes Induced by Gamma Rays and Fe Ions

    Science.gov (United States)

    Sunagawa, Mayumi; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2014-01-01

    Chromosomal translocations and inversions are considered stable, and cells containing these types of chromosome aberrations can survive multiple cell divisions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. Detailed analysis of chromosome break ends participating in exchanges revealed a greater fraction of break ends involved in intrachromosome aberrations in the 7- and 14-day samples in comparison to the fraction at first mitosis. In particular, simple inversions were found at 7 and 14 days, but not at the first mitosis, suggesting that some of the aberrations might be formed days post irradiation. In contrast, at the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Comparison between low and high doses of Fe ion irradiation in the induction of late damages will also be discussed.

  1. Phosphatidylinositol-3-kinase pathway aberrations in gastric and colorectal cancer: meta-analysis, co-occurrence and ethnic variation.

    Science.gov (United States)

    Chong, Mei-Ling; Loh, Marie; Thakkar, Bhavin; Pang, Brendan; Iacopetta, Barry; Soong, Richie

    2014-03-01

    Inhibition of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a cancer treatment strategy that has entered into clinical trials. We performed a meta-analysis on the frequency of prominent genetic (PIK3CA mutation, PIK3CA amplification and PTEN deletion) and protein expression (high PI3K, PTEN loss and high pAkt) aberrations in the PI3K pathway in gastric cancer (GC) and colorectal cancer (CRC). We also performed laboratory analysis to investigate the co-occurrence of these aberrations. The meta-analysis indicated that East Asian and Caucasian GC patients differ significantly for the frequencies of PIK3CA Exon 9 and 20 mutations (7% vs. 15%, respectively), PTEN deletion (21% vs. 4%) and PTEN loss (47% vs. 78%), while CRC patients differed for PTEN loss (57% vs. 26%). High study heterogeneity (I(2) > 80) was observed for all aberrations except PIK3CA mutations. Laboratory analysis of tumors from East Asian patients revealed significant differences between GC (n = 79) and CRC (n = 116) for the frequencies of PIK3CA amplification (46% vs. 4%) and PTEN loss (54% vs. 78%). The incidence of GC cases with 0, 1, 2 and 3 concurrent aberrations was 14%, 52%, 27% and 8%, respectively, while for CRC it was 10%, 60%, 25% and 4%, respectively. Our study consolidates knowledge on the frequency, co-occurrence and clinical relevance of PI3K pathway aberrations in GC and CRC. Up to 86% of GC and 90% of CRC have at least one aberration in the PI3K pathway, and there are significant differences in the frequencies of these aberrations according to cancer type and ethnicity.

  2. Spatial-temporal-covariance-based modeling, analysis, and simulation of aero-optics wavefront aberrations.

    Science.gov (United States)

    Vogel, Curtis R; Tyler, Glenn A; Wittich, Donald J

    2014-07-01

    We introduce a framework for modeling, analysis, and simulation of aero-optics wavefront aberrations that is based on spatial-temporal covariance matrices extracted from wavefront sensor measurements. Within this framework, we present a quasi-homogeneous structure function to analyze nonhomogeneous, mildly anisotropic spatial random processes, and we use this structure function to show that phase aberrations arising in aero-optics are, for an important range of operating parameters, locally Kolmogorov. This strongly suggests that the d5/3 power law for adaptive optics (AO) deformable mirror fitting error, where d denotes actuator separation, holds for certain important aero-optics scenarios. This framework also allows us to compute bounds on AO servo lag error and predictive control error. In addition, it provides us with the means to accurately simulate AO systems for the mitigation of aero-effects, and it may provide insight into underlying physical processes associated with turbulent flow. The techniques introduced here are demonstrated using data obtained from the Airborne Aero-Optics Laboratory.

  3. Genotoxicity and mutagenicity of water contaminated with tannery effluents, as evaluated by the micronucleus test and comet assay using the fish Oreochromis niloticus and chromosome aberrations in onion root-tips

    Directory of Open Access Journals (Sweden)

    Silvia Tamie Matsumoto

    2006-01-01

    Full Text Available Cytotoxicity of metals is important because some metals are potential mutagens able to induce tumors in humans and experimental animals. Chromium can damage DNA in several ways, including DNA double strand breaks (DSBs which generate chromosomal aberrations, micronucleus formation, sister chromatid exchange, formation of DNA adducts and alterations in DNA replication and transcription. In our study, water samples from three sites in the Córrego dos Bagres stream in the Franca municipality of the Brazilian state of São Paulo were subjected to the comet assay and micronucleus test using erythrocytes from the fish Oreochromis niloticus. Nuclear abnormalities of the erythrocytes included blebbed, notched and lobed nuclei, probably due to genotoxic chromium compounds. The greatest comet assay damage occurred with water from a chromium-containing tannery effluent discharge site, supporting the hypothesis that chromium residues can be genotoxic. The mutagenicity of the water samples was assessed using the onion root-tip cell assay, the most frequent chromosomal abnormalities observed being: c-metaphases, stick chromosome, chromosome breaks and losses, bridged anaphases, multipolar anaphases, and micronucleated and binucleated cells. Onion root-tip cell mutagenicity was highest for water samples containing the highest levels of chromium.

  4. 荧光原位杂交技术在检测胎儿染色体亚显微结构异常中的应用%Application of the fluorescent in situ hybridization (FISH) on the prenatal diagnosis of the subtle chromosomal aberrations

    Institute of Scientific and Technical Information of China (English)

    尹爱华; 刘舒; 潘小英; 傅文婷; 王继成; 卢建; 杨洁霞

    2012-01-01

    Objective To study the diagnostic value of the fluorescent in situ hybridization on detection of subtle chromosomal aberrations in cultured amniotic fluid cells. Methods Amniocenteses were performed in a pregnant women of 18 gestational weeks, and metaphase FISH was followed because the results of amniotic fluid karyotype and ultrasound were disagree with each other. The metaphase chromosomes were hybridized in situ with the human centromere probes of chromosome 18,X,Y and site specific probe of chromosome 13,21. The treated slides were examined and taken photos under the carl zeiss fluoromicroscope. Result Subtle translocation of chromosome Y was detected by FISH. Conclusion Our result indicated that it is very helpful for the diagnosis of subtle chromosomal aberrations by combining FISH with traditional karyotype analysis.%目的 探讨荧光原位杂交(FISH)技术在诊断培养后的羊水细胞染色体亚显微结构异常中的应用价值.方法 对1例18孕周,经典细胞遗传学羊水染色体核型分析结果与B超检查结果有不符合的胎儿,应用FISH的18号、X、Y染色体着丝粒探针和13、21号染色体位点特异性探针,对培养后的羊水中期细胞标本进行检测.结果 共分析了22个独立细胞克隆的分裂象,发现胎儿染色体存在两种核型嵌合,结果记为:mos 45,X[20]/46,XY[2];FISH检测发现此胎儿核型存在Y染色体亚显微小片段易位.结论 FISH技术结合传统细胞遗传学核型分析,对于诊断染色体亚显微结构异常非常重要.

  5. Comparative analysis by chromosome painting of the sex chromosomes in arvicolid rodents.

    Science.gov (United States)

    Acosta, M J; Romero-Fernández, I; Sánchez, A; Marchal, J A

    2011-01-01

    Sex chromosome evolution in mammals has been extensively investigated through chromosome-painting analyses. In some rodent species from the subfamily Arvicolinae the sex chromosomes contain remarkable features such as giant size, a consequence of heterochromatic enlargement, or asynaptic behaviour during male meiosis. Here, we have made a comparative study of the sex chromosomes in 6 arvicolid species using different probes from the X and Y chromosomes of 3 species, in order to gain knowledge about intra- or interspecific preservation of euchromatic regions. Our results clearly reveal poor conservation of the euchromatic region of the Y chromosome within these species, while the euchromatin on the X chromosome is extremely well preserved. Furthermore, we detected no clear correlation between the synaptic/asynaptic behaviour of the sex chromosomes, and the presence or absence of sequence homology within their euchromatic regions. Notably, our study has shown a new relationship between the giant sex chromosomes of 2 species, Microtus agrestis and Microtus cabrerae, that is, both X and Y share a novel region of common sequences in the euchromatin that is not present in the other species analysed. This interspecific euchromatic conservation, limited to the giant sex chromosomes, could point towards a common evolutionary origin for the heterochromatic enlargement process that has characterized the evolution of the sex chromosomes in some arvicolid species.

  6. Exclusion of APC and VHL gene deletions by array-based comparative hybridization in two patients with microscopically visible chromosomal aberrations.

    Science.gov (United States)

    Wallerstein, Robert J; Brooks, Susan Sklower; Streck, Deanna L; Kurvathi, Rohini; Toruner, Gokce A

    2007-10-15

    Karyotyping is a major component of the genetic work-up of patients with dysmorphism. Cytogenetic aberrations close to a known tumor suppressor gene raise important clinical issues because deletion of that tumor suppressor gene can cause genetic predisposition to cancer. We present two cancer-free dysmorphic patients with karyotypes of 46,XX,del(5)(q15q22.3) and 46,XX,del(3)(p25.2~pter). These deletions are close to the APC and VHL genes that confer susceptibility to familial Adenomatous polyposis (OMIM #17510) and von-Hippel-Lindau syndrome (OMIM #193300), respectively. The array-based comparative genomic hybridization (array-CGH) analysis using a custom Agilent 44K oligonucleotide array demonstrated an interstitial 20.7-megabase (Mb) deletion on 5q (chr5: 89,725,638-110,491,345) and a terminal 9.45-Mb deletion on 3p (chr3:pter-9,450,984). According to the March 2006 human reference sequence, the APC gene is located at chr5: 112,101,483-112,209,835 and the VHL gene is located at chr3: 10,158,319-10,168,746. These results indicate that the APC gene is 2,300 kilobases (kb) and the VHL gene is 700 kb away from deleted regions. Southern blot analysis for APC and VHL genes were negative, consistent with array-CGH findings. These results demonstrate the power of array-CCH to assess potential tumor suppressor gene involvement and cancer risk in patients with microscopically visible deletions in areas near tumor suppressors.

  7. 应用染色体G显带技术评估辐射剂量和染色体畸变的量效关系%The value of G·banding chromosomal assay in ionizing·radiation·induced chromosomal aberration

    Institute of Scientific and Technical Information of China (English)

    施常备; 陈晓泉; 姚俊涛; 袁勇; 赵征; 袁彬; 赵明刚; 陈葳; 王翔

    2011-01-01

    OBJECTIVE: To validate the value of G-banding chromosomal assay in ionizing-radiation induced chromosomal aberration. METHODS: Blood was irradiated with 0.5, 1, 2 and 4 Gy, by 4 MV X-ray. The G banding chromosomal aberration was assayed including dicentrics, deletions, translocations, rings, and fragments of chromosomes. RESULTS: Chromosomal aberration rates of dicentrics, deletions, translocations, and fragments all showed linear increase with radiation dose, with correlations of Y=24.1X-13.3(R2=0.975); Y=10.5X-2.7(R2=0.887);Y=30.2X-17.8(R2=0.913); Y=53.3X-38.7 (R2=0.976), respectively. CONCLUSION: G-banding chromosomal aberration assay deserve more attention in radiation biology.%目的:应用染色体G显带技术观察4MV的X线辐射后的染色体畸变情况,分析不同类型的染色体畸变和辐射剂量的关系.方法:以4MV的X线0.5、1、2、4 Gy对离体人外周血进行辐照,其淋巴细胞培养后,采用染色体G显带分析不同类型的染色体畸变率.结果:染色体双着丝粒、缺失、易位以及片段畸变和辐射剂量呈线性正相关,其线性趋势线和R值依次分别为:Y=24.1X-13.3(R=0.975);Y=10.5X-2.7(R=0.887);Y=30.2X-17.8(R=0.913);Y=53.3X-38.7(R=0.976).结论:染色体G显带技术可以较非显带技术提供更多更准确的畸变信息,为进一步研究提供借鉴.

  8. Factor Analysis and Norms for Parent Ratings on the Aberrant Behavior Checklist-Community for Young People in Special Education.

    Science.gov (United States)

    Brown, Elaine C.; Aman, Michael G.; Havercamp, Susan M.

    2002-01-01

    Parents of 601 children and adolescents with mental retardation rated their children on the Aberrant Behavior Checklist-Community (ABC). Factor analysis revealed a factor structure similar to the original ABC but without the inappropriate speech factor. Analysis of subject variables revealed main effects for gender, age, and classroom assignment…

  9. Delimiting the origin of a B chromosome by FISH mapping, chromosome painting and DNA sequence analysis in Astyanax paranae (Teleostei, Characiformes).

    Science.gov (United States)

    Silva, Duílio M Z de A; Pansonato-Alves, José Carlos; Utsunomia, Ricardo; Araya-Jaime, Cristian; Ruiz-Ruano, Francisco J; Daniel, Sandro Natal; Hashimoto, Diogo Teruo; Oliveira, Cláudio; Camacho, Juan Pedro M; Porto-Foresti, Fábio; Foresti, Fausto

    2014-01-01

    Supernumerary (B) chromosomes have been shown to contain a wide variety of repetitive sequences. For this reason, fluorescent in situ hybridisation (FISH) is a useful tool for ascertaining the origin of these genomic elements, especially when combined with painting from microdissected B chromosomes. In order to investigate the origin of B chromosomes in the fish species Astyanax paranae, these two approaches were used along with PCR amplification of specific DNA sequences obtained from the B chromosomes and its comparison with those residing in the A chromosomes. Remarkably, chromosome painting with the one-arm metacentric B chromosome probe showed hybridization signals on entire B chromosome, while FISH mapping revealed the presence of H1 histone and 18S rDNA genes symmetrically placed in both arms of the B chromosome. These results support the hypothesis that the B chromosome of A. paranae is an isochromosome. Additionally, the chromosome pairs Nos. 2 or 23 are considered the possible B chromosome ancestors since both contain syntenic H1 and 18S rRNA sequences. The analysis of DNA sequence fragments of the histone and rRNA genes obtained from the microdissected B chromosomes showed high similarity with those obtained from 0B individuals, which supports the intraspecific origin of B chromosomes in A. paranae. Finally, the population hereby analysed showed a female-biased B chromosome presence suggesting that B chromosomes in this species could influence sex determinism.

  10. 健康成人自发染色体畸变率与微核率的本底状况再分析%Re-investigation on spontaneous frequencies of chromosome aberration and micronucleus in healthy adults

    Institute of Scientific and Technical Information of China (English)

    张学清; 陈英; 王治东; 王远; 周平坤

    2014-01-01

    目的:了解环境因素对人类遗传物质的影响,以便正确评估放射从业人员以及低剂量辐射的健康效应。方法:选自北京市87名接受健康体检的成年人,每人用肝素钠抗凝管抽取外周静脉血2 mL。采用提前加秋水仙素和松胞素B法分别制备染色体与微核标本,Metafer自动分析系统结合人工分析染色体畸变与双核淋巴细胞微核,按不同年龄段与不同性别分组进行统计比较。结果:87名受检者的染色单体型畸变率平均为0.70%,染色体型畸变率为0.20%,其中双着丝粒体+环为0.13%,单纯无着丝粒体为0.06%。微核与微核细胞率分别为25.30‰和21.56‰。除单体型畸变外,染色体型畸变率与微核率均随年龄的增加而增加(P0.05)。结论:健康成人染色体型畸变(双着丝粒体+环)率与双核淋巴细胞微核率未超过国内外报道的本底范围,但较国内以往报道的本底值有增高趋势。P%OBJECTIVE: In order to understand genetic effect from environment factors and to assess correctly the health effect of low dose radiation on occupational personnel. METHODS:The investigated objects came from 87 healthy adults who took routine physical examination and living in Beijing city. 2 mL peripheral venous blood from each person was drawn into heparinized tubes. Conventional chromosome culture with adding colchicines at the beginning and Cyt-B micronuclei (MN) methods were applied. Chromosomal aberrations (CA) and binucleated lymphocyte MN were analyzed using Metafer scanning system combined with manual work. Comparisons according to different age groups and both genders were carried out. RESULTS:The average spontaneous frequencies of chromatid-type and chromosomal-type aberrations in 87 tested persons were 0.70%and 0.20%,respectively. In chromosomal-type aberrations,the dicentrics plus rings (dic+r) were 0.13%,acentrics alone were 0.06%. Spontaneous MN and MNC frequencies were 23.43

  11. Analysis of chromosome conservation in Lemur catta studied by chromosome paints and BAC/PAC probes.

    Science.gov (United States)

    Cardone, Maria Francesca; Ventura, Mario; Tempesta, Sergio; Rocchi, Mariano; Archidiacono, Nicoletta

    2002-12-01

    A panel of human chromosome painting probes and bacterial and P1 artificial chromosome (BAC/PAC) clones were used in fluorescence in situ hybridization (FISH) experiments to investigate the chromosome conservation of the ring-tailed lemur (Lemur catta, LCA) with respect to human. Whole chromosome paints specific for human chromosomes 7, 9, 11, 13, 14, 17, 18, 20, 21, and X were found to identify a single chromosome or an uninterrupted chromosomal region in LCA. A large set of partial chromosome paints and BAC/PAC probes were then used to refine the characterization of the rearrangements differentiating the two karyotypes. The results were also used to reconstruct the ancestral Lemuridae karyotype. Lemur catta, indeed, can be used as an outgroup, allowing symplesiomorphic (ancestral) rearrangements to be distinguished from apomorphic (derived) rearrangements in lemurs. Some LCA chromosomes are difficult to distinguish morphologically. The 'anchorage' of most LCA chromosomes to specific probes will contribute to the standardization of the karyotype of this species.

  12. In situ hybridization analysis of isodicentric X-chromosomes with short arm fusion

    DEFF Research Database (Denmark)

    Koch, J E; Kølvraa, S; Hertz, Jens Michael;

    1990-01-01

    We present here an alternative approach to the study of mosaic cell lines containing dicentric chromosomes. The approach is based on chromosome-specific non-radioactive in situ hybridization with centromere (alpha satellite DNA) probes. The hybridization analysis may be used as an alternative...... it for the analysis of two cases of isodicentric X-chromosomes. The approach is expected to be generally applicable, so that it may be applied to the scoring of other types of chromosomal mosaicism as well....

  13. Three dimensional analysis of chromatic aberration in diffractive elements with extended depth of focus.

    Science.gov (United States)

    Mas, D; Espinosa, J; Perez, J; Illueca, C

    2007-12-24

    The paper presents the polychromatic analysis of two diffractive optical elements with extended depth of focus: the linear axicon and the light sword optical element. Chromatic aberration produces axial displacement of the focal segment line. Thus, we explore the possibility of extending the focal depth of these elements to permit superposition of the chromatic foci. In the case of an axicon, we achieve an achromatic zone where focusing is produced. In the case of the light sword element, we show that the focusing segment is out of axis. Therefore a superposition of colors is produced, but not on axis overlapping. Instead, three colored and separated foci are simultaneously obtained in a single plane. Three dimensional structures of the propagated beams are analyzed in order to provide better understanding of the properties and applications of such elements.

  14. Molecular-Cytological Identification and Chromosome Behavior Analysis of Telotetrasomic in Rice

    Institute of Scientific and Technical Information of China (English)

    GONG Zhi-yun; GAO Qing-song; YU Heng-xiu; YI Chuan-deng; GU Ming-hong

    2008-01-01

    From the progenies of a telotrisomic of chromosome 9 short arm of an indica rice variety, Zhongxian 3037, a phenotypical variant was selected. The variant plant had rolled leaves, dispersed plant type, as well as a low seed-setting rate. Cytological and molecular cytological investigations revealed two extra chromosomes, which were the shortest in somatic cells of the variant. Fluorescent in situ hybridization (FISH) analysis using a rice centromere specific DNA (RCS2) and a DNA sequence specific for chromosome 9 on premetaphase and pachytene chromosomes showed that these two chromosomes were the short arms of chromosome 9. That is to say, the variant was a telotetrasomic of chromosome 9. Among the 25 pachytene cells, the two telosomic chromosomes paired each other to form a bivalent and didn't pair with other normal chromosome 9 as multivalents in 96% cells. However, the bivalent was easy to disassociate in advance.

  15. Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population

    Directory of Open Access Journals (Sweden)

    Sameer A

    2011-07-01

    Full Text Available Abstract The development and progression of colorectal cancer (CRC is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC and β-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and β-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR of the APC gene and exon 3 of the β-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR. The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86. Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86 of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05. Although the number of mutations in the APC and β-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.

  16. Analysis of repetitive DNA in chromosomes by flow cytometry.

    Science.gov (United States)

    Brind'Amour, Julie; Lansdorp, Peter M

    2011-06-01

    We developed a flow cytometry method, chromosome flow fluorescence in situ hybridization (FISH), called CFF, to analyze repetitive DNA in chromosomes using FISH with directly labeled peptide nucleic acid (PNA) probes. We used CFF to measure the abundance of interstitial telomeric sequences in Chinese hamster chromosomes and major satellite sequences in mouse chromosomes. Using CFF we also identified parental homologs of human chromosome 18 with different amounts of repetitive DNA.

  17. Association of MTHFR Polymorphisms and Chromosomal Abnormalities in Leukemia

    Directory of Open Access Journals (Sweden)

    Thivaratana Sinthuwiwat

    2012-01-01

    Full Text Available Genetic variation in MTHFR gene might explain the interindividual differences in the reduction of DNA repaired and the increase of chromosome breakage and damage. Nowadays, chromosomal rearrangement is recognized as a major cause of lymphoid malignancies. In addition, the association of MTHFR polymorphisms with aneuploidy was found in several studies, making the MTHFR gene as a good candidate for leukemia etiology. Therefore, in this study, we investigated the common sequence variation, 677C>T and 1298A>C in the MTHFR gene of 350 fixed cell specimens archived after chromosome analysis. The distribution of the MTHFR polymorphisms frequency was compared in leukemic patients with structural chromosome abnormality and chromosome aneuploidy, as well as in those with no evidence of chromosome abnormalities. We observed a significant decrease in the distribution of T allele in 677C>T polymorphisms among patients with chromosomal abnormalities including both structural aberration and aneuploidy. The same significance result also found in patients with structural aberration when compare with the normal karyotype patients. Suggesting that polymorphism in the MTHFR gene was involved in chromosome abnormalities of leukemia. However, further investigation on the correlation with the specific types of chromosomal aberrations is needed.

  18. 放线菌素D对仓鼠成纤维细胞V79靶细胞和旁观者细胞活力和染色体畸变的影响%Effect of actinomycin D on cell viability and chromosome aberration in hamster fibroblast V79 target and bystander cells

    Institute of Scientific and Technical Information of China (English)

    靳翠红; 巫生文; 逯晓波; 刘秋芳; 蔡原; 肖云

    2012-01-01

    目的:观察放线菌素D (actinomycinD,ACTD)对中国仓鼠成纤维细胞V79靶细胞和旁观者细胞的细胞活力和染色体畸变的影响,以确定ACTD能否诱导旁观者效应的发生.方法:用不同剂量ACTD(0、0.25、0.5、1.0、2.0、4.0和8.0 mg/L处理V79靶细胞1h,并选择其中4 mg/L ACTD作用1h开始计时,分别在第4、8、12和24h时取靶细胞去细胞培养液(conditioned medium,CM),培养正常细胞24h后,进行旁观者效应的观察.用MTT法测定靶细胞和旁观者细胞活力;并对靶细胞和旁观者细胞进行染色体畸变分析.结果:随着ACTD剂量的增加,靶细胞的活力下降,存在明显的剂量-效应关系(P<0.05).4 mg/L ACTD作用1h时细胞活力接近50%且稳定.旁观者细胞活力在用4-12 h CM培养时逐渐增加(P<0.05),用24h CM时又下降(P<0.05),4h CM诱导旁观者细胞损伤的作用最强.靶细胞的染色体畸变率随ACTD剂量的增加而增高,具有剂量-效应关系(P<.05).旁观者细胞染色体畸变以4hCM诱导的作用最强,随着加入CM时段的延后,损伤逐渐减轻(P<0.05),在24hCM又趋严重(P<0.05);旁观者细胞与靶细胞染色体畸变类型相似,以断裂为主,伴有少量环形染色体、碎片和双着丝粒染色体.结论:ACTD可以诱导旁观者效应的发生,染色体畸变在靶细胞和旁观者细胞均以断裂为主.%OBJECTIVE: To observe the effect of actinomycin D (ACTD) and conditioned medium on cell viability and chromosome aberration in hamster fibroblast V79 cells to determine whether actinomycin D could induce bystander effect. METHODS: V79 cells were treated with ACTD for 1 h at different doses (0, 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/L). The 4 mg/L ACTD-conditioned medium(CM) was collected at 4, 8, 12 and 24 h after treatment for 1 h to culture bystander cells to observe the bystander effect. Cell viability was evaluated by MTT assay; chromosome damage was detected using the conventional analysis of

  19. Clinical Presentation and Microarray Analysis of Peruvian Children with Atypical Development and/or Aberrant Behavior

    Directory of Open Access Journals (Sweden)

    Merlin G. Butler

    2014-01-01

    Full Text Available We report our experience with high resolution microarray analysis in infants and young children with developmental disability and/or aberrant behavior enrolled at the Centro Ann Sullivan del Peru in Lima, Peru, a low income country. Buccal cells were collected with cotton swabs from 233 participants for later DNA isolation and identification of copy number variation (deletions/duplications and regions of homozygosity (ROH for estimating consanguinity status in 15 infants and young children (12 males, 3 females; mean age ± SD = 28.1 m ±   7.9 m; age range 14 m–41 m randomly selected for microarray analysis. An adequate DNA yield was found in about one-half of the enrolled participants. Ten participants showed deletions or duplications containing candidate genes reported to impact behavior or cognitive development. Five children had ROHs which could have harbored recessive gene alleles contributing to their clinical presentation. The coefficient of inbreeding was calculated and three participants showed first-second cousin relationships, indicating consanguinity. Our preliminary study showed that DNA isolated from buccal cells using cotton swabs was suboptimal, but yet in a subset of participants the yield was adequate for high resolution microarray analysis and several genes were found that impact development and behavior and ROHs identified to determine consanguinity status.

  20. Analysis of nodal aberration properties in off-axis freeform system design.

    Science.gov (United States)

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design.

  1. Transcript analysis of 250 novel yeast genes from chromosome XIV.

    Science.gov (United States)

    Planta, R J; Brown, A J; Cadahia, J L; Cerdan, M E; de Jonge, M; Gent, M E; Hayes, A; Kolen, C P; Lombardia, L J; Sefton, M; Oliver, S G; Thevelein, J; Tournu, H; van Delft, Y J; Verbart, D J; Winderickx, J

    1999-03-15

    The European Functional Analysis Network (EUROFAN) is systematically analysing the function of novel Saccharomyces cerevisiae genes revealed by genome sequencing. As part of this effort our consortium has performed a detailed transcript analysis for 250 novel ORFs on chromosome XIV. All transcripts were quantified by Northern analysis under three quasi-steady-state conditions (exponential growth on rich fermentative, rich non-fermentative, and minimal fermentative media) and eight transient conditions (glucose derepression, glucose upshift, stationary phase, nitrogen starvation, osmo-stress, heat-shock, and two control conditions). Transcripts were detected for 82% of the 250 ORFs, and only one ORF did not yield a transcript of the expected length (YNL285w). Transcripts ranged from low (62%), moderate (16%) to high abundance (2%) relative to the ACT1 mRNA. The levels of 73% of the 206 chromosome XIV transcripts detected fluctuated in response to the transient states tested. However, only a small number responded strongly to the transients: eight ORFs were induced upon glucose upshift; five were repressed by glucose; six were induced in response to nitrogen starvation; three were induced in stationary phase; five were induced by osmo-stress; four were induced by heat-shock. These data provide useful clues about the general function of these ORFs and add to our understanding of gene regulation on a genome-wide basis.

  2. PRE-EXPOSURE OF MICE TO LOW DOSE OR LOW DOSE RATE IONIZING RADIATION REDUCES CHROMOSOME ABERRATIONS INDUCED BY SUBSEQUENT EXPOSURE TO HIGH DOSE OF RADIATION OR MITOMYCIN C

    Institute of Scientific and Technical Information of China (English)

    于文儒; 王明东; 蔡露; 金玉珂

    1995-01-01

    The phenomenon of cytogenetic adaptive and cross-adaptive response induced by low dose irradiation and chemical mutagen in mice is described. We found, firstly, that adapration can be induced by acute low dose X-irracliation (0—100 mGy). Secondly, a cross-adaptation can occur between X-irradiatlon and rrdto-mycin C (MMC). And finally, mice pre-exposed to chronic low dose rate 60Co-Gamma irradiation (0-226. 0 mGy/day) are less susceptible to chromosome aberration induced by subsequent acute higher X-irradiation. Therefore, our data suggest that radioadaptlve respotrse depends on dose, dose rate and time interval. Possible mechanisms are also discussed.

  3. Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett syndrome

    DEFF Research Database (Denmark)

    Borg, Isabella; Freude, Kristine; Kübart, Sabine;

    2005-01-01

    hybridisations, utilizing probes derived from breakpoint spanning BACs, detected several aberrant fragments specific for the patient. Sequence analysis of the cloned junction fragment indicated that on chromosome 1 the predominantly brain-expressed Netrin G1 (NTNG1) gene is disrupted, whereas on chromosome 7...

  4. Radiation sensitivity of the gastrula-stage embryo: Chromosome aberrations and mutation induction in lacZ transgenic mice: The roles of DNA double-strand break repair systems.

    Science.gov (United States)

    Jacquet, Paul; van Buul, Paul; van Duijn-Goedhart, Annemarie; Reynaud, Karine; Buset, Jasmine; Neefs, Mieke; Michaux, Arlette; Monsieurs, Pieter; de Boer, Peter; Baatout, Sarah

    2015-10-01

    At the gastrula phase of development, just after the onset of implantation, the embryo proper is characterized by extremely rapid cell proliferation. The importance of DNA repair is illustrated by embryonic lethality at this stage after ablation of the genes involved. Insight into mutation induction is called for by the fact that women often do not realize they are pregnant, shortly after implantation, a circumstance which may have important consequences when women are subjected to medical imaging using ionizing radiation. We screened gastrula embryos for DNA synthesis, nuclear morphology, growth, and chromosome aberrations (CA) shortly after irradiation with doses up to 2.5Gy. In order to obtain an insight into the importance of DNA repair for CA induction, we included mutants for the non-homologous end joining (NHEJ) and homologous recombination repair (HRR) pathways, as well as Parp1-/- and p53+/- embryos. With the pUR288 shuttle vector assay, we determined the radiation sensitivity for point mutations and small deletions detected in young adults. We found increased numbers of abnormal nuclei 5h after irradiation; an indication of disturbed development was also observed around this time. Chromosome aberrations 7h after irradiation arose in all genotypes and were mainly of the chromatid type, in agreement with a cell cycle dominated by S-phase. Increased frequencies of CA were found for NHEJ and HR mutants. Gastrula embryos are unusual in that they are low in exchange induction, even after compromised HR. Gastrula embryos were radiation sensitive in the pUR288 shuttle vector assay, giving the highest mutation induction ever reported for this genetic toxicology model. On theoretical grounds, a delayed radiation response must be involved. The compromised developmental profile after doses up to 2.5Gy likely is caused by both apoptosis and later cell death due to large deletions. Our data indicate a distinct radiation-sensitive profile of gastrula embryos, including

  5. Oxidative Damage to Nucleic Acids and Benzo(apyrene-7,8-diol-9,10-epoxide-DNA Adducts and Chromosomal Aberration in Children with Psoriasis Repeatedly Exposed to Crude Coal Tar Ointment and UV Radiation

    Directory of Open Access Journals (Sweden)

    Lenka Borska

    2014-01-01

    Full Text Available The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19 treated by Goeckerman therapy (GT. The study describes adverse (side effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation. After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine, significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE DNA adducts (BPDE-DNA, and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1 time of UV exposure and total number of aberrated cells and (2 daily topical application of 3% crude coal tar ointment (% of body surface and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score.

  6. 用高分辨G带和人工细菌染色体荧光原位杂交技术分析中国儿童孤独症患者的染色体改变%Detection of chromosome aberrations in Chinese children with autism using G-banding and BAC FISH

    Institute of Scientific and Technical Information of China (English)

    刘青杰; 陈晓宁; 沈岩; 马芬; 李丹; 王晓维; 田文雁; 陈艳; 封江彬; 陆雪; 陈德清

    2005-01-01

    Objective To detect the characteristic chromosomal changes in Chinese children with infantile autism. Methods Chromosome aberrations in 68 cases of infantile autism were analyzed by high-resolution G-banding and fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones. Results Chromosomal changes were detected in 4 cases by high-resolution G-banding: one case with t(4;6)(q23-24;p21), one case with longer p arm of chromosome 21 (21p+), and two cases with pericentric inversion of chromosome 9 (inv(9)) which was confirmed by C-banding. BAC FISH analysis was performed to confirm these observations and changes in chromosomes 2, 7 and 15, which are often found in autistic children. There could exist the translocation of t(4;6) (q25-26;p21.1). Chromosome changes often reported previously in chromosomes 2, 7 and 15 were not detected in this study. Inv(9) and 21p+ were not confirmed with present BAC clones. Conclusion Chromosomal changes were detected in four cases of infantile autism, with a detectability of 5.9%, far lower than that (10% to 48%) reported in literature. The breakpoint of translocation could be detected more accurately using BAC FISH method.%目的检测中国儿童孤独症患者的特征性染色体改变.方法应用高分辨G带和人工细菌染色体(bacterial artificial chromosome, BAC)荧光原位杂交(flourescence in situ hybridization, FISH)分析68例中国儿童孤独症患者的染色体改变.结果用G带分析观察到有染色体改变的4例患者,分别为1例t(4;6)(q23-24;p21)、1例21p+和2例9号染色体臂间倒位.BAC FISH进一步证实易位病例,而且更精确[t(4;6)(q25-26;p21.1)];涉及7号、15号、2号染色体的BAC FISH均未观察到文献中报道的染色体改变;而9号染色体的臂间倒位和21p+因无BAC克隆而无法证实.结论用G带和BAC FISH发现少数中国孤独症患者有染色体改变,但远没有文献中报道的10%~48%那么高.BAC FISH有助于精确地确定染色体易位断裂点.

  7. IMACULAT - an open access package for the quantitative analysis of chromosome localization in the nucleus.

    Directory of Open Access Journals (Sweden)

    Ishita Mehta

    Full Text Available The alteration in the location of the chromosomes within the nucleus upon action of internal or external stimuli has been implicated in altering genome function. The effect of stimuli at a whole genome level is studied by using two-dimensional fluorescence in situ hybridization (FISH to delineate whole chromosome territories within a cell nucleus, followed by a quantitative analysis of the spatial distribution of the chromosome. However, to the best of our knowledge, open access software capable of quantifying spatial distribution of whole chromosomes within cell nucleus is not available. In the current work, we present a software package that computes localization of whole chromosomes - Image Analysis of Chromosomes for computing localization (IMACULAT. We partition the nucleus into concentric elliptical compartments of equal area and the variance in the quantity of any chromosome in these shells is used to determine its localization in the nucleus. The images are pre-processed to remove the smudges outside the cell boundary. Automation allows high throughput analysis for deriving statistics. Proliferating normal human dermal fibroblasts were subjected to standard a two-dimensional FISH to delineate territories for all human chromosomes. Approximately 100 images from each chromosome were analyzed using IMACULAT. The analysis corroborated that these chromosome territories have non-random gene density based organization within the interphase nuclei of human fibroblasts. The ImageMagick Perl API has been used for pre-processing the images. The source code is made available at www.sanchak.com/imaculat.html.

  8. Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML

    DEFF Research Database (Denmark)

    Preiss, Birgitte S; Bergman, Olav J; Friis, Lone S;

    2010-01-01

    During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients...... (P = 0.01). We conclude that population-based cytogenetic studies of adult s-AML and age- and sex-matched de novo AML show comparable distributions of chromosome abnormalities....

  9. Hematoxylin: a simple, multiple-use dye for chromosome analysis

    Directory of Open Access Journals (Sweden)

    Guerra Marcelo

    1999-01-01

    Full Text Available A staining mixture of hematoxylin-iron alum combined with a strong hydrochloric hydrolysis was successfully applied for chromosome observation of several kinds of plants and some animals. Slightly different procedures were developed for different materials and objectives. For plant cells, the most important technical aspect was the use of 5 N HCl hydrolysis, which resulted in a very transparent cytoplasm, combined with an intense, specific hematoxylin stain. This technique is recommended for cytogenetical analysis in general, and it is especially indicated for practical classes, due to its simplicity and high reproducibility of results. Moreover, the deep contrast observed makes this technique very useful for sequential staining of cells previously analyzed with other stains, as well as for materials with fixation problems.

  10. Linkage analysis on chromosome 2 in essential hypotension pedigrees

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is a new approach to study the important genes related to the control of blood pressure by probing into hypotension and hypertension at the same time. Genome scanning on whole chromosome 2 in 8 hypotension pedigrees has been done and parameter (LOD score) and non-pa- rameter (NPL score) were used in the linkage analysis by GENEHUNTER software. The results show the evidence of linkage between D2S112 and D2S117, indicating a number of critical genes may lie in thisregion and contribute to the mechanism of blood pressure regulation. Also this region has been found in the previous study in hypertension pedigrees. These genes may play an important role in the regulation of blood pressure and can also be the important candidate genes in hypertension studies.

  11. Cytogenetic heterogeneity and their serial dynamic changes during acquisition of cytogenetic aberrations in cultured mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung-Ah [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Im, Kyong Ok; Park, Si Nae; Kwon, Ji Seok [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Seon Young [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Oh, Keunhee; Lee, Dong-Sup [Laboratory of Immunology and Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul (Korea, Republic of); Transplantation Research Institute, Seoul National University College of Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Min Kyung; Kim, Seong Who [Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jang, Mi; Lee, Gene [Lab of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Oh, Yeon-Mok; Lee, Sang Do [Department of Pulmonary and Critical Care Medicine, Asthma Center and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Dong Soon, E-mail: soonlee@snu.ac.kr [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-07-15

    Highlights: • We evaluated cytogenetic aberrations of MSC during culture using G-banding and FISH. • We tracked the quantitative changes of each clone among heterogeneity upon passages. • The changes of cytogenetic profile upon passages were similar to cancer stem cell. - Abstract: To minimize the risk of tumorigenesis in mesenchymal stem cells (MSCs), G-banding analysis is widely used to detect chromosomal aberrations in MSCs. However, a critical limitation of G-banding is that it only reflects the status of metaphase cells, which can represent as few as 0.01% of tested cells. During routine cytogenetic testing in MSCs, we often detect chromosomal aberrations in minor cell populations. Therefore, we aimed to investigate whether such a minority of cells can expand over time or if they ultimately disappear during MSC passaging. We passaged MSCs serially while monitoring quantitative changes for each aberrant clone among heterogeneous MSCs. To investigate the cytogenetic status of interphase cells, which represent the main population, we also performed interphase FISH analysis, in combination with G-banding and telomere length determination. In human adipose tissue-derived MSCs, 4 types of chromosomal aberrations were found during culturing, and in umbilical cord MSCs, 2 types of chromosomal aberrations were observed. Sequential dynamic changes among heterogeneous aberrant clones during passaging were similar to the dynamic changes observed in cancer stem cells during disease progression. Throughout all passages, the quantitative G-banding results were inconsistent with those of the interphase FISH analysis. Interphase FISH revealed hidden aberrations in stem cell populations with normal karyotypes by G-banding analysis. We found that telomere length gradually decreased during passaging until the point at which cytogenetic aberrations appeared. The present study demonstrates that rare aberrant clones at earlier passages can become predominant clones during

  12. Numerical analysis of low chromatic aberration of a gradient refractive index rod lens.

    Science.gov (United States)

    Lv, Hao; Liu, Aimei; Yi, Xunong; Li, Qianguang

    2009-01-20

    The oxide compositions (OCs) model is established for discussing the chromatic aberrations of a gradient refractive index rod lens. The chromatic aberrations for Na(+)/Li(+), K(+)/Cs(+), and K(+)/Tl(+) ion exchanges are discussed based on the OC model and the Huggins-Sun-Davis (HSD) model. Theoretical results indicate that the function value mainly depends on base glass properties and the nature of exchanging ion pairs, and rarely depends on the quantity of ion exchange. Experimental results show that the chromatic aberrations using the OC model have smaller errors than with the HSD model. The estimating average errors between the OC model and the HSD model are -0.051, -0.0067, and 0.0047 for the K(+)/Tl(+), Li(+)/Na(+), and K(+)/Cs(+) ion exchanges, respectively.

  13. Aberration analysis based on pinhole-z-scan method near the focal point of refractive systems

    Science.gov (United States)

    Castro-Marín, Pablo; Garduño-Mejía, Jesús; Rosete-Aguilar, Martha; Bruce, Neil C.; Reid, Derryck T.; Farrell, C.; Sandoval-Romero, Gabriel E.

    2016-09-01

    In this work we present a method used to study the spherical and chromatic aberrations contribution near the focal point of a refractive optical system. The actual focal position is measured by scanning a pinhole attached on the front of a power detector, which are scanned along the optical axis using a motorized stage with 1 μm resolution. Spherical aberration contribution was analyzed by changing the pupil aperture, by modifying the size of the input iris diaphragm and for each case, measuring the actual laser power vs the detector position. Chromatic aberration was analyzed by performing the same procedure but in this case we used an ultra-broad-band femtosecond laser. The results between ML and CW operation were compare. Experimental results are presented.

  14. Experimental Researches on Carcinogenesis or Tumorigenicity of MDCK Canine Kidney Cell(CKC) Lines and Analysis of Their Chromosome Karyotypes

    Institute of Scientific and Technical Information of China (English)

    ZHANG De-li; FANG Fu-de; LI Liu-jin; XIA Geng-tian; HE Xu-yu; GAO Bu-xian; BAI Xiao-hong; HUANG Gao-sheng; LIU Shang-gao; YAN Long-fei

    2002-01-01

    The chromosomal number variations & structural aberrations of the MDCK cell line, primary feline or canine kidney cell(FKC or CKC) and Hela cell line were investigated and their karyotypes of conventional chromosome bands were analyzed. The carcinogenesis or tumorigenicity testing of these cell lines in about 232 nude mice and for colony formation in soft agarose and for haemagglutination under different concentration of plant lectins of these cells were carried out. Under the prerequisite that the incidence of cancer or tumor in negative-control nude mice inoculated subcutaneously with primary feline or canine kidney cell cultures purified in vitro at passage 3 was 0 (0/22) and 0 (0/10), respectively. The incidence of the progressively-growing malignant tumor(MT) in positive-control nude mice inoculated subcutaneously with Hela cell cultures of KB, X, or NM20/X strain was 10/10, 25/25 and 5/51, respectively. The results showed that the incidence of tumor in nude mice with tetrapioid YA strain of MDCK cell during 20 - 45 passages, with hypodiploid JB strain of MDCK cell on passage 25, with di-and hypoploid JC strain of MDCK cell during 2 - 15passages or with hypoploid M strain of MDCK cell during 9 - 27 passages was 28/58, 1/5, 4/18 and 0/31,respectively. The chromosomal analysis results showed that the ratio of difference in the rate of modal chromosome number between high (mcs + n) and lowest (mcs)passages was not more than 5 % - 15 % and the structure aberrations was generally 0 - 3%. These results proved that the genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species-specific. MDCK line has tumorigenicity no matter what its chromosome karyotype is, at least it has very low tumorigenicity even when its modal chromosome number is hypoploid. The repeatedly frozen, thawed and split controls of tumorigenicity-positive cell lines(X strain of Hela, M strain of BHK-21, JA strain of Vero, YA strain of MDCK) have

  15. Advances in understanding paternally transmitted Chromosomal Abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate the types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.

  16. Holocentric chromosomes: convergent evolution, meiotic adaptations, and genomic analysis.

    Science.gov (United States)

    Melters, Daniël P; Paliulis, Leocadia V; Korf, Ian F; Chan, Simon W L

    2012-07-01

    In most eukaryotes, the kinetochore protein complex assembles at a single locus termed the centromere to attach chromosomes to spindle microtubules. Holocentric chromosomes have the unusual property of attaching to spindle microtubules along their entire length. Our mechanistic understanding of holocentric chromosome function is derived largely from studies in the nematode Caenorhabditis elegans, but holocentric chromosomes are found over a broad range of animal and plant species. In this review, we describe how holocentricity may be identified through cytological and molecular methods. By surveying the diversity of organisms with holocentric chromosomes, we estimate that the trait has arisen at least 13 independent times (four times in plants and at least nine times in animals). Holocentric chromosomes have inherent problems in meiosis because bivalents can attach to spindles in a random fashion. Interestingly, there are several solutions that have evolved to allow accurate meiotic segregation of holocentric chromosomes. Lastly, we describe how extensive genome sequencing and experiments in nonmodel organisms may allow holocentric chromosomes to shed light on general principles of chromosome segregation.

  17. Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis.

    Science.gov (United States)

    Godler, David E; Inaba, Yoshimi; Schwartz, Charles E; Bui, Quang M; Shi, Elva Z; Li, Xin; Herlihy, Amy S; Skinner, Cindy; Hagerman, Randi J; Francis, David; Amor, David J; Metcalfe, Sylvia A; Hopper, John L; Slater, Howard R

    2015-07-01

    Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility.

  18. Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration.

    Science.gov (United States)

    Van Opstal, Diane; Srebniak, Malgorzata I

    2016-01-01

    It has been shown that in non-invasive prenatal testing (NIPT) there is a small chance of a false-positive or false-negative result. This is partly due to the fact that the fetal cell-free DNA present in maternal plasma is derived from the cytotrophoblast of chorionic villi (CV), which is not always representative for the fetal karyotype due to chromosomal mosaicism. Therefore, a positive NIPT result should always be confirmed with invasive testing, preferably amniocentesis, in order to investigate the fetal karyotype. However, since this invasive test can only be safely performed after 15.5 weeks of gestation while NIPT can be done from the 10(th) week of gestation, this potentially means an unacceptable long waiting time for the prospective parents to receive a definitive result. Based on our experience with cytogenetic investigations in CV and the literature, we determined whether CV sampling may be appropriate for confirmation of an abnormal NIPT result.

  19. Nuclei size in relation to nuclear status and aneuploidy rate for 13 chromosomes in donated four cells embryos

    DEFF Research Database (Denmark)

    Agerholm, I E; Hnida, C; Crüger, D G;

    2008-01-01

    PURPOSE: The aim was to elucidate if the nuclear size and number are indicative of aberrant chromosome content in human blastomeres and embryos. METHODS: The number of nuclei and the nucleus and blastomere size were measured by a computer controlled system for multilevel analysis. Then the nuclei...... were enumerated for 13 chromosomes by a combination of PNA and DNA probes. RESULTS: In the mononucleated embryos there was no difference in the mean size of chromosomally normal and abnormal nuclei but a significant difference in the mean nuclei size of nuclei that had gained chromosomes compared...... to nuclei that had lost chromosomes. The nuclei from multinucleated blastomeres had a significant smaller mean size and the frequency of chromosomally aberrant blastomeres was significantly higher. CONCLUSION: The mean nuclear size is not a marker for the chromosome content in mononucleated embryos. However...

  20. Porcine UCHL1: genomic organization, chromosome localization and expression analysis

    DEFF Research Database (Denmark)

    Larsen, Knud; Madsen, Lone Bruhn; Bendixen, Christian

    2012-01-01

    to and protection from Parkinson’s disease. Here we report cloning, characterization, expression analysis and mapping of porcine UCHL1. The UCHL1 cDNA was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) using oligonucleotide primers derived from in silico sequences. The porcine cDNA codes...... for a protein of 223 amino acids which shows a very high similarity to human (98%) and to mouse (97%) UCHL1. In addition, the genomic organization of the porcine UCHL1 gene was determined. The porcine UCHL1 gene was mapped to chromosome 8(½p21)–p23. Three SNPs were found in the porcine UCHL1 sequence....... Expression analysis by quantitative real time RT-PCR demonstrated that porcine UCHL1 mRNA is differentially expressed in various organs and tissues and similar to its human counterpart. UCHL1 transcript is most abundant in brain tissues and in the spinal cord. The UCHL1 mRNA expression was also investigated...

  1. Identification of Chromosome Abnormalities in Subtelomeric Regions by Microarray Analysis: A Study of 5,380 Cases

    Science.gov (United States)

    Shao, Lina; Shaw, Chad A.; Lu, Xin-Yan; Sahoo, Trilochan; Bacino, Carlos A.; Lalani, Seema R.; Stankiewicz, Pawel; Yatsenko, Svetlana A.; Li, Yinfeng; Neill, Sarah; Pursley, Amber N.; Chinault, A. Craig; Patel, Ankita; Beaudet, Arthur L.; Lupski, James R.; Cheung, Sau W.

    2009-01-01

    Subtelomeric imbalances are a significant cause of congenital disorders. Screening for these abnormalities has traditionally utilized GTG-banding analysis, fluorescence in situ hybridization (FISH) assays, and multiplex ligation-dependent probe amplification. Microarray-based comparative genomic hybridization (array-CGH) is a relatively new technology that can identify microscopic and submicroscopic chromosomal imbalances. It has been proposed that an array with extended coverage at subtelomeric regions could characterize subtelomeric aberrations more efficiently in a single experiment. The targeted arrays for chromosome microarray analysis (CMA), developed by Baylor College of Medicine, have on average 12 BAC/PAC clones covering 10 Mb of each of the 41 subtelomeric regions. We screened 5,380 consecutive clinical patients using CMA. The most common reasons for referral included developmental delay (DD), and/or mental retardation (MR), dysmorphic features (DF), multiple congenital anomalies (MCA), seizure disorders (SD), and autistic, or other behavioral abnormalities. We found pathogenic rearrangements at subtelomeric regions in 236 patients (4.4%). Among these patients, 103 had a deletion, 58 had a duplication, 44 had an unbalanced translocation, and 31 had a complex rearrangement. The detection rates varied among patients with a normal karyotype analysis (2.98%), with an abnormal karyotype analysis (43.4%), and with an unavailable or no karyotype analysis (3.16%). Six patients out of 278 with a prior normal subtelomere-FISH analysis showed an abnormality including an interstitial deletion, two terminal deletions, two interstitial duplications, and a terminal duplication. In conclusion, genomic imbalances at subtelomeric regions contribute significantly to congenital disorders. Targeted array-CGH with extended coverage (up to 10 Mb) of subtelomeric regions will enhance the detection of subtelomeric imbalances, especially for submicroscopic imbalances. PMID

  2. 137Cesium-induced chromosome aberrations analyzed by fluorescence in situ hybridization: eight years follow up of the Goiânia radiation accident victims.

    Science.gov (United States)

    Natarajan, A T; Santos, S J; Darroudi, F; Hadjidikova, V; Vermeulen, S; Chatterjee, S; Berg, M; Grigorova, M; Sakamoto-Hojo, E T; Granath, F; Ramalho, A T; Curado, M P

    1998-05-25

    The radiation accident in focus here occurred in a section of Goiânia (Brazil) where more than a hundred individuals were contaminated with 137Cesium on September 1987. In order to estimate the absorbed radiation doses, initial frequencies of dicentrics and rings were determined in 129 victims [A.T. Ramalho, PhD Thesis, Subsidios a tecnica de dosimetria citogenetica gerados a partir da analise de resultados obtidos com o acidente radiologico de Goiânia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 1992]. We have followed some of these victims cytogenetically over the years seeking for parameters that could be used as basis for retrospective radiation dosimetry. Our data on translocation frequencies obtained by fluorescence in situ hybridization (FISH) could be directly compared to the baseline frequencies of dicentrics available for those same victims. Our results provided valuable information on how precise these estimates are. The frequencies of translocations observed years after the radiation exposure were two to three times lower than the initial dicentrics frequencies, the differences being larger at higher doses (>1 Gy). The accuracy of such dose estimates might be increased by scoring sufficient amount of cells. However, factors such as the persistence of translocation carrying lymphocytes, translocation levels not proportional to chromosome size, and inter-individual variation reduce the precision of these estimates.

  3. Systematic analysis of S. cerevisiae chromosome VIII genes.

    Science.gov (United States)

    Niedenthal, R; Riles, L; Güldener, U; Klein, S; Johnston, M; Hegemann, J H

    1999-12-01

    To begin genome-wide functional analysis, we analysed the consequences of deleting each of the 265 genes of chromosome VIII of Saccharomyces cerevisiae. For 33% of the deletion strains a growth phenotype could be detected: 18% of the genes are essential for growth on complete glucose medium, and 15% grow significantly more slowly than the wild-type strain or exhibit a conditional phenotype when incubated under one of 20 different growth conditions. Two-thirds of the mutants that exhibit conditional phenotypes are pleiotropic; about one-third of the mutants exhibit only one phenotype. We also measured the level of expression directed by the promoter of each gene. About half of the promoters direct detectable transcription in rich glucose medium, and most of these exhibited only low or medium activity. Only 1% of the genes are expressed at about the same level as ACT1. The number of active promoters increased to 76% upon growth on a non-fermentable carbon source, and to 93% in minimal glucose medium. The majority of promoters fluctuated in strength, depending on the medium.

  4. Laboratory intercomparison of the dicentric chromosome analysis assay.

    Science.gov (United States)

    Beinke, C; Barnard, S; Boulay-Greene, H; De Amicis, A; De Sanctis, S; Herodin, F; Jones, A; Kulka, U; Lista, F; Lloyd, D; Martigne, P; Moquet, J; Oestreicher, U; Romm, H; Rothkamm, K; Valente, M; Meineke, V; Braselmann, H; Abend, M

    2013-08-01

    The study design and obtained results represent an intercomparison of various laboratories performing dose assessment using the dicentric chromosome analysis (DCA) as a diagnostic triage tool for individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-5 Gy) as well as blind samples (0.1-6.4 Gy) were sent to the participants. DCA was performed according to established protocols. The time taken to report dose estimates was documented for each laboratory. Additional information concerning laboratory organization/characteristics as well as assay performance was collected. The mean absolute difference (MAD) was calculated and radiation doses were merged into four triage categories reflecting clinical aspects to calculate accuracy, sensitivity and specificity. The earliest report time was 2.4 days after sample arrival. DCA dose estimates were reported with high and comparable accuracy, with MAD values ranging between 0.16-0.5 Gy for both manual and automated scoring. No significant differences were found for dose estimates based either on 20, 30, 40 or 50 cells, suggesting that the scored number of cells can be reduced from 50 to 20 without loss of precision of triage dose estimates, at least for homogenous exposure scenarios. Triage categories of clinical significance could be discriminated efficiently using both scoring procedures.

  5. Analysis of pupil and corneal wave aberration data supplied by the SN CT 1000 topography system

    Science.gov (United States)

    Comastri, S. A.; Martin, G.; Pfortner, T.

    2006-11-01

    Ocular aberrations depend on pupil size and centring and the retinal image quality under natural conditions differs from that corresponding to laboratory ones. In the present article, pupil and wave aberration data supplied by the Shin Nippon CT 1000 (SN CT 1000) topography system are analysed. Two groups of eyes under natural viewing conditions are considered ((260+/-20) lux at the eye under study). The first group consists of 10 normal eyes (-1.25 to 3 D sphere; 0 to -1.75 D cylinder) of five young subjects (age between 18 and 33 years). For this group, five determinations per eye are performed and the repeatability of results is analysed. Pupil centre is displaced from corneal vertex towards the temporal region, the largest displacement being (0.5+/-0.1) mm. The variation of pupil diameter in each eye is less than 21% while the inter-subject variability is large since diameters are between (3+/-0.3) and (5.3+/-0.6) mm. Aberrations are evaluated for two different pupil sizes, the natural one and a fictitious one of 6 mm. The corneal higher-order root-mean square wavefront error (RMSHO) for a 6 mm pupil centred in the corneal vertex, averaged across all eyes, is (0.37+/-0.06) [mu]m while, considering the natural pupil diameter, the average in each eye is significantly lower, up to eight times smaller. The fourth-order spherical aberration is an important aberration in the considered eyes, its maximum value for a 6 mm pupil being (0.38+/-0.02) [mu]m. The second group consists of 24 eyes of 12 subjects (age between 25 and 68 years) such that four eyes are of normal adults (1.25 to +6 D sphere; 0 to -0.5 D cylinder), eight have astigmatisms (-5.5 to +3.25 D sphere; -1.5 to -4.5 D cylinder), six have post-refractive surgery (+0.5 to +3.5 D sphere; -0.5 to -4 D cylinder) and six have keratoconus (-9.5 to +1 D sphere; -1 to -4.5 D cylinder). For this group only one determination per eye is performed. Pupil centre is displaced from corneal vertex towards the temporal

  6. Optical Aberrations and Wavefront

    Directory of Open Access Journals (Sweden)

    Nihat Polat

    2014-08-01

    Full Text Available The deviation of light to create normal retinal image in the optical system is called aberration. Aberrations are divided two subgroup: low-order aberrations (defocus: spherical and cylindrical refractive errors and high-order aberrations (coma, spherical, trefoil, tetrafoil, quadrifoil, pentafoil, secondary astigmatism. Aberrations increase with aging. Spherical aberrations are compensated by positive corneal and negative lenticular spherical aberrations in youth. Total aberrations are elevated by positive corneal and positive lenticular spherical aberrations in elderly. In this study, we aimed to analyze the basic terms regarding optic aberrations which have gained significance recently. (Turk J Ophthalmol 2014; 44: 306-11

  7. Comprehensive 5-Year Study of Cytogenetic Aberrations in 668 Infertile Men

    Science.gov (United States)

    Yatsenko, Alexander N.; Yatsenko, Svetlana A.; Weedin, John W.; Lawrence, Amy E.; Patel, Ankita; Peacock, Sandra; Matzuk, Martin M.; Lamb, Dolores J.; Cheung, Sau Wai; Lipshultz, Larry I.

    2010-01-01

    Purpose The causes of male infertility are heterogeneous but more than 50% of cases have a genetic basis. Specific genetic defects have been identified in less than 20% of infertile males and, thus, most causes remain to be elucidated. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions. To refine the incidence and nature of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 668 infertile men with oligozoospermia and azoospermia. Materials and Methods High resolution Giemsa banding chromosome analysis and/or fluorescence in situ hybridization were done in 668 infertile males referred for routine cytogenetic analysis between January 2004 and March 2009. Results The overall incidence of chromosomal abnormalities was about 8.2%. Of the 55 patients with abnormal cytogenetic findings sex chromosome aneuploidies were observed in 29 (53%), including Klinefelter syndrome in 27 (49%). Structural chromosome abnormalities involving autosomes (29%) and sex chromosomes (18%) were detected in 26 infertile men. Abnormal cytogenetic findings were observed in 35 of 264 patients (13.3%) with azoospermia and 19 of 365 (5.2%) with oligozoospermia. Conclusions Structural chromosomal defects and low level sex chromosome mosaicism are common in oligozoospermia cases. Extensive cytogenetic assessment and fluorescence in situ hybridization may improve the detection rate in males with oligozoospermia. These findings highlight the need for efficient genetic testing in infertile men so that couples may make informed decisions on assisted reproductive technologies to achieve parenthood. PMID:20172548

  8. Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

    Science.gov (United States)

    Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

    2016-05-01

    Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies.

  9. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole;

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  10. Impact of personal and environmental factors on the rate of chromosome aberrations named translocations - Part 1: age, gender, smoking, alcohol; Impact des facteurs individuels et environnementaux sur le taux d'aberrations chromosomiques de type translocations - Partie 1: age, sexe, tabac, alcool

    Energy Technology Data Exchange (ETDEWEB)

    Gregoire, E.; Gruel, G.; Martin, C.; Roch-Lefevre, S.; Vaurijoux, A.; Voisin, P.; Roy, L. [IRSN, Laboratoire de Dosimetrie Biologique, 92 - Fontenay-aux-Roses (France)

    2010-04-15

    The assessment of exposure to ionizing radiation, carried out long time after exposure, is currently performed by scoring of translocations, a specific type of chromosomal aberrations. The translocations rate observed in peripheral blood lymphocytes of exposed subjects is compared to that observed in a control population. However, the translocation specificity towards radiation exposure is not clearly identified. To avoid any hasty conclusion, it is necessary to identify all the factors likely to induce translocation. To our knowledge, no study has thus far examined the effects of all these different factors on translocation rates. A review of the literature thus allowed us to assess the impact of host factors and lifestyle on the production of translocations. This study confirms that age appears to be the factor having the greatest impact on the rate of translocations, especially over 60 years. To date, the factor 'age' is already considered in estimating the impact of radiation on the rate of translocation for all age groups. However, the study also shows that this rate varies significantly when the patient is exposed simultaneously and significantly towards many lifestyle agents. A precise threshold translocation rate should thus be established as a function of known behavioral exposures, below which it is impossible to conclude that radiological exposure has occurred. The effects of chemicals on the translocation rate after occupational exposure will be the subject of a second part. (authors)

  11. Chromosome arm-specific BAC end sequences permit comparative analysis of homoeologous chromosomes and genomes of polyploid wheat

    Directory of Open Access Journals (Sweden)

    Sehgal Sunish K

    2012-05-01

    Full Text Available Abstract Background Bread wheat, one of the world’s staple food crops, has the largest, highly repetitive and polyploid genome among the cereal crops. The wheat genome holds the key to crop genetic improvement against challenges such as climate change, environmental degradation, and water scarcity. To unravel the complex wheat genome, the International Wheat Genome Sequencing Consortium (IWGSC is pursuing a chromosome- and chromosome arm-based approach to physical mapping and sequencing. Here we report on the use of a BAC library made from flow-sorted telosomic chromosome 3A short arm (t3AS for marker development and analysis of sequence composition and comparative evolution of homoeologous genomes of hexaploid wheat. Results The end-sequencing of 9,984 random BACs from a chromosome arm 3AS-specific library (TaaCsp3AShA generated 11,014,359 bp of high quality sequence from 17,591 BAC-ends with an average length of 626 bp. The sequence represents 3.2% of t3AS with an average DNA sequence read every 19 kb. Overall, 79% of the sequence consisted of repetitive elements, 1.38% as coding regions (estimated 2,850 genes and another 19% of unknown origin. Comparative sequence analysis suggested that 70-77% of the genes present in both 3A and 3B were syntenic with model species. Among the transposable elements, gypsy/sabrina (12.4% was the most abundant repeat and was significantly more frequent in 3A compared to homoeologous chromosome 3B. Twenty novel repetitive sequences were also identified using de novo repeat identification. BESs were screened to identify simple sequence repeats (SSR and transposable element junctions. A total of 1,057 SSRs were identified with a density of one per 10.4 kb, and 7,928 junctions between transposable elements (TE and other sequences were identified with a density of one per 1.39 kb. With the objective of enhancing the marker density of chromosome 3AS, oligonucleotide primers were successfully designed from

  12. The DNA Sequence And Comparative Analysis Of Human Chromosome5

    Energy Technology Data Exchange (ETDEWEB)

    Schmutz, Jeremy; Martin, Joel; Terry, Astrid; Couronne, Olivier; Grimwood, Jane; Lowry, Steve; Gordon, Laurie A.; Scott, Duncan; Xie,Gary; Huang, Wayne; Hellsten, Uffe; Tran-Gyamfi, Mary; She, Xinwei; Prabhakar, Shyam; Aerts, Andrea; Altherr, Michael; Bajorek, Eva; Black,Stacey; Branscomb, Elbert; Caoile, Chenier; Challacombe, Jean F.; Chan,Yee Man; Denys, Mirian; Detter, John C.; Escobar, Julio; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Israni, Sanjay; Jett, Jamie; Kadner,Kristen; Kimball, Heather; Kobayashi, Arthur; Lopez, Frederick; Lou,Yunian; Martinez, Diego; Medina, Catherine; Morgan, Jenna; Nandkeshwar,Richard; Noonan, James P.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Priest, James; Ramirez, Lucia; Retterer, James; Rodriguez, Alex; Rogers,Stephanie; Salamov, Asaf; Salazar, Angelica; Thayer, Nina; Tice, Hope; Tsai, Ming; Ustaszewska, Anna; Vo, Nu; Wheeler, Jeremy; Wu, Kevin; Yang,Joan; Dickson, Mark; Cheng, Jan-Fang; Eichler, Evan E.; Olsen, Anne; Pennacchio, Len A.; Rokhsar, Daniel S.; Richardson, Paul; Lucas, SusanM.; Myers, Richard M.; Rubin, Edward M.

    2004-08-01

    Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.

  13. The sequence and analysis of duplication rich human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J; Han, C; Gordon, L A; Terry, A; Prabhakar, S; She, X; Xie, G; Hellsten, U; Chan, Y M; Altherr, M; Couronne, O; Aerts, A; Bajorek, E; Black, S; Blumer, H; Branscomb, E; Brown, N; Bruno, W J; Buckingham, J; Callen, D F; Campbell, C S; Campbell, M L; Campbell, E W; Caoile, C; Challacombe, J F; Chasteen, L A; Chertkov, O; Chi, H C; Christensen, M; Clark, L M; Cohn, J D; Denys, M; Detter, J C; Dickson, M; Dimitrijevic-Bussod, M; Escobar, J; Fawcett, J J; Flowers, D; Fotopulos, D; Glavina, T; Gomez, M; Gonzales, E; Goodstein, D; Goodwin, L A; Grady, D L; Grigoriev, I; Groza, M; Hammon, N; Hawkins, T; Haydu, L; Hildebrand, C E; Huang, W; Israni, S; Jett, J; Jewett, P B; Kadner, K; Kimball, H; Kobayashi, A; Krawczyk, M; Leyba, T; Longmire, J L; Lopez, F; Lou, Y; Lowry, S; Ludeman, T; Manohar, C F; Mark, G A; McMurray, K L; Meincke, L J; Morgan, J; Moyzis, R K; Mundt, M O; Munk, A C; Nandkeshwar, R D; Pitluck, S; Pollard, M; Predki, P; Parson-Quintana, B; Ramirez, L; Rash, S; Retterer, J; Ricke, D O; Robinson, D; Rodriguez, A; Salamov, A; Saunders, E H; Scott, D; Shough, T; Stallings, R L; Stalvey, M; Sutherland, R D; Tapia, R; Tesmer, J G; Thayer, N; Thompson, L S; Tice, H; Torney, D C; Tran-Gyamfi, M; Tsai, M; Ulanovsky, L E; Ustaszewska, A; Vo, N; White, P S; Williams, A L; Wills, P L; Wu, J; Wu, K; Yang, J; DeJong, P; Bruce, D; Doggett, N A; Deaven, L; Schmutz, J; Grimwood, J; Richardson, P; Rokhsar, D S; Eichler, E E; Gilna, P; Lucas, S M; Myers, R M; Rubin, E M; Pennacchio, L A

    2005-04-06

    Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes, and 3 RNA pseudogenes. These genes include metallothionein, cadherin, and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. While the segmental duplications of chromosome 16 are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events likely to have had an impact on the evolution of primates and human disease susceptibility.

  14. Systematic analysis of human protein complexes identifies chromosome segregation proteins.

    Science.gov (United States)

    Hutchins, James R A; Toyoda, Yusuke; Hegemann, Björn; Poser, Ina; Hériché, Jean-Karim; Sykora, Martina M; Augsburg, Martina; Hudecz, Otto; Buschhorn, Bettina A; Bulkescher, Jutta; Conrad, Christian; Comartin, David; Schleiffer, Alexander; Sarov, Mihail; Pozniakovsky, Andrei; Slabicki, Mikolaj Michal; Schloissnig, Siegfried; Steinmacher, Ines; Leuschner, Marit; Ssykor, Andrea; Lawo, Steffen; Pelletier, Laurence; Stark, Holger; Nasmyth, Kim; Ellenberg, Jan; Durbin, Richard; Buchholz, Frank; Mechtler, Karl; Hyman, Anthony A; Peters, Jan-Michael

    2010-04-30

    Chromosome segregation and cell division are essential, highly ordered processes that depend on numerous protein complexes. Results from recent RNA interference screens indicate that the identity and composition of these protein complexes is incompletely understood. Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes, many of which had not or had only incompletely been characterized. This work has led to the discovery of previously unknown, evolutionarily conserved subunits of the anaphase-promoting complex and the gamma-tubulin ring complex--large complexes that are essential for spindle assembly and chromosome segregation. The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells.

  15. Chromosomal evolution in the Drosophila cardini group (Diptera: Drosophilidae): photomaps and inversion analysis.

    Science.gov (United States)

    Cordeiro, Juliana; De Toni, Daniela Cristina; da Silva, Gisele de Souza; Valente, Vera Lucia da Silva

    2014-10-01

    Detailed chromosome photomaps are the first step to develop further chromosomal analysis to study the evolution of the genetic architecture in any set of species, considering that chromosomal rearrangements, such as inversions, are common features of genome evolution. In this report, we analyzed inversion polymorphisms in 25 different populations belonging to six neotropical species in the cardini group: Drosophila cardini, D. cardinoides, D. neocardini, D. neomorpha, D. parthenogenetica and D. polymorpha. Furthermore, we present the first reference photomaps for the Neotropical D. cardini and D. parthenogenetica and improved photomaps for D. cardinoides, D. neocardini and D. polymorpha. We found 19 new inversions for these species. An exhaustive pairwise comparison of the polytene chromosomes was conducted for the six species in order to understand evolutionary patterns of their chromosomes.

  16. Novel Integrated Lab-on-Chip System for Chromosome Translocations Analysis

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Lange, Jacob Moresco; Shah, Pranjul Jaykumar

    2009-01-01

    This presentation will focus on the development of a chromosome total analysis system (C-TAS) starting from the design strategy and simulations to the integration into a final monolithic plug and play device. Individual modules which perform the sample preprocessing and analysis tasks like - cell...... isolation, cell culture, cell lysing, chromosome extraction and Fluorescence In-Situ Hybridization will be presented. How we solved connecting the individual chips and adjusting the microfluidic flows, by using simulations will be discussed....

  17. A sugar beet (Beta vulgaris L.) reference FISH karyotype for chromosome and chromosome-arm identification, integration of genetic linkage groups and analysis of major repeat family distribution.

    Science.gov (United States)

    Paesold, Susanne; Borchardt, Dietrich; Schmidt, Thomas; Dechyeva, Daryna

    2012-11-01

    We developed a reference karyotype for B. vulgaris which is applicable to all beet cultivars and provides a consistent numbering of chromosomes and genetic linkage groups. Linkage groups of sugar beet were assigned to physical chromosome arms by FISH (fluorescent in situ hybridization) using a set of 18 genetically anchored BAC (bacterial artificial chromosome) markers. Genetic maps of sugar beet were correlated to chromosome arms, and North-South orientation of linkage groups was established. The FISH karyotype provides a technical platform for genome studies and can be applied for numbering and identification of chromosomes in related wild beet species. The discrimination of all nine chromosomes by BAC probes enabled the study of chromosome-specific distribution of the major repetitive components of sugar beet genome comprising pericentromeric, intercalary and subtelomeric satellites and 18S-5.8S-25S and 5S rRNA gene arrays. We developed a multicolor FISH procedure allowing the identification of all nine sugar beet chromosome pairs in a single hybridization using a pool of satellite DNA probes. Fiber-FISH was applied to analyse five chromosome arms in which the furthermost genetic marker of the linkage group was mapped adjacently to terminal repetitive sequences on pachytene chromosomes. Only on two arms telomere arrays and the markers are physically linked, hence these linkage groups can be considered as terminally closed making the further identification of distal informative markers difficult. The results support genetic mapping by marker localization, the anchoring of contigs and scaffolds for the annotation of the sugar beet genome sequence and the analysis of the chromosomal distribution patterns of major families of repetitive DNA.

  18. Molecular cloning and analysis of breakpoints on ring chromosome 17 in a patient with autism.

    Science.gov (United States)

    Vazna, Alzbeta; Havlovicova, Marketa; Sedlacek, Zdenek

    2008-01-15

    The breakpoint junction on a ring chromosome 17 in a girl with autism, mental retardation, mild dysmorphism and neurofibromatosis was identified and analysed at the nucleotide level. The extent of the deleted segments was about 1.9 Mb on 17p and about 1.0 Mb on 17q. The structure of the junction between the 17p and 17q arms, especially the lack of significant homology between the juxtaposed genomic regions and the presence of short microhomology at the junction site, indicated non-homologous end joining as the most likely mechanism leading to the rearrangement. In addition to the 17p-17q junction itself, a de novo 1 kb deletion in a distance of 400 bp from the junction was identified, which arose most likely as a part of the rearrangement. The defect directly inactivated 3 genes, and the deleted terminal chromosome segments harboured 27 and 14 protein-coding genes from 17p and 17q, respectively. Several of the genes affected by the rearrangement are candidates for the symptoms observed in the patient. Additional rearrangements similar to the 1 kb deletion observed in our patient may remain undetected but can participate in the phenotype of patients with chromosomal aberrations. They can also be the reason for repeated failures to clone breakpoint junctions in other patients described in the literature.

  19. Genomic Imbalances in Neonates With Birth Defects: High Detection Rates by Using Chromosomal Microarray Analysis

    Science.gov (United States)

    Lu, Xin-Yan; Phung, Mai T.; Shaw, Chad A.; Pham, Kim; Neil, Sarah E.; Patel, Ankita; Sahoo, Trilochan; Bacino, Carlos A.; Stankiewicz, Pawel; Lee Kang, Sung-Hae; Lalani, Seema; Chinault, A. Craig; Lupski, James R.; Cheung, Sau W.; Beaudet, Arthur L.

    2009-01-01

    OBJECTIVES Our aim was to determine the frequency of genomic imbalances in neonates with birth defects by using targeted array-based comparative genomic hybridization, also known as chromosomal microarray analysis. METHODS Between March 2006 and September 2007, 638 neonates with various birth defects were referred for chromosomal microarray analysis. Three consecutive chromosomal microarray analysis versions were used: bacterial artificial chromosome-based versions V5 and V6 and bacterial artificial chromosome emulated oligonucleotide-based version V6 Oligo. Each version had targeted but increasingly extensive genomic coverage and interrogated >150 disease loci with enhanced coverage in genomic rearrangement-prone pericentromeric and subtelomeric regions. RESULTS Overall, 109 (17.1%) patients were identified with clinically significant abnormalities with detection rates of 13.7%, 16.6%, and 19.9% on V5, V6, and V6 Oligo, respectively. The majority of these abnormalities would not be defined by using karyotype analysis. The clinically significant detection rates by use of chromosomal microarray analysis for various clinical indications were 66.7% for “possible chromosomal abnormality” ± “others” (other clinical indications), 33.3% for ambiguous genitalia ± others, 27.1% for dysmorphic features + multiple congenital anomalies ± others, 24.6% for dysmorphic features ± others, 21.8% for congenital heart disease ± others, 17.9% for multiple congenital anomalies ± others, and 9.5% for the patients referred for others that were different from the groups defined. In all, 16 (2.5%) patients had chromosomal aneuploidies, and 81 (12.7%) patients had segmental aneusomies including common microdeletion or microduplication syndromes and other genomic disorders. Chromosomal mosaicism was found in 12 (1.9%) neonates. CONCLUSIONS Chromosomal microarray analysis is a valuable clinical diagnostic tool that allows precise and rapid identification of genomic imbalances

  20. Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.

    Directory of Open Access Journals (Sweden)

    Yuichi Shiraishi

    Full Text Available Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV-related hepatocellular carcinomas (HCCs and their matched controls. Comparison of whole genome sequence (WGS and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3, and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.

  1. Complex aberrations in lymphocytes exposed to mixed beams of (241)Am alpha particles and X-rays.

    Science.gov (United States)

    Staaf, Elina; Deperas-Kaminska, Marta; Brehwens, Karl; Haghdoost, Siamak; Czub, Joanna; Wojcik, Andrzej

    2013-08-30

    Modern radiotherapy treatment modalities are associated with undesired out-of-field exposure to complex mixed beams of high and low energy transfer (LET) radiation that can give rise to secondary cancers. The biological effectiveness of mixed beams is not known. The aim of the investigation was the analysis of chromosomal damage in human peripheral blood lymphocytes (PBL) exposed to a mixed beam of X-rays and alpha particles. Using a dedicated exposure facility PBL were exposed to increasing doses of alpha particles (from (241)Am), X-rays and a mixture of both. Chromosomal aberrations were analysed in chromosomes 2, 8 and 14 using fluorescence in situ hybridisation. The found and expected frequencies of simple and complex aberrations were compared. Simple aberrations showed linear dose-response relationships with doses. A higher than expected frequency of simple aberrations was only observed after the highest mixed beam dose. A linear-quadratic dose response curve for complex aberrations was observed after mixed-beam exposure. Higher than expected frequencies of complex aberrations were observed for the two highest doses. Both the linear-quadratic dose-response relationship and the calculation of expected frequencies show that exposure of PBL to mixed beams of high and low LET radiation leads to a higher than expected frequency of complex-type aberrations. Because chromosomal changes are associated with cancer induction this result may imply that the cancer risk of exposure to mixed beams in radiation oncology may be higher than expected based on the additive action of the individual dose components.

  2. Mosaic small supernumerary marker chromosome 1 at amniocentesis: prenatal diagnosis, molecular genetic analysis and literature review.

    Science.gov (United States)

    Chen, Chih-Ping; Chen, Ming; Su, Yi-Ning; Huang, Jian-Pei; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Chang, Shun-Ping; Chen, Yu-Ting; Lee, Chen-Chi; Chen, Li-Feng; Pan, Chen-Wen; Wang, Wayseen

    2013-10-15

    We present prenatal diagnosis and molecular cytogenetic analysis of mosaic small supernumerary marker chromosome 1 [sSMC(1)]. We review the literature of sSMC(1) at amniocentesis and chromosome 1p21.1-p12 duplication syndrome. We discuss the genotype-phenotype correlation of the involved genes of ALX3, RBM15, NTNG1, SLC25A24, GPSM2, TBX15 and NOTCH2 in this case.

  3. The sequence and analysis of duplication rich human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Joel; Han, Cliff; Gordon, Laurie A.; Terry, Astrid; Prabhakar, Shyam; She, Xinwei; Xie, Gary; Hellsten, Uffe; Man Chan, Yee; Altherr, Michael; Couronne, Olivier; Aerts, Andrea; Bajorek, Eva; Black, Stacey; Blumer, Heather; Branscomb, Elbert; Brown, Nancy C.; Bruno, William J.; Buckingham, Judith M.; Callen, David F.; Campbell, Connie S.; Campbell, Mary L.; Campbell, Evelyn W.; Caoile, Chenier; Challacombe, Jean F.; Chasteen, Leslie A.; Chertkov, Olga; Chi, Han C.; Christensen, Mari; Clark, Lynn M.; Cohn, Judith D.; Denys, Mirian; Detter, John C.; Dickson, Mark; Dimitrijevic-Bussod, Mira; Escobar, Julio; Fawcett, Joseph J.; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Goodwin, Lynne A.; Grady, Deborah L.; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Hildebrand, Carl E.; Huang, Wayne; Israni, Sanjay; Jett, Jamie; Jewett, Phillip E.; Kadner, Kristen; Kimball, Heather; Kobayashi, Arthur; Krawczyk, Marie-Claude; Leyba, Tina; Longmire, Jonathan L.; Lopez, Frederick; Lou, Yunian; Lowry, Steve; Ludeman, Thom; Mark, Graham A.; Mcmurray, Kimberly L.; Meincke, Linda J.; Morgan, Jenna; Moyzis, Robert K.; Mundt, Mark O.; Munk, A. Christine; Nandkeshwar, Richard D.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Parson-Quintana, Beverly; Ramirez, Lucia; Rash, Sam; Retterer, James; Ricke, Darryl O.; Robinson, Donna L.; Rodriguez, Alex; Salamov, Asaf; Saunders, Elizabeth H.; Scott, Duncan; Shough, Timothy; Stallings, Raymond L.; Stalvey, Malinda; Sutherland, Robert D.; Tapia, Roxanne; Tesmer, Judith G.; Thayer, Nina; Thompson, Linda S.; Tice, Hope; Torney, David C.; Tran-Gyamfi, Mary; Tsai, Ming; Ulanovsky, Levy E.; Ustaszewska, Anna; Vo, Nu; White, P. Scott; Williams, Albert L.; Wills, Patricia L.; Wu, Jung-Rung; Wu, Kevin; Yang, Joan; DeJong, Pieter; Bruce, David; Doggett, Norman; Deaven, Larry; Schmutz, Jeremy; Grimwood, Jane; Richardson, Paul; et al.

    2004-08-01

    We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility.

  4. Analysis of Recombination and Chromosome Structure during Yeast Meiosis.

    Science.gov (United States)

    Börner, G Valentin; Cha, Rita S

    2015-11-02

    Meiosis is a diploid-specific differentiation program that consists of a single round of genome duplication followed by two rounds of chromosome segregation. These events result in halving of the genetic complement, which is a requirement for formation of haploid reproductive cells (i.e., spores in yeast and gametes in animals and plants). During meiosis I, homologous maternal and paternal chromosomes (homologs) pair and separate, whereas sister chromatids remain connected at the centromeres and separate during the second meiotic division. In most organisms, accurate homolog disjunction requires crossovers, which are formed as products of meiotic recombination. For the past two decades, studies of yeast meiosis have provided invaluable insights into evolutionarily conserved mechanisms of meiosis.

  5. The Sequence and Analysis of Duplication Rich Human Chromosome 16

    Science.gov (United States)

    Martin, Joel; Han, Cliff; Gordon, Laurie A.; Terry, Astrid; Prabhakar, Shyam; She, Xinwei; Xie, Gary; Hellsten, Uffe; Man Chan, Yee; Altherr, Michael; Couronne, Olivier; Aerts, Andrea; Bajorek, Eva; Black, Stacey; Blumer, Heather; Branscomb, Elbert; Brown, Nancy C.; Bruno, William J.; Buckingham, Judith M.; Callen, David F.; Campbell, Connie S.; Campbell, Mary L.; Campbell, Evelyn W.; Caoile, Chenier; Challacombe, Jean F.; Chasteen, Leslie A.; Chertkov, Olga; Chi, Han C.; Christensen, Mari; Clark, Lynn M.; Cohn, Judith D.; Denys, Mirian; Detter, John C.; Dickson, Mark; Dimitrijevic-Bussod, Mira; Escobar, Julio; Fawcett, Joseph J.; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Goodwin, Lynne A.; Grady, Deborah L.; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Hildebrand, Carl E.; Huang, Wayne; Israni, Sanjay; Jett, Jamie; Jewett, Phillip E.; Kadner, Kristen; Kimball, Heather; Kobayashi, Arthur; Krawczyk, Marie-Claude; Leyba, Tina; Longmire, Jonathan L.; Lopez, Frederick; Lou, Yunian; Lowry, Steve; Ludeman, Thom; Mark, Graham A.; Mcmurray, Kimberly L.; Meincke, Linda J.; Morgan, Jenna; Moyzis, Robert K.; Mundt, Mark O.; Munk, A. Christine; Nandkeshwar, Richard D.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Parson-Quintana, Beverly; Ramirez, Lucia; Rash, Sam; Retterer, James; Ricke, Darryl O.; Robinson, Donna L.; Rodriguez, Alex; Salamov, Asaf; Saunders, Elizabeth H.; Scott, Duncan; Shough, Timothy; Stallings, Raymond L.; Stalvey, Malinda; Sutherland, Robert D.; Tapia, Roxanne; Tesmer, Judith G.; Thayer, Nina; Thompson, Linda S.; Tice, Hope; Torney, David C.; Tran-Gyamfi, Mary; Tsai, Ming; Ulanovsky, Levy E.; Ustaszewska, Anna; Vo, Nu; White, P. Scott; Williams, Albert L.; Wills, Patricia L.; Wu, Jung-Rung; Wu, Kevin; Yang, Joan; DeJong, Pieter; Bruce, David; Doggett, Norman; Deaven, Larry; Schmutz, Jeremy; Grimwood, Jane; Richardson, Paul; et al.

    2004-01-01

    We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility.

  6. Cytogenetic analysis of quinoa chromosomes using nanoscale imaging and spectroscopy techniques

    Science.gov (United States)

    Yangquanwei, Zhong; Neethirajan, Suresh; Karunakaran, Chithra

    2013-11-01

    Here we present a high-resolution chromosomal spectral map derived from synchrotron-based soft X-ray spectromicroscopy applied to quinoa species. The label-free characterization of quinoa metaphase chromosomes shows that it consists of organized substructures of DNA-protein complex. The analysis of spectra of chromosomes using the scanning transmission X-ray microscope (STXM) and its superposition of the pattern with the atomic force microscopy (AFM) and scanning electron microscopy (SEM) images proves that it is possible to precisely locate the gene loci and the DNA packaging inside the chromosomes. STXM has been successfully used to distinguish and quantify the DNA and protein components inside the quinoa chromosomes by visualizing the interphase at up to 30-nm spatial resolution. Our study represents the successful attempt of non-intrusive interrogation and integrating imaging techniques of chromosomes using synchrotron STXM and AFM techniques. The methodology developed for 3-D imaging of chromosomes with chemical specificity and temporal resolution will allow the nanoscale imaging tools to emerge from scientific research and development into broad practical applications such as gene loci tools and biomarker libraries.

  7. Cytogenetic analysis of quinoa chromosomes using nanoscale imaging and spectroscopy techniques.

    Science.gov (United States)

    Yangquanwei, Zhong; Neethirajan, Suresh; Karunakaran, Chithra

    2013-01-01

    Here we present a high-resolution chromosomal spectral map derived from synchrotron-based soft X-ray spectromicroscopy applied to quinoa species. The label-free characterization of quinoa metaphase chromosomes shows that it consists of organized substructures of DNA-protein complex. The analysis of spectra of chromosomes using the scanning transmission X-ray microscope (STXM) and its superposition of the pattern with the atomic force microscopy (AFM) and scanning electron microscopy (SEM) images proves that it is possible to precisely locate the gene loci and the DNA packaging inside the chromosomes. STXM has been successfully used to distinguish and quantify the DNA and protein components inside the quinoa chromosomes by visualizing the interphase at up to 30-nm spatial resolution. Our study represents the successful attempt of non-intrusive interrogation and integrating imaging techniques of chromosomes using synchrotron STXM and AFM techniques. The methodology developed for 3-D imaging of chromosomes with chemical specificity and temporal resolution will allow the nanoscale imaging tools to emerge from scientific research and development into broad practical applications such as gene loci tools and biomarker libraries.

  8. Plummer Vinson syndrome in a male and his chromosomal study – A case report

    Directory of Open Access Journals (Sweden)

    Santosh K. Swain

    2015-07-01

    Full Text Available Plummer Vinson syndrome (PVS is a triad of iron deficiency anemia, esophageal web and dysphagia. The exact etiology of PVS remains controversial but it has been associated with nutritional deficiency, autoimmune disorders, hereditary factors and remarkable high female predominance. This paper reports an atypical presentation of PVS in a 38 year old Indian male with special emphasis given on chromosomal analysis. Chromosomal assessment is done as it is a good predictor of the possibility of development of post-cricoid carcinoma (PCC in patients with PVS. Chromosomal aberrations like translocation, gain, loss, breakpoints and duplications are studied and they revealed normal male chromosomal pairing.

  9. A new chromosome fluorescence banding technique combining DAPI staining with image analysis in plants.

    Science.gov (United States)

    Liu, Jing Yu; She, Chao Wen; Hu, Zhong Li; Xiong, Zhi Yong; Liu, Li Hua; Song, Yun Chun

    2004-08-01

    In this study, a new chromosome fluorescence banding technique was developed in plants. The technique combined 4',6-diamidino-2-phenylindole (DAPI) staining with software analysis including three-dimensional imaging after deconvolution. Clear multiple and adjacent DAPI bands like G-bands were obtained by this technique in the tested species including Hordeum vulgare L., Oryza officinalis, Wall & Watt, Triticum aestivum L., Lilium brownii, Brown, and Vicia faba L. During mitotic metaphase, the numbers of bands for the haploid genomes of these species were about 185, 141, 309, 456 and 194, respectively. Reproducibility analysis demonstrated that banding patterns within a species were stable at the same mitotic stage and they could be used for identifying specific chromosomes and chromosome regions. The band number fluctuated: the earlier the mitotic stage, the greater the number of bands. The technique enables genes to be mapped onto specific band regions of the chromosomes by only one fluorescence in situ hybridisation (FISH) step with no chemical banding treatments. In this study, the 45S and 5S rDNAs of some tested species were located on specific band regions of specific chromosomes and they were all positioned at the interbands with the new technique. Because no chemical banding treatment was used, the banding patterns displayed by the technique should reflect the natural conformational features of chromatin. Thus it could be expected that this technique should be suitable for all eukaryotes and would have widespread utility in chromosomal structure analysis and physical mapping of genes.

  10. Nonparaxial Fourier propagation tool for aberration analysis and point spread function calculation

    Science.gov (United States)

    Cain, Stephen C.; Watts, Tatsuki

    2016-08-01

    This paper describes a Fourier propagator for computing the impulse response of an optical system, while including terms ignored in Fresnel and Fraunhofer calculations. The propagator includes a Rayleigh-Sommerfeld diffraction formula calculation from a distant point through the optical system to its image point predicted by geometric optics. The propagator then approximates the neighboring field points via the traditional binomial approximation of the Taylor series expansion around that field point. This technique results in a propagator that combines the speed of a Fourier transform operation with the accuracy of the Rayleigh-Sommerfeld diffraction formula calculation and extends Fourier optics to cases that are nonparaxial. The proposed propagator facilitates direct calculation of aberration coefficients, making it more versatile than the angular spectrum propagator. Bounds on the phase error introduced by the approximations are derived, which show that it should be more widely applicable than the Fresnel propagator. Guidance on how to sample the pupil and detector planes of a simulated imaging system is provided. This report concludes by showing examples of diffraction calculations for a laboratory setup and comparing them to measured diffraction patterns to demonstrate the utility of the propagator.

  11. Physical mapping, expression analysis and polymorphism survey of resistance gene analogues on chromosome 11 of rice

    Indian Academy of Sciences (India)

    Irfan A Ghazi; Prem S Srivastava; Vivek Dalal; Kishor Gaikwad; Ashok K Singh; Tilak R Sharma; Nagendra K Singh; Trilochan Mohapatra

    2009-06-01

    Rice is the first cereal genome with a finished sequence and a model crop that has important syntenic relationships with other cereal species. The objectives of our study were to identify resistance gene analogue (RGA) sequences from chromosome 11 of rice, understand their expression in other cereals and dicots by in silico analysis, determine their presence on other rice chromosomes, and evaluate the extent of polymorphism and actual expression in a set of rice genotypes. A total of 195 RGAs were predicted and physically localised. Of these, 91.79% expressed in rice, and 51.28% expressed in wheat, which was the highest among other cereals. Among monocots, sugarcane showed the highest (78.92%) expression, while among dicots, RGAs were maximally expressed in Arabidopsis (11.79%). Interestingly, two of the chromosome 11-specific RGAs were found to be expressing in all the organisms studied. Eighty RGAs of chromosome 11 had significant homology with chromosome 12, which was the maximum among all the rice chromosomes. Thirty-one per cent of the RGAs used in polymerase chain reaction (PCR) amplification showed polymorphism in a set of rice genotypes. Actual gene expression analysis revealed post-inoculation induction of one RGA in the rice line IRBB-4 carrying the bacterial blight resistance gene Xa-4. Our results have implications for the development of sequence-based markers and functional validation of specific RGAs in rice.

  12. DCB - DNA and Chromosome Aberrations Research

    Science.gov (United States)

    Part of NCI's Division of Cancer Biology's research portfolio, this research area is focused on making clear the genetic and epigenetic mechanisms of tumorigenesis and mechanisms of chemical and physical carcinogenesis.

  13. Molecular Network Analysis Suggests Aberrant CREB-Mediated Gene Regulation in the Alzheimer Disease Hippocampus

    Directory of Open Access Journals (Sweden)

    Jun-ichi Satoh

    2009-01-01

    Full Text Available The pathogenesis of Alzheimer disease (AD involves the complex interaction between genetic and environmental factors affecting multiple cellular pathways. Recent advances in systems biology provide a system-level understanding of AD by elucidating the genome-wide molecular interactions. By using KeyMolnet, a bioinformatics tool for analyzing molecular interactions on the curated knowledgebase, we characterized molecular network of 2,883 all stages of AD-related genes (ADGs and 559 incipient AD-related genes (IADGs identified by global gene expression profiling of the hippocampal CA1 region of AD brains in terms of significant clinical and pathological correlations (Blalock et al., Proc Natl Acad Sci USA 101: 2173-2178, 2004. By the common upstream search, KeyMolnet identified cAMP-response element-binding protein (CREB as the principal transcription factor exhibiting the most significant relevance to molecular networks of both ADGs and IADGs. The CREB-regulated transcriptional network included upregulated and downregulated sets of ADGs and IADGs, suggesting an involvement of generalized deregulation of the CREB signaling pathway in the pathophysiology of AD, beginning at the early stage of the disease. To verify the in silico observations in vivo, we conducted immunohistochemical studies of 11 AD and 13 age-matched control brains by using anti-phoshorylated CREB (pCREB antibody. An abnormal accumulation of pCREB imunoreactivity was identified in granules of granulovacuolar degeneration (GVD in the hippocampal neurons of AD brains. These observations suggest that aberrant CREB-mediated gene regulation serves as a molecular biomarker of AD-related pathological processes, and support the hypothesis that sequestration of pCREB in GVD granules is in part responsible for deregulation of CREB-mediated gene expression in AD hippocampus.

  14. From DNA Copy Number to Gene Expression: Local aberrations, Trisomies and Monosomies

    Science.gov (United States)

    Shay, Tal

    aberration profile' is then combined with chromosomal arm status (gain/loss) to define a succinct genomic signature for each tumor. Unsupervised clustering of the samples based on these genomic signatures can reveal novel tumor subtypes. This approach was applied to datasets from three types of brain tumors: Glioblastoma, Medulloblastoma and Neuroblastoma, and identified a new subtype in Medulloblastoma, characterized by many chromosomal aberrations. Elucidating the transcriptional effect of monosomy and trisomy. Trisomy and monosomy are expected to impact the expression of genes that are located on the affected chromosome. Analysis of several cancer datasets revealed that not all the genes on the aberrant chromosome are affected by the change of copy number. Affected genes exhibit a wide range of expression changes with varying penetrance. Specifically, (1) The effect of trisomy is much more conserved among individuals than the effect of monosomy and (2) the expression level of a gene in the diploid is significantly correlated with the level of change between the diploid and the trisomy or monosomy.

  15. Chromosome region-specific libraries for human genome analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Fa-Ten.

    1991-01-01

    We have made important progress since the beginning of the current grant year. We have further developed the microdissection and PCR- assisted microcloning techniques using the linker-adaptor method. We have critically evaluated the microdissection libraries constructed by this microtechnology and proved that they are of high quality. We further demonstrated that these microdissection clones are useful in identifying corresponding YAC clones for a thousand-fold expansion of the genomic coverage and for contig construction. We are also improving the technique of cloning the dissected fragments in test tube by the TDT method. We are applying both of these PCR cloning technique to human chromosomes 2 and 5 to construct region-specific libraries for physical mapping purposes of LLNL and LANL. Finally, we are exploring efficient procedures to use unique sequence microclones to isolate cDNA clones from defined chromosomal regions as valuable resources for identifying expressed gene sequences in the human genome. We believe that we are making important progress under the auspices of this DOE human genome program grant and we will continue to make significant contributions in the coming year. 4 refs., 4 figs.

  16. Chromosomal imbalances in nasopharyngeal carcinoma: a meta-analysis of comparative genomic hybridization results

    Directory of Open Access Journals (Sweden)

    Jin Ping

    2006-01-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a highly prevalent disease in Southeast Asia and its prevalence is clearly affected by genetic background. Various theories have been suggested for its high incidence in this geographical region but to these days no conclusive explanation has been identified. Chromosomal imbalances identifiable through comparative genomic hybridization may shed some light on common genetic alterations that may be of relevance to the onset and progression of NPC. Review of the literature, however, reveals contradictory results among reported findings possibly related to factors associated with patient selection, stage of disease, differences in methodological details etc. To increase the power of the analysis and attempt to identify commonalities among the reported findings, we performed a meta-analysis of results described in NPC tissues based on chromosomal comparative genomic hybridization (CGH. This meta-analysis revealed consistent patters in chromosomal abnormalities that appeared to cluster in specific "hot spots" along the genome following a stage-dependent progression.

  17. Chromosomes and karyotype analysis of a liver fluke, Opisthorchis viverrini, by scanning electron microscopy.

    Science.gov (United States)

    Kaewkong, Worasak; Choochote, Wej; Kanla, Pipatpong; Maleewong, Wanchai; Intapan, Pewpan M; Wongkham, Sopit; Wongkham, Chaisiri

    2012-09-01

    Opisthorchis viverrini, a human liver fluke, has been categorized as the carcinogenic organism according to the strong association with carcinogenesis of cholangiocarcinoma (CCA). The infection of this food-borne parasite is a major impact on the health of humans, especially CCA patients in the northeast of Thailand. Taxonomy, morphology, epidemiology and molecular study of O. viverrini have been publicized increasingly but the precise karyotypic study is still incomplete. In this study, the chromosomes of O. viverrini were prepared from the testes of adult worms retrieved from metacercariae infected-hamsters. The chromosomes of O. viverrini were identified in haploid (n=6) meiotic metaphase and in diploid (2n=12) mitotic metaphase by light microscopy. The chromosome number, length and nomenclature of each chromosome were determined by scanning electron microscopy. The six chromosomes consist of one large-sized metacentric, one medium-sized metacentric, two small-sized metacentric, one small-sized submetacentric and one small-sized acrocentric chromosomes with the lengths of 2.84±0.03, 2.12±0.10, 1.71±0.13, 1.44±0.04, 1.23±0.03 and 0.84±0.13 μm, respectively. This is the first karyotype analysis of O. viverrini with defined complete nomenclature.

  18. High-resolution mapping and transcriptional activity analysis of chicken centromere sequences on giant lampbrush chromosomes.

    Science.gov (United States)

    Krasikova, Alla; Fukagawa, Tatsuo; Zlotina, Anna

    2012-12-01

    Exploration into morphofunctional organisation of centromere DNA sequences is important for understanding the mechanisms of kinetochore specification and assembly. In-depth epigenetic analysis of DNA fragments associated with centromeric nucleosome proteins has demonstrated unique features of centromere organisation in chicken karyotype: there are both mature centromeres, which comprise chromosome-specific homogeneous arrays of tandem repeats, and recently evolved primitive centromeres, which consist of non-tandemly organised DNA sequences. In this work, we describe the arrangement and transcriptional activity of chicken centromere repeats for Cen1, Cen2, Cen3, Cen4, Cen7, Cen8, and Cen11 and non-repetitive centromere sequences of chromosomes 5, 27, and Z using highly elongated lampbrush chromosomes, which are characteristic of the diplotene stage of oogenesis. The degree of chromatin packaging and fine spatial organisations of tandemly repetitive and non-tandemly repetitive centromeric sequences significantly differ at the lampbrush stage. Using DNA/RNA FISH, we have demonstrated that during the lampbrush stage, DNA sequences are transcribed within the centromere regions of chromosomes that lack centromere-specific tandem repeats. In contrast, chromosome-specific centromeric repeats Cen1, Cen2, Cen3, Cen4, Cen7, Cen8, and Cen11 do not demonstrate any transcriptional activity during the lampbrush stage. In addition, we found that CNM repeat cluster localises adjacent to non-repetitive centromeric sequences in chicken microchromosome 27 indicating that centromere region in this chromosome is repeat-rich. Cross-species FISH allowed localisation of the sequences homologous to centromeric DNA of chicken chromosomes 5 and 27 in centromere regions of quail orthologous chromosomes.

  19. Modified C-band technique for the analysis of chromosome abnormalities in irradiated human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, Akifumi; Akiyama, Miho; Yamada, Yuji [Biodosimetry Section, Department of Radiation Dosimetry, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Yoshida, Mitsuaki A., E-mail: myoshida@cc.hirosaki-u.ac.jp [Biodosimetry Section, Department of Radiation Dosimetry, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2011-10-15

    A modified C-band technique was developed in order to analyze more accurately dicentric, tricentric, and ring chromosomes in irradiated human peripheral lymphocytes. Instead of the original method relying on treatment with barium hydroxide Ba(OH){sub 2}, C-bands were obtained using a modified form of heat treatment in formamide followed with DAPI staining. This method was tentatively applied to the analysis of dicentric chromosomes in irradiated human lymphocytes to examine its availability. The frequency of dicentric chromosome was almost the same with conventional Giemsa staining and the modified C-band technique. In the analysis using Giemsa staining, it is relatively difficult to identify the centromere on the elongated chromosomes, over-condensed chromosomes, fragment, and acentric ring. However, the modified C-band method used in this study makes it easier to identify the centromere on such chromosomes than with the use of Giemsa staining alone. Thus, the modified C-band method may give more information about the location of the centromere. Therefore, this method may be available and more useful for biological dose estimation due to the analysis of the dicentric chromosome in human lymphocytes exposed to the radiation. Furthermore, this method is simpler and faster than the original C-band protocol and fluorescence in situ hybridization (FISH) method with the centromeric DNA probe. - Highlights: > The dicentric (dic) assay is the most effective for the radiation biodosimetry. > It is important to recognize the centromere of the dic. > We improved a C-band technique based on heat denaturation. > This technique enables the accurate detection of a centromere. > This method may be available and more useful for biological dose estimation.

  20. A simple and rapid fluorescence in situ hybridization microwave protocol for reliable dicentric chromosome analysis.

    Science.gov (United States)

    Cartwright, Ian M; Genet, Matthew D; Kato, Takamitsu A

    2013-03-01

    Fluorescence in situhybridization (FISH) is an extremely effective and sensitive approach to analyzing chromosome aberrations. Until recently, this procedure has taken multiple days to complete. The introduction of telomeric and centromeric peptide nucleic acid (PNA) probes has reduced the procedure's duration to several hours, but the protocols still call for a high temperature (80-90°C) step followed by 1-3 h of hybridization. The newest method to speed up the FISH protocol is the use of a microwave to shorten the heating element to less than a minute; however this protocol still calls for a 1-h hybridization period. We have utilized PNA centromere/telomere probes in conjunction with a microwave oven to show telomere and centromere staining in as little as 30 s. We have optimized the hybridization conditions to increase the sensitivity and effectiveness of the new protocol and can effectively stain chromosomes in 2 min and 30 s of incubation. We have found that our new approach to FISH produces extremely clear and distinct signals. Radiation-induced dicentric formation in mouse and human fibroblast cells was analyzed by two individual scorers and the observed dicentrics matched very well.

  1. Sequence and expression analysis of gaps in human chromosome 20

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Seemann, Stefan; Mang, Yuan;

    2012-01-01

    The finished human genome-assemblies comprise several hundred un-sequenced euchromatic gaps, which may be rich in long polypurine/polypyrimidine stretches. Human chromosome 20 (chr 20) currently has three unfinished gaps remaining on its q-arm. All three gaps are within gene-dense regions and....../or overlap disease-associated loci, including the DLGAP4 locus. In this study, we sequenced ~99% of all three unfinished gaps on human chr 20, determined their complete genomic sizes and assessed epigenetic profiles using a combination of Sanger sequencing, mate pair paired-end high-throughput sequencing...... and chromatin, methylation and expression analyses. We found histone 3 trimethylated at Lysine 27 to be distributed across all three gaps in immortalized B-lymphocytes. In one gap, five novel CpG islands were predominantly hypermethylated in genomic DNA from peripheral blood lymphocytes and human cerebellum...

  2. A Semi-Closed Device for Chromosome Spreading for Cytogenetic Analysis

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Mednova, Olga; Vedarethinam, Indumathi;

    2014-01-01

    Metaphase chromosome spreading is the most crucial step required for successful karyotyping and FISH analysis. These two techniques are routinely used in cytogenetics to assess the chromosome abnormalities. The spreading process has been studied for years but it is still considered an art more than......, and thus allow for better quality spreads. Further cytogenetic analysis depends on the quality of the spreads, which is dependent on the skills of the personnel and is thus limited to laboratory settings. Here, we present a semi-closed microfluidic chip for preparation of the metaphase spreads on a glass...

  3. Analysis of the peripheral blood chromosomal karyotype from 780 genetic consultants%780例遗传咨询者外周血染色体核型分析

    Institute of Scientific and Technical Information of China (English)

    朱蕊; 曾爱群; 杜晶春

    2016-01-01

    Objective To evaluate the role of peripheral blood chromosomal karyotype analysis in disease diag-nosis of chromosomal disorder. Methods The cytogenetic karyotype of peripheral blood derived from 780 genetic counseling cases were analyzed during January 2013 to August 2015. Results There were 30 cases of chromosomal ab-errations to be detected and the abnormal rate was 3.85%, including 12 cases of numeric aberrations and 18 cases of structural aberrations. In neonatal disorder group, developmental disorder group and infertile group, the main type of chromosomal aberrations was the numeric abnormality, and it was mainly structural abnormality in the abnormal gesta-tion and birth group. Conclusion The detection of the peripheral blood chromosomal karyotype may play an important role in the diagnosis of neonatal disorder, developmental disorder, infertility and abnormal gestation and birth.%目的:探讨外周血染色体核型分析在染色体病诊断中的价值。方法对2013年1月至2015年8月期间来我院进行遗传咨询的780例患者行外周血染色体核型分析。结果780例患者中共检出异常核型30例,异常核型检出率为3.85%,其中染色体数目异常12例,染色体结构异常18例,新生儿表现异常、生长发育异常和不孕不育中以染色体数目异常为主,不良孕产史中以染色体结构异常为主。结论外周血染色体核型分析对染色体病导致的新生儿表现异常、生长发育异常、不孕不育和不良孕产史等疾病的诊断具有重要价值。

  4. Study on unstable chromosome aberrations in human Epstein-Barr virus-lymphocytes induced by heavy ion 12 C%碳-12重离子诱导正常人疱疹病毒-转化淋巴细胞非稳定性染色体畸变研究

    Institute of Scientific and Technical Information of China (English)

    张睿凤; 刘建功; 刘红艳; 王超; 邢利红; 张淑贤; 段志凯

    2015-01-01

    目的:探讨碳-12(12C)重离子诱导正常人疱疹病毒(EBV)-转化淋巴细胞染色体畸变的生物效应。方法以照射能量为165 MeV/u,剂量率为0.3~0.5 Gy/min,照射剂量分别为0.0、0.1、0.3、0.5、0.7、1.0和2.0 Gy的12 C重离子来辐照对数增长期正常人EBV-淋巴细胞,分别培养至照后48、72 h收获细胞(分别设为48和72 h组),收获前2h加秋水仙素,制片,计算染色体畸变细胞率、“双+环”畸变率以及总非稳定性畸变率,并拟合剂量-效应回归方程。结果48 h组的“双+环”畸变率在0.3~2.0 Gy约为72 h组的2倍。2组染色体畸变细胞数量均随照射剂量的增加而增加,呈剂量-效应关系(P<0.01)。48 h组的畸变细胞率、“双+环”畸变率以及非稳定性畸变率在0.0~2.0 Gy的剂量-效应回归方程分别为Y=0.024+0.708 D-0.175 D2[校正决定系数( R2c )=0.963,P<0.01]、Y=-0.034+0.531 D-0.128 D2(R2c =0.950,P<0.01)和Y=0.009+0.868 D-0.089 D2(R2c =0.980,P<0.01);72 h组的上述指标分别为Y=0.039+0.388 D-0.084 D2( R2c =0.976,P<0.01)、Y=-0.013+0.247 D-0.062 D2(R2c =0.900,P<0.01)和Y=0.034+0.490 D-0.046 D2(R2c =0.987,P<0.01)。结论12C重离子诱导正常人EBV-转化淋巴细胞畸变随照射剂量增加而增加;染色体畸变在0.0~2.0 Gy存在一定剂量-效应关系,符合二次多项式回归模型。%Objective To study the biological effect of chromosome aberrations in human Epstein-Barr virus-lymphocytes induced by heavy ion 12 C irradiation.Methods Human Epstein-Barr virus-lymphocytes in exponential phase were exposed to heavy ion 12 C at the irradiation doses of 0.0, 0.1, 0.3, 0.5, 0.7, 1.0 and 2.0 Gy respectively, with the beam energy was 165 MeV/u and the dose rate was 0.3-0.5 Gy/min.The division metaphase cells were collected after different

  5. Gonadoblastomas in 45,X/46,XY mosaicism: analysis of Y chromosome distribution by fluorescence in situ hybridization.

    Science.gov (United States)

    Iezzoni, J C; Von Kap-Herr, C; Golden, W L; Gaffey, M J

    1997-08-01

    Gonadoblastomas are composed of nests of neoplastic germ cells and sex cord derivatives surrounded by ovarian-type stroma. These tumors are found almost exclusively in persons with gonadal dysgenesis associated with a Y chromosome or Y chromosome fragment, and accordingly, the Y chromosome has been implicated in gonadoblastoma oncogenesis. To evaluate this association, we used two-color fluorescence in situ hybridization with chromosome-specific probes to determine the distribution of the X and Y chromosomes in the tumor nests and surrounding stromal cells in paraffin tissue sections of three gonadoblastomas in two patients with gonadal dysgenesis and 45,X/46,XY mosaicism. Statistical analysis of the data from the fluorescence in situ hybridization demonstrated that in all three gonadoblastomas, the proportion of nuclei with a Y chromosome signal was significantly higher in the tumor cells than in the nontumoral cells of the surrounding stroma (P<.001). These results suggest that Y chromosome material participates in gonadoblastoma tumorigenesis.

  6. Linkage analysis of chromosome 14 and essential hypertension in Chinese population

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wei-yan; HUANG Jian-feng; GE Dong-liang; SU Shao-yong; LI Biao; GU Dong-feng

    2005-01-01

    Background Hypertension is a complex biological trait that influenced by multiple factors. The encouraging results for hypertension research showed that the linkage analysis can be used to replicate other studies and discover new genetic risk factors. Previous studies linked human chromosome 14 to essential hypertension or blood pressure traits. With a Chinese population, we tried to replicate these findings. Methods A linkage scan was performed on chromosome 14 with 14-microsatellite markers with a density of about 10 centi Morgen (cM) in 147 Chinese hypertensive nuclear families. Multipoint non-parametric linkage analysis and exclusion mapping were performed with the GENEHUNTER software, whereas quantitative analysis was performed with the variance component method integrated in the SOLAR package. Results In the qualitative analysis, the highest non-parametric linkage score is 1.0 (P=0.14) at D14S261 in the single point analysis, and no loci achieved non-parametric linkage score more than 1.0 in the multipoint analysis. Maximum-likelihood mapping showed no significant results, either. Subsequently the traditional exclusion criteria of the log-of-the-odds score-2 were adopted, and the chromosome 14 with λs≥2.4 was excluded. In the quantitative analysis of blood pressure with the SOLAR software, two-point analysis and multipoint analysis suggested no evidence for linkage occurred on chromosome 14 for systolic and diastolic blood pressure. Conclusion There was no substantial evidence to support the linkage of chromosome 14 and essential hypertension or blood pressure trait in Chinese hypertensive subjects in this study.

  7. Sperm FISH analysis of a 46,XY,t(3;6)(p24;p21.2),inv (8)(p11;2q21.2) double chromosomal rearrangement.

    Science.gov (United States)

    Ferfouri, Fatma; Boitrelle, Florence; Tapia, Sylvie; Molina Gomes, Denise; Selva, Jacqueline; Vialard, François

    2012-02-01

    A complex chromosome rearrangement (CCR) can be defined as a structural chromosomal aberration that involves at least three breakpoints located on two or more chromosomes. Highly unbalanced gametes may lead to infertility or congenital malformations. Here is reported a double rearrangement considered as the simplest possible CCR and, in a sense, not a true CCR, meiotic segregation for a 46,XY,t(3;6)(p24;p21.2),inv(8)(p11;2q21.2) male patient referred after his partner had undergone three early miscarriages. Sperm fluorescence in-situ hybridization was used to screen for translocation and inversion segregation and an interchromosomal effect (ICE) for 13 chromosomes not involved in CCR. The malsegregation rates for the reciprocal translocation and pericentric inversion were 61.2% and 1.7%, respectively. ICE analysis revealed that the observed chromosome aneuploidy rates of between 0.1% and 0.8% did not differ significantly from control values. A slight increase in cumulative ICE (P=0.049) was observed in the patient, relative to control spermatozoa (with rates of 4.6% and 3.1%). The sperm DNA fragmentation rate differed significantly from control values (5.0%; P=0.001). Reciprocal translocation had no impact on meiotic segregation of the pericentric inversion in this double rearrangement. No conclusion could be drawn regarding the impact of pericentric inversion on translocation.

  8. Performance analysis of adaptive fiber laser array propagating in atmosphere with correction of high order aberrations in sub-aperture

    Science.gov (United States)

    Li, Feng; Geng, Chao; Li, Xinyang; Qiu, Qi

    2016-10-01

    Recently developed adaptive fiber laser array technique provides a promising way incorporating aberrations correction with laser beams transmission. Existing researches are focused on sub-aperture low order aberrations (pistons and tips/tilts) compensation and got excellent correction results for weak and moderate turbulence in short range. While such results are not adequate for future laser applications which face longer range and stronger turbulence. So sub-aperture high aberrations compensation is necessary. Relationship between corrigible orders of sub-aperture aberrations and far-field metrics as power-in-the-bucket (PIB) and Strehl ratio is investigated with numeric simulation in this paper. Numerical investigation results shows that increment in array number won't result in effective improvement of the far-field metric if sub-aperture size is fixed. Low order aberrations compensation in sub-apertures gets its best performances only when turbulence strength is weak. Pistons compensation becomes invalid and higher order aberrations compensation is necessary when turbulence gets strong enough. Cost functions of the adaptive fiber laser array with high order aberrations correction in sub-apertures are defined and the optimum corrigible orders are discussed. Results shows that high order (less than first ten Zernike orders) compensation is acceptable where balance between increment of the far-field metric and the cost and complexity of the system could be reached.

  9. Four parameters increase the sensitivity and specificity of the exon array analysis and disclose 25 novel aberrantly spliced exons in myotonic dystrophy.

    Science.gov (United States)

    Yamashita, Yoshihiro; Matsuura, Tohru; Shinmi, Jun; Amakusa, Yoshinobu; Masuda, Akio; Ito, Mikako; Kinoshita, Masanobu; Furuya, Hirokazu; Abe, Koji; Ibi, Tohru; Sahashi, Ko; Sahashi, Koo; Ohno, Kinji

    2012-06-01

    Myotonic dystrophy type 1 (DM1) is an RNA gain-of-function disorder in which abnormally expanded CTG repeats of DMPK sequestrate a splicing trans-factor MBNL1 and upregulate another splicing trans-factor CUGBP1. To identify a diverse array of aberrantly spliced genes, we performed the exon array analysis of DM1 muscles. We analyzed 72 exons by RT-PCR and found that 27 were aberrantly spliced, whereas 45 were not. Among these, 25 were novel and especially splicing aberrations of LDB3 exon 4 and TTN exon 45 were unique to DM1. Retrospective analysis revealed that four parameters efficiently detect aberrantly spliced exons: (i) the signal intensity is high; (ii) the ratio of probe sets with reliable signal intensities (that is, detection above background P-value=0.000) is high within a gene; (iii) the splice index (SI) is high; and (iv) SI is deviated from SIs of the other exons that can be estimated by calculating the deviation value (DV). Application of the four parameters gave rise to a sensitivity of 77.8% and a specificity of 95.6% in our data set. We propose that calculation of DV, which is unique to our analysis, is of particular importance in analyzing the exon array data.

  10. Analysis of transverse RMS emittance growth of a beam induced by spherical and chromatic aberration in a solenoidal field

    Energy Technology Data Exchange (ETDEWEB)

    Dash, Radhakanta, E-mail: radhakanta.physics@gmail.com [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094 (India); Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Nayak, Biswaranjan [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094 (India); Sharma, Archana; Mittal, Kailash C. [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094 (India); Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

    2016-01-21

    In a medium energy beam transport line transverse rms emittance growth associated with spherical aberration is analysed. An analytical expression is derived for beam optics in a solenoid field considering terms up to the third order in the radial displacement. Two important phenomena: effect of spherical aberrations in axial-symmetric focusing lens and influence of nonlinear space charge forces on beam emittance growth are discussed for different beam distributions. In the second part nonlinear effect associated with chromatic aberration that describes the growth of emittance and distortion of phase space area is discussed.

  11. Analysis of transverse RMS emittance growth of a beam induced by spherical and chromatic aberration in a solenoidal field

    Science.gov (United States)

    Dash, Radhakanta; Nayak, Biswaranjan; Sharma, Archana; Mittal, Kailash C.

    2016-01-01

    In a medium energy beam transport line transverse rms emittance growth associated with spherical aberration is analysed. An analytical expression is derived for beam optics in a solenoid field considering terms up to the third order in the radial displacement. Two important phenomena: effect of spherical aberrations in axial-symmetric focusing lens and influence of nonlinear space charge forces on beam emittance growth are discussed for different beam distributions. In the second part nonlinear effect associated with chromatic aberration that describes the growth of emittance and distortion of phase space area is discussed.

  12. Specific genomic aberrations in primary colorectal cancer are associated with liver metastases

    Directory of Open Access Journals (Sweden)

    Wessels Lodewyk F

    2010-12-01

    Full Text Available Abstract Background Accurate staging of colorectal cancer (CRC with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases. Methods Array Comparative Genomic Hybridization (aCGH was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36, metastases (PM; n = 37 and a group that remained metastases-free (M0; n = 25. A novel statistical method for identifying recurrent copy number changes, KC-SMART, was used to find specific locations of genomic aberrations specific for various groups. We created a classifier for organ specific metastases based on the aCGH data using Prediction Analysis for Microarrays (PAM. Results Specifically in the tumors of primary CRC patients who subsequently developed liver metastasis, KC-SMART analysis identified genomic aberrations on chromosome 20q. LM-PAM, a shrunken centroids classifier for liver metastases occurrence, was able to distinguish the LM group from the other groups (M0&PM with 80% accuracy (78% sensitivity and 86% specificity. The classification is predominantly based on chromosome 20q aberrations. Conclusion Liver specific CRC metastases may be predicted with a high accuracy based on specific genomic aberrations in the primary CRC tumor. The ability to predict the site of metastases is important for improvement of personalized patient management.

  13. Transmission of clonal chromosomal abnormalities in human hematopoietic stem and progenitor cells surviving radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kraft, Daniela, E-mail: d.kraft@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Institute for Transfusion Medicine und Immunohematology, DRK-Blutspendedienst Baden-Wuerttemberg—Hessen, Johann Wolfgang Goethe-University Hospital, Sandhofstrasse 1, 60528 Frankfurt (Germany); Ritter, Sylvia, E-mail: s.ritter@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Durante, Marco, E-mail: m.durante@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Institute for Condensed Matter Physics, Physics Department, Technical University Darmstadt, Hochschulstraße 6-8, 64289 Darmstadt (Germany); Seifried, Erhard, E-mail: e.seifried@blutspende.de [Institute for Transfusion Medicine und Immunohematology, DRK-Blutspendedienst Baden-Wuerttemberg—Hessen, Johann Wolfgang Goethe-University Hospital, Sandhofstrasse 1, 60528 Frankfurt (Germany); Fournier, Claudia, E-mail: c.fournier@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Tonn, Torsten, E-mail: t.tonn@blutspende.de [Institute for Transfusion Medicine und Immunohematology, DRK-Blutspendedienst Baden-Wuerttemberg—Hessen, Johann Wolfgang Goethe-University Hospital, Sandhofstrasse 1, 60528 Frankfurt (Germany); Technische Universität Dresden, Med. Fakultät Carl Gustav Carus, Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Blasewitzer Straße 68/70, 01307 Dresden (Germany)

    2015-07-15

    Highlights: • Radiation induced formation and transmission of chromosomal aberrations were assessed. • Cytogenetic analysis was performed in human CD34+ HSPC by mFISH. • We report transmission of stable aberrations in irradiated, clonally expanded HSPC. • Unstable aberrations in clonally expanded HSPC occur independently of irradiation. • Carbon ions and X-rays bear a similar risk for propagation of cytogenetic changes. - Abstract: In radiation-induced acute myeloid leukemia (rAML), clonal chromosomal abnormalities are often observed in bone marrow cells of patients, suggesting that their formation is crucial in the development of the disease. Since rAML is considered to originate from hematopoietic stem and progenitor cells (HSPC), we investigated the frequency and spectrum of radiation-induced chromosomal abnormalities in human CD34{sup +} cells. We then measured stable chromosomal abnormalities, a possible biomarker of leukemia risk, in clonally expanded cell populations which were grown for 14 days in a 3D-matrix (CFU-assay). We compared two radiation qualities used in radiotherapy, sparsely ionizing X-rays and densely ionizing carbon ions (29 and 60–85 keV/μm, doses between 0.5 and 4 Gy). Only a negligible number of de novo arising, unstable aberrations (≤0.05 aberrations/cell, 97% breaks) were measured in the descendants of irradiated HSPC. However, stable aberrations were detected in colonies formed by irradiated HSPC. All cells of the affected colonies exhibited one or more identical aberrations, indicating their clonal origin. The majority of the clonal rearrangements (92%) were simple exchanges such as translocations (77%) and pericentric inversions (15%), which are known to contribute to the development of rAML. Carbon ions were more efficient in inducing cell killing (maximum of ∼30–35% apoptotic cells for 2 Gy carbon ions compared to ∼25% for X-rays) and chromosomal aberrations in the first cell-cycle after exposure (∼70% and

  14. In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Ahituv, Nadav; Moses, Alan M.; Nobrega,Marcelo; Prabhakar, Shyam; Shoukry, Malak; Minovitsky, Simon; Visel,Axel; Dubchak, Inna; Holt, Amy; Lewis, Keith D.; Plajzer-Frick, Ingrid; Akiyama, Jennifer; De Val, Sarah; Afzal, Veena; Black, Brian L.; Couronne, Olivier; Eisen, Michael B.; Rubin, Edward M.

    2006-02-01

    The identification of enhancers with predicted specificitiesin vertebrate genomes remains a significant challenge that is hampered bya lack of experimentally validated training sets. In this study, weleveraged extreme evolutionary sequence conservation as a filter toidentify putative gene regulatory elements and characterized the in vivoenhancer activity of human-fish conserved and ultraconserved1 noncodingelements on human chromosome 16 as well as such elements from elsewherein the genome. We initially tested 165 of these extremely conservedsequences in a transgenic mouse enhancer assay and observed that 48percent (79/165) functioned reproducibly as tissue-specific enhancers ofgene expression at embryonic day 11.5. While driving expression in abroad range of anatomical structures in the embryo, the majority of the79 enhancers drove expression in various regions of the developingnervous system. Studying a set of DNA elements that specifically droveforebrain expression, we identified DNA signatures specifically enrichedin these elements and used these parameters to rank all ~;3,400human-fugu conserved noncoding elements in the human genome. The testingof the top predictions in transgenic mice resulted in a three-foldenrichment for sequences with forebrain enhancer activity. These datadramatically expand the catalogue of in vivo-characterized human geneenhancers and illustrate the future utility of such training sets for avariety of iological applications including decoding the regulatoryvocabulary of the human genome.

  15. The Utility of Chromosomal Microarray Analysis in Developmental and Behavioral Pediatrics

    Science.gov (United States)

    Beaudet, Arthur L.

    2013-01-01

    Chromosomal microarray analysis (CMA) has emerged as a powerful new tool to identify genomic abnormalities associated with a wide range of developmental disabilities including congenital malformations, cognitive impairment, and behavioral abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism…

  16. Diagnostic Yield of Chromosomal Microarray Analysis in an Autism Primary Care Practice: Which Guidelines to Implement?

    Science.gov (United States)

    McGrew, Susan G.; Peters, Brittany R.; Crittendon, Julie A.; Veenstra-VanderWeele, Jeremy

    2012-01-01

    Genetic testing is recommended for patients with ASD; however specific recommendations vary by specialty. American Academy of Pediatrics and American Academy of Neurology guidelines recommend G-banded karyotype and Fragile X DNA. The American College of Medical Genetics recommends Chromosomal Microarray Analysis (CMA). We determined the yield of…

  17. Economic analysis of chromosome testing in couples with recurrent miscarriage to prevent handicapped offspring.

    NARCIS (Netherlands)

    Leeuwen, M. van; Vansenne, F.; Korevaar, J.C.; Veen, F. van der; Goddijn, M.; Mol, B.W.J.

    2013-01-01

    Study Question: Which strategy is least expensive to prevent the birth of a handicapped child in couples with recurrent miscarriage (RM); parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents, or amniocentesis in all ongoing pregnancies without the kn

  18. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. 798.5385 Section 798.5385 Protection of Environment ENVIRONMENTAL... used. Examples of commonly used rodent species are rats, mice, and hamsters. (ii) Age. Healthy...

  19. MMCT-mediated chromosome engineering technique applicable to functional analysis of lncRNA and nuclear dynamics.

    Science.gov (United States)

    Meguro-Horike, Makiko; Horike, Shin-Ichi

    2015-01-01

    Recent evidence implicated several long noncoding RNA (lncRNA) in gene expression in cis or trans through regulating the local chromosomal architecture. However, the mechanisms underlying the lncRNA mediated silencing of multiple genes remain unknown. We believe that Microcell Mediated Chromosome Transfer (MMCT) is a suitable approach for functional analysis of lncRNAs and nuclear dynamics. MMCT is a unique research technique that can be generally used to transfer a single chromosome from one mammalian cell to another. Transferred chromosomes can be stably maintained as functioning in the recipient cells. Since there is no size limit to introducing genomic locus, an approach using the chromosome transfer technique is suitable for functional analysis of a large chromosomal domain. Here we describe a general strategy of MMCT, applications of which have potential to be an alternative tool of existing gene delivery system.

  20. A New Method for Finding Optical Aberrations on the Basis of Analysis of the Object Hologram Without Additional Measurements

    Science.gov (United States)

    Matkivsky, V. A.; Moiseev, A. A.; Shilyagin, P. A.; Shabanov, D. V.; Gelikonov, G. V.; Gelikonov, V. M.

    2016-11-01

    We propose a new method of compensating for the wavefront aberrations during the image processing. The method employs the digital-holography potential. The developed algorithms allow one to find the wavefront distortions caused by the optical-path nonuniformities during the interference recording of images without additional measurements (i.e., without using the reference point source and measuring the wavefront distortions). The possibility of decreasing the wavefront aberrations from tens to several radians using digital methods is demonstrated.

  1. Transcriptomic analysis of fiber strength in upland cotton chromosome introgression lines carrying different Gossypium barbadense chromosomal segments.

    Directory of Open Access Journals (Sweden)

    Lei Fang

    Full Text Available Fiber strength is the key trait that determines fiber quality in cotton, and it is closely related to secondary cell wall synthesis. To understand the mechanism underlying fiber strength, we compared fiber transcriptomes from different G. barbadense chromosome introgression lines (CSILs that had higher fiber strengths than their recipient, G. hirsutum acc. TM-1. A total of 18,288 differentially expressed genes (DEGs were detected between CSIL-35431 and CSIL-31010, two CSILs with stronger fiber and TM-1 during secondary cell wall synthesis. Functional classification and enrichment analysis revealed that these DEGs were enriched for secondary cell wall biogenesis, glucuronoxylan biosynthesis, cellulose biosynthesis, sugar-mediated signaling pathways, and fatty acid biosynthesis. Pathway analysis showed that these DEGs participated in starch and sucrose metabolism (328 genes, glycolysis/gluconeogenesis (122 genes, phenylpropanoid biosynthesis (101 genes, and oxidative phosphorylation (87 genes, etc. Moreover, the expression of MYB- and NAC-type transcription factor genes were also dramatically different between the CSILs and TM-1. Being different to those of CSIL-31134, CSIL-35431 and CSIL-31010, there were many genes for fatty acid degradation and biosynthesis, and also for carbohydrate metabolism that were down-regulated in CSIL-35368. Metabolic pathway analysis in the CSILs showed that different pathways were changed, and some changes at the same developmental stage in some pathways. Our results extended our understanding that carbonhydrate metabolic pathway and secondary cell wall biosynthesis can affect the fiber strength and suggested more genes and/or pathways be related to complex fiber strength formation process.

  2. Transcriptomic analysis of fiber strength in upland cotton chromosome introgression lines carrying different Gossypium barbadense chromosomal segments.

    Science.gov (United States)

    Fang, Lei; Tian, Ruiping; Chen, Jiedan; Wang, Sen; Li, Xinghe; Wang, Peng; Zhang, Tianzhen

    2014-01-01

    Fiber strength is the key trait that determines fiber quality in cotton, and it is closely related to secondary cell wall synthesis. To understand the mechanism underlying fiber strength, we compared fiber transcriptomes from different G. barbadense chromosome introgression lines (CSILs) that had higher fiber strengths than their recipient, G. hirsutum acc. TM-1. A total of 18,288 differentially expressed genes (DEGs) were detected between CSIL-35431 and CSIL-31010, two CSILs with stronger fiber and TM-1 during secondary cell wall synthesis. Functional classification and enrichment analysis revealed that these DEGs were enriched for secondary cell wall biogenesis, glucuronoxylan biosynthesis, cellulose biosynthesis, sugar-mediated signaling pathways, and fatty acid bios