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Sample records for chromosomal aberration production

  1. 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.

  2. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    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

  3. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    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

  4. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. 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.

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. 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

  11. Radiotherapeutical chromosomal aberrations in laryngeal cancer patients

    Directory of Open Access Journals (Sweden)

    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

  12. Chromosome Aberrations in Human Lymphocytes Irradiated with Ionizing Radiation

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    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.

  13. Pattern of chromosomal aberrations in patients from north East iran.

    Science.gov (United States)

    Ghazaey, Saeedeh; Mirzaei, Farzaneh; Ahadian, Mitra; Keifi, Fatemeh; Semiramis, Tootian; Abbaszadegan, Mohammad Reza

    2013-01-01

    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. 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. 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. 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.

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

    Science.gov (United States)

    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.

  15. Chromosome aberrations in pesticide-exposed greenhouse workers

    DEFF Research Database (Denmark)

    Lander, B F; Knudsen, Lisbeth E.; Gamborg, M O

    2000-01-01

    OBJECTIVES: The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. METHODS: In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116 ...... pesticide exposure. In general, the findings indicate the importance of personal protection, during high-exposure re-entry activities, in preventing pesticide uptake and genetic damage.......OBJECTIVES: The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. METHODS: In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116...... workers when they were compared with the referents. After a summer season of pesticide spraying in the greenhouses, the total frequencies of cells with chromosome aberrations were significantly higher than in the preseason samples (P=0.02) and also higher than for the referents (P=0.05). This finding...

  16. 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.

  17. Intrachanges as part of complex chromosome-type exchange aberrations

    NARCIS (Netherlands)

    Boei, JJWA; Vermeulen, S; Moser, J; Mullenders, LHF; Natarajan, AT

    2002-01-01

    The chromosome-type exchange aberrations induced by ionizing radiation during the G(0)/G(1) phase of the cell cycle are believed to be the result of illegitimate rejoining of chromosome breaks. From numerous studies using chromosome painting, it has emerged that even after a moderate dose of

  18. 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.

  19. CYTOGENETIC STUDY OF CHROMOSOMAL ABERRATIONS ASSOCIATED WITH CHRONIC LEUKEMIA

    National Research Council Canada - National Science Library

    Dharma Niranjan Mishra; Sitansu Kumar Panda; Saurjya Ranjan Das; Jami Sagar Prusti; Santosh Sahu; Priyambada Panda; Chinmayi Mohapatra

    2016-01-01

    ... in the Hematology section of Pathology Department from the coastal District of Orissa. The chromosomal aberrations were taken into account in this present study and arranged in tables, Bar charts and Pie charts for comparison...

  20. Chromosomal aberrations in plants under magnetic fluid influence

    Energy Technology Data Exchange (ETDEWEB)

    Pavel, Angela [University of Medicine and Pharmacy Gr.T. Popa, Fac. of Pharmacy, Iasi (Romania)]. E-mail: angelapavel04@yahoo.com; Creanga, Dorina-Emilia [Faculty of Physics, University of Al. I. Cuza, Bd. Copou 11A, Iasi (Romania)]. E-mail: dorinacreanga@yahoo.com

    2005-03-15

    The study was focussed on the influence of a petroleum magnetic fluid upon the cell proliferation in young plants of agricultural interest. Zea mays plants, in their early ontogenetic stages were treated with magnetic fluid in relatively low concentrations (up to 100{mu}l/l) and root meristem was investigated by cytogenetical methods. The cell proliferation rate was found significantly enhanced as well as the percentage of chromosomal aberrations. Micronuclei, bridges, chromosome fragments and three-polar anaphases were the main types of chromosomal aberrations.

  1. 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.

  2. 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.

  3. 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.

  4. Chromosomal aberrations in benign prostatic hyperplasia patients

    Directory of Open Access Journals (Sweden)

    Muammer Altok

    2016-01-01

    Full Text Available Purpose: To investigate the chromosomal changes in patients with benign prostatic hyperplasia (BPH. Materials and Methods: A total of 54 patients diagnosed with clinical BPH underwent transurethral prostate resection to address their primary urological problem. All patients were evaluated by use of a comprehensive medical history and rectal digital examination. The preoperative evaluation also included serum prostate-specific antigen (PSA measurement and ultrasonographic measurement of prostate volume. Prostate cancer was detected in one patient, who was then excluded from the study. We performed conventional cytogenetic analyses of short-term cultures of 53 peripheral blood samples obtained from the BPH patients. Results: The mean (±standard deviation age of the 53 patients was 67.8±9.4 years. The mean PSA value of the patients was 5.8±7.0 ng/mL. The mean prostate volume was 53.6±22.9 mL. Chromosomal abnormalities were noted in 5 of the 53 cases (9.4%. Loss of the Y chromosome was the most frequent chromosomal abnormality and was observed in three patients (5.7%. There was no statistically significant relationship among age, PSA, prostate volume, and chromosomal changes. Conclusions: Loss of the Y chromosome was the main chromosomal abnormality found in our study. However, this coexistence did not reach a significant level. Our study concluded that loss of the Y chromosome cannot be considered relevant for the diagnosis of BPH as it is for prostate cancer. Because BPH usually occurs in aging men, loss of the Y chromosome in BPH patients may instead be related to the aging process.

  5. Chromosomal aberrations and aneuploidies of spermatozoa.

    Science.gov (United States)

    Piomboni, Paola; Stendardi, Anita; Gambera, Laura

    2014-01-01

    Chromosomal abnormalities are relevant causes of human infertility, affecting 2 -14 % of infertile males. Patients with seminal anomalies could be affected by improper meiotic recombination and increased sperm chromosome aneuploidy. Since the transmission of a haploid chromosomal asset is fundamental for embryo vitality and development, the study of sperm chromosomes has become fundamental because intracytoplasmic sperm injection allows fertilization in cases of severe male infertility.In this chapter we summarize the data on the incidence of sperm aneuploidy, detected by fluorescence in situ hybridization (FISH), in infertile men with normal or abnormal karyotype. The possibility of reducing sperm chromosomal imbalance is also reported.Among control males, the lowest aneuploidy rate was detected (range: 0.09 -0.14 % for autosomes; 0.04 -0.10 % for gonosomes). In infertile patients with normal karyotype, the severity of semen alteration is correlated with the frequency of aneuploidy, particularly for X and Y chromosomes. Among patients with abnormal karyotype, 47,XXY and 47,XYY carriers showed a high variability of sperm aneuploidy both for gonosomes and autosomes. In Robertsonian translocation carriers, the increase in aneuploidy rate was particularly evident for total sex disomy, and resulted mainly from interchromosomal effect (ICE). In reciprocal translocation carriers, a high percentage of unbalanced sperm (approximately 50 %) was detected, perhaps mostly related to ICE.Sperm chromosomal constitution could be analyzed to obtain more accurate information about the causes of male infertility. It would be worthwhile to evaluate the benefits of a therapy with recombinant Follicle Stimulating Hormone (rFSH) on sperm chromosome segregation in selected infertile males.

  6. 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).

  7. 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.

  8. [Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007].

    Science.gov (United States)

    Gregor, V; Sípek, A; Sípek, A; Horácek, J '; Langhammer, P; Petrzílková, L; Calda, P

    2009-02-01

    An analysis of prenatal diagnostics efficiency of selected types of chromosomal aberrations in the Czech Republic in 2007. Update of 1994-2007 data according to particular selected diagnoses. Retrospective epidemiological analysis of pre- and postnatal chromosomal aberrations diagnostics and its efficiency. Data on pre- and postnatally diagnosed birth defects in the Czech Republic during 1994-2007 were used. Data on prenatally diagnosed birth defects (and for terminated pregnancies) were collected from particular departments of prenatal diagnostics, medical genetics and ultrasound diagnostics in the Czech Republic, data on birth defects in births from the National Birth Defects Register (Institute for Health Information and Statistics). Total numbers over the period under the study, mean incidences of selected types of chromosomal aberrations and mean prenatal diagnostics efficiencies were analyzed. Following chromosomal aberrations were studied: Down, Edwards, Patau, Turner and Klinefelter syndromes and syndromes 47,XXX and 47,XYY. A relative proportion of Down, Edwards and Patau syndromes as well as other autosomal and gonosomal aberration is presented in figures. Recently, trisomies 13, 18 and 21 present around 70% of all chromosomal aberrations in selectively aborted fetuses, in other pregnancies, "other chromosomal aberrations" category (mostly balanced reciprocal translocations and inversions) present more than 2/3 of all diagnoses. During the period under the study, following total numbers, mean relative incidences (per 10,000 live births, in brackets) and mean prenatal diagnostics efficiency (in %) were found in following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%. The study gives updated results of

  9. 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....

  10. Chromosomal Aberrations in Monozygotic and Dizygotic Twins Versus Singletons in Denmark During 1968-2009

    DEFF Research Database (Denmark)

    Kristensen, Lone Krøldrup; Larsen, Lisbeth A; Fagerberg, Christina

    2017-01-01

    BACKGROUND: Hall (Embryologic development and monozygotic twinning. Acta Geneticae Medicae et Gemellologiae, Vol. 45, 1996, pp. 53-57) hypothesized that chromosomal aberrations can lead to monozygotic (MZ) twinning. However, twinning and chromosomal aberrations increase prenatal mortality and could...

  11. 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

  12. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. [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).

  1. 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...

  2. Chromosome aberrations in pesticide-exposed greenhouse workers.

    Science.gov (United States)

    Lander, B F; Knudsen, L E; Gamborg, M O; Järventaus, H; Norppa, H

    2000-10-01

    The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116 greenhouse workers exposed to a complex mixture of almost 50 insecticides, fungicides, and growth regulators and also for 29 nonsmoking, nonpesticide-exposed referents. The preseason frequencies of chromosome aberrations were slightly but not statistically significantly elevated for the greenhouse workers when they were compared with the referents. After a summer season of pesticide spraying in the greenhouses, the total frequencies of cells with chromosome aberrations were significantly higher than in the preseason samples (P=0.02) and also higher than for the referents (P=0.05). This finding was especially due to an increased number of cells with chromatid gaps between the first and second samples (P=0.001). The results may reflect an additive genotoxic effect of the spraying season, for which the use of insecticides and growth regulators (but not fungicides) culminates. The highest elevation in the risk of chromatid gaps was observed for persons who did not use gloves during re-entry activities such as nipping, cutting, pricking, and potting (risk ratio 2.88, 95% confidence interval 1.63-5.11). The present results suggest a genotoxic effect from a complex subtoxic occupational pesticide exposure. In general, the findings indicate the importance of personal protection, during high-exposure re-entry activities, in preventing pesticide uptake and genetic damage.

  3. Prompt cytomolecular identification of chromosome aberration in irradiated blood cells

    Directory of Open Access Journals (Sweden)

    Seyed Akbar Moosavi

    2017-02-01

    Full Text Available Background: understanding the genomic alteration induced by ionizing radiation still remains to be a methodological challenge in genetic field. The energy released from this type of radiation can potentially causes structural and numerical alterations in lymphocytes, which in turn converts them into abnormal tumor cells. Chromosomal abnormalities associated with specific type of hematological malignancies are determinant factors in evaluation of radiation dose and its potential in harming the body. None the less early detection of chromosomal aberration (CA is crucial in prognosis and selection of therapy for the people exposed to irradiations. The aim of this study was to explore a swift and accurate genetic test that identifies CAs in radiologist exposed to X-rays. In addition synergistic effect of other clastogens in irradiated workers was also evaluated. Material and methods: thirty four heparinized blood samples were obtained from radiology workers exposed to X-rays. Blood samples were cultured in RPMI 1640 and F-10 Medias with and without PHA stimulation. Lymphocytes were harvested, separated and arrested at metaphase and their chromosomes were analyzed by solid and G-Banding techniques. Lymphocytic CA was also analyzed through whole chromosome painting FISH. Results: of the 37 blood sample from workers, 60% had various structural aberrations in which both the frequency and type of CAs were intensified among tobacco smokers. Conclusion: the results did not show any significant differences between the genders but other carcinogen like smoking can significantly increases the rate of CAs

  4. 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

  5. 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.

  6. MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility.

    Science.gov (United States)

    Röpke, Albrecht; Tüttelmann, Frank

    2017-06-13

    Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo- or azoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistently with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the male associated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased CNV burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: 1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). 2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. 3) Copy Number Variations (CNVs) affecting the X chromosome. 4) Point mutations disrupting X-chromosomal genes. All of these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years.

  7. Combining Chromosomal Arm Status and Significantly Aberrant Genomic Locations Reveals New Cancer Subtypes

    Directory of Open Access Journals (Sweden)

    Tal Shay

    2009-01-01

    Full Text Available Many types of tumors exhibit characteristic chromosomal losses or gains, as well as local amplifications and deletions. Within any given tumor type, sample specific amplifications and deletions are also observed. Typically, a region that is aberrant in more tumors, or whose copy number change is stronger, would be considered as a more promising candidate to be biologically relevant to cancer. We sought for an intuitive method to define such aberrations and prioritize them. We define V, the “volume” associated with an aberration, as the product of three factors: (a fraction of patients with the aberration, (b the aberration’s length and (c its amplitude. Our algorithm compares the values of V derived from the real data to a null distribution obtained by permutations, and yields the statistical significance (p-value of the measured value of V. We detected genetic locations that were significantly aberrant, and combine them with chromosomal arm status (gain/loss to create a succinct fingerprint of the tumor genome. This genomic fingerprint is used to visualize the tumors, highlighting events that are co-occurring or mutually exclusive. We apply the method on three different public array CGH datasets of Medulloblastoma and Neuroblastoma, and demonstrate its ability to detect chromosomal regions that were known to be altered in the tested cancer types, as well as to suggest new genomic locations to be tested. We identified a potential new subtype of Medulloblastoma, which is analogous to Neuroblastoma type 1.

  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. 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

    Full text of publication follows: The Ignalina Nuclear Power Plant (I.N.P.P.) workers and outside workers including visitors constitute the largest occupational group exposed to low doses of ionizing radiation in Lithuania. In 2004, the annual collective dose to these workers (4392 persons) was 6,83 man Sv. The maximum annual individual dose of I.N.P.P. workers was 19,16 mSv, and of outside workers was 29,41 mSv. However, according to calculations performed by the Lithuanian Radiation Protection Centre, the decommissioning of I.N.P.P. (the I.N.P.P. is to be shut down by 2009) will result in collective dose of 35 man Sv. Therefore, a special attention should be given to implementation of radiation protection programme. The importance of cytogenetic studies in the medical surveillance of radiation-exposed persons is generally acknowledged. The aim of the present study was to analyse chromosome aberration frequencies in lymphocytes of I.N.P.P. workers. The blood sampling of 27 male workers was performed in October 2004, after planned outage of I.N.P.P.. It was estimated that outages of I.N.P.P. Units contributed 84% to all annual occupational collective dose. Average cumulative dose of 18 workers was 290,7 mSv (group A), and of 9 workers - 71,7 mSv (group B). The mean annual doses averaged over the three-year-period were 15,2 mSv and 0,76 mSv, respectively. None of the exposed workers had ever exceeded the permissible dose limit. The average age of group A workers was 45,2 years, and group B 48,2 years. A questionnaire form with details on age, occupational history, smoking habit and alcohol intake, medication, history of recent illness was completed for each person at the time of blood collection. 64 non-exposed male donors approximately matched by age were used as controls (group C). Heparinized venous blood samples were taken and cultures were initiated within 24 h according to the standard procedures. At least 500 first cycle metaphases were analysed from each

  10. 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.

  11. Chromosomal aberrations found in Paracalanus aculeatus (Giesbrecht) at the time of solar eclipse

    Digital Repository Service at National Institute of Oceanography (India)

    Goswami, U.; Goswami, S.C.

    Chromosomal aberrations in the form of an unequal heteromorphic homologous pair and a supernumerary chromosome were observed in the gonad of a copepod - @iParacalanus aculeatus@@ after being exposed to the total solar eclipse of Feb. 16, 1980...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Aggressive osteoblastoma: a case report involving a unique chromosomal aberration.

    Science.gov (United States)

    Baker, Allyson C; Rezeanu, Luminita; Klein, Michael J; Pitt, Michael J; Buecker, Peter; Hersh, Joseph H; Buchino, John J; Siegal, Gene P

    2010-06-01

    Osteoblastomas are rare bone-producing neoplasms that generally occur in the young and can be misdiagnosed as an osteosarcoma if correlation with clinical history, radiology, and histology is not carefully considered or if the several variants of osteoblastoma are not recognized. These variants lie on a morphologic spectrum between conventional osteoblastoma and osteosarcoma. Aggressive osteoblastoma is one such subtype. As the name implies, the histologic features of aggressive osteoblastoma may appear malignant, and its biologic behavior may separate it from conventional osteoblastoma. We report a case of aggressive osteoblastoma occurring in the femoral diaphysis of a 12-year-old girl; this osetoblastoma was dyssynchronous from the radiologic appearance and a diagnostic challenge. Cytogenetic evaluation of the neoplasm revealed a pseudodiploid clone with a balanced translocation involving chromosomes 4, 7, and 14. Using the premise that cytogenetics might be useful as a diagnostic tool for a more specific classification, we reviewed the literature in order to compare our findings with known chromosomal aberrations.

  17. 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.

  18. 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.

  19. 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

  20. 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)

  1. 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.

  2. 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.

  3. Chromosomal aberrations accumulate in polyploid cells of high-grade squamous intraepithelial lesions (HSIL)

    National Research Council Canada - National Science Library

    Méhes, Gábor; Speich, Norbert; Bollmann, Magdolna; Bollmann, Reinhard

    2004-01-01

    ...), the oncogenic potential of which is unclear in a given time point of monitoring. HPVinduced genetic instability result in polyploidization as well as in low frequency random chromosome aberrations in squamous cells...

  4. Cell Lines Derived From Feline Fibrosarcoma Display Unstable Chromosomal Aneuploidy and Additionally Centrosome Number Aberrations

    National Research Council Canada - National Science Library

    Erichsen, J. von; Hecht, W; Löhberg-Gruene, C; Reinacher, M

    2012-01-01

    The purpose of the study was to evaluate clonality and presence of numerical chromosomal and centrosomal aberrations in 5 established feline fibrosarcoma cell lines and in a fetal dermal fibroblast...

  5. 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.

  6. 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.

  7. 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.

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

    Science.gov (United States)

    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

  9. 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,

  10. 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

  11. 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.

  12. [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.

  13. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... poorly to in vivo chemotherapy treatment as compared with t(9;11) AML originating from HPCs....

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Formation of chromosome aberrations in androgenetic rainbow trout Oncorhynchus mykiss.

    Science.gov (United States)

    Ocalewicz, K; Dobosz, S; Kuzminski, H; Goryczko, K

    2009-12-01

    Residues of maternal nuclear DNA in the form of chromosome fragments were observed in the healthy and morphologically normal androgenetic rainbow trout Oncorhynchus mykiss. A hypothetical model for formation of chromosome re-arrangements caused by the incomplete maternal nuclear DNA inactivation in the androgenetic rainbow trout was proposed in the present paper.

  19. Cytogenetic aberrations in osteosarcomas. Nonrandom deletions, rings, and double-minute chromosomes.

    Science.gov (United States)

    Fletcher, J A; Gebhardt, M C; Kozakewich, H P

    1994-10-01

    Relatively few karyotypes have been reported from short-term cultures and/or direct harvests of osteosarcomas. We describe clonal aberrations in 17 high-grade osteosarcoma specimens and in one low-grade osteosarcoma. The high-grade osteosarcomas were karyotyped after direct harvest (four cases) or after short-term culture periods of osteosarcoma and two lung metastases, were from the same patient and shared a number of clonal aberrations. No consistent chromosome translocations were identified in the overall group of high-grade osteosarcomas, but potential nonrandom deletions involved 6q21-->qter, 9p21-->pter, chromosome 10, chromosome 13, 17p12-pter, and chromosome 20. Ring chromosomes were detected in three cases, and double-minute (dmin) chromosomes were detected in six. All high-grade osteosarcomas had numerous nonclonal chromosome aberrations superimposed on complex clonal events. The single low-grade osteosarcoma was characterized by a balanced, nonconstitutional, t(5;10) (p13;p14-15), together with an addition to the short arm of chromosome X. This is the first translocation reported in low-grade osteosarcoma, and the simplicity of the karyotype contrasts strikingly with those in the high-grade osteosarcomas.

  20. 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.

  1. [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.

  2. 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.

  3. 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)

  4. 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)

  5. 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.

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  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. 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...

  14. 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.

  15. Evaluation of genotoxic potential of chromium (VI) in Channa punctata fish in terms of chromosomal aberrations.

    Science.gov (United States)

    Yadav, K K; Trivedi, S P

    2006-01-01

    Chromium, a widely recognized carcinogenic, mutagenic and redox active metal, is released into aquatic environments by electroplating, tannery and textile industries. Elevated concentrations in sediments and interstitial waters are well documented. Fishes dwelling in chromium waste infested waters are presumed to be affected by its deposits. To evaluate the genotoxic potential of chromium [Cr(VI)] on aquatic bio-system, bottom feeding fishes, Channa punctata, as model fish, were exposed to [Cr(VI)]. The chromosomal aberration test (CAT) was used as biomarker of [Cr(VI)] induced toxicity. The fish were divided into three groups:Group I non-treated controls; group II positive controls, treated with an intra-muscular injection of mitomycin-C at 1 mg/kg body wt; group III exposed to a sublethal concentration (7.689 mg/l) of [Cr(VI)], dissolved in the water. For CAT estimation, short term static bioassays were conducted and samples were collected from the kidneys of fish after 24, 48, 72, 96 and 168 hrs of exposure. The remarkable chromosomal aberrations recorded in the present investigation included chromatid breaks, chromosome breaks, chromatid deletions, fragments, acentric fragments, and ring and di-centric chromosomes, along with chromatid and chromosome gaps. A significant increase in chromosomal aberrations was observed after 72 hrs of [Cr(VI)] exposure. The present study, thus reveals that even for acute exposure, [Cr(VI)] is a genotoxic agent for C. punctata.

  16. 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.

  17. FISH and FICTION to detect chromosomal aberrations in lymphomas.

    Science.gov (United States)

    Giefing, Maciej; Siebert, Reiner

    2013-01-01

    Fluorescence In Situ Hybridization (FISH) is a powerful and robust technique allowing the visualization of target sequences like genes in interphase nuclei. It is widely used in routine diagnostics to identify cancer specific aberrations including lymphoma associated translocations or gene copy number changes in single tumor cells. By combining FISH with immunophenotyping-a technique called Fluorescence Immunophenotyping and Interphase Cytogenetic as a Tool for Investigation Of Neoplasia (FICTION)-it is moreover possible to identify a cell population of interest. Here we describe standard protocols for FISH and FICTION as used in our laboratory in diagnosis and research.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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....

  4. 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.

  5. 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.

  6. 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)

  7. 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

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

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    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.

  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. 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.

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

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    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.

  12. 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.

  13. 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)

  14. 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.

  15. Alternative Lengthening of Telomeres: Recurrent Cytogenetic Aberrations and Chromosome Stability under Extreme Telomere Dysfunction

    Directory of Open Access Journals (Sweden)

    Despoina Sakellariou

    2013-11-01

    Full Text Available Human tumors using the alternative lengthening of telomeres (ALT exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines.We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted.We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth.

  16. 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.

  17. 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.

  18. 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.

  19. RBE of Energetic Iron Ions for the Induction of Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Zhang, Ye; Yeshitla, Samrawit; Hada, Megumi; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2014-01-01

    Numerous published studies have reported the RBE values for chromosome chromosomes induced by charged particles of different LET. The RBE for chromosome aberrations in human lymphocytes exposed ex vivo showed a similar relationship as the quality factor for cancer induction. Consequently, increased chromosome aberrations in the astronauts' white blood cells post long-duration missions are used to determine the biological doses from exposures to space radiation. The RBE value is known to be very different for different types of cancer. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. After multiple cell divisions post irradiation, the RBE was significantly smaller. To test the hypothesis that the RBE values for chromosome aberrations are different between early and late damages and also different between different cell types, we exposed human lymphocytes ex vivo, and human fibroblast cells and human mammary epithelial cells in vitro to 600 MeV/u Fe ions. Post irradiation, the cells were collected at first mitosis, or cultured for multiple generations for collections of remaining or late arising chromosome aberrations. The chromosome aberrations were quantified using fluorescent in situ hybridization (FISH) with whole chromosome specific probes. This study attempts to offer an explanation for the varying RBE values for different cancer types.

  20. 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.

  1. Structural chromosomal aberrations as potential risk markers in incident cancer patients.

    Science.gov (United States)

    Vodenkova, Sona; Polivkova, Zdenka; Musak, Ludovit; Smerhovsky, Zdenek; Zoubkova, Hana; Sytarova, Sylvie; Kavcova, Elena; Halasova, Erika; Vodickova, Ludmila; Jiraskova, Katerina; Svoboda, Miroslav; Ambrus, Miloslav; Hemminki, Kari; Vodicka, Pavel

    2015-07-01

    Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) were observed in lung and breast cancer patients as compared to healthy controls. In colorectal cancer (CRC) patients, only CTAs were significantly elevated. Binary logistic regression, adjusted for main confounders, indicates that all the analysed cytogenetic parameters along with smoking were significantly associated with breast and lung cancer risks. Significant differences in terminal deletions between breast cancer patients and corresponding female controls were recorded (0.39 vs. 0.18; P ≤ 0.05). We did not find any association of CAs with TNM (tumor nodus metastasis) stages or histopathological grade in either cancer type. CAs were neither associated with additional tumor characteristics-invasivity, ductal and lobular character, estrogene/progesterone receptors in breast tumors nor with non-small/small cell and bronchogenic/pulmonary types of lung tumors. Our study demonstrates that CAs serve as a predictive marker for breast and lung cancer, whereas only CTAs were elevated in incident CRC patients. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. [Assessment of relative biological effectiveness of tritium using chromosome aberration frequency in human blood lymphocytes].

    Science.gov (United States)

    Snigireva, G P; Khaĭmovich, T I; Nagiba, V I

    2010-01-01

    The aim of this work is to determine Relative Biological Effectiveness (RBE) of tritium beta-irradiation using chromosome aberration frequency in peripheral blood lymphocytes after radiation exposure in vitro and in vivo. The results of the experimental estimation of tritium beta-irradiation RBE in comparison with 60Co gamma-irradiation using analysis of unstable chromosome aberration frequencies in peripheral blood lymphocytes in reference to concrete conditions of the investigation were presented. It was demonstrated that tritium beta-irradiation is in total more effective than gamma-irradiation up to 1 Gy. RBE of tritium beta-irradiation was determined as 2.2 at minimum doses and decreased at higher doses (1 Gy) up to 1.25. For the first time results of the comparative analysis of frequencies of stable chromosome aberrations in two groups of professional nuclear workers (town Sarov) exposed to chronic tritium beta- and gamma-irradiation in remote period were presented. The grater RBE of tritium beta-irradiation was demonstrated. It has been estimated as 2.5.

  3. [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.

  4. Chromosomal aberrations, reproductive success, life span, and mortality in irradiated Neanthes arenaceodentata (polychaeta)

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.L.; Harrison, F.L.; Chan, G.; Moore, D.H. II

    1987-10-01

    The polychaete worm Neanthes arenaceodentata ws used in experiments to determine possible relationships between short-term genotoxicity tests and reproductive and lethal consequences of exposure to ionizing radiation. Groups of juvenile N. arenaceodentata received one of four different radiation doses (2, 4, 8, and 16 Gy) to determine dose-effect estimates for chromosomal aberration induction, and groups of both adult and juveniles received one of seven different radiation doses (1, 4, 8.4, 46, 102, 500, and 1000 Gy) to determine dose-effect estimates for reproduction, mortality, and life span. Effects on reproduction and genetic material were observed at the lowest doses and in the same range; detrimental reproductive effects were observed at 1 to 4 Gy, and the frequency of chromosomal aberrations were significantly increased at 2 Gy. Only high doses resulted in acute mortality (>500 Gy) and decreased life span (>100 Gy). Dose-effect estimates for chromosomal aberration induction were dependant on radiation dose and on the stage of the cell cycle at the time of irradiation. Dose-effect estimates for reproduction were dependant on dose and the potential for repopulation of gonadal tissue. Such knowledge is required because factors, such as cell-cycle effects, may modify dose-effect estimates. It is concluded that short-term genotoxicity tests can be predictive of detrimental reproductive effects in those model systems for which basic cell kinetics and reproductive parameters are well known. 4 refs., 11 figs., 13 tabs.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. The impact of physical activity on the level of chromosome aberrations

    Directory of Open Access Journals (Sweden)

    Šošić Gordana M.

    2015-01-01

    Full Text Available During the lifetime, people are constantly exposed to the chemicals and agents of exogenic and endogenic sources, which through reaction with a molecule of DNA can cause the damage of genomes and their instability. The formation of micronuclei is a consequence of chromosomal aberrations caused by the influence of different genetic and environmental factors. Micronuclei are cytoplasmic chromatin masses that look like small nuclei and can originate from whole or parts of chromosomes. Micronucleus test ( MN test is used to detect genotoxic effects of various chemical , physical or biological mutagens, as well as the test for determination of chromosomal instability in a variety of cell types. Micronucleus frequency is directly proportional to the degree of chromosomal aberrations. It has been shown that genome damage may occur as a result of environmental exposure to genotoxins and medical procedures, due to deficiency of micronutrients and under the influence of various lifestyles and genetic factors. Unbalanced diet, lack of physical exercise, lack of sleep and overwork contribute significantly to increased frequency of micronuclei. It was also shown that strenuous exercise causes DNA damage, which results in the formation of micronuclei. As a professional athlete conduct highly Intensive physical training, these populations are at risk for the development of genomic instability and carcinogenesis. A healthy lifestyle, the optimal intake of antioxidants and regular moderate physical activity significantly reduced the frequency of micronuclei, and contribute to the stability of the genome.

  10. Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review

    Directory of Open Access Journals (Sweden)

    Bani Bandana Ganguly

    2016-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q, monosomy 5/7, trisomy 8/19, i(17q, and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations. Chromosome analysis was carried out following unstimulated marrow culture and G-banding. In addition to known MDS-aberrations, der(9p, der(12 dic(12;?19, +15, −18, and ring and marker chromosomes were recorded having, at least, nine abnormal chromosomes/cell. To our knowledge, this is the first case with all MDS-aberrations in one single individual. The case has been discussed in relevance to current MDS research. In the present case, i(17q/-17, der(12p, del(5q26, del(7q36, and del(20q11 indicate possible alterations in TP53, ETV6, IDH2, EZH2, and SRSF2 genes, which are responsible for pathomechanism, genetic instability, clonal evolution, and advancement of disease condition.

  11. [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.

  12. Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

    Directory of Open Access Journals (Sweden)

    Mohr Brigitte

    2003-01-01

    Full Text Available Abstract Background The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression. Results We developed a simplified computer readable cytogenetic notation (SCCN by which chromosome findings are normalised at a resolution of 400 bands. Lost or gained chromosomes or chromosome segments are specified in detail, and ranges of chromosome breakpoint assignments are recorded. Software modules were written to summarise the recorded chromosome changes with regard to the respective chromosome involvement. To assess the degree of karyotype alterations the ploidy levels and numbers of numerical and structural changes were recorded separately, and summarised in a complex karyotype aberration score (CKAS. The SCCN and CKAS were used to analyse the extend and the spectrum of additional chromosome aberrations in 94 patients with Philadelphia chromosome positive (Ph-positive acute lymphoblastic leukemia (ALL and secondary chromosome anomalies. Dosage changes of chromosomal material represented 92.1% of all additional events. Recurring regions of chromosome losses were identified. Structural rearrangements affecting (pericentromeric chromosome regions were recorded in 24.6% of the cases. Conclusions SCCN and CKAS provide unifying elements between karyotypes and computer processable data formats. They proved to be useful in the investigation of additional chromosome aberrations in Ph-positive ALL, and may represent a step towards full automation of the analysis of large and complex karyotype databases.

  13. 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.

  14. 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

  15. 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

  16. Chromosome Aberrations in Normal and Ataxia-Telangiectasia Cells Exposed to Heavy Ions

    Science.gov (United States)

    Kawata, T.; Ito, H.; Liu, C.; Shigematsu, N.; George, K.; Cucinotta, F. A.

    2007-01-01

    Although cells derived from Ataxia Telangiectasia (AT) patients are known to exhibit abnormal responses to ionizing radiations, its underlying mechanism still remains unclear. Previously, the authors reported that at the same gamma-irradiation dose AT cells show higher frequencies of misrepair and deletions compared to normal human fibroblast cells. In this study, 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/m), 500 MeV/u Iron (LET 185 keV/m) and 200 MeV/u Iron (LET 440 keV/m) 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 exanges) 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/m and then decreased at 440 keV/m. 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/m 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 AT cells when it was compared at 185 keV/m 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

  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. 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.

  19. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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)

  2. Study on the cytotoxicity and chromosome aberration following implantation of sea coral in rabbits

    Directory of Open Access Journals (Sweden)

    Kannan TP

    2006-03-01

    Full Text Available Coral has been used as a bone substitute in many experimental studies. It has been proven to be biocompatible, biodegradable and easy to handle: and it has not been found to cause any inflammatory responses. The present study was undertaken to determine the cytotoxicity in terms of mitotic index as well as the clastogenic effect (chromosome aberration of sea coral implantation in rabbits. The animals comprised of five male adult healthy New Zealand White (Oryctolagus cuniculus rabbits. The biomaterial, sea coral granules used in this study was obtained from Porites species and processed by the tissue bank of Universiti Sains Malaysia, Health Campus, Kubang Kerian, Malaysia. The blood samples were collected twice from the rabbits, once before the implantation of the sea coral granules (which acted as the control and the other, one week after the implantation (which acted as the treatment and lymphocyte cultures were set up. The cultures were then harvested and the chromosomes were prepared for analysis. The diploid number of chromosomes in the rabbits (Oryctolagus cuniculus was found to be 44. Mean mitotic indices of 3.84 ± 0.54 per cent and 3.76 ± 0.23 per cent were obtained before and after implantation of sea coral granules respectively. There were no structural or numerical chromosomal aberrations observed in both the cases. The mitotic index values and chromosomal analyses in this preliminary study carried out indicate that the biomaterial, sea coral granules is non-cytotoxic and non-clastogenic under the present test conditions.

  3. 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.

  4. 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.

  5. 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.

  6. Prediction of human cell radiosensitivity: Comparison of clonogenic assay with chromosome aberrations scored using premature chromosome condensation with fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Sasai, K.; Evans, J.W.; Kovacs, M.S. [Stanford Univ. School of Medicine, CA (United States)] [and others

    1994-12-01

    The purpose of the present investigation was to determine whether chromosome aberrations scored by premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) can predict the radiosensitivity of human cell lines, thereby providing a possible means of assessing the in situ radiosensitivity of normal tissues and the radiocurability of individual human cancers. We used four cells lines of different radiosensitivity: normal human fibroblasts (AG1522), ataxia-telangiectasia fibroblasts (AT2052), a human fibrosarcoma cell line (HT1080), and a human melanoma cell line (melanoma 903). These were irradiated in plateau phase with a range of doses and assessed both for clonogenic cell survival and for aberrations in a single chromosome (number 4) immediately after, and 24 h after irradiation. The initial number of breaks in chromosome 4 was proportional to irradiation dose and was identical for all the different human cell lines, irrespective of radiosensitivity. On the other hand, the number of chromosome 4 breaks remaining 24 h after irradiation reflected the radiosensitivity of the cells such that the relationship between residual chromosome aberrations and cell survival was the same for the different cell lines. These results suggest that the scoring of chromosome aberrations in interphase using FISH with PCC holds considerable promise for predicting the radiosensitivity of normal and tumor tissues in situ. 28 refs., 4 figs.

  7. 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.

  8. 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.

  9. In Vitro Chromosome Aberrations Study in Chinese Hamster Ovary (CHO) Cells

    Science.gov (United States)

    2016-06-07

    CELLS Project No. ILS A073-004 Sponsor’s Study Number DAADOS-91-C-00 18 Test Substance FE-13 ILS Repository No. 96-01 Final Report Date May...Drive Durham, NC 27713 P.O. Box 13501 Research Triangle Park, NC 27709 QUALITY ASSURANCE INSPECTION STATEMENT ILS Project No.: Test Substance ID... ILS Repository No.: ILS A073-004 FE-13 96-01 Study Title: In Vitro Chromosome Aberrations Study in Chinese Hamster Ovary (CHO) Cells This study

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. UV-induced chromosome aberrations, sister-chromatid exchanges and cell survival in cultured lymphocytes from malnourished children

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, P.B.; Rahiman, M.A.; Tulpule, P.G.

    1982-08-01

    Cultured lymphocytes from children with kwashiorkor and from normal children were examined for their susceptibility to ultraviolet (UV)-induced chromosome aberrations, sister-chromatid exchanges and cell survival. Cells from kwashiorkor exhibited increased chromosome aberrations, but not sister-chromatid exchanges, when exposed to higher doses of UV. Furthermore, when cells from these patients were exposed to higher doses of UV, there was a significant reduction in viability. These results indicate that, as compared to normals, cells from kwashiorkor were more sensitive to the lethal effects of UV.

  8. 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.

  9. Chromosomal aberrations and DNA damage in human populations exposed to the processing of electronics waste.

    Science.gov (United States)

    Liu, Qiang; Cao, Jia; Li, Ke Qiu; Miao, Xu Hong; Li, Guang; Fan, Fei Yue; Zhao, Yong Cheng

    2009-05-01

    It has been known that the pollutants of electronic wastes (E-wastes) can lead to severe pollution to the environment. It has been reported that about 50% to 80% of E-wastes from developed countries are exported to Asia and Africa. It has become a major global environmental problem to deal with 'E-wastes'. E-waste recycling has remained primitive in Jinghai, China. This not only produces enormous environmental pollution but also can bring about toxic or genotoxic effects on the human body, threatening the health of both current residents and future generations living in the local environment. The concentration of lead in the blood of children in the E-waste polluted area in China is higher than that of the control area. But little is known about the cytogenetic effect to human beings caused by the pollution of E-wastes. In the present study, experiments have been performed to investigate the genetics of permanent residents of three villages with numerous E-waste disposal sites and to analyze the harmful effects of exposure to E-wastes. In total, 171 villagers (exposed group) were randomly selected from permanent residents of three villages located in Jinghai County of Tianjin, China, where there has been massive disposal of E-wastes. Thirty villagers were selected from the neighboring towns without E-waste disposal sites to serve as controls. Chromosomal aberrations and cytokinesis blocking micronucleus were performed to detect the cytogenetic effect, dic + r (dicentric and ring chromosome), monomer, fragments (acentric fragments, minute chromosomes, and acentric rings), translocation, satellite, quadriradial, total aberrations, and micronuclear rate were scored for each subject. DNA damage was detected using comet assay; the DNA percentage in the comet tail (TDNA%), tail moment (TM), and Olive tail moment (OTM) were recorded to describe DNA damage to lymphocytes. The total chromosome aberration rates (5.50%) and micronuclear rates (16.99%) of the exposure group

  10. 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.

  11. 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.

  12. 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.

  13. Validation of two-channel sequencing-by-synthesis for noninvasive prenatal testing of fetal whole and partial chromosome aberrations

    NARCIS (Netherlands)

    Neveling, K.; Thung, G.W.D.T.; Beulen, L.; Rens-Buijsman, W. van; Gomes, I.; Heuvel, S. van den; Mieloo, H.; Derks-Prinsen, I.; Kater-Baats, E.; Faas, B.H.W.

    2016-01-01

    OBJECTIVE: To validate Illumina's two-channel NextSeq 500 sequencing system for noninvasive prenatal testing (NIPT) of fetal whole chromosome and partial aberrations. METHODS: A total of 162 plasma samples, previously sequenced for NIPT on a SOLiD 5500xl platform, were sequenced on the NextSeq 500 u

  14. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Bonassi, S; Hagmar, L; Strömberg, U

    2000-01-01

    An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role p...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

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

    Science.gov (United States)

    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.

  2. 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.

  3. 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...

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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.

  7. [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.

  8. 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.

  9. 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.

  10. Effect of taxol on chromosome aberrations induced by gamma radiation or by doxorubicin in Chinese hamster ovary cells

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Francisca da Luz; Takahashi, Catarina S. [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras; Antunes, Lusania M.G. [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Medicina

    1997-09-01

    Combined therapy with radiation and chemotherapy has being increasingly used in cancer treatment. The effect of combinations of taxol (0.08 {mu}g/ml) with doxorubicin (DXR, 0,5 or 1.0 {mu}g/ml) or gamma radiation (20 or 40 cGy) was examined in two different treatment schedules (pretreatment or simultaneous treatment) using Chinese hamster ovary (CHO) cells treated at the G2 phase of the cell cycle. The results showed that taxol did not have a radiosensitizing effect on the chromosomal aberrations induced by gamma radiation nor did it have a potentiating effect on the chromosomal aberrations induced by DXR in CHO cells treated in the G2 phase of the cell cycle. (author) 43 refs., 3 tabs.

  11. Diethylstilbestrol-diphosphate induces chromosomal aberrations but not sister chromatid exchanges in murine bone marrow cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Ivett, J.L. (North Carolina State Univ., Raleigh); Tice, R.R.

    1981-01-01

    Diethylstilbestrol diphosphate (DES-dp) clastogenesis was examined in the bone marrow of C57B1/6 male and female mice. Significant and sex-related dose effects were observed for the induction of chromatid-type chromosomal aberrations and for the inhibition of cellular proliferation. Females were more sensitive to the effects of DES-dp than males when assessed for either induced chromosomal aberrations or proliferative inhibition. Contrary to other published results, we did not observe either an increase in sister chromatid exchanges or an increased incidence of aneuploidy. Ovariectomy reduced the ability of DES-dp to inhibit cellular proliferation and decreased the high degree of variability between animals at high doses of DES-dp. The results of our studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.

  12. 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

  13. 21q22 balanced chromosome aberrations in therapy-related hematopoietic disorders: report from an international workshop.

    Science.gov (United States)

    Slovak, Marilyn L; Bedell, Victoria; Popplewell, Leslie; Arber, Daniel A; Schoch, Claudia; Slater, Rosalyn

    2002-04-01

    The International Workshop on the relationship between prior therapy and balanced chromosome aberrations in therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute leukemia (t-AL) identified 79 of 511 (15.5%) patients with balanced 21q22 translocations. Patients were treated for their primary disease, including solid tumors (56%), hematologic malignancy (43%), and juvenile rheumatoid arthritis (single case), by radiation therapy (5 patients), chemotherapy (36 patients), or combined-modality therapy (38 patients). 21q translocations involved common partner chromosomes in 81% of cases: t(8;21) (n = 44; 56%), t(3;21) (n = 16; 20%), and t(16;21) (n = 4; 5%). Translocations involving 15 other partner chromosomes were also documented with involvement of AML1(CBFA2/RUNX1), identifying a total of 23 different 21q22/AML1 translocations. The data analysis was carried out on the basis of five subsets of 21q22 cases, that is, t(8;21) with and without additional aberrations, t(3;21), t(16;21), and other 21q22 translocations. Dysplastic features were present in all 21q22 cases. Therapy-related acute myeloid leukemia (t-AML) at presentation was highest in t(8;21) (82%) and lowest in t(3;21) (37.5%) patients. Cumulative drug dose exposure scores for alkylating agents (AAs) and topoisomerase II inhibitors indicated that t(3;21) patients received the most intensive therapy among the five 21q22 subsets, and the median AA score for patients with secondary chromosome 7 aberrations was double the AA score for the entire 21q22 group. All five patients who received only radiation therapy had t(8;21) t-AML. The median latency and overall survival (OS) for 21q22 patients were 39 and 14 months (mo), compared to 26 and 8 mo for 11q23 patients, 22 and 28 mo for inv(16), 69 and 7 mo for Rare recurring aberrations, and 59 and 7 mo for Unique (nonrecurring) balanced aberration (latency P MDS/t-AML with balanced 21q22 aberrations was associated with prior exposure to radiation

  14. 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).

  15. 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.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    Jørs, Erik; Gonzáles, Ana Rosa; Ascarrunz, Maria Eugenia; Tirado, Noemi; Takahashi, Catharina; Lafuente, Erika; Dos Santos, Raquel A; Bailon, Natalia; Cervantes, Rafael; O, Huici; Bælum, Jesper; Lander, Flemming

    2007-11-12

    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. 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. 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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Ability of root canal antiseptics used in dental practice to induce chromosome aberrations in human dental pulp cells.

    Science.gov (United States)

    Nishimura, Hiroyuki; Higo, Yukari; Ohno, Maki; Tsutsui, Takeo W; Tsutsui, Takeki

    2008-01-08

    Root canal antiseptics are topically applied to root canals within the pulpless teeth to treat the root canal and periapical infections. Because the antiseptics that are applied to root canals can penetrate through dentin or leak out through an apical foramen into the periodontium and distribute by the systemic circulation, it is important to study the safety of these antiseptics. In the present study, we examined the ability to induce chromosome aberrations in human dental pulp cells of five root canal antiseptics, namely, carbol camphor (CC), camphorated p-monochlorophenol (CMCP), formocresol (FC), calcium hydroxide, and iodoform which are most commonly used in dental practice. Statistically significant increases in the levels of chromosome aberrations were induced by CC, FC, or iodoform in a concentration-dependent manner. Conversely, CMCP and calcium hydroxide failed to induce chromosome aberrations in the absence or presence of exogenous metabolic activation. The percentages of cells with polyploid or endoreduplication were enhanced by FC or iodoform. Our results indicate that the root canal antiseptics that exhibited a positive response are potentially genotoxic to human cells.

  1. Chromosomal aberrations are shared by malignant plasma cells and a small fraction of circulating CD19+ cells in patients with myeloma and monoclonal gammopathy of undetermined significance

    National Research Council Canada - National Science Library

    Zojer, Niklas; Schuster-Kolbe, Judith; Assmann, Irene; Ackermann, Jutta; Strasser, Kathrin; Hubl, Wolfgang; Drach, Johannes; Ludwig, Heinz

    2002-01-01

    In the present study, we aimed to identify distinct structural and numerical chromosomal aberrations in peripheral blood B cells of patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS...

  2. 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

  3. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach.

    Science.gov (United States)

    Moretti, Massimo; Grollino, Maria Giuseppa; Pavanello, Sofia; Bonfiglioli, Roberta; Villarini, Milena; Appolloni, Massimo; Carrieri, Mariella; Sabatini, Laura; Dominici, Luca; Stronati, Laura; Mastrangelo, Giuseppe; Barbieri, Anna; Fatigoni, Cristina; Bartolucci, Giovanni Battista; Ceretti, Elisabetta; Mussi, Francesca; Monarca, Silvano

    2015-08-01

    Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD. Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses' clothes (pads). The concentration of unmetabolized CP—as a biomarker of internal dose—was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well. We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p < 0.0001) in exposed nurses versus controls, as well as in CA detection (3.30 ± 2.05 and 1.84 ± 1.67; p < 0.0001), exposed subjects versus controls. Our results provide evidence that, despite safety controlled conditions, ANPD handling still represents a considerable genotoxic risk for occupationally exposed personnel. Because both MN and CA have been described as being predictive of group-increased cancer risk, our findings point to a need for improving specific safety procedures in handling and administering ANPD.

  4. Comprehensive retrospective evaluation of existing in vitro chromosomal aberration test data by cytotoxicity index transformation.

    Science.gov (United States)

    Fujita, Yurika; Morita, Takeshi; Matsumura, Shoji; Kawamoto, Taisuke; Ito, Yuichi; Nishiyama, Naohiro; Honda, Hiroshi

    2016-05-01

    New OECD test guidelines have been issued, in which the cytotoxicity index relative cell count (RCC) is replaced with a new index, RICC or RPD (relative increase in cell count/relative population doubling), with the goal of reducing the high proportion of false positive results in in vitro chromosomal aberration tests. Using a mathematical approach to estimate new indices from the RCC, we constructed an evaluation flow that quantitatively estimates how often the previous test conclusions change when applying the updated cytotoxicity criteria. The new evaluation flow was applied to a retrospective evaluation of 285 chemicals in two databases. The effects of the employment of new cytotoxicity indices are investigated at a large scale. Using the new evaluation flow, 90 chemicals were estimated as positive, 39 were designated as estimated negative (13 probably negative and 26 possibly negative), and 140 were designated as negative. Moreover, we also applied a prioritization index to indicate the likelihood of a chemical being re-evaluated as negative and assigned priorities for testing. Most of the chemicals that were designated as estimated negative and had negative results in the in vivo micronucleus tests were considered as false-positives that would be correctly judged under the new test guideline. Furthermore, statistical analysis of the frequency of estimated negatives revealed that the results for Ames-positive chemicals, especially those with a strong response, are unlikely to change. Therefore, we concluded that the new indices would likely reduce the proportion of false positive results and not increase the proportion of false negative results. This study is the first report of a comprehensive re-evaluation of test results in terms of new cytotoxicity indices. The evaluation flow we have developed facilitates efficient retrospective evaluation of genotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 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.

  6. 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)

  7. Assessment of genotoxicity of 14 chemical agents used in dental practice: ability to induce chromosome aberrations in Syrian hamster embryo cells.

    Science.gov (United States)

    Hagiwara, Makoto; Watanabe, Eiko; Barrett, J Carl; Tsutsui, Takeki

    2006-02-28

    To assess the genotoxicity of 14 chemical agents used as locally applied agents in dental practice, the ability of these agents to elicit chromosome aberrations was examined using Syrian hamster embryo (SHE) cells. Chromosome aberrations in SHE cells were induced by treatment with three of eight chemical agents used as endodontic medicaments, i.e. ethylenediaminetetraacetic acid (EDTA), formocresol (a mixture of formalin and tricresol), and sodium arsenite. The other five chemical agents, i.e. chloramphenicol, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, and tetracycline hydrochloride exhibited a negative response for chromosome aberrations. Assessment of three dyes used for disclosing dental plaque showed chromosome aberrations induced by basic fuchsin but not by acid fuchsin and erythrosine B. Three local anesthetics, lidocaine hydrochloride, prilocaine hydrochloride, and procaine hydrochloride, were negative for chromosome aberrations. Among the ten chemical agents that exhibited a negative response in the assay, p-chlorophenol, sodium hypochlorite, and erythrosine B induced chromosome aberrations in SHE cells when treated in the presence of exogenous metabolic activation. The percentages of cells with polyploidy or endoreduplication were enhanced by formocresol, sodium arsenite, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, erythrosine B, prilocaine hydrochloride, and procaine hydrochloride in the absence or presence of exogenous metabolic activation. Our results indicate that the chemical agents that had a positive response in the present study are potentially genotoxic to mammalian cells.

  8. 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.

  9. 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.

  10. A study to verify a reported excess of chromosomal aberrations in blood lymphocytes of Namibian uranium miners.

    Science.gov (United States)

    Lloyd, D C; Lucas, J N; Edwards, A A; Deng, W; Valente, E; Hone, P A; Moquet, J E

    2001-06-01

    This report describes a study to verify an earlier report of excess chromosomal damage in the blood lymphocytes of uranium miners. Coded blood samples from 10 miners and 10 controls were analyzed conventionally for unstable aberrations and by FISH for translocations. Conventional analysis, scoring 1000 metaphases per subject, showed no significant difference between miners and controls in the frequencies of chromosome- and chromatid-type aberrations. Investigators at two laboratories undertook FISH analyses, each scoring 4000 metaphases per subject. When the data from each laboratory were examined separately, one found slightly more translocations in the miners while the other found fewer. In neither case was the difference significant at the 95% level of confidence. Combining the data likewise showed no significant excess of damage in the miners. This applied to simple one- and two-way translocations and to cells with complex exchanges. There was no correlation between levels of translocations and total lifetime doses from occupational and/or background irradiation. A borderline significant excess of rogue cells was found in the miners. This may be a chance observation, as these rare, highly abnormal cells are considered to be unrelated to radiation exposure and are probably due to a virus. The overall conclusion is that the frequency of chromosomal damage in the miners did not exceed that in the controls. Therefore, the result of the earlier study was not confirmed.

  11. 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...

  12. 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

  13. Chromosomal aberrations and polymorphic evaluation in males with primary infertility from Indian population.

    Science.gov (United States)

    Kate, Ushang V; Pokale, Yamini S; Jadhav, Ajinkya M; Gangane, Suresh D

    2014-10-01

    The chromosomal abnormalities are one of the important causes of male infertility. In view of the genetic risks for the next generation, the importance of careful evaluation of karyotype is essential. The objective of this study was to determine the frequency of chromosomal abnormalities in infertile men with primary infertility from Indian population. The 78 infertile men with primary infertility, out of which 26 men were azoospermic, 19 men were oligospermic, 4 men were asthenospermic and 29 men were oligoasthenospermic were studied. Karyoptying was performed on peripheral blood lymphocytes by using the Giemsa trypsin banding (GTG) banding technique. Additional data was collected from published studies in Indian population leading to a total of 1814 cases. Chromosome analysis of 78 infertile males showed major chromosome abnormalities in 10.2%, with 6.4% in autosomal chromosome abnormalities and 3.8% in sex chromosome abnormalities. The incidence of major chromosome abnormalities in oligospermic males were 21% and azoospermic males were 15.4 %. Chromosomal polymorphic variants were identified to be 16.7%. Combining the data from other published studies identified 153/ 1814 (8.4%) infertile men of chromosomal abnormalities; with 10.8% in azoospermia, 7.3% in oligospermia and 7.3% in oligoasthenoteratospermic from India. The overall high prevalence of chromosomal abnormalities in infertile males suggests that the conventional chromosomal analysis is an important investigative tool for male infertility, especially prior to use of any assisted reproductive techniques.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. [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.

  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. Detection of chromosomal aberrations in seminomatous germ cell tumours using comparative genomic hybridization

    DEFF Research Database (Denmark)

    Ottesen, A M; Kirchhoff, M; Rajpert-De Meyts, Ewa

    1997-01-01

    Comparative genomic hybridization (CGH) was used to evaluate tissue specimens from 16 seminomas in order to elucidate the pathogenesis of germ cell tumours in males. A characteristic pattern of losses and gains within the entire genomes was detected in 94% of the seminomas by comparing the ratio...... was demonstrated in the seminomas by improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in clinical stage II...

  4. 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.

  5. 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.

  6. 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...

  7. GeneBreak: detection of recurrent DNA copy number aberration-associated chromosomal breakpoints within genes [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Evert van den Broek

    2017-07-01

    Full Text Available Development of cancer is driven by somatic alterations, including numerical and structural chromosomal aberrations. Currently, several computational methods are available and are widely applied to detect numerical copy number aberrations (CNAs of chromosomal segments in tumor genomes. However, there is lack of computational methods that systematically detect structural chromosomal aberrations by virtue of the genomic location of CNA-associated chromosomal breaks and identify genes that appear non-randomly affected by chromosomal breakpoints across (large series of tumor samples. ‘GeneBreak’ is developed to systematically identify genes recurrently affected by the genomic location of chromosomal CNA-associated breaks by a genome-wide approach, which can be applied to DNA copy number data obtained by array-Comparative Genomic Hybridization (CGH or by (low-pass whole genome sequencing (WGS. First, ‘GeneBreak’ collects the genomic locations of chromosomal CNA-associated breaks that were previously pinpointed by the segmentation algorithm that was applied to obtain CNA profiles. Next, a tailored annotation approach for breakpoint-to-gene mapping is implemented. Finally, dedicated cohort-based statistics is incorporated with correction for covariates that influence the probability to be a breakpoint gene. In addition, multiple testing correction is integrated to reveal recurrent breakpoint events. This easy-to-use algorithm, ‘GeneBreak’, is implemented in R (www.cran.r-project.org and is available from Bioconductor (www.bioconductor.org/packages/release/bioc/html/GeneBreak.html.

  8. 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)

  9. 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

  10. 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

  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. Analyses of numerical aberrations of chromosome 17 and tp53 gene deletion/amplification in human oral squamous cell carcinoma using dual-color fluorescence in situ hybridization

    Directory of Open Access Journals (Sweden)

    Noemi MESZAROS

    2010-05-01

    Full Text Available In Romania, oral and facial cancers represent approximately 5% of all cancers. Deactivation and unregulated expression of oncogenes and tumor suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma. The genomic change results in numerical and structural chromosomal alterations, particularly in chromosomes 3, 9, 11 and 17. The aim of our study was to identify numerical aberrations of chromosome 17, deletion or amplification of p53 gene and to reveal correlations between abnormalities of chromosome 17and of p53 gene with TNM status and grading in 15 subjects with oral squamous cell carcinoma. 80 % of cases presented chromosome 17 polysomy and only 20% of cases had chromosome 17 monosomy. 46.6 % of samples revealed p53 gene amplification and 33.3 % of them p53 deletion. Polysomy of chromosome 17 was also detected in tumor-adjacent epithelia. The degree of the cytogenetic abnormality did not correlate with the stage of the disease, the histological differentiation of oral squamous cell carcinoma and lymph node metastasis. Molecular cytogenetic techniques, using fluorescence in situ hybridization with chromosome-specific DNA probes, facilitate the confirmation of presumed chromosomal aberrations with high sensitivity and specificity.

  13. 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.

  14. 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.

  15. Psoralen/UVA treatment and chromosomes. I. Aberrations and sister chromatid exchange in human lymphocytes in vitro and synergism with caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Waksvik, H.; Brogger, A.; Stene, J.

    1977-09-22

    Treatment of human lymphocytes in vitro with trimethylpsoralen or 8-methoxypsoralen and UVA irradiation (PUVA) induced chromosome damage, mainly constrictions and gaps, but also breaks and exchanges, and increased the frequency of sister chromatid exchange (SCE). The localization of the chromosome aberrations was nonrandom. The coincidence of many PUVA hits with mercaptoenthanol hits suggests that PUVA may have other targets in the cell than the DNA, perhaps the folding proteins of the chromosomes and the nuclear membrane/chromatin attachment organelles. Caffeine increased in a synergistic way the chromosome aberration yield if added after PUVA treatment, but there was no effect when caffeine was present before and during PUVA treatment. The SCE frequency was increased in the presence of caffeine.

  16. 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...... similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility........ No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were...

  17. 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.

  18. 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)

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization

    Directory of Open Access Journals (Sweden)

    Zakaria Zubaidah

    2012-11-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is a heterogeneous form of hematological cancer consisting of various subtypes. We are interested to study the genetic aberration in precursor B-cell ALL with specific t(12;21 translocation in childhood ALL patients. A high resolution 244K array-based Comparative Genomic Hybridization (array-CGH was used to study eleven ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL patients. Result 155 chromosomal aberrations (119 losses, 36 gains were reported in the array findings, corresponding to 76.8% deletions and 23.2% amplifications. The ETV6 gene deletion occurred in 4 of the patients, corresponding to 45% of the sample. The most common alterations above 1 Mb were deletion 6q (13%, 12p (12% and 9p (8%, and duplication 4q (6% and Xq (4%. Other genes important in ALL were also identified in this study including RUNX1, CDKN2A, FHIT, and PAX5. The array-CGH technique was able to detect microdeletion as small as 400 bp. Conclusion The results demonstrate the usefulness of high resolution array-CGH as a complementary tool in the investigation of ALL.

  5. [Investigation of chromosome 1 aberrations in patients with multiple myeloma using cIg-FISH method and its significance].

    Science.gov (United States)

    Yang, Rui-Fang; Li, Chun-Ming; Qiu, Hai-Rong; Lu, Hua; Wu, Han-Xin; Xu, Jia-Ren; Li, Jian-Yong; Chen, Li-Juan

    2010-12-01

    To investigate the incidence of 1q21 amplification and 1p12 deletion, and analyze the correlation between these aberrations with disease progression, prognosis and outcome in patients with multiple myeloma (MM). Cytoplasm light chain immunofluorescence with simultaneous interphase fluorescence in situ hybridization (cIg-FISH) was used to detecte the 1q21 amplification and 1p12 deletion in 48 patients with MM. 1q21 amplification (≥ 3 red signals) was determined in 26 of 48(54.2%) cases. The mortality of patients with 1q21 amplification was significantly higher than that of those lacking 1q21 amplification (P 0.05). There was a significant difference in D-S stage and mortality between patients with 3 and with 4 copies of 1q21 (P 0.05). 1p12 deletion (< 2 green signals) was found in 14 of 48 (29.2%) cases. There was no significant difference in sex, age, D-S stage, ISS stage, isotype, subgroup, and mortality between patients with and without 1p12 deletion. The frequency of chromosome 1 aberrations in multiple myeloma is high and 1q21 amplification is a poor prognosis factor.

  6. 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)

  7. 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 as a biomar...

  8. 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

  9. 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.

  10. Chromosomal aberrations in benign and malignant Bilharzia-associated bladder lesions analyzed by comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Ibrahim Muntaser

    2002-03-01

    Full Text Available Abstract Background Bilharzia-associated bladder cancer (BAC is a major health problem in countries where urinary schistosomiasis is endemic. Characterization of the genetic alterations in this cancer might enhance our understanding of the pathogenic mechanisms of the disease but, in contrast to nonbilharzia bladder cancer, BAC has rarely been the object of such scrutiny. In the present study, we aimed to characterize chromosomal imbalances in benign and malignant post-bilharzial lesions, and to determine whether their unique etiology yields a distinct cytogenetic profile as compared to chemically induced bladder tumors. Methods DNAs from 20 archival paraffin-embedded post-bilharzial bladder lesions (6 benign and 14 malignant obtained from Sudanese patients (12 males and 8 females with a history of urinary bilharziasis were investigated for chromosomal imbalances using comparative genomic hybridization (CGH. Subsequent FISH analysis with pericentromeric probes was performed on paraffin sections of the same cases to confirm the CGH results. Results Seven of the 20 lesions (6 carcinomas and one granuloma showed chromosomal imbalances varying from 1 to 6 changes. The most common chromosomal imbalances detected were losses of 1p21-31, 8p21-pter, and 9p and gain of 19p material, seen in three cases each, including the benign lesion. Conclusion Most of the detected imbalances have been repeatedly reported in non-bilharzial bladder carcinomas, suggesting that the cytogenetic profiles of chemical- and bilharzia-induced carcinomas are largely similar. However, loss of 9p seems to be more ubiquitous in BAC than in bladder cancer in industrialized countries.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Chromosomal aberration in peripheral lymphocytes and doses to the active bone marrow in radiotherapy of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gershkevitsh, E. [Clinicum of the University of Tartu (Estonia). Dept. of Radiotherapy; Hildebrandt, G.; Wolf, U.; Kamprad, F. [Leipzig Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie; Realo, E. [Lab. of Nuclear Spectroscopy, Inst. of Physics, Tartu (Estonia); Trott, K.R. [Queen Mary and Westfield Coll., London (United Kingdom). St. Bartholomew' s and the Royal London School of Medicine and Dentistry

    2002-01-01

    Purpose: Radiotherapy plays an important role in the management of prostate cancer. Epidemiological data indicate a small but significant risk of radiation-induced leukemia after radiotherapy which might be related to the high mean bone marrow dose associated with radiotherapy of prostate cancer. The purpose of the study was to investigate the relation between the mean bone marrow dose and unstable chromosome aberrations in peripheral blood lymphocytes in patients undergoing conformal radiotherapy for prostate cancer as a possible indicator of risk. Endometrial cancer patients were also included for comparison. Patients and Methods: Nine patients, six with prostate cancer (60-73 years old) and three with endometrial cancer (61-81 years old) treated with radiotherapy were included in the study. The non-bony spaces inside the pelvic bones were outlined on every CT slice using the treatment planning system and mean doses to the bone marrow calculated. Blood samples of the patients were obtained at different times before, during and at the end of treatment. Lymphocytes were cultured in the usual way and metaphases scored for dicentric aberrations. Results: 46 samples from nine patients were obtained. The mean number of metaphases analyzed per sample was 180 with a range from 52 to 435. The mean bone marrow doses for prostate cancer patients ranged from 2.8 to 4.2 Gy and for endometrial cancer patients from 12.8 to 14.8 Gy. The aberration yield increased with the planning target volume and the mean bone marrow dose. Conclusion: The yield of dicentric aberrations for prostate cancer patients correlated closely with the mean bone marrow dose albeit the induction of dicentrics occurred in mature T lymphocytes most of which were probably in transit through the irradiated volumes. Therefore, the observed relationship between dicentrics and mean bone marrow doses are indirect. (orig.) [German] Hintergrund: Bei der kurativen Behandlung des Prostatakarzinoms besitzt die

  8. 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.

  9. 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.

  10. [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.

  11. 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.

  12. 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.

  13. 1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma

    Science.gov (United States)

    Fournier, Alexandra; McLeer-Florin, Anne; Lefebvre, Christine; Duley, Samuel; Barki, Leila; Ribeyron, Juliana; Kassambara, Alboukadel; Hamaidia, Sieme; Granjon, Aurélie; Gressin, Rémy; Lajmanovich, Alicia; Bonnefoix, Thierry; Chauvelier, Stéphanie; Debernardi, Alexandra; Rousseaux, Sophie; de Fraipont, Florence; Figeac, Martin; Kerckaert, Jean-Pierre; De Vos, John; Usson, Yves; Delaval, Katia; Grichine, Alexei; Vourc'h, Claire; Khochbin, Saadi; Feil, Robert; Leroux, Dominique; Callanan, Mary B

    2010-01-01

    Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here, we report the first evidence that a distinct category of chromosomal translocations observed in human tumours—those targeting 1q12 satellite DNA—can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localized to the nuclear periphery and to arise as a consequence of long range ‘pairing’ between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localization and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in diffuse large B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression via long range epigenetic mechanisms. PMID:20432501

  14. 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

  15. 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.

  16. Combined spectral karyotyping, comparative genomic hybridization, and in vitro apoptyping of a panel of Burkitt's lymphoma-derived B cell lines reveals an unexpected complexity of chromosomal aberrations and a recurrence of specific abnormalities in chemoresistant cell lines

    National Research Council Canada - National Science Library

    Karpova, Maria B; Schoumans, Jacqueline; Blennow, Elisabeth; Ernberg, Ingemar; Henter, Jan-Inge; Smirnov, Aleksandr F; Nordenskjöld, Magnus; Fadeel, Bengt

    2006-01-01

    ...). Spectral karyotyping (SKY) revealed a large number of structural and numerical chromosomal aberrations, many of which had not been previously identified or resolved by conventional G-banding techniques...

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

    Directory of Open Access Journals (Sweden)

    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

  18. The genes of interferons and interferon-related factors: localization and relationships with chromosome aberrations in cancer.

    Science.gov (United States)

    Haus, O

    2000-01-01

    The paper presents a review of data on the localization of interferons (IFNs) and IFN system genes and their relationship with human diseases, mainly cancer. Genes of interferon system proteins are located at the sites of breakpoints of the structural chromosome aberrations in cancer. Thus, any of them are rearranged or translocated in various tumor types. As the activity of these genes plays a role in cancer development, their rearrangements may be one of the crucial points in the pathogenesis of some cancer types. Besides, they also take part in organism immunity against viral infections. Transfection experiments with IFN system genes have proved the influence of these genes on cancer behavior and may serve as a basis for clinical gene therapy. IFN-alpha and IFN-beta genes are located at 9p21-22, the site of frequent homozygotic deletions in cancer. Their loss sensitizes cells to the growth inhibitory actions of exogenous IFNs. The IFN-gamma gene, a representative of class II genes, is located at 12q24.1. Transfection of class II IFNs genes to cancer cell lines causes cell proliferation arrest and augments the expression of HLA antigens, which may be clinically useful in stimulating the immune destruction of tumor cells. The interferon regulatory factor 1 (IRF-1) gene is located at 5q31, the site of common deletions in myelodysplastic syndromes (MDS) and secondary leukemias. The loss of heterozygosity of this gene was found in MDS, which proves that IRF-1 may be a tumor suppressor. A transfection of its gene causes neoplastic transformation arrest. The double-stranded RNA-activated protein kinase (PKR) gene is located at 2p21-22, a region which is frequently rearranged in leukemia. Transfection of a wild type PKR gene reverses neoplastic transformation caused by transfection of a mutated PKR gene, proving that PKR acts as a dominant negative cancer suppressor.

  19. Radiation-induced chromosome aberrations in ataxia telangiectasia cells: high frequency of deletions and misrejoining detected by fluorescence in situ hybridization

    Science.gov (United States)

    Kawata, Tetsuya; Ito, Hisao; George, Kerry; Wu, Honglu; Uno, Takashi; Isobe, Kouichi; Cucinotta, Francis A.

    2003-01-01

    The mechanisms underlying the hyper-radiosensitivity of AT cells were investigated by analyzing chromosome aberrations in the G(2) and M phases of the cell cycle using a combination of chemically induced premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with chromosome painting probes. Confluent cultures of normal fibroblast cells (AG1522) and fibroblast cells derived from an individual with AT (GM02052) were exposed to gamma rays and allowed to repair at 37 degrees C for 24 h. At doses that resulted in 10% survival, GM02052 cells were approximately five times more sensitive to gamma rays than AG1522 cells. For a given dose, GM02052 cells contained a much higher frequency of deletions and misrejoining than AG1522 cells. For both cell types, a good correlation was found between the percentage of aberrant cells and cell survival. The average number of color junctions, which represent the frequency of chromosome misrejoining, was also found to correlate well with survival. However, in a similar surviving population of GM02052 and AG1522 cells, induced by 1 Gy and 6 Gy, respectively, AG1522 cells contained four times more color junctions and half as many deletions as GM02052 cells. These results indicate that both repair deficiency and misrepair may be involved in the hyper-radiosensitivity of AT cells.

  20. 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.

  1. Ultrasoft 1.5 keV aluminum K X rays are efficient producers of complex chromosome exchange aberrations as revealed by fluorescence in situ hybridization.

    Science.gov (United States)

    Griffin, C S; Stevens, D L; Savage, J R

    1996-08-01

    The electron pairs generated by ultrasoft 1.5 keV aluminum K X-ray photons deposit their energy in tracks of length < 70 nm and provide an ideal tool for analyzing the spatial distribution of breaks and misrepair processes. We have undertaken the analysis of changes in chromosome structure produced by aluminum K X rays in untransformed HF12 human fibroblasts in G1 phase using fluorescence in situ hybridization (FISH). Multicolored chromosome-specific DNA probes for chromosomes 1 and 2 and an alpha-satellite pan-centromeric probe were used to examine in vitro radiation-induced chromosome-type exchange aberrations. After mean doses of 0.37-2.93 Gy the relative frequencies of complex exchanges, derived from three or more breaks in two or more chromosomes, ranged from 15-35%. For the classic break-age-and-rejoining theory to hold, very large interaction distances are needed to account for this high frequency of multibreak interactions, unless many sites pre-exist where several different chromosomes come very close together. Alternatively, damaged DNA may be able to interact with adjacent undamaged DNA, obviating the need for large rejoining distances.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Evaluation of chromosomal aberrations caused by air pollutants in some taxi drivers from two polluted districts of urban Tehran and its comparison with drivers from rural areas of Lahijan: a pilot study.

    Science.gov (United States)

    Taghizadeh, Sara; Najmabadi, Hossein; Kamali, Koorosh; Behjati, Farkhondeh

    2014-01-01

    Chromosome instability is the most common form of genomic instability. Genomic instability can lead to tumorogenesis. High level of chromosomal aberrations in peripheral blood lymphocytes can be used as a biomarker for cancer. Air pollution is one of the most important factors that cause chromosomal instability (CIN). In this comparative study we used classic Cytogenetic technique to analyze the effects of air pollutants on chromosome stability. We collected peripheral blood from 30 taxi drivers of two polluted districts (districts 6 and 7) in Tehran and 30 taxi drivers from rural areas of Lahijan, north of Iran. Comparison of the level of chromosome breakage in the two groups showed an increased level of chromosome breakage in the drivers from polluted districts of Tehran, although not significant, using Fisher exact test (p-value = 0.300). However, the overall chromosome aberration rate (including both chromosome and chromatid gaps), the difference was significant using Chi-square test (p-value = 0.012). An increased level of chromosome aberration was present in the drivers from polluted districts of Tehran compared to drivers from non-polluted areas in Lahijan.

  12. 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.

  13. Chromosome-wise Protein Interaction Patterns and Their Impact on Functional Implications of Large-Scale Genomic Aberrations

    DEFF Research Database (Denmark)

    Kirk, Isa Kristina; Weinhold, Nils; Belling, Kirstine González-Izarzugaza

    2017-01-01

    Gene copy-number changes influence phenotypes through gene-dosage alteration and subsequent changes of protein complex stoichiometry. Human trisomies where gene copy numbers are increased uniformly over entire chromosomes provide generic cases for studying these relationships. In most trisomies......, gene and protein level alterations have fatal consequences. We used genome-wide protein-protein interaction data to identify chromosome-specific patterns of protein interactions. We found that some chromosomes encode proteins that interact infrequently with each other, chromosome 21 in particular. We...

  14. 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)

  15. 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 ...

  16. Investigating 22q11.2 deletion and other chromosomal aberrations in fetuses with heart defects detected by prenatal echocardiography.

    Science.gov (United States)

    Bellucco, Fernanda Teixeira da Silva; Belangero, Sintia Iole Nogueira; Farah, Leila Montenegro Silveira; Machado, Maria Virgínia Lima; Cruz, Adriano Pastor; Lopes, Lílian Maria; Lopes, Marco Antonio Borges; Zugaib, Marcelo; Cernach, Mirlene Cecília; Melaragno, Maria Isabel

    2010-11-01

    Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated.

  17. Genotoxic biomonitoring study of population residing in pesticide contaminated regions in Göksu Delta: micronucleus, chromosomal aberrations and sister chromatid exchanges.

    Science.gov (United States)

    Ergene, Serap; Celik, Ayla; Cavaş, Tolga; Kaya, Filiz

    2007-10-01

    Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless, exposure to pesticides represents a potential risk to humans. This paper describes a study of possible genetic damage in the people living in regions contaminated with complex mixture of pesticides in Göksu Delta. In this study, used methods were chromosomal aberration (CA), sister chromatid exchange analysis (SCE) in the peripheral blood lymphocytes, and micronucleus (MN) assay in the buccal epithelial cells. In the present investigation, 32 affected subjects consist of 16 smoking and 16 non-smokings and an equal number of control subjects were assessed for genome damage. Micronucleus (MN), Broken egg (BE), Karyorrhexis (KR), Karyolysis (KL) and Binucleus (BN) frequencies were higher in affected subjects than in controls. Smoking had a statistically significant effect on the Micronucleus, Karyorrhexis and Binucleus frequencies for both the control and the exposed group. Also smoking and exposure affected the frequency of sister chromatid exchange and chromosomal aberrations compared with control groups.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. Induction of chromosome aberrations is non-linear within the low dose region and depends on dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Oudalova, A.A.; Geras' kin, S.A.; Dikarev, V.G.; Nesterov, Y.B.; Dikareva, N.S

    2002-07-01

    The low dose region was evaluated for meristem cells of spring barley. A study of the cytogenetic damage in the low dose range was carried out to determine the genuine shape of the dose curve. The relationship between the frequency of aberrant cells and the absorbed dose is shown to be non-linear with a site at low doses within which the cytogenetic damage exceeds the control level significantly and does not depend on dose value. Within the tested exposure region, the aberrant cell frequency is found to decrease with increasing dose rate, but the shape of the dose curve remained invariable. The piecewise linear model fits the experimental data much better than the linear one. (author)

  7. [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.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. [Prevalence of selected congenital anomalies in the Czech Republic: renal and cardiac anomalies and congenital chromosomal aberrations].

    Science.gov (United States)

    Šípek, Antonín; Gregor, Vladimír; Horáček, Jiří; Šípek, Antonín; Langhammer, Pavel

    2013-09-01

    Edwards syndrome was on the rise while that of postnatally diagnosed cases was declining. The rate of prenatally diagnosed cases rose from 63% to 96% over the last two years. The mean prevalence rate of postnatally diagnosed cases was 0.72 per 10,000 live births and the mean overall prevalence rate was 3.78 per 10,000 live births. Similarly, the rate of prenatally diagnosed Patau syndrome increased from 30% in 1997 to 100% in 2009 and the rate of postnatally diagnosed cases was declining. The mean prevalence rate of postnatally diagnosed cases was 0.40 per 10,000 live births and the mean overall prevalence rate was 1.38 per 10,000 live births. The overall prevalence rates of the monitored diagnoses from the group of congenital kidney disease (cystic kidney disease and renal agenesis/hypoplasia) were on the rise in the monitored -period mainly due to advances in imaging technologies (ultrasonography) and their use in both prenatal and postnatal diagnosis. Increase in postnatally diagnosed cases can be attributed primarily to the reporting of less severe cases (cystic kidney disease) or unilateral anomalies (renal agenesis and hypoplasia). As for the monitored congenital heart defects, advances in ultrasonographic imaging diagnosis played a considerable role in the increase of cases. The overall prevalence rate show a slow upward trend, but there is a significant decline in postnatally diagnosed cases due to prenatal diagnosis of a severe anomaly, left heart hypoplasia. As for congenital chromosomal aberrations, several interconnected factors influenced the final rate. Firstly, the proportion of prenatally diagnosed cases increases due to quantitative and qualitative improvements of the screening tests. They resulted in greater efficiency of prenatal diagnosis and, at the same time, in less need for invasive prenatal diagnostic procedures. Another factor is increase in average age at first birth and in the first birth rate for women aged over 35 years resulting in higher

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  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. 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

  2. [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).

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia.

    Science.gov (United States)

    Deneberg, Stefan; Kanduri, Meena; Ali, Dina; Bengtzen, Sofia; Karimi, Mohsen; Qu, Ying; Kimby, Eva; Mansouri, Larry; Rosenquist, Richard; Lennartsson, Andreas; Lehmann, Sören

    2014-06-01

    A commonly deleted region in chronic lymphocytic leukemia (CLL) is the 11q22-23 region, which encompasses the ATM gene. Evidence suggests that tumor suppressor genes other than ATM are likely to be involved in CLL with del(11q). A microRNA (miR) cluster including the miR-34b and miR-34c genes is located, among other genes, within the commonly deleted region (CDR) at 11q. Interestingly, these miRs are part of the TP53 network and have been shown to be epigenetically regulated. In this study, we investigated the expression and methylation status of these miRs in a well-characterized cohort of CLL, including cases with/without 11q-deletion. We show that the miR-34b/c promoter was aberrantly hypermethylated in a large proportion of CLL cases (48%, 25/52 cases). miR-34b/c expression correlated inversely to DNA methylation (P = 0.003), and presence of high H3K37me3 further suppressed expression regardless of methylation status. Furthermore, increased miR-34b/c methylation inversely correlated with the presence of 11q-deletion, indicating that methylation and del(11q) independently silence these miRs. Finally, 5-azacytidine and trichostatin A exposure synergistically increased the expression of miR-34b/c in CLL cells, and transfection of miR-34b or miR-34c into HG3 CLL cells significantly increased apoptosis. Altogether, our novel data suggest that miR-34b/c is a candidate tumor suppressor that is epigenetically silenced in CLL.

  9. 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.

  10. 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.

  11. 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.)

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Strain of Synechocystis PCC 6803 with Aberrant Assembly of Photosystem II Contains Tandem Duplication of a Large Chromosomal Region.

    Science.gov (United States)

    Tichý, Martin; Bečková, Martina; Kopečná, Jana; Noda, Judith; Sobotka, Roman; Komenda, Josef

    2016-01-01

    Cyanobacterium Synechocystis PCC 6803 represents a favored model organism for photosynthetic studies. Its easy transformability allowed construction of a vast number of Synechocystis mutants including many photosynthetically incompetent ones. However, it became clear that there is already a spectrum of Synechocystis "wild-type" substrains with apparently different phenotypes. Here, we analyzed organization of photosynthetic membrane complexes in a standard motile Pasteur collection strain termed PCC and two non-motile glucose-tolerant substrains (named here GT-P and GT-W) previously used as genetic backgrounds for construction of many photosynthetic site directed mutants. Although, both the GT-P and GT-W strains were derived from the same strain constructed and described by Williams in 1988, only GT-P was similar in pigmentation and in the compositions of Photosystem II (PSII) and Photosystem I (PSI) complexes to PCC. In contrast, GT-W contained much more carotenoids but significantly less chlorophyll (Chl), which was reflected by lower level of dimeric PSII and especially trimeric PSI. We found that GT-W was deficient in Chl biosynthesis and contained unusually high level of unassembled D1-D2 reaction center, CP47 and especially CP43. Another specific feature of GT-W was a several fold increase in the level of the Ycf39-Hlip complex previously postulated to participate in the recycling of Chl molecules. Genome re-sequencing revealed that the phenotype of GT-W is related to the tandem duplication of a large region of the chromosome that contains 100 genes including ones encoding D1, Psb28, and other PSII-related proteins as well as Mg-protoporphyrin methylester cyclase (Cycl). Interestingly, the duplication was completely eliminated after keeping GT-W cells on agar plates under photoautotrophic conditions for several months. The GT-W strain without a duplication showed no obvious defects in PSII assembly and resembled the GT-P substrain. Although, we do not exactly

  18. Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.

    Science.gov (United States)

    Wafa, Abdulsamad; As'sad, Manar; Liehr, Thomas; Aljapawe, Abdulmunim; Al Achkar, Walid

    2017-04-07

    The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20. Moreover, the translocation t(1;19) correlates with known clinical high risk factors, such as elevated white blood cell count, high serum lactate dehydrogenase levels, and central nervous system involvement; early reports indicated that patients with translocation t(1;19) had a poor outcome under standard treatment. We report the case of a 15-year-old Syrian boy with pre-B cell acute lymphoblastic leukemia with abnormal karyotype with a der(19)t(1;19)(q21.1;p13.3) and two yet unreported chromosomal aberrations: an interstitial deletion 6q12 to 6q26 and a der(13)t(1;13)(q21.1;p13). According to the literature, cases who are translocation t(1;19)-positive have a significantly higher incidence of central nervous system relapse than patients with acute lymphoblastic leukemia without the translocation. Of interest, central nervous system involvement was also seen in our patient. To the best of our knowledge, this is the first case of childhood pre-B cell acute lymphoblastic leukemia with an unbalanced translocation t(1;19) with two additional chromosomal aberrations, del(6)(q12q26) and t(1;13)(q21.3;p13), which seem to be recurrent and could influence clinical outcome. Also the present case confirms the impact of the translocation t(1;19) on central nervous system relapse, which should be studied for underlying mechanisms in future.

  19. 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.

  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. 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

  2. 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

  3. 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

  4. 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)

  5. 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.

  6. 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

  7. Novel recurrent chromosomal aberrations detected in clonal plasma cells of light chain amyloidosis patients show potential adverse prognostic effect: first results from a genome-wide copy number array analysis.

    Science.gov (United States)

    Granzow, Martin; Hegenbart, Ute; Hinderhofer, Katrin; Hose, Dirk; Seckinger, Anja; Bochtler, Tilmann; Hemminki, Kari; Goldschmidt, Hartmut; Schönland, Stefan O; Jauch, Anna

    2017-07-01

    Immunoglobulin light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by the deposition of abnormal amyloid fibrils in multiple organs, thus impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization (iFISH). We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%) and 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by iFISH was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with the breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by iFISH almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event-free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in AL amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered. Copyright© 2017 Ferrata Storti Foundation.

  8. High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration.

    Science.gov (United States)

    Paulsson, K; Heidenblad, M; Strömbeck, B; Staaf, J; Jönsson, G; Borg, A; Fioretos, T; Johansson, B

    2006-05-01

    Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic--possibly primary--genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing >98% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8 Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. Production of alien chromosome additions and their utility in plant genetics

    NARCIS (Netherlands)

    Chang, S.B.; Jong, de J.H.S.G.M.

    2005-01-01

    Breeding programs aiming at transferring desirable genes from one species to another through interspecific hybridization and backcrossings often produce monosomic and disomic additions as intermediate crossing products. Such aneuploids contain alien chromosomes added to the complements of the recipi

  15. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    Science.gov (United States)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Identification of Unbalanced Aberrations in the Genome of Equine Sarcoid Cells Using CGH Technique

    National Research Council Canada - National Science Library

    Monika Bugno-Poniewierska; Beata Staroń; Leszek Potocki; Artur Gurgul; Maciej Wnuk

    2016-01-01

    ...) technique identifying the unbalanced chromosome aberrations was used to analyze the genome of equine sarcoid cells and to diagnose the chromosome rearrangements involving large deletions or amplification...

  1. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)

    DEFF Research Database (Denmark)

    Huebner, K; Kastury, K; Druck, T;

    1994-01-01

    Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding "...

  2. 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

  3. Chromosomal Engineering of Escherichia coli for Efficient Production of Coenzyme Q10

    Institute of Scientific and Technical Information of China (English)

    黄明涛; 陈韵妍; 刘建忠

    2014-01-01

    The plasmid-expression system is routinely plagued by potential plasmid instability. Chromosomal in-tegration is one powerful approach to overcome the problem. Herein we report a plasmid-free hyper-producer E. coli strain for coenzyme Q10 production. A series of integration expression vectors, pxKC3T5b and pxKT5b, were constructed for chemically inducible chromosomal evolution (multiple copy integration) and replicon-free and markerless chromosomal integration (single copy integration), respectively. A coenzyme Q10 hyper-producer Es-cherichia coli TBW20134 was constructed by applying chemically inducible chromosomal evolution, replicon-free and markerless chromosomal integration as well as deletion of menaquinone biosynthetic pathway. The engineered E. coli TBW20134 produced 10.7 mg per gram of dry cell mass (DCM) of coenzyme Q10 when supplemented with 0.075 g·L-1 of 4-hydroxy benzoic acid;this yield is unprecedented in E. coli and close to that of the commercial producer Agrobacterium tumefaciens. With this strain, the coenzyme Q10 production capacity was very stable after 30 sequential transfers and no antibiotics were required during the fermentation process. The strategy presented may be useful as a general approach for construction of stable production strains synthesizing natural products where various copy numbers for different genes are concerned.

  4. Frecuencia de aberraciones cromosómicas en sujetos con gonosomopatías: Experiencia en 19 años de trabajo Frequency of chromosomal aberrations in subjects with gonosomopathies: Experience in 19 years of work

    Directory of Open Access Journals (Sweden)

    Marlén Quesada Dorta

    2004-08-01

    Full Text Available El objetivo de este trabajo fue determinar la frecuencia de aberraciones cromosómicas en un grupo de pacientes portadores de gonosomopatías y relacionar en cada caso el significado de las diferentes aberraciones cromosómicas encontradas con el diagnóstico clínico realizado. Se estudiaron desde el punto de vista citogenético 656 pacientes con diagnóstico presuntivo de gonosomopatías, recibidos en el laboratorio de genética molecular del Hospital Clinicoquirúrgico "Hermanos Ameijeiras" entre los años 1982 y 2001, procedentes de distintas instituciones hospitalarias del país. Del total de pacientes con diagnóstico presuntivo de gonosomopatías, en el 32,7 % (215/656 se confirmó el diagnóstico clínico con el estudio citogenético. El estudio cromosómico se realizó por técnicas de bandas G. Los reordenamientos cromosómicos encontrados se clasificaron en 4 grupos; el de mayor frecuencia fue el de las gonosomopatías numéricas, con 110 pacientes que representan el 51 % del total. En orden de frecuencia siguieron el grupo de las alteraciones numéricas y estructurales (mosaicos con 59 pacientes (27,0, las inversiones de sexo con 24 (12,0 y el grupo de las gonosomopatías estructurales con 22 (10,0. Las aberraciones cromosómicas más comunes fueron las gonosomopatías numéricas (síndromes de Turner y Klinefelter. El estudio cromosómico en estos pacientes constituye un indicador de valor diagnóstico de gran importancia para la conducta terapéutica a seguir en cada caso.This paper was aimed at determining the frequency of chromosomal aberrations in a group of patients carriers of gonosomopathies and at relating in each case the meaning of the different chromosomal aberrations found to the patients' clinical diagnosis. 656 patients with presumptive diagnosis of gonosomopathies from different hospital institutions of the country that were received at the mollecular genetics laboratory of "Hermanos Ameijeiras" Clinical and Surgical

  5. 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.

  6. Mutual exclusion of t(11;18)(q21;q21) and numerical chromosomal aberrations in the development of different types of primary gastric lymphomas.

    NARCIS (Netherlands)

    Schreuder, M.I.; Hoeve, M.A.; Hebeda, K.M.; Verdijk, M.A.J.; Ligtenberg, M.J.L.; Bot, F.J.; Chott, A.; Krieken, J.H.J.M. van

    2003-01-01

    Gastric non-Hodgkin's lymphomas can be divided histologically into mucosa-associated lymphoid tissue (MALT) lymphoma (ML) and diffuse large cell lymphoma (DLCL) with or without evidence of preceding/accompanying ML (DLCL + ML). We studied the incidence of the most frequent structural chromosomal abe

  7. 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

  8. Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells.

    Science.gov (United States)

    Yamano, Noriko; Takahashi, Mai; Ali Haghparast, Seyed Mohammad; Onitsuka, Masayoshi; Kumamoto, Toshitaka; Frank, Jana; Omasa, Takeshi

    2016-08-01

    Chromosomal instability is a characteristic of Chinese hamster ovary (CHO) cells. Cultures of these cells gradually develop heterogeneity even if established from a single cell clone. We isolated cells containing different numbers of chromosomes from a CHO-DG44-based human granulocyte-macrophage colony stimulating factor (hGM-CSF)-producing cell line and found that high chromosome number cells showed higher hGM-CSF productivity. Therefore, we focused on the relationship between chromosome aneuploidy of CHO cells and high recombinant protein-producing cell lines. Distribution and stability of chromosomes were examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes were isolated from the original CHO-DG44 cell line to investigate the effect of aneuploid cells on recombinant protein production. Both cell lines were stably transfected with a vector that expresses immunoglobulin G3 (IgG3), and specific antibody production rates were compared. Cells containing more than 30 chromosomes had higher specific antibody production rates than those with normal chromosome number. Single cell analysis of enhanced green fluorescent protein (Egfp)-gene transfected cells revealed that increased GFP expression was relative to the number of gene integration sites rather than the difference in chromosome numbers or vector locations. Our results suggest that CHO cells with high numbers of chromosomes contain more sites for vector integration, a characteristic that could be advantageous in biopharmaceutical production.

  9. 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.

  10. 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.

  11. Production and distribution of aberrations in resting or cycling human lymphocytes following Fe-ion or Cr-ion irradiation: Emphasis on single track effects

    Science.gov (United States)

    Deperas-Standylo, Joanna; Lee, Ryonfa; Nasonova, Elena; Ritter, Sylvia; Gudowska-Nowak, Ewa

    2012-09-01

    In the present study we examined the cytogenetic effects of 177 MeV/u Fe-ions (LET = 335 keV/μm) and 4.1 MeV/u Cr-ions (LET = 3160 keV/μm) in human lymphocytes under exposure conditions that result on average in one particle hit per cell nucleus. In non-cycling (G0-phase) lymphocytes the induction and the repair of excess fragments was measured by means of the premature chromosome condensation (PCC) technique and the distribution of breaks among cells was analysed. The PCC-data were further compared with those reported recently for stimulated lymphocytes at the first post-irradiation mitosis. Our experiments show that a single nuclear traversal by a Fe-ion produced more initial chromatin breakage than one Cr-ion, but after 24 h of repair the number of excess fragments/cell was similar for both ion species. All distributions of aberrations were overdispersed. For low energy Cr-ions, where the track radius is smaller than the radius of the cell nucleus, the data could be well described by a Neyman type A distribution. In contrast, the data obtained for high energy Fe-ions were fitted with a convoluted Poisson-Neyman distribution to account for the fact that the dose is deposited not only in the cell actually traversed but also in neighbouring cells. By applying metaphase analysis a different picture emerged with respect to the aberration yield, i.e. more aberrations were detected in cells exposed to Fe-ions than in those irradiated with Cr-ions. Yet, as observed for non-cycling lymphocytes all aberration distributions generated for metaphase cells were overdispersed. The obtained results are discussed with respect to differences in particle track structure. Additionally, the impact of confounding factors such as apoptosis that affect the number of aberrations expressed in a cell population is addressed.

  12. Chromosomal aberrations in bladder cancer: fresh versus formalin fixed paraffin embedded tissue and targeted FISH versus wide microarray-based CGH analysis.

    Directory of Open Access Journals (Sweden)

    Elena Panzeri

    Full Text Available Bladder carcinogenesis is believed to follow two alternative pathways driven by the loss of chromosome 9 and the gain of chromosome 7, albeit other nonrandom copy number alterations (CNAs were identified. However, confirmation studies are needed since many aspects of this model remain unclear and considerable heterogeneity among cases has emerged. One of the purposes of this study was to evaluate the performance of a targeted test (UroVysion assay widely used for the detection of Transitional Cell Carcinoma (TCC of the bladder, in two different types of material derived from the same tumor. We compared the results of UroVysion test performed on Freshly Isolated interphasic Nuclei (FIN and on Formalin Fixed Paraffin Embedded (FFPE tissues from 22 TCCs and we didn't find substantial differences. A second goal was to assess the concordance between array-CGH profiles and the targeted chromosomal profiles of UroVysion assay on an additional set of 10 TCCs, in order to evaluate whether UroVysion is an adequately sensitive method for the identification of selected aneuploidies and nonrandom CNAs in TCCs. Our results confirmed the importance of global genomic screening methods, that is array based CGH, to comprehensively determine the genomic profiles of large series of TCCs tumors. However, this technique has yet some limitations, such as not being able to detect low level mosaicism, or not detecting any change in the number of copies for a kind of compensatory effect due to the presence of high cellular heterogeneity. Thus, it is still advisable to use complementary techniques such as array-CGH and FISH, as the former is able to detect alterations at the genome level not excluding any chromosome, but the latter is able to maintain the individual data at the level of single cells, even if it focuses on few genomic regions.

  13. 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....

  14. 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

    目的:了解铀矿工人周围血淋巴细胞染色体畸变情况。方法采用整群随机抽样方法,选择江西省某铀矿98名铀矿工人为矿工组,48名接受放射工作人员培训但还未上岗的人员或行政工作人员为对照组,采集2组人员肘静脉血,采用培养开始加秋水仙素法培养50 h后收获细胞,常规方法制片,吉姆萨染液染色,显微镜下分析染色体畸变。结果矿工组染色体总畸变率为2.70%,对照组为2.49%,2组比较差异无统计学意义( Z=0.74,P=0.459)。矿工组“双着丝粒体+着丝粒环”(以下简称“双+环”)率为(0.25±0.05)%,对照组为(0.12±0.05)%。调整性别、年龄、工龄、吸烟和饮酒等因素后进行负二项回归分析,矿工组“双+环”率为对照组的5.76倍( Z=2.28,P=0.023)。结论铀矿工人的周围血淋巴细胞染色体非稳定性畸变水平较高,需要加强铀矿工人的职业性放射性疾病危害防治工作。%Objective To analyze the chromosome aberration of peripheral blood lymphocytes among uranium workers. Methods According to cluster sampling totally 98 workers from a uranium mine in Jiangxi province were randomly selected as the miner group.A total of 48 new employees who had received radiation pre-job training before going on duty or executive staff were selected as the control group.Their venous blood samples were collected.After 50 hours of cultivation by using colchicines at the beginning of cultivation method, blood cells were harvested and made into slides according to the conventional method.The slides were stained with Giemsa and chromosome aberrations were analyzed with microscope.Results The total aberration rate was 2.70%in the miner group and was 2.49%in the control group.There was no statistical significant difference between the two groups ( Z=0.74, P=0.459) .The rate of“dicentric and centric ring”(“dic+r”) was ( 0.25 ±0

  15. Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes.

    Science.gov (United States)

    Grutzmacher, Cathy; Park, SunYoung; Zhao, Yun; Morrison, Margaret E; Sheibani, Nader; Sorenson, Christine M

    2013-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease and is a major risk factor for cardiovascular disease. In the United States, microvascular complications during diabetic nephropathy contribute to high morbidity and mortality rates. However, the cell-autonomous impact of diabetes on kidney endothelial cell function requires further investigation. Male Akita/+ [autosomal dominant mutation in the insulin II gene (Ins2)] mice reproducibly develop diabetes by 4 wk of age. Here, we examined the impact a short duration of diabetes had on kidney endothelial cell function. Kidney endothelial cells were prepared from nondiabetic and diabetic mice (4 wk of diabetes) to delineate the early changes in endothelial cell function. Kidney endothelial cells from Akita/+ mice following 4 wk of diabetes demonstrated aberrant expression of extracellular matrix proteins including decreased osteopontin and increased fibronectin expression which correlated with increased α5-integrin expression. These changes were associated with the attenuation of migration and capillary morphogenesis. Kidney endothelial cells from Akita/+ mice had decreased VEGF levels but increased levels of endothelial nitric oxide synthase(eNOS) and NO, suggesting uncoupling of VEGF-mediated NO production. Knocking down eNOS expression in Akita/+ kidney endothelial cells increased VEGF expression, endothelial cell migration, and capillary morphogenesis. Furthermore, attenuation of sprouting angiogenesis of aortas from Akita/+ mice with 8 wk of diabetes was restored in the presence of the antioxidant N-acetylcysteine. These studies demonstrate that aberrant endothelial cell function with a short duration of diabetes may set the stage for vascular dysfunction and rarefaction at later stages of diabetes.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Production of alien chromosome additions and their utility in plant genetics.

    Science.gov (United States)

    Chang, S-B; de Jong, H

    2005-01-01

    Breeding programs aiming at transferring desirable genes from one species to another through interspecific hybridization and backcrossings often produce monosomic and disomic additions as intermediate crossing products. Such aneuploids contain alien chromosomes added to the complements of the recipient parent and can be used for further introgression programs, but lack of homoeologous recombination and inevitable segregation of the alien chromosome at meiosis make them often less ideal for producing stable introgression lines. Monosomic and disomic additions can have specific morphological characteristics, but more often they need additional confirmation of molecular marker analyses and assessment by fluorescence in situ hybridization with genomic and chromosome-specific DNA as probes. Their specific genetic and cytogenetic properties make them powerful tools for fundamental research elucidating regulation of homoeologous recombination, distribution of chromosome-specific markers and repetitive DNA sequences, and regulation of heterologous gene expression. In this overview we present the major characteristics of such interspecific aneuploids highlighting their advantages and drawbacks for breeding and fundamental research. Copyright 2005 S. Karger AG, Basel.

  1. 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.

  2. 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

  3. Chromosome-level genome assembly and transcriptome of the green alga Chromochloris zofingiensis illuminates astaxanthin production

    Science.gov (United States)

    Roth, Melissa S.; Cokus, Shawn J.; Gallaher, Sean D.; Walter, Andreas; Lopez, David; Erickson, Erika; Endelman, Benjamin; Westcott, Daniel; Larabell, Carolyn A.; Merchant, Sabeeha S.; Pellegrini, Matteo

    2017-01-01

    Microalgae have potential to help meet energy and food demands without exacerbating environmental problems. There is interest in the unicellular green alga Chromochloris zofingiensis, because it produces lipids for biofuels and a highly valuable carotenoid nutraceutical, astaxanthin. To advance understanding of its biology and facilitate commercial development, we present a C. zofingiensis chromosome-level nuclear genome, organelle genomes, and transcriptome from diverse growth conditions. The assembly, derived from a combination of short- and long-read sequencing in conjunction with optical mapping, revealed a compact genome of ∼58 Mbp distributed over 19 chromosomes containing 15,274 predicted protein-coding genes. The genome has uniform gene density over chromosomes, low repetitive sequence content (∼6%), and a high fraction of protein-coding sequence (∼39%) with relatively long coding exons and few coding introns. Functional annotation of gene models identified orthologous families for the majority (∼73%) of genes. Synteny analysis uncovered localized but scrambled blocks of genes in putative orthologous relationships with other green algae. Two genes encoding beta-ketolase (BKT), the key enzyme synthesizing astaxanthin, were found in the genome, and both were up-regulated by high light. Isolation and molecular analysis of astaxanthin-deficient mutants showed that BKT1 is required for the production of astaxanthin. Moreover, the transcriptome under high light exposure revealed candidate genes that could be involved in critical yet missing steps of astaxanthin biosynthesis, including ABC transporters, cytochrome P450 enzymes, and an acyltransferase. The high-quality genome and transcriptome provide insight into the green algal lineage and carotenoid production. PMID:28484037

  4. The Dicentric Chromosome dic(20;22) Is a Recurrent Abnormality in Myelodysplastic Syndromes and Is a Product of Telomere Fusion.

    Science.gov (United States)

    MacKinnon, Ruth N; Duivenvoorden, Hendrika M; Campbell, Lynda J; Wall, Meaghan

    2016-01-01

    We describe a recurrent dicentric chromosome formed by telomere fusion between chromosome 20 and chromosome 22 in 4 cases of myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). In particular, the presence of residual telomere sequences at the site of translocation in 3 of the 4 cases makes a compelling case for telomere fusion. This is the first description of a recurrent telomere fusion event in any malignant condition. The 20q subtelomeric region was retained in all 4 examples despite deletion of the 20q12 region closer to the centromere. The original dicentric chromosome in all 4 cases contained nucleolus organiser region material from the short arm of chromosome 22 and had also undergone secondary rearrangements that produced amplification of the common gained region on 20q. We propose that the sequence of events producing this chromosome abnormality is: degradation of the telomeres, formation of an unstable dicentric chromosome by 20q and 22p telomere fusion, breakage-fusion-bridge cycles causing copy number aberration between the centromeres, selection of cells with 20q12 deletion, and further selection of cells with 20q11.2 gain. The last 2 steps are driver events responsible for the abnormal chromosomes found in the malignant cells. Finding recurrent patterns in the complex genome reorganisation events that characterise poor-prognosis, complex-karyotype AML and MDS will help us understand the mechanisms and oncogenic driver mutations in these poorly understood malignancies. © 2017 S. Karger AG, Basel.

  5. 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.

  6. From DNA Copy Number to Gene Expression: Local aberrations, Trisomies and Monosomies

    Science.gov (United States)

    Shay, Tal

    The goal of my PhD research was to study the effect of DNA copy number changes on gene expression. DNA copy number aberrations may be local, encompassing several genes, or on the level of an entire chromosome, such as trisomy and monosomy. The main dataset I studied was of Glioblastoma, obtained in the framework of a collaboration, but I worked also with public datasets of cancer and Down's Syndrome. The molecular basis of expression changes in Glioblastoma. Glioblastoma is the most common and aggressive type of primary brain tumors in adults. In collaboration with Prof. Hegi (CHUV, Switzerland), we analyzed a rich Glioblastoma dataset including clinical information, DNA copy number (array CGH) and expression profiles. We explored the correlation between DNA copy number and gene expression at the level of chromosomal arms and local genomic aberrations. We detected known amplification and over expression of oncogenes, as well as deletion and down-regulation of tumor suppressor genes. We exploited that information to map alterations of pathways that are known to be disrupted in Glioblastoma, and tried to characterize samples that have no known alteration in any of the studied pathways. Identifying local DNA aberrations of biological significance. Many types of tumors exhibit chromosomal losses or gains and local amplifications and deletions. A region that is aberrant in many tumors, or whose copy number change is stronger, is more likely to be clinically relevant, and not just a by-product of genetic instability. We developed a novel method that defines and prioritizes aberrations by formalizing these intuitions. The method scores each aberration by the fraction of patients harboring it, its length and its amplitude, and assesses the significance of the score by comparing it to a null distribution obtained by permutations. This approach detects genetic locations that are significantly aberrant, generating a 'genomic aberration profile' for each sample. The 'genomic

  7. 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.

  8. Species-Specific Chromosome Engineering Greatly Improves Fully Human Polyclonal Antibody Production Profile in Cattle.

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsushita

    Full Text Available Large-scale production of fully human IgG (hIgG or human polyclonal antibodies (hpAbs by transgenic animals could be useful for human therapy. However, production level of hpAbs in transgenic animals is generally very low, probably due to the fact that evolutionarily unique interspecies-incompatible genomic sequences between human and non-human host species may impede high production of fully hIgG in the non-human environment. To address this issue, we performed species-specific human artificial chromosome (HAC engineering and tested these engineered HAC in cattle. Our previous study has demonstrated that site-specific genomic chimerization of pre-B cell receptor/B cell receptor (pre-BCR/BCR components on HAC vectors significantly improves human IgG expression in cattle where the endogenous bovine immunoglobulin genes were knocked out. In this report, hIgG1 class switch regulatory elements were subjected to site-specific genomic chimerization on HAC vectors to further enhance hIgG expression and improve hIgG subclass distribution in cattle. These species-specific modifications in a chromosome scale resulted in much higher production levels of fully hIgG of up to 15 g/L in sera or plasma, the highest ever reported for a transgenic animal system. Transchromosomic (Tc cattle containing engineered HAC vectors generated hpAbs with high titers against human-origin antigens following immunization. This study clearly demonstrates that species-specific sequence differences in pre-BCR/BCR components and IgG1 class switch regulatory elements between human and bovine are indeed functionally distinct across the two species, and therefore, are responsible for low production of fully hIgG in our early versions of Tc cattle. The high production levels of fully hIgG with hIgG1 subclass dominancy in a large farm animal species achieved here is an important milestone towards broad therapeutic applications of hpAbs.

  9. Human chromosomes: Structure, behavior, and effects

    Energy Technology Data Exchange (ETDEWEB)

    Therman, E.; Susman, M.

    1993-12-31

    The book `Human Chromosomes: Structure, Behavior, and Effects` covers the most important topics regarding human chromosomes and current research in cytogenetics. Attention is given both to structure and function of autosomes and sex chromosomes, as well as definitions and causes of chromosomal aberrations. This often involves discussion about various aspects of the cell cycle (both mitosis and meiosis). Methods and techniques involved in researching and mapping human chromosomes are also discussed.

  10. 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

  11. Detection of structural and numerical chromosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients.

    Science.gov (United States)

    Schmid, T E; Brinkworth, M H; Hill, F; Sloter, E; Kamischke, A; Marchetti, F; Nieschlag, E; Wyrobek, A J

    2004-06-01

    Modern reproductive technologies are enabling the treatment of infertile men with severe disturbances of spermatogenesis. The possibility of elevated frequencies of genetically and chromosomally defective sperm has become an issue of concern with the increased usage of ICSI, which can enable men with severely impaired sperm production to father children. Several papers have been published reporting aneuploidy in oligozoospermic patients, but relatively little is known about chromosome structural aberrations in the sperm of these patients. We examined sperm from infertile, oligozoospermic individuals for structural and numerical chromosomal abnormalities using a multicolour ACM fluorescence in situ hybridization (FISH) assay that utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical chromosomal abnormalities plus two categories of structural aberrations: duplications and deletions of 1pter and 1cen, and chromosomal breaks within the 1cen-1q12 region. There was a significant increase in the average frequencies of sperm with duplications and deletions in the infertility patients compared with the healthy concurrent controls. There was also a significantly elevated level of breaks within the 1cen-1q12 region. There was no evidence for an increase in chromosome 1 disomy, or in diploidy. Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities, suggesting that oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.

  12. 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.

  13. Production and cytogenetics of Brassica campestris-alboglabra chromosome addition lines

    DEFF Research Database (Denmark)

    Chen, B.Y.; Cheng, B.F.; Bagger Jørgensen, Rikke

    1997-01-01

    was homoeologous with the long arm of B. alboglabra chromosome 4, while its short arm with the short arms of B. alboglabra chromosomes 8 and 9. Such an intergenomic homoeology relationship supports the hypothesis that B. campestris and B. alboglabra share a common ancestor but that chromosomal rearrangements have...... occurred during the evolution of the two species. Intergenomic introgression was observed in the progenies of the addition lines. The introgression of an entire B. alboglabra marker synteny group into the B. campestris genome implied the possible occurrence of interspecific chromosomal substitution....

  14. Chicago aberration correction work.

    Science.gov (United States)

    Beck, V D

    2012-12-01

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system.

  15. Chicago aberration correction work

    Energy Technology Data Exchange (ETDEWEB)

    Beck, V.D., E-mail: vnlbeck@earthlink.net [1 Hobby Drive, Ridgefield, CT 06877-01922 (United States)

    2012-12-15

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system. -- Highlights: Black-Right-Pointing-Pointer Crewe and his group made significant advances in aberration correction and reduction. Black-Right-Pointing-Pointer A deeper understanding of the quadrupole octopole corrector was developed. Black-Right-Pointing-Pointer A scheme to correct spherical aberration using hexapoles was developed. Black-Right-Pointing-Pointer Chromatic aberration was corrected using a uniform field mirror.

  16. 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

  17. 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.

  18. 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.

  19. A simple method to generate chromosomal mutations in Lactobacillus plantarum strain TF103 to eliminate undesired fermentation products.

    Science.gov (United States)

    Liu, Siqing

    2006-01-01

    Gram-positive bacteria have been explored to convert lignocellulosic biomass to biofuel and bioproducts. Our long-term goal is to create genetically engineered lactic acid bacteria (LAB) strains that convert agricultural biomass into ethanol and other value-added products. The immediate approaches toward this goal involve genetic manipulations by either introducing ethanol production pathway genes or inactivating pathways genes that lead to production of undesired byproducts. The widely studied species Lactobacillus plantarum is now considered a model for genetic manipulations of LAB. In this study, L. plantarum TF103 strain, in which two of the chromosomal L-ldh and D-ldh genes are inactivated, was used to introduce additional mutations on the chromosome to eliminate undesired fermentation products. We targeted the acetolactate synthase gene (als) that converts pyruvate to acetolactate, to eliminate the production of acetoin and 2,3-butanodial. A pBluescript derivative containing sections of the als coding region and an erythromycin resistance gene was directly introduced into L. plantarum TF103 cells to create mutations under selection pressure. The resulting erythromycin resistant (Emr) TF103 strain appears to have chromosomal mutations of both the als and the adjacent lysP genes as revealed by polymerase chain reaction and Southern blot analyses. Mutations were thus generated via targeted homologous recombination using a Gram-negative cloning vector, eliminating the use of a shuttle vector. This method should facilitate research in targeted inactivation of other genes in LAB.

  20. Human Sperm Chromosome Analysis—Study on Human Sperm Chromosome Mutagenesis Induced by Carbon Disulfide

    Institute of Scientific and Technical Information of China (English)

    LEJUN-YI; FUXIAO-MIN

    1996-01-01

    The aim of this study was to investigate the effect CS2 of on human sperm chromosomal aberration.The human sperm/hamster egg fusion techniquse was used to analyze 203 human sperm chromosome complement form 9 healthy volunteers.The incidence of numerical aberration was 1.0%,and that of structural chromosome aberration was 5.9% and total abnormalities was 6.9%.Structural aberrations consisted of breaks,deletions, centric rings,fragments,and chromatid exchange.The results from high concentration group(10μmol·L-1 CS2)showed that the incidence of chromosomal aberration rate was significantly higher than that of the control group.The results indicate that high concentration of CS2 might directly cause mutatenesis f the germ cell.

  1. 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

  2. 原发性皮肤边缘区B细胞淋巴瘤的BCL10表达与染色体异常%BCL10 expression and chromosomal aberration in primary cutaneous marginal zone B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    李百周; 孔蕴毅; 杨文涛; 周晓燕; 范月珍; 陆洪芬; 施达仁

    2008-01-01

    目的 探讨原发性皮肤边缘区B细胞淋巴瘤(PCMZL)中BCL10蛋白的表达和相关染色体的异常.方法 收集17例PCMZL,用免疫组化检测BCL10的表达,用荧光原位杂交(FISH)的方法分别检测API2-MALT1、BCL10、MALT1和IgH基因的异常.结果 在17例PCMZL中,BCL10的阳性率为94.1%(16/17),其中细胞质阳性率为64.7%(11/17),细胞核阳性率为29.4%(5/17).在FISH检测中,所有病例都不存在t(11;18),t(1;14)和t(14;18)染色体异常.与其他部位的MALT淋巴瘤相比较,在PCMZL中染色体易位的发生率不常见,可能这些遗传学异常不是PCMZL发生中的重要因素,而有其他目前未知的因素参与肿瘤的发生.结论 BCL10的核表达与是否出现上述的染色体异常无关,是否代表更具侵袭性的一种预后标记,尚需长期随访观察.%Objective To study the expression of BCL10 and associated chromosomal aberration in primary cutaneous marginal zone B-cell lymphoma (PCMZL). Methods Tissue specimens were collected from 17 patients with PCMZL. Immunohistochemistry was used to detect the expression of BCL10. Fluorescence in situ hybridization (FISH) was performed to examine the presence of API2-MALT1 fusion gene and chromosomal aberration in BCL10, MALT1 as well as IgH genes in these cases. Results Of these patients,94.1% (16/17) expressed BCL10 protein. The cytoplasmic expression of BCL10 was observed in 64.7% (11/17) of the patients, and nuclear expression in 29.4% (5/17). As shown by FISH test, neither API2-MALT1 fusion gene nor chromosomal aberration in BCL10, MALT1 or IgH genes was present in these patients. Conclusions Compared with MALT lymphomas originating from tissues other than skin, PCMZL is uncommonly associated with chromosomal abnormalities; it is possible that there are unknown factors contributing to its tumorigenesis. Nuclear BCL10 is unrelated to the presence of chromosomal aberration in BCL10, MALT1 or IgH genes. Further follow-up is required to clarify the

  3. MDMA(3,4亚甲基二氧甲基苯丙胺)对小鼠睾丸细胞微核率及染色体畸变率的影响%Effect of MDMA on Micronucleus Frequency and Chromosomal Aberration Ratio of Rats’ Testicle Cells

    Institute of Scientific and Technical Information of China (English)

    赵忠桂; 刘霜; 刘艳华; 李雅欣; 伍爱荣; 周业成

    2015-01-01

    通过连续20 d对雄性小鼠灌胃染毒3,4-亚甲基二氧基甲基苯丙胺(3,4-methylenedioxymethamphetamine, MDMA)后,探究MDMA对雄性小鼠睾丸组织细胞微核率及染色体畸变率的影响.将雄性小鼠随机分为MDMA低(5.0mg/kg)、中(10.0mg/kg)、高(20.0 mg/kg)三个染毒剂量组,采用生理盐水做阴性对照,每日染毒1次.于末次给药后第二天,取小鼠睾丸组织细胞,采用常规微核( micronucleus,MN)试验,检测小鼠睾丸细胞微核率的改变;同时采用染色体畸变试验( chromosomal aberration test)探究MDMA对小鼠睾丸细胞染色体畸变率的影响.微核试验结果表明MDMA中、低剂量组小鼠睾丸细胞微核率与阴性对照组比较差异无显著性(P>0.05),而高剂量与低剂量组小鼠睾丸细胞微核率及阴性对照组比较,差异均有显著性(P0. 05), while that in high dose group was significantly different from the control group and low dose group ( P<0 . 01 ) . Compared with the control group, the chromosomal aberration ratios in testis of rats in high and middle dose group increased, the difference was not significant (P<0. 05), but that in low dose group was also significantly different from the control group(P<0. 05). It suggested that high dose of MDMA lead to the increase of micronucleus frequency. Besides,high dose group and middle dose group could make the chro-mosomal aberration ratio increase. So MDMA might damage genetic material of rat testicle cells. 4figs. , 2tabs. ,10refs.

  4. 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.

  5. Dexamethasone normalizes aberrant elastic fiber production and collagen 1 secretion by Loeys-Dietz syndrome fibroblasts: a possible treatment?

    Science.gov (United States)

    Barnett, Christopher P; Chitayat, David; Bradley, Timothy J; Wang, Yanting; Hinek, Aleksander

    2011-06-01

    Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by facial dysmorphism, cleft palate, dilation of the aortic arch, blood vessel tortuosity and a high risk of aortic dissection. It is caused by mutations in the transforming growth factor β-receptor 1 and 2 (TGFβ-R1 and TGFβ-R2) genes. Fibroblasts derived from 12 Loeys-Dietz syndrome patients, six with TGFB-R1 mutations and six with TGFB-R2 mutations, were analyzed using RT-PCR, biochemical assays, immunohistochemistry and electron microscopy for production of elastin, fibrillin 1, fibulin 1 and fibulin 4 and deposition of collagen type I. All LDS fibroblasts with TGFβ-R1 mutations demonstrated decreased expression of elastin and fibulin 1 genes and impaired deposition of elastic fibers. In contrast, fibroblasts with TGFβ-R2 mutations consistently demonstrated intracellular accumulation of collagen type I in the presence of otherwise normal elastic fiber production. Treatment of the cell cultures with dexamethasone induced remarkable upregulation in the expression of tropoelastin, fibulin 1- and fibulin 4-encoding mRNAs, leading to normalization of elastic fiber production in fibroblasts with TGFβ-R1 mutations. Treatment with dexamethasone also corrected the abnormal secretion of collagen type I from fibroblasts with TGFβ-R2 gene mutations. As the organogenesis-relevant elastic fiber production occurs exclusively in late fetal and early neonatal life, these findings may have implications for treatment in early life. Further studies are required to determine if dexamethasone treatment of fetuses prenatally diagnosed with LDS would prevent or alleviate the connective tissue and vascular defects seen in this syndrome.

  6. Chromosomal aberration leads to recurrent pregnancy loss and partial trisomy of 5p12-15.3 in the offspring: report of a Syrian couple and review of the literature .

    Science.gov (United States)

    Al-Achkar, Walid; Moassass, Faten; Al-Ablog, Ayman; Liehr, Thomas; Fan, Xiaobo; Wafa, Abdulsamad

    2015-03-01

    Here we describe a Syrian couple having recurrent pregnancy loss in the first trimester, fetal malformations, and/or neonatal death. The father had a balanced chromosomal translocation t(5;15), an sY125 microdeletion of locus b in the azoospermia factor (AZF) gene, and an MTHFR C677T homozygous polymorphism with normal phenotype. Interestingly, his healthy wife had another MTHFR A1298C homozygous polymorphism. The couple experienced two pregnancy losses and had two stillborn children with severe malformations due to partial trisomy of the short arm of chromosome 5. The couple does not have any living offspring after 10 years of marriage.

  7. Chromosomal abnormalities, meiotic behavior and fertility in domestic animals.

    Science.gov (United States)

    Villagómez, D A F; Pinton, A

    2008-01-01

    Since the advent of the surface microspreading technique for synaptonemal complex analysis, increasing interest in describing the synapsis patterns of chromosome abnormalities associated with fertility of domestic animals has been noticed during the past three decades. In spite of the number of scientific reports describing the occurrence of structural chromosome abnormalities, their meiotic behavior and gametic products, little is known in domestic animal species about the functional effects of such chromosome aberrations in the germ cell line of carriers. However, some interesting facts gained from recent and previous studies on the meiotic behavior of chromosome abnormalities of domestic animals permit us to discuss, in the frame of recent knowledge emerging from mouse and human investigations, the possible mechanism implicated in the well known association between meiotic disruption and chromosome pairing failure. New cytogenetic techniques, based on molecular and immunofluorescent analyses, are allowing a better description of meiotic processes, including gamete production. The present communication reviews the knowledge of the meiotic consequences of chromosome abnormalities in domestic animals.

  8. 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.

  9. Aberration Corrected Emittance Exchange

    CERN Document Server

    Nanni, Emilio A

    2015-01-01

    Full exploitation of emittance exchange (EEX) requires aberration-free performance of a complex imaging system including active radio-frequency (RF) elements which can add temporal distortions. We investigate the performance of an EEX line where the exchange occurs between two dimensions with normalized emittances which differ by orders of magnitude. The transverse emittance is exchanged into the longitudinal dimension using a double dog-leg emittance exchange setup with a 5 cell RF deflector cavity. Aberration correction is performed on the four most dominant aberrations. These include temporal aberrations that are corrected with higher order magnetic optical elements located where longitudinal and transverse emittance are coupled. We demonstrate aberration-free performance of emittances differing by 4 orders of magnitude, i.e. an initial transverse emittance of $\\epsilon_x=1$ pm-rad is exchanged with a longitudinal emittance of $\\epsilon_z=10$ nm-rad.

  10. Identification of two quantitative trait loci involved in antibody production on mouse chromosome 8.

    Science.gov (United States)

    Puel, A; Mevel, J C; Bouthillier, Y; Decreusefond, C; Fridman, W H; Feingold, N; Mouton, D

    1998-03-01

    Several quantitative trait loci (QTLs) contributing to the extreme phenotypes of the selected high (H) and low (L) antibody-responder lines of mice were mapped on distinct chromosomes. Successive backcrosses were bred to reduce the length of the QTL-bearing segment detected on chromosome 8 and to produce congenic lines to test gene effect independently of the other QTLs. An increase in antibody responses was repeatedly found to be associated with inheritance of the H-line allele at two markers separated by 30 cM on that chromosome. In the successive backcrosses, background and unlinked involved genes of H-line origin were progressively eliminated; however, unexpected within-progeny variations persisted in the third and even fourth backcross. Nevertheless, the presence of two QTLs within the considered interval was definitely demonstrated in distinct progenies of the fourth backcross which separately inherited one of the two gene-marker H-line alleles. The previously identified chromosome 8 segment therefore contains at least two QTLs involved in antibody responsiveness.

  11. Study on micronucleus frequency and chromosomal aberration ratios of mouse testicle cells induced by methylene-dioxymethamphetamine%3,4亚甲基二氧基甲基苯丙胺对小鼠微核率及染色体畸变率的影响

    Institute of Scientific and Technical Information of China (English)

    赵忠桂; 刘霜; 刘艳华; 李雅欣; 伍爱荣; 周业成

    2015-01-01

    Objective To study the effects of 3,4-methylenedioxymethamphetamine (MDMA) on micronucleus frequency and chromosomal aberration ratios of male mouse testicle cells. Methods Healthy adult male rats were randomly divided into four groups. Different doses of MDMA (0, 5, 10 and 20 mg/kg) were administrated to the rats every days for 20 days. The rats were killed after the last test substance given for 24 h. Each rat′s micronucleus frequency and chromosomal aberration ratio of testicle cell were detected by using micronucleus test and chromosomal aberration test. Results The micronucleus frequencies of rats testicle cell in high dose group was significantly different from the control group and low dose group(P<0.01). With the control group, the chromosomal aberration ratios in testis of rats in high and middle dose group increased, the difference was significant (P<0.05), that in high dose group was also significantly different from the low and middle dose group (P<0.05). Conclusion It was suggested that MDMA might damage genetic material of rat testicle cells.%目的:通过连续20 d对雄性小鼠灌胃染毒3,4亚甲基二氧基甲基苯丙胺(MDMA)后,探究MDMA对雄性小鼠睾丸组织细胞微核率及染色体畸变率的影响。方法将雄性小鼠随机数字表法分为 MDMA 低(5.0 mg/kg)、中(10.0 mg/kg)、高(20.0 mg/kg)3个染毒剂量组,采用0.9%氯化钠注射液做阴性对照,每日染毒1次。于末次给药后第2天,取小鼠睾丸组织细胞,采用常规微核(MN)试验,检测小鼠睾丸细胞微核率的改变;同时采用染色体畸变试验探究MDMA对小鼠睾丸细胞染色体畸变率的影响。结果微核试验结果表明MDMA高剂量与低剂量组小鼠睾丸细胞微核率及阴性对照组比较,差异有统计学意义(P<0.01)。染色体畸变试验结果中,MDM高、中剂量组染色体畸变率分别与阴性对照组比较,差异有统计学意义(P<0.05),高

  12. 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

  13. Barth Syndrome:From mitochondrial dysfunctions associated with aberrant production of reactive oxygen species to pluripotent stem cell studies

    Directory of Open Access Journals (Sweden)

    Ana eSaric

    2016-01-01

    Full Text Available Mutations in the gene encoding the enzyme tafazzin, TAZ, cause Barth syndrome (BTHS. Individuals with this X-linked multisystem disorder present cardiomyopathy (often dilated, skeletal muscle weakness, neutropenia, growth retardation and 3-methylglutaconic aciduria. Biopsies of the heart, liver and skeletal muscle of patients have revealed mitochondrial malformations and dysfunctions. It is the purpose of this review to summarize recent results of studies on various animal or cell models of Barth syndrome, which have characterized biochemically the strong cellular defects associated with TAZ mutations. Tafazzin is a mitochondrial phospholipid-lysophospholipid transacylase that shuttles acyl groups between phospholipids and regulates the remodeling of cardiolipin (CL, a unique inner mitochondrial membrane phospholipid dimer consisting of two phosphatidyl residues linked by a glycerol bridge. After their biosynthesis, the acyl chains of CLs may be modified in remodeling processes involving up to three different enzymes. Their characteristic acyl chain composition depends on the function of tafazzin, although the enzyme itself surprisingly lacks acyl specificity. CLs are crucial for correct mitochondrial structure and function. In addition to their function in the basic mitochondrial function of ATP production, CLs play essential roles in cardiac function, apoptosis, autophagy, cell cycle regulation and Fe-S cluster biosynthesis. Recent developments in tafazzin research have provided strong insights into the link between mitochondrial dysfunction and the production of reactive oxygen species (ROS. An important tool has been the generation of BTHS-specific induced pluripotent stem cells (iPSCs from BTHS patients. In a complementary approach, disease-specific mutations have been introduced into wild-type iPSC lines enabling direct comparison with isogenic controls. iPSC-derived cardiomyocytes were then characterized using biochemical and classical

  14. 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.

  15. Nonrandom involvement of chromosomal segments in human hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J. D.

    1977-01-01

    The consistent occurrence of nonrandom chromosome changes in human malignancies suggests that they are not trivial epiphenomena. Whereas we do not understand their significance at present, one possible role which they may fulfill is to provide the chromosomally aberrant cells with a proliferative advantage as the result of alteration of the number and/or location of genes related to nucleic acid biosynthesis. It would be expected that the proliferative advantage provided by various chromosome aberrations differs in patients with different genetic constitutions.

  16. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID during Inflammation-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tsutomu Chiba

    2011-06-01

    Full Text Available Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID, a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  17. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Atsushi; Marusawa, Hiroyuki, E-mail: maru@kuhp.kyoto-u.ac.jp; Chiba, Tsutomu [Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

    2011-06-22

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  18. Genetic aberration in primary hepatocellular carcinoma:correlation between p53 gene mutation and loss—of—heterozygosity on chromosome 16q21—q23 and 9p21—p23

    Institute of Scientific and Technical Information of China (English)

    WANGGANG; CHANGHUIHUANG; 等

    2000-01-01

    To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC),we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9,16 and 17.Loss-of-heterozygosity(LOH) is observed with high frequency on chromosomal region 17p13(36k/55,65%),9q21-p23(28/55,51%),16q21-23(27/55,49%) in tumors.Meanwhile,microsatellite instability is rarely found in these microsatellite loci.Direct sequencing was performed to detect the tentative mutation of tumor wuppressor genes in these regions:p53,MTS1/p16,and CDH1/E-cadherin.Wihin exon 5-9 of p53 gene,14 out of 55 HCC specimens(24%) have somatic mutations,and nucleotide deletion of this gene is reported in HCC for the first time.Mutation in MTS1/p16 is found only in one tumor case.We do not find mutations in CDH1/E-cadherin.Furthermore,a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23,which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.

  19. Chromosomal assignment of human DNA fingerprint sequences by simultaneous hybridization to arbitrarily primed PCR products from human/rodent monochromosome cell hybrids

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Jun; Sekiya, Takao [National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Navarro, J.M. [Burnham Institute, La Jolla, CA (United States)] [and others

    1996-05-15

    We have developed a technique for the simultaneous chromosomal assignment of multiple human DNA sequences from DNA fingerprints obtained by the arbitrarily primed polymerase chain reaction (AP-PCR). Radioactively labeled human AP-PCR products are hybridized to DNA fingerprints generated with the same arbitrary primer from human/rodent monochromosome cell hybrids after electroblotting to a nylong membrane. Human-specific hybridization bands in the human/rodent fingerprints unambiguously determine their chromosome of origin. We named this method simultaneous hybridization of arbitrarily primed PCR DNA fingerprinting products (SHARP). Using this approach, we determined the chromosomal origins of most major bands of human AP-PCR fingerprints obtained with two arbitrary primers. Altogether, the chromosomal localization of near 50 DNA fragments, comprehensive of all human chromosomes except chromosomes 21 and Y, was achieved in this simple manner. Chromosome assignment of fingerprint bands is essential for molecular karyotyping of cancer by AP-PCR DNA fingerprinting. The SHARP method provides a convenient and powerful tool for this purpose. 23 refs., 3 figs., 2 tabs.

  20. Smoking-induced chromosomal segregation anomalies identified by FISH analysis of sperm

    National Research Council Canada - National Science Library

    Pereira, Ciro Silveira; Juchniuk de Vozzi, Maria Silvina; Dos Santos, Silvio Avelino; Vasconcelos, Maria Aparecida C; de Paz, Cláudia Cp; Squire, Jeremy A; Martelli, Lucia

    2014-01-01

    .... Previous studies have shown that toxic substances from cigarette smoke induce structural and numerical chromosomal aberrations in vitro and could potentially increase levels of aneusomy in sperm...

  1. Genetic and epigenetic changes of genes on chromosome 3 in human urogenital tumors

    Directory of Open Access Journals (Sweden)

    Gordiyuk V. V.

    2011-02-01

    Full Text Available Numerous disorders of genes and alterations of their expression are observed on a short arm of human chromosome 3, particularly in 3p14, 3p21, 3p24 compact regions in epithelial tumors. These aberrations affect the key biological processes specific for cancerogenesis. Such genes or their products could be used for diagnostics and prognosis of cancer. Genetical and epigenetical changes of a number of genes on chromosome 3 in human urogenital cancer, their role in cellular processes and signal pathways and perspectives as molecular markers of cancer diseases are analyzed in the review

  2. Aberrant meiotic behavior in Agave tequilana Weber var. azul

    Directory of Open Access Journals (Sweden)

    Rodríguez-Garay Benjamin

    2002-10-01

    Full Text Available Abstract Background Agave tequilana Weber var. azul, is the only one variety permitted by federal law in México to be used for tequila production which is the most popular contemporary alcoholic beverage made from agave and recognized worldwide. Despite the economic, genetic, and ornamental value of the plant, it has not been subjected to detailed cytogenetic research, which could lead to a better understanding of its reproduction for future genetic improvement. The objective of this work was to study the meiotic behavior in pollen mother cells and its implications on the pollen viability in Agave tequilana Weber var. azul. Results The analysis of Pollen Mother Cells in anaphase I (A-I showed 82.56% of cells with a normal anaphase and, 17.44% with an irregular anaphase. In which 5.28% corresponded to cells with side arm bridges (SAB; 3.68% cells with one bridge and one fragment; 2.58% of irregular anaphase showed cells with one or two lagging chromosomes and 2.95% showed one acentric fragment; cells with two bridges and cells with two bridges and one acentric fragment were observed in frequencies of 1.60% and 1.35% respectively. In anaphase II some cells showed bridges and fragments too. Aberrant A-I cells had many shrunken or empty pollen grains (42.00% and 58.00 % viable pollen. Conclusion The observed meiotic irregularities suggest that structural chromosome aberrations have occurred, such as heterozygous inversions, sister chromatid exchanges, deletions and duplications which in turn are reflected in a low pollen viability.

  3. Genetics Home Reference: Y chromosome infertility

    Science.gov (United States)

    ... Home Health Conditions Y chromosome infertility Y chromosome infertility Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Y chromosome infertility is a condition that affects the production of ...

  4. Improved recombinant antibody production by CHO cells using a production enhancer DNA element with repeated transgene integration at a predetermined chromosomal site.

    Science.gov (United States)

    Kawabe, Yoshinori; Inao, Takanori; Komatsu, Shodai; Huang, Guan; Ito, Akira; Omasa, Takeshi; Kamihira, Masamichi

    2017-03-01

    Chinese hamster ovary (CHO) cells are one of the most useful host cell lines for the production of biopharmaceutical proteins. Although a series of production processes have been refined to improve protein productivity and cost performance, establishing producer cells is still time-consuming and labor-intensive. Recombinase-mediated site-specific gene integration into a predetermined chromosomal locus may enable predictable protein expression, reducing the laborious process of cell screening. We previously developed an accumulative site-specific gene integration system (AGIS) using Cre recombinase and mutated loxP sites for transgene integration and amplification in the CHO cell genome. Epigenetic modifier elements such as insulators are effective DNA cis-regulatory elements for stabilizing transgene expression. Here, we attempted to enhance transgene expression in recombinant CHO cells generated by AGIS using a production enhancer DNA element (PE) derived from the CHO genome. The PE was introduced into an expression unit for a recombinant scFv-Fc antibody. The effect on scFv-Fc productivity of PE position and orientation within the transgene was evaluated, while keeping the background chromosomal structure constant. For the optimal PE arrangement, scFv-Fc productivity was enhanced 2.6-fold compared with an expression unit without a PE. The enhancing effect of the PE on transgene expression was also observed when two or three PE-flanked expression units were inserted as tandem repeats. These results indicate that AGIS using the PE-flanked expression unit is a promising approach for establishing producer cell lines for biopharmaceutical protein production.

  5. IDENTIFICATION OF A TUMOR-MARKER CHROMOSOME BY FLOW SORTING, DNA AMPLIFICATION INVITRO, AND INSITU HYBRIDIZATION OF THE AMPLIFIED PRODUCT

    NARCIS (Netherlands)

    BOSCHMAN, GA; BUYS, CHCM; VANDERVEEN, AY; RENS, W; OSINGA, J; SLATER, RM; ATEN, JA

    1993-01-01

    A method combining flow sorting and molecular cytogenetic techniques for the identification of unknown marker chromosomes is described. In this study, the bladder tumor cell line J82 was used, which was known to carry a marker chromosome of the size of chromosome 7 in every cell. From the cytogeneti

  6. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  7. 氯化钠对分蘖葱头根尖细胞有丝分裂的影响及其致畸效应%Effect of Sodium Chloride on Mitotic Index and Chromosome Aberration of Root Tip Cell of Allium cepa var. aggreatum

    Institute of Scientific and Technical Information of China (English)

    杨丽娟; 齐莹; 王晓伟; 李岩; 顾地周

    2013-01-01

    With the root tip as experimental materials, toxic effect of sodium chloride on Allium cepa var. aggreatum root tip was investigated. The Allium cepa var. aggreatum root tip cells were exposed to aqueous solution of sodium chloride with different concentration (0.05, 0.1, 0.2, 0.3 mol/L) for 12 h, 24 h and 48 h, respectively. And then the mitotic index, micronucleus rate and chromosome aberration of the Allium cepa var. aggreatum root tip cell were investigated. The experimental results indicated that with the elevated concentrations of sodium chloride aqueous and the increase of exposing time, the mitotic index decreased, chromosome aberration rate and micronucleus rate increased gradually. Moreover, the maximum value was reached when the concentration of sodium chloride aqueous was 0.3 mol/L and the exposure time was 48 h, which indicated that sodium chloride is a kind of stress factor.%以分蘖葱头根尖为试验材料,研究了氯化钠对分蘖葱头根尖的毒性效应.用不同浓度(0.05、0.1、0.2、0.3 mol/L)的氯化钠水溶液对分蘖葱头根尖细胞染毒12h、24 h、48 h,观察分蘖葱头根尖细胞有丝分裂指数、微核率以及染色体畸变情况.结果表明:在试验剂量范围内,随着氯化钠水溶液浓度的升高,染毒时间增长,分蘖葱头根尖细胞的有丝分裂指数逐渐降低,染色体畸变率和微核率逐渐升高,并且均在氯化钠水溶液浓度为0.3 mol/L、染毒时间为48 h时达到最大值,说明氯化钠是一种胁迫因子.

  8. Bacterial artificial chromosomes (BACs)-on-Beads™ as a diagnostic platform for the rapid aneuploidy screening of products of conception.

    Science.gov (United States)

    Sheath, Karen L; Duffy, Lisa; Asquith, Philip; Love, Donald R; George, Alice M

    2013-08-01

    The aim of the present study was to evaluate the use of KaryoLite™ bacterial artificial chromosomes (BACs)‑on‑Beads™ (BoBs) technology for the rapid screening of products of conception (POC). Validation and prospective studies were carried out on 85 and 95 patient samples, respectively. Validation studies had previously been analyzed using routine culture and G-banded karyotyping. BoBs resulted in an abnormality detection frequency of 27%, with a failure rate of <3%. The time required for processing was significantly lower compared with that of tissue culture. In conclusion, BoBs technology decreased the failure rate, while increasing the analytical sensitivity compared with G-banded karyotype analysis alone. Additionally, significant cost savings may be achieved with regard to the time of processing and analysis of specimens.

  9. Characterization of B chromosomes in Lilium hybrids through GISH and FISH

    NARCIS (Netherlands)

    Xie, S.L.; Marasek-Ciolakowska, A.; Ramanna, M.S.; Arens, P.F.P.; Visser, R.G.F.; Tuyl, van J.M.

    2014-01-01

    Supernumerary (B) chromosomes and small aberrant chromosomes were detected in Lilium hybrids and characterized through genomic in situ hybridization (GISH) and florescence in situ hybridization (FISH). Two small, supernumerary or B chromosomes were detected as extra chromosomes in a tetraploid plant

  10. Development of Special Biological Products

    Science.gov (United States)

    1981-01-01

    5 TOTAL GAPS - 4 DICENTRICS - 1 MARKER CHROMOSOMES - 98 Hyperdiploidy was 89% while only 10% was diploidy. This indicates CV-1 (P41) is no longer...cells observed (98%) had chromosome aberration(s), which included breaks, gaps, dicentric and stable marker chromosomes . Most of the marker chromosomes ...9 No. 4 Chromosome Analysis on Three Lots of FRhL-2 (P17) ------------- 10 No. 5 Certification and Testing Status of Three Lots

  11. Persistent radiation-induced chromosomal changes in native pocket mouse populations of the Nevada Test Site. Summary report, April 18, 1964-April 18, 1965

    Energy Technology Data Exchange (ETDEWEB)

    Towner, J.W.; Lindberg, R.G.

    Preliminary results are reported from a study of chromosome aberrations in a population of the long-tailed pocket mouse (Perognathus formosus) at the Nevada Test Site. Somatic or germinal tissues from 158 animals were sampled and more than 3000 chromosome preparations of mitosis and meiosis were accumulated for study of gross structural and numerical aberrations. An attempt was made to distinguish between those chromosome aberrations that might persist in the population by gametic transmission in successive generations and those aberrations acquired by the individual or transitory on the population level. The effects of exposure of the population to chronic radiation from fallout on chromosome aberrations will be evaluated.

  12. Molecular markers associated with leptinine production are located on chromosome 1 in Solanum chacoense

    NARCIS (Netherlands)

    Hutvagner, G.; Banfalvi, Z.; Milankovics, I.; Silhavy, D.; Polgar, Z.; Horvath, S.; Wolters, P.; Nap, J.P.H.

    2001-01-01

    Leptines of Solanum chacoense are effective natural deterrents against the Colorado potato beetle. Leptines are the acetylated forms of the glycoalkaloids solanine and chaconine and are supposed to be synthesised via hydroxylated derivatives, called leptinines. Inheritance of leptinine production wa

  13. [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.

  14. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

    Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

  15. Yeast artificial chromosomes employed for random assembly of biosynthetic pathways and production of diverse compounds in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Mitra Partha P

    2009-08-01

    Full Text Available Abstract Background Natural products are an important source of drugs and other commercially interesting compounds, however their isolation and production is often difficult. Metabolic engineering, mainly in bacteria and yeast, has sought to circumvent some of the associated problems but also this approach is impeded by technical limitations. Here we describe a novel strategy for production of diverse natural products, comprising the expression of an unprecedented large number of biosynthetic genes in a heterologous host. Results As an example, genes from different sources, representing enzymes of a seven step flavonoid pathway, were individually cloned into yeast expression cassettes, which were then randomly combined on Yeast Artificial Chromosomes and used, in a single transformation of yeast, to create a variety of flavonoid producing pathways. Randomly picked clones were analysed, and approximately half of them showed production of the flavanone naringenin, and a third of them produced the flavonol kaempferol in various amounts. This reflected the assembly of 5–7 step multi-species pathways converting the yeast metabolites phenylalanine and/or tyrosine into flavonoids, normally only produced by plants. Other flavonoids were also produced that were either direct intermediates or derivatives thereof. Feeding natural and unnatural, halogenated precursors to these recombinant clones demonstrated the potential to further diversify the type of molecules that can be produced with this technology. Conclusion The technology has many potential uses but is particularly suited for generating high numbers of structurally diverse compounds, some of which may not be amenable to chemical synthesis, thus greatly facilitating access to a huge chemical space in the search for new commercially interesting compounds

  16. Comparación en la frecuencia espontánea e inducida de aberraciones cromosómicas en médula ósea de ratones OF-1 y C57BL/6/cenp Comparison between induced and spontaneous chromosomal aberrations in OF-1 and C57BL/6/cenp bone marrow mice

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    Daniel Francisco Arencibia Arrebola

    2010-12-01

    Full Text Available El ensayo citogenético in vivo es un ensayo de mutagenicidad a corto plazo de gran sensibilidad, útil para detectar fundamentalmente aberraciones cromosómicas estructurales in vivo. El objetivo del trabajo consistió en determinar el biomodelo experimental más eficiente en este ensayo mediante la comparación de la frecuencia espontánea e inducida de aberraciones cromosómicas en células de la médula ósea, en uno y otro sexos de 2 líneas de ratones (OF-1 y C-57BL/6/cenp. Se formaron 4 grupos experimentales, uno control negativo, dos tratados durante 14 días con sustancias vehículos por vía oral, NaCl (0,9 % y tween 65 (2 %, y uno control positivo tratado a las 48 y 24 h antes del sacrificio con ciclofosfamida (50 mg/kg por vía intraperitoneal. La línea de ratones OF-1 resultó tener una frecuencia espontánea más baja en las variables analizadas que la C-57BL/6/cenp, obteniéndose un menor número espontáneo de células totales con aberraciones y mayor sensibilidad a la ciclofosfamida que la línea C-57BL/6/cenp. Se concluye que los ratones OF-1 y C-57BL/6/cenp, constituyen buenos modelos a emplear en los estudios genotoxicológicos, dada la baja frecuencia espontánea de aberraciones cromosómicas estructurales y numéricas analizadas aunque se recomienda el uso de la línea OF-1.The in vivo cytogenetics array is a very sensible short term mutagenesis method useful to detect mainly the in vivo the structural chromosomal aberrations. The aim of present paper was to determine the more effective experimental bio-model in this type of model to compare the spontaneous and induced frequency of the above mentioned aberrations in bone marrow cells in both sexes of two mice species (OF-1 and C-57BL/6/cenp. Four experimental groups were designed, one of negative control, twotreated during 14 days using oral vehicle substancesm NaCI (0.9 % and tween 65 (2 % and one of positive control treated at 48 and 24 h before sacrifice using

  17. 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

  18. 75 FR 8575 - Testing of Certain High Production Volume Chemicals; Third Group of Chemicals

    Science.gov (United States)

    2010-02-25

    ... to allow for it to be reproduced. vi. Provide specific examples to illustrate your concerns and... toxicity (gene mutations and chromosomal aberrations), repeated dose toxicity, and developmental and... toxicity. Genetic toxicity (gene mutations and chromosomal aberrations). Ecotoxicity (studies in...

  19. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

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    Yerle Martine

    2003-11-01

    Full Text Available Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+ translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5 were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2 from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

  20. Efectos del D-003, mezcla de ácidos alifáticos en el ensayo de aberraciones cromosómicas in vivo Effects of D-003, a mixture of aliphatic acids in a trial of in vivo chromosomal aberrations

    Directory of Open Access Journals (Sweden)

    Daniel Francisco Arencibia Arrebola

    2010-06-01

    Full Text Available El D-003 es una mezcla