Science.gov

Sample records for additional chromosome aberrations

  1. [Study on chromosomes aberration in wheat-rye disomics addition lines induced by the gametocidal chromosome 2C].

    PubMed

    Sun, Zhong-Ping; Wang, Zhan-Bin; Xu, Xiang-Ling; Li, Ji-Lin

    2004-11-01

    In the present study,Chinese Spring-Imperial (1 R-7R) wheat-rye disomic addition lines were hybridized with Chinese Spring-2C (derived from Aegilops cylindrica) disomic addition lines. The F1 hybrids were examined by mitotic and meiotic analysis. There were observed abnormal chromosome configurations. A total of 430 F2 plants were obtained by self-pollination. Chromosomes aberrations, such as translocation, deletions, isobrachial and dicentromere chromosomes, are identified in F2 individual plants by C-banding combined with fluorescent in situ hybridization (FISH). Additionally, chromosome spontaneous substitutions such as 2C substituting for wheat chromosomes 2A, 2B and 2D were also observed. The rule and frequency of chromosome aberration in F2 are the following: 22 out of 430 F2 plants (5.11%) were found involving aberration rye chromosomes. Among them, 10 plants were identified as wheat-rye chromosome translocation lines comprising 2.3%. Rye chromosome deletions comprised 12 of them (2.79%). 3 isobrachial aberrations were detected (about 0.7%), too. Most of the translocation lines are with wheat centromere, only one of them is with rye centromere. Rye chromosome aberrations occurred unevenly among homoeologous groups. There were 5 in 1R, 3 in 2R, 1 in 3R, 3 in 4R, 6 in 5R and 4 in 6R. The majority of the translocation lines are terminal translocation. 54 out of the total 430 progenies are wheat deletions,and 27 are distributed in the A group, 20 in the B group and 7 in the D group respectively. Finally,we discussed the possible cause for the uneven chromosome aberration among homoeologous groups in wheat and rye as well as the effect characteristics of 2C on wheat and rye chromosome. PMID:15651680

  2. Interpreting Chromosome Aberration Spectra

    NASA Technical Reports Server (NTRS)

    Levy, Dan; Reeder, Christopher; Loucas, Bradford; Hlatky, Lynn; Chen, Allen; Cornforth, Michael; Sachs, Rainer

    2007-01-01

    Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

  3. Chromosome aberrations induced by zebularine in triticale.

    PubMed

    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. PMID:27334255

  4. The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations.

    PubMed

    Stengel, Anna; Kern, Wolfgang; Haferlach, Torsten; Meggendorfer, Manja; Haferlach, Claudia

    2016-10-01

    Deletions in the long arm of chromosome 5 (del(5q)) are recurrent abnormalities in myeloid malignancies. We analyzed del(5q) and accompanying molecular mutations in MDS, MPN and MDS/MPN cases. A high del(5q) frequency was revealed in MDS (1869/11398 cases; 16%), followed by MDS/MPN (37/1107; 3%) and MPN (97/6373; 2%). To investigate potential associations of the del(5q) size with the respective phenotypes, we applied array CGH analyses in selected cohorts of 61 MDS, 22 MDS/MPN and 23 MPN cases. The size varied between 16 and 119 Mb with no differences between the entities. However, MPN and MDS/MPN cases with del(5q) sole showed a significantly smaller del(5q) than cases with additional aberrations. Sequence analysis of 27 genes revealed ≥1 mutation in 91% of patients. The highest mutation frequencies in the total cohort were observed for TP53 (31%), JAK2 (23%) and DNMT3A (18%). The molecular mutation patterns in the del(5q) cohorts were different between the entities but resembled known patterns of cohorts not selected for del(5q). Further, TP53 mutations were significantly more frequent in cases with a larger deletion size (P = 0.003). The results suggest a correlation of large del(5q) with TP53 mutations and with additional chromosomal aberrations possibly contributing to more severe courses of these cases. © 2016 Wiley Periodicals, Inc. PMID:27218649

  5. Chromosome Aberrations in Astronauts

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

    A review of currently available data on in vivo induced chromosome damage in the blood lymphocytes of astronauts proves that, after protracted exposure of a few months or more to space radiation, cytogenetic biodosimetry analyses of blood collected within a week or two of return from space provides a reliable estimate of equivalent radiation dose and risk. Recent studies indicate that biodosimetry estimates from single spaceflights lie within the range expected from physical dosimetry and biophysical models, but very large uncertainties are associated with single individual measurements and the total sample population remains low. Retrospective doses may be more difficult to estimate because of the fairly rapid time-dependent loss of "stable" aberrations in blood lymphocytes. Also, biodosimetry estimates from individuals who participate in multiple missions, or very long (interplanetary) missions, may be complicated by an adaptive response to space radiation and/or changes in lymphocyte survival and repopulation. A discussion of published data is presented and specific issues related to space radiation biodosimetry protocols are discussed.

  6. Relationships between chromosome structure and chromosomal aberrations

    NASA Astrophysics Data System (ADS)

    Eidelman, Yuri; Andreev, Sergey

    An interphase nucleus of human lymphocyte was simulated by the novel Monte Carlo tech-nique. The main features of interphase chromosome structure and packaging were taken into account: different levels of chromatin organisation; nonrandom localisation of chromosomes within a nucleus; chromosome loci dynamics. All chromosomes in a nucleus were modelled as polymer globules. A dynamic pattern of intra/interchromosomal contacts was simulated. The detailed information about chromosomal contacts, such as distribution of intrachromoso-mal contacts over the length of each chromosome and dependence of contact probability on genomic separation between chromosome loci, were calculated and compared to the new exper-imental data obtained by the Hi-C technique. Types and frequencies of simple and complex radiation-induced chromosomal exchange aberrations (CA) induced by X-rays were predicted with taking formation and decay of chromosomal contacts into account. Distance dependence of exchange formation probability was calculated directly. mFISH data for human lymphocytes were analysed. The calculated frequencies of simple CA agreed with the experimental data. Complex CA were underestimated despite the dense packaging of chromosome territories within a nucleus. Possible influence of chromosome-nucleus structural organisation on the frequency and spectrum of radiation-induced chromosome aberrations is discussed.

  7. Chromosome Aberrations by Heavy Ions

    NASA Astrophysics Data System (ADS)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  8. Chromosome aberrations in decondensed sperm DNA

    SciTech Connect

    Preston, R.J.

    1982-01-01

    Factors that could influence the chromosomal aberration frequency observed at first cleavage following in vivo exposure of germ cells to chemical mutagens are discussed. The techniques of chromosome aberration analysis following sperm DNA condensation by in vitro fertilization or fusion seem to be viable research areas for providing information of human germ cell exposures. However, the potential sensitivity of the assay needs to be better understood, and factors that can influence this sensitivity require a great deal of further study using animal models.

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

    PubMed

    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. PMID:25482192

  10. Quantitative analysis of radiation-induced chromosome aberrations.

    PubMed

    Sachs, R K; Levy, D; Hahnfeldt, P; Hlatky, L

    2004-01-01

    We review chromosome aberration modeling and its applications, especially to biodosimetry and to characterizing chromosome geometry. Standard results on aberration formation pathways, randomness, dose-response, proximity effects, transmissibility, kinetics, and relations to other radiobiological endpoints are summarized. We also outline recent work on graph-theoretical descriptions of aberrations, Monte-Carlo computer simulations of aberration spectra, software for quantifying aberration complexity, and systematic links of apparently incomplete with complete or truly incomplete aberrations. PMID:15162028

  11. DNA Repair Defects and Chromosomal Aberrations

    NASA Technical Reports Server (NTRS)

    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

  12. Patterns of Chromosomal Aberrations in Solid Tumors

    PubMed Central

    Grade, Marian; Difilippantonio, Michael J.

    2016-01-01

    Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality. PMID:26376875

  13. Patterns of Chromosomal Aberrations in Solid Tumors.

    PubMed

    Grade, Marian; Difilippantonio, Michael J; Camps, Jordi

    2015-01-01

    Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality. PMID:26376875

  14. Chromosomal aberrations in ISS crew members

    NASA Astrophysics Data System (ADS)

    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.

  15. Chromosomal aberrations in lymphocytes from car painters.

    PubMed

    Silva, J M; Santos-Mello, R

    1996-05-01

    In the present paper we report the results of biological monitoring of a group of 25 car painters working in different automobile shops in Brasília. There was a significantly higher frequency of aneuplodies and chromosome deletions in the peripheral lymphocytes of car painters than in control subjects. We also detected a significant correlation between the time worked as a car painter and the frequency of aneuploidy. Smoking habits do not represent a significant factor in terms of production of the various types of chromosome aberrations among car painters. These results permitted us to conclude that the individuals studied represent a risk group and should be medically followed up with judicious periodic examinations. PMID:8637507

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

    PubMed

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

    2013-01-01

    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. PMID:23884766

  17. Lymphocyte chromosomal aberration assay in radiation biodosimetry

    PubMed Central

    Agrawala, Paban K.; Adhikari, J. S.; Chaudhury, N. K.

    2010-01-01

    Exposure to ionizing radiations, whether medical, occupational or accidental, leads to deleterious biological consequences like mortality or carcinogenesis. It is considered that no dose of ionizing radiation exposure is safe. However, once the accurate absorbed dose is estimated, one can be given appropriate medical care and the severe consequences can be minimized. Though several accurate physical dose estimation modalities exist, it is essential to estimate the absorbed dose in biological system taking into account the individual variation in radiation response, so as to plan suitable medical care. Over the last several decades, lots of efforts have been taken to design a rapid and easy biological dosimeter requiring minimum invasive procedures. The metaphase chromosomal aberration assay in human lymphocytes, though is labor intensive and requires skilled individuals, still remains the gold standard for radiation biodosimetry. The current review aims at discussing the human lymphocyte metaphase chromosomal aberration assay and recent developments involving the application of molecular cytogenetic approaches and other technological advancements to make the assay more authentic and simple to use even in the events of mass radiation casualties. PMID:21829315

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

    PubMed Central

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

    2013-01-01

    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. PMID:24027668

  19. Chromosomal aberrations in lymphocytes of pharmaceutical factory workers

    SciTech Connect

    Pushpavathi, K.; Prasad, M.H.; Reddy, P.P.

    1986-10-01

    Chromosomes were analyzed in peripheral lymphocytes of 31 male workers who were exposed to sulfonamide drugs in a pharmaceutical factory. The number of cells with structural chromosomal aberrations was significantly increased as compared to 15 unexposed individuals (controls). The chromosomal damage observed was mainly gaps and breaks.

  20. [Fetal diagnosis from the mother's blood--noninvasive screening of chromosomal aberrations].

    PubMed

    Anttonen, Anna-Kaisa; Stefanovic, Vedran; Aittomäki, Kristiina

    2015-01-01

    In Finland, the screening of fetal chromosome aberrations is currently based on combined screening in the first trimester. Non-invasive prenatal testing (NIPT) is a new method enabling a more accurate screening than combined screening of fetal chromosome aberrations from the mother's blood sample by analyzing cell-free fetal DNA (cffDNA). In addition, it is possible to determine the gender of the fetus or assess the number of sex chromosomes. Although NIPT is an accurate screening method, an aberrant result should always be confirmed by an invasive fetal diagnostic test. PMID:26749901

  1. Chromatin structure and ionizing-radiation-induced chromosome aberrations

    SciTech Connect

    Muehlmann-Diaz, M.C.

    1993-01-01

    The possible influence of chromatic structure or activity on chromosomal radiosensitivity was studied. A cell line was isolated which contained some 10[sup 5] copies of an amplified plasmid in a single large mosquito artificial chromosome (MAC). This chromosome was hypersensitive to DNase I. Its radiosensitivity was some three fold greater than normal mosquito chromosomes in the same cell. In cultured human cells irradiated during G[sub 0], the initial breakage frequency in chromosome 4, 19 and the euchromatic and heterochromatic portions of the Y chromosome were measured over a wide range of doses by inducing Premature Chromosome Condensation (PCC) immediately after irradiation with Cs-137 gamma rays. No evidence was seen that Y heterochromatin or large fragments of it remained unbroken. The only significant deviation from the expected initial breakage frequency per Gy per unit length of chromosome was that observed for the euchromatic portion of the Y chromosome, with breakage nearly twice that expected. The development of aberrations involving X and Y chromosomes at the first mitosis after irradation was also studied. Normal female cells sustained about twice the frequency of aberrations involving X chromosomes for a dose of 7.3 Gy than the corresponding male cells. Fibroblasts from individuals with supernumerary X chromosomes did not show any further increase in X aberrations for this dos. The frequency of aberrations involving the heterochromatic portion of the long arm of the Y chromosome was about what would be expected for a similar length of autosome, but the euchromatic portion of the Y was about 3 times more radiosensitive per unit length. 5-Azacytidine treatment of cultured human female fibroblasts or fibroblasts from a 49,XXXXY individual, reduced the methylation of cytosine residues in DNA, and resulted in an increased chromosomal radiosensitivity in general, but it did not increase the frequency of aberrations involving the X chromosomes.

  2. Metaphase chromosome aberrations as markers of radiation exposure and dose

    SciTech Connect

    Brooks, A.L.; Khan, M.A.; Jostes, R.F.; Cross, F.T.

    1992-10-01

    Chromosome aberration frequency provides the most reliable biological marker of dose for detecting acute accidental radiation exposure. Significant radiation-induced changes in the frequency of chromosome aberrations can be detected at very low doses. Our paper provides information on using molecular chromosome probes ``paints`` to score chromosome damage and illustrates how technical advances make it possible to understand mechanisms involved during formation of chromosome aberrations. In animal studies chromosome aberrations provide a method to relate cellular damage to cellular dose. Using an In vivo/In vitro approach aberrations provided a biological marker of dose from radon progeny exposure which was used to convert WLM to dose in rat tracheal epithelial cells. Injection of Chinese hamsters with {sup 144}Ce which produced a low dose rate exposure of bone marrow to either low-LET radiation increased the sensitivity of the cells to subsequent external exposure to {sup 60}Co. These studies demonstrated the usefulness of chromosome damage as a biological marker of dose and cellular responsiveness.

  3. Metaphase chromosome aberrations as markers of radiation exposure and dose

    SciTech Connect

    Brooks, A.L.; Khan, M.A.; Jostes, R.F.; Cross, F.T.

    1992-10-01

    Chromosome aberration frequency provides the most reliable biological marker of dose for detecting acute accidental radiation exposure. Significant radiation-induced changes in the frequency of chromosome aberrations can be detected at very low doses. Our paper provides information on using molecular chromosome probes paints'' to score chromosome damage and illustrates how technical advances make it possible to understand mechanisms involved during formation of chromosome aberrations. In animal studies chromosome aberrations provide a method to relate cellular damage to cellular dose. Using an In vivo/In vitro approach aberrations provided a biological marker of dose from radon progeny exposure which was used to convert WLM to dose in rat tracheal epithelial cells. Injection of Chinese hamsters with [sup 144]Ce which produced a low dose rate exposure of bone marrow to either low-LET radiation increased the sensitivity of the cells to subsequent external exposure to [sup 60]Co. These studies demonstrated the usefulness of chromosome damage as a biological marker of dose and cellular responsiveness.

  4. [Radioulnar synostosis as characteristic feature of chromosome aberrations (author's transl)].

    PubMed

    Küsswetter, W; Heisel, A

    1981-02-01

    Among 13 patients with congenital proximal radioulnar synostosis the chromosomal analysis revealed a 47, XXY-constellation in an 8 years old boy and a 47, XXX-syndrome in a 12-year-old girl. The investigations show, that the congenital radio-ulnar synostosis may be combined with the chromosome aberration more often than it was commonly thought. PMID:7281903

  5. Induction of chromosome aberrations in human cells by charged particles

    NASA Technical Reports Server (NTRS)

    Wu, H.; Durante, M.; George, K.; Yang, T. C.

    1997-01-01

    Chromosome aberrations induced by high-energy charged particles in normal human lymphocytes and human fibroblasts have been investigated. The charged particles included 250 MeV/nucleon protons, 290 MeV/nucleon carbon ions and 1 GeV/nucleon iron ions. The energies of the charged particles were higher than in most of the studies reported in the literature. Lymphocytes were stimulated to grow immediately after irradiation, while fibroblasts were incubated at 37 degrees C for 24 h for repair. Chromosomes were collected at the first mitosis after irradiation and chromosome aberrations were scored using the fluorescence in situ hybridization (FISH) technique with a whole-chromosome 4 probe. Chromosome aberrations were classified as reciprocal exchanges, incomplete exchanges, deletions and complex exchanges. The relative biological effectiveness (RBE) for each type of aberration was calculated by dividing a dose of 4 Gy by the dose of the charged particles producing the same effect as 4 Gy of gamma rays. Results of this study showed that complex aberrations have the highest RBE for radiation of high linear energy transfer (LET) for human lymphocytes, but for fibroblasts, the greatest effect was for incomplete exchanges. For both lymphocytes and fibroblasts, iron ions induced a similar fraction of aberrant cells.

  6. Risk estimation based on chromosomal aberrations induced by radiation

    NASA Technical Reports Server (NTRS)

    Durante, M.; Bonassi, S.; George, K.; Cucinotta, F. A.

    2001-01-01

    The presence of a causal association between the frequency of chromosomal aberrations in peripheral blood lymphocytes and the risk of cancer has been substantiated recently by epidemiological studies. Cytogenetic analyses of crew members of the Mir Space Station have shown that a significant increase in the frequency of chromosomal aberrations can be detected after flight, and that such an increase is likely to be attributed to the radiation exposure. The risk of cancer can be estimated directly from the yields of chromosomal aberrations, taking into account some aspects of individual susceptibility and other factors unrelated to radiation. However, the use of an appropriate technique for the collection and analysis of chromosomes and the choice of the structural aberrations to be measured are crucial in providing sound results. Based on the fraction of aberrant lymphocytes detected before and after flight, the relative risk after a long-term Mir mission is estimated to be about 1.2-1.3. The new technique of mFISH can provide useful insights into the quantification of risk on an individual basis.

  7. Increased frequency of chromosomal aberrations in railroad car painters.

    PubMed

    Piña-Calva, A; Madrigal-Bujaidar, E; Fuentes, M V; Neria, P; Pérez-Lucio, C; Vélez-Zamora, N M

    1991-01-01

    The purpose of this study was to determine if exposure to paints and solvents contributes to chromosomal alterations in occupationally exposed individuals. A total of 25 male railroad and underground railroad car painters were studied. This group had a mean age of 32.7 y and a mean exposure time of 5.2 y. The results were compared with those obtained for 25 healthy (unexposed) males. The scoring of structural chromosome aberrations clearly revealed an increase in the number of all types of aberrations considered in the population of painters. This suggests that exposure to a combination of chemicals may increase genotoxicity in industrial workers. PMID:1772257

  8. Chromosome aberrations in plants as a monitoring system.

    PubMed Central

    Grant, W F

    1978-01-01

    The potential of higher plants as a first-tier assay system for detecting chemical mutagens is evaluated. The use of plant tissue (primarily root tips and pollen mother cells) for studying the induction of chromosomal aberrations is one of the oldest, simplest, most reliable, and inexpensive methods available. Specific types of abnormalities have been induced by different classes of pesticides. Chromosome clumping, contraction, stickiness, paling, fragmentation, dissolution, chromosome and chromatid bridges, C-mitosis, and endoploidy have been reported in the literature. Examples of cytogenetic studies with pesticides demonstrating the usefulness of higher plants as a monitoring system are reviewed. Pesticides which cause chromosome aberrations in plant cells also produce chromosome aberrations in cultured animal cells. Frequently, the aberrations are identical. For example, studies have shown that compounds which have a C-mitotic effect on plant cells have the same effect on animal cells. It is recommended that plant systems be accepted as a first-tier assay system for the detection of possible genetic damage by environmental chemicals. PMID:367773

  9. Cytogenetic effects of radiotherapy. Breakpoint distribution in induced chromosome aberrations

    SciTech Connect

    Barrios, L.; Miro, R.; Caballin, M.R.; Fuster, C.; Guedea, F.; Subias, A.; Egozcue, J. )

    1989-08-01

    A total of 660 breakpoints were identified in the chromosome aberrations detected in lymphocytes from cancer patients after radiotherapy. The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in vivo. Chromosome arms 1p, 1q, 7q, and 11p were also significantly more affected. Some bands also showed a special sensitivity to radiation, and band 1q32 was the most affected. This band is proposed as a hot point for the clastogenic effect of ionizing radiation. A significant clustering of breakpoints in G bands was also found, especially at the telomeres, as previously described by other authors. Clustering of breakpoints was also observed in bands where fragile sites, protooncogenes, breakpoints involved in chromosomal cancer rearrangements, and breakpoints involved in chromosomal evolution of the Hominoidea are located.

  10. Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis

    PubMed Central

    Rakanović-Todić, Maida; Burnazović-Ristić, Lejla; Ibrulj, Slavka; Mulabegović, Nedžad

    2014-01-01

    Endogenous opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL). However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted. PMID:24856378

  11. Chromosome aberrations in Norwegian reindeer following the Chernobyl accident.

    PubMed

    Røed, K H; Jacobsen, M

    1995-03-01

    Chromosome analyses were carried out on peripheral blood lymphocytes of semi-domestic reindeer in Norway which had been exposed to varying amounts of radiocesium emanating from the Chernobyl accident. The sampling was done in the period 1987-1990. The material included 192 reindeer, originating from four herds in central Norway, an area considerably affected by fallout from the Chernobyl accident, and from three herds in northern Norway which was unaffected by fallout from the accident. Significant heterogeneity in the distribution of chromosome aberrations between herds was observed. The pattern of chromosome aberration frequencies between herds was not related to the variation in radiocesium exposure from the Chernobyl accident. Other factors than the Chernobyl accident appear therefore to be of importance for the distribution of aberration frequencies found among present herds. Within the most contaminated area the reindeer born in 1986 showed significantly more chromosome aberrations than those born both before and after 1986. This could suggest that the Chernobyl accident fallout created an effect particularly among calves, during the immediate post-accident period in the most exposed areas. PMID:7700280

  12. Induction of chromosomal aberrations in the mussel Mytilus galloprovincialis watch

    SciTech Connect

    Al-Sabti, K.; Kurelec, B.

    1985-11-01

    In this paper the authors present an investigation into the occurrence of chromosomal aberration (CA) induction in mussels. The feasibility of using this as an indicator of genotoxins under actual field conditions has been evaluated. Benzo(a)pyrene was used in these experiments.

  13. Modelling chromosomal aberration induction by ionising radiation: The influence of interphase chromosome architecture

    NASA Astrophysics Data System (ADS)

    Ottolenghi, A.; Ballarini, F.; Biaggi, M.

    Several advances have been achieved in the knowledge of nuclear architecture and functions during the last decade, thus allowing the identification of interphase chromosome territories and sub-chromosomal domains (e.g. arm and band domains). This is an important step in the study of radiation-induced chromosome aberrations; indeed, the coupling between track-structure simulations and reliable descriptions of the geometrical properties of the target is one of the main tasks in modelling aberration induction by radiation, since it allows one to clarify the role of the initial positioning of two DNA lesions in determining their interaction probability. In the present paper, the main recent findings on nuclear and chromosomal architecture are summarised. A few examples of models based on different descriptions of interphase chromosome organisation (random-walk models, domain models and static models) are presented, focussing on how the approach adopted in modelling the target nuclei and chromosomes can influence the simulation of chromosomal aberration yields. Each model is discussed by taking into account available experimental data on chromosome aberration induction and/or interphase chromatin organisation. Preliminary results from a mechanistic model based on a coupling between radiation track-structure features and explicitly-modelled, non-overlapping chromosome territories are presented.

  14. Comparison of chromosomal aberrations detected by fluorescence in situ hybridization with clinical parameters, DNA ploidy and Ki 67 expression in renal cell carcinoma.

    PubMed Central

    Wada, Y.; Igawa, M.; Shiina, H.; Shigeno, K.; Yokogi, H.; Urakami, S.; Yoneda, T.; Maruyama, R.

    1998-01-01

    To evaluate the significance of chromosomal aberrations in renal cell carcinoma, fluorescence in situ hybridization (FISH) was used to determine its prevalence and correlation with clinical parameters of malignancy. In addition, correlation of chromosomal aberration with Ki 67 expression was analysed. We performed FISH with chromosome-specific DNA probes, and the signal number of pericentromeric sequences on chromosomes 3, 7, 9 and 17 was detected within interphase nuclei in touch preparations from tumour specimen. The incidence of loss of chromosome 3 was significantly higher than those of chromosomes 7, 9 and 17 (P < 0.001, P = 0.03 and P < 0.001 respectively). Hyperdiploid aberration of chromosomes 3 and 17 was significantly correlated with tumour stage (P = 0.03, P = 0.02 respectively), whereas hyperdiploid aberration of chromosome 9 was associated with nuclear grade (P = 0.04). Disomy of chromosome 7 was correlated with venous involvement (P = 0.04). Ki 67 expression was significantly associated with hyperdiploid aberration of chromosome 17 (P = 0.01), but not with aberration of chromosome 3. There was a significant relationship between hyperdiploid aberration of chromosome 7 and Ki 67 expression (P = 0.01). In conclusions, gain of chromosome 17 may reflect tumour development, and aberration of chromosome 7 may affect metastatic potential of malignancy, whereas loss of chromosome 3 may be associated with early stage of tumour development in renal cell carcinoma. PMID:9667682

  15. [The number of aberrations in aberrant cells as a parameter of chromosomal instability. 1. Characterization of dose dependency].

    PubMed

    Kutsokon', N K; Bezrukov, V F; Lazarenko, L M; Rashydov, N M; Hrodzyns'kyĭ, D M

    2003-01-01

    Analysis of chromosome instability (CI) is of great importance in view of pollution of the environment by genotoxic factors. Frequency of aberrant cells, spectrum of chromosome aberrations, damages of aberrant cell and distribution of aberrations in the cells are the most conventional parameters of CI. We have carried out the comparative analysis of the frequency of aberrant cells and the dynamics of aberrant cell damages induced by different mutagenic factors (alpha-irradiation from 241Am, gamma-irradiation from 60Co and tioTEPA) in Allium-test. This comparative analysis denotes that the studied parameters have different dynamics characterizing different mechanisms of CI in Allium cepa L. PMID:14569619

  16. Benzene-induced chromosome aberrations: a follow-up study.

    PubMed Central

    Forni, A

    1996-01-01

    To study the evolution of cytogenetic damage from past exposure to high concentrations of benzene and its health significance, chromosome aberrations (CA) in lymphocytes were reinvestigated after approximately 20 years in four subjects with past severe hemopathy and in seven controls studied in the late 1960s. Increased chromosome-type aberrations were still present up to 30 years after benzene toxicity, but blood counts were normal. The vital status at the end of 1993 was ascertained for 32 subjects with a history of benzene toxicity and for 31 controls studied for CA from 1965 to 1970, who differed significantly for CA rates. Of the 32 benzene-exposed subjects, 1 was lost to follow-up, 20 were still alive, and 11 had died at ages 36 to 83, between 1 and 20 years after the last CA study. Five deaths were from neoplasia (acute erythroleukemia, brain tumor, cancer of lung, paranasal cavity, esophagus). The decreased subjects had significantly higher rates of chromosome-type aberrations than those alive, and those who died of neoplasia had the highest rates of these aberrations in the last study before death or diagnosis of cancer. Out of the 31 controls, 12 had died from 4 to 23 years after the CA study. Three deaths were from neoplasia (two lung cancer, one brain tumor). Even if this is a small sample, the results suggest a higher risk of cancer for the benzene-exposed cohort, who had persistently high CA rates in lymphocytes. PMID:9118911

  17. Time sequence of events leading to chromosomal aberration formation

    SciTech Connect

    Moore, R.C. ); Bender, M.A. )

    1993-01-01

    Investigations have been carried out which have measured the influence of the repair polymerases on the yield of different types of chromosomal aberrations. The studies were mainly concerned with the effect of inhibiting the polymerases on the yield of aberrations. The polymerases fill in single strand regions, and the fact that their inhibition affects the yield of aberrations suggests that single strand lesions are influential in aberration formation. The results indicate that: (1) There are two actions of polymerases in clastogenesis. One is in their involvement in a G2 repair system, in which the pair of chromatids is concerned, and which does not yield aberrations unless the inhibition is still operating when the cells enter mitosis. The second also operates in G1 and S, and is such that when repair is inhibited, further damage accrues. (2) The second action is affected by inhibiting polymerase but operates even when the repair enzymes are active. (3) The production of chromosomal exchanges involves a series of reactions, some of which are reversible. (4) The time span over which the reactions occur is much longer than has been envisaged previously (e.g., most of a cell cycle). 29 refs., 1 fig.

  18. Time sequence of events leading to chromosomal aberration formation

    SciTech Connect

    Moore, R.C. ); Bender, M.A. )

    1993-01-01

    Investigations have been carried out on the influence of the repair polymerases on the yield of different types of chromosomal aberrations. The studies were mainly concerned with the effect of inhibiting the polymerases on the yield of aberrations. The polymerases fill in single-strand regions, and the fact that their inhibition affects the yield of aberrations suggests that single-strand lesions are influential in aberration formation. The results indicate that there are two actions of polymerases in clastogenesis. One is in their involvement in a G[sub 2] repair system, in which either of the two chromatids is concerned, and which does not yield aberrations unless the inhibition is still operating when the cells enter mitosis. The second is such that when repair is inhibited, further damage accrues. The second action is affected by inhibiting polymerase repair, but also operates even when the repair enzymes are active. The production of chromosomal exchanges involves a series of reactions, some of which are reversible. The time span over which the reactions occur is much longer than has been envisaged previously.

  19. Time sequence of events leading to chromosomal aberration formation

    SciTech Connect

    Moore, R.C.; Bender, M.A.

    1993-05-01

    Investigations have been carried out on the influence of the repair polymerases on the yield of different types of chromosomal aberrations. The studies were mainly concerned with the effect of inhibiting the polymerases on the yield of aberrations. The polymerases fill in single-strand regions, and the fact that their inhibition affects the yield of aberrations suggests that single-strand lesions are influential in aberration formation. The results indicate that there are two actions of polymerases in clastogenesis. One is in their involvement in a G{sub 2} repair system, in which either of the two chromatids is concerned, and which does not yield aberrations unless the inhibition is still operating when the cells enter mitosis. The second is such that when repair is inhibited, further damage accrues. The second action is affected by inhibiting polymerase repair, but also operates even when the repair enzymes are active. The production of chromosomal exchanges involves a series of reactions, some of which are reversible. The time span over which the reactions occur is much longer than has been envisaged previously.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Antimutagenic effects of garlic extract on chromosomal aberrations.

    PubMed

    Shukla, Yogeshwer; Taneja, Pankaj

    2002-02-01

    Garlic (Allium sativum) has been used since ancient times, as a spice and also for its medicinal properties. In present set of investigations antimutagenic effect of garlic extract (GE) has been evaluated using 'in vivo chromosomal aberration assay' in Swiss albino mice. Cyclophosphamide (CP), a well-known mutagen, was given at a single dose of 25 mg/kg b.w. intraperitoneally. Pretreatment with 1, 2.5 and 5% of freshly prepared GE was given through oral intubation for 5 days prior to CP administration. Animals from all the groups were sacrificed at sampling times of 24 and 48 h and their bone marrow tissue was analyzed for chromosomal damage. The animals of the positive control group (CP alone) shows a significant increase in chromosomal aberrations both at 24 and 48 h sampling time. GE, alone did not significantly induced aberrations at either sampling time, confirming its non-mutagenicity. However in the GE pre-treated and CP post-treated groups, a dose dependent decrease in cytogenetic damage was recorded. A significant suppression in the chromosomal aberrations was recorded following pretreatment with 2.5 and 5% GE administration. The anticytotoxic effects of GE were also evident, as observed by significant increase in mitotic index, when compared to positive control group. Reduction in CP induced clastogenicity by GE was evident at 24 h and to a much greater extent at 48 h of cell cycle. Thus results of the present investigations revealed that GE has chemopreventive potential against CP induced chromosomal mutations in Swiss albino mice. PMID:11790451

  2. Nonrandom chromosomal aberrations and cytogenetic heterogeneity in gallbladder carcinomas.

    PubMed

    Gorunova, L; Parada, L A; Limon, J; Jin, Y; Hallén, M; Hägerstrand, I; Iliszko, M; Wajda, Z; Johansson, B

    1999-12-01

    Chromosome banding analysis of 11 short-term cultured gallbladder carcinomas revealed acquired clonal aberrations in seven tumors (five primary and two metastases). Three of these had one clone, whereas the remaining four were cytogenetically heterogeneous, displaying two to seven aberrant clones. Of a total of 21 abnormal clones, 18 had highly complex karyotypes and three exhibited simple numerical deviations. Double minutes and homogeneously staining regions were observed in one and two carcinomas, respectively. To characterize the karyotypic profile of gallbladder cancer more precisely, we have combined the present findings with our three previously reported cases, thereby providing the largest cytogenetic database on this tumor type to date. A total of 287 chromosomal breakpoints were identified, 251 of which were found in the present study. Chromosome 7 was rearranged most frequently, followed by chromosomes 1, 3, 11, 6, 5, and 8. The bands preferentially involved were 1p32, 1p36, 1q32, 3p21, 6p21, 7p13, 7q11, 7q32, 19p13, 19q13, and 22q13. Nine recurrent abnormalities could, for the first time, be identified in gallbladder carcinoma: del(3)(p13), i(5)(p10), del(6)(q13), del(9)(p13), del(16)(q22), del(17)(p11), i(17)(q10), del(19)(p13), and i(21)(q10). The most common partial or whole-arm gains involved 3q, 5p, 7p, 7q, 8q, 11q, 13q, and 17q, and the most frequent partial or whole-arm losses affected 3p, 4q, 5q, 9p, 10p, 10q, 11p, 14p, 14q, 15p, 17p, 19p, 21p, 21q, and Xp. These chromosomal aberrations and imbalances provide some starting points for molecular analyses of genomic regions that may harbor genes of pathogenetic importance in gallbladder carcinogenesis. Genes Chromosomes Cancer 26:312-321, 1999. PMID:10534766

  3. Evaluation of an automated karyotyping system for chromosome aberration analysis

    NASA Technical Reports Server (NTRS)

    Prichard, Howard M.

    1987-01-01

    Chromosome aberration analysis is a promising complement to conventional radiation dosimetry, particularly in the complex radiation fields encountered in the space environment. The capabilities of a recently developed automated karyotyping system were evaluated both to determine current capabilities and limitations and to suggest areas where future development should be emphasized. Cells exposed to radiometric chemicals and to photon and particulate radiation were evaluated by manual inspection and by automated karyotyping. It was demonstrated that the evaluated programs were appropriate for image digitization, storage, and transmission. However, automated and semi-automated scoring techniques must be advanced significantly if in-flight chromosome aberration analysis is to be practical. A degree of artificial intelligence may be necessary to realize this goal.

  4. Long-term persistence of chromosome aberrations in uranium miners.

    PubMed

    Mészáros, Gabriella; Bognár, Gabriella; Köteles, G J

    2004-07-01

    Chromosome aberration analyses were performed on blood samples from 165 active underground uranium miners between 1981 and 1985. After decommissioning the mine in 1997 chromosome aberration analyses were also included in the medical laboratory investigations of health conditions of 141 subjects between 1998 and 2002 within the framework of a follow-up-study. The numerical data are presented as functions of the exposure categories expressed in working level month up to 600. In the active groups the dicentric level was 7 to 12 times higher than in the unexposed population, the acentrics also higher with more than an order of magnitude, the frequency of total aberrations--including dicentrics, acentrics, rings, deletions, minits and numerical aberrations, i.e. both chromatid and chromosome type of aberrations were also well above the control level. In the group of former uranium miners although there were slight decreases in the dicentrics after 8 to 25 yr, the values were not significantly different from the values of active miners. The frequency of deletions was also maintained in the post-mining period. The frequency of acentrics, however, decreased significantly, but even the lowest values remained 2-3 times higher than the values in the unexposed population.The possibility is suggested that for the long-term persistence of cytogenetic alterations the permanent production and presence of clastogenic factors might be responsible. The comparison of the two datasets suggest a long-term persistence of cytogenetic alterations above the population average values in a large fraction of persons investigated. PMID:15308832

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

    PubMed Central

    Staub, Eike; Gröne, Jörn; Mennerich, Detlev; Röpcke, Stefan; Klamann, Irina; Hinzmann, Bernd; Castanos-Velez, Esmeralda; Mann, Benno; Pilarsky, Christian; Brümmendorf, Thomas; Weber, Birgit; Buhr, Heinz-Johannes; Rosenthal, André

    2006-01-01

    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. PMID:16982006

  6. Role of chromosomal aberrations in clonal diversity and progression of acute myeloid leukemia.

    PubMed

    Bochtler, T; Fröhling, S; Krämer, A

    2015-06-01

    Genetic abnormalities are a hallmark of cancer. Hereby, cytogenetic aberrations and small-scale abnormalities, such as single-nucleotide variations and insertion/deletion mutations, have emerged as two alternative modes of genetic diversification. Both mechanisms are at work in acute myeloid leukemia (AML), in which conventional karyotyping and molecular studies demonstrate that gene mutations occur predominantly in cytogenetically normal AML, whereas chromosomal changes are a driving force of development and progression of disease in aberrant karyotype AML. All steps of disease evolution in AML, ranging from the transformation of preleukemic clones into overt leukemia to the expansion and recurrence of malignant clones, are paralleled by clonal evolution at either the gene mutation or chromosome aberration level. Preleukemic conditions, such as Fanconi anemia and Bloom syndrome, demonstrate that the acquisition of chromosomal aberrations can contribute to leukemic transformation. Similar to what has been shown at the mutational level, expansion and recurrence of AML clones goes along with increasing genetic diversification. Hereby, cytogenetically more evolved subclones are at a proliferative advantage and outgrow ancestor clones or have evolved toward a more aggressive behavior with additional newly acquired aberrations as compared with the initial leukemic clone, respectively. PMID:25673237

  7. A Monte-Carlo Model for the Formation of Radiation-induced Chromosomal Aberrations

    NASA Technical Reports Server (NTRS)

    Ponomarev, Artem L.; Cornforth, Michael N.; Loucas, Brad D.; Cucinotta, Francis A.

    2009-01-01

    Purpose: To simulate radiation-induced chromosome aberrations in mammalian cells (e.g., rings, translocations, and dicentrics) and to calculate their frequency distributions following exposure to DNA double strand breaks (DSBs) produced by high-LET ions. Methods: The interphase genome was assumed to be comprised of a collection of 2 kbp rigid-block monomers following the random-walk geometry. Additional details for the modeling of chromosomal structure, such as chromosomal domains and chromosomal loops, were included. A radial energy profile for heavy ion tracks was used to simulate the high-LET pattern of induced DSBs. The induced DSB pattern depended on the ion charge and kinetic energy, but always corresponded to the DSB yield of 25 DSBs/cell/Gy. The sum of all energy contributions from Poisson-distributed particle tracks was taken to account for all possible one-track and multi-track effects. The relevant output of the model was DNA fragments produced by DSBs. The DSBs, or breakpoints, were defined by (x, y, z, l) positions, where x, y, z were the Euclidian coordinates of a DSB, and where l was the relative position along the genome. Results: The code was used to carry out Monte Carlo simulations for DSB rejoinings at low doses. The resulting fragments were analyzed to estimate the frequencies of specific types of chromosomal aberrations. Histograms for relative frequencies of chromosomal aberrations and P.D.F.s (probability density functions) of a given aberration type were produced. The relative frequency of dicentrics to rings was compared to empirical data to calibrate rejoining probabilities. Of particular interest was the predicted distribution of ring sizes, irrespective of their frequencies relative to other aberrations. Simulated ring sizes were . 4 kbp, which are far too small to be observed experimentally (i.e., by microscopy) but which, nevertheless, are conjectured to exist. Other aberrations, for example, inversions, translocations, as well as

  8. Class II Analphoid Chromosome in a Child with Aberrant Chromosome 7: A Rare Cytogenetic Association.

    PubMed

    Kumar, Madhavan Jeevan; Kumar, Rangasamy Ashok; Subhashree, Venugopal; Jayasudha, Thanikachalam; Hemagowri, Venkatasubramanian; Koshy, Teena; Gowrishankar, Kalpana

    2015-01-01

    A neocentromere is a functional centromere that has arisen within a region not known to have a centromere. We present a case with a very rarely reported class II neocentromere formation in an aberrant chromosome 7. A 22-month-old male was referred because of dysmorphic features. Banding cytogenetics was performed, and a ring 7 and a supernumerary marker chromosome along with a normal chromosome 7 were found. In situ hybridization using a centromeric probe revealed 46 signals, of which 2 signals for chromosome 7 were observed, one on the normal and one on the ring chromosome. Further analysis using FISH revealed that the linear acentric fragment was part of the 7q region, which suggests that there could be a possible McClintock mechanism. PMID:26226839

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

    PubMed

    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. PMID:25800034

  10. Painting Analysis of Chromosome Aberrations Induced by Energetic Heavy Ions in Human Cells

    NASA Technical Reports Server (NTRS)

    Wu, Honglu

    2006-01-01

    FISH, mFISH, mBAND, telomere and centromere probes have been used to study chromosome aberrations induced in human cells exposed to low-and high-LET radiation in vitro. High-LET induced damages are mostly a single track effect. Unrejoined chromosome breaks (incomplete exchanges) and complex type aberrations were higher for high-LET. Biosignatures may depend on the method the samples are collected. Recent mBAND analysis has revealed more information about the nature of intra-chromosome exchanges. Whether space flight/microgravity affects radiation-induced chromosome aberration frequencies is still an open question.

  11. Chromosome aberrations induced by high-LET radiations

    NASA Technical Reports Server (NTRS)

    Kawata, Tetsuya; Ito, Hisao; George, Kerry; Wu, Honglu; Cucinotta, Francis A.

    2004-01-01

    Measurements of chromosome aberrations in peripheral blood lymphocytes are currently the most sensitive and reliable indicator of radiation exposure that can be used for biological dosimetry. This technique has been implemented recently to study radiation exposures incurred by astronauts during space flight, where a significant proportion of the dose is delivered by high-LET particle exposure. Traditional methods for the assessing of cytogenetic damage in mitotic cells collected at one time point after exposure may not be suitable for measuring high-LET radiation effects due to the drastic cell cycle perturbations and interphase cell death induced by this type of exposure. In this manuscript we review the recent advances in methodology used to study high-LET induced cytogenetic effects and evaluate the use of chemically-induced Premature Chromosome Condensation (PCC) as an alternative to metaphase analysis. Published data on the cytogenetic effects of in vitro exposures of high-LET radiation is reviewed, along with biodosimetry results from astronauts after short or long space missions.

  12. Evaluation of Bleomycin-induced chromosome aberrations under simulated microgravity conditions in human lymphocytes using "FISH" techniques

    NASA Astrophysics Data System (ADS)

    Mosesso, P.; Schuber, M.; Seibt, D.; Schatz, A.; Fosci, A.; Fonti, E.; Palitti, F.

    In the present investigation we report the effects of simulated microgravity conditions (clinostat) on the induction of chromosomal aberrations in human lymphocytes in vitro by ®Bleomycin. Chromosomal aberrations have been analysed by means of fluorescent in situ hybridisation (FISH) and chromosome-specific composite DNA probes (chromosome painting). The results obtained show that, under simulated microgravity conditions, the levels of both symmetrical and asymmetrical (dicentrics, rings), the number of cells bearing "complex" aberrations and hence the total numbers of aberrations were significantly elevated at any of the dose-levels assayed, compared to the parallel treatments performed as 1g control ("ground"). Furthermore, the ratio symmetrical:asymmetrical translocations was markedly elevated under simulated microgravity conditions, compared to the findings usually observed under "normal" 1g conditions. On these bases, we are much inclined to believe that simulated microgravity, rather than limiting the resealing of DNA double strand breaks (DSB's) induced by genotoxic agents is influencing in terms of enhancement the misrejoining of DSB's which is actually responsible for the fixation of the original lesions to DNA into chromosomal aberrations. In addition, the possible different misrepair processes leading to the formation of symmetrical and asymmetrical translocations might be differentially influenced by microgravity being the symmetrical translocations significantly more represented.

  13. Induction of chromosome aberrations by cis-platinum(II)diamminodichloride in Drosophila melanogaster

    SciTech Connect

    Brodberg, R.K.; Lyman, R.F.; Woodruff, R.C.

    1983-01-01

    The authors have determined the in vivo effects of cis-platinum(II)diamminodichloride (cis-PDD) treatment on the induction of chromosome aberrations in Drosophila melanogaster germ cells. cis-PDD treatment induces significant increases in chromosome breakage in all stages of spermatogenesis in a battery of test systems using ring or rod-X males and repair-proficient or deficient females. Since no increase in nondisjunction was induced by cis-PDD in either male or female germ cells, any aneuploidy inducing effects of this compound should result from its clastogenic action. They also find that mei-9 excision repair function is involved in the repair of cis-PDD-induced DNA lesions in a manner that provides additional evidence that partital and ring chromosome losses are not completely homologous.

  14. Intra- and interindividual variability in lymphocyte chromosomal aberrations: implications for cancer risk assessment.

    PubMed

    Peters, Susan; Portengen, Lützen; Bonassi, Stefano; Sram, Radim; Vermeulen, Roel

    2011-08-15

    Chromosomal aberration frequency in peripheral lymphocytes of healthy individuals has been found to be predictive of future cancer risk. The variability of chromosomal aberrations over time, which is largely unknown, should be clarified to interpret the strength of this association and to determine its use in cancer prediction. Intra- and interindividual variability in chromosomal aberration frequency was therefore determined. From a pooled database comprising 11 national cohorts (1965-2002), the authors included 9,433 blood samples from 3,550 subjects with at least one repeated chromosomal aberration measurement. The generalized concordance correlation coefficient of 0.19 was low, indicating high intraindividual variability compared with interindividual variability, resulting in a high likelihood of misclassification. The relation between chromosomal aberration frequency and future cancer risk has probably been underestimated in previous studies. A single chromosomal aberration measurement seems not to be representative of the whole lifespan level of chromosome instability and greatly limits the use of chromosomal aberration frequency-as measured with Giemsa staining-for individual risk assessment. PMID:21652601

  15. An Overview on Prenatal Screening for Chromosomal Aberrations.

    PubMed

    Hixson, Lucas; Goel, Srishti; Schuber, Paul; Faltas, Vanessa; Lee, Jessica; Narayakkadan, Anjali; Leung, Ho; Osborne, Jim

    2015-10-01

    This article is a review of current and emerging methods used for prenatal detection of chromosomal aneuploidies. Chromosomal anomalies in the developing fetus can occur in any pregnancy and lead to death prior to or shortly after birth or to costly lifelong disabilities. Early detection of fetal chromosomal aneuploidies, an atypical number of certain chromosomes, can help parents evaluate their pregnancy options. Current diagnostic methods include maternal serum sampling or nuchal translucency testing, which are minimally invasive diagnostics, but lack sensitivity and specificity. The gold standard, karyotyping, requires amniocentesis or chorionic villus sampling, which are highly invasive and can cause abortions. In addition, many of these methods have long turnaround times, which can cause anxiety in mothers. Next-generation sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive, and reasonably rapid analysis of fetal chromosomal anomalies and can be of clinical utility to parents. This review covers traditional methods and next-generation sequencing techniques for diagnosing aneuploidies in terms of clinical utility, technological characteristics, and market potential. PMID:25587000

  16. The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.

    PubMed

    Hu, Qinyong; Chu, Yuxin; Song, Qibin; Yao, Yi; Yang, Weihong; Huang, Shiang

    2016-08-01

    This study aims to investigate the prevalence and distribution of diverse chromosomal aberrations associated with myelodysplastic syndromes (MDS) in China. Bone marrow samples were collected from multiple cities in China. Metaphase cytogenetic (MC) analysis and fluorescence in situ hybridization (FISH) were initially used to test chromosomal lesions. Affymetrix CytoScan 750 K genechip platform performed a genome-wide detection of chromosomal aberrations. Chromosomal gain was identified in 76 patients; the most prevalent was trisomy 8(17.9 %). New chromosomal gain was detected on chromosome 9, 19p, and X. Chromosomal loss was detected in 101 patients. The most frequent was loss 5q (21.0 %). Some loss and gain were not identified by MC or FISH but identified by genechip. UPD was solely identified by genechip in 51 patients; the most prevalent were UPD 7q (4.94 %) and UPD 17p (4.32 %). Furthermore, complex chromosomal aberrations were detected in 56 patients. In conclusion, Affymetrix CytoScan 750 K genechip was more precise than MC and FISH in detection of cryptic chromosomal aberrations relevant to MDS. Analysis of the prevalence and distribution of diverse chromosomal aberrations in China may improve strategies for MDS diagnosis and therapies. PMID:27225263

  17. Prognostic value of numerical chromosome aberrations in multiple myeloma: A FISH analysis of 15 different chromosomes.

    PubMed

    Pérez-Simón, J A; García-Sanz, R; Tabernero, M D; Almeida, J; González, M; Fernández-Calvo, J; Moro, M J; Hernández, J M; San Miguel, J F; Orfão, A

    1998-05-01

    Recent observations indicate that chromosome aberrations are important prognostic factors in patients with multiple myeloma (MM) treated with high-dose chemotherapy. Nevertheless, the inherent problems of conventional cytogenetics have hampered the systematic evaluation of this parameter in series of patients treated with conventional chemotherapy. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical chromosomal changes. In the present study, we analyze the relationship between aneuploidies of 15 different chromosomes assessed by FISH and prognosis in a series of 63 patients with MM treated with conventional chemotherapy. After a median follow-up of 61 months (range, 6 to 109), 49% of patients are still alive with a median survival of 33 months. The overall incidence of numerical chromosome abnormalities was 70%. This incidence significantly increased when seven or more chromosomes were analyzed (53 patients), reaching 81%. Trisomies of chromosomes 6, 9, and 17 were associated with prolonged survival (P = .033, P = .035, and P = .026, respectively); by contrast, overall survival (OS) was lower in cases with monosomy 13 (as assessed by deletion of Rb gene, P = .0012). From the clinical point of view, loss of Rb gene was associated with a poor performance status; low hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone lytic lesions; and advanced clinical stage. Other chromosome abnormalities such as trisomy of chromosome 9 and 17 were associated with good prognostic features including high hemoglobin levels, early clinical stage, beta2microglobulin less than 6 micro/mL, and low percentage of BMPC. A multivariate analysis for OS showed that S-phase PC greater than 3% (P = .010) and beta2microglobulin serum levels greater than 6 micro/mL (P = .024), together with monosomy of chromosome 13 (P = .031) and

  18. X-ray-induced chromosome aberrations in Down lymphocytes: an explanation of their increased sensitivity

    SciTech Connect

    Preston, R.J.

    1981-01-01

    Unstimulated lymphocytes from individuals with Down Syndrome (trisomy 21) are more sensitive to the induction of dicentric and ring aberrations by X rays than normal lymphocytes. Several explanations involving the more rapid rejoining of X-ray--induced lesions in Down cells have been offered. It is shown here that the repair of the DNA damage converted into chromosome aberrations is more rapid in Down cells than normal cells. This more rapid repair results in a higher probability of producing chromosomes aberrations, and hence higher aberration frequencies in Down than normal cells.

  19. X-ray-induced chromosome aberrations in Down lymphocytes: an explanation of their increased sensitivity

    SciTech Connect

    Preston, R.J.

    1981-01-01

    Unstimulated lymphocytes from individuals with Down Syndrome (trisomy 21) are more sensitive to the induction of dicentric and ring aberrations by X rays than normal lymphocytes. Several explanations involving the more rapid rejoining of X-ray-induced lesions in Down cells have been offered. It is shown here that the repair of the DNA damage converted into chromosome aberrations is more rapid in Down cells than normal cells. This more rapid repair results in a higher probability of producing chromosome aberrations, and hence higher aberration frequencies in Down than normal cells.

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

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  1. Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

    NASA Technical Reports Server (NTRS)

    Hada, Megumi; Chappell, Lori J.; Wang, Minli; George, Kerry A.; Cucinotta, Francis A.

    2014-01-01

    The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

  2. Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.

    PubMed Central

    Fatma, N; Jain, A K; Rahman, Q

    1991-01-01

    Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were chromatid gap and break types. PMID:1998603

  3. Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.

    PubMed

    Fatma, N; Jain, A K; Rahman, Q

    1991-02-01

    Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were chromatid gap and break types. PMID:1998603

  4. Analysis of chromosomal aberrations and recombination by allelic bias in RNA-Seq.

    PubMed

    Weissbein, Uri; Schachter, Maya; Egli, Dieter; Benvenisty, Nissim

    2016-01-01

    Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration and utilizes already available gene expression profiles to determine chromosomal aberrations. PMID:27385103

  5. Analysis of chromosomal aberrations and recombination by allelic bias in RNA-Seq

    PubMed Central

    Weissbein, Uri; Schachter, Maya; Egli, Dieter; Benvenisty, Nissim

    2016-01-01

    Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration and utilizes already available gene expression profiles to determine chromosomal aberrations. PMID:27385103

  6. Modifying influence of occupational inflammatory diseases on the level of chromosome aberrations in coal miners.

    PubMed

    Volobaev, Valentin P; Sinitsky, Maxim Yu; Larionov, Aleksey V; Druzhinin, Vladimir G; Gafarov, Nikolay I; Minina, Varvara I; Kulemin, Jury E

    2016-03-01

    Coal miners are exposed to a wide range of genotoxic agents that can induce genome damage. In addition, miners are characterised by a high risk of the initiation of different occupational inflammatory as well as non-inflammatory diseases. The aim of this investigation is to analyse the modifying influence of occupational pulmonary inflammatory diseases on the level of chromosome aberrations (CAs) in miners working in underground coal mines in Kemerovo Region (Russian Federation). The study group included 90 coal miners with the following pulmonary diseases: chronic dust-induced bronchitis (CDB) and coal-workers' pneumoconiosis (CWP) (mean age = 53.52±2.95 years; mean work experience in coal-mining conditions = 27.70±3.61 years). As a population control (control 1), we have used venous blood extracted from 124 healthy unexposed men. The mean age in this group was 50.92±4.56 years. Control 2 was the venous blood extracted from 42 healthy coal miners (mean age = 51.56±6.38 years; mean work experience in coal-mining conditions = 25.43±8.14 years). We have discovered that coal miners are characterised by an increased general level of CAs as well as an increased frequency of several types of CAs. The significant increase in the frequency of aberration per 100 cells and aberration of chromosome type was discovered in the group of pulmonary disease patients (study group). No correlations of the level of chromosome damage with age, smoking status and work experience in coal-mining conditions were discovered. PMID:26609129

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

    NASA Technical Reports Server (NTRS)

    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.

  8. Mosaic chromosomal aberrations in synovial fibroblasts of patients with rheumatoid arthritis, osteoarthritis, and other inflammatory joint diseases

    PubMed Central

    Kinne, Raimund W; Liehr, Thomas; Beensen, Volkmar; Kunisch, Elke; Zimmermann, Thomas; Holland, Heidrun; Pfeiffer, Robert; Stahl, Hans-Detlev; Lungershausen, Wolfgang; Hein, Gert; Roth, Andreas; Emmrich, Frank; Claussen, Uwe; Froster, Ursula G

    2001-01-01

    Chromosomal aberrations were comparatively assessed in nuclei extracted from synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases. Peripheral blood lymphocytes (PBL) and skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n = 4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centromere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 RA patients (19%), with involvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 21 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomies of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were detected in SFB of OA and spondylarthropathy patients. No aberrations were detected in i) PBL or skin FB from the same patients (except for one OA patient with a karyotype 45,X[10]/46,XX[17] in PBL and variable polysomies in long-term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joints or of patients with joint trauma. In conclusion, qualitatively comparable chromosomal aberrations were observed in synovial tissue and early-passage SFB of patients with RA, OA, and other inflammatory joint diseases. Thus, although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic inflammatory stress in rheumatic diseases. PMID:11549374

  9. Influence of radiofrequency radiation on chromosome aberrations in CHO cells and its interaction with DNA-damaging agents.

    PubMed

    Kerbacher, J J; Meltz, M L; Erwin, D N

    1990-09-01

    A limited number of contradictory reports have appeared in the literature about the ability of radiofrequency (rf) radiation to induce chromosome aberrations in different biological systems. The technical documentation associated with such reports is often absent or deficient. In addition, no information is available as to whether any additional genotoxic hazard would result from a simultaneous exposure of mammalian cells to rf radiation and a chemical which (by itself) induces chromosome aberrations. In the work described, we have therefore tested two hypotheses. The first is that rf radiation by itself, at power densities and exposure conditions which are higher than is consistent with accepted safety guidelines, can induce chromosome aberrations in mammalian cells. The second is that, during a simultaneous exposure to a chemical known to be genotoxic, rf radiation can affect molecules, biochemical processes, or cellular organelles, and thus result in an increase or decrease in chromosome aberrations. Mitomycin C (MMC) and Adriamycin (ADR) were selected because they act by different mechanisms, and because they might put normal cells at risk during combined-modality rf radiation (hyperthermia)-chemotherapy treatment of cancer. The studies were performed with suitable 37 degrees C and equivalent convection heating-temperature controls in a manner designed to discriminate between any thermal and possible nonthermal action. Radiofrequency exposures were conducted for 2 h under conditions resulting in measurable heating (a maximum increase of 3.2 degrees C), with pulsed-wave rf radiation at a frequency of 2450 MHz and an average net forward power of 600 W, resulting in an SAR of 33.8 W/kg. Treatments with MMC or ADR were for a total of 2.5 h and encompassed the 2-h rf radiation exposure period. The CHO cells from each of the conditions were subsequently analyzed for chromosome aberrations. In cells exposed to rf radiation alone, and where a maximum temperature of

  10. Persistence of chromosome aberrations in mice acutely exposed to 56Fe+26 ions.

    PubMed

    Tucker, James D; Marples, Brian; Ramsey, Marilyn J; Lutze-Mann, Louise H

    2004-06-01

    Space exploration has the potential to yield exciting and significant discoveries, but it also brings with it many risks for flight crews. Among the less well studied of these are health effects from space radiation, which includes the highly charged, energetic particles of elements with high atomic numbers that constitute the galactic cosmic rays. In this study, we demonstrated that 1 Gy iron ions acutely administered to mice in vivo resulted in highly complex chromosome damage. We found that all types of aberrations, including dicentrics as well as translocations, insertions and acentric fragments, disappear rapidly with time after exposure, probably as a result of the death of heavily damaged cells, i.e. cells with multiple and/or complex aberrations. In addition, numerous cells have apparently simple exchanges as their only aberrations, and these cells appear to survive longer than heavily damaged cells. Eight weeks after exposure, the frequency of cells showing cytogenetic damage was reduced to less than 20% of the levels evident at 1 week, with little further decline apparent over an additional 8 weeks. These results indicate that exposure to 1 Gy iron ions produces heavily damaged cells, a small fraction of which appear to be capable of surviving for relatively long periods. The health effects of exposure to high-LET radiation in humans on prolonged space flights should remain a matter of concern. PMID:15161355

  11. [Identification of chromosomal aberration in esophageal cancer cells by mixed BAC DNA probes of chromosome arms and regions].

    PubMed

    Jiajie, Hao; Chunli, Wang; Wenyue, Gu; Xiaoyu, Cheng; Yu, Zhang; Xin, Xu; Yan, Cai; Mingrong, Wang

    2014-06-01

    Chromosomal aberration is an important genetic feature of malignant tumor cells. This study aimed to clarify whether BAC DNA could be used to identify chromosome region and arm alterations. For each chromosome region, five to ten 1 Mb BAC DNA clones were selected to construct mixed BAC DNA clones for the particular region. All of the mixed clones from regions which could cover the whole chromosome arm were then mixed to construct mixed BAC DNA clones for the arms. Mixed BAC DNA probes of arms and regions were labeled by degenerate oligonucleotide primed PCR (DOP-PCR) and Nick translation techniques, respectively. The specificities of these probes were validated by fluorescence in situ hybridization (FISH) on the metaphase chromosomes of normal human peripheral blood lymphocytes. FISH with arm-specific mixed BAC DNA probes showed that chromosomal rearrangements and involved chromosome arms were confirmed in several esophageal cancer cells. By using region-specific mixed probes, the breakpoint on 1q from the derivative chromosome t(1q;7q) was identified in 1q32-q41 in esophageal KYSE140 cells. In conclusion, we established an effective labeling method for 1 Mb BAC DNA mixed clone probes, and chromosome arm and region rearrangements could be identified in several esophageal cancer cells by using these probes. Our study provides a more precise method for identification of chromosomal aberration by M-FISH, and the established method may also be applied to the karyotype analysis of hematological malignancies and prenatal diagnosis. PMID:24929514

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

    NASA Technical Reports Server (NTRS)

    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.

  13. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation

    PubMed Central

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-01-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  14. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

    PubMed

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-12-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  15. [Revision of th distribution of chromosome aberrations induced by chemical mutagens using the BUDR label].

    PubMed

    Chebotarev, A N; Chernyshova, N A

    1990-08-01

    Cell distribution was analysed with the help of the BrDU label for the number of chromosome aberrations and breaks induced by one-center (thiophosphamide and phosphamide) and two-center (dipine and fotrine) mutagens at the stage G0 in the Ist mitosis of human lymphocytes harvested at different times of culturing (from 56 to 96 h). The comparison was made between the type of aberration distribution in cells and the dependence of their frequency on the harvesting point for various mutagens. Poisson aberration distribution in cells for two-center mutagens was found to correspond to their constant frequency observed at different times of harvesting. On the other hand, for one-center mutagens, a geometrical distribution of chromosome breaks corresponded to an exponential decrease in their frequency in time. It is suggested that two-center chemical mutagens and ionizing radiation cause largely short-live damages which are realized into chromosome aberrations rather quickly (during one cell cycle). One-center mutagens, however, cause such damages that the probability of their transformation into chromosome aberrations is decreasing rather slowly in time, under the exponential law, and their realization into chromosome aberrations can occur in subsequent cell cycle. PMID:2258036

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

    NASA Astrophysics Data System (ADS)

    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.

  17. p-Aramid RFP do not induce chromosomal aberrations in a standardized in vitro genotoxicity assay using human lymphocytes.

    PubMed

    Warheit, D B; Donner, M; Murli, H

    2001-12-01

    Genotoxicity evaluations have been proposed as regulatory requirements for establishing German MAK values for inhaled fibrous dusts. The objective of this in vitro assay was to assess the potential for para-aramid (p-aramid) respirable-sized, fiber-shaped particulates (RFP) to induce chromosomal aberrations in cultured human peripheral blood lymphocytes without metabolic activation. The highest concentration tested in this assay was limited by the physical characteristics of p-aramid RFP. The test substance was suspended in fully supplemented RPMI culture medium with 1% Pluronic F68. All dosing was achieved using a dosing volume of 90% (900 microl/ml), and the vehicle control cultures were treated with 900 microl/ml of fully supplemented RPMI culture medium with 1% Pluronic F68. In the chromosomal aberrations assay, the treatments were either 3 or 19 h without metabolic activation. Cultures were harvested 22 h from the initiation of treatment. Replicated cultures of human whole blood lymphocytes were incubated with p-aramid RFP concentrations of 6.30, 12.6, 25.2, 50.4, 101, 201, and 401 microg/ml. Cultures treated with concentrations to 50.4 microg/ml for 3 h and 6.30, 12.6, 25.2, and 201 microg/ml for 19 h were analyzed for structural and numerical chromosomal aberrations. No significant increase in cells with chromosomal aberrations, polyploidy, or endoreduplication was observed in the cultures analyzed. The results demonstrated that p-aramid RFP was negative for inducing chromosomal aberrations in cultured human peripheral blood lymphocytes without metabolic activation. In addition, we conclude that the utility of these tests for evaluating the genotoxicity of fibrous or particulate materials is questionable. PMID:11696875

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

    NASA Technical Reports Server (NTRS)

    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

  19. Simulation of the Formation of DNA Double Strand Breaks and Chromosome Aberrations in Irradiated Cells

    NASA Technical Reports Server (NTRS)

    Plante, Ianik; Ponomarev, Artem L.; Wu, Honglu; Blattnig, Steve; George, Kerry

    2014-01-01

    The formation of DNA double-strand breaks (DSBs) and chromosome aberrations is an important consequence of ionizing radiation. To simulate DNA double-strand breaks and the formation of chromosome aberrations, we have recently merged the codes RITRACKS (Relativistic Ion Tracks) and NASARTI (NASA Radiation Track Image). The program RITRACKS is a stochastic code developed to simulate detailed event-by-event radiation track structure: [1] This code is used to calculate the dose in voxels of 20 nm, in a volume containing simulated chromosomes, [2] The number of tracks in the volume is calculated for each simulation by sampling a Poisson distribution, with the distribution parameter obtained from the irradiation dose, ion type and energy. The program NASARTI generates the chromosomes present in a cell nucleus by random walks of 20 nm, corresponding to the size of the dose voxels, [3] The generated chromosomes are located within domains which may intertwine, and [4] Each segment of the random walks corresponds to approx. 2,000 DNA base pairs. NASARTI uses pre-calculated dose at each voxel to calculate the probability of DNA damage at each random walk segment. Using the location of double-strand breaks, possible rejoining between damaged segments is evaluated. This yields various types of chromosomes aberrations, including deletions, inversions, exchanges, etc. By performing the calculations using various types of radiations, it will be possible to obtain relative biological effectiveness (RBE) values for several types of chromosome aberrations.

  20. Aberrations Involving Chromosome 1 as a Possible Predictor of Odds Ratio for Colon Cancer - Results from the Krakow Case-Control Study

    PubMed Central

    Galas, Aleksander; Miszczyk, Justyna

    2016-01-01

    Background There is still an open question how to predict colorectal cancer risk before any morphological changes appear in the colon. Objective The purpose was to investigate aberrations in chromosomes 1, 2 and 4 in peripheral blood lymphocytes analyzed by fluorescence in situ hybridization technique as a tool to assess the likelihood of colorectal cancer. Methods A hospital-based case-control study included 20 colon cancer patients and 18 hospital-based controls. Information about potential covariates was collected by interview. The frequency of stable and unstable chromosome aberrations in chromosome 1, 2 and 4 was assessed by fluorescence in situ hybridization technique. Results Colorectal cancer patients, as compared to controls, had a relatively higher frequency of chromosome 1 translocations (median: 3.5 versus 1.0 /1000 cells, p = 0.006), stable aberrations (3.8 versus 1.0 /1000 cells, p = 0.007) and total aberrations (p = 0.009). There were no differences observed for chromosomes 2 and 4. Our results showed an increase in the odds of having colon cancer by about 50–80% associated with an increase by 1/1000 cells in the number of chromosome 1 aberrations. Conclusions The results revealed that the frequency of chromosomal aberrations, especially translocations in chromosome 1, seems to be a promising method to show a colon cancer risk. Additionally, our study suggests the reasonableness of use of biomarkers such as chromosome 1 aberrations in peripheral blood lymphocytes in screening prevention programs for individuals at higher colon cancer risk to identify those who are at increased risk and require more frequent investigations, e.g. by sigmoidoscopy. PMID:26824604

  1. Chromosome aberrations in relation to radiation dose following partial-body exposures in three populations

    SciTech Connect

    Kleinerman, R.A.; Littlefield, L.G.; Tarone, R.E.; Sayer, A.M.; Hildreth, N.G.; Pottern, L.M.; Machado, S.G.; Boice, J.D. Jr. )

    1990-07-01

    Structural chromosome aberrations were evaluated in peripheral blood samples obtained from three populations exposed to partial-body irradiation. These included 143 persons who received radiotherapy for enlarged thymus glands during infancy and 50 sibling controls; 79 persons irradiated for enlarged tonsils and 81 persons surgically treated for the same condition during childhood; and 77 women frequently exposed as young adults to fluoroscopic chest X rays during lung collapse treatment for tuberculosis (TB) and 66 women of similar ages treated for TB with other therapies. Radiation exposures occurred 30 and more years before blood was drawn. Doses to active bone marrow averaged over the entire body were 21, 6, and 14 cGy for the exposed thymic, tonsil, and TB subjects, respectively. Two hundred metaphases were scored for each subject, and the frequencies of symmetrical (stable) and asymmetrical (unstable) chromosome aberrations were quantified in 97,200 metaphases. Cells with stable aberrations were detected with greater frequency in the irradiated subjects compared with nonirradiated subjects in all three populations, and an overall test for an association between stable aberrations and partial-body ionizing radiation was highly significant (P less than 0.001). We found no evidence that radiation-induced aberrations varied by age at exposure. These data show that exposure of children or young adults to partial-body fractionated radiation can result in detectable increased frequencies of stable chromosome aberrations in circulating lymphocytes 30 years later, and that these aberrations appear to be informative as biological markers of population exposure.

  2. Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.

    PubMed Central

    Smerhovsky, Z; Landa, K; Rössner, P; Brabec, M; Zudova, Z; Hola, N; Pokorna, Z; Mareckova, J; Hurychova, D

    2001-01-01

    We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, 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 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals. PMID:11171523

  3. Behavior of Aberrant Chromosome Configurations in Drosophila melanogaster Female Meiosis I

    PubMed Central

    Gilliland, William D.; Colwell, Eileen M.; Lane, Fiona M.; Snouffer, Ashley A.

    2014-01-01

    One essential role of the first meiotic division is to reduce chromosome number by half. Although this is normally accomplished by segregating homologous chromosomes from each other, it is possible for a genome to have one or more chromosomes that lack a homolog (such as compound chromosomes), or have chromosomes with multiple potential homologs (such as in XXY females). These configurations complete meiosis but engage in unusual segregation patterns. In Drosophila melanogaster females carrying two compound chromosomes, the compounds can accurately segregate from each other, a process known as heterologous segregation. Similarly, in XXY females, when the X chromosomes fail to cross over, they often undergo secondary nondisjunction, where both Xs segregate away from the Y. Although both of these processes have been known for decades, the orientation mechanisms involved are poorly understood. Taking advantage of the recent discovery of chromosome congression in female meiosis I, we have examined a number of different aberrant chromosome configurations. We show that these genotypes complete congression normally, with their chromosomes bioriented at metaphase I arrest at the same rates that they segregate, indicating that orientation must be established during prometaphase I before congression. We also show that monovalent chromosomes can move out on the prometaphase I spindle, but the dot 4 chromosomes appear required for this movement. Finally, we show that, similar to achiasmate chromosomes, heterologous chromosomes can be connected by chromatin threads, suggesting a mechanism for how heterochromatic homology establishes these unusual biorientation patterns. PMID:25491942

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

    PubMed

    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. PMID:25864414

  5. Behavior of aberrant chromosome configurations in Drosophila melanogaster female meiosis I.

    PubMed

    Gilliland, William D; Colwell, Eileen M; Lane, Fiona M; Snouffer, Ashley A

    2015-02-01

    One essential role of the first meiotic division is to reduce chromosome number by half. Although this is normally accomplished by segregating homologous chromosomes from each other, it is possible for a genome to have one or more chromosomes that lack a homolog (such as compound chromosomes), or have chromosomes with multiple potential homologs (such as in XXY females). These configurations complete meiosis but engage in unusual segregation patterns. In Drosophila melanogaster females carrying two compound chromosomes, the compounds can accurately segregate from each other, a process known as heterologous segregation. Similarly, in XXY females, when the X chromosomes fail to cross over, they often undergo secondary nondisjunction, where both Xs segregate away from the Y. Although both of these processes have been known for decades, the orientation mechanisms involved are poorly understood. Taking advantage of the recent discovery of chromosome congression in female meiosis I, we have examined a number of different aberrant chromosome configurations. We show that these genotypes complete congression normally, with their chromosomes bioriented at metaphase I arrest at the same rates that they segregate, indicating that orientation must be established during prometaphase I before congression. We also show that monovalent chromosomes can move out on the prometaphase I spindle, but the dot 4 chromosomes appear required for this movement. Finally, we show that, similar to achiasmate chromosomes, heterologous chromosomes can be connected by chromatin threads, suggesting a mechanism for how heterochromatic homology establishes these unusual biorientation patterns. PMID:25491942

  6. Why it is crucial to analyze non clonal chromosome aberrations or NCCAs?

    PubMed

    Heng, Henry H Q; Regan, Sarah M; Liu, Guo; Ye, Christine J

    2016-01-01

    Current cytogenetics has largely focused its efforts on the identification of recurrent karyotypic alterations, also known as clonal chromosomal aberrations (CCAs). The rationale of doing so seems simple: recurrent genetic changes are relevant for diseases or specific physiological conditions, while non clonal chromosome aberrations (NCCAs) are insignificant genetic background or noise. However, in reality, the vast majority of chromosomal alterations are NCCAs, and it is challenging to identify commonly shared CCAs in most solid tumors. Furthermore, the karyotype, rather than genes, represents the system inheritance, or blueprint, and each NCCA represents an altered genome system. These realizations underscore the importance of the re-evaluation of NCCAs in cytogenetic analyses. In this concept article, we briefly review the definition of NCCAs, some historical misconceptions about them, and why NCCAs are not insignificant "noise," but rather a highly significant feature of the cellular population for providing genome heterogeneity and complexity, representing one important form of fuzzy inheritance. The frequencies of NCCAs also represent an index to measure both internally- and environmentally-induced genome instability. Additionally, the NCCA/CCA cycle is associated with macro- and micro-cellular evolution. Lastly, elevated NCCAs are observed in many disease/illness conditions. Considering all of these factors, we call for the immediate action of studying and reporting NCCAs. Specifically, effort is needed to characterize and compare different types of NCCAs, to define their baseline in various tissues, to develop methods to access mitotic cells, to re-examine/interpret the NCCAs data, and to develop an NCCA database. PMID:26877768

  7. Induction of chromosome aberrations in mammalian cells after heavy ion exposure.

    PubMed

    Ritter, S; Kraft-Weyrather, W; Scholz, M; Kraft, G

    1992-01-01

    The induction of chromosome aberrations by heavy charged particles was studied in V79 Chinese hamster cells over a wide range of energies (3-100 MeV/u) and LET (20-16000 keV/micrometer). For comparison, X-ray experiments were performed. Our data indicate quantitative and qualitative differences in the response of cells to particle and x-ray irradiation. For the same level of cell survival the amount of damaged cells which can be observed is smaller in heavy ion (11.4 MeV/u Ar) irradiated samples. The highest yield of damaged cells is found 8 to 12 hours after particle irradiation and 4 hours after x-irradiation. Differences in the amount of damaged cells are attributed to cell cycle perturbations which interfere with the expression of damage. After heavy ion exposure the amount of cells reaching mitosis (mitotic index) decreases drastically and not all damaged cells reach mitosis within 48 hours after exposure. A portion of cells die in interphase. Cell cycle delays induced by x-ray irradiation are less pronounced and all cells reach the first post-irradiation mitosis within 24 hours after irradiation. Additionally, the damage produced by charged particles seems to be more severe. The disintegration of chromosomes was only observed after high LET radiation: an indication of the high and local energy deposition in the particle track. Only cross sections for the induction of chromosome aberrations in mitotic cells were reported in this paper because of the problems arising from the drastic cell cycle perturbations. In this case, cells were irradiated in mitosis and assayed immediately. PMID:11536999

  8. Induction of chromosome aberrations in mammalian cells after heavy ion exposure

    NASA Astrophysics Data System (ADS)

    Ritter, S.; Kraft-Weyrather, W.; Scholz, M.; Kraft, G.

    The induction of chromosome aberrations by heavy charged particles was studied in V79 Chinese hamster cells over a wide range of energies (3-100 MeV/u) and LET (20-16000 keV/μm). For comparison, X-ray experiments were performed. Our data indicate quantitative and qualitative differences in the response of cells to particle and x-ray irradiation. For the same level of cell survival the amount of damaged cells which can be observed is smaller in heavy ion (11.4 MeV/u Ar) irradiated samples. The highest yield of damaged cells is found 8 to 12 hours after particle irradiation and 4 hours after x-irradiation. Differences in the amount of damaged cells are attributed to cell cycle perturbations which interfere with the expression of damage. After heavy ion exposure the amount of cells reaching mitosis (mitotic index) decreases drastically and not all damaged cells reach mitosis within 48 hours after exposure. A portion of cells die in interphase. Cell cycle delays induced by x-ray irradiation are less pronounced and all cells reach the first post-irradiation mitosis within 24 hours after irradiation. Additionally, the damage produced by charged particles seems to be more severe. The disintegration of chromosomes was only observed after high LET radiation: an indication of the high and local energy deposition in the particle track. Only cross sections for the induction of chromosome aberrations in mitotic cells were reported in this paper because of the problems arising from the drastic cell cycle perturbations. In this case, cells were irradiated in mitosis and assayed immediately.

  9. Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice.

    PubMed

    Rosenfeld, S V; Togo, E F; Mikheev, V S; Popovich, I G; Khavinson, V Kh; Anisimov, V N

    2002-03-01

    The incidence of chromosome aberrations in bone marrow cells of 12-month-old SAMP-1 female mice characterized by accelerated aging was 1.8 times higher than in wild-type SAMR-1 females and 2.2 times higher than in SHR females of the same age. Treatment with Epithalon (Ala-Glu-Asp-Gly) starting from the age of 2 months decreased the incidence of chromosome aberrations in SAMP-1, SAMR-1, and SHR mice by 20%, 30.1%, and 17.9%, respectively, compared to age-matched controls (p<0.05). Treatment with melatonin (given with drinking water in a dose of 20 mg/liter in night hours) had no effect on the incidence of chromosome aberrations in SHR mice. These data indicate antimutagenic effect of Epithalon, which probably underlies the geroprotective effect of this peptide. PMID:12360351

  10. Constitutional genomic instability, chromosome aberrations in tumor cells and retinoblastoma.

    PubMed

    Amare Kadam, P S; Ghule, P; Jose, J; Bamne, M; Kurkure, P; Banavali, S; Sarin, R; Advani, S

    2004-04-01

    Although retinoblastoma (Rb) is initiated as a result of biallelic inactivation of the RB1 gene, additional genetic events (M3) in tumor cells are indicative of their role in the full transformation of retinal cells. We investigated the constitutional genetic instability by fragile site (FS) expression studies and checked its relationship with loci of tumor cytogenetics in a series of 36 retinoblastoma patients (34 nonfamilial and 2 familial cases). Tumor cytogenetics revealed -13/+13, del/t(13)(q14) (50%), +1/del/t(1p/q) (65%), +6/i(6p) (60%), and del(16)(q13)/(q22 approximately q23) (60%). Conventional cytogenetics in leukocytes revealed constitutional del(13q14) in five unilateral Rb (URB) and one trilateral Rb (TRB). Constitutional del(16)(q22) and t(6;12) were also identified in two cases. Constitutional FS analysis showed a significant increase in the cellular fragility, with high prevalence at 13q14, 3p14, 6p23, 16q22 approximately q23, and 13q22 loci in retinoblastoma patients (P<0.05). Patients with constitutional del(13)(q14) demonstrated higher fragility than those with normal constitution. A strong correlation between loci of constitutional FSs and loci of recurrent chromosomal abnormalities in tumors strengthen and support the proposal that FS loci present as inherent genomic instability in retinoblastoma. The chromosomal changes and resultant genetic mutations, along with RB1 mutation events, probably contribute synergistically to the development and progression of Rb malignancy. Implementation of fluorescence in situ hybridization to nonfamilial Rb on a large scale (113 cases) could detect constitutional RB1 deletion in 12.3% of cases, with equally higher incidence in URB (14.7%) and bilateral Rb (13.6%), demonstrating that the true prevalence of patients with predisposition to RB1 mutation in sporadic URB is definitely higher in our populations. Also, higher incidence of constitutional RB1 deletion mosaicism in unilateral than in bilateral Rb

  11. Analysis of Heavy Ion-Induced Chromosome Aberrations in Human Fibroblast Cells Using In Situ Hybridization

    NASA Technical Reports Server (NTRS)

    Wu, Honglu; Durante, Marco; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

    2003-01-01

    Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon Si, or with Fe ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 0 C for 24 hours after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Unrejoined chromosomal breaks and complex exchanges were analyzed in the irradiated samples. In order to verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after high-LET radiation, and consequently, the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/micron, the highest LET value in the present study. For samples exposed to 200 MeV/nucleon Fe ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy dose of the Fe ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges, values for which were higher than those obtained after a 6 Gy gamma exposure. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating the maximum number of chromosome domains traversed by a single Fe ion track. 2

  12. Automatic aberration scoring using whole chromosome F. I. S. H

    SciTech Connect

    Piper, J.; Bayley, R.; Boyle, S.; Fantes, J.A.; Green, D.K.; Gordon, J.; Hill, W.; Ji, L.; Malloy, P.; Perry, P.; Rutovitz, D.; Stark, M.; Whale, D. )

    1993-01-01

    A radiation-induced rearrangement involving a painted and a non-painted chromosome will usually result in two partly-painted chromosomes, typically either a dicentric chromosome and associated fragment, or a reciprocal translocation pair. A consequence of such a rearrangement is that the number of painted image regions in the metaphase is increased by one, and their size distribution is altered. More complex rearrangements are uncommon, particularly at low doses. A high proportion of damaged cells can therefore be registered simply by detecting when the distribution of painted components differs from the expected number and size. A system has been constructed to pre-screen for damaged cells. It comprises automatic fluorescence metaphase finding followed by relocation and digitization of probe and counterstain channels at high resolution. Fully automatic segmentation in counterstain discriminates chromosomes from interphase nuclei and determines whether a metaphase is approximately diploid. The painted regions are segmented and their relative sizes estimated. Rules are applied which reduce the false positives due to artifacts such as overlapped painted chromosomes. More than 70% of cells with radiation damage involving painted and unpainted chromosomes were detected in a preliminary experiment using a small data set, with a low false positive rate. Results from a larger experiment in progress are presented.

  13. Identification of Novel Chromosomal Aberrations Induced by 60Co-γ-Irradiation in Wheat-Dasypyrum villosum Lines

    PubMed Central

    Zhang, Jie; Jiang, Yun; Guo, Yuanlin; Li, Guangrong; Yang, Zujun; Xu, Delin; Xuan, Pu

    2015-01-01

    Mutations induced by radiation are widely used for developing new varieties of plants. To better understand the frequency and pattern of irradiation-induced chromosomal rearrangements, we irradiated the dry seeds of Chinese Spring (CS)-Dasypyrum villosum nullisomic-tetrasomic (6A/6D) addition (6V) line (2n = 44), WD14, with 60Co-γ-rays at dosages of 100, 200, and 300 Gy. The M0 and M1 generations were analyzed using Feulgen staining and non-denaturing fluorescence in situ hybridization (ND-FISH) by using oligonucleotide probes. Abnormal mitotic behavior and chromosomes with structural changes were observed in the M0 plants. In all, 39 M1 plants had structurally changed chromosomes, with the B genome showing the highest frequency of aberrations and tendency to recombine with chromosomes of the D genome. In addition, 19 M1 plants showed a variation in chromosome number. The frequency of chromosome loss was considerably higher for 6D than for the alien chromosome 6V, indicating that 6D is less stable after irradiation. Our findings suggested that the newly obtained γ-induced genetic materials might be beneficial for future wheat breeding programs and functional gene analyses. PMID:26694350

  14. Identification of Novel Chromosomal Aberrations Induced by (60)Co-γ-Irradiation in Wheat-Dasypyrum villosum Lines.

    PubMed

    Zhang, Jie; Jiang, Yun; Guo, Yuanlin; Li, Guangrong; Yang, Zujun; Xu, Delin; Xuan, Pu

    2015-01-01

    Mutations induced by radiation are widely used for developing new varieties of plants. To better understand the frequency and pattern of irradiation-induced chromosomal rearrangements, we irradiated the dry seeds of Chinese Spring (CS)-Dasypyrum villosum nullisomic-tetrasomic (6A/6D) addition (6V) line (2n = 44), WD14, with (60)Co-γ-rays at dosages of 100, 200, and 300 Gy. The M₀ and M₁ generations were analyzed using Feulgen staining and non-denaturing fluorescence in situ hybridization (ND-FISH) by using oligonucleotide probes. Abnormal mitotic behavior and chromosomes with structural changes were observed in the M₀ plants. In all, 39 M₁ plants had structurally changed chromosomes, with the B genome showing the highest frequency of aberrations and tendency to recombine with chromosomes of the D genome. In addition, 19 M₁ plants showed a variation in chromosome number. The frequency of chromosome loss was considerably higher for 6D than for the alien chromosome 6V, indicating that 6D is less stable after irradiation. Our findings suggested that the newly obtained γ-induced genetic materials might be beneficial for future wheat breeding programs and functional gene analyses. PMID:26694350

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

    NASA Technical Reports Server (NTRS)

    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

  16. Painting Analysis of Chromosome Aberrations Induced by Energetic Heavy Ions in Human Cells

    NASA Technical Reports Server (NTRS)

    Wu, Honglu; Hada, Megumi; Cucinotta, Francis

    2007-01-01

    This viewgraph presentation reviews some of the techniques used to analyze the damage done to chromosome from ion radiation. Fluorescence in situ hybridization (FISH), mFISH, mBAND, telomere and centromereprobes have been used to study chromosome aberrations induced in human cells exposed to low-and high-LET radiation in vitro. There is some comparison of the different results from the various techniques. The results of the study are summarized.

  17. Chromosome aberrations and their relevance to metal carcinogenesis.

    PubMed Central

    Vainio, H; Sorsa, M

    1981-01-01

    Scoring for structural chromosome abnormalities is one of the only practical methods available for detecting visual damage in human genetic material. Cytogenetic tests in vivo and in vitro have shown the clastogenic potential of a number of metals and metal compounds. The difficulties in in vivo studies lie in identifying a specific clastogen in an occupational setting, where simultaneous exposure to a number of organic and inorganic chemicals is a common phenomenon. Metals known to be carcinogens in animals also tend to possess chromosome-damaging properties, even though more extensive studies are needed before any conclusive evidence can be reached. The visible chromosomal damage produced by exposure to metal compounds should be considered as a warning indication of potentially adverse genetic and somatic effects in humans. PMID:7023931

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

    PubMed

    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. PMID:17059348

  19. Effect of resveratrol on chromosomal aberrations induced by doxorubicin in rat bone marrow cells.

    PubMed

    Bingöl, Günsel; Gülkaç, Mehmet Doğan; Dillioğlugil, Meltem Özlen; Polat, Fikriye; Kanli, Aylin Özön

    2014-05-15

    This study investigated the effects of resveratrol (RES) on doxorubicin (DXR) induced rat bone marrow cell chromosome aberrations. RES, a polyphenolic compound, has attracted considerable attention because of its antioxidant and antimutagenic effects. DXR, a chemotherapeutic agent, is known to cause chromosomal aberrations in healthy cells in cancer patients. In this study, Wistar albino male rats were divided into 6 groups with 6 animals each. The control group received distilled water i.p. and the DXR group received an i.p. injection of doxorubicin (90mg/kgbw). For the 2 RES dose groups (12.5 and 25mg/kgbw, respectively), RES was injected i.p. 5 times during the 24h study period to coincide with the schedule for the DXR+RES groups. The DXR-RES groups received DXR (90mg/kgbw) and RES at either 12.5 or 25mg/kgbw, i.p. 30min before, concurrently, and then every 6h after DXR administration. Bone marrow collection was timed to coincide with 24h after DXR administration in all groups. RES administration alone did not induce any significant increase in frequency of chromosome aberrations or abnormal metaphases compared with controls (p>0.05) while DXR alone did (p<0.05). In the DXR-RES 12.5mg/kgbw group, frequency of chromosome aberrations and abnormal metaphases were slightly reduced compared to DXR alone, but this was not statistically significant. However, in the DXR-RES 25mg/kgbw group, RES resulted in a statistically significant reduction in the frequency of chromosome aberrations and abnormal metaphases compared to those induced by DXR alone (p<0.05). These results indicate that RES (25mg/kgbw) significantly reduces frequency of DXR induced chromosome damage in bone marrow cells. PMID:24713549

  20. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    PubMed Central

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-01-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10−9), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10−3). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection. PMID:25924914

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

    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.

  4. Dynamics of chromosomal aberrations in male mice of various strains during aging.

    PubMed

    Rozenfel'd, S V; Togo, E F; Mikheev, V S; Popovich, I G; Zabezhinskii, M A; Anisimov, V N

    2001-05-01

    We studied the incidence of chromosome aberrations in bone marrow cells and primary spermatocytes in various mouse strains. Experiments were performed on SAMP mice (accelerated aging), control SAMR mice, and long-living CBA and SHR mice. Experiments revealed a positive correlation between the age and the incidence of mutations in their somatic cells and gametes. PMID:11550060

  5. 40 CFR 799.9538 - TSCA mammalian bone marrow chromosomal aberration test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... cells are analyzed for chromosome aberrations. (2) Description—(i) Preparations—(A) Selection of animal... 70% other than during room cleaning, the aim should be 50-60%. Lighting should be artificial, the..., and treatment regimen to be used in the main study (an approach to dose selection is presented in...

  6. 40 CFR 799.9538 - TSCA mammalian bone marrow chromosomal aberration test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... cells are analyzed for chromosome aberrations. (2) Description—(i) Preparations—(A) Selection of animal... 70% other than during room cleaning, the aim should be 50-60%. Lighting should be artificial, the..., and treatment regimen to be used in the main study (an approach to dose selection is presented in...

  7. 40 CFR 799.9538 - TSCA mammalian bone marrow chromosomal aberration test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... cells are analyzed for chromosome aberrations. (2) Description—(i) Preparations—(A) Selection of animal... 70% other than during room cleaning, the aim should be 50-60%. Lighting should be artificial, the..., and treatment regimen to be used in the main study (an approach to dose selection is presented in...

  8. Modeling low and high LET FISH data on simple and complex chromosome aberrations

    SciTech Connect

    Chen, A.M. |; Lucas, J.N.; Sachs, R.K.; Simpson, P.J.; Griffin, C.S.; Savage, R.K.; Brenner, D.J.

    1997-12-31

    With fluorescent in situ hybridization (FISH) many different categories of chromosome aberrations can be scored. The spectrum of aberration frequencies indicates aberration formation mechanisms and reflects radiation quality. Analyzing the implications of observed yields requires a model, explicit or implicit. There is evidence that: (a) the classic random breakage and reunion model is appropriate; and (b) proximity plays a role, i.e., free ends from DSBs initially formed far apart are less likely to undergo illegitimate reunion than free ends from DSBs initially close together. Chen et al. developed a Monte-Carlo computer implementation of the random breakage and reunion model, modified to incorporate proximity effects by assuming the cell nucleus is divided into interaction sites. It was assumed all DSB free ends eventually rejoin. They analyzed FISH data on chromosome aberration yields in human lymphocytes after acute low LET irradiation. The model has two adjustable parameters: the number of interaction sites per cell nucleus and the average number of reactive DSBs per Gy. Reasonable fits were obtained to data on a considerable number of different aberration types. The present paper extends the model of Chen et al. to high LET and applies it to published FISH aberration data for fibroblasts subjected to x-ray or {sup 238}Pu {alpha}-particle radiation.

  9. Zero-inflated regression models for radiation-induced chromosome aberration data: A comparative study.

    PubMed

    Oliveira, María; Einbeck, Jochen; Higueras, Manuel; Ainsbury, Elizabeth; Puig, Pedro; Rothkamm, Kai

    2016-03-01

    Within the field of cytogenetic biodosimetry, Poisson regression is the classical approach for modeling the number of chromosome aberrations as a function of radiation dose. However, it is common to find data that exhibit overdispersion. In practice, the assumption of equidispersion may be violated due to unobserved heterogeneity in the cell population, which will render the variance of observed aberration counts larger than their mean, and/or the frequency of zero counts greater than expected for the Poisson distribution. This phenomenon is observable for both full- and partial-body exposure, but more pronounced for the latter. In this work, different methodologies for analyzing cytogenetic chromosomal aberrations datasets are compared, with special focus on zero-inflated Poisson and zero-inflated negative binomial models. A score test for testing for zero inflation in Poisson regression models under the identity link is also developed. PMID:26461836

  10. Chromosome aberration assays in Pisum for the study of environmental mutagens.

    PubMed

    Grant, W F; Owens, E T

    2001-05-01

    From a literature survey, 117 chemicals are tabulated that have been assayed in 179 assays for their clastogenic effects in Pisum. Of the 117 chemicals that have been assayed, 65 are reported at giving a positive reaction (i.e. causing chromosome aberrations), 30 positive with a dose response, five borderline positive. Seventeen chemicals gave a negative response. Eighty-one percent of the chemicals gave a definite positive response. A c-mitotic effect was detected from treatment with 17 chemicals. In addition to the above tabulation of chemicals, 39 chemicals have been reported with an antimitotic effect. Thirteen assays have been recorded for five types of radiation, which with the exception of ultrasound reacted positively. The results of assays with 38 chemicals and/or radiations in combined treatments, as well as 15 chemicals and three types of radiations that induce somatic mutations are tabulated. The Pisum sativum (2n=14) bioassay has been shown to be a very good plant bioassay for assessing chromosome damage both in mitosis and meiosis for somatic mutations induced by chemicals, radiations, and environmental pollutants. For some chemicals, the Pisum assay is not as sensitive in assessing clastogenicity as the Allium assay, although this should be considered in relative terms. Pisum fulvum (2n=14) has been used in clastogenic studies also, but to a much lesser extent. PMID:11344039

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Technical Reports Server (NTRS)

    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.

  13. Chromosome aberrations in the blood lymphocytes of astronauts after space flight

    NASA Technical Reports Server (NTRS)

    George, K.; Durante, M.; Wu, H.; Willingham, V.; Badhwar, G.; Cucinotta, F. A.

    2001-01-01

    Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.

  14. Stability of chromosome aberrations in the blood lymphocytes of astronauts measured after space flight by FISH chromosome painting

    NASA Technical Reports Server (NTRS)

    George, K.; Willingham, V.; Cucinotta, F. A.

    2005-01-01

    Follow-up measurements of chromosome aberrations in the blood lymphocytes of astronauts were performed by FISH chromosome painting at various intervals from 5 months to more than 5 years after space flight and compared to preflight baseline measurements. For five of the six astronauts studied, the analysis of individual time courses for translocations revealed a temporal decline of yields with half-lives ranging from 10 to 58 months. The yield of exchanges remained unchanged for the sixth astronaut during an observation period of 5 months after flight. These results may indicate complications with the use of stable aberrations for retrospective dose reconstruction, and the differences in the decay time may reflect individual variability in risk from space radiation exposure.

  15. Chromosome aberrations induced in human lymphocytes by D-T neutrons

    SciTech Connect

    Lloyd, D.C.; Edwards, A.A.; Prosser, J.S.; Bolton, D.; Sherwin, A.G.

    1984-06-01

    Unstable chromosome aberrations induced by in vitro irradiation with D-T neutrons have been analyzed in human blood lymphocytes. With respect to 250 kVp X rays a maximum limiting RBE at low doses of 4.1 was obtained for dicentric aberrations. Using aberrations as markers in mixed cultures of irradiated and unirradiated cells permits an assessment of interphase death plus mitotic delay. The low-dose RBE for this effect is 2.5. Assuming all unstable aberrations observed at metaphase would lead to cell death by nondisjunction allows an assessment of mitotic death. The low-dose RBE for this effect is 4.5. The data are compared with similar work obtained earlier with /sup 242/Cm ..cap alpha.. particles. The application of the present work to cytogenetic assessment of dose after accidental exposure to D-T neutrons is discussed.

  16. Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Grossi, G. F.; Gialanella, G.; Pugliese, M.; Nappo, M.; Yang, T. C.

    1995-01-01

    We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

  17. The Distribution of Chromosomal Aberrations in Human Cells Predicted by a Generalized Time-Dependent Model of Radiation-Induced Formation of Aberrations

    NASA Technical Reports Server (NTRS)

    Ponomarev, Artem L.; George, K.; Cucinotta, F. A.

    2011-01-01

    New experimental data show how chromosomal aberrations for low- and high-LET radiation are dependent on DSB repair deficiencies in wild-type, AT and NBS cells. We simulated the development of chromosomal aberrations in these cells lines in a stochastic track-structure-dependent model, in which different cells have different kinetics of DSB repair. We updated a previously formulated model of chromosomal aberrations, which was based on a stochastic Monte Carlo approach, to consider the time-dependence of DSB rejoining. The previous version of the model had an assumption that all DSBs would rejoin, and therefore we called it a time-independent model. The chromosomal-aberrations model takes into account the DNA and track structure for low- and high-LET radiations, and provides an explanation and prediction of the statistics of rare and more complex aberrations. We compared the program-simulated kinetics of DSB rejoining to the experimentally-derived bimodal exponential curves of the DSB kinetics. We scored the formation of translocations, dicentrics, acentric and centric rings, deletions, and inversions. The fraction of DSBs participating in aberrations was studied in relation to the rejoining time. Comparisons of simulated dose dependence for simple aberrations to the experimental dose-dependence for HF19, AT and NBS cells will be made.

  18. Low level radiation and chromosome aberrations. January, 1970-May, 1981 (citations from Pollution Abstracts). Report, for January 1970-May 1981

    SciTech Connect

    Not Available

    1981-05-01

    This retrospective bibliography contains citations concerning low level radiation and the incidence of chromosome aberration. Many types of chromosome abnormalities are covered and include aneuploidy and nondisjunction. Hematopoietic pathology and the increased risk of cancer are noted. The cytological methods available to study chromosomes are mentioned. (Contains 61 citations fully indexed and including a title list.)

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

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

    Numerous published studies have reported the Relative Biological Effectiveness (RBE) values for chromosome aberrations induced by charged particles of different LET. The RBE for chromosome aberrations in human lymphocytes exposed ex vivo has been suggested to show a similar relationship as the quality factor for cancer induction. Therefore, 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. However, the RBE value is known to be very different for different types of cancer. Previously, we reported that, even though the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions, the RBE was significantly reduced after multiple cell divisions post irradiation. To test the hypothesis that RBE values for chromosome aberrations are cell type dependent, and different between early and late damages, we exposed human lymphocytes ex vivo, and human mammary epithelial cells in vitro to various charged particles. Chromosome aberrations were quantified using the samples collected at first mitosis post irradiation for initial damages, and the samples collected after multiple generations for the remaining or late arising aberrations. Results of the study suggested that the effectiveness of high-LET charged particles for late chromosome aberrations may be cell type dependent, even though the RBE values are similar for early damages.

  20. Chromosome aberrations of clonal origin are present in astronauts' blood lymphocytes

    NASA Technical Reports Server (NTRS)

    George, K.; Durante, M.; Willingham, V.; Cucinotta, F. A.

    2004-01-01

    Radiation-induced chromosome translocations remain in peripheral blood cells over many years, and can potentially be used to measure retrospective doses or prolonged low-dose rate exposures. However, several recent studies have indicated that some individuals possess clones of cells with balanced chromosome abnormalities, which can result in an overestimation of damage and, therefore, influence the accuracy of dose calculations. We carefully examined the patterns of chromosome damage found in the blood lymphocytes of twelve astronauts, and also applied statistical methods to screen for the presence of potential clones. Cells with clonal aberrations were identified in three of the twelve individuals. These clonal cells were present in samples collected both before and after space flight, and yields are higher than previously reported for healthy individuals in this age range (40-52 years of age). The frequency of clonal damage appears to be even greater in chromosomes prematurely condensed in interphase, when compared with equivalent analysis in metaphase cells. The individuals with clonal aberrations were followed-up over several months and the yields of all clones decreased during this period. Since clonal aberrations may be associated with increased risk of tumorigenesis, it is important to accurately identify cells containing clonal rearrangements for risk assessment as well as biodosimetry. Copyright 2003 S. Karger AG, Basel.

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

    NASA Technical Reports Server (NTRS)

    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.

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

    SciTech Connect

    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.

  3. Track structure based modelling of chromosome aberrations after photon and alpha-particle irradiation.

    PubMed

    Friedland, Werner; Kundrát, Pavel

    2013-08-30

    A computational model of radiation-induced chromosome aberrations in human cells within the PARTRAC Monte Carlo simulation framework is presented. The model starts from radiation-induced DNA damage assessed by overlapping radiation track structures with multi-scale DNA and chromatin models, ranging from DNA double-helix in atomic resolution to chromatin fibre loops, heterochromatic and euchromatic regions, and chromosome territories. The repair of DNA double-strand breaks via non-homologous end-joining is followed. Initial spatial distribution and complexity, diffusive motion, enzymatic processing, synapsis and ligation of individual DNA ends from the breaks are simulated. To enable scoring of different chromosome aberration types resulting from improper joining of DNA fragments, the repair module has been complemented by tracking the chromosome origin of the ligated fragments and the positions of centromeres. The modelled motion of DNA ends has sub-diffusive characteristics and corresponds to measured chromatin mobility within time-scales of a few hours. The calculated formation of dicentrics after photon and α-particle irradiation in human fibroblasts is compared to experimental data (Cornforth et al., 2002, Radiat Res 158, 43). The predicted yields of dicentrics overestimate the measurements by factors of five for γ-rays and two for α-particle irradiation. Nevertheless, the observed relative dependence on radiation dose is correctly reproduced. Calculated yields and size distributions of other aberration types are discussed. The present work represents a first mechanistic approach to chromosome aberrations and their kinetics, combining full track structure simulations with detailed models of chromatin and accounting for the kinetics of DNA repair. PMID:23811166

  4. Alternative lengthening of telomeres: recurrent cytogenetic aberrations and chromosome stability under extreme telomere dysfunction.

    PubMed

    Sakellariou, Despoina; Chiourea, Maria; Raftopoulou, Christina; Gagos, Sarantis

    2013-11-01

    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. PMID:24339742

  5. G2-chromosome aberrations induced by high-LET radiations

    NASA Astrophysics Data System (ADS)

    Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Ito, H.; Wu, H.; Cucinotta, F. A.

    We report measurements of initial G2-chromatid breaks in normal human fibroblasts exposed to various types of high-LET particles. Exponentially growing AG 1522 cells were exposed to γ-rays or heavy ions. Chromosomes were prematurely condensed by calyculin A. Chromatid-type breaks and isochromatid-type breaks were scored separately. The dose response curves for the induction of total chromatid breaks (chromatid-type + isochromatid-type) and chromatid-type breaks were linear for each type of radiation. However, dose response curves for the induction of isochromatid-type breaks were linear for high-LET radiations and linear-quadratic for γ-rays. Relative biological effectiveness (RBE), calculated from total breaks, showed a LET dependent tendency with a peak at 55 keV/μm silicon (2.7) or 80 keV/μm carbon (2.7) and then decreased with LET (1.5 at 440 keV/μm). RBE for chromatid-type break peaked at 55 keV/μm (2.4) then decreased rapidly with LET. The RBE of 440 keV/μm iron particles was 0.7. The RBE calculated from induction of isochromatid-type breaks was much higher for high-LET radiations. It is concluded that the increased production of isochromatid-type breaks, induced by the densely ionizing track structure, is a signature of high-LET radiation exposure.

  6. Identifying the structural requirements for chromosomal aberration by incorporating molecular flexibility and metabolic activation of chemicals.

    PubMed

    Mekenyan, Ovanes; Todorov, Milen; Serafimova, Rossitsa; Stoeva, Stoyanka; Aptula, Aynur; Finking, Robert; Jacob, Elard

    2007-12-01

    Modeling the potential of chemicals to induce chromosomal damage has been hampered by the diversity of mechanisms which condition this biological effect. The direct binding of a chemical to DNA is one of the underlying mechanisms that is also responsible for bacterial mutagenicity. Disturbance of DNA synthesis due to inhibition of topoisomerases and interaction of chemicals with nuclear proteins associated with DNA (e.g., histone proteins) were identified as additional mechanisms leading to chromosomal aberrations (CA). A comparative analysis of in vitro genotoxic data for a large number of chemicals revealed that more than 80% of chemicals that elicit bacterial mutagenicity (as indicated by the Ames test) also induce CA; alternatively, only 60% of chemicals that induce CA have been found to be active in the Ames test. In agreement with this relationship, a battery of models is developed for modeling CA. It combines the Ames model for bacterial mutagenicity, which has already been derived and integrated into the Optimized Approach Based on Structural Indices Set (OASIS) tissue metabolic simulator (TIMES) platform, and a newly derived model accounting for additional mechanisms leading to CA. Both models are based on the classical concept of reactive alerts. Some of the specified alerts interact directly with DNA or nuclear proteins, whereas others are applied in a combination of two- or three-dimensional quantitative structure-activity relationship models assessing the degree of activation of the alerts from the rest of the molecules. The use of each of the alerts has been justified by a mechanistic interpretation of the interaction. In combination with a rat liver S9 metabolism simulator, the model explained the CA induced by metabolically activated chemicals that do not elicit activity in the parent form. The model can be applied in two ways: with and without metabolic activation of chemicals. PMID:18052113

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

    SciTech Connect

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke; Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea; Wieczorek, Stefan; Epplen, Joerg Thomas; Tilkorn, Daniel; Steinstraesser, Lars

    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.

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

    NASA Technical Reports Server (NTRS)

    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.

  9. The effect of track structure on the induction of chromosomal aberrations in murine cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Cella, L.; Furusawa, Y.; George, K.; Gialanella, G.; Grossi, G.; Pugliese, M.; Saito, M.; Yang, T. C.

    1998-01-01

    PURPOSE: To measure chromosome aberrations in C3H 10T1/2 mouse fibroblasts using FISH painting at the first mitosis following exposure to 30 keV/microm hydrogen or neon ions. MATERIALS AND METHODS: Cells in plateau-phase were irradiated with 0.86 MeV protons at the TTT-3 Tandem accelerator in Naples (Italy), or with 400 MeV/n Ne ions at the HIMAC accelerator in Chiba (Japan). Colcemid-blocked cells were harvested at the first mitosis following exposure, and chromosome spreads were hybridized in situ with a fluorescein-labelled composite mouse DNA probe specific for chromosomes 2 and 8. RESULTS: Protons were more efficient than neon ions at the same LET in the induction of chromosome interchanges and breaks. Yields of complex exchanges were similar for both particles at the same dose, but protons produced mostly insertions, while with Ne exposure non-reciprocal exchanges were the most frequent complex-type exchange. CONCLUSIONS: Charged particles with the same LET produce different yields of chromosome aberrations, and some observed differences can be explained based on the available track-structure models.

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

    PubMed Central

    2012-01-01

    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<0.05) to that of the control group. The treatment of BR for 60 days and single dose of EMS or MMS on day 61, resulted in significant (p <0.05) reduction in the frequency of chromosomal aberrations in comparison to EMS or MMS treatment alone, indicating a protective effect of BR. Constitutive base excision repair capacity was also increased in BR treated animals. 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. PMID:22853637

  11. The inhibition of CHO-K1-BH4 cell proliferation and induction of chromosomal aberrations by brevetoxins in vitro.

    PubMed

    Sayer, A N; Hu, Q; Bourdelais, A J; Baden, D G; Gibson, J E

    2006-07-01

    Brevetoxins (PbTxs) are highly potent trans-syn polyether neurotoxins produced during blooms of several species of marine dinoflagellates, most notably Karenia brevis. These neurotoxins act on voltage-sensitive sodium channels prolonging the active state. During red tides, the commercial fishing and tourism industries experience millions of dollars of lost revenue. Human consumption of shellfish contaminated with PbTxs results in neurotoxic shellfish poisoning (NSP). Additionally, blooms of K. brevis are potentially responsible for adverse human health effects such as respiratory irritation and airway constriction in coastal residents. There is little information regarding the full range of potential toxic effects caused by PbTxs. Recent evidence suggests that PbTxs are genotoxic substances. The purpose of this study was to determine if PbTxs could induce chromosomal aberrations and inhibit cellular proliferation in CHO-K1-BH4 cells, and if so, could the damage be negated or reduced by the PbTx antagonist brevenal. Results from the chromosomal aberrations assay demonstrated that PbTxs are potent inducers of CHO-K1-BH4 chromosome damage. Results from the inhibition of cellular proliferation assays demonstrated that PbTxs inhibit the ability of CHO-K1-BH4 cells to proliferate, an effect which can be reduced with brevenal. PMID:16487644

  12. The inhibition of CHO-K1-BH4 cell proliferation and induction of chromosomal aberrations by brevetoxins in vitro

    PubMed Central

    Sayer, A.N.; Hu, Q.; Bourdelais, A.J.; Baden, D.G.; Gibson, J.E.

    2009-01-01

    Brevetoxins (PbTxs) are highly potent trans-syn polyether neurotoxins produced during blooms of several species of marine dinoflagellates, most notably Karenia brevis. These neurotoxins act on voltage-sensitive sodium channels prolonging the active state. During red tides, the commercial fishing and tourism industries experience millions of dollars of lost revenue. Human consumption of shellfish contaminated with PbTxs results in neurotoxic shellfish poisoning (NSP). Additionally, blooms of K. brevis are potentially responsible for adverse human health effects such as respiratory irritation and airway constriction in coastal residents. There is little information regarding the full range of potential toxic effects caused by PbTxs. Recent evidence suggests that PbTxs are genotoxic substances. The purpose of this study was to determine if PbTxs could induce chromosomal aberrations and inhibit cellular proliferation in CHO-K1-BH4 cells, and if so, could the damage be negated or reduced by the PbTx antagonist brevenal. Results from the chromosomal aberrations assay demonstrated that PbTxs are potent inducers of CHO-K1-BH4 chromosome damage. Results from the inhibition of cellular proliferation assays demonstrated that PbTxs inhibit the ability of CHO-K1-BH4 cells to proliferate, an effect which can be reduced with brevenal. PMID:16487644

  13. RBE of d(50)-Be neutrons for induction of chromosome aberrations in Allium cepa onion roots.

    PubMed

    Wambersie, A; Laublin, G; Octave-Prignot, M; Meulders, J P

    1979-11-01

    RBE/absorbed dose relationship of d(50)-Be neutrons was determined for the induction of chromosome aberrations in Allium cepa onion roots. Neutrons are produced at the cyclotron "Cyclone" by bombarding a thick beryllium target with 50 MeV deuterons. Two biological criteria were selected: (1) mean number of aberrations (mainly breaks) per cell in anaphase and telophase, (2) fraction of intact cells in anaphase and telophase. For the two criteria, RBE increases continuously from about 7 to 12 as the neutron absorbed dose decreases from 0.4 to 0.1 Gy. RBE values for the first criterion are slightly higher than for the second one. This observation is interpreted in terms of the analysis of the distribution of the aberrations in the cells. In logarithmic coordinates, RBE/absorbed dose relationships for the two criteria are almost linear with a slope close to -1/2. RBE values observed for induction of chromosome aberrations in Allium cepa are higher than those generally observed for biological effects related to mammalian cell lethality. PMID:516100

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

    PubMed

    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. PMID:21434393

  15. Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (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 radiation induced higher 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 chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further

  16. Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease

    SciTech Connect

    Kleinerman, R.A.; Boice, J.D. Jr.; Inskip, P.D.; Tarone, R.E.; Littlefield, L.G.; Sayer, A.M.; Cookfair, D.L.; Wactawski-Wende, J.

    1994-07-01

    Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow. High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received. 30 refs., 4 tabs.

  17. Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans.

    PubMed

    Dickinson, Peter J; York, Dan; Higgins, Robert J; LeCouteur, Richard A; Joshi, Nikhil; Bannasch, Danika

    2016-07-01

    Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy. PMID:27251041

  18. Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans.

    PubMed

    Schröder, H; Heimers, A; Frentzel-Beyme, R; Schott, A; Hoffmann, W

    2003-01-01

    Chromosome aberrations and sister chromatid exchanges (SCEs) were determined in standard peripheral lymphocyte metaphase preparations of 13 British Gulf War veterans, two veterans of the recent war in the Balkans and one veteran of both wars. All 16 volunteers suspect exposures to depleted uranium (DU) while deployed at the two different theatres of war in 1990 and later on. The Bremen laboratory control served as a reference in this study. Compared with this control there was a statistically significant increase in the frequency of dicentric chromosomes (dic) and centric ring chromosomes (cR) in the veterans' group. indicating a previous exposure to ionising radiation. The statistically significant overdispersion of die and cR indicates non-uniform irradiation as would be expected after non-uniform exposure and/or exposure to radiation with a high linear energy transfer (LET). The frequency of SCEs was decreased when compared with the laboratory control. PMID:12678382

  19. Biphasic Effects of Nitric Oxide Radicals on Radiation-Induced Lethality and Chromosome Aberrations in Human Lung Cancer Cells Carrying Different p53 Gene Status

    SciTech Connect

    Su Xiaoming; Takahashi, Akihisa; Guo Guozhen; Mori, Eiichiro; Okamoto, Noritomo; Ohnishi, Ken; Iwasaki, Toshiyasu; Ohnishi, Takeo

    2010-06-01

    Purpose: The aim of this study was to clarify the effects of nitric oxide (NO) on radiation-induced cell killing and chromosome aberrations in two human lung cancer cell lines with a different p53 gene status. Methods and Materials: We used wild-type (wt) p53 and mutated (m) p53 cell lines that were derived from the human lung cancer H1299 cell line, which is p53 null. The wtp53 and mp53 cell lines were generated by transfection of the appropriate p53 constructs into the parental cells. Cells were pretreated with different concentrations of isosorbide dinitrate (ISDN) (an NO donor) and/or 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) (an NO scavenger) and then exposed to X-rays. Cell survival, apoptosis, and chromosome aberrations were scored by use of a colony-forming assay, Hoechst 33342 staining assay and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP [deoxyuridine triphosphate] nick end labeling) assay, and chromosomal banding techniques, respectively. Results: In wtp53 cells the induction of radioresistance and the inhibition of apoptosis and chromosome aberrations were observed in the presence of ISDN at low 2- to 10-{mu}mol/L concentrations before X-irradiation. The addition of c-PTIO and ISDN into the culture medium 6 h before irradiation almost completely suppressed these effects. However, at high concentrations of ISDN (100-500 {mu}mol/L), clear evidence of radiosensitization, enhancement of apoptosis, and chromosome aberrations was detected. However, these phenomena were not observed in mp53 cells at either concentration range with ISDN. Conclusions: These results indicate that low and high concentrations of NO radicals can choreograph inverse radiosensitivity, apoptosis, and chromosome aberrations in human lung cancer cells and that NO radicals can affect the fate of wtp53 cells.

  20. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

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

    NASA Technical Reports Server (NTRS)

    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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Chaudhary, Manu; Payasi, Anurag

    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 The ability of Trois to induce reverse mutations was evaluated in Salmonella 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 There were no increases in the number of revertant colonies at any concentrations of 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. Conclusions Results of this study suggest that Trois is non-mutagenic.

  4. M-Band Analysis of Chromosome Aberrations in Human Epithelial Cells Induced By Low- and High-Let Radiations

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

    Energetic primary and secondary particles pose a health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET radiation is much more effective than low-LET radiation in the induction of various biological effects, including cell inactivation, genetic mutations, cataracts and cancer. Most of these biological endpoints are closely correlated to chromosomal damage, which can be utilized as a biomarker for radiation insult. In this study, human epithelial cells were exposed in vitro to gamma rays, 1 GeV/nucleon Fe ions and secondary neutrons whose spectrum is similar to that measured inside the Space Station. Chromosomes were condensed using a premature chromosome condensation technique and chromosome aberrations were analyzed with the multi-color banding (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of both interchromosomal (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Results of the study confirmed the observation of higher incidence of inversions for high-LET irradiation. 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. Half of the inversions observed in the low-LET irradiated samples were accompanied by other types of intrachromosome aberrations, but few inversions were accompanied by interchromosome aberrations. In contrast, Fe ions induced a significant fraction of inversions that involved complex rearrangements of both the inter- and intrachromosome exchanges.

  5. SYNAPTONEMAL COMPLEX DAMAGE IN RELATION TO MEIOTIC CHROMOSOME ABERRATIONS AFTER EXPOSURE OF MALE MICE TO CYCLOPHOSPHAMIDE (JOURNAL VERSION)

    EPA Science Inventory

    Cyclophosphamide (CP) has been reported to cause structural and numerical chromosome aberrations in mouse spermatocyte metaphase chromosomes. Further, it was concluded to be one of the few chemicals for which there appears to be reliable data suggesting that it can induce germ ce...

  6. Effect of chromosome size on aberration levels caused by gamma radiation as detected by fluorescence in situ hybridization.

    PubMed

    Pandita, T K; Gregoire, V; Dhingra, K; Hittelman, W N

    1994-01-01

    Fluorescence in situ hybridization (FISH) is a powerful technique for detecting genomic alterations at the chromosome level. To study the effect of chromosome size on aberration formation, we used FISH to detect initial damage in individual prematurely condensed chromosomes (PCC) of gamma-irradiated G0 human cells. A linear dose response for breaks and a nonlinear dose response for exchanges was obtained using a chromosome 1-specific probe. FISH detected more chromosome 1 breaks than expected from DNA based extrapolation of Giemsa stained PCC preparations. The discrepancy in the number of breaks detected by the two techniques raised questions as to whether Giemsa staining and FISH differ in their sensitivities for detecting breaks, or is chromosome 1 uniquely sensitive to gamma-radiation. To address the question of technique sensitivity, we determined total chromosome damage by FISH using a total genomic painting probe; the results obtained from Giemsa-staining and FISH were nearly identical. To determine if chromosome 1 was uniquely sensitive, we selected four different sized chromosomes for paint probes and scored them for gamma-ray induced aberrations. In these studies the number of chromosome breaks per unit DNA increased linearly with an increase in the DNA content of the chromosomes. However, the number of exchanges per unit of DNA did not increase with an increase in chromosome size. This suggests that chromosome size may influence the levels of aberrations observed. Extrapolation from measurements of a single chromosome's damage to the whole genome requires that the relative DNA content of the measured chromosome be considered. PMID:8039428

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

    PubMed Central

    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. Images Figure 2 PMID:9374370

  8. Comparison of hprt variant frequencies and chromosome aberration frequencies in lymphocytes from radiotherapy and chemotherapy patients: A prospective study

    SciTech Connect

    Ammenheuser, M.M.; Au, W.W.; Whorton, E.B. Jr.; Belli, J.A.; Ward, J.B. Jr. )

    1991-01-01

    The autoradiographic 6-thioguanine-resistant mutant lymphocyte assay and a chromosome aberration assay were used to determine the time-course of appearance and persistence of elevated frequencies of hprt variants and dicentric chromosomes in patients receiving x-irradiation therapy. The hprt mutation assays were done with frozen/thawed lymphocytes isolated from aliquots of the same blood samples used for the chromosome aberration assays. Five multiple sclerosis patients were also studied before and at 2 and 4 wk intervals after treatment with monthly i.v. doses of 750 mg/m{sup 2} of cyclophosphamide (CP). There were no significant elevations in chromosome aberrations at these post-treatment sample times. The results demonstrate the complementary nature of these two human monitoring assays and emphasize the importance of careful selection of optimal sampling times.

  9. Effect of LET and track structure on the statistical distribution of chromosome aberrations

    NASA Astrophysics Data System (ADS)

    Gudowska-Nowak, E.; Lee, R.; Nasonova, E.; Ritter, S.; Scholz, M.

    Chromosome aberration data obtained for various types of mammalian cells after exposure to low and high LET radiation clearly demonstrate differences in the energy deposition pattern of both radiation qualities. In the present study we focus on the distributions of chromosome aberrations induced in human peripheral blood lymphocytes after exposure to 990 MeV/u Fe ions (LET = 155 keV/μm) or X-rays. For the analysis three different types of distributions were applied, namely a Poisson distribution, a compound Poisson-Poisson (Neyman type A) distribution and a convoluted Poisson-Neyman distribution. The analysis showed that after low LET radiation the distribution of aberrations can be well described by Poisson statistics, reflecting a simple random distribution of damages as expected according to the homogeneous pattern of energy depositions. In contrast, for particles the energy is deposited spatially very inhomogeneous and concentrated along the ion trajectories. After exposure to high energy, high LET particles where the track radius is much larger than the cell nucleus, best fits to the data were achieved by a convoluted Poisson-Neyman statistics. The analysis indicates that, under this exposure condition, the distribution of aberrations is determined by two independent components. The first component is determined by the damage induced by a center of the tracks and follows the Neyman distribution. The second component is determined by the overlapping part of tracks which in the case of very high energetic particles leads to a "photon-like" background dose and is thus characterized by a Poisson distribution.

  10. Unraveling the chromosomal aberrations of head and neck squamous cell carcinoma: a review.

    PubMed

    Patmore, Harriet S; Cawkwell, Lynn; Stafford, Nicholas D; Greenman, John

    2005-10-01

    Information from the genetic analysis of head and neck cancer has grown enormously in the last 20 years. The advent of high-resolution genetic analysis techniques such as microarray technology will further expand this field in the future. Here we review the data on chromosomal aberrations of head and neck squamous cell carcinoma, focusing on the data generated by comparative genomic hybridization analysis, and suggest how such findings will be taken forward over the next decade. With the search engine PUBMED, the key words "comparative genomic hybridisation," "head and neck," "oral," "hypopharyngeal," "laryngeal," and "squamous cell carcinoma" were used. Publications unavailable in English were excluded. PMID:16132373

  11. Effects of infliximab on sister chromatid exchanges and chromosomal aberration in patients with rheumatoid arthritis.

    PubMed

    Atteritano, M; Mazzaferro, S; Mantuano, S; Bagnato, G L; Bagnato, G F

    2016-03-01

    The aim of this study was to evaluate in a 24-weeks the effect of anti-TNF-alpha, infliximab, on cytogenetic biomarkers in peripheral lymphocytes of patients with rheumatoid arthritis (RA). A total of 40 patients with RA met the criteria to be treated with methotrexate (15 mg/week) were evaluated. Twenty patients, randomly selected, were treated with infliximab in addition to methotrexate (group I), whereas the other 20 patients continued with only methotrexate treatment (group M). Twenty healthy volunteers matched for age, gender and smoking habits served as control group (group C). At baseline, sister chromatid exchange rate was 7.20 ± 2.21 in group I, 7.40 ± 1.60 in group M and 4.97 ± 1.32 in group C (P < 0.01 vs group I and M). After 24-weeks, sister chromatid exchange rate was 7.87 ± 2.54 in group I and 7.81 ± 1.95 in group M (P = ns). High frequency cells count was 4.9 % and 4.7 % in the groups I and M, respectively, at the end of the study (P = ns). The basal chromosomal aberration frequency was 4.90 % in group I and 5.20 % in groups M; after 24-weeks, this was 5.10 % in group I and 5.10 % in groups M (P = ns). Infliximab treatment, for 24 weeks, did not increase the cytogenetic biomarkers in patients with RA. Our data show that the use of infliximab has not a genotoxic effect in patients with RA. PMID:26012953

  12. Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

    PubMed Central

    Misenko, Sarah M.; Bunting, Samuel F.

    2014-01-01

    Defective DNA repair leads to increased genomic instability, which is the root cause of mutations that lead to tumorigenesis. Analysis of the frequency and type of chromosome aberrations in different cell types allows defects in DNA repair pathways to be elucidated. Understanding mammalian DNA repair biology has been greatly helped by the production of mice with knockouts in specific genes. The goal of this protocol is to quantify genomic instability in mouse B lymphocytes. Labeling of the telomeres using PNA-FISH probes (peptide nucleic acid - fluorescent in situ hybridization) facilitates the rapid analysis of genomic instability in metaphase chromosome spreads. B cells have specific advantages relative to fibroblasts, because they have normal ploidy and a higher mitotic index. Short-term culture of B cells therefore enables precise measurement of genomic instability in a primary cell population which is likely to have fewer secondary genetic mutations than what is typically found in transformed fibroblasts or patient cell lines. PMID:25177909

  13. Chromosomal aberrations in onion (Allium cepa) induced by water chlorination by-products

    SciTech Connect

    Al-Sabti, K.; Kurelec, B.

    1985-01-01

    It has recently come to light that water chlorination generates mutagens and carcinogens. The mutagenicity of nonvolatile mutagenic by-products of water chlorination has been demonstrated in short-term biological testings. The predictive value of short-term tests is considerably enhanced by the use of more than one test system. A scientifically stringent approach in formulating a testing program for the assessment of genotoxins is to rely on tests that directly measure gene mutations and chromosome alterations. Chromosome aberrations (CA) become such a relevant bioassay. The CA measurement in the allium test is suitable for measuring the cytogenotoxic potential of chemicals present in water; it is simple, cheap, sensitive, and it does not require a generally undefined step of concentrating chemicals present in polluted waters. In the present investigation CA in Allium were chosen for the detection of mutagenic potential of a polluted river waters before and after the under-breakpoint chlorination.

  14. Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chromosome painting is an efficient tool for chromosome research. However, plant chromosome painting is relatively underdeveloped. In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat-Thinopyrum intermedium addition line, and chromosomes of...

  15. Chromosomal aberrations in a fish, Channa punctata after in vivo exposure to three heavy metals.

    PubMed

    Yadav, Kamlesh K; Trivedi, Sunil P

    2009-08-01

    The studies were designed to assess the extent of chromosomal aberrations (CA) under the exposure of three common heavy metalic compounds, viz. mercuric chloride, arsenic trioxide and copper sulphate pentahydrate, in vivo using fish, Channa punctata (2n=32), as a test model. Prior acclimatized fishes were divided into five groups. Group I and II served as negative and positive control, respectively. An intramuscular injection of Mitomycin-C (@ 1mg/kg body wt.) was administered to group II only. Fishes of groups III, IV and V were subjected to sublethal concentrations (10% of 96h LC(50)), of HgCl(2) (0.081mg/L), As(2)O(3) (6.936mg/L) and CuSO(4)x5H(2)O (0.407mg/L). Fishes of all the groups were exposed uninterrupted for 24, 48, 72, 96 and 168h. Observations of kidney cells of exposed fishes revealed chromatid and chromosome breaks, chromatid and chromosome gaps along with ring and di-centric chromosomes. A significant increase over negative control in the frequency of chromosomal aberrations (CA) was observed in fish exposed to Mitomycin-C, Hg(II), As(III) and Cu(II). As the average + or - SE total number of CA, average number of CA per metaphase and %incidence of aberrant cells in Hg(II) was 104.40 + or - 8.189, 0.347 + or - 0.027 and 10.220 + or - 0.842, respectively; in As(III) 109.20 + or - 8.309, 0.363 + or - 0.027 and 10.820 + or - 2.347, respectively and in Cu(II) 89.00 + or - 19.066, 0.297 + or - 0.028 and 8.900 + or - 0.853, respectively. Hence, it reveals that the order of induction of frequency of CA was Cu

  16. Inter- and Intra-Chromosomal Aberrations in Human Cells Exposed in vitro to High and Low LET Radiations

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

    Energetic heavy ions pose a health risk to astronauts in extended ISS and future Mars missions. High-LET heavy ions are particularly effective in causing various biological effects including cell inactivation, genetic mutations 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 chromosome aberrations in human lymphocytes and fibroblasts induced by both low- and high-LET radiation using FISH and multicolor fluorescence in situ hybridization (mFISH) techniques. In this study, we exposed human epithelial cells in vitro to gamma rays and energetic particles of varying types and energies and dose rates, and analyzed chromosomal damages using the multicolor banding in situ hybridization (mBAND) procedure. Confluent human epithelial cells (CH184B5F5/M10) were exposed to energetic heavy ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory, high energy neutron at the Los Alamos Nuclear Science Center (LANSCE) or Cs-137-gamma radiation source at the University of Texas, MD Anderson Cancer Center. After colcemid and Calyculin A treatment, cells were fixed and painted with XCyte3 mBAND kit (MetaSystems) and chromosome aberrations were analyzed with mBAND analysis system (MetaSystems). 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). The results of the mBAND study showed a higher ratio of inversion involved with interchromosomal exchange in heavy ions compared to -ray irradiation. Analysis of chromosome aberrations using mBAND has the potential to provide useful information on human cell response to space-like radiation.

  17. Ability of fourteen chemical agents used in dental practice to induce chromosome aberrations in Syrian hamster embryo cells.

    PubMed

    Hikiba, Hirohito; Watanabe, Eiko; Barrett, J Carl; Tsutsui, Takeki

    2005-01-01

    To assess the genotoxicity of 14 chemical agents used in dental practice, the ability of these agents to induce chromosome aberrations was examined using Syrian hamster embryo (SHE) cells. Statistically significant increases in the frequencies of chromosome aberrations were induced in SHE cells treated with 7 of 10 chemical agents used as endodontic medicaments, that is, carbol camphor, m-cresol, eugenol, guaiacol, zinc oxide, hydrogen peroxide, and formaldehyde. The other 3 chemical agents, that is, thymol, glutaraldehyde, and iodoform, did not increase the levels of chromosome aberrations. Of the 4 chemical agents that are used as an antiseptic on the oral mucosa, chromosome aberrations were induced by iodine, but not by the other 3 antiseptics, benzalkonium chloride, benzethonium chloride, and chlorhexidine. Among the 6 chemical agents exhibiting a negative response in the assay, only thymol induced chromosome aberrations in the presence of exogenous metabolic activation. Our results indicate that chemical agents having a positive response in the present study are potentially genotoxic to mammalian cells and need to be studied further in detail. PMID:15665446

  18. Differences in the effectiveness of EDTA to induce SCEs and chromosomal aberrations in CHO and Allium cepa chromosomes.

    PubMed

    Ortíz, T; Cortés, F

    1990-01-01

    The chelating agent EDTA was able to produce chromosome aberrations (CA) in CHO cells when it was administered simultaneously with BrdUrd (2 x 10(-5) M), without any concomitant effect on the yield of sister chromatid exchanges (SCEs). Root meristematic cells of Allium cepa did not show any type of CA when they were treated with different doses of EDTA (with or without BrdUrd 10(-4) M) while the SCE frequency was increased in a dose-dependent fashion. These effects of EDTA have not been previously reported. It is suggested that deprivation of divalent cations (Ca(+)+/Mg(+)+) probably play an important role in DNA replication and repair processes. PMID:2114256

  19. Genetic control of chromosome breakage and rejoining in Drosophila melanogaster: spontaneous chromosome aberrations in X-linked mutants defective in DNA metabolism.

    PubMed Central

    Gatti, M

    1979-01-01

    Eight X-linked recombination-defective meiotic mutants (representing five loci) and 12 X-linked mutagen-sensitive mutants (representing seven loci) of Drosophila melanogaster have been examined cytologically in neuroblast metaphases for their effects on the frequencies and types of spontaneous chromosome aberrations. Twelve mutants, representing five loci, significantly increase the frequency of chromosomal aberrations. The mutants at these five loci, however, differ markedly both in the types of aberrations produced and the localization of their effects along the chromosome. According to these criteria, the mutants can be assigned to four groups: (i) mutants producing almost exclusively chromatid breaks in both euchromatin and heterochromatin; (ii) mutants producing chromatid and isochromatid breaks in both euchromatin and heterochromatin; (iii) mutants producing chromatid mutants producing chromatid and isochromatid breaks clustered in the heterochromatin. Images PMID:108678

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

    NASA Technical Reports Server (NTRS)

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Chromosomal Aberrations in Wild Mice Captured in Areas Differentially Contaminated by the Fukushima Dai-Ichi Nuclear Power Plant Accident.

    PubMed

    Kubota, Yoshihisa; Tsuji, Hideo; Kawagoshi, Taiki; Shiomi, Naoko; Takahashi, Hiroyuki; Watanabe, Yoshito; Fuma, Shoichi; Doi, Kazutaka; Kawaguchi, Isao; Aoki, Masanari; Kubota, Masahide; Furuhata, Yoshiaki; Shigemura, Yusaku; Mizoguchi, Masahiko; Yamada, Fumio; Tomozawa, Morihiko; Sakamoto, Shinsuke H; Yoshida, Satoshi

    2015-08-18

    Following the Fukushima Dai-ichi Nuclear Power Plant accident, radiation effects on nonhuman biota in the contaminated areas have been a great concern. The induction of chromosomal aberrations in splenic lymphocytes of small Japanese field mice (Apodemus argenteus) and house mice (Mus musculus) inhabiting Fukushima Prefecture was investigated. In mice inhabiting the slightly contaminated area, the average frequency of dicentric chromosomes was similar to that seen in mice inhabiting a noncontaminated control area. In contrast, mice inhabiting the moderately and heavily contaminated areas showed a significant increase in the average frequencies of dicentric chromosomes. Total absorbed dose rate was estimated to be approximately 1 mGy d(-1) and 3 mGy d(-1) in the moderately and heavily contaminated areas, respectively. Chromosomal aberrations tended to roughly increase with dose rate. Although theoretically, the frequency of chromosomal aberrations was considered proportional to the absorbed dose, chromosomal aberrations in old mice (estimated median age 300 days) did not increase with radiation dose at the same rate as that observed in young mice (estimated median age 105 days). PMID:26217955

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

    PubMed

    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. PMID:25033729

  4. The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis.

    PubMed

    Ben-David, Uri; Ha, Gavin; Khadka, Prasidda; Jin, Xin; Wong, Bang; Franke, Lude; Golub, Todd R

    2016-01-01

    Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalogue of chromosomal aberrations in cancer GEMMs. Mining this resource, we find that most chromosomal aberrations accumulate late during breast tumorigenesis, and observe marked differences in CNA prevalence between mouse mammary tumours initiated with distinct drivers. Some aberrations are recurrent and unique to specific GEMMs, suggesting distinct driver-dependent routes to tumorigenesis. Synteny-based comparison of mouse and human tumours narrows critical regions in CNAs, thereby identifying candidate driver genes. We experimentally validate that loss of Stratifin (SFN) promotes HER2-induced tumorigenesis in human cells. These results demonstrate the power of GEMM CNA analysis to inform the pathogenesis of human cancer. PMID:27374210

  5. The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis

    PubMed Central

    Ben-David, Uri; Ha, Gavin; Khadka, Prasidda; Jin, Xin; Wong, Bang; Franke, Lude; Golub, Todd R.

    2016-01-01

    Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalogue of chromosomal aberrations in cancer GEMMs. Mining this resource, we find that most chromosomal aberrations accumulate late during breast tumorigenesis, and observe marked differences in CNA prevalence between mouse mammary tumours initiated with distinct drivers. Some aberrations are recurrent and unique to specific GEMMs, suggesting distinct driver-dependent routes to tumorigenesis. Synteny-based comparison of mouse and human tumours narrows critical regions in CNAs, thereby identifying candidate driver genes. We experimentally validate that loss of Stratifin (SFN) promotes HER2-induced tumorigenesis in human cells. These results demonstrate the power of GEMM CNA analysis to inform the pathogenesis of human cancer. PMID:27374210

  6. Effect of lead chromate on chromosome aberration, sister-chromatid exchange and DNA damage in mammalian cells in vitro.

    PubMed

    Douglas, G R; Bell, R D; Grant, C E; Wytsma, J M; Bora, K C

    1980-02-01

    Possible mutagenic activity of lead chromate in mammalian cells was studied using assays for chromosome aberrations and sister-chromatid exchanges in cultured human lymphocytes, and DNA fragmentation as detected by alkaline-sucrose gradient sedimentation in cultured Chinese hamster ovary (CHO) cells. Lead chromate caused dose-related increases in chromosome aberration and sister-chromatid exchange in human lymphocytes. No increase in DNA damage was observed in CHO cells, possibly due to the relative insensitivity of the CHO cells and the limited solubility of lead chromate in tissue culture medium. The mutagenicity of lead chromate in human lymphocytes appears to be entirely due to the chromate ion since chromosome aberrations were induced by potassium chromate but not lead chloride. PMID:7374664

  7. Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China

    SciTech Connect

    Wang, Z.Y.; Boice, J.D. Jr.; Wei, L.X.; Beebe, G.W.; Zha, Y.R.; Kaplan, M.M.; Tao, Z.F.; Maxon, H.R. III; Zhang, S.Z.; Schneider, A.B. )

    1990-03-21

    Thyroid nodularity following continuous low-dose radiation exposure in China was determined in 1,001 women aged 50-65 years who resided in areas of high background radiation (330 mR/yr) their entire lives, and in 1,005 comparison subjects exposed to normal levels of radiation (114 mR/yr). Cumulative doses to the thyroid were estimated to be of the order of 14 cGy and 5 cGy, respectively. Personal interviews and physical examinations were conducted, and measurements were made of serum thyroid hormone levels, urinary iodine concentrations, and chromosome aberrations in circulating lymphocytes. For all nodular disease, the prevalences in the high background and control areas were 9.5% and 9.3%, respectively. For single nodules, the prevalences were 7.4% in the high background area and 6.6% in the control area (prevalence ratio = 1.13; 95% confidence interval = 0.82-1.55). There were no differences found in serum levels of thyroid hormones. Women in the high background region, however, had significantly lower concentrations of urinary iodine and significantly higher frequencies of stable and unstable chromosome aberrations. Increased intake of allium vegetables such as garlic and onions was associated with a decreased risk of nodular disease, which seems consistent with experimental studies suggesting that allium compounds can inhibit tumor growth and proliferation. The prevalence of mild diffuse goiter was higher in the high background radiation region, perhaps related to a low dietary intake of iodine. These data suggest that continuous exposure to low-level radiation throughout life is unlikely to appreciably increase the risk of thyroid cancer. However, such exposure may cause chromosomal damage.

  8. Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China.

    PubMed

    Wang, Z Y; Boice, J D; Wei, L X; Beebe, G W; Zha, Y R; Kaplan, M M; Tao, Z F; Maxon, H R; Zhang, S Z; Schneider, A B

    1990-03-21

    Thyroid nodularity following continuous low-dose radiation exposure in China was determined in 1,001 women aged 50-65 years who resided in areas of high background radiation (330 mR/yr) their entire lives, and in 1,005 comparison subjects exposed to normal levels of radiation (114 mR/yr). Cumulative doses to the thyroid were estimated to be of the order of 14 cGy and 5 cGy, respectively. Personal interviews and physical examinations were conducted, and measurements were made of serum thyroid hormone levels, urinary iodine concentrations, and chromosome aberrations in circulating lymphocytes. For all nodular disease, the prevalences in the high background and control areas were 9.5% and 9.3%, respectively. For single nodules, the prevalences were 7.4% in the high background area and 6.6% in the control area (prevalence ratio = 1.13; 95% confidence interval = 0.82-1.55). There were no differences found in serum levels of thyroid hormones. Women in the high background region, however, had significantly lower concentrations of urinary iodine and significantly higher frequencies of stable and unstable chromosome aberrations. Increased intake of allium vegetables such as garlic and onions was associated with a decreased risk of nodular disease, which seems consistent with experimental studies suggesting that allium compounds can inhibit tumor growth and proliferation. The prevalence of mild diffuse goiter was higher in the high background radiation region, perhaps related to a low dietary intake of iodine. These data suggest that continuous exposure to low-level radiation throughout life is unlikely to appreciably increase the risk of thyroid cancer. However, such exposure may cause chromosomal damage. PMID:2313719

  9. Analysis of Chromosomal Aberrations in the Blood Lymphocytes of Astronauts after Space Flight

    NASA Technical Reports Server (NTRS)

    George, K.; Kim, M. Y.; Elliott, T.; Cucinotta, F. A.

    2007-01-01

    It is a NASA requirement that biodosimetry analysis be performed on all US astronauts who participate in long duration missions of 3 months or more onboard the International Space Station. Cytogenetic analysis of blood lymphocytes is the most sensitive and reliable biodosimetry method available at present, especially if chromosome damage is assessed before as well as after space flight. Results provide a direct measurement of space radiation damage in vivo that takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. We present data obtained from all twenty-five of the crewmembers who have participated in the biodosimetry program so far. The yield of chromosome exchanges, measured using fluorescence in situ hybridization (FISH) technique with chromosome painting probes, increased after space flight for all these individuals. In vivo dose was derived from frequencies of chromosome exchanges using preflight calibration curves of in vitro exposed cells from the same individual, and RBE was compared with individually measured physically absorbed dose and projected organ dose equivalents. Biodosimetry estimates using samples collected within a few weeks of return from space lie within the range expected from physical dosimetry. For some of these individuals chromosome aberrations were assessed again several months after their respective missions and a temporal decline in stable exchanges was observed in some cases, suggesting that translocations are unstable with time after whole body exposure to space radiation. This may indicate complications with the use of translocations for retrospective dose reconstruction. Data from one crewmember who has participated in two separate long duration space missions and has been followed up for over 10 years provides limited data on the effect of repeat flights and shows a possible adaptive response to space radiation exposure.

  10. Inter- and Intra-Chromosomal Aberrations in Human Cells Exposed in vitro to Space-like Radiations

    NASA Technical Reports Server (NTRS)

    Hada, Megumi; Cucinotta, F. A.; Gonda, S. R.; Wu, H.

    2005-01-01

    Energetic heavy ions pose a great health risk to astronauts in extended ISS and future exploration missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations 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 chromosome aberrations in human lymphocytes and fibroblasts induced by both low- and high-LET radiation using FISH and multicolor fluorescence in situ hybridization (mFISH) techniques. In this study, we exposed human cells in vitro to gamma rays and energetic particles of varying types and energies and dose rates, and analyzed chromosomal damages using the multicolor banding in situ hybridization (mBAND) procedure. Confluent human epithelial cells and lymphocytes were exposed to energetic heavy ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory (Upton, NY) or Cs-137 gamma radiation source at the Baylor College (Houston, TX). After colcemid and Calyculin A treatment, cells were fixed and painted with XCyte3 mBAND kit (MetaSystems) and chromosome aberrations were analyzed with mBAND analysis system (MetaSystems). 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). The possible relationship between the frequency of inter- and intra-chromosomal exchanges and the track structure of radiation is discussed. The work was supported by the NASA Space Radiation Health Program.

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

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

  12. Dynamics of chromosomal aberrations, induction of apoptosis, BRCA2 degradation and sensitization to radiation by hyperthermia.

    PubMed

    Bergs, Judith W J; Oei, Arlene L; Ten Cate, Rosemarie; Rodermond, Hans M; Stalpers, Lukas J; Barendsen, Gerrit W; Franken, Nicolaas A P

    2016-07-01

    Hyperthermia can transiently degrade BRCA2 and thereby inhibit the homologous recombination pathway. Induced DNA-double strand breaks (DSB) then have to be repaired via the error prone non-homologous end-joining pathway. In the present study, to investigate the role of hyperthermia in genotoxicity and radiosensitization, the induction of chromosomal aberrations was examined by premature chromosome condensation and fluorescence in situ hybridisation (PCC-FISH), and cell survival was determined by clonogenic assay shortly (0-1 h) and 24 h following exposure to hyperthermia in combination with ionizing radiation. Prior to exposure to 4 Gy γ-irradiation, confluent cultures of SW‑1573 (human lung carcinoma) and RKO (human colorectal carcinoma) cells were exposed to mild hyperthermia (1 h, 41˚C). At 1 h, the frequency of chromosomal translocations was higher following combined exposure than following exposure to irradiation alone. At 24 h, the number of translocations following combined exposure was lower than following exposure to irradiation only, and was also lower than at 1 h following combined exposure. These dynamics in translocation frequency can be explained by the hyperthermia-induced transient reduction of BRCA2 observed in both cell lines. In both cell lines exposed to radiation only, potentially lethal damage repair (PLDR) correlated with a decreased number of chromosomal fragments at 24 h compared to 1 h. With combined exposure, PLDR did not correlate with a decrease in fragments, as in the RKO cells at 24 h following combined exposure, the frequency of fragments remained at the level found after 1 h of exposure and was also significantly higher than that found following exposure to radiation alone. This was not observed in the SW‑1573 cells. Cell survival experiments demonstrated that exposure to hyperthermia radiosensitized the RKO cells, but not the SW‑1573 cells. This radiosensitization was at least partly due to the induction

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

    NASA Technical Reports Server (NTRS)

    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

  14. Structural chromosome aberrations in lymphocytes from children previously treated for Wilms' tumor or Hodgkin's disease

    SciTech Connect

    Brogger, A.; Kolmannskog, S.; Nicolaysen, R.B.; Wesenberg, F.; Nygaard, R. )

    1989-01-01

    Nineteen children treated for Wilms' tumor (thirteen cases) or Hodgkin's disease (six cases) with cytostatic agents and/or radiotherapy were studied cytogenetically on lymphocytes cultivated from blood samples drawn after at least 1 year of complete remission after end of therapy. A reference group of children was matched for age, sex, and residence. The frequencies of sister chromatid exchange (5.4 versus 5.6 SCE/cell), and chromosome damage type gaps (6.6 versus 7.1%) and breaks (1.9 versus 1.9%) were not different in the two groups, but exchange type aberrations were more frequent in the patients (0.9 versus 0.06%). Fifty karyotypes were analyzed in all but two cases of Hodgkin's disease. The overall frequency of stable (3.1 versus 3.8%) and unstable (1.7 versus 1.4%) structural chromosome changes such as translocations, deletions, chromatid exchanges, and dicentrics were not different in the patient and the control groups. If the chromosome data reflect a general cancer risk, this risk cannot be considerably higher among the cancer-treated children.

  15. Chromosome aberrations in peripheral blood lymphocytes of welders and characterization of their exposure by biological samples analysis

    SciTech Connect

    Elias, Z.; Mur, J.M.; Pierre, F.; Gilgenkrantz, S.; Schneider, O.; Baruthio, F.; Daniere, M.C.; Fontana, J.M.

    1989-05-01

    Chromosomal aberrations in cultured lymphocytes obtained from 55 welders and 55 matched controls were analyzed. Depending on the welding techniques and the nature of the consumables and metals welded, three separate groups of welders were examined. Chromium, nickel, and manganese levels in serum and urine were measured to assess the exposure to welding fumes. A statistically significant increase of chromosomal aberrations was found in one of the three analyzed groups of welders. This group used the semi-automatic metal active gas welding process with cored wire containing nickel for welding mild steel. These welders had significantly higher concentrations of serum and urine manganese and, unlike the other welders, significantly elevated concentrations of nickel, both in serum and urine. However, no significant correlations between nickel or manganese levels and the frequency of chromosomal aberrations were found. There was a significant correlation between the length of welding employment of these welders and the frequency of chromosomal breaks, although there was no significant correlation between age and the frequency of chromosomal aberrations. The other two groups of welders, for which the analyses of biologic fluids proved chromium and manganese exposure, had no statistically significant higher frequency of chromosomal aberrations. One of these groups used the manual metal arc welding process with coated electrodes for welding mainly mild steel and the other group used the tungsten inert gas welding process for welding stainless steel. A significant correlation between the daily amount of cigarettes smoked and the frequency of chromosomal breakages, in controls as in welders, was observed. The present data indicate that certain welding processes may generate fumes that seem to have a clastogenic activity.

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

    NASA Technical Reports Server (NTRS)

    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.

  17. Quercetin induces structural chromosomal aberrations and uncommon rearrangements in bovine cells transformed by the E7 protein of bovine papillomavirus type 4.

    PubMed

    Leal, A M; Ferraz, O P; Carvalho, C; Freitas, A C; Beniston, R G; Beçak, W; Campo, M S; Stocco dos Santos, R C

    2003-03-01

    Bovine papillomavirus type 4 (BPV-4) and bracken fern are cofactors in the carcinogenesis of the upper gastrointestinal (GI) tract of cattle. An experimental in vitro model system has been developed to analyse the co-operation between the viral transforming protein E7, the cellular ras oncogene and quercetin, one of the mutagens of bracken fern, during neoplastic progression of primary bovine cells. We now report cytogenetic studies of these cells at different stages of malignant transformation: parental primary non-transformed PalF cells; E7R cells transformed by BPV-4 E7 and activated ras but not tumorigenic, and tumorigenic E7Q cells derived from E7R cells after treatment with quercetin. All cell lines presented increased numbers of aneuploid cells. The rate of structural chromosomal aberrations observed was increased in transformed cells. In addition, E7Q cells showed chromosomes with peculiar rearrangements, which resulted in metacentric and submetacentric marker chromosomes, with an increase in the mean chromosome arm number. These markers were the products of possible centric fusions. These aberrations and rearrangements were distributed throughout the karyotype, no specific chromosome was involved and the heterochromatic centromeric regions appeared to be preserved. PMID:19379326

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed Central

    2011-01-01

    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, 14.7 ± 5.1, 15.3 ± 5.9 and

  20. Maize chromosome and chromosome segment additions to oat including new B73 and Mo17 addition lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oat-maize addition (OMA) lines with one, or occasionally more, chromosomes of maize (Zea mays L., 2n=2x=20) added to oat (Avena sativa L., 2n=6x=42) can be developed from oat x maize crosses. Self-fertile disomic addition lines for maize chromosomes 1, 2, 3, 4, 5, 6, 7, 9, short arm of 10, and a mon...

  1. Variation in sensitivity to. gamma. -ray-induced chromosomal aberrations during the mitotic cycle of the sea urchin egg

    SciTech Connect

    Ejima, Y.; Nakamura, I.; Shiroya, T.

    1982-11-01

    Sea urchin eggs were irradiated with /sup 137/Cs ..gamma.. rays at various stages of the mitotic cycle, and chromosomal aberrations at the first postirradiation mitosis and embryonic abnormalities at later developmental stages were examined. The radiosensitivity of the eggs to both endpoints varied in parallel with the mitotic stage at the time of irradiation, suggesting a possible relationship between chromosomal damage and embryonic abnormalities.

  2. Gender differences in the induction of chromosomal aberrations and gene mutations in rodent germ cells

    SciTech Connect

    Adler, Ilse-Dore; Carere, Angelo; Eichenlaub-Ritter, Ursula

    2007-05-15

    Germ cell mutagenicity testing provides experimental data to quantify genetic risk for exposed human populations. The majority of tests are performed with exposure of males, and female data are relatively rare. The reason for this paucity lies in the differences between male and female germ cell biology. Male germ cells are produced throughout reproductive life and all developmental stages can be ascertained by appropriate breeding schemes. In contrast, the female germ cell pool is limited, meiosis begins during embryogenesis and oocytes are arrested over long periods of time until maturation processes start for small numbers of oocytes during the oestrus cycle in mature females. The literature data are reviewed to point out possible gender differences of germ cells to exogenous agents such as chemicals or ionizing radiation. From the limited information, it can be concluded that male germ cells are more sensitive than female germ cells to the induction of chromosomal aberrations and gene mutations. However, exceptions are described which shed doubt on the extrapolation of experimental data from male rodents to the genetic risk of the human population. Furthermore, the female genome may be more sensitive to mutation induction during peri-conceptional stages compared to the male genome of the zygote. With few exceptions, germ cell experiments have been carried out under high acute exposure to optimize the effects and to compensate for the limited sample size in animal experiments. Human exposure to environmental agents, on the other hand, is usually chronic and involves low doses. Under these conditions, gender differences may become apparent that have not been studied so far. Additionally, data are reviewed that suggest a false impression of safety when responses are negative under high acute exposure of male rodents while a mutational response is induced by low chronic exposure. The classical (morphological) germ cell mutation tests are not performed anymore

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

    PubMed

    Rossner, Pavel; Rossnerova, Andrea; Beskid, Olena; Tabashidze, Nana; Libalova, Helena; Uhlirova, Katerina; Topinka, Jan; Sram, Radim J

    2014-01-01

    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 <2.5μm (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 24h with the following concentrations of tested chemicals: B[a]P: 1μM, 10μM, 25μM; EOMs: 1μg/ml, 10μg/ml, 25μg/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 25μM 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 NHEJ after treatment of human embryonic lung fibroblasts with B[a]P and complex mixtures containing PAHs. PMID:24694657

  4. [Chromosomal aberrations and genetic polymorphism in genes of the xenobiotic detoxification and DNA repair enzymes in thermoelectric power plant employers].

    PubMed

    Savchenko, Ia A; Minina, V I; Bakanova, M L

    2012-01-01

    The results of the investigation of the interrelationship between frequency of chromosomal aberrations and detoxification enzymes (GSTM1, GSTT1) and DNA repair (hOGG1, XPD) genes in the employees of fuel energy complex in Kemerovo are presented In the group of the workers frequency of metaphases with aberrations (3,9 +/- 0,2%: n = 288) was shown to be significantly higher than in the comparison group (2,1 0, 2%: n = +/- 141). In the group of workers and control donors statistically significant differences were revealed in the frequency of distribution of the GSTT1 and hOGG1 genes. The level of chromosomal aberrations was established to be higher in patients with GSTM1 genotype "0/0" in the group of control donors. PMID:23458003

  5. The DrosDel collection: a set of P-element insertions for generating custom chromosomal aberrations in Drosophila melanogaster.

    PubMed

    Ryder, Edward; Blows, Fiona; Ashburner, Michael; Bautista-Llacer, Rosa; Coulson, Darin; Drummond, Jenny; Webster, Jane; Gubb, David; Gunton, Nicola; Johnson, Glynnis; O'Kane, Cahir J; Huen, David; Sharma, Punita; Asztalos, Zoltan; Baisch, Heiko; Schulze, Janet; Kube, Maria; Kittlaus, Kathrin; Reuter, Gunter; Maroy, Peter; Szidonya, Janos; Rasmuson-Lestander, Asa; Ekström, Karin; Dickson, Barry; Hugentobler, Christoph; Stocker, Hugo; Hafen, Ernst; Lepesant, Jean Antoine; Pflugfelder, Gert; Heisenberg, Martin; Mechler, Bernard; Serras, Florenci; Corominas, Montserrat; Schneuwly, Stephan; Preat, Thomas; Roote, John; Russell, Steven

    2004-06-01

    We describe a collection of P-element insertions that have considerable utility for generating custom chromosomal aberrations in Drosophila melanogaster. We have mobilized a pair of engineered P elements, p[RS3] and p[RS5], to collect 3243 lines unambiguously mapped to the Drosophila genome sequence. The collection contains, on average, an element every 35 kb. We demonstrate the utility of the collection for generating custom chromosomal deletions that have their end points mapped, with base-pair resolution, to the genome sequence. The collection was generated in an isogenic strain, thus affording a uniform background for screens where sensitivity to genetic background is high. The entire collection, along with a computational and genetic toolbox for designing and generating custom deletions, is publicly available. Using the collection it is theoretically possible to generate >12,000 deletions between 1 bp and 1 Mb in size by simple eye color selection. In addition, a further 37,000 deletions, selectable by molecular screening, may be generated. We are now using the collection to generate a second-generation deficiency kit that is precisely mapped to the genome sequence. PMID:15238529

  6. Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans.

    PubMed

    Försti, Asta; Frank, Christoph; Smolkova, Bozena; Kazimirova, Alena; Barancokova, Magdalena; Vymetalkova, Veronika; Kroupa, Michal; Naccarati, Alessio; Vodickova, Ludmila; Buchancova, Janka; Dusinska, Maria; Musak, Ludovit; Vodicka, Pavel; Hemminki, Kari

    2016-10-01

    Non-specific chromosomal aberrations (CAs) are microscopically detected in about 1% of lymphocytes drawn from healthy persons. Causes of CAs in general population are not known but they may be related to risk of cancer. In view of the importance of the mitotic checkpoint machinery on maintaining chromosomal integrity we selected 9 variants in main checkpoint related genes (BUB1B, BUB3, MAD2L1, CENPF, ESPL1/separase, NEK2, PTTG1/securin, ZWILCH and ZWINT) for a genotyping study on samples from healthy individuals (N = 330 to 729) whose lymphocytes had an increased number of CAs compared to persons with a low number of CAs. Genetic variation in individual genes played a minor importance, consistent with the high conservation and selection pressure of the checkpoint system. However, gene pairs were significantly associated with CAs: PTTG1-ZWILCH and PTTG1-ZWINT. MAD2L1 and PTTG1 were the most common partners in any of the two-way interactions. The results suggest that interactions at the level of cohesin (PTTG1) and kinetochore function (ZWINT, ZWILCH and MAD2L1) contribute to the frequency of CAs, suggesting that gene variants at different checkpoint functions appeared to be required for the formation of CAs. PMID:27424524

  7. Cadmium chloride strongly enhances cyclophosphamide-induced chromosome aberrations in mouse bone marrow cells

    SciTech Connect

    Pandurangarao, V.L.; Blazina, S.; Bherje, R.

    1997-10-01

    Earlier we reported that a single 5 mg cadmium chloride (CdCl{sub 2})/kg ip dose enhanced chromosome aberrations (ca) with 50 mg/kg cyclophosphamide (CP) in mouse bone marrow cells. In this report groups of 4 mice were injected ip with saline, 0.31, 0.62, 1.25, 2.5 or 5.0 mg/kg CdCl{sub 2}, followed by saline injections at 24 h. Other mice similarly uninjected at 0 h were injected with 50 mg/kg CP at 24 h. All the mice were injected ip with 4 mg colchicine/kg at 44 h. At 48 h the bone marrow cells were processed for chromosome spreads. After dissection, visual examination revealed obvious internal hemorrhaging of the testes at 1.25 CdCl{sub 2} mg/kg and higher doses. This effect was not further increased by CP treatment. The lowest ca enhancing dose of CdCl{sub 2} on CP was 0.625 mg/kg. Our hypothesis is that Cd replaces zinc presents in numerous DNA repair enzymes and proteins resulting in diminished repair. Subsequently, the excess of unrepaired DNA damage is seen as chromatid breaks, deletions, fragments and exchanges.

  8. Biomarker for Space Radiation Risk: Painting Analysis of Chromosome Aberrations Induced by Energetic Heavy Ions in Human Cells

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

    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. Over the years, we have studied chromosomal damage in human fibroblast, epithelia and lymphocyte cells exposed in vitro to energetic charged particles generated at several accelerator facilities in the world. We have also studied chromosome aberrations in astronaut s peripheral blood lymphocytes before and after space flight. Various fluorescence in situ hybridization painting techniques have been used to identify from only the telomere region of the chromosome to every chromosome in a human cell. We will summarize the results of the investigations, and discuss the unique radiation signatures and biomarkers for space radiation exposure.

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

    SciTech Connect

    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.

  10. Generalized time-dependent model of radiation-induced chromosomal aberrations in normal and repair-deficient human cells.

    PubMed

    Ponomarev, Artem L; George, Kerry; Cucinotta, Francis A

    2014-03-01

    We have developed a model that can simulate the yield of radiation-induced chromosomal aberrations (CAs) and unrejoined chromosome breaks in normal and repair-deficient cells. The model predicts the kinetics of chromosomal aberration formation after exposure in the G₀/G₁ phase of the cell cycle to either low- or high-LET radiation. A previously formulated model based on a stochastic Monte Carlo approach was updated to consider the time dependence of DNA double-strand break (DSB) repair (proper or improper), and different cell types were assigned different kinetics of DSB repair. The distribution of the DSB free ends was derived from a mechanistic model that takes into account the structure of chromatin and DSB clustering from high-LET radiation. The kinetics of chromosomal aberration formation were derived from experimental data on DSB repair kinetics in normal and repair-deficient cell lines. We assessed different types of chromosomal aberrations with the focus on simple and complex exchanges, and predicted the DSB rejoining kinetics and misrepair probabilities for different cell types. The results identify major cell-dependent factors, such as a greater yield of chromosome misrepair in ataxia telangiectasia (AT) cells and slower rejoining in Nijmegen (NBS) cells relative to the wild-type. The model's predictions suggest that two mechanisms could exist for the inefficiency of DSB repair in AT and NBS cells, one that depends on the overall speed of joining (either proper or improper) of DNA broken ends, and another that depends on geometric factors, such as the Euclidian distance between DNA broken ends, which influences the relative frequency of misrepair. PMID:24611656

  11. Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrow in patients treated for cancer of the cervix

    SciTech Connect

    Kleinerman, R.A.; Littlefield, L.G.; Tarone, R.E.; Machado, S.G.; Blettner, M.; Peters, L.J.; Boice, J.D. Jr. )

    1989-07-01

    An international study of cervical cancer patients reported a doubling of the risk for leukemia following radiotherapy. To evaluate the extent of residual chromosome damage in circulating T-cell lymphocytes in this population, approximately 200 metaphases were examined from each of 96 irradiated and 26 nonirradiated cervical cancer patients treated more than 17 years ago (average 23 years). Radiation dose averaged over the total red bone marrow was estimated to be 8.1 Gy. The type and frequency of stable and unstable chromosome aberrations were quantified in 24,117 metaphases. Unstable aberrations did not differ significantly between irradiated and nonirradiated patients (P greater than 0.5). Stable aberrations (i.e., translocations, inversions, or chromosomes with deleted segments), however, were significantly higher among irradiated (2.8 per 100 cells) compared to nonirradiated (0.7 per 100 cells) women (P less than 10(4)). The frequency of these stable aberrations was found to increase significantly with increasing dose to the bone marrow. These data indicate that a direct relationship between radiation dose and extent of damage to somatic cells persists in populations and can be detected many years after partial-body radiation exposure. The stable aberration rate in irradiated cervical cancer patients was 50 to 75% lower than those observed 25 years or more after radiation exposure in atomic bomb survivors and in ankylosing spondylitis patients treated with radiotherapy. The average marrow dose was only 1 Gy in the examined atomic bomb survivors and 3.5 Gy in the ankylosing spondylitis patients. It appears, then, that a very high dose delivered to the pelvic cavity in fractionated doses resulted in far fewer persistent stable aberrations than lower doses delivered either in acute whole-body exposure or in fractionated doses to the spinal column and sacroiliac joints.

  12. Chromosome aberrations induced in human lymphocytes after partial-body irradiation

    SciTech Connect

    Fong, L.; Lai-Lei Ting; Po-Ming Wang

    1995-10-01

    Chromosomal aberrations in peripheral blood lymphocytes obtained from two patients before and after they received one fraction of partial-body irradiation for palliative treatment were analyzed. Blood samples were taken 30 min and 24 h after radiation treatment. The yield of dicentrics obtained from case A 30 min after a partial-body (about 21%) treatment with 8 Gy was 0.066/cell, while the yield obtained 24 h radiation treatment was 0.071/cell. The fraction of irradiated lymphocytes that reached metaphase at 52 h was 0.08 as evaluated by mixing cultures of in vitro irradiated and unirradiated blood. The yield of dicentrics for blood from case B 30 min after 6 Gy partial-body (about 24%) irradiation was 0.655/cell, while the yield 24 h after irradiation was 0.605/cell. The fraction of irradiated cells was 0.29. Estimation of doses and irradiated fractions for the two cases using the method proposed by Dolphin and the Qdr method is discussed. Although there was no significant difference between the mean yields of dicentrics per cell obtained 30 min and 24 h after radiation treatment, the data obtained at 24 h seemed more useful for the purpose of dose estimation. When a higher dose (8 Gy) was delivered to a smaller percentage of the body, underestimation of the dose was encountered. 18 refs., 4 tabs.

  13. Chromosome aberration and sister chromatid exchange test results with 42 chemicals.

    PubMed

    Anderson, B E; Zeiger, E; Shelby, M D; Resnick, M A; Gulati, D K; Ivett, J L; Loveday, K S

    1990-01-01

    Forty-two chemicals were tested for their ability to induce cytogenetic change in Chinese hamster ovary cells using assays for chromosome aberrations (ABS) and sister chromatid exchanges (SCE). These chemicals were included in the National Toxicology Program's evaluation of the ability of four in vitro short-term genetic toxicity assays to distinguish between rodent carcinogens and noncarcinogens. The conclusions of this comparison are presented in Zeiger et al. [Zeiger E, Haseman JK, Shelby MD, Margolin BH, Tennant RW (1990): [Environ Molec Mutagen 16(Suppl 18): 1-14]. The in vitro cytogenetic testing was conducted at four laboratories, each using a standard protocol to evaluate coded chemicals with and without exogenous metabolic activation. Most chemicals were tested in a single laboratory; however, two chemicals, tribromomethane and p-chloroaniline, were tested at two laboratories as part of an interlaboratory comparison. Four chemicals (C.I. basic red 9 HCl, 2-mercaptobenzothiazole, oxytetracycline HCl, and rotenone) were tested for SCE in one laboratory and in a different laboratory for ABS. Tetrakis(hydroxymethyl)phosphonium sulfate was tested at one laboratory and the chloride form was tested at a different laboratory. Twenty-five of the 42 chemicals tested induced SCE. Sixteen of these also induced ABS; all chemicals that induced ABS also induced SCE. There was approximately 79% reproducibility of results in repeat tests, thus, we conclude that this protocol is effective and reproducible in detecting ABS and SCE. PMID:2091924

  14. Chromosome aberrations produced by radiation: The relationship between excess acentric fragments and dicentrics

    SciTech Connect

    Hahnfeldt, P.; Hlatky, L.R.; Brenner, D.J.; Sachs, R.K.

    1995-02-01

    Most chromosome aberrations produced by ionizing radiation develop from DNA double-strand breaks (DSBs). Published date on the yield and variance of excess acentric fragments after in vitro irradiation of human lymphocytes were compared with corresponding data on dicentrics. At low LET the number of excess acentric fragments is about 60% of the number of dicentrics, independent of dose and perhaps of dose rate, suggesting that dicentrics and excess acentric fragments arise from similar kinetics rather than from fundamentally different reactions. Only a weak dependence of the ratio on LET is observed. These results are quantified using generalizations of models for pairwise DSB interactions suggested by Brewen and Brock based on data for marsupial cells. By allowing singly incomplete and some {open_quotes}doubly incomplete{close_quotes} exchanges, the models can also account for the experimental observation that the dispersion for excess acentric fragments, a measure of cell-to-cell variance, is systematically larger than the dispersion for dicentrics. Numerical estimates of an incompleteness parameter are derived. 47 refs., 8 figs., 4 tabs.

  15. Organic-solvent extraction of model biomaterials for use in the in vitro chromosome aberration test.

    PubMed

    Matsuoka, Atsuko; Haishima, Yuji; Hasegawa, Chie; Matsuda, Yoshie; Tsuchiya, Toshie

    2008-07-01

    We prepared polyurethane (PU) containing 0.4% or 4% 4,4'-methylenedianiline (MDA) as model materials to investigate the effectiveness of sample preparation by organic-solvent extraction for the in vitro chromosome aberration (CA) test. MDA itself (0.4 mg/mL) was positive only in the presence of an exogenous metabolizing system (S9 mix). The culture medium extract of PU containing 4% MDA (PU/4% MDA) was negative with and without S9 mix. Methanol and acetone extracts, on the other hand, induced structural CAs without S9 mix, which we did not expect because MDA requires S9 mix for activity. On chemical analysis, however, we found that the ratio of MDA extracted by the organic solvents to that extracted by the culture medium of PU/4% MDA was about 15:1. Interestingly, oligomers consisting of poly(tetramethyleneglycol) derivatives (OTMG) were also extracted by the organic solvents. The data suggest that the induction of structural CAs in the absence of S9 mix may have been partly due to synergism of MDA and OTMG. CA tests of MDA and PTMG-1000 in combination confirmed that to be the case. Thus, organic-solvent extraction may be more effective than medium extraction in evaluating the biological safety of biomaterials. Detailed chemical analysis of extracts was performed. PMID:17941025

  16. Chromosome aberrations as a means to determine occupational exposure: an alternative

    SciTech Connect

    Sullivan, C.A.

    1980-09-01

    The methodology developed to study chromosome aberrations in vitro, and the results gained in application of the method in in vivo studies of individuals receiving ionizing radiation, may provide a basis to more definitively assess occupational exposure in radiographers and radiation therapy technologists. The need for more definitive methods in measuring occupational exposure is given impetus by the fact that there is now a large group of individuals in whom a significant duration of occupational exposure may be measured. Further, increased knowledge of the effects of radiation has resulted in lower and lower levels of maximum permissible dose. And there is the undeniable, albeit relatively unproven, claim of radiation hazard in occupations not previously considered. As a group, technologists are now better organized and more aware of occupational hazards than in the past. It behooves us as professionals to act in our own behalf to improve the state of knowledge and methods of evaluation of occupational hazards that we have endured for several decades. There is no longer any more time to waste in the light of what we now know. In the author's opinion, the method described herein has the potential to determine occupational dose more accurately and definitively than has been possible heretofore and, therefore, should be tested as an alternative to present methods of personnel monitoring. History, rationale, and method are presented, and a protocol for a research study is described.

  17. The effects of boric acid on sister chromatid exchanges and chromosome aberrations in cultured human lymphocytes

    PubMed Central

    Arslan, Mehmet; Topaktas, Mehmet

    2007-01-01

    The aim of this study was to determine the possible genotoxic effects of boric acid (BA) (E284), which is used as an antimicrobial agent in food, by using sister chromatid exchange (SCEs) and chromosome aberration (CAs) tests in human peripheral lymphocytes. The human lymphocytes were treated with 400, 600, 800, and 1000 μg/mL concentrations of BA dissolved in dimethyl sulfoxide (DMSO), for 24 h and 48 h treatment periods. BA did not increase the SCEs for all the concentrations and treatment periods when compared to control and solvent control (DMSO). BA induced structural and total CAs at all the tested concentrations for 24 and 48 h treatment periods. The induction of the total CAs was dose dependent for the 24 h treatment period. However, BA did not cause numerical CAs. BA showed a cytotoxic effect by decreasing the replication index (RI) and mitotic index (MI). BA decreased the MI in a dose-dependent manner for the 24 h treatment period. PMID:19002846

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

    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. PMID:12539753

  20. Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

    PubMed Central

    Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

    2013-01-01

    Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. This trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374. PMID:23065509

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    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/cm 2 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.

  3. Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions

    DOEpatents

    Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.

    1998-01-01

    A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration.

  4. Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions

    DOEpatents

    Lucas, J.N.; Straume, T.; Bogen, K.T.

    1998-03-24

    A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration. 14 figs.

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

    NASA Astrophysics Data System (ADS)

    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.

  6. In vitro irradiation of blood with 99mTc: evaluation of dose and chromosome aberrations in irradiated lymphocytes.

    PubMed

    Amaral, A; Colas-Linhart, N; Stabin, M; Petiet, A; Guiraud-Vitaux, F; Jacquet, N

    2001-05-01

    The use of ionizing radiation for diagnostic or therapeutic purposes in medicine represents the principal source of artificial radiation to humans. Calculation of radiation dose is essential to the analysis of risks (biological effects) and benefits in any application, including nuclear medicine. The dose assessment in many cases is not necessarily straightforward. Many radiopharmaceuticals are labelled with radionuclides that undergo not only gamma-emission but also emission of Auger and internal conversion electrons. A typical example is technetium-99m (99mTc), which is used in more than 80% of nuclear medicine applications. In this work, in vitro studies have been carried out to evaluate the dose delivered to lymphocytes by human serum albumin microspheres (HSAM) labelled with 99mTc. Experiments were performed in order to score unstable chromosomal aberrations induced by 99mTc-HSAM, using conventional cytogenetic techniques. Henceforth, the relationship between activities introduced into blood samples and induced chromosomal aberrations were evaluated. To assess the dose absorbed in lymphocytes, electron and photon transport was performed in a simple model representing the system used for irradiating the cells using the MCNP Monte Carlo code. In this report, analysis of dose-effect curve demonstrates a linear quadratic response for unstable chromosome aberrations. PMID:11441962

  7. Allium cepa chromosome aberration and micronucleus tests applied to study genotoxicity of extracts from pesticide-treated vegetables and grapes.

    PubMed

    Feretti, D; Zerbini, I; Zani, C; Ceretti, E; Moretti, M; Monarca, S

    2007-06-01

    The Allium cepa assay is an efficient test for chemical screening and in situ monitoring for genotoxicity of environmental contaminants. The test has been used widely to study genotoxicity of many pesticides revealing that these compounds can induce chromosomal aberrations in root meristems of A. cepa. Pesticide residues can be present in fruit and vegetables and represent a risk for human health. The mutagenic and carcinogenic action of herbicides, insecticides and fungicides on experimental animals is well known. Several studies have shown that chronic exposure to low levels of pesticides can cause birth defects and that prenatal exposure is associated with carcinogenicity. This study evaluated the potential application of plant genotoxicity tests for monitoring mutagens in edible vegetables. The presence of pesticides and genotoxic compounds extracted from 21 treated vegetables and eight types of grapes sampled from several markets in Campania, a region in Southern Italy, was monitored concurrently. The extracts were analysed for pesticides by gas chromatography and high-performance liquid chromatography, and for genotoxicity using two plant tests: the micronucleus test and the chromosomal aberration test in A. cepa roots. Thirty-three pesticides were detected, some of which are not approved. Genotoxicity was found in some of the vegetables and grapes tested. Allium cepa tests proved to be sensitive in monitoring genotoxicity in food extracts. The micronucleus test in interphase cells gave a much higher mutagenicity than the chromosomal aberration test in anaphase-telophase cells. PMID:17487597

  8. Choice of model and uncertainties of the gamma-ray and neutron dosimetry in relation to the chromosome aberrations data in Hiroshima and Nagasaki.

    PubMed

    Rühm, W; Walsh, L; Chomentowski, M

    2003-07-01

    Chromosome data pertaining to blood samples from 1,703 survivors of the Hiroshima and Nagasaki A-bombs, were utilized and different models for chromosome aberration dose response investigated. Models applied included those linear or linear-quadratic in equivalent dose. Models in which neutron and gamma doses were treated separately (LQ-L model) were also used, which included either the use of a low-dose limiting value for the relative biological effectiveness (RBE) of neutrons of R(0)=70+/-10 or an RBE value of R(1)=15+/-5 at 1 Gy. The use of R(1) incorporates the assumption that it is much better known than R(0), with much less associated uncertainty. In addition, error-reducing transformations were included which were found to result in a 50% reduction of the standard error associated with one of the model fit parameters which is associated with the proportion of cells with at least one aberration, at 1 Gy gamma dose. Several justifiable modifications to the DS86 doses according to recent nuclear retrospective dosimetry measurements were also investigated. Gamma-dose modifications were based on published thermoluminescence measurements of quartz samples from Hiroshima and on a tentative reduction for Nagasaki factory worker candidates by a factor of 0.6. Neutron doses in Hiroshima were modified to become consistent with recent fast neutron activation data based on copper samples. The applied dose modifications result in an increase in non-linearity of the dose-response curve for Hiroshima, and a corresponding decrease in that for Nagasaki, an effect found to be most pronounced for the LQ-L models investigated. As a result the difference in the dose-response curves observed for both cities based on DS86 doses, is somewhat reduced but cannot be entirely explained by the dose modifications applied. The extent to which the neutrons contribute to chromosome aberration induction in Hiroshima depends significantly on the model used. The LQ-L model including an R(1

  9. Role of quercetin on mitomycin C induced genotoxicity: analysis of micronucleus and chromosome aberrations in vivo.

    PubMed

    Mazumdar, Mehnaz; Giri, Sarbani; Giri, Anirudha

    2011-04-01

    Quercetin, a flavonol group of plant flavonoid, has generated immense interest because of its potential antioxidant, anti-proliferative, chemoprotective, anti-inflammatory and gene expression modulating properties. However, the pro-oxidant chemistry of quercetin is important as it is related to the generation of mutagenic quinone-type metabolites. In the present study, 25mg/kg, 50mg/kg and 100mg/kg of quercetin given through the intra peritoneal (i.p.) route induced 2.31 ± 0.27%, 4.72 ± 0.58% and 6.38 ± 0.68% (control value=0.67 ± 0.30%) respectively, of cells with micronucleus (MN) in polychromatic erythrocytes in bone marrow cells and 10.93 ± 0.98%, 10.00 ± 0.89% and 14.27 ± 3.94% (control 2.61 ± 0.48) of cells with chromosome aberrations (CA) following 24h of the treatments. Higher frequencies of MN and CA were also observed after 48h of the treatments. To verify the effect of route of treatment on the quercetin induced damage, 100mg/kg b.w. was given through oral route which declined frequency of MN (P<0.001) as well as CA (P<0.05) as compared to the i.p. route for the same dose. Quercetin also induced higher frequency of metaphases with sticky chromosomes and C-mitosis. Pre-treatment with quercetin significantly reduced the frequency of mitomycin C (MMC) induced MN as well as CA, but no clear correlation between the dose and effect could be observed. Further studies are required to elucidate the possible interaction of quercetin with DNA as well as with other DNA damaging agents like MMC in vivo. The protective action of quercetin was not enhanced when given orally. Our findings suggest that quercetin may result in genomic instability in the tested dose range and significant reduction in MMC induced genotoxicity in the highest dose tested. These effects of quercetin are to be taken into consideration while evaluating the possible use of quercetin as a therapeutic agent. PMID:21256974

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

    PubMed Central

    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

  11. Chromosome aberration assays in Allium. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

    PubMed

    Grant, W F

    1982-11-01

    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 the clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction (i.e., causing chromosome aberrations), 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. PMID:7177154

  12. Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde.

    PubMed

    Costa, Solange; Carvalho, Sandra; Costa, Carla; Coelho, Patrícia; Silva, Susana; Santos, Luís S; Gaspar, Jorge F; Porto, Beatriz; Laffon, Blanca; Teixeira, João P

    2015-07-01

    Formaldehyde (FA) is a commonly used chemical in anatomy and pathology laboratories as a tissue preservative and fixative. Because of its sensitising properties, irritating effects and cancer implication, FA accounts probably for the most important chemical-exposure hazard concerning this professional group. Evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting, particularly in regard to the ability of inhaled FA to induce toxicity on other cells besides first contact tissues, such as buccal and nasal cells. To evaluate the effects of exposure to FA in human peripheral blood lymphocytes, a group of 84 anatomy pathology laboratory workers exposed occupationally to FA and 87 control subjects were tested for chromosomal aberrations (CAs) and DNA damage (comet assay). The level of exposure to FA in the workplace air was evaluated. The association between genotoxicity biomarkers and polymorphic genes of xenobiotic-metabolising and DNA repair enzymes were also assessed. The estimated mean level of FA exposure was 0.38±0.03 ppm. All cytogenetic endpoints assessed by CAs test and comet assay % tail DNA (%TDNA) were significantly higher in FA-exposed workers compared with controls. Regarding the effect of susceptibility biomarkers, results suggest that polymorphisms in CYP2E1 and GSTP1 metabolic genes, as well as, XRCC1 and PARP1 polymorphic genes involved in DNA repair pathways are associated with higher genetic damage in FA-exposed subjects. Data obtained in this study show a potential health risk situation of anatomy pathology laboratory workers exposed to FA (0.38 ppm). Implementation of security and hygiene measures may be crucial to decrease risk. The obtained information may also provide new important data to be used by health care programs and by governmental agencies responsible for occupational health and safety. PMID:25711496

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

    PubMed

    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. PMID:27169375

  14. Comparison of chromosome aberration frequencies in pre- and post-flight astronaut lymphocytes irradiated in vitro with gamma rays

    NASA Technical Reports Server (NTRS)

    Wu, H.; George, K.; Willingham, V.; Cucinotta, F. A.

    2001-01-01

    If radiosensitivity is altered in a microgravity environment, it will affect the accuracy of assessing astronauts' risk from exposure to space radiation. To investigate the effects of space flight on radiosensitivity, we exposed a crewmember's blood to gamma rays at doses ranging from 0 to 3 Gy and analyzed chromosome aberrations in mitotic lymphocytes. The blood samples were collected 10 days prior to an 8-day Shuttle mission, the day the flight returned, and 14 days after the flight. After exposure, lymphocytes were stimulated to grow in media containing phytohaemagglutinin (PHA) and mitotic cells were harvested for chromosome analysis using a fluorescence in situ hybridization (FISH) with whole chromosome specific probes. The dose response of total exchanges showed no changes in the radiosensitivity after the mission.

  15. Genomic copy number analysis of a spectrum of blue nevi identifies recurrent aberrations of entire chromosomal arms in melanoma ex blue nevus.

    PubMed

    Chan, May P; Andea, Aleodor A; Harms, Paul W; Durham, Alison B; Patel, Rajiv M; Wang, Min; Robichaud, Patrick; Fisher, Gary J; Johnson, Timothy M; Fullen, Douglas R

    2016-03-01

    Blue nevi may display significant atypia or undergo malignant transformation. Morphologic diagnosis of this spectrum of lesions is notoriously difficult, and molecular tools are increasingly used to improve diagnostic accuracy. We studied copy number aberrations in a cohort of cellular blue nevi, atypical cellular blue nevi, and melanomas ex blue nevi using Affymetrix's OncoScan platform. Cases with sufficient DNA were analyzed for GNAQ, GNA11, and HRAS mutations. Copy number aberrations were detected in 0 of 5 (0%) cellular blue nevi, 3 of 12 (25%) atypical cellular blue nevi, and 6 of 9 (67%) melanomas ex blue nevi. None of the atypical cellular blue nevi displayed more than one aberration, whereas complex aberrations involving four or more regions were seen exclusively in melanomas ex blue nevi. Gains and losses of entire chromosomal arms were identified in four of five melanomas ex blue nevi with copy number aberrations. In particular, gains of 1q, 4p, 6p, and 8q, and losses of 1p and 4q were each found in at least two melanomas. Whole chromosome aberrations were also common, and represented the sole finding in one atypical cellular blue nevus. When seen in melanomas, however, whole chromosome aberrations were invariably accompanied by partial aberrations of other chromosomes. Three melanomas ex blue nevi harbored aberrations, which were absent or negligible in their precursor components, suggesting progression in tumor biology. Gene mutations involving GNAQ and GNA11 were each detected in two of eight melanomas ex blue nevi. In conclusion, copy number aberrations are more common and often complex in melanomas ex blue nevi compared with cellular and atypical cellular blue nevi. Identification of recurrent gains and losses of entire chromosomal arms in melanomas ex blue nevi suggests that development of new probes targeting these regions may improve detection and risk stratification of these lesions. PMID:26743478

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

    NASA Technical Reports Server (NTRS)

    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.

  17. Comparison of cell repair mechanisms by means of chromosomal aberration induced by proton and gamma irradiation - preliminary results

    NASA Astrophysics Data System (ADS)

    Kowalska, A.; Czerski, K.; Kaczmarski, M.; Lewocki, M.; Masojć, B.; Łukowiak, A.

    2015-03-01

    DNA damage of peripheral blood lymphocytes exposed to gamma and proton irradiation is studied by means of chromosome aberrations to validate the efficiency of the repair mechanisms of individual cells. A new method based on an observed deviation from the Poisson statistics of the chromosome aberration number is applied for estimation of a repair factor ( RF) defined as a ratio between originally damaged cells to the amount of finally observed aberrations. The repair factors are evaluated by studying the variance of individual damage factors in a collective of healthy persons at a given dose as well as by using the chi-square analysis for the dose-effect curves. The blood samples from fifteen donors have been irradiated by Co60 gamma rays and from nine persons by 150 MeV protons with different doses up to 2 Gy. A standard extraction of lymphocyte has been used whereby dicentrics, acentrics and rings have been scored under a microscope. The RF values determined for the proton radiation are slightly larger than for gamma rays, indicating that up to 70% DNA double strand breaks can be repaired.

  18. Effect of copper on morphology, weight, and chromosomal aberrations in the spiny lobster, Panulirus homarus (Linnaeus, 1758).

    PubMed

    Maharajan, A; Vaseeharan, B; Rajalakshmi, S; Vijayakumaran, M; Kumarasamy, P; Chen, J C

    2011-12-01

    Spiny lobster Panulirus homarus which had been exposed to cupric ion at 9.55 and 19.1 μg/l for 28 days was examined for sub-lethal effects including morphology, wet weight, and induced genotoxic effect on the chromosome. Following cupric exposure, the color of lobster P. homarus changed from yellowish-brown to greenish black in the hepatopancreas, changed from normal creamy white to yellowish white in the muscle, and changed to greenish black in the gill. A significant change in the percentage of wet weight of muscle (28.70 ± 0.41-23.47 ± 0.45), hepatopancreas (4.03 ± 0.12-2.63 ± 0.17), and gills (3.63 ± 0.45-3.87 ± 0.12) were observed in the copper-treated lobsters. The diploid number of chromosomes of P. homarus was over 200 metaphases from ten lobsters, as 2n = 58, and consisted of 16 acrocentric, seven metacentric, and six sub-metacentric chromosomes. The lobsters exposed to cupric ion at 9.55 and 19.1 μg/l showed different types of chromosomal aberrations such as centromeric gaps, chromatid breaks, centromeric fusion, stickiness, ring chromosomes, and acrocentric association region. The frequency of aberrations increased with duration of exposure. In conclusion, it was suggested that cupric ion interacts with the spindle formation and consequently distorts the normal karyomorphology, indicating cytogenetic effect on lobster. PMID:21691798

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

    PubMed

    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. PMID:11352763

  20. Effect of hormones on the variation of radiosensitivity in females as measured by induction of chromosomal aberrations.

    PubMed Central

    Roberts, C J; Morgan, G R; Danford, N

    1997-01-01

    The frequency of dicentrics + ring (dic/cell) and total chromosome aberrations (dicentrics, rings and excess acentrics, etc.) per cell (TAb/cell) has been studied in 50 male and female volunteers after high or low dose rate (HDR, LDR) irradiation of peripheral blood lymphocytes. The mean male aberration frequencies per cell after HDR irradiation were 0.38 dic/cell and 0.61 TAb/cell; following LDR irradiation, the mean aberration frequencies were 0.28 dic/cell and 0.45 TAb/cell. Equivalent female values after HDR irradiation were 0.42 dic/cell and 0.71 TAb/cell; after LDR irradiation, the mean aberration frequencies were 0.30 dic/cell and 0.48 TAb/cell. Analysis of variance showed that there was a highly significant difference between males and females have a greater HDR, but not LDR, irradiation It is concluded from this study that females have a greater variability in their radioresponse, and that this variability is related to progesterone, which has a profound effect upon radiosensitivity, as measured by cytogenetic end points. PMID:9467065

  1. Effect of hormones on the variation of radiosensitivity in females as measured by induction of chromosomal aberrations.

    PubMed

    Roberts, C J; Morgan, G R; Danford, N

    1997-12-01

    The frequency of dicentrics + ring (dic/cell) and total chromosome aberrations (dicentrics, rings and excess acentrics, etc.) per cell (TAb/cell) has been studied in 50 male and female volunteers after high or low dose rate (HDR, LDR) irradiation of peripheral blood lymphocytes. The mean male aberration frequencies per cell after HDR irradiation were 0.38 dic/cell and 0.61 TAb/cell; following LDR irradiation, the mean aberration frequencies were 0.28 dic/cell and 0.45 TAb/cell. Equivalent female values after HDR irradiation were 0.42 dic/cell and 0.71 TAb/cell; after LDR irradiation, the mean aberration frequencies were 0.30 dic/cell and 0.48 TAb/cell. Analysis of variance showed that there was a highly significant difference between males and females have a greater HDR, but not LDR, irradiation It is concluded from this study that females have a greater variability in their radioresponse, and that this variability is related to progesterone, which has a profound effect upon radiosensitivity, as measured by cytogenetic end points. PMID:9467065

  2. Report from the working group on the in vivo mammalian bone marrow chromosomal aberration test.

    PubMed

    Tice, R R; Hayashi, M; MacGregor, J T; Anderson, D; Blakey, D H; Holden, H E; Kirsch-Volders, M; Oleson, F B; Pacchierotti, F; Preston, R J

    1994-06-01

    The following summary represents a consensus of the working group, except where noted. The goal of this working group was to identify the minimal requirements needed to conduct a scientifically valid and practical in vivo chromosomal aberration assay. For easy reference, the items discussed are listed in the order in which they appear in OECD guideline 475. Specific disagreement with the current and/or proposed OECD guideline is presented in the text. Introduction, purpose, scope, relevance, application, and limits of test: This test would not be appropriate in situations where there was sufficient evidence to indicate that the test article or reactive metabolites could not reach the bone marrow. Test substances: Solid and liquid test substances should be dissolved, if possible, in water or isotonic saline. If insoluble in water/saline, the test substance should be dissolved or homogeneously suspended in an appropriate vehicle (e.g., vegetable oil). A suspension was not considered suitable for an intravenous injection. The use of dimethyl sulfoxide as an organic solvent was not recommended. The use of any uncommonly used solvent/vehicle should be justified. Freshly prepared solutions or suspensions of the test substance should be employed unless stability data demonstrate the acceptability of storage. Selection of species: Any commonly used rodent species was deemed acceptable but rats or mice were preferred, with no strain preference. Number and sex: A consensus could not be reached as to the requirement for both sexes versus one sex in this assay. It was suggested that a single sex should be used unless pharmacokinetic and/or toxicity data indicated a difference in metabolism and/or sensitivity between males and females. The size of the experiment (i.e., number of cells per animal, number of animals per treatment group) should be based on statistical considerations. Lacking a formal analysis, it was agreed that at least 100 metaphase cells should be scored per

  3. M-BAND Analysis of Chromosome Aberration In Human Epithelial Cells exposed to Gamma-ray and Secondary Neutrons of Low Dose Rate

    NASA Technical Reports Server (NTRS)

    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 with the atmosphere, spacecraft structure and planetary surfaces, contribute to a significant fraction to the dose equivalent in crew members and passengers during commercial aviation travel, and astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility's "30L" beam line 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 spacecraft 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 at an entrance dose rate of 2.5 cGy/hr or gamma-ray at 1.7cGy/hr, and assessed the induction of chromosome aberrations that were identified with mBAND. 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 for gamma-rays and 600 MeV/nucleon Fe ions of high dose rate, the neutron data showed a 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. The low dose rate gamma-rays induced a lower frequency of chromosome aberrations than high dose rate gamma-rays, but the inversion spectrum was similar for the same cytotoxic effect. The distribution of damage sites on chromosome 3 for different radiation types will also be discussed.

  4. Cryptic and Complex Chromosomal Aberrations in Early-Onset Neuropsychiatric Disorders

    PubMed Central

    Brand, Harrison; Pillalamarri, Vamsee; Collins, Ryan L.; Eggert, Stacey; O’Dushlaine, Colm; Braaten, Ellen B.; Stone, Matthew R.; Chambert, Kimberly; Doty, Nathan D.; Hanscom, Carrie; Rosenfeld, Jill A.; Ditmars, Hillary; Blais, Jessica; Mills, Ryan; Lee, Charles; Gusella, James F.; McCarroll, Steven; Smoller, Jordan W.; Talkowski, Michael E.; Doyle, Alysa E.

    2014-01-01

    Structural variation (SV) is a significant component of the genetic etiology of both neurodevelopmental and psychiatric disorders; however, routine guidelines for clinical genetic screening have been established only in the former category. Genome-wide chromosomal microarray (CMA) can detect genomic imbalances such as copy-number variants (CNVs), but balanced chromosomal abnormalities (BCAs) still require karyotyping for clinical detection. Moreover, submicroscopic BCAs and subarray threshold CNVs are intractable, or cryptic, to both CMA and karyotyping. Here, we performed whole-genome sequencing using large-insert jumping libraries to delineate both cytogenetically visible and cryptic SVs in a single test among 30 clinically referred youth representing a range of severe neuropsychiatric conditions. We detected 96 SVs per person on average that passed filtering criteria above our highest-confidence resolution (6,305 bp) and an additional 111 SVs per genome below this resolution. These SVs rearranged 3.8 Mb of genomic sequence and resulted in 42 putative loss-of-function (LoF) or gain-of-function mutations per person. We estimate that 80% of the LoF variants were cryptic to clinical CMA. We found myriad complex and cryptic rearrangements, including a “paired” duplication (360 kb, 169 kb) that flanks a 5.25 Mb inversion that appears in 7 additional cases from clinical CNV data among 47,562 individuals. Following convergent genomic profiling of these independent clinical CNV data, we interpreted three SVs to be of potential clinical significance. These data indicate that sequence-based delineation of the full SV mutational spectrum warrants exploration in youth referred for neuropsychiatric evaluation and clinical diagnostic SV screening more broadly. PMID:25279985

  5. Changes in Sperm Motility and Capacitation Induce Chromosomal Aberration of the Bovine Embryo following Intracytoplasmic Sperm Injection

    PubMed Central

    Kato, Yoku; Nagao, Yoshikazu

    2015-01-01

    Intracytoplasmic sperm injection (ICSI) has become the method of choice to treat human male infertility. One of the outstanding problems associated with this technique is our current lack of knowledge concerning the effect of sperm capacitation and motility upon the subsequent development of oocytes following ICSI. In the present study, we first examined the capacitation state of sperm exhibiting normal motility, along with sperm that had been activated, and examined the effect of reactive oxygen species (ROS) produced by these sperm types upon embryogenesis following bovine in vitro fertilization (IVF) and ICSI. Data showed that activated sperm reduced the chromosomal integrity of IVF/ICSI embryos at the blastocyst stage, while capacitated sperm produced ROS in capacitation media. Secondly, we treated sperm with carbonyl cyanide m-chlorophenyl hydrazine (CCCP), a chemical known to uncouple cell respiration within the mitochondria, and investigated the effect of this treatment upon blastocyst formation and chromosomal integrity at the blastocyst stage. Activated sperm in which the mitochondria had been treated with CCCP reduced levels of chromosomal aberration at the blastocyst stage following ICSI, by reducing mitochondrial activity in activated sperm. In conclusion, these findings suggest that capacitated sperm exhibiting activated motility induced chromosomal aberration during development to the blastocyst stage following ICSI. The injection of sperm exhibiting normal motility, or activated sperm in which mitochondrial activity had been reduced, improved the quality of ICSI-derived embryos. Therefore, the selection of sperm exhibiting progressive motility may not always be better for early embryo development and fetal growth following human ICSI, and that the use of a bovine model may contribute to a deeper understanding of sperm selection for human ICSI embryo development. PMID:26061876

  6. CHROMOSOMAL ABERRATIONS IN PERIPHERAL LYMPHOCYTES OF STUDENTS EXPOSED TO AIR POLLUTANTS

    EPA Science Inventory

    The research program was initiated with the overall objective of determining whether or not photochemical air pollutants have the potential to cause chromosome breakage in environmentally exposed individuals; if so, could chromosomal changes be used as a biological indicator of e...

  7. Induction and prevention of micronuclei and chromosomal aberrations in cultured human lymphocytes exposed to the light of halogen tungsten lamps.

    PubMed

    D'Agostini, F; Caimo, A; De Filippi, S; De Flora, S

    1999-07-01

    Previous studies have shown that the light emitted by halogen tungsten lamps contains UV radiation in the UV-A, UV-B and UV-C regions, induces mutations and irreparable DNA damage in bacteria, enhances the frequency of micronuclei in cultured human lymphocytes and is potently carcinogenic to the skin of hairless mice. The present study showed that the light emitted by an uncovered, traditional halogen lamp induces a significant, dose-related and time-related increase not only in micronuclei but also in chromosome-type aberrations, such as breaks, and even more in chromatid-type aberrations, such as isochromatid breaks, exchanges and isochromatid/chromatid interchanges, all including gaps or not, in cultured human lymphocytes. All these genotoxic effects were completely prevented by shielding the same lamp with a silica glass cover, blocking UV radiation. A new model of halogen lamp, having the quartz bulb treated in order to reduce the output of UV radiation, was considerably less genotoxic than the uncovered halogen lamp, yet induction of chromosomal alterations was observed at high illuminance levels. PMID:10390512

  8. [Genotoxic effects of pesticide-treated vegetable extracts using the Allium cepa chromosome aberration and micronucleus tests].

    PubMed

    Biscardi, D; De Fusco, R; Feretti, D; Zerbini, I; Izzo, C; Esposito, V; Nardi, G; Monarca, S

    2003-01-01

    The presence of chemical residues in vegetables and fruit is a source of human exposure to toxic and genotoxic chemicals. The mutagenic and carcinogenic action of herbicides, insecticides and fungicides on experimental animals is already known. Several studies have shown that chronic exposure to low levels of pesticides can cause adverse health effects and that many pesticides are mutagenic/carcinogenic. In the present research we monitored concurrently the presence of pesticides and genotoxic compounds extracted from 21 treated vegetables and 8 types of grapes sampled from the markets of a region in Southern Italy. The extracts were analysed for pesticides by gas-chromatography and HPLC, and for genotoxicity with two plant tests in Allium cepa roots: the micronucleus test and the chromosomal aberration test. We found 33 pesticides, some of which are outlawed. Genotoxicity was found in some of the vegetables and grapes tested. Allium cepa tests were sensitive for monitoring genotoxicity in food extracts. The micronucleus test in interphase cells gave much higher mutagenicity than the chromosomal aberration test in anaphase-telophase cells. PMID:15049565

  9. Analysis of chromosome aberrations and sister chromatid exchanges in peripheral blood lymphocytes of newborns after vitamin K prophylaxis at birth.

    PubMed

    Cornelissen, M; Smeets, D; Merkx, G; De Abreu, R; Kollee, L; Monnens, L

    1991-12-01

    In many countries vitamin K prophylaxis at birth is recommended to prevent bleeding in infants due to vitamin K deficiency. Because the incidence of clinical vitamin K deficiency is very low, such a vitamin K administration should be completely safe. However, an increase in sister chromatid exchanges in lymphocytes of fetal sheep 24 h after injection of vitamin K1 has been reported. Therefore, a study concerning genotoxicity of vitamin K1 in man was conducted. Sister chromatid exchanges and chromosome aberrations were analyzed in peripheral blood lymphocytes of six newborns 24 h after intramuscular administration of 1 mg vitamin K1 and in six control neonates. The mean number of sister chromatid exchanges per metaphase in the vitamin K group was 8.88 +/- 1.22 as compared with 9.05 +/- 1.14 in the control group (NS). The mean number of chromosome aberrations per 100 mitoses was 3.00 +/- 2.61 in the vitamin K group and 2.50 +/- 1.87 in the control group (NS). Vitamin K1 plasma concentrations ranged from 115 to 1150 ng/mL (255 to 2555 x 10(-9) M) in the supplemented group, a 5000-fold rise as compared with the control group (p less than 0.01). We did not find any evidence for genetic toxicity due to the administration of 1 mg vitamin K1 intramuscularly to the newborn child. PMID:1805152

  10. The fate of cells with chromosome aberrations after total-body irradiation and bone marrow transplantation

    SciTech Connect

    Carbonell, F.; Ganser, A.; Fliedner, T.M.; Arnold, R.; Kubanek, B.

    1983-03-01

    Cytogenetic studies were done on bone marrow cells and peripheral lymphocytes of four patients (three with acute nonlymphocytic leukemia, one with aplastic anemia) at various intervals up to 861 days after total-body X irradiation (TBI) at doses between 4.5 and 10 Gy (450-1000 rad) followed by syngeneic or allogeneic bone marrow transplantation. Whereas no radiation-induced aberrations could be found in the bone marrow, apart from a transient finding in the patient with the lowest radiation dose, aberrant metaphases were seen in the peripheral lymphocytes of three patients in the range from 2.5 to 46% even at 861 days after the exposure. There were no demonstrable aberrations related to TBI in the only patient developing graft-versus-host disease. The dicentric yield as determined in the aberrant metaphases with 46 centromeres ranged between 3.4 +/- 1.3 and 4.9 +/- 0.4. In one patient it was demonstrated by BUdR-labeling that after 10 Gy (1000 rad) TBI the surviving and heavily damaged lymphocytes can go into cell cycle and reach at least the third mitosis. The percentage of aberrant cells diminished by about 25% at each mitotic division.

  11. Genetic and Chromosomal Aberrations and Their Clinical Significance in Renal Neoplasms

    PubMed Central

    Yap, Ning Yi; Rajandram, Retnagowri; Ng, Keng Lim; Pailoor, Jayalakshmi; Fadzli, Ahmad; Gobe, Glenda Carolyn

    2015-01-01

    The most common form of malignant renal neoplasms is renal cell carcinoma (RCC), which is classified into several different subtypes based on the histomorphological features. However, overlaps in these characteristics may present difficulties in the accurate diagnosis of these subtypes, which have different clinical outcomes. Genomic and molecular studies have revealed unique genetic aberrations in each subtype. Knowledge of these genetic changes in hereditary and sporadic renal neoplasms has given an insight into the various proteins and signalling pathways involved in tumour formation and progression. In this review, the genetic aberrations characteristic to each renal neoplasm subtype are evaluated along with the associated protein products and affected pathways. The potential applications of these genetic aberrations and proteins as diagnostic tools, prognostic markers, or therapeutic targets are also assessed. PMID:26448938

  12. mBAND and mFISH analysis of chromosomal aberrations and breakpoint distribution in chromosome 1 of AG01522 human fibroblasts that were exposed to radiation of different qualities.

    PubMed

    Berardinelli, F; De Vitis, M; Nieri, D; Cherubini, R; De Nadal, V; Gerardi, S; Tanzarella, C; Sgura, A; Antoccia, A

    2015-11-01

    High-resolution multicolour banding FISH (mBAND) and multiplex FISH (mFISH) were used to analyse the aberrations of chromosome 1 in irradiated-AG01522 human primary fibroblasts. The cells were exposed to 1Gy of a panel of radiation of different qualities, such as X-rays, low-energy protons (28keV/μm), helium-ions (62keV/μm) and carbon-ions (96 and 252keV/μm). mBAND and mFISH analysis in calyculin-A G2-condensed chromosome spreads allowed us to detect intra- and interchromosome aberrations involving chromosome 1, including simple and complex-type exchanges, inversions (both para- and pericentric ones), deletions and rings. The data indicate that the induction of chromosomal exchanges was influenced by both Linear energy transfer (LET) and particle types. Moreover, the complex-to-simple exchanges ratio (C-ratio) and interchromosome to intrachromosome exchanges ratio (F-ratio) were evaluated by mFISH and mBAND techniques, respectively. Our results indicate that the C-ratio is a more reliable marker of radiation quality, with values that increased linearly in an LET-dependent manner. In addition, by means of mBAND analysis, the distribution of radiation-induced breakpoints along chromosome 1 was analyzed and compared with the expected distributions of the breaks. The expected values were calculated assuming a random distribution of the breakpoints. The data indicate that, irrespective of the radiation that was used, the breakpoints were non-randomly distributed along chromosome 1. In particular, breaks in the pericentromeric region were encountered at a higher frequency than expected. A deeper analysis revealed that breaks were not located in the constitutive heterochromatin (G-bands 1p11/1q11 and 1q12), but rather in a region comprised between 1p11.2 and 1p22.1, which includes G-light and G-dark bands. PMID:26520373

  13. Assessing the level of chromosome aberrations in peripheral blood lymphocytes in long-term resident children under conditions of high exposure to radon and its decay products.

    PubMed

    Druzhinin, Vladimir G; Sinitsky, Maxim Yu; Larionov, Aleksey V; Volobaev, Valentin P; Minina, Varvara I; Golovina, Tatiana A

    2015-09-01

    In this study, the frequency and spectrum of chromosomal aberrations were analysed in samples of peripheral blood from 372 (mean age = 12.24 ± 2.60 years old) long-term resident children in a boarding school (Tashtagol city, Kemerovo Region, Russian Federation) under conditions of high exposure to radon and its decay products. As a control group, we used blood samples from people living in Zarubino village (Kemerovo Region, Russian Federation). We discovered that the average frequencies of single and double fragments, chromosomal exchanges, total number of aberrations, chromatid type, chromosome type and all types of aberrations were significantly increased in the exposed group. This is evidence of considerable genotoxicity to children living under conditions of high exposure to radon compared to children living under ecological conditions without increased radon radiation. PMID:25904585

  14. Protective effects of pomegranate peel against hematotoxicity, chromosomal aberrations, and genotoxicity induced by barium chloride in adult rats.

    PubMed

    Elwej, Awatef; Ben Salah, Ghada; Kallel, Choumous; Fakhfakh, Faiza; Zeghal, Najiba; Ben Amara, Ibtissem

    2016-06-01

    Context Pomegranate peel (PP) has health benefits including antibacterial, antioxidant, anti-inflammatory, and antimutagenic properties. Objective This study investigated the biochemical composition and protective effects of PP against hematotoxicity and genotoxicity induced by barium chloride (BaCl2) in adult rats. Materials and methods Adult Wistar rats were divided into four groups of six each: control, barium (67 ppm via drinking water), PP (5% via diet), and their combination during 21 d. Oxidative stress was determined by MDA, AOPP, and antioxidant status: CAT, GPx, GSH, Vit C. Osmotic fragility (OF), chromosomal aberrations (CAs), and micronucleus (MN) assays were also studied. Results PP showed a rich composition of antioxidant compounds. DPPH test found IC50 value= 5.3 μg/mL and a high polysaccharides content (315 ± 5 mg/g of extract). In vivo study showed a decrease in red blood cells (70%) and platelet counts (46%), hemoglobin content (8%), hematocrit percent (7%), and an 80% increase of white blood cells in Ba-treated rats. A reduction in antioxidant status: catalase, glutathione peroxidase activities, glutathione, and vitamin C levels by 31, 21, 28, and 29%, respectively, and an increase in MDA (46%) and AOPP levels (72%) were also observed compared with controls. BaCl2-treatment showed a significant increase in the frequencies of total chromosomal aberrations with abnormal metaphases and micronucleus in bone-marrow cells. Oxidative stress induced by BaCl2 might be the major cause for chromosomal abnormalities leading to DNA damage. Discussion and conclusion A decrease in hematotoxic and genotoxic effects induced by PP is due to its powerful antioxidant capacity. PMID:26971618

  15. Analysis of Terminal Deletions using a Generalized Time-Dependent Model of Radiation-Induced Formation of Chromosomal Aberrations

    NASA Technical Reports Server (NTRS)

    Ponomarev, Artem L.; George, K.; Cucinotta, Francis A.

    2011-01-01

    We have developed a model that can simulate different types of radiation induced chromosomal aberrations (CA's) and can provide predictions on the frequency and size of chromosomes with terminal deletions. Chromosomes with terminal deletions lack telomeres and this can elicit sister chromatid unions and the prolonged breakage/fusion/bridge (B/F/B) cycles that have been observed in mammalian tumors. The loss of a single telomere has been shown to cause extensive genomic instability through the B/F/B cycle process. Our model uses a stochastic process of DNA broken end joining, in which a realistic spectrum of CA's is created from improperly joined DNA free ends formed by DNA double strand breaks (DSBs). The distribution of the DNA free ends is given by a mechanistic model that takes into account the chromatin structure and track structure for high-LET radiation. The model allows for DSB clustering from high-LET radiation and simulates the formation of CA's in stages that correspond to the actual time after radiation exposure. The time scale for CA formation is derived from experimental data on DSB repair kinetics. At any given time a nucleus may have intact chromosomes, CA's, and/or unrepaired fragments, some of which are defined as terminal deletions, if they are capped by one telomere. The model produces a spectrum of terminal deletions with their corresponding probabilities and size distributions for different heavy ions exposures for the first division after exposure. This data provides valuable information because there is limited experimental data available in the literature on the on the actual size of terminal deletions. We compare our model output to the available experimental data and make a reasonable extrapolation on the number of chromosomes lacking telomeres in human lymphocytes exposed to heavy ions. This model generates data which may lead to predictions on the rate of genomic instability in cells after exposure to high charge and energy nuclei

  16. Painting analysis of chromosome aberrations induced by energetic heavy ions in human cells

    NASA Astrophysics Data System (ADS)

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

    Energetic heavy ions pose a great health risk to astronauts in extended ISS and future exploration missions High-LET heavy ions are particularly effective in causing various biological effects including cell inactivation genetic mutations and cancer induction Most of these biological endpoints are closely related to chromosomal damage which can be utilized as a biomarker for radiation insults Over the years we have studied chromosomal damage in human fibroblast epithelia and lymphocyte cells exposed in vitro to energetic charged particles generated at several accelerator facilities in the world Various fluorescence in situ hybridization painting techniques have been used to identify from only the telomere region of the chromosome to every chromosome in a human cell We will summarize the results of the investigations and discuss the unique radiation signatures and biomarkers for space radiation exposure

  17. mFISH analysis of chromosome aberrations induced in vitro by α-particle radiation: examination of dose-response relationships.

    PubMed

    Curwen, Gillian B; Tawn, E Janet; Cadwell, Kevin K; Guyatt, Laura; Thompson, James; Hill, Mark A

    2012-11-01

    A multicolored FISH (mFISH) technique was used to characterize the cytogenetic damage associated with exposure to α-particle radiation with particular emphasis on the quality and quantity that is likely to be transmitted through cell division to descendant cells. Peripheral blood lymphocytes were irradiated in vitro with (238)Pu α particles with a range of mean doses up to 936 mGy and were cultured for 47 h. The dose responses for total aberrant cells, stable and unstable cells, and cells with one simple chromosome aberration and multiple chromosome aberrations were predominantly linear for doses that resulted in cell nuclei receiving a single α-particle traversal. However, there was a decrease per unit dose in aberrant cells of all types at higher doses because of cells increasingly receiving multiple traversals. The proportion of radiation-induced aberrant cells containing multiple aberrations ranged from 48 to 74% with little evidence of dose dependency. Ninety-one percent of all cells with multiple aberrations were classified as unstable. Resolving the chromosome rearrangements into simple categories resulted in a linear dose response for dicentrics of 24.9 ± 3.3 × 10(-2) per Gy. The predominant aberration in stable transmissible cells was a single translocation with a dose response for predominantly single hit cell nuclei of 4.1 ± 1.3 × 10(-2) per Gy. Thus, translocations are the most likely aberration to be observed in peripheral blood lymphocytes from individuals with incorporated α-emitting radionuclides resulting in long-term chronic exposure. PMID:23083107

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

    NASA Technical Reports Server (NTRS)

    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

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

    NASA Astrophysics Data System (ADS)

    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

  20. Identification of Clinically Important Chromosomal Aberrations in Acute Myeloid Leukemia by Array-Based Comparative Genomic Hybridization

    PubMed Central

    Mehrotra, Meenakshi; Luthra, Rajyalakshmi; Ravandi, Farhad; Sargent, Rachel L.; Barkoh, Bedia A; Abraham, Ronald; Mishra, Bal Mukund; Medeiros, L. Jeffrey; Patel, Keyur P.

    2014-01-01

    Array-based comparative genomic hybridization (aCGH) chromosomal analysis facilitates rapid detection of cytogenetic abnormalities previously undetectable by conventional cytogenetics. In this study, we analyze 48 uniformly treated acute myeloid leukemia (AML) patients by 44K aCGH and correlated the findings with clinical outcome. aCGH identified previously undetected aberrations, as small as 5 kb, of currently unknown significance. The 36.7 Mb minimally deleted region on chromosome 5 lies between 5q14.3 to 5q33.3 contains 634 genes and 15 microRNAs whereas loss of chromosome 17 spans 3,194 kb involves 342 genes and 12 microRNAs. Loss of 155 kilobase (kb) region on 5q33.3 (p<0.05) is associated with achievement of complete remission. In contrast, loss of 17p11.2-q11.1 was associated with lower CR rate and poorer overall survival (Kaplan-Meier analysis, p<0.0096). aCGH detected loss of 17p in 12/48 patients as compared to 9/48 by conventional karyotyping. In conclusion, aCGH analysis adds to the prognostic stratification of AML patients. PMID:24446873

  1. Assessment of chromosomal aberrations and micronuclei in peripheral lymphocytes from tunisian hospital workers exposed to ionizing radiation.

    PubMed

    Sakly, Amina; Ayed, Yosra; Chaari, Neila; Akrout, Mohamed; Bacha, Hassen; Cheikh, Hassen Ben

    2013-09-01

    Epidemiological studies suggest that cytogenetic biomarkers, such as micronuclei (MN) in peripheral blood lymphocytes may predict cancer risk because they indicate genomic instability. The objective of the present study was to evaluate the frequencies of MN and chromosome aberrations (CA) in peripheral blood lymphocytes of hospital workers exposed to ionizing radiation and healthy subjects. The study was conducted using peripheral blood lymphocytes from 30 workers from the radiology department and 30 from the cardiology department. This study included 27 healthy age- and sex-matched individuals as the control group. The assessment of chromosomal damage was carried out by the use of CA and micronucleus assays in peripheral lymphocytes. Our results show that CA and micronucleus frequencies were significantly higher among the exposed groups when compared to controls. Our finding of significant increase of CA and MN frequencies in peripheral lymphocytes in exposed workers indicates a potential cytogenetic hazard due to this exposure. The enhanced chromosomal damage of subjects exposed to genotoxic agents emphasizes the need to develop safety programs. PMID:23216272

  2. Effect of lET and track structure on the statistical analysis of chromosome aberrations: Use of the convoluted Poisson-Neyman distribution.

    NASA Astrophysics Data System (ADS)

    Gudowska-Nowak, E.; Lee, R.; Nasonova, E.; Scholz, M.

    Chromosome aberration data obtained for various types of mammalian cells including human lymphocytes after exposure to low and high LET clearly demonstrate the differences in the energy deposition pattern of both radiation qualities In our paper the distribution of chromosome aberrations observed in human peripheral blood lymphocytes after exposure to 900 MeV u Fe ions are analyzed and compared to the effects of 250 kV X-rays After low LET exposure the distribution of aberrations among cells at the first post-irradiation mitosis is characterized by a Poisson distribution reflecting a simple random distribution of damages as expected according to the homogeneous pattern of energy distribution On the contrary after high LET exposure the distribution of aberrations reflects the microscopic inhomogeneity of energy depositions If particle hits to the cell nucleus can be viewed as independent events each contributing with an average number of aberrations per hit the overall distribution of aberrations can be represented by a compound Poisson Neyman statistics However in the case of high energetic particles the radial extension of the particle tracks cannot be neglected due to overlap effects from different tracks the particle traversals cannot be treated as independent In this case the distribution of aberrations is characterized by a mixture of a Neyman distribution with a background of a Poisson-type distribution representing the contributions from the center part of the tracks and the outer overlapping part of the tracks respectively

  3. Unstable Chromosome Aberrations Do Not Accumulate in Normal Human Fibroblast after Fractionated X-Irradiation

    PubMed Central

    Ojima, Mitsuaki; Ito, Maki; Suzuki, Keiji; Kai, Michiaki

    2015-01-01

    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. PMID:25723489

  4. High Performance DNA Probes for Perinatal Detection of Numerical Chromosome Aberrations

    PubMed Central

    Lemke, Kalistyn H; Weier, Jingly F; Weier, Heinz-Ulrich G; Lawin-O’Brien, Anna R

    2016-01-01

    Human reproduction is a tightly controlled process of stepwise evolution with multiple, mostly yet unknown milestones and checkpoints. Healthy halpoid gametes have to be produced by the parents, which will fuse to form the diploid zygote that implants in the female uterus and grows to become first an embryo, then a fetus and finally matures into a newborn. There are several known risk factors that interfere with normal production of gametes, spermatocytes or oocytes, and often cause embryonic mortality and fetal demise at an early stage. Yet some embryos with chomosomal abnormalities can develop beyond the critical first trimester of pregnancy and, while those with supernumary chromosomes in their hyperdiploid cells will be spontaneously aborted, a small fraction of fetuses with an extra chromosome continues to grow to term and will be delivered as a liveborn baby. While minor clinical symptoms displayed by children with trisomies are manageable for many parents, the burden of caring for a child with numerical chromosome abnormalities can be overwhelming to partners or individual families. It also poses a significant financial burden to the society and poses ethical dilemma. In this communication, we will review the progress that has been made in the development of molecular techniques to test individual fetal cells for chromosomal imbalances. We will focus our discussion on the direct visualization of chromosome-specific DNA sequences in live or fixed specimens using fluorescence in situ hybridization (FISH) and, more specifically, talk about the groundbreaking progress that in recent years has been achieved towards an improved diagnosis with novel, chromosome-specific DNA probes. PMID:26855976

  5. Down's Syndrome and Leukemia: Mechanism of Additional Chromosomal Abnormalities

    ERIC Educational Resources Information Center

    And Others; Goh, Kong-oo

    1978-01-01

    Chromosomal abnormalities, some appearing in a stepwise clonal evoluation, were found in five Down's syndrome patients (35 weeks to 12 years old), four with acute leukemia and one with abnormal regulation of leukopoiesis. (Author/SBH)

  6. SYNAPTONEMAL COMPLEX ABERRATIONS IN THE PSEUDOAUTOSOMAL REGION OF X,Y CHROMOSOMES IN IRRADIATED HAMSTERS

    EPA Science Inventory

    Armenian hamsters were treated with X-radiation, bleomycin or amsacrine (m-AMSA) and the effects on meiotic chromosomes determined by electron microscopic analysis of synaptonemal complex (SC) formation. achytene cells were analyzed five or six days following their treatment at p...

  7. Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000.

    PubMed

    Stoupel, Eliahu G; Frimer, Helena; Appelman, Zvi; Ben-Neriah, Ziva; Dar, Hanna; Fejgin, Moshe D; Gershoni-Baruch, Ruth; Manor, Esther; Barkai, Gad; Shalev, Stavit; Gelman-Kohan, Zully; Reish, Orit; Lev, Dorit; Davidov, Bella; Goldman, Boleslaw; Shohat, Mordechai

    2005-09-01

    The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth--138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices--sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999--were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected--r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS. PMID:15988607

  8. Anti-genotoxic effect of the Sargassum dentifolium extracts: prevention of chromosomal aberrations, micronuclei, and DNA fragmentation.

    PubMed

    Gamal-Eldeen, Amira M; Abo-Zeid, Mona A M; Ahmed, Eman F

    2013-01-01

    The alga Sargassum dentifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown seaweed in red sea shores in Egypt. This work aimed to extract different water-soluble polysaccharide extracts (E1, E2, and E3) from S. dentifolium and to investigate their protective effect against cyclophosphamide (CP)-induced genotoxicity. Mice bone marrow cells (BMCs) were collected and analyzed for the chromosomal aberration, micronucleated BMCs (MN-BMCs), the mitotic index, DNA fragmentation by comet assay, and histone deacetylases (HDACs), and radical scavenging capacity of extracts was evaluated by the oxygen radical absorbance capacity assay. The results indicated that E2 and E3 significantly inhibited CP-induced multiple chromosomal aberrations, where E1 and E3 significantly suppressed the number of CP-induced formation of tetraploidy. The extracts prohibited the cytotoxic effect of CP and recovered the mitotic activity, whereas E1 possessed the highest recovery and mitosis. In absence of MN, CP induced formation of bi- and poly-nucleated BMCs. E1 prohibited CP-induced formation of bi-nucleated BMCs, while E2 and E3 prohibited CP-induced formation of poly-nucleated BMCs. CP-induced MN-BMCs were accompanied with mono-, bi- and poly-nucleated cells. E1 and E3 remarkably suppressed mono-nucleated MN-BMCs, while E2 inhibited bi-nucleated MN-BMCs. All the extracts significantly inhibited the CP-induced formation of poly-nucleated MN-BMCs. CP-induced DNA fragmentation was inhibited by all extracts, where E1 was the strongest inhibitor as concluded from the comet tail moment. All the extracts were strong OH scavengers, while only E3 was ROO scavenger. The results revealed a drastic decline in HDACs activity by E1 and E3. In conclusion, S. dentifolium polysaccharide extracts E1 and E3 possessed a potential anti-genotoxic and a promising anti-mutagenic activity. PMID:21652192

  9. Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000

    NASA Astrophysics Data System (ADS)

    Stoupel, Eliahu G.; Frimer, Helena; Appelman, Zvi; Ben-Neriah, Ziva; Dar, Hanna; Fejgin, Moshe D.; Gershoni-Baruch, Ruth; Manor, Esther; Barkai, Gad; Shalev, Stavit; Gelman-Kohan, Zully; Reish, Orit; Lev, Dorit; Davidov, Bella; Goldman, Boleslaw; Shohat, Mordechai

    2005-09-01

    The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth—138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices—sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999—were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected—r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS.

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

    NASA Technical Reports Server (NTRS)

    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.

  11. Synthesis and characterization of advanced durum wheat hybrids and addition lines with thinopyrum chromosomes.

    PubMed

    Jauhar, Prem P; Peterson, Terrance S

    2013-01-01

    Durum wheat (Triticum turgidum L., 2n = 4x = 28; AABB genomes) is a natural hybrid-an allotetraploid between 2 wild species, Triticum urartu Tumanian (AA genome) and Aegilops speltoides Tausch (BB genome). Even at the allotetraploid level, durum wheat can tolerate chromosomal imbalance, for example, addition of alien chromosome 1E of diploid wheatgrass, Lophopyrum elongatum. Therefore, one way to broaden its genetic base is to add a desirable chromosome(s) from diploid wild relatives. We attempted chromosomal engineering with chromosomes of a diploid wheatgrass, Thinopyrum bessarabicum-a source of resistance to some diseases including Fusarium head blight. Several advanced hybrids and alien addition lines were studied using traditional cytology, multicolor fluorescent genomic in situ hybridization, and molecular markers. Hybrid derivatives varied in chromosome number from F1 to F8 generations and in backcross generations. In advanced generations, we exercised selection against 28-chromosome plants and in favor of 30-chromosome plants that helped recover 14 addition lines in the F8 generation, as indicated by the absence of segregation for 29-chromosome plants. Disomic additions showed regular meiosis with 15 bivalents, 14 of durum wheat, and 1 of Th. bessarabicum. The addition lines will facilitate further chromosome engineering work on durum wheat for broadening its genetic base. PMID:23396879

  12. Dose-response of x-ray-induced anaphase aberrations in the mitotic root tip chromosomes of allium

    SciTech Connect

    Ma, T.H.; Lee, K.H.; Kong, M.S.

    1995-11-01

    A simplified Allium root mitotic chromosome aberration assay by using only the aberrant anaphases (fragments, laggards and bridges) as the end-points were developed by Rank and Nielsen (1993) for screening water soluble chemicals and complex mixtures. A dose-response curve was established by Meir et al., (1994) using a known clastogen, 4-nitroquinolene-N-oxide between the dose range of 0.1-0.5 ug/ml. In order to further validate this assay for clastogen detection, a series of X-ray dose response experiments was carried out. Allium roots were germinated in tapwater for 48 h and treated with a series of 10, 20, 30, 40, 50, 60 R (80 Kvp, 5 ma, dose rate 60 R/min) dosages. After an 18 hr recovery time, the root tips were hydrolyzed in 45% acetic and 1 N HC1 acid (9:1 ratio) solution under 50{degrees} C for 5 min and stained with aceto-carmine. Each of the data points were derived from scoring 7-10 slides (15-50 anaphases/slide). The corrrelation coefficient, slope and intercept values of the dose-response curve are: 0.954, 0.515 and 1.155 respectively.

  13. Chromosome aberrations and aneuploidy in sperm of Hodgkin`s disease patients before and {approximately}15 years after MOPP-chemotherapy analyzed by multi-color FISH

    SciTech Connect

    Hummelen, P.V.; Lowe, X.; Wyrobek, A.J.

    1997-10-01

    MOPP-chemistry includes potent mutagens which induce chromosomal abnormalities in human somatic and rodent germ cells. Sperm samples five pre- and four rodent germ cells. Sperm samples (five pre- and four post-treatment) from 8 Hodgkin`s patients were analyzed using fluorescence in situ hybridization (FISH) to detect 3 categories of chromosomal defects in sperm: (1) terminal duplications of deletions in chr. 1p, (2) aneuploidy involving chr. 1 or 8, and (3) diploidy. In 3 pre-treatment and 2 post-treatment samples, each from a different donor, the levels of chromosomal damage were comparable to those of healthy controls. For one patient significantly higher proportions of sperm carrying structural chromosome aberrations were detected in a 15 years post-treatment sample, compared to his pre-treatment sample and pre-treatment samples of other patients. This patient also showed significantly elevated levels of hyperploid and diploid sperm in both his pre- and post-treatment samples. Elevated levels of diploid sperm were also observed in a pre-treatment sample of a second patient. In a 23 years post-treatment sample of another patient the fraction of sperm carrying chromosome aberrations was also significantly higher than in pre-treatment samples. To conclude, elevated frequencies of sperm with structural chromosome damage were observed in at least one patient, suggesting clonal outgrowth of chromosomal aberrant stem cells due to MOPP treatment. Although MOPP does not seem to increase numerical aberrations in sperm significant inter-individual differences were present among the Hodgkin`s patient.

  14. ANALYSIS OF THE DISTRIBUTION AND DOSE RESPONSE OF CHROMOSOME ABERRATIONS IN HUMAN LYMPHOCYTES AFTER IN VITRO EXPOSURE TO (137) CESIUM GAMMA RADIATION

    EPA Science Inventory

    The chromosome aberration yield for human lymphocytes exposed in vitro to various doses of (137) Cesium has been studied. Dicentric, total acentric, and excess acentric data were seen to follow a Poisson distribution. Calculated total hits demonstrated over-dispersion which could...

  15. Appearance of chromosomal aberrations in females heterozygous for deletion MS2-10: Maternal effect

    SciTech Connect

    Artemova, E.V.; Chadov, B.F.

    1995-01-01

    The mutagenic effect of the paracentromeric heterochromatin deletion MS2-10 was studied in direct and reciprocal crosses of laboratory and wild-type lines of Drosophila melanogaster. The effect of deletion MS2-10 depended on the opposite chromosome. This was shown for the combination of autosome MS2-10 with autosome 2 from the Berlin wild line, but when MS2-10 was combined with an autosome 2 from lines Canton S and pr pk cn, the effect was absent. When deletion MS2-10 was inherited from the female parent and the opposite chromosome from the male parent, the effect of the deletion was present, but it was absent in males heterozygous for MS2-10, obtained in reciprocal crosses. In maternal effect, this case of mutagenesis is similar to hybrid dysgenesis. However, the pattern of P-M dysgenesis was shown to differ from the type of mutagenesis described in the present work.

  16. Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair

    SciTech Connect

    Marchetti, Francesco; Bishop, Jack; Gingerich, John; Wyrobek, Andrew J.

    2015-01-08

    De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction. We report that treatment of male mice with melphalan (MLP), a bifunctional alkylating agent widely used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development. After fertilization, unrepaired sperm DNA lesions are mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally abnormal offspring. In conclusion, these findings highlight the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus.

  17. Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair

    DOE PAGESBeta

    Marchetti, Francesco; Bishop, Jack; Gingerich, John; Wyrobek, Andrew J.

    2015-01-08

    De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction. We report that treatment of male mice with melphalan (MLP), a bifunctional alkylating agent widelymore » used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development. After fertilization, unrepaired sperm DNA lesions are mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally abnormal offspring. In conclusion, these findings highlight the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus.« less

  18. Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair

    PubMed Central

    Marchetti, Francesco; Bishop, Jack; Gingerich, John; Wyrobek, Andrew J.

    2015-01-01

    De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction. We report that treatment of male mice with melphalan (MLP), a bifunctional alkylating agent widely used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development. After fertilization, unrepaired sperm DNA lesions are mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally abnormal offspring. These findings highlight the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus. PMID:25567288

  19. Effects of radiation on frequency of chromosomal aberrations and sister chromatid exchange in the benthic worm Neanthes arenaceodentata

    SciTech Connect

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

    1983-04-01

    Traditional bioassays are unsuitable for assessing sublethal effects of low levels of radioactivity because mortality and phenotypic responses are not anticipated. We compared the usefulness of chromosomal aberration (CA) and sister chromatid exchange (SCE) induction as measures of low-level radiation effects in a sediment-dwelling marine worm, Neanthes arenaceodentata. Newly hatched larvae were exposed to two radiation exposure regimes. Groups of 100 larvae were exposed to either x rays delivered at high dose rates (0.7 Gy min/sup -1/) or to /sup 60/Co gamma rays delivered at low dose rates (4.8 X 10/sup -5/ to 1.2 X 10/sup -1/ Gy h/sup -1/). 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). Slides of larval cells were prepared for observation of CAs and SCEs. Frequencies of CAs were determined in first division cells; frequencies of SCEs were determined in second division cells. Results from x-ray irradiation indicated that dose-related increases occur in chromosome and chromatid deletions, but an x-ray dose greater than or equal to 2 Gy was required to observe a significant increase. Worm larvae receiving /sup 60/Co irradiation showed elevated SCE frequencies; a significant increase in SCE frequency was observed at 0.6 Gy. 49 references, 2 figures.

  20. The extent of chromosomal aberrations induced by chemotherapy in non-human primates depends on the schedule of administration.

    PubMed

    Rao, V Koneti; Knutsen, Turid; Ried, Thomas; Wangsa, Darawalee; Flynn, Bernard Mike; Langham, Gregory; Egorin, Merrill J; Cole, Diane; Balis, Frank; Steinberg, Seth M; Bates, Susan; Fojo, Tito

    2005-06-01

    We utilized a non-human primate model, the rhesus monkey (Macaca mulatta), to quantitate the extent of chromosomal damage in bone marrow cells following chemotherapy. Thiotepa, etoposide, and paclitaxel were chosen as the chemotherapy agents due to their distinct mechanisms of action. Chromosomal aberrations were quantitated using traditional Giemsa stain. We sought to evaluate the extent to which genotoxicity was dependent on the schedule of administration by giving chemotherapy as either a bolus or a 96 h continuous infusion. Neutropenia and areas under the concentration curve (AUCs) were monitored to ensure comparable cytotoxicity and dose administered. At least 100 metaphases were scored in each marrow sample by an investigator unaware of the treatment history of the animals. All three drugs produced a statistically significant higher percentage of abnormal metaphases following bolus chemotherapy (p<0.0001, p=0.0015 and p<0.0001 for thiotepa, etoposide and paclitaxel, respectively). We conclude that infusional administration of thiotepa, etoposide and paclitaxel is less genotoxic to normal bone marrow cells than is bolus administration. These results suggest infusional regimens may be considered where there are concerns about long-term genotoxic sequelae, including secondary cancer, teratogenicity, or possibly the development of drug resistance. We believe this approach provides a reproducible model in which drugs and eventually, regimens can be compared. PMID:15927870

  1. Application of polymer graded-index materials for aberration correction of progressive addition lenses

    NASA Astrophysics Data System (ADS)

    Shitanoki, Yuki; Tagaya, Akihiro; Koike, Yasuhiro

    2009-02-01

    Graded-index (GRIN) progressive addition lens (PAL) was successfully fabricated, and GRIN's potential for aberration correction of PAL was confirmed. GRIN material was prepared by partial diffusion of methyl methacrylate (MMA (nd at polymer = 1.492)) monomer into cross-linked benzyl methacrylate (BzMA (nd at polymer=1.568)) flat gel, and GRINPAL was prepared by polymerization of the GRIN material attached to a mold of commercially available PAL. GRIN polymer materials have been used for various applications such as rod lenses and optical fibers. GRIN represents gradual change of refractive index in a material, which adds or reduces light focusing power of the material. PAL is a multifocal spectacle lens for presbyopia. However, some localized aberrations (especially astigmatism) in PAL have not yet been reduced satisfactorily for decades by optimizing surface geometry of a lens. In this research, we propose to employ GRIN materials for astigmatism reduction of PALs. BzMA flat gel was prepared by UV polymerization of BzMA, crosslinking agent ethylene glycol dimethacrylate (EDMA) and photopolymerization initiator DAROCURE 1173. MMA monomer was diffused into BzMA flat gel from a portion of periphery for several hours. The obtained GRIN material was attached to a mold of commercially available PAL and polymerized by UV. As a result, reduction of astigmatism was confirmed locally in the fabricated PAL and GRIN-PAL using lens meter. In conclusion, GRIN-PAL was successfully fabricated. The validity of GRIN employment for the astigmatism reduction in PAL was demonstrated experimentally.

  2. 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)

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:20338263

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

    SciTech Connect

    Oh, J; Deasy, J

    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

  5. Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes

    PubMed Central

    Kim, Tae-Min; Xi, Ruibin; Luquette, Lovelace J.; Park, Richard W.; Johnson, Mark D.; Park, Peter J.

    2013-01-01

    A large database of copy number profiles from cancer genomes can facilitate the identification of recurrent chromosomal alterations that often contain key cancer-related genes. It can also be used to explore low-prevalence genomic events such as chromothripsis. In this study, we report an analysis of 8227 human cancer copy number profiles obtained from 107 array comparative genomic hybridization (CGH) studies. Our analysis reveals similarity of chromosomal arm-level alterations among developmentally related tumor types as well as a number of co-occurring pairs of arm-level alterations. Recurrent (“pan-lineage”) focal alterations identified across diverse tumor types show an enrichment of known cancer-related genes and genes with relevant functions in cancer-associated phenotypes (e.g., kinase and cell cycle). Tumor type-specific (“lineage-restricted”) alterations and their enriched functional categories were also identified. Furthermore, we developed an algorithm for detecting regions in which the copy number oscillates rapidly between fixed levels, indicative of chromothripsis. We observed these massive genomic rearrangements in 1%–2% of the samples with variable tumor type-specific incidence rates. Taken together, our comprehensive view of copy number alterations provides a framework for understanding the functional significance of various genomic alterations in cancer genomes. PMID:23132910

  6. Pigmentary abnormalities and mosaicism for chromosomal aberration: association with clinical features similar to hypomelanosis of Ito.

    PubMed

    Sybert, V P; Pagon, R A; Donlan, M; Bradley, C M

    1990-04-01

    Thirteen patients with hypopigmentation of the skin characteristic of hypomelanosis of Ito, and with developmental disabilities or structural malformations, or both, were examined at our center. Eight were found to have abnormal karyotypes in lymphocytes, fibroblasts, or both. No single clinical feature was predictive of chromosome imbalance in this group of patients. Cytogenetic findings included a balanced de novo X-autosome translocation; ring 10; 45,X/46,X,+ring; mosaic del 13q11 (fibroblasts); mosaic triploidy (fibroblasts); mosaic tetrasomy 12p (fibroblasts); mosaic apparently balanced 15;22 translocation (peripheral blood); and mosaic trisomy 18 (peripheral blood). Hypomelanosis of Ito is characterized by swirly hypopigmentation or depigmentation of the skin with or without other malformations. Autosomal dominant, autosomal recessive, and X-linked dominant inheritance have been suggested but not confirmed. Chromosomal aneuploidy has also been reported. We believe that hypomelanosis of Ito is an etiologically heterogeneous physical finding, and recommend karyotyping of multiple tissues of all patients with abnormal cutaneous pigmentation associated with developmental delay or structural malformations. PMID:2319405

  7. Loss of centromeric histone H2AT120 phosphorylation accompanies somatic chromosomes inactivation in the aberrant spermatocytes of Acricotopus lucidus (Diptera, Chironomidae).

    PubMed

    Staiber, Wolfgang

    2016-01-01

    In the germ line of the chironomid Acricotopus lucidus, two cells with quite different chromosome constitutions result from the last unequal gonial mitosis. In the male, the future primary spermatocyte receives all the germ line-limited chromosomes (=Ks) together with somatic chromosomes (=Ss), and later on undergoes meiotic divisions, while the connected aberrant spermatocyte gets only Ss and remains undivided with chromosomes inactivated in a metaphase-like condensed state. This raises the question whether the centromeres of the permanently condensed Ss of the aberrant spermatocyte remain active during meiosis of the connected regular spermatocyte. Active centromeres exhibit an epigenetic phosphorylation mark at threonine 120 of histone H2A. To visualise the centromeric H2A phosphorylation of the Ss in the aberrant spermatocyte, meiotic stages were immunostained with different anti-phospho histone H2AT120 antibodies. Clear H2AT120ph signals appear at the centromeres of the Ss during prophase, persist on the metaphase-like condensed Ss during meiosis I of the connected primary spermatocyte and disappear during transition to meiosis II. The centromeres of the Ss and Ks of the regular spermatocytes display H2AT120ph signals from prophase I to anaphase II. The loss of the H2AT120 phosphorylation detected on the centromeres of the Ss of the aberrant spermatocyte indicating their deactivation supports the idea of a programmed inactivation of the Ss to block the entry of the germ line-derived aberrant spermatocyte, lacking Ks, into meiosis, and thus to prevent the generation of sperms possessing only Ss. This mechanism would ensure the presence of the Ks in the germ line. PMID:25820679

  8. Prevalence of the 14/20 centric fusion chromosomal aberration in US Simmental cattle.

    PubMed

    Weber, A F; Buoen, L C; Zhang, T; Ruth, G R

    1992-05-01

    Cytogenetic evaluation was made on 353 Simmental cattle (166 male, 187 female) from 113 herds in 26 states. One hundred thirty-eight (39%) were found to be heterozygous-positive for the 14/20 centric fusion chromosomal translocation, including 41 (25%) males and 97 (52%) females. One submitted heparinized blood sample from a Simbrah bull was found to be positive for 14/20 and 1/29 centric fusions. Sampling, which was based on requests, was highly selective. Thus, the 39% prevalence found was not representative of 14/20 centric fusion in the national Simmental breed. On the basis of our findings, cytogenetic evaluation of breeding stock was consistent with modern management practice. PMID:1601712

  9. Accumulation of DSBs in {gamma}-H2AX domains fuel chromosomal aberrations

    SciTech Connect

    Scherthan, H. Hieber, L.; Braselmann, H.; Meineke, V.; Zitzelsberger, H.

    2008-07-11

    DNA double strand breaks (DSBs) pose a severe hazard to the genome as erroneous rejoining of DSBs can lead to mutation and cancer. Here, we have investigated the correlation between X irradiation-induced {gamma}-H2AX foci, theoretically induced DSBs, and the minimal number of mis-rejoined DNA breaks (MNB) in irradiated lymphocytes obtained from two healthy humans by painting of the whole chromosome complement by spectral karyotyping. There were less {gamma}-H2AX foci/dose than theoretically expected, while misrepair, as expressed by MNB/{gamma}-H2AX focus, was similar at 0.5 and 1 Gy but 3.6-fold up at 3 Gy. Hence, our results suggest that X-ray-induced {gamma}-H2AX foci in G0 lymphocyte nuclei contain more than one DSB and that the increasing number of DSBs per {gamma}-H2AX repair factory lead to an increased rate of misrepair.

  10. Clinico-Pathological Association of Delineated miRNAs in Uveal Melanoma with Monosomy 3/Disomy 3 Chromosomal Aberrations

    PubMed Central

    Venkatesan, Nalini; Kanwar, Jagat; Deepa, Perinkulam Ravi; Khetan, Vikas; Crowley, Tamsyn M.; Raguraman, Rajeswari; Sugneswari, Ganesan; Rishi, Pukhraj; Natarajan, Viswanathan; Biswas, Jyotirmay; Krishnakumar, Subramanian

    2016-01-01

    Purpose To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort. Methods Based on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52). Results Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated. Conclusion UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness. PMID:26812476

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

    NASA Technical Reports Server (NTRS)

    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.

  12. Mechanisms of induction of SCE and mutations by BrdU and CldU and the use of inhibitors of DNA repair to study mechanisms of radiation-induced chromosome aberrations

    SciTech Connect

    Heartlein, M.W.

    1984-01-01

    The induction of sister chromatid exchanges (SCE) and specific locus mutations was studied by utilizing incorporation into DNA of the nucleoside analogues 5-bromo-and 5-chlorodeoxyuridine (BrdU and CldU). CldU was found to induce SCE seven-times more efficiently than BrdU at equal extracellular concentrations. This induction was linearly associated with substitution for thymidine from 0.5-20 ..mu..M. In these experiments, specific locus mutations were not detected at concentrations less than 50 ..mu..M and were not correlated with SCE induction. At concentrations greater than 50 ..mu..M, the mutagenicity of CldU and BrdU was similar, although BrdU was slightly more mutagenic than CldU. In the examination of radiation-induced chromosome aberrations in mammalian lymphocytes, 3-aminobenzamide and cytosine arabinoside, which are excision repair inhibitors, were used to show that the induction of chromosome aberrations depends upon the ratio of base damage to directly-induced DNA strand breaks for a particular radiation quality. In addition, it was shown that sensitivity of various mammalian species to X ray-induced aberrations depends upon the rate of repair of base damage.

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Technical Reports Server (NTRS)

    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.

  15. Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro III: Results with 27 chemicals

    SciTech Connect

    Gulati, D.K. ); Witt, K.; Anderson, B.; Zeiger, E.; Shelby, M.D. )

    1989-01-01

    Twenty-seven chemicals previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations (ABS) and sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. Seventeen of the chemicals tested were carcinogens; only two of these were negative for both ABS and SCE. Of the eight noncarcinogens tested, four were negative for both endpoints and four gave a positive response for at least one endpoint. Of the remaining two chemicals, one, diallylphthalate, gave an equivocal response in the bioassay and a positive response in these CHO cell cytogenetics tests. The other chemical, 2,4-toluene diisocyanate, was tested for carcinogenicity as a mixture with the 2,6-isomer; the mixture was carinogenic, but the cytogenetic test results for the 2,4-isomer were negative. Experiments with unsynchronized CHO cells demonstrated that mean SCE frequency increased with increasing culture time, and this may have been a factor in the positive results obtained for five chemicals in the SCE test under conditions of delayed harvest.

  16. Chromosome aberration and micronucleus frequencies in Allium cepa cells exposed to petroleum polluted water--a case study.

    PubMed

    Leme, Daniela Morais; Marin-Morales, Maria Aparecida

    2008-01-31

    In the present study, we applied Chromosome Aberration (CA) and Micronucleus (MN) tests to Allium cepa root cells, in order to evaluate the water quality of Guaecá river. This river, located in the city of São Sebastião, SP, Brazil, had been affected by an oil pipeline leak. Chemical analyses of Total Petroleum Hydrocarbons (TPHs) and Polycyclic Aromatic Hydrocarbons (PAHs) were also carried out in water samples, collected in July 2005 (dry season) and February 2006 (rainy season) in 4 different river sites. The largest CA and MN incidence in the meristematic cells of A. cepa was observed after exposure to water sample collected during the dry season, at the spring of the river, where the oil leak has arisen. The F(1) cells from roots exposed to such sample (non-merismatic region) were also analyzed for the incidence of MN, showing a larger frequency of irregularities, indicating a possible development of CA into MN. Lastly, our study reveals a direct correlation between water chemical analyses (contamination by TPHs and PAHs) and both genotoxic and mutagenic effects observed in exposed A. cepa cells. PMID:18068420

  17. Assessment of chromosomal aberration in the bone marrow cells of Swiss Albino mice treated by 4-methylimidazole.

    PubMed

    Norizadeh Tazehkand, Mostafa; Topaktas, Mehmet; Yilmaz, Mehmet Bertan

    2016-07-01

    4-Methylimidazole (4-MEI) is formed during the production of certain caramel coloring agents used in many food and drink products. It may also be formed during the cooking, roasting, or other processing of some foods and beverages. So it was unintentionally consumed in worldwide. This study was aimed to investigate the genotoxic and cytotoxic effects of 4-MEI using chromosome aberration (CA) and mitotic index (MI) in Swiss Albino mice. In this research, CA and MI of the mouse bone marrow cells were analyzed after treating the animals with 4-MEI (100, 130 and 160 mg/kg) for 12 h and 24 h treatment times. All data were analyzed using statistical methods. 4-MEI significantly increased the percentage of CAs at all concentrations for 12 h and at highest concentration for 24 h treatment periods. 4-MEI at highest concentration for 12 h and at all concentrations for 24 h decreased the MI in comparison with control. Genotoxic and cytotoxic effects of 4-MEI at 24 h treatment periods were concentration dependent. Consequently, it can be said that 4-MEI have genotoxic and cytotoxic effect in mouse. PMID:26634952

  18. Aberrant activation-induced cytidine deaminase expression in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.

    PubMed

    Shi, Yang; Zhao, Xiaoxian; Durkin, Lisa; Rogers, Heesun Joyce; Hsi, Eric D

    2016-06-01

    Activation-induced cytidine deaminase (AID) is expressed in germinal center B cells and plays a critical role in somatic hypermutation and class-switch recombination of immunoglobulin genes. Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) carries a poor prognosis and is specifically treated with tyrosine kinase inhibitors. Interestingly, AID has been shown to be aberrantly expressed and functional in Ph+ ALL and is thought to contribute to genetic instability. We hypothesized that AID might be detectable in routinely processed bone marrow biopsies by immunohistochemistry (IHC) and assist in identifying Ph+ ALL. We found that AID was expressed in 26 (70%) of 37 cases of Ph+ ALL but only 1 (2.9%) of 38 cases of Ph- ALL cases. There was a significant difference in AID expression between these 2 ALL groups (P < .001, Fisher exact test). The expression of AID was confirmed by RT-PCR (reverse-transcriptase polymerase chain reaction) and correlated with IHC scoring. AID protein is expressed in a large proportion of Ph+ ALL cases at levels detectable by IHC in clinical samples and might be useful to rapidly identify cases likely to have a BCR/ABL1 fusion. PMID:26980048

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

    SciTech Connect

    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.

  20. Analysis of chromosomal aberrations, sister-chromatid exchanges and micronuclei in peripheral lymphocytes of pharmacists before and after working with cytostatic drugs.

    PubMed

    Roth, S; Norppa, H; Järventaus, H; Kyyrönen, P; Ahonen, M; Lehtomäki, J; Sainio, H; Sorsa, M

    1994-12-01

    The frequencies of chromosome aberrations, SCEs and micronuclei (cytokinesis-block method) in blood lymphocytes were compared among six nonsmoking female pharmacists before and after 1 year of working with cytostatic drugs. All possible precautions were taken to avoid exposure to cytostatics, including proper protective clothing and a monitored, negative-pressured working environment with vertical laminar flow cabinet. As referents, an age-matched group of six nonsmoking female hospital workers not dealing with cytostatics was simultaneously sampled twice with the same time interval. The pharmacists showed a marginally higher mean frequency of SCEs/cell (6.3; P = 0.049) after the working period than 1 year earlier (5.8). On the other hand, the referents, with no obvious exposure, had a higher mean number of cells with chromatid-type aberrations, gaps excluded, in the second sampling (2.0%; P = 0.048) than in the first one (0.5%). In addition, a slight (P = 0.055) trend towards a higher frequency of micronucleated binucleate cells was observed in the second sampling for both the exposed and control subjects. As such findings suggest technical variation in the cytogenetic parameters, the small difference observed in SCEs for the pharmacists between the two samplings was probably not related to the cytostatics exposure. No statistically significant differences were observed for any of the cytogenetic parameters in comparisons between the pharmacists and the referents. The findings suggest that caution should be exercised in comparing results obtained from two different samplings in prospective cytogenetic studies. PMID:7527908

  1. Alterations and Abnormal Mitosis of Wheat Chromosomes Induced by Wheat-Rye Monosomic Addition Lines

    PubMed Central

    Fu, Shulan; Yang, Manyu; Fei, Yunyan; Tan, Feiquan; Ren, Zhenglong; Yan, Benju; Zhang, Huaiyu; Tang, Zongxiang

    2013-01-01

    Background Wheat-rye addition lines are an old topic. However, the alterations and abnormal mitotic behaviours of wheat chromosomes caused by wheat-rye monosomic addition lines are seldom reported. Methodology/Principal Findings Octoploid triticale was derived from common wheat T. aestivum L. ‘Mianyang11’×rye S. cereale L. ‘Kustro’ and some progeny were obtained by the controlled backcrossing of triticale with ‘Mianyang11’ followed by self-fertilization. Genomic in situ hybridization (GISH) using rye genomic DNA and fluorescence in situ hybridization (FISH) using repetitive sequences pAs1 and pSc119.2 as probes were used to analyze the mitotic chromosomes of these progeny. Strong pSc119.2 FISH signals could be observed at the telomeric regions of 3DS arms in ‘Mianyang11’. However, the pSc119.2 FISH signals were disappeared from the selfed progeny of 4R monosomic addition line and the changed 3D chromosomes could be transmitted to next generation stably. In one of the selfed progeny of 7R monosomic addition line, one 2D chromosome was broken and three 4A chromosomes were observed. In the selfed progeny of 6R monosomic addition line, structural variation and abnormal mitotic behaviour of 3D chromosome were detected. Additionally, 1A and 4B chromosomes were eliminated from some of the progeny of 6R monosomic addition line. Conclusions/Significance These results indicated that single rye chromosome added to wheat might cause alterations and abnormal mitotic behaviours of wheat chromosomes and it is possible that the stress caused by single alien chromosome might be one of the factors that induced karyotype alteration of wheat. PMID:23936213

  2. Hormone dependency of chromosome aberrations induced by 7,12-dimethylbenz(a)anthracene in rat bone marrow cells: site-specific increase by erythropoietin

    SciTech Connect

    Ueda, N.; Suglyama, T.; Chattopadhyay, S.C.; Goto-Mimura, K.; Maeda, S.

    1981-08-01

    The frequency of chromosome aberrations (CA) 6 hours after iv injection of 50 mg 7,12-dimethylbenz(a)anthracene (DMBA0/kg was studied in bone marrow cells of the noninbred Long-Evans rat under various hematopoietic conditions. The percentage of metaphase cells with CA was enhanced by anemia and suppressed by polycythemia. The low incidence of CA in polycythemic rats was reversed by 6 U of sheep erythropoietin (EP) injected at the time of DMBA treatment. The interchromosomal and intrachromosomal distribution of CA indicated that hematopoietic stimuli, more specifically EP, greatly enhanced DMBA-induced CA in specific chromosomal regions.

  3. 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.

    PubMed

    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. PMID:1962281

  4. Micronucleus and chromosome aberrations induced in onion (Allium cepa) by a petroleum refinery effluent and by river water that receives this effluent.

    PubMed

    Hoshina, Márcia M; Marin-Morales, Maria A

    2009-11-01

    In this study, micronucleus (MN) and chromosome aberration (CA) tests in Allium cepa (onion) were carried out in order to make a preliminary characterization of the water quality of the Atibaia River in an area that is under the influence of petroleum refinery and also to evaluate the effectiveness of the treatments used by the refinery. For these evaluations, seeds of A. cepa were germinated in waters collected in five different sites related with the refinery in ultra-pure water (negative control) and in methyl methanesulfonate solution (positive control). According to our results, we can suggest that even after the treatments (physicochemical, biological and stabilization pond) the final refinery effluent could induce chromosome aberrations and micronucleus in meristematic cells of A. cepa and that the discharge of the petroleum refinery effluents in the Atibaia River can interfere in the quality of this river. PMID:19647317

  5. Lack of Mutagenicity Potential of Periploca sepium Bge. in Bacterial Reverse Mutation (Ames) Test, Chromosomal Aberration and Micronucleus Test in Mice

    PubMed Central

    Zhang, Mei-Shu; Bang, In-Seok

    2012-01-01

    Objectives The root barks of Periploca sepium Bge. (P. sepium) has been used in traditional Chinese medicine for healing wounds and treating rheumatoid arthritis. However, toxicity in high-doses was often diagnosed by the presence of many glycosides. The potential mutagenicity of P. sepium was investigated both in vitro and in vivo. Methods This was examined by the bacterial reverse mutation (Ames) test using Escherichia coli WP2uvrA and Salmonella typhimurium strains, such as TA98, TA100, TA1535, and TA1537. Chromosomal aberrations were investigated using Chinese hamster lung cells, and the micronucleus test using mice. Results P. sepium did not induce mutagenicity in the bacterial test or chromosomal aberrations in Chinese hamster lung cells, although metabolic activation and micronucleated polychromatic erythrocytes were seen in the mice bone marrow cells. Conclusions Considering these results, it is suggested that P. sepium does not have mutagenic potential under the conditions examined in each study. PMID:22888473

  6. The induction of SCE and chromosomal aberrations with relation to specific base methylation of DNA in Chinese hamster cells by N-methyl-N-nitrosourea and dimethyl sulphate.

    PubMed

    Connell, J R; Medcalf, A S

    1982-01-01

    Chinese hamster cells (V79) were treated, either as exponentially proliferating cultures or under conditions where they were density-inhibited, with various doses of the potent carcinogen N-methyl-N-nitrosourea (MNU) or the relatively weak carcinogen dimethylsulphate (DMS). The colony forming ability of these cells and the induced frequencies of sister chromatid exchanges (SCEs) and chromosomal aberrations were assayed. Following the exposure of density-inhibited cells to radio-labelled methylating agents (labelled in the methyl group) these phenomena were related to the levels of 7-methylguanine (7-meGua), O6-methylguanine (O6-meGua) and 3-methyladenine (3-me-Ade) in the DNA. At equitoxic doses MNU and DMS induced similar frequencies of SCEs and chromosomal aberrations. Since, at equitoxic doses, MNU produces approximately 20 times more O6-meGua in V79 cell DNA than does DMS, this indicates that the formation of O6-meGua in DNA is not a major cause of SCEs and chromosomal aberrations. DMS-induced SCEs may be mediated via the production of both 3-meAde and 7-meGua in the DNA; these two methylated purines may also be responsible for MNU-induced SCEs. Therefore, no one specific methylated purine was identified as being solely accountable for the formation of SCEs. Also, the repair of lesions in the DNA of non-replicating V79 cells leads to a reduction in the SCE frequency on their subsequent release from the density-inhibited state, suggesting that repair is not intimately responsible for their formation. No association was discernable between chromosomal aberrations and any of the three methylated purines studied. PMID:7094205

  7. Increasing effect of tri-n-butyltins and triphenyltins on the frequency of chemically induced chromosome aberrations in cultured Chinese hamster cells.

    PubMed

    Sasaki, Y F; Yamada, H; Sugiyama, C; Kinae, N

    1993-06-01

    Organotins have been widely used as anti-fouling coatings for fishing nets and ship bottoms, and marine pollution by them has become a serious environmental problem. In this communication, the potentiating effects of three kinds of tri-n-butyltins and three thiphenyltins on chromosome aberrations were studied in Chinese hamster CHO K1 cells. None of the organotins studied showed any clastogenic activity under the experimental conditions without rat liver S9. Post-treatment with organotins, however, increased the number of breakage-type (but not exchange-type) chromatid aberrations induced by five kinds of S-phase-dependent clastogens: MMC, cisPt, 4NQO, MMS, and AMD). Enhancement of the induction of chromosome aberrations by MMC was observed when cells were treated with organotins during the G2 phase. These results suggest that organotin G2 effect causes potentiating effects. Organotins also enhanced the induction of breakage-type chromatid aberrations by clastogenic pollutants in chlorinated tap water, indicating their potential for a more realistic health risk. PMID:7683769

  8. High resolution SNP array genomic profiling of peripheral T cell lymphomas, not otherwise specified, identifies a subgroup with chromosomal aberrations affecting the REL locus.

    PubMed

    Hartmann, Sylvia; Gesk, Stefan; Scholtysik, René; Kreuz, Markus; Bug, Stefanie; Vater, Inga; Döring, Claudia; Cogliatti, Sergio; Parrens, Marie; Merlio, Jean-Philippe; Kwiecinska, Anna; Porwit, Anna; Piccaluga, Pier Paolo; Pileri, Stefano; Hoefler, Gerald; Küppers, Ralf; Siebert, Reiner; Hansmann, Martin-Leo

    2010-02-01

    Little is known about genomic aberrations in peripheral T cell lymphoma, not otherwise specified (PTCL NOS). We studied 47 PTCL NOS by 250k GeneChip single nucleotide polymorphism arrays and detected genomic imbalances in 22 of the cases. Recurrent gains and losses were identified, including gains of chromosome regions 1q32-43, 2p15-16, 7, 8q24, 11q14-25, 17q11-21 and 21q11-21 (> or = 5 cases each) as well as losses of chromosome regions 1p35-36, 5q33, 6p22, 6q16, 6q21-22, 8p21-23, 9p21, 10p11-12, 10q11-22, 10q25-26, 13q14, 15q24, 16q22, 16q24, 17p11, 17p13 and Xp22 (> or = 4 cases each). Genomic imbalances affected several regions containing members of nuclear factor-kappaB signalling and genes involved in cell cycle control. Gains of 2p15-16 were confirmed in each of three cases analysed by fluorescence in situ hybridization (FISH) and were associated with breakpoints at the REL locus in two of these cases. Three additional cases with gains of the REL locus were detected by FISH among 18 further PTCL NOS. Five of 27 PTCL NOS investigated showed nuclear expression of the REL protein by immunohistochemistry, partly associated with genomic gains of the REL locus. Therefore, in a subgroup of PTCL NOS gains/rearrangements of REL and expression of REL protein may be of pathogenetic relevance. PMID:19863542

  9. The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18.

    PubMed

    Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

    2015-09-01

    The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain

  10. Investigation of DNA-damage and Chromosomal Aberrations in Blood Cells under the Influence of New Silver-based Antiviral Complex

    PubMed Central

    Plotnikov, Evgenii; Silnikov, Vladimir; Gapeyev, Andrew; Plotnikov, Vladimir

    2016-01-01

    Purpose: The problem of infectious diseases and drug resistance is becoming increasingly important worldwide. Silver is extensively used as an anti-infective agent, but it has significant toxic side effects. In this regard, it is topical to develop new silver compounds with high biological activity and low toxicity. This work is aimed to study DNA damage and chromosomal aberrations in blood cells under the influence of new silver-based compound of general formula C6H19Ag2N4LiO6S2, with antiviral activity. Methods: The comet assay was applied for the genotoxic affects assessment on mice blood leukocytes. DNA damage was determined bases on the percentage of DNA in a comet tail (tail DNA), under the influence of silver complex in different concentrations. Genotoxic effect of the tested substance on the somatic cells was determined by chromosomal aberration test of bone marrow cells of mice. Results: In the course of the experiments, no essential changes in the level of DNA damage in the cells were found, even at highest concentrations. The administration of the substance in doses up to 2.5 g/kg in mice did not cause any increase in the frequency of chromosomal aberration in bone marrow cells. Conclusion: Taking into account known silver drug genotoxic properties, the use of a given complexed silver compound has possible great advantages for potential applications in the treatment of infectious diseases. PMID:27123420

  11. Allium cepa anaphase-telophase root tip chromosome aberration assay on N-methyl-N-nitrosourea, maleic hydrazide, sodium azide, and ethyl methanesulfonate.

    PubMed

    Rank, J; Nielsen, M H

    1997-04-24

    The Allium anaphase-telophase assay was used to show genotoxicity of N-methyl-N-nitrosourea (MNU), maleic hydrazide (MH), sodium azide (NaN3) and ethyl methanesulfonate (EMS). All agents induced chromosome aberrations at statistically significant levels. The rank of the lowest doses with positive effect was as follows: NaN3 0.3 mg/l < MH 1 mg/l < MNU 41 mg/l < EMS 100 mg/l. The results were compared with results from other plant assays (Arabidopsis, Vicia, Tradescantia) and for MH and MNU the values were found to be within the same range, whereas the results in the Allium test for NaN3 and EMS were in a lower range than that found for the other plant assays. EMS and MMS (methyl methanesulfonate), two chemicals used as positive controls in mutagenicity testing, were compared in the Allium test, and MMS was found to be about ten times more potent in inducing chromosome aberrations than EMS. Recording of micronuclei in interphase cells showed that this endpoint does not give more information of clastogenicity than recording of chromosome aberrations in anaphase-telophase cells. PMID:9150760

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

    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.

  14. Chaetophractus villosus as a sentinel organism: Baseline values of mitotic index, chromosome aberrations and sister chromatid exchanges.

    PubMed

    Rossi, Luis Francisco; Luaces, Juan Pablo; Browne, Melanie; Chirino, Mónica Gabriela; Merani, María Susana; Mudry, Marta Dolores

    2016-01-15

    Sentinel species are useful tools for studying the deleterious effects of xenobiotics on wildlife. The large hairy armadillo (Chaetophractus villosus) is the most abundant and widely distributed mammal in Argentina. It is a long-lived, omnivorous, burrowing species, with fairly restricted home ranges. To evaluate the level of spontaneous genetic damage in this mammal, we determined the baseline values of several genotoxicity biomarkers. The study included 20 C. villosus adults of both sexes from eight pristine localities within its geographic distribution range. Genotoxicity analysis was performed on 72-h lymphocyte cultures, using mitomycin C as positive control. We obtained the baseline values of mitotic index (MI=10.52±0.30 metaphases/total cells, n=20), chromosome aberrations (CA=0.13±0.22, n=20), sister chromatid exchanges (SCE)=6.55±0.26, n=6) and replication index (RI=1.66, n=6). MI and CA did not show significant differences (P>0.05) among localities or between sexes. No significant differences in MI, CA, SCE, and RI (P>0.05) were found between values from the pristine localities and historical data. There were significant differences in CA, SCE, and RI (P<0.05) between lymphocyte cultures from pristine localities and those exposed to mitomycin C. We propose the large hairy armadillo as a sentinel organism for environmental biomonitoring of genotoxic chemicals due to its abundance, easy manipulation, well-known biology, the fact that it is usually exposed to different mixtures and concentrations of environmental contaminants, and the baseline values of genetic damage characterized by MI, CA, SCE and RI as biomarkers. PMID:26778508

  15. Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration1

    PubMed Central

    Berbegall, Ana P.; Villamón, Eva; Tadeo, Irene; Martinsson, Tommy; Cañete, Adela; Castel, Victoria; Navarro, Samuel; Noguera, Rosa

    2014-01-01

    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. PMID:25077701

  16. A mutation in PLC1, a candidate phosphoinositide-specific phospholipase C gene from Saccharomyces cerevisiae, causes aberrant mitotic chromosome segregation.

    PubMed Central

    Payne, W E; Fitzgerald-Hayes, M

    1993-01-01

    We identified a putative Saccharomyces cerevisiae homolog of a phosphoinositide-specific phospholipase C (PI-PLC) gene, PLC1, which encodes a protein most similar to the delta class of PI-PLC enzymes. The PLC1 gene was isolated during a study of yeast strains that exhibit defects in chromosome segregation. plc1-1 cells showed a 10-fold increase in aberrant chromosome segregation compared with the wild type. Molecular analysis revealed that PLC1 encodes a predicted protein of 101 kDa with approximately 50 and 26% identity to the highly conserved X and Y domains of PI-PLC isozymes from humans, bovines, rats, and Drosophila melanogaster. The putative yeast protein also contains a consensus EF-hand domain that is predicted to bind calcium. Interestingly, the temperature-sensitive and chromosome missegregation phenotypes exhibited by plc1-1 cells were partially suppressed by exogenous calcium. Images PMID:8391635

  17. Chromosome

    MedlinePlus

    ... if you are born a boy or a girl (your gender). They are called sex chromosomes: Females have 2 X chromosomes. Males have 1 X and 1 Y chromosome. The mother gives an X chromosome to the ... baby is a girl or a boy. The remaining chromosomes are called ...

  18. The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers

    PubMed Central

    Yao, Baojin; Wang, Qiuqing; Liu, Chia-Feng; Bhattaram, Pallavi; Li, Wei; Mead, Timothy J.; Crish, James F.; Lefebvre, Véronique

    2015-01-01

    Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –­350/–50-kb region 5′ of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at –250 kb) confines its activity to condensed prechondrocytes, E195 mainly targets proliferating chondrocytes, and E84 is potent in all differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to be active in most Sox9-expressing somatic tissues, including cartilage. While SOX9 protein powerfully activates E70, it does not control E250. It requires its SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors to activate E84. Altogether, these results indicate that SOX9 expression in chondrocytes relies on widely spread transcriptional modules whose synergistic and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They help elucidate mechanisms underlying campomelic dysplasia and will likely help uncover other disease mechanisms. PMID:25940622

  19. M-FISH Analysis of Chromosome Aberrations in Human Fibroblast Cells After In Vitro Exposure to Low- and High-LET Radiation

    NASA Technical Reports Server (NTRS)

    Wu, Honglu; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis

    2002-01-01

    The recently commercialized multiplex fluorescence in situ hybridization (m-FISH) technique, which allows human chromosomes to be painted in 24 different colors, was used to analyze chromosome aberrations in diploid human fibroblast cells after in vitro radiation exposure. Confluent flasks of a normal primary fibroblast cell line (AG 1522) were irradiated at high dose rates with either gamma rays or 200 MeV/nucleon Fe ions (LET = 440 keV/micron), incubated at 37 C for 24 hours after exposure, and subsequently subcultured. A chemically induced premature chromosome condensation technique was used to collect chromosome samples 32 hours after subculture. Results showed that the fraction of exchanges which were identified as complex, i.e. involving misrejoining of three or more DSB, were higher in the Fe-irradiated samples compared with the gamma-irradiated samples, as has been shown previously using FISH with one or two painted chromosomes . The ratios of complex/simple type exchanges were similar for samples irradiated with 0.7 Gy and 3 Gy of Fe ions, although exchanges involving five or more breaks were found only in 3 Gy irradiated samples. The fraction of incomplete exchanges was also higher in Fe- than gamma-irradiated samples. Data on the distribution of individual chromosome involvement in interchromosomal exchanges will be presented.

  20. Chromosome

    MedlinePlus

    ... genes . It is the building block of the human body. Chromosomes also contain proteins that help DNA exist ... come in pairs. Normally, each cell in the human body has 23 pairs of chromosomes (46 total chromosomes). ...

  1. Induction of Chromosomal Aberrations in Human Cells after Irradiation with Filtered and Unfiltered Beams of 1 Gev/amu Iron Ions

    NASA Astrophysics Data System (ADS)

    Wilson, P.; Williams, A.; Nagasawa, H.; Peng, Y.; Chatterjee, A.; Bedford, J.

    To determine whether shielding materials that might be utilized for radiation protection of astronauts would affect the RBE of HZE particles such as those of concern for deep space missions we irradiated non cycling G0 monolayer cultures of contact inhibited normal human fibroblasts with 1 Gev amu iron ions with and without filtration with various thicknesses of Aluminum Al or polyethylene CH 2 and then measured the frequencies of chromosome-type aberrations dicentrics and excess fragments in the first post-irradiation mitosis Irradiations were carried out at the NRSL facility at Brookhaven National Laboratory For doses ranging up to 4 to 6 Gy the dose response for the total of these aberrations per cell was not significantly affected by beam filtrations up to 5 4 cm Al or up to 11 cm polyethylene relative to the unfiltered beam Neither was the dose response significantly different for unfiltered beams of 300 or 600 Mev amu iron ions relative to the 1 Gev amu iron ions The studies with 1 Gev amu iron ions were repeated four different times over a period of four years in each case with coded samples so the individual scoring aberrations would not know the irradiation conditions employed Comparison of the same effects in parallel experiments using 137 Cs gamma-rays allowed us to estimate that the RBE for aberration induction by these HZE iron ions for these acute high dose-rate exposures was approximately

  2. Molecular and biochemical identification of alien chromosome additions in shallot (Allium cepa L. Aggregatum group) carrying extra chromosome(s) of bunching onion (A. fistulosum L.).

    PubMed

    Yaguchi, Shigenori; Hang, Tran Thi Minh; Tsukazaki, Hikaru; Hoa, Vu Quynh; Masuzaki, Shin-ichi; Wako, Tadayuki; Masamura, Noriya; Onodera, Shuichi; Shiomi, Norio; Yamauchi, Naoki; Shigyo, Masayoshi

    2009-02-01

    To develop the bunching onion (Allium fistulosum L.; genomes, FF) chromosome-specific genetic markers for identifying extra chromosomes, eight shallot (A. cepa L. Aggregatum group; genomes, AA)--A. fistulosum monosomic addition plants (AA+nF) and 62 shallot--A. fistulosum single-alien deletion plants (AAF-nF) were analyzed by 23 different chromosome-specific genetic markers of shallot. The eight monosomic addition plants consisted of one AA+2F, two AA+6F, and five AA+8F. Of the 62 single-alien deletion plants, 60 could be identified as six different single-alien deletion lines (AAF-1F, -3F, -4F, -6F, -7F, and -8F) out of the eight possible types. Several single-alien deletion lines were classified on the basis of leaf and bulb characteristics. AAF-8F had the largest number of expanded leaves of five deletion plants. AAF-7F grew most vigorously, as expressed by its long leaf blade and biggest bulb size. AAF-4F had very small bulbs. AAF-7F and AAF-8F had different bulbs from those of shallot as well as other types of single-alien deletion lines in skin and outer scale color. Regarding the sugar content of the bulb tissues, the single-alien deletion lines showed higher fructan content than shallot. Moreover, shallot could not produce fructan with degree of polymerization (DP) 12 or higher, although the single-alien deletion lines showed DP 20 or higher. The content of S-alk(en)yl-L-cysteine sulfoxide (ACSO) in the single-alien deletion lines was significantly lower than that in shallot. These results indicated that chromosomes from A. fistulosum might carry anonymous factors to increase the highly polymerized fructan production and inhibit the synthesis of ACSO in shallot bulbs. Accordingly, alien chromosomes from A. fistulosum in shallot would contribute to modify the quality of shallot bulbs. PMID:19420800

  3. Addition of Individual Chromosomes of Maize Inbreds B73 and Mo17 to Oat Cultivars Starter and SunII: Maize Chromosome Retention, Transmission, and Plant Phenotype

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oat-maize addition (OMA) lines with one, or occasionally more, chromosomes of maize (Zea mays L., 2n = 2x = 20) added to an oat (Avena sativa L., 2n = 6x = 42) genomic background can be produced from sexual crosses of oat x maize. Self-fertile disomic addition lines for maize chromosomes 1, 2, 3, 4,...

  4. Enhancement of aluminum tolerance in wheat by addition of chromosomes from the wild relative Leymus racemosus

    PubMed Central

    Mohammed, Yasir Serag Alnor; Eltayeb, Amin Elsadig; Tsujimoto, Hisashi

    2013-01-01

    Aluminum (Al) toxicity is the key factor limiting wheat production in acid soils. Soil liming has been used widely to increase the soil pH, but due to its high cost, breeding tolerant cultivars is more cost-effective mean to mitigate the problem. Tolerant cultivars could be developed by traditional breeding, genetic transformation or introgression of genes from wild relatives. We used 30 wheat alien chromosome addition lines to identify new genetic resources to improve wheat tolerance to Al and to identify the chromosomes harboring the tolerance genes. We evaluated these lines and their wheat background Chinese Spring for Al tolerance in hydroponic culture at various Al concentrations. We also investigated Al uptake, oxidative stress and cell membrane integrity. The L. racemosus chromosomes A and E significantly enhanced the Al tolerance of the wheat in term of relative root growth. At the highest Al concentration tested (200 μM), line E had the greatest tolerance. The introgressed chromosomes did not affect Al uptake of the tolerant lines. We attribute the improved tolerance conferred by chromosome E to improved cell membrane integrity. Chromosome engineering with these two lines could produce Al-tolerant wheat cultivars. PMID:24399913

  5. Enhancement of aluminum tolerance in wheat by addition of chromosomes from the wild relative Leymus racemosus.

    PubMed

    Mohammed, Yasir Serag Alnor; Eltayeb, Amin Elsadig; Tsujimoto, Hisashi

    2013-12-01

    Aluminum (Al) toxicity is the key factor limiting wheat production in acid soils. Soil liming has been used widely to increase the soil pH, but due to its high cost, breeding tolerant cultivars is more cost-effective mean to mitigate the problem. Tolerant cultivars could be developed by traditional breeding, genetic transformation or introgression of genes from wild relatives. We used 30 wheat alien chromosome addition lines to identify new genetic resources to improve wheat tolerance to Al and to identify the chromosomes harboring the tolerance genes. We evaluated these lines and their wheat background Chinese Spring for Al tolerance in hydroponic culture at various Al concentrations. We also investigated Al uptake, oxidative stress and cell membrane integrity. The L. racemosus chromosomes A and E significantly enhanced the Al tolerance of the wheat in term of relative root growth. At the highest Al concentration tested (200 μM), line E had the greatest tolerance. The introgressed chromosomes did not affect Al uptake of the tolerant lines. We attribute the improved tolerance conferred by chromosome E to improved cell membrane integrity. Chromosome engineering with these two lines could produce Al-tolerant wheat cultivars. PMID:24399913

  6. INCIDENCE OF CHROMOSOME ABERRATIONS IN MAMMALIAN SPERM STAINED WITH HOECHST 33342 AND UV-LASER IRRADIATED DURING FLOW SORTING

    EPA Science Inventory

    The separation of two sperm populations is possible using the technique of flow sorting, provided that a significant difference exists in the DNA content of X- and Y-bearing sperm. In order to ascertain whether or not chromosome damage was induced in sorted sperm, chromosome prep...

  7. Anticlastogenic effects of a polyvitamin product, 'Pharmavit', on gamma-ray induction of somatic and germ cell chromosome aberrations in the mouse.

    PubMed

    Benova, D K

    1992-10-01

    The polyvitamin product 'Pharmavit' (Pv), comprising vitamins A, D2, B1, B2, B6, C, E, nicotinamide, and calcium pantothene, was tested for anticlastogenic properties against gamma-rays in mice. Pretreatment with Pv consisted of daily administration by gavage for 30 days at dose levels corresponding to clinical recommendations for an adult human, as recalculated in terms of mg/kg. Findings indicated a reduction of chromosome aberrations in bone marrow cells from mice exposed to 3.0 Gy 137Cs gamma-rays; the reduction concerned predominantly fragments of the chromatid type. Furthermore, a reduction factor of 1.6 was obtained for the frequency of reciprocal translocations induced by spermatogonial irradiation in mice exposed to 4.0 Gy gamma-rays. Pretreatment with vitamin C alone, at the dose present in Pv, proved nearly ineffective in protecting from chromosome aberrations in bone marrow cells. Pharmavit is believed to be a promising agent for application to human populations exposed to the carcinogenic and genetic hazards of ionizing radiation. PMID:1383709

  8. Transient presence of clonal chromosomal aberrations in Ph-negative cells in patients with chronic myeloid leukemia remaining in deep molecular response on tyrosine kinase inhibitor treatment.

    PubMed

    Gniot, Michał; Lewandowski, Krzysztof; Ratajczak, Błażej; Lewandowska, Maria; Lehmann-Kopydłowska, Agata; Jarmuż-Szymczak, Małgorzata; Komarnicki, Mieczysław

    2014-01-01

    Advancements in treatment of chronic myeloid leukemia (CML) turned this formerly fatal neoplasm into a manageable chronic condition. Therapy with tyrosine kinase inhibitors (TKIs) often leads to significant reduction of disease burden, known as the deep molecular response (DMR). Herein, we decided to analyze the cohort of CML patients treated in our center with TKIs, who obtain and retain DMR for a period longer than 24 months. The aim of the study was to evaluate the frequency of clonal cytogenetic aberrations in Philadelphia-negative (Ph-) cells in patients with DMR during TKI treatment. The analyzed data was obtained during routine molecular and cytogenetic treatment monitoring, using G-banded trypsin and Giemsa stain (GTG) karyotyping and reverse transcription quantitative PCR. We noticed that approximately 50% of patients (28 of 55) in DMR had, at some follow-up point, transient changes in the karyotype of their Ph- bone marrow cells. In 9.1% of cases (5 of 55), the presence of the same aberrations was observed at different time points. The most frequently appearing aberrations were monosomies of chromosomes 19, 20, 21, and Y. Statistical analysis suggests that the occurrence of such abnormalities in CML patients correlates with the TKI treatment time. PMID:25496750

  9. Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified.

    PubMed Central

    Cropp, C S; Lidereau, R; Campbell, G; Champene, M H; Callahan, R

    1990-01-01

    The loss of heterozygosity (LOH) at specific regions of the human genome in tumor DNA is recognized as evidence for a tumor-suppressor gene located within the corresponding region of the homologous chromosome. Restriction fragment length polymorphism analysis of a panel of primary human breast tumor DNAs has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by LOH. Deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas. Previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have LOH on chromosomes 1p and 3p. This suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas. Images PMID:1977164

  10. 'BioQuaRT' project: design of a novel in situ protocol for the simultaneous visualisation of chromosomal aberrations and micronuclei after irradiation at microbeam facilities.

    PubMed

    Patrono, C; Monteiro Gil, O; Giesen, U; Langner, F; Pinto, M; Rabus, H; Testa, A

    2015-09-01

    The aim of the 'BioQuaRT' (Biologically weighted Quantities in RadioTherapy) project is to develop measurement techniques for characterising charged particle track structure on different length scales, and to correlate at the cellular level the track structure properties with the biological effects of radiation. This multi-scale approach will allow characterisation of the radiation qualities used in radiotherapy and the related biological effects. Charged-particle microbeam facilities were chosen as the platforms for all radiobiology experiments in the 'BioQuaRT' project, because they allow targeting single cells (or compartments of a cell) with a predefined number of ionising particles and correlating the cell-by-cell induced damage with type and energy of the radiation and with the number of ions per cell. Within this project, a novel in situ protocol was developed for the analysis of the misrepaired and/or unrepaired chromosome damage induced by charged-particle irradiations at the Physikalisch-Technische Bundesanstalt (PTB) ion microbeam facility. Among the cytogenetic biomarkers to detect and estimate radiation-induced DNA damage in radiobiology, chromosomal aberrations and micronuclei were chosen. The characteristics of the PTB irradiation system required the design of a special in situ assay: specific irradiation dishes with a base made from a biofoil 25-µm thick and only 3000-4000 cells seeded and irradiated per dish. This method was developed on Chinese hamster ovary (CHO) cells, one of the most commonly used cell lines in radiobiology in vitro experiments. The present protocol allows the simultaneous scoring of chromosome aberrations and micronuclei on the same irradiated dish. Thanks to its versatility, this method could also be extended to other radiobiological applications besides the single-ion microbeam irradiations. PMID:25877532

  11. Induction of asymmetrical type of chromosomal aberrations in cultured human lymphocytes by ion beams of different energies at varying LET from HIMAC and RRC.

    PubMed

    Ohara, H; Okazaki, N; Monobe, M; Watanabe, S; Kanayama, M; Minamihisamatsu, M

    1998-01-01

    Frequencies of asymmetrical type of chromosome aberration were scored in cultured human blood lymphocytes irradiated with carbon and neon beams. Blood cells were irradiated with various doses to establish dose response curves for chromosome aberration frequency vs. dose, and chromosome preparation was made by conventional method. Dose response curves for the per cell frequencies of the dicentrics and centric rings as well as the excess amount of acentric fragments were described for 7 different qualities (LET = 22.4, 40.0, 41.5, 69.9, 70.0, 100.0 and 150 KeV/micrometer) of carbon and neon beams with three different energies, 135, 290 and 400 MeV/u. From the analysis of those dose response curves, the maximum effect was found in the region of LET value at near 70 KeV/micrometer together with linear expression in the response from all endpoints examined. The 135 MeV/u of carbons (69.9 KeV/micrometer) and neons(70.0 KeV/micrometer) showed linear response. The 290 MeV/u of carbons (100 KeV/m) and neons (150 KeV/micrometer) showed medium effects with different shape of response, linear with a plateau and upward concavity. The 2 carbon beams (41.5 and 40 KeV/micrometer) from 2 different accelerators showed much discrepancy in the response. RBE-LET relationship was also described by comparing the coefficient alpha of the 7 different dose responses. The peak (near 70 KeV/m) was localized close to that (80 KeV/m) for the survivals of dsb repair deficient cells (Eguchi-Kasai et al. 1998), but in different position from that previously reported in many other studies (100-200 KeV/mm). Identification of the RBEmax in the present study has yet to be definitive. PMID:11542411

  12. Identification of aberrant chromosomes on the basis of morphometry of synaptonemal complexes in the sterile male mouse

    SciTech Connect

    Kalinskaya, E.I.; Chepyzhov, V.V.; Bogdanov, Yu.F.

    1989-01-01

    The results of an investigation of the synaptonemal complexes (SCs) of spermatocytes of sterile males of the house mouse from the progeny of parents subjected to the action of a mutagen are presented in this study. A nonreciprocal translocation was readily identified by the configuration of the SCs. The translocation was observed at pachytene in 100% of cells; at diakinesis-metaphase I, in 58% of cells. A different pattern of association of the X chromosome with the rearrangement region was found in pachytene spermatocytes. Computer analysis of the relative lengths of the synaptonemal complex during the pachytene stage permitted the determination that the translocation took place from the 4th autosome to the 16th. The translocated segment was 66-75% of chromosome 4. In chromosome 16 the point of rupture is close to the distal end, and it was not possible to find the broken-off telomeric fragment of this chromosome in the male under study.

  13. Recombination between the mouse Y chromosome short arm and an additional Y short arm-derived chromosomal segment attached distal to the X chromosome PAR.

    PubMed

    Decarpentrie, Fanny; Ojarikre, Obah A; Mitchell, Michael J; Burgoyne, Paul S

    2016-06-01

    In a male mouse, meiosis markers of processed DNA double strand breaks (DSBs) such as DMC1 and RAD51 are regularly seen in the non-PAR region of the X chromosome; these disappear late in prophase prior to entry into the first meiotic metaphase. Marker evidence for DSBs occurring in the non-PAR region of the Y chromosome is limited. Nevertheless, historically it has been documented that recombination can occur within the mouse Y short arm (Yp) when an additional Yp segment is attached distal to the X and/or the Y pseudoautosomal region (PAR). A number of recombinants identified among offsprings involved unequal exchanges involving repeated DNA segments; however, equal exchanges will have frequently been missed because of the paucity of markers to differentiate between the two Yp segments. Here, we discuss this historical data and present extensive additional data obtained for two mouse models with Yp additions to the X PAR. PCR genotyping enabled identification of a wider range of potential recombinants; the proportions of Yp exchanges identified among the recombinants were 9.7 and 22.4 %. The frequency of these exchanges suggests that the Yp segment attached to the X PAR is subject to the elevated level of recombinational DSBs that characterizes the PAR. PMID:26596988

  14. Structural aberration of the X chromosome in a patient with gonadal dysgenesis: an approach to karyotype-phenotype correlation.

    PubMed Central

    Varella-Garcia, M; Tajara, E H; Gagliardi, A R

    1981-01-01

    An 18-year-old female with some stigmata of pure dysgenesis had a chromosome constitution of 46,X,dir dup(X) (pter leads to q27: :q21 leads to qter). The abnormal chromosome was always late replicating. The clinical and cytogenetic picture is compared with that of patients with X;X translocation and some problems of karyotype-phenotype correlation are discussed. Images PMID:7241547

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

    PubMed

    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. PMID:26601536

  16. MFISH Measurements of Chromosomal Aberrations Individuals Exposed in Utero to Gamma-ray Doses from 5 to 20 cGy

    SciTech Connect

    Brenner, David J.

    2009-11-17

    Our plan was to identify and obtain blood from 36 individuals from the Mayak-in-utero exposed cohort who were exposed in utero only to gamma ray does doses fro 5 to 20 cGy. Our goal is to do mFISH and in a new development, single-arm mFISH on these samples to measure stable chromosome aberrations in these now adult individuals. The results were compared with matched control individuals (same age, same gender) available from the large control population which we are studying in the context of our plutonium worker study. The long term goal was to assess the results both in terms of the sensitivity of the developing embryo/fetus to low doses of ionizing radiation, and in terms of different potential mechanisms (expanded clonal origin vs. induced instability) for an increased risk.

  17. SISTER CHROMATID EXCHANGE AND CHROMOSOME ABERRATION ANALYSES IN MICE AFTER IN VIVO EXPOSURE TO ACRYLONITRILE, STYRENE, OR BUTADIENE MONOXIDE

    EPA Science Inventory

    The use of polymers in plastic and rubber products has generated concern that monomers potentially active in biological systems may be eluted from these substances. The authors have evaluated two such monomers, acrylonitrile and styrene, for the induction of chromosome damage in ...

  18. CHROMOSOME 11 ABERRATIONS IN SMALL COLONY L5178Y TK-/-MUTANTS EARLY IN THEIR CLONAL HISTORY

    EPA Science Inventory

    The authors have developed a cytogenetic technique that allows observation of chromosome rearrangements associated with TK-/- mutagenesis of the L5178Y/TK+/-3.7.2C cell line early in mutant clonal history. For a series of mutagenic treatments they show that the major proportion (...

  19. 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.

    PubMed

    Holmes, Amie L; Joyce, Kellie; Xie, Hong; Falank, Carolyne; Hinz, John M; Wise, John Pierce

    2014-04-01

    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. PMID:24561002

  20. Search for additional replication terminators in the Bacillus subtilis 168 chromosome.

    PubMed

    Griffiths, A A; Wake, R G

    1997-05-01

    The Bacillus subtilis 168 chromosome is known to contain at least six DNA replication terminators in the terminus region of the chromosome. By using a degenerate DNA probe for the consensus terminator sequence and low-stringency hybridization conditions, several additional minor hybridizing bands were identified. DNA corresponding to the most intense of these bands was cloned and characterized. Although localized in the terminus region, it could not bind RTP and possibly represents a degenerate terminator. A search of the SubtiList database identified an additional terminator sequence in the terminus region, near glnA. It was shown to bind RTP and to function in blocking replication fork movement in a polar manner. Its orientation conformed to the replication fork trap arrangement of the other terminators. The low-stringency hybridization experiments failed to identify any terminus region-type terminators in the region of the chromosome where postinitiation control sequences (STer sites) are known to reside. The two most likely terminators in STer site regions, in terms of sequence similarity to terminus region terminators, were identified through sequence searching. They were synthesized and were found not to bind RTP under conditions that allowed binding to terminus region terminators. Neither did they elicit fork arrest, when present in a plasmid, under stringent conditions. It is concluded that the STer site terminators, at least the first two to the left of oriC, do not have the typical consensus A+B site makeup of terminus region terminators. PMID:9150236

  1. Transition from a plasmid to a chromosomal mode of replication entails additional regulators

    PubMed Central

    Venkova-Canova, Tatiana; Chattoraj, Dhruba K.

    2011-01-01

    Plasmid origins of replication are rare in bacterial chromosomes, except in multichromosome bacteria. The replication origin of Vibrio cholerae chromosome II (chrII) closely resembles iteron-bearing plasmid origins. Iterons are repeated initiator binding sites in plasmid origins and participate both in replication initiation and its control. The control is mediated primarily by coupling of iterons via the bound initiators (“handcuffing”), which causes steric hindrance to the origin. The control in chrII must be different, since the timing of its replication is cell cycle-specific, whereas in plasmids it is random. Here we show that chrII uses, in addition to iterons, another kind of initiator binding site, named 39-mers. The 39-mers confer stringent control by increasing handcuffing of iterons, presumably via initiator remodeling. Iterons, although potential inhibitors of replication themselves, restrain the 39-mer–mediated inhibition, possibly by direct coupling (“heterohandcuffing”). We propose that the presumptive transition of a plasmid to a chromosomal mode of control requires additional regulators to increase the stringency of control, and as will be discussed, to gain the capacity to modulate the effectiveness of the regulators at different stages of the cell cycle. PMID:21444815

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

    PubMed Central

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

    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. PMID:22042656

  3. Focal Chromosomal Copy Number Aberrations Identify CMTM8 and GPR177 as New Candidate Driver Genes in Osteosarcoma

    PubMed Central

    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, <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. PMID:25551557

  4. Chromosome elimination, addition and introgression in intertribal partial hybrids between Brassica rapa and Isatis indigotica

    PubMed Central

    Tu, Yuqin; Sun, Jian; Ge, Xianhong; Li, Zaiyun

    2009-01-01

    Background and Aims Partial hybrids with female-parent-type phenotypes and chromosome numbers but altered genomic compositions have been reported in wide crosses of several plants. In order to introgress desirable genes from a wild relative, Isatis indigotica (a dye and medicinal plant; 2n = 14), into Brassica crops, intertribal sexual hybridizations were carried out with B. rapa (2n = 20), and the resulting hybrids and their progenies were characterized. Methods Using genomic in situ hybridization (GISH) and amplified fragment length polymorphism (AFLP), chromosomal/genomic components of the hybrids and their progenies were analysed. Key Results Many hybrid plants were obtained from the mature seeds harvested from the B. rapa × I. indigotica cross, and these exhibited different morphological traits. However, the majority of them did not survive and only three plants grew to maturity. These three hybrids showed poor growth and much smaller stature than the two parents, but had some morphological traits and chemical composition of I. indigotica. One plant had 2n = 10, the haploid chromosome number of B. rapa, and was absolutely sterile. The other two plants had 20 and 22 somatic chromosomes and were male sterile but produced seeds following pollinations with B. rapa. All back-cross progenies over several generations maintained a B. rapa-type phenotype and also displayed some variations in morphological characters and fatty acid compositions. They were all 2n = 20 and showed good seed-set. The hybrid with 2n = 22 produced some progeny plants with 2n = 21 and 2n = 22. GISH detected two chromosomes of I. indigotica in the hybrid with 2n = 22 but none in the one with 2n = 20. AFLP bands specific for I. indigotica, novel for two parents or absent in B. rapa, were detected in the two hybrids and their progenies. These progeny plants were novel B. rapa types with an altered genomic constitution or alien additions. Conclusions Complete or partial chromosome elimination and

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

    PubMed

    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. PMID:25752428

  6. Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

    PubMed Central

    Cervera, José; Montesinos, Pau; Hernández-Rivas, Jesús M.; Calasanz, María J.; Aventín, Anna; Ferro, María T.; Luño, Elisa; Sánchez, Javier; Vellenga, Edo; Rayón, Chelo; Milone, Gustavo; de la Serna, Javier; Rivas, Concha; González, José D.; Tormo, Mar; Amutio, Elena; González, Marcos; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2010-01-01

    Background Acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the t(15;17). The incidence and prognostic significance of additional chromosomal abnormalities in acute promyelocytic leukemia is still a controversial matter. Design and Methods Based on cytogenetic data available for 495 patients with acute promyelocytic leukemia enrolled in two consecutive PETHEMA trials (LPA96 and LPA99), we analyzed the incidence, characteristics, and outcome of patients with acute promyelocytic leukemia with and without additional chromosomal abnormalities who had been treated with all-trans retinoic acid plus anthracycline monochemotherapy for induction and consolidation. Results Additional chromosomal abnormalities were observed in 140 patients (28%). Trisomy 8 was the most frequent abnormality (36%), followed by abn(7q) (5%). Patients with additional chromosomal abnormalities more frequently had coagulopathy (P=0.03), lower platelet counts (P=0.02), and higher relapse-risk scores (P=0.02) than their counterparts without additional abnormalities. No significant association with FLT3/ITD or other clinicopathological characteristics was demonstrated. Patients with and without additional chromosomal abnormalities had similar complete remission rates (90% and 91%, respectively). Univariate analysis showed that additional chromosomal abnormalities were associated with a lower relapse-free survival in the LPA99 trial (P=0.04), but not in the LPA96 trial. However, neither additional chromosomal abnormalities overall nor any specific abnormality was identified as an independent risk factor for relapse in multivariate analysis. Conclusions The lack of independent prognostic value of additional chromosomal abnormalities in acute promyelocytic leukemia does not support the use of alternative therapeutic strategies when such abnormalities are found. PMID:19903674

  7. Genotoxicity evaluation of Guibi-Tang extract using an in vitro bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus test

    PubMed Central

    2014-01-01

    Background Guibi-Tang is a traditional herbal prescription made from 12 different herbs that is used in the treatment of amnesia and poor memory. Methods In the present study, we evaluated the acute oral toxicity and genotoxic potential of Guibi-Tang water extract (GBT) at doses up to 2000 μg/plate an using a bacterial reverse mutation test (Ames test) with Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537, and Escherichia coli strain WP2uvrA. Acute toxicity and genotoxic potential were measured in the presence and absence of an exogenous source of metabolic activation, in an in vitro chromosome aberration assay with Chinese hamster lung (CHL) cells, and in an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Food and Drug Administration. An acute oral toxicity test of GBT was performed in Sprague Dawley rats. The Ames test showed that GBT did not induce gene mutations in S. typhimurium or in E. coli in the presence or absence of S9 activation. Results GBT did not significantly increase the number of structural aberrations in CHL cells with or without S9 activation. The oral administration of GBT at a dose of up to 2000 mg/kg caused no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes. Conclusions However, as we did not identify the components of GBT responsible for these effects, other assays are needed to confirm its genotoxicity. PMID:24985139

  8. 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.

    PubMed

    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. PMID:25986082

  9. Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.

    PubMed

    Krause, Lutz; Nones, Katia; Loffler, Kelly A; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J; Watson, David I; Lord, Reginald V; Phillips, Wayne A; Gotley, David; Smithers, B Mark; Whiteman, David C; Hayward, Nicholas K; Grimmond, Sean M; Waddell, Nicola; Barbour, Andrew P

    2016-04-01

    The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. PMID:26905591

  10. Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma

    PubMed Central

    Krause, Lutz; Nones, Katia; Loffler, Kelly A.; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J.; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J.; Watson, David I.; Lord, Reginald V.; Phillips, Wayne A.; Gotley, David; Smithers, B.Mark; Whiteman, David C.; Hayward, Nicholas K.; Grimmond, Sean M.; Waddell, Nicola; Barbour, Andrew P.

    2016-01-01

    The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett’s esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. PMID:26905591

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

    PubMed Central

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

    2014-01-01

    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. PMID:24957674

  12. The Allium cepa chromosome aberration test reliably measures genotoxicity of soils of inhabited areas in the Ukraine contaminated by the Chernobyl accident.

    PubMed

    Kovalchuk, O; Kovalchuk, I; Arkhipov, A; Telyuk, P; Hohn, B; Kovalchuk, L

    1998-07-01

    The accident on the Chernobyl Nuclear Power Plant reactor IV in April 1986 led to the release of an enormous amount of radioactive material into the biosphere and to the formation of a complex pattern of nuclear contamination over a large area. As a consequence more than 5 million km2 of the soil in the Ukraine became contaminated with more than 1 Ci/km2 [1,2]. An assessment of the genetic consequences of the nuclear pollution is one of the most important problems. We applied the Allium cepa test to estimate the impact on plant chromosomes of nuclear pollution in the inhabited zones of the Ukraine. We tested soil from the obligatory resettlement zone (zone 2), where the mean density of pollution is 15-40 Ci/km2; zones of enhanced radiological control-zone 3, 5-15 Ci/km2 and zone 4, 1-5 Ci/km2. We found a dose-dependent increase in the fraction of aberrant mitoses from control values of 1.6 +/- 0.9% up to 23.8 +/- 5.0%, and a corresponding monotonous decrease of the mitotic index from 49.4 +/- 4.8% to a limiting value of 22.5 +/- 4.0% at pollution levels exceeding 35 Ci/km2 (activity of the soil samples exceeding 6000 Bq/kg, respectively). We observed a strong, significant correlation of 137Cs activity of soil samples with the percentage of chromosomal abnormalities, r = 0.97 (P < 0.05), and with the mitotic index, r = -0.93 (P < 0.05), in the roots of A. cepa, respectively. The results showed high toxicity and genotoxicity of radioactively polluted soils and confirmed the efficiency of the A. cepa test as a quick and inexpensive biological test for ecological and genetic risk assessment in the 'Chernobyl' zones. PMID:9711261

  13. Chromosome studies in the aquatic monocots of Myanmar: A brief review with additional records

    PubMed Central

    2014-01-01

    Abstract Myanmar (Burma) constitutes a significant component of the Indo-Myanmar biodiversity hotspot, with elements of the Indian, the Indochina, and the Sino-Japanese floristic regions, yet thus far only a few reliable sources of the country's flora have been available. As a part of a contribution for the floristic inventory of Myanmar, since it is important in a floristic survey to obtain as much information as possible, in addition to previous two reports, here we present three more chromosome counts in the aquatic monocots of Myanmar: Limnocharis flava with 2n = 20, Sagittaria trifolia with 2n = 22 (Alismataceae), and Potamogeton distinctus × Potamogeton nodosus with 2n = 52 (Potamogetonaceae); the third one is new to science. A brief review of cytological researches in the floristic regions' 45 non-hybrid aquatic monocots plus well investigated two inter-specific hybrids that are recorded in Myanmar is given, indicating that the further works with a focus on species in Myanmar that has infra-specific chromosome variation in the floristic regions will address the precise evolutionary history of the aquatic flora of Myanmar. PMID:24891826

  14. In vitro assessment of clastogenicity of mobile-phone radiation (835 MHz) using the alkaline comet assay and chromosomal aberration test.

    PubMed

    Kim, Ji-Young; Hong, Sae-Yong; Lee, Young-Mi; Yu, Shin-Ae; Koh, Woo Suk; Hong, Joong-Rak; Son, Taeho; Chang, Sung-Keun; Lee, Michael

    2008-06-01

    Recently we demonstrated that 835-MHz radiofrequency radiation electromagnetic fields (RF-EMF) neither affected the reverse mutation frequency nor accelerated DNA degradation in vitro. Here, two kinds of cytogenetic endpoints were further investigated on mammalian cells exposed to 835-MHz RF-EMF (the most widely used communication frequency band in Korean CDMA mobile phone networks) alone and in combination with model clastogens: in vitro alkaline comet assay and in vitro chromosome aberration (CA) test. No direct cytogenetic effect of 835-MHz RF-EMF was found in the in vitro CA test. The combined exposure of the cells to RF-EMF in the presence of ethylmethanesulfonate (EMS) revealed a weak and insignificant cytogenetic effect when compared to cells exposed to EMS alone in CA test. Also, the comet assay results to evaluate the ability of RF-EMF alone to damage DNA were nearly negative, although showing a small increase in tail moment. However, the applied RF-EMF had potentiation effect in comet assay when administered in combination with model clastogens (cyclophosphamide or 4-nitroquinoline 1-oxide). Thus, our results imply that we cannot confidently exclude any possibility of an increased risk of genetic damage, with important implications for the possible health effects of exposure to 835-MHz electromagnetic fields. PMID:18214898

  15. Assessment of Genotoxic Potential of Hridayarnava Rasa (A Herbo-Mineralo-Metallic Ayurvedic Formulation) Using Chromosomal Aberration and Sperm Abnormality Assays

    PubMed Central

    Jagtap, Chandrashekhar Y.; Chaudhari, Swapnil Y.; Thakkar, Jalaram H.; Galib, R.; Prajapati, P. K.

    2014-01-01

    Objectives: Herbo-mineral formulations are being successfully used in therapeutics since centuries. But recently, they came under the scanner for their metallic contents especially the presence of heavy metals. Hence it is the need of the hour to assess and establish the safety of these formulations through toxicity studies. In line with the various toxicity studies that are being carried out, Government of India expressed the need for conducting genotoxicity studies of different metal- or mineral-based drugs. Till date very few Ayurvedic herbo-mineral formulations have been studied for their genotoxic potential. The present study is aimed to evaluate the genotoxic potential of Hridayarnava Rasa. Materials and Methods: It was prepared as per classical guidelines and administered to Swiss albino mice for 14 consecutive days. Chromosomal aberration and sperm abnormality assay were done to evaluate the genotoxic potential of the test drugs. Cyclophosphamide (CP) was taken as positive group and results were compared. Results: All treated groups exhibited significant body weight gain in comparison to CP group. Results revealed no structural deformity in the above parameters in comparison to the CP-treated group. Conclusion: Reported data showed that both tested samples of Hridayarnava Rasa does not possess genotoxic potential under the experimental conditions and can be safely used. PMID:25948961

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

    PubMed Central

    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

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

    PubMed

    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. Effect of reducing the top concentration used in the in vitro chromosomal aberration test in CHL cells on the evaluation of industrial chemical genotoxicity.

    PubMed

    Morita, Takeshi; Honma, Masamitsu; Morikawa, Kaoru

    2012-01-24

    A current concern with in vitro mammalian cell genotoxicity testing is the high frequency of false or misleading positive results caused in part by the past use of excessively high test concentrations. A dataset of 249 industrial chemicals used in Japan and tested for genotoxicity was analyzed. Of these, 116 (46.6%) were positive in the in vitro chromosomal aberration (CA) test, including 6 that were positive only at test concentrations >10mM. There were 59 CA-positive chemicals at test concentrations ≤ 1mM. At >1mM, 51 chemicals were CA-positive, including 13 Ames-positive chemicals, which were therefore not "missed" by the test battery. Thus, 38 potentially positive chemicals would not have been detected in the test battery if the top test concentration was limited to 1mM in CA test. Analysis of the relevance of CA results on the 38 missed chemicals was conducted based on a weight of evidence approach, including evaluations of effects of extreme culture conditions (low pH, high toxicity, or precipitation), in silico structural alert analysis, in vivo genotoxicity and carcinogenicity test data (where available), mode of action, or information from closely related chemicals. After an exhaustive review, there were four chemicals with some concern for human health risk assessment, nine with minimal concern, and the remaining 25 with negligible concern. We apply different top concentrations to the 38 missed chemicals to identify the most accurate approach for predicting the genotoxicity of industrial chemicals. Of these 2mM or 1mg/mL, whichever is higher, was the most effective in detecting these chemicals, i.e., relatively higher (8/13) or lower (17/25) detection among 13 chemicals with some or minimal concern, or 25 with negligible concern, respectively. Lower top concentration limits, 1mM or 0.5mg/mL, whichever is higher, are not as effective (2/13) for detecting these chemicals with concern. Therefore, we conclude 2mM or 1mg/mL, whichever is higher, would be an

  19. Modeling cell response to low doses of photon irradiation: Part 2-application to radiation-induced chromosomal aberrations in human carcinoma cells.

    PubMed

    Cunha, Micaela; Testa, Etienne; Komova, Olga V; Nasonova, Elena A; Mel'nikova, Larisa A; Shmakova, Nina L; Beuve, Michaël

    2016-03-01

    The biological phenomena observed at low doses of ionizing radiation (adaptive response, bystander effects, genomic instability, etc.) are still not well understood. While at high irradiation doses, cellular death may be directly linked to DNA damage, at low doses, other cellular structures may be involved in what are known as non-(DNA)-targeted effects. Mitochondria, in particular, may play a crucial role through their participation in a signaling network involving oxygen/nitrogen radical species. According to the size of the implicated organelles, the fluctuations in the energy deposited into these target structures may impact considerably the response of cells to low doses of ionizing irradiation. Based on a recent simulation of these fluctuations, a theoretical framework was established to have further insight into cell responses to low doses of photon irradiation, namely the triggering of radioresistance mechanisms by energy deposition into specific targets. Three versions of a model are considered depending on the target size and on the number of targets that need to be activated by energy deposition to trigger radioresistance mechanisms. These model versions are applied to the fraction of radiation-induced chromosomal aberrations measured at low doses in human carcinoma cells (CAL51). For this cell line, it was found in the present study that the mechanisms of radioresistance could not be triggered by the activation of a single small target (nanometric size, 100 nm), but could instead be triggered by the activation of a large target (micrometric, [Formula: see text]) or by the activation of a great number of small targets. The mitochondria network, viewed either as a large target or as a set of small units, might be concerned by these low-dose effects. PMID:26708100

  20. A comparative biomonitoring study of populations residing in regions with low and high risk of lung cancer using the chromosome aberration and the micronucleus tests.

    PubMed

    Heepchantree, Worapa; Paratasilpin, Thipmani; Kangwanpong, Daoroong

    2005-11-10

    Chromosome aberration (CA) and micronucleus (MN) tests were performed in peripheral blood lymphocytes from people residing in two districts of Chiang Mai, Thailand, a high-risk area, Saraphi (n=107), where the lung cancer incidence is three-fold higher than in a low-risk area, Chom Thong (n=118). The percentage of cells with CAs was significantly lower in the Saraphi population than in the Chom Thong population (0.47+/-0.91 versus 1.04+/-1.18, P=0.0001) as was the percentage of CAs (0.49+/-0.91 versus 1.08+/-1.21, P<0.0001) and the mitotic indices (1.25+/-0.44 versus 1.33+/-0.33, P=0.025). The frequency of MN in binucleated (BN) cells, however, was significantly higher in the Saraphi population (12.01+/-3.57 versus 9.99+/-3.11, P<0.0001) as was the percentage of BN cells with MN (1.14+/-0.31 versus 0.93+/-0.23, P<0.0001). There was no difference in the nuclear division indices (1.49+/-0.07 versus 1.47+/-0.11, P=0.1759) between the two populations. With regard to the effect of confounding factors, it was found that cigarette smoking influenced both CA and MN frequencies, and that the chewing of fermented tea leaves or betel nuts affected CA and sex affected MN frequencies. An increasing of CA and MN frequencies were seen in smokers and chewers over non-smokers and non-chewers, with CA frequencies being higher in Chom Thong smokers and chewers and MN frequency being higher in Saraphi smokers. However, pesticide exposure and alcohol consumption had no impact on CA and MN frequencies. Due to the conflicting results obtained in the two tests, we cannot make a clear statement regarding the potential effects of the environmental exposures in the two study populations. PMID:16185913

  1. Suppression of aflatoxin B1- or methyl methanesulfonate-induced chromosome aberrations in rat bone marrow cells after treatment with S-methyl methanethiosulfonate.

    PubMed

    Ito, Y; Nakamura, Y; Nakamura, Y

    1997-10-24

    The suppressive effect of S-methyl methanethiosulfonate (MMTS) on aflatoxin B1 (AFB1)- or methyl methanesulfonate (MMS)-induced chromosome aberrations (CA) in rat bone marrow cells was studied. MMTS significantly suppressed CA induced by both AFB1 (an indirect-acting carcinogen) and MMS (a direct-acting carcinogen). Suppression was observed at all periods (6, 12, 18, 24 and 48 h) after AFB1 or MMS treatment and in all doses of AFB1 (5, 10 and 20 mg/kg) or MMS (50, 75 and 100 mg/kg) investigated. AFB1-induced CA was potently suppressed by MMTS given between 2 h before and 6 h after the AFB1 injection. The suppression of AFB1-induced CA by MMTS paralleled the dose of MMTS when MMTS was given in a dose range of 1-20 mg/kg body weight. MMS-induced CA was potently suppressed by MMTS given between 2 h before and 2 h after the MMS injection. The suppressive effect of MMTS on MMS-induced CA paralleled the dose of MMTS when MMTS was given in a dose range of 1-15 mg/kg body weight. Diphenyl disulfide, which modifies -SH groups in proteins like MMTS, also significantly suppressed both AFB1- and MMS-induced CA. Although other mechanisms are not excluded, the suppression of carcinogen-induced CA by MMTS may result from the ability of MMTS to modify -SH groups in proteins. The juices of cabbage and onion, which contain considerable amounts of MMTS and S-methyl-L-cysteinesulfoxide (the precursor of MMTS), also significantly suppressed AFB1- or MMS-induced CA. These results suggest that MMTS is a possible chemopreventive agent against cancer. PMID:9393623

  2. Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

    PubMed

    Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

    2007-03-01

    Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose. PMID:17174592

  3. Genomic in situ hybridization analysis of Thinopyrum chromatin in a wheat-Th. intermedium partial amphiploid and six derived chromosome addition lines

    PubMed

    Chen; Conner; Laroche; Ji; Armstrong; Fedak

    1999-12-01

    The genomic origin of alien chromosomes present in a wheat-Thinopyrum intermedium partial amphiploid TAF46 (2n = 8x = 56) and six derived chromosome addition lines were analyzed by genomic in situ hybridization (GISH) using S genomic DNA from Pseudoroegneria strigosa (2n = 2x = 14, SS) as a probe. The GISH analysis clearly showed that the chromosome complement of the partial amphiploid TAF46 consists of an entire wheat genome plus one synthetic genome consisting of a mixture of six S genome chromosomes and eight J (=E) genome chromosomes derived from Th. intermedium (2n = 6x = 42, JJJ(s)J(s)SS). There were no Js genome chromosomes present in TAF46. The J genome chromosomes present in TAF46 displayed a unique GISH hybridization pattern with the S genomic DNA probe, in which S genome DNA strongly hybridized at the terminal regions and weakly hybridized over the remaining parts of the chromosomes. This provides a diagnostic marker for distinguishing J genome chromosomes from Js or S genome or wheat ABD genome chromosomes. The genomic origin of the alien chromosomes present in the six derived chromosome addition lines were identified by their characteristic GISH hybridization patterns with S genomic DNA probe. GISH analysis showed that addition lines L1, L2, L3, and L5 carried one pair of J genome chromosomes, while addition lines L4 and L7 each carried one pair of S genome chromosomes. GISH patterns detected by the S genome probe on addition line of L1 were identical to those of the J genome chromosomes present in the partial amphiploid TAF46, suggesting that these chromosomes were not structurally altered when they were transferred from TAF46 to addition lines. PMID:10659790

  4. Scoliosis and vertebral anomalies: additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement.

    PubMed

    Al-Kateb, Hussam; Khanna, Geetika; Filges, Isabel; Hauser, Natalie; Grange, Dorothy K; Shen, Joseph; Smyser, Christopher D; Kulkarni, Shashikant; Shinawi, Marwan

    2014-05-01

    The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement. PMID:24458548

  5. Development and Characterization of a Psathyrostachys huashanica Keng 7Ns Chromosome Addition Line with Leaf Rust Resistance

    PubMed Central

    Du, Wanli; Wang, Jing; Wang, Liangming; Zhang, Jun; Chen, Xinhong; Zhao, Jixin; Yang, Qunhui; Wu, Jun

    2013-01-01

    The aim of this study was to characterize a Triticum aestivum-Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs) disomic addition line 2-1-6-3. Individual line 2-1-6-3 plants were analyzed using cytological, genomic in situ hybridization (GISH), EST-SSR, and EST-STS techniques. The alien addition line 2-1-6-3 was shown to have two P. huashanica chromosomes, with a meiotic configuration of 2n = 44 = 22 II. We tested 55 EST-SSR and 336 EST-STS primer pairs that mapped onto seven different wheat chromosomes using DNA from parents and the P. huashanica addition line. One EST-SSR and nine EST-STS primer pairs indicated that the additional chromosome of P. huashanica belonged to homoeologous group 7, the diagnostic fragments of five EST-STS markers (BE404955, BE591127, BE637663, BF482781 and CD452422) were cloned, sequenced and compared. The results showed that the amplified polymorphic bands of P. huashanica and disomic addition line 2-1-6-3 shared 100% sequence identity, which was designated as the 7Ns disomic addition line. Disomic addition line 2-1-6-3 was evaluated to test the leaf rust resistance of adult stages in the field. We found that one pair of the 7Ns genome chromosomes carried new leaf rust resistance gene(s). Moreover, wheat line 2-1-6-3 had a superior numbers of florets and grains per spike, which were associated with the introgression of the paired P. huashanica chromosomes. These high levels of disease resistance and stable, excellent agronomic traits suggest that this line could be utilized as a novel donor in wheat breeding programs. PMID:23976963

  6. Recurrent 12q13-15 chromosomal aberrations, high frequency of isocitrate dehydrogenase 1 mutations, and absence of high mobility group AT-hook 2 expression in periosteal chondromas

    PubMed Central

    PANAGOPOULOS, IOANNIS; GORUNOVA, LUDMILA; TAKSDAL, INGEBORG; BJERKEHAGEN, BODIL; HEIM, SVERRE

    2015-01-01

    Periosteal chondroma is a benign cartilage tumor that accounts for <2% of chondromas. In the present study, four cases of periosteal chondromas were cytogenetically investigated and studied for the expression of high-mobility group AT-hook 2 (HMGA2), mutations in codons 132 of isocitrate dehydrogenase (IDH)1 and 172 of IDH2; mutations -C228T and -C250T in the promoter region of telomerase reverse transcriptase (TERT); and for methylation in the promoter regions of O-6-methylguanine-DNA methyltransferase (MGMT) and cellular retinol binding protein 1 (CRBP1). Chromosome aberrations of 12q13-15 were found in two out of the four tumors, while two had a normal karyotype. Two periosteal chondromas carried the mutation IDH1R132C (CGT>TGT), and two carried the mutation IDH1R132L (CGT>CTT). However, none of the four tumors had methylated MGMT and CRBP1 promoters or mutations at codon 172 of IDH2. In addition, -C228T and -C250T mutations were not present in the promoter region of TERT, nor was HMGA2 demonstrated to be expressed. The present study indicated that in periosteal chondromas, the involvement of 12q13-15 in structural rearrangements may be recurrent but that HMGA2 is not expressed. Additionally, the periosteal chondromas investigated in the study carried a heterozygous IDH1R132 mutation, the MGMT and CRBP1 promoters were not methylated, and -C228T and -C250T mutations in the promoter region of TERT were absent. PMID:26170993

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

    PubMed

    Rithidech, Kanokporn Noy; Honikel, Louise M; Reungpathanaphong, Paiboon; Tungjai, Montree; Jangiam, Witawat; Whorton, Elbert B

    2015-11-01

    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 (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 (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 (5 mC) and 5-hydroxymethylcytosine (5 hmC). 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 (28)Si ions. Slight increases in the levels of 5 mC were observed in all treatment groups, as compared to the sham-control level. In contrast, there was a significant reduction in levels of 5 hmC (ANOVA, p<0.01). Since these endpoints were evaluated in the same mouse, our data suggested for the first time a link between a reduction in 5 hmC and genomic instability in HSPC-derived myeloid colonies of CBA/CaJ mice exposed to 300 Me

  8. Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma.

    PubMed

    Yen, Chueh-Chuan; Chen, Wei-Ming; Chen, Tain-Hsiung; Chen, Winby York-Kwan; Chen, Paul Chih-Hsueh; Chiou, Hong-Jen; Hung, Giun-Yi; Wu, Hung-Ta Hondar; Wei, Chao-Jung; Shiau, Cheng-Ying; Wu, Yu-Chung; Chao, Ta-Chung; Tzeng, Cheng-Hwai; Chen, Po-Min; Lin, Chi-Hung; Chen, Yann-Jang; Fletcher, Jonathan A

    2009-10-01

    Five osteosarcoma (OS) cell lines, 37 OS tumors and 9 corresponding non-neoplastic samples were genotyped by Affymetrix 10 K 2.0 SNP array. Regions of high level amplification and homozygous deletion were identified and validated by quantitative PCR and FISH. Certain recurrent cytogenetic alterations were more frequent in recurrent/metastatic than in primary OS. These included deletion of 6q14.1, 6q16.2-q22.31, and 8p23.2-p12, amplification of 8q21.12, 8q22.3-q24.3 and 17p12, and loss of heterozygosity (LOH) at 2q24.3-q31.2, 5q11.2, 6p21.31-p21.1, 6q14.1-q16.2, 8p22-p12, 9q22.1, 10q21.1-q22.1, 10q23.31-q24.1, 12q15-q21.1 and 21q21.2-q21.3. Most of the LOH calls were associated with deletion, but a subset of them was associated with normal or increased copy number (CN). A consensus 3q13.31 deletion localized to a region within the limbic system-associated membrane protein (LSAMP) gene was also identified. The FISH evaluations demonstrated highly-localized homozygous or heterozygous LSAMP deletions in 6 of 11 primary OS. qRT-PCR evaluations of the two major alternative LSAMP transcripts demonstrated reduced expression of 1b isoform transcript in each of three OS with LSAMP exon 1b deletion. Further, the 1a isoform transcripts in these same OS had either reduced expression or a premature termination codon in LSAMP exon 2. This SNP genotyping study identified chromosomal aberrations associated with disease progression in OS and disclosed LSAMP as a novel tumor suppressor gene in OS. The study also demonstrated that CN and LOH analyses were able to detect distinct subsets of genetic abnormalities in OS. PMID:19724913

  9. Screening and incorporation of rust resistance from Allium cepa into bunching onion (Allium fistulosum) via alien chromosome addition.

    PubMed

    Wako, Tadayuki; Yamashita, Ken-ichiro; Tsukazaki, Hikaru; Ohara, Takayoshi; Kojima, Akio; Yaguchi, Shigenori; Shimazaki, Satoshi; Midorikawa, Naoko; Sakai, Takako; Yamauchi, Naoki; Shigyo, Masayoshi

    2015-04-01

    Bunching onion (Allium fistulosum L.; 2n = 16), bulb onion (Allium cepa L. Common onion group), and shallot (Allium cepa L. Aggregatum group) cultivars were inoculated with rust fungus, Puccinia allii, isolated from bunching onion. Bulb onions and shallots are highly resistant to rust, suggesting they would serve as useful resources for breeding rust resistant bunching onions. To identify the A. cepa chromosome(s) related to rust resistance, a complete set of eight A. fistulosum - shallot monosomic alien addition lines (MAALs) were inoculated with P. allii. At the seedling stage, FF+1A showed a high level of resistance in controlled-environment experiments, suggesting that the genes related to rust resistance could be located on shallot chromosome 1A. While MAAL, multi-chromosome addition line, and hypoallotriploid adult plants did not exhibit strong resistance to rust. In contrast to the high resistance of shallot, the addition line FF+1A+5A showed reproducibly high levels of rust resistance. PMID:26218854

  10. 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.

    PubMed

    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. PMID:27017218

  11. Synthesis and characterization of advanced durum wheat hybrids and addition lines with thinopyrum chromosomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Durum wheat (Triticum turgidum L., 2n = 4x = 28; AABB genomes) is a natural hybrid – an allotetraploid between two wild species, Triticum urartu Tumanian (AA genome) and Aegilops speltoides Tausch (BB genome). As shown earlier, even at the allotetraploid level, durum wheat can tolerate chromosomal ...

  12. Seedling tolerance to Rhizoctonia and Pythium in wheat chromosome group 4 addition lines from Thinopyrum spp

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chromosome 4 from Thinopyrum spp. confers regrowth after a sexual cycle and senescence in hexaploid wheat (Triticum aestivum), and is associated with resistance to the necrotrophic eyespot pathogen, Tapesia yallundae. We sought to determine whether robust root growth or other traits expressed in ch...

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Chromosome and cell genetics

    SciTech Connect

    Sharma, A.K.; Sharma, A.

    1985-01-01

    This book contains 11 chapters. Some of the titles are: Chromosomes in differentiation; Chromosome axis; Nuclear and organelle split genes; Chemical mutagenesis; and Chromosome architecture and additional elements.

  15. Array-Based Comparative Genomic Hybridization Analysis Reveals Chromosomal Copy Number Aberrations Associated with Clinical Outcome in Canine Diffuse Large B-Cell Lymphoma

    PubMed Central

    Bresolin, Silvia; Marconato, Laura; Comazzi, Stefano; Te Kronnie, Geertruy; Aresu, Luca

    2014-01-01

    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. PMID:25372838

  16. Chromosomal Disorders and Autism.

    ERIC Educational Resources Information Center

    Gillberg, Christopher

    1998-01-01

    This paper reviews the literature on chromosomal aberrations in autism, especially possible gene markers. It notes that Chromosome 15 and numerical and structural abnormalities of the sex chromosomes have been most frequently reported as related to the genesis of autism. (Author/DB)

  17. Chromosomal development of cancer

    SciTech Connect

    1993-12-31

    Chapter 30, describes the chromosomal development of cancer. It has been established through cytological research that the number of chromosomes in cancer cells often deviates greatly from the usual number in healthy cells of the host organism. This chapter includes discussions on chromosome studies in ascites tumors, stemline and tumor development, mitotic aberrations in cancer, and selection and tumor progression. 25 refs., 2 figs.

  18. FISH to mitotic chromosomes and extended DNA fibres of Beta procumbens in a series of monosomic additions to beet (B. vulgaris).

    PubMed

    Mesbah, M; Wennekes-Van Eden, J; De Jong, J H; De Bock, T S; Lange, W

    2000-01-01

    The physical localization and organization of a Procumbentes-specific repetitive DNA sequence, PB6-4, on the chromosomes of Beta procumbens (2n = 18) were studied, using FISH (fluorescence in situ hybridization) to mitotic chromosomes and extended DNA fibres. The chromosomes of B. procumbens were studied in metaphase complements of the species itself, as well as in preparations of a series of eight different B. procumbens-derived monosomic additions to B. vulgaris (2n = 18). FISH to chromosome spreads of B. procumbens revealed that PB6-4 hybridizes to all chromosomes, predominantly in the pericentromeric regions, but with differences in size and brightness of the signals. Hybridization of PB6-4 to metaphase complements of B. vulgaris revealed no signals, indicating that cross-hybridization with the genome of this species was negligible. Consequently, hybridization of PB6-4 to metaphase complements of the monosomic additions yielded fluorescent signals on the alien chromosomes only. The previously observed differences in size and brightness of the fluorescent spots were confirmed using the single alien chromosomes. FISH of PB6-4 to extended DNA fibres of the monosomic additions indicated differences in the fluorescent track lengths between the alien chromosomes. Measurements of the fluorescent tracts allowed classification into discrete groups, varying from one to three groups per B. procumbens chromosome. The data revealed that the brightness or size of the signal at mitotic metaphase and the length of the fluorescent tracks on the DNA fibres were correlated. PMID:10919719

  19. Loss of sex chromosomes in the hematopoietic disorders: Questions, concerns and data interpretation

    SciTech Connect

    Slovak, M.L.

    1994-09-01

    The significance of sex chromosome aberrations in the hematopoietic disorders has not yet been defined. Interpretive problems stem from (1) the loss of a sex chromosome associated with aging, (2) sex chromosome loss as the sole aberration in leukemia is rare, (3) random -(X or Y) is observed frequently in bone marrow samples, and (4) constitutional sex chromosome anomalies must be ruled out in cancer and follow-up may not be possible. The COH database identified 41 patients (pts) with sex chromosome loss. Loss of a sex chromosome was common in myeloid disorders (21/41). In t(8;21) leukemia (n=10), -(X or Y) was a common secondary karyotypic change. Additionally, -Y was associated with clonal evolution in 2 Ph + CML pts. In 2 elderly pts with myeloid disorders, -(X or Y) was observed in complex karyotypes with dmins; however, in the lymphoproliferative disorders -(X or Y) was noted in elderly pts without apparent pathogenetic significance. Three pts had constitutional sex chromosome aberrations: CML in 45,X; ALL in 47, XXY; and RAEB-IT in mos45,X/46,XX. In the mos45,X/46,XX pt, the leukemic clone was associated with the 45,X line without other karyotypic changes. Non-clonal aberrations were observed in 11 cases; in 3 cases these non-clonal losses were observed in serial samples. In a sex-mismatched BMT case, -(X or Y) in 4 cells was one of the first pathogenetic signs of leukemia relapse. These data suggest (1) interpretation of sex chromosome loss in leukemia must be made with caution and after a baseline sample, (2) non-clonal aberrations should be recorded, and (3) -(X or Y) appears to have pathogenetic significance in the myeloid disorders. Multi-institutional studies are needed to define (1) the incidence of leukemia in pts with constitutional sex chromosome anomalies and (2) the incidence and significance of sex chromosome aberrations as the primary (sole) cytogenetic aberration in leukemia.

  20. The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34.

    PubMed Central

    von Lindern, M; Poustka, A; Lerach, H; Grosveld, G

    1990-01-01

    The specific (6;9)(p23;q34) chromosomal translocation is associated with a defined subtype of acute nonlymphocytic leukemia (ANLL). The 9q34 breakpoint is located at the telomeric side of the c-abl gene. Through a combination of chromosome jumping, long-range mapping, and chromosome walking, the chromosome 9 breakpoints of several t(6;9) ANLL patients were localized within a defined region of 8 kilobases (kb), 360 kb telomeric of c-abl. Subsequent cDNA cloning revealed that this region represented an intron in the middle of a gene, called Cain (can), encoding a 7.5-kb transcript. Disruption of the can gene by the translocation resulted in the expression of a new 5.5-kb can mRNA from the 6p- chromosome. Isolation of chromosome 6 sequences showed that breakpoints on 6p23 also clustered within a limited stretch of DNA. These data strongly suggest a direct involvement of the translocation in the leukemic process of t(6;9) ANLL. Images PMID:2370860

  1. A new chromosome was born: comparative chromosome painting in Boechera.

    PubMed

    Koch, Marcus A

    2015-09-01

    Comparative chromosome painting is a powerful tool to study the evolution of chromosomes and genomes. Analyzing karyotype evolution in cruciferous plants highlights the origin of aberrant chromosomes in apomictic Boechera and further establishes the cruciferous plants as important model system for our understanding of plant chromosome and genome evolution. PMID:26228436

  2. Seed colour loci, homoeology and linkage groups of the C genome chromosomes revealed in Brassica rapa–B. oleracea monosomic alien addition lines

    PubMed Central

    Heneen, Waheeb K.; Geleta, Mulatu; Brismar, Kerstin; Xiong, Zhiyong; Pires, J. Chris; Hasterok, Robert; Stoute, Andrew I.; Scott, Roderick J.; King, Graham J.; Kurup, Smita

    2012-01-01

    Background and Aims Brassica rapa and B. oleracea are the progenitors of oilseed rape B. napus. The addition of each chromosome of B. oleracea to the chromosome complement of B. rapa results in a series of monosomic alien addition lines (MAALs). Analysis of MAALs determines which B. oleracea chromosomes carry genes controlling specific phenotypic traits, such as seed colour. Yellow-seeded oilseed rape is a desirable breeding goal both for food and livestock feed end-uses that relate to oil, protein and fibre contents. The aims of this study included developing a missing MAAL to complement an available series, for studies on seed colour control, chromosome homoeology and assignment of linkage groups to B. oleracea chromosomes. Methods A new batch of B. rapa–B. oleracea aneuploids was produced to generate the missing MAAL. Seed colour and other plant morphological features relevant to differentiation of MAALs were recorded. For chromosome characterization, Snow's carmine, fluorescence in situ hybridization (FISH) and genomic in situ hybridization (GISH) were used. Key Results The final MAAL was developed. Morphological traits that differentiated the MAALs comprised cotyledon number, leaf morphology, flower colour and seed colour. Seed colour was controlled by major genes on two B. oleracea chromosomes and minor genes on five other chromosomes of this species. Homoeologous pairing was largely between chromosomes with similar centromeric positions. FISH, GISH and a parallel microsatellite marker analysis defined the chromosomes in terms of their linkage groups. Conclusions A complete set of MAALs is now available for genetic, genomic, evolutionary and breeding perspectives. Defining chromosomes that carry specific genes, physical localization of DNA markers and access to established genetic linkage maps contribute to the integration of these approaches, manifested in the confirmed correspondence of linkage groups with specific chromosomes. Applications include marker

  3. Genetic markers on chromosome 7.

    PubMed Central

    Tsui, L C

    1988-01-01

    Chromosome 7 is frequently associated with chromosome aberrations, rearrangements, and deletions. It also contains many important genes, gene families, and disease loci. This brief review attempts to summarise these and other interesting aspects of chromosome 7. With the rapid accumulation of cloned genes and polymorphic DNA fragments, this chromosome has become an excellent substrate for molecular genetic studies. PMID:3290488

  4. High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase

    NASA Technical Reports Server (NTRS)

    George, K.; Wu, H.; Willingham, V.; Furusawa, Y.; Kawata, T.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

    2001-01-01

    PURPOSE: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. MATERIALS AND METHODS: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or gamma-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258 harlequin staining. RESULTS: There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48 h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. CONCLUSION: The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided.

  5. Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

    PubMed

    Bakhmutsky, Marina V; Squibb, Katherine; McDiarmid, Melissa; Oliver, Marc; Tucker, James D

    2013-10-01

    Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans. PMID:23933231

  6. Molecular Cytogenetic Identification of a New Wheat-Rye 6R Chromosome Disomic Addition Line with Powdery Mildew Resistance.

    PubMed

    An, Diaoguo; Zheng, Qi; Luo, Qiaoling; Ma, Pengtao; Zhang, Hongxia; Li, Lihui; Han, Fangpu; Xu, Hongxing; Xu, Yunfeng; Zhang, Xiaotian; Zhou, Yilin

    2015-01-01

    Rye (Secale cereale L.) possesses many valuable genes that can be used for improving disease resistance, yield and environment adaptation of wheat (Triticum aestivum L.). However, the documented resistance stocks derived from rye is faced severe challenge due to the variation of virulent isolates in the pathogen populations. Therefore, it is necessary to develop desirable germplasm and search for novel resistance gene sources against constantly accumulated variation of the virulent isolates. In the present study, a new wheat-rye line designated as WR49-1 was produced through distant hybridization and chromosome engineering protocols between common wheat cultivar Xiaoyan 6 and rye cultivar German White. Using sequential GISH (genomic in situ hybridization), mc-FISH (multicolor fluorescence in situ hybridization), mc-GISH (multicolor GISH) and EST (expressed sequence tag)-based marker analysis, WR49-1 was proved to be a new wheat-rye 6R disomic addition line. As expected, WR49-1 showed high levels of resistance to wheat powdery mildew (Blumeria graminis f. sp. tritici, Bgt) pathogens prevalent in China at the adult growth stage and 19 of 23 Bgt isolates tested at the seedling stage. According to its reaction pattern to different Bgt isolates, WR49-1 may possess new resistance gene(s) for powdery mildew, which differed from the documented powdery mildew gene, including Pm20 on chromosome arm 6RL of rye. Additionally, WR49-1 was cytologically stable, had improved agronomic characteristics and therefore could serve as an important bridge for wheat breeding and chromosome engineering. PMID:26237413

  7. Molecular Cytogenetic Identification of a New Wheat-Rye 6R Chromosome Disomic Addition Line with Powdery Mildew Resistance

    PubMed Central

    An, Diaoguo; Zheng, Qi; Luo, Qiaoling; Ma, Pengtao; Zhang, Hongxia; Li, Lihui; Han, Fangpu; Xu, Hongxing; Xu, Yunfeng; Zhang, Xiaotian; Zhou, Yilin

    2015-01-01

    Rye (Secale cereale L.) possesses many valuable genes that can be used for improving disease resistance, yield and environment adaptation of wheat (Triticum aestivum L.). However, the documented resistance stocks derived from rye is faced severe challenge due to the variation of virulent isolates in the pathogen populations. Therefore, it is necessary to develop desirable germplasm and search for novel resistance gene sources against constantly accumulated variation of the virulent isolates. In the present study, a new wheat-rye line designated as WR49-1 was produced through distant hybridization and chromosome engineering protocols between common wheat cultivar Xiaoyan 6 and rye cultivar German White. Using sequential GISH (genomic in situ hybridization), mc-FISH (multicolor fluorescence in situ hybridization), mc-GISH (multicolor GISH) and EST (expressed sequence tag)-based marker analysis, WR49-1 was proved to be a new wheat-rye 6R disomic addition line. As expected, WR49-1 showed high levels of resistance to wheat powdery mildew (Blumeria graminis f. sp. tritici, Bgt) pathogens prevalent in China at the adult growth stage and 19 of 23 Bgt isolates tested at the seedling stage. According to its reaction pattern to different Bgt isolates, WR49-1 may possess new resistance gene(s) for powdery mildew, which differed from the documented powdery mildew gene, including Pm20 on chromosome arm 6RL of rye. Additionally, WR49-1 was cytologically stable, had improved agronomic characteristics and therefore could serve as an important bridge for wheat breeding and chromosome engineering. PMID:26237413

  8. Similar rates of chromosomal aberrant secondary oocytes in two indigenous cattle (Bos taurus) breeds as determined by dual-color FISH.

    PubMed

    Pauciullo, A; Nicodemo, D; Cosenza, G; Peretti, V; Iannuzzi, A; Di Meo, G P; Ramunno, L; Iannuzzi, L; Rubes, J; Di Berardino, D

    2012-02-01

    In vitro-matured metaphase II (MII) oocytes with corresponding first polar bodies (I pb) from two indigenous cattle (Bos taurus) breeds have been investigated to provide specific data upon the incidence of aneuploidy. A total of 165 and 140 in vitro-matured MII oocytes of the Podolian (PO) and Maremmana (MA) breeds, respectively, were analyzed by fluorescence in situ hybridization using Xcen and five chromosome-specific painting probes. Oocytes with unreduced chromosome number were 13.3% and 6.4% in the two breeds, respectively, averaging 10.2%. In the PO, out of 100 MII oocytes + I pb analyzed, two oocytes were nullisomic for chromosome 5 (2.0%) and one disomic for the same chromosome (1.0%). In the MA, out of 100 MII oocytes + I pb, one oocyte was found nullisomic for chromosome 5 (1.0%) and one was disomic for the X chromosome (1.0%). Out of 200 MII oocytes + I pb, the mean rate of aneuploidy (nullisomy + disomy) for the two chromosomes scored was 2.5%, of which 1.5% was due to nullisomy and 1.0% due to disomy. By averaging these data with those previously reported on dairy cattle, the overall incidence of aneuploidy in cattle, as a species, was 2.25%, of which 1.25% was due to nullisomy and 1.0% due to disomy. The results so far achieved indicate similar rates of aneuploidy among the four cattle breeds investigated. Interspecific comparison between cattle (Xcen-5 probes) and pig (Sus scrofa domestica) (1-10 probes) also reveal similar rates. Further studies are needed that use more probes to investigate the interchromosomal effect. Establishing a baseline level of aneuploidy for each species/breed could also be useful for improving the in vitro production of embryos destined to the embryo transfer industry as well as for monitoring future trends of the reproductive health of domestic animals in relation to management errors and/or environmental hazards. PMID:22056011

  9. Chromosome aberrations in workers with exposure to α-particle radiation from internal deposits of plutonium: expectations from in vitro studies and comparisons with workers with predominantly external γ-radiation exposure.

    PubMed

    Curwen, Gillian B; Sotnik, Natalia V; Cadwell, Kevin K; Azizova, Tamara V; Hill, Mark A; Tawn, E Janet

    2015-05-01

    mFISH analysis of chromosome aberration profiles of 47 and 144 h lymphocyte cultures following exposure to 193 mGy α-particle radiation confirmed that the frequency of stable aberrant cells and stable cells carrying translocations remains constant through repeated cell divisions. Age-specific rates and in vitro dose-response curves were used to derive expected translocation yields in nine workers from the Mayak nuclear facility in Russia. Five had external exposure to γ-radiation, two of whom also had exposure to neutrons, and four had external exposure to γ-radiation and internal exposure to α-particle radiation from incorporated plutonium. Doubts over the appropriateness of the dose response used to estimate translocations from the neutron component made interpretation difficult in two of the workers with external exposure, but the other three had translocation yields broadly in line with expectations. Three of the four plutonium workers had translocation yields in line with expectations, thus supporting the application of the recently derived in vitro α-particle dose response for translocations in stable cells. Overall this report demonstrates that with adequate reference in vitro dose-response curves, translocation yield has the potential to be a useful tool in the validation of red bone marrow doses resulting from mixed exposure to external and internal radiation. PMID:25649482

  10. Oxidative Damage to Nucleic Acids and Benzo(a)pyrene-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

    PubMed Central

    Andrys, Ctirad; Palicka, Vladimir; Chmelarova, Marcela; Hamakova, Kvetoslava

    2014-01-01

    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). PMID:25197429

  11. Cytogenetics of nine species of mediterranean blennies and additional evidence for an unusual multiple sex-chromosome system in Parablennius tentacularis (Perciformes, Blenniidae).

    PubMed

    Caputo, V; Machella, N; Nisi-Cerioni, P; Olmo, E

    2001-01-01

    The chromosomal complements of nine species of Blenniidae (Aidablennius sphylnx, Blennius ocellaris, Lypophris adriaticus, L. pavo, L. trigloides, Parcablennius gattorugine, P. ponticus, P. sanguinolentus, P. tentacularis) from the Adriatic Sea were analysed with several banding methods and in-situ hybridization. In all species, the diploid set consists of 48 mostly acrocentric chromosomes and has a similar location (terminal centromeric) of NORs, except for L. pavo (interstitial pericentric) and P. ponticus (terminal on the long arm). There are major differences in karyotype with regard to the amount and distribution of heterochromatin. Parablennius tentacularis shows a distinctive sex-chromosome system involving 2n = 48 males with a large totally heterochromatic Y chromosome, and males with 2n = 47. This difference is likely to be the consequence of a translocation of an autosome on the original Y. This finding constitutes an additional instance of the great variability in origins of multiple sex chromosome systems in vertebrates. PMID:11272790

  12. Polarization Aberrations

    NASA Technical Reports Server (NTRS)

    Mcguire, James P., Jr.; Chipman, Russell A.

    1990-01-01

    The analysis of the polarization characteristics displayed by optical systems can be divided into two categories: geometrical and physical. Geometrical analysis calculates the change in polarization of a wavefront between pupils in an optical instrument. Physical analysis propagates the polarized fields wherever the geometrical analysis is not valid, i.e., near the edges of stops, near images, in anisotropic media, etc. Polarization aberration theory provides a starting point for geometrical design and facilitates subsequent optimization. The polarization aberrations described arise from differences in the transmitted (or reflected) amplitudes and phases at interfaces. The polarization aberration matrix (PAM) is calculated for isotropic rotationally symmetric systems through fourth order and includes the interface phase, amplitude, linear diattenuation, and linear retardance aberrations. The exponential form of Jones matrices used are discussed. The PAM in Jones matrix is introduced. The exact calculation of polarization aberrations through polarization ray tracing is described. The report is divided into three sections: I. Rotationally Symmetric Optical Systems; II. Tilted and Decentered Optical Systems; and Polarization Analysis of LIDARs.

  13. Transmission of alien chromosomes from selfed progenies of a complete set of Allium monosomic additions: the development of a reliable method for the maintenance of a monosomic addition set.

    PubMed

    Shigyo, M; Wako, T; Kojima, A; Yamauchi, N; Tashiro, Y

    2003-12-01

    Selfed progeny of a complete set of Allium fistulosum - Allium cepa monosomic addition lines (2n = 2x + 1 = 17, FF+1A-FF+8A) were produced to examine the transmission rates of respective alien chromosomes. All eight types of the selfed monosomic additions set germinable seeds. The numbers of chromosomes (2n) in the seedlings were 16, 17, or 18. The eight extra chromosomes varied in transmission rate (%) from 9 (FF+2A) to 49 (FF+8A). The complete set of monosomic additions was reproduced successfully by self-pollination. A reliable way to maintain a set of Allium monosomic additions was developed using a combination of two crossing methods, selfing and female transmission. FF+8A produced two seedlings with 18 chromosomes. Cytogenetical analyses, including GISH, showed that the seedlings were disomic addition plants carrying two entire homologous chromosomes from A. cepa in an integral diploid background of A. fistulosum. Flow cytometry analysis showed that a double dose of the alien 8A chromosome caused fluorescence intensity values spurring in DNA content, and isozyme analysis showed increased glutamate dehydrogenase activity at the gene locus Gdh-1. PMID:14663528

  14. Aberrant protein expression of transcription factors BACH1 and ERG, both encoded on chromosome 21, in brains of patients with Down syndrome and Alzheimer's disease.

    PubMed

    Shim, K S; Ferrando-Miguel, R; Lubec, G

    2003-01-01

    Down syndrome (DS; trisomy 21) is a genetic disorder associated with early mental retardation and patients inevitably develop Alzheimer's disease (AD)-like neuropathological changes. The molecular defects underlying the DS-phenotype may be due to overexpression of genes encoded on chromosome 21. This so-called gene dosage hypothesis is still controversial and demands systematic work on protein expression. A series of transcription factors (TF) are encoded on chromosome 21 and are considered to play a pathogenetic role in DS. We therefore decided to study brain expression of TF encoded on chromosome 21 in patients with DS and AD compared to controls: Frontal cortex of 6 male DS patients, 6 male patients with AD and 6 male controls were used for the experiments. Immunoblotting was used to determine protein levels of TF BACH1, ERG, SIM2 and RUNX1. SIM2 and RUNX1 were comparable between groups, while BACH1 was significantly reduced in DS, and ERG was increased in DS and AD as compared to controls. These findings may indicate that DS pathogenesis cannot be simply explained by the gene dosage effect hypothesis and that results of ERG expression in DS were paralleling those in AD probably reflecting a common pathogenetic mechanism possibly explaining why all DS patients develop AD like neuropathology from the fourth decade. We conclude that TF derangement is not only due to the process of neurodegeneration and propose that TFs BACH1 and ERG play a role for the development of AD-like neuropathology in DS and pathogenesis of AD per se and the manifold increase of ERG in both disorders may form a pivotal pathogenetic link. PMID:15068237

  15. Canine urothelial carcinoma: genomically aberrant and comparatively relevant

    PubMed Central

    Shapiro, S. G.; Raghunath, S.; Williams, C.; Motsinger-Reif, A. A.; Cullen, J. M.; Liu, T.; Albertson, D.; Ruvolo, M.; Lucas, A. Bergstrom; Jin, J.; Knapp, D. W.; Schiffman, J. D.

    2015-01-01

    Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97% and 84% of cases, respectively, and losses on CFA 19 were present in 77% of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and custom Agilent SureFISH probes, was performed to detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to

  16. Increased total number of genetic aberrations and changes affecting specific chromosomal regions may underlie prostate cancer recurrence and development of hormone-independent growth

    SciTech Connect

    Hyytinen, E.; Visakorpi, T.; Kallioniemi, A.

    1994-09-01

    At the time of diagnosis, prostate carcinomas are often rather slowly proliferating and shows a favorable response to anti-androgen treatment. However, often the tumors metastasize or recur locally and thereafter show an aggressive behavior and rapid growth despite of the endocrine therapy. In order to understand the genetic basis of this change in phenotype and clinical behavior, we used comparative genomic hybridization to analyze for losses and gains of DNA sequences along all human chromosomes in primary prostate carcinomas as well as in local recurrencies during hormonal therapy. The total number of genetic changes in 9 recurrences was almost three times higher than that observed in 31 primary prostate carcinomas. Whereas gains and amplifications were only seen in 6/31 primary tumors, all recurrences showed gains of at least one chromosomal site. Gain of 8q was seen at 89% of recurrences as compared to 6% in the primary tumors. Other prominent increases of prevalence were +X (56% vs. 0%), +7 (50% vs. 6%), and 8p- (78% vs. 32%). In one case where DNA was available from both the primary tumor and recurrence of the same patient, appearance of some of these gains during tumor progression was validated. Analysis of archival formalin-fixed paraffin-embedded tissues by CGH is in progress and will make it possible to extensively compare genetic changes between the primary tumor and its local recurrence or metastasis.

  17. Direct determination of the chromosomal location of bunching onion and bulb onion markers using bunching onion-shallot monosomic additions and allotriploid-bunching onion single alien deletions.

    PubMed

    Tsukazaki, Hikaru; Yamashita, Ken-ichiro; Yaguchi, Shigenori; Yamashita, Koichiro; Hagihara, Takuya; Shigyo, Masayoshi; Kojima, Akio; Wako, Tadayuki

    2011-02-01

    To determine the chromosomal location of bunching onion (Allium fistulosum L.) simple sequence repeats (SSRs) and bulb onion (A. cepa L.) expressed sequence tags (ESTs), we used a complete set of bunching onion-shallot monosomic addition lines and allotriploid bunching onion single alien deletion lines as testers. Of a total of 2,159 markers (1,198 bunching onion SSRs, 324 bulb onion EST-SSRs and 637 bulb onion EST-derived non-SSRs), chromosomal locations were identified for 406 markers in A. fistulosum and/or A. cepa. Most of the bunching onion SSRs with identified chromosomal locations showed polymorphism in bunching onion (89.5%) as well as bulb onion lines (66.1%). Using these markers, we constructed a bunching onion linkage map (1,261 cM), which consisted of 16 linkage groups with 228 markers, 106 of which were newly located. All linkage groups of this map were assigned to the eight basal Allium chromosomes. In this study, we assigned 513 markers to the eight chromosomes of A. fistulosum and A. cepa. Together with 254 markers previously located on a separate bunching onion map, we have identified chromosomal locations for 766 markers in total. These chromosome-specific markers will be useful for the intensive mapping of desirable genes or QTLs for agricultural traits, and to obtain DNA markers linked to these. PMID:20938763

  18. Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration.

    PubMed

    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. PMID:26864482

  19. Spectral karyotyping analysis of human and mouse chromosomes

    PubMed Central

    Padilla-Nash, Hesed M; Barenboim-Stapleton, Linda; Difilippantonio, Michael J; Ried, Thomas

    2016-01-01

    Classical banding methods provide basic information about the identities and structures of chromosomes on the basis of their unique banding patterns. Spectral karyotyping (SKY), and the related multiplex fluorescence in situ hybridization (M-FISH), are chromosome-specific multicolor FISH techniques that augment cytogenetic evaluations of malignant disease by providing additional information and improved characterization of aberrant chromosomes that contain DNA sequences not identifiable using conventional banding methods. SKY is based on cohybridization of combinatorially labeled chromosome-painting probes with unique fluorochrome signatures onto human or mouse metaphase chromosome preparations. Image acquisition and analysis use a specialized imaging system, combining Sagnac interferometer and CCD camera images to reconstruct spectral information at each pixel. Here we present a protocol for SKY analysis using commercially available SkyPaint probes, including procedures for metaphase chromosome preparation, slide pretreatment and probe hybridization and detection. SKY analysis requires approximately 6 d. PMID:17406576

  20. 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.

    PubMed

    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

  1. Commentary: Unravelling the Effects of Additional Sex Chromosomes on Cognition and Communication--Reflections on Lee et al. (2012)

    ERIC Educational Resources Information Center

    Bishop, Dorothy V. M.

    2012-01-01

    Most people have 23 pairs of chromosomes; one set from the mother and one from the father. However, nondisjunction errors during meiosis can lead to a case of trisomy, where there are three rather than two chromosomes. Although such events are not uncommon, they are usually lethal, and account for a high proportion of spontaneous abortions. There…

  2. Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice.

    PubMed

    Bernstein, Lori R; Mackenzie, Amelia C L; Lee, Se-Jin; Chaffin, Charles L; Merchenthaler, István

    2016-03-01

    Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called "egg infertility." A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women. PMID:26713784

  3. FIGO Stage III Metastatic Gestational Choriocarcinoma Developed From an Antecedent Partial Hydatidiform Molar Pregnancy Bearing a Numerical Chromosomal Aberration 68, XX: A Case Report and Literature Review.

    PubMed

    Ma, Naili; Litkouhi, Babak; Mannion, Ciaran M

    2016-03-01

    A 36-yr-old, gravida 5 para 4 woman presented with uterine bleeding and was discovered to have a 3.7-cm uterine mass with multiple, bilateral, lung metastases. Six months earlier, the patient was diagnosed with a partial hydatidiform mole that demonstrated a rare chromosomal karyotype 68, XX[12]. The patient's serum β-human chorionic gonadotropin was elevated from baseline to 12,039 mIU/mL before the treatment. A total hysterectomy was performed and revealed a markedly hemorrhagic, extensively necrotic choriocarcinoma. The tumor mass invaded to a depth of 1/3 of the uterine wall thickness. Cytogenetic analysis of the choriocarcinoma revealed the same 68, XX karyotype, as observed in the antecedent partial hydatidiform mole. A clinical diagnosis of advanced stage invasive choriocarcinoma was rendered, with a risk factor score of 5. Following the development of chemoresistance to a single-agent (methotrexate) regimen, the patient subsequently received 5 cycles of chemotherapy (EMA-CO), without any major complication. She is currently >5 yr posttreatment and is asymptomatic. Her most recent imaging studies, including scans of chest and brain, show no evidence of disease, and her serum β-human chorionic gonadotropin level has remained consistently below detectable levels. PMID:26352546

  4. Proximity within interphase chromosome contributes to the breakpoint distribution in radiation-induced intrachromosomal exchanges

    NASA Astrophysics Data System (ADS)

    Zhang, Ye; Uhlemeyer, Jimmy; Hada, Megumi; Asaithamby, A.; Chen, David J.; Wu, Honglu

    2014-07-01

    Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome 3 in human mammary epithelial cells after exposures to either low- or high-LET radiation. In particular, breaks in certain regions of the chromosome tended to rejoin with each other to form an intrachromosome exchange event. This study tests the hypothesis that proximity within a single chromosome in interphase cell nuclei contributes to the distribution of radiation-induced chromosome breaks. Chromosome 3 in G1 human mammary epithelial cells was hybridized with the multicolor banding in situ hybridization (mBAND) probes that distinguish the chromosome in six differently colored regions, and the location of these regions was measured with a laser confocal microscope. Results of the study indicated that, on a multi-mega base pair scale of the DNA, the arrangement of chromatin was non-random. Both telomere regions tended to be located towards the exterior of the chromosome domain, whereas the centromere region towards the interior. In addition, the interior of the chromosome domain was preferentially occupied by the p-arm of the chromatin, which is consistent with our previous finding of intrachromosome exchanges involving breaks on the p-arm and in the centromere region of chromosome 3. Other factors, such as the fragile sites in the 3p21 band and gene regulation, may also contribute to the breakpoint distribution in radiation-induced chromosome aberrations.

  5. Isolation of a homozygous X-linked translocation stock with two additional sex-chromosomes in the onion fly Hylemya antiqua Meigen.

    PubMed

    van Heemert, K

    1977-05-01

    The onion fly, Hylemya antiqua Meigen, was subjected to irradiation and selection based on observations of fertility and cytogenetics, in order to isolate structural chromosome mutations which might be used for genetic control of this species. To the present time, only a "simple" X-linked translocation could be obtained as a homozygous stock. Sibcrossing was carried out using translocation trisomics (TN + X) obtained from test-crossed translocation heterozygous females (TN) showing numerical nondisjunction. A homozygous stock was obtained with two additional sex-chromosomes. This is a unique case because normally an X-linked translocation can not be made homozygous in the male sex, which normally only carries one X-chromosome. PMID:24407169

  6. A recurrent marker chromosome involving chromosome 1 in two mammary tumors of the dog.

    PubMed

    Bartnitzke, S; Motzko, H; Caselitz, J; Kornberg, M; Bullerdiek, J; Schloot, W

    1992-01-01

    An apparently identical marker chromosome resulting from a chromosome 1. translocation was found in the mammary carcinomas of two bitches. Although these karyotypic aberrations were the sole clonal aberrations detected, it was not possible to unambiguously identify the material translocated to the chromosome 1 in either animal. Our observations, however, represent the first report of a recurring marker chromosome in mammary tumors of the dog and suggest that these tumors may become an interesting model for human breast cancer. PMID:1319309

  7. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  8. DCB - DNA and Chromosome Aberrations Research

    Cancer.gov

    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.

  9. Human chromosomes: Structure, behavior, and effects

    SciTech Connect

    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. Historical aspects of aberration correction.

    PubMed

    Rose, Harald H

    2009-06-01

    A brief history of the development of direct aberration correction in electron microscopy is outlined starting from the famous Scherzer theorem established in 1936. Aberration correction is the long story of many seemingly fruitless efforts to improve the resolution of electron microscopes by compensating for the unavoidable resolution-limiting aberrations of round electron lenses over a period of 50 years. The successful breakthrough, in 1997, can be considered as a quantum step in electron microscopy because it provides genuine atomic resolution approaching the size of the radius of the hydrogen atom. The additional realization of monochromators, aberration-free imaging energy filters and spectrometers has been leading to a new generation of analytical electron microscopes providing elemental and electronic information about the object on an atomic scale. PMID:19254915

  11. Chromosomal rearrangements in patients with clinical features of Silver-Russell syndrome.

    PubMed

    Fokstuen, Siv; Kotzot, Dieter

    2014-06-01

    Silver-Russell syndrome (SRS) is characterized by pre- and postnatal growth retardation, relative macrocephaly, asymmetry, and a triangular facial gestalt. In 5-10% of the patients the phenotype is caused by maternal UPD 7, and 38-64% of the patients present with hypomethylation at the imprinting center region 1 (ICR1) on 11p15.5. The etiology of the remaining cases is so far not known and various (sub-)microscopic chromosome aberrations with a phenotype resembling SRS have been published, especially duplication 11p15 (n = 15), deletion 12q14 (n = 19), ring chromosome 15, deletion 15qter, and various other mostly unique chromosomal aberrations (n = 30). In this study the phenotypes of these chromosomal aberrations were revisited and compared with the phenotypes of maternal UPD 7 and hypomethylation at ICR1 on 11p15.5. In some patients with a unique chromosomal aberration even the hallmarks of SRS were missing. Patients with duplication 11p15 show a more variable occipitofrontal head circumference at birth, a higher frequency of intellectual disability, and additional anomalies not reported in SRS. Deletion 12q14 is characterized by less severe pre- and postnatal growth retardation and less impressive relative macrocephaly. Patients with ring chromosome 15 and deletion 15qter have no relative macrocephaly (mostly even microcephaly) and more severe intellectual disability. Finally, deletion 15qter lacks the triangular facial gestalt. In summary, as SRS seems not an adequate diagnosis in many of these patients, diagnosis should focus on the chromosomal aberration than on SRS. PMID:24664587

  12. Highly informative Y-chromosomal haplotypes by the addition of three new STRs DYS437, DYS438 and DYS439.

    PubMed

    Grignani, P; Peloso, G; Fattorini, P; Previderè, C

    2000-01-01

    The Y chromosome STRs DYS437, DYS438 and DYS439 were selected from publicly available genome databases and used to analyse an Italian population sample. A tetraplex PCR reaction including the highly informative DYS385 locus, was set up and used for the analysis of 131 male samples to determine allele frequencies and STR diversity values. The number of different haplotypes and the haplotype diversity value found from the analysis of the STRs included in the tetraplex reaction were very similar to those found from the analysis of the basic set of 7 Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392 and DYS393) previously carried out on the same population sample. By combining the allelic states of the 11 Y-chromosomal STRs we could construct highly informative haplotypes that allowed the discrimination of 93.8% (120 out of 128) of the samples tested. This approach represents a very powerful tool for individual identification and paternity testing in forensic medicine. PMID:11197619

  13. A computer simulation of chromosomal instability

    NASA Astrophysics Data System (ADS)

    Goodwin, E.; Cornforth, M.

    The transformation of a normal cell into a cancerous growth can be described as a process of mutation and selection occurring within the context of clonal expansion. Radiation, in addition to initial DNA damage, induces a persistent and still poorly understood genomic instability process that contributes to the mutational burden. It will be essential to include a quantitative description of this phenomenon in any attempt at science-based risk assessment. Monte Carlo computer simulations are a relatively simple way to model processes that are characterized by an element of randomness. A properly constructed simulation can capture the essence of a phenomenon that, as is often the case in biology, can be extraordinarily complex, and can do so even though the phenomenon itself is incompletely understood. A simple computer simulation of one manifestation of genomic instability known as chromosomal instability will be presented. The model simulates clonal expansion of a single chromosomally unstable cell into a colony. Instability is characterized by a single parameter, the rate of chromosomal rearrangement. With each new chromosome aberration, a unique subclone arises (subclones are defined as having a unique karyotype). The subclone initially has just one cell, but it can expand with cell division if the aberration is not lethal. The computer program automatically keeps track of the number of subclones within the expanding colony, and the number of cells within each subclone. Because chromosome aberrations kill some cells during colony growth, colonies arising from unstable cells tend to be smaller than those arising from stable cells. For any chosen level of instability, the computer program calculates the mean number of cells per colony averaged over many runs. These output should prove useful for investigating how such radiobiological phenomena as slow growth colonies, increased doubling time, and delayed cell death depend on chromosomal instability. Also of

  14. Proximity Within Interphase Chromosome Contributes to the Breakpoint Distribution in Radiation-Induced Intrachromosomal Exchanges

    NASA Technical Reports Server (NTRS)

    Zhang, Ye; Uhlemeyer, Jimmy; Hada, Megumi; Asaithamby, A.; Chen, David J.; Wu, Honglu

    2015-01-01

    Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome3 in human mammary epithelial cells after exposures to either low-or high-LET radiation. In particular, breaks in certain regions of the chromosome tended to rejoin with each other to form an intrachromosome exchange event. This study tests the hypothesis that proximity within a single chromosome in interphase cell nuclei contributes to the distribution of radiation-induced chromosome breaks. Chromosome 3 in G1 human mammary epithelial cells was hybridized with the multicolor banding in situ hybridization (mBAND) probes that distinguish the chromosome in six differently colored regions, and the location of these regions was measured with a laser confocal microscope. Results of the study indicated that, on a multi-mega base pair scale of the DNA, the arrangement of chromatin was non-random. Both telomere regions tended to be located towards the exterior of the chromosome domain, whereas the centromere region towards the interior. In addition, the interior of the chromosome domain was preferentially occupied by the p-arm of the chromatin, which is consistent with our previous finding of intrachromosome exchanges involving breaks on the p-arm and in the centromere region of chromosome3. Other factors, such as the fragile sites in the 3p21 band and gene regulation, may also contribute to the breakpoint distribution in radiation-induced chromosome aberrations. Further investigations suggest that the 3D chromosome folding is cell type and culture condition dependent.

  15. PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis.

    PubMed

    He, Jinxue; Zhang, Zhong; Ouyang, Meng; Yang, Fan; Hao, Hongbo; Lamb, Kristy L; Yang, Jingyi; Yin, Yuxin; Shen, Wen H

    2016-01-01

    Architectural integrity of the mitotic spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the mitotic kinesin motor EG5 for proper spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of spindle geometry, manifested prominently by shorter spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the mitotic spindle apparatus, leading to spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling mitotic spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate mitotic phosphorylation for proper spindle formation and faithful genomic transmission. PMID:27492783

  16. PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis

    PubMed Central

    He, Jinxue; Zhang, Zhong; Ouyang, Meng; Yang, Fan; Hao, Hongbo; Lamb, Kristy L.; Yang, Jingyi; Yin, Yuxin; Shen, Wen H.

    2016-01-01

    Architectural integrity of the mitotic spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the mitotic kinesin motor EG5 for proper spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of spindle geometry, manifested prominently by shorter spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the mitotic spindle apparatus, leading to spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling mitotic spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate mitotic phosphorylation for proper spindle formation and faithful genomic transmission. PMID:27492783

  17. Cytological and Molecular Characterization of Homoeologous Group-1 Chromosomes in Hybrid Derivatives of a Durum Disomic Alien Addition Line

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium head blight (FHB) is a devastating disease of durum wheat (Triticum turgidum L., 2n = 4x = 28; AABB). To incorporate FHB resistance from diploid wheatgrass (Lophopyrum elongatum (Host) Á. Löve, 2n = 2x = 14; EE) we produced earlier a stable alien disomic addition line, DGE-1, incorporating...

  18. Chromosomal Analysis of Couples with Repeated Spontaneous Abortions in Northeastern Iran

    PubMed Central

    Ghazaey, Saeedeh; Keify, Fatemeh; Mirzaei, Farzaneh; Maleki, Masumeh; Tootian, Semiramis; Ahadian, Mitra; Abbaszadegan, Mohammad Reza

    2015-01-01

    Background Cytogenetic study of reproductive wastage is an important aspect in determining the genetic background of early embryogenesis. Approximately 15 to 20% of all pregnancies in humans are terminated as recurrent spontaneous abortions (RSAs). The aim of this study was to detect chromosome abnormalities in couples with RSAs and to compare our results with those reported previously. Materials and Methods In this retrospective study, the pattern of chromosomal aberrations was evaluated during a six-year period from 2005 to 2011. The population under study was 728 couples who attended genetic counseling services for their RSAs at Pardis Clinical and Genetics Laboratory, Mashhad, Iran. Results In this study, about 11.7% of couples were carriers of chromosomal aberrations. The majority of abnormalities were found in couples with history of abortion, without stillbirth or livebirth. Balanced reciprocal translocations, Robertsonian translocations, inversions and sex chromosome aneuploidy were seen in these cases. Balanced reciprocal translocations were the most frequent chromosomal anomalies (62.7%) detected in current study. Conclusion These findings suggest that chromosomal abnormalities can be one of the important causes of RSAs. In addition, cytogenetic study of families who experienced RSAs may prevent unnecessary treatment if RSA are caused by chromosomal abnormalities. The results of cytogenetic studies of RSA cases will provide a standard protocol for the genetic counselors in order to follow up and to help these families. PMID:25918592

  19. BLEOMYCIN EFFECTS ON MOUSE MEIOTIC CHROMOSOMES

    EPA Science Inventory

    The effects of a radiomimetic chemical, bleomycin (BLM), on meiotic chromosomes was evaluated in mice. hromosome aberrations were analyzed at meiotic metaphase I, and damage to the synaptonemal complex was analyzed in meiotic prophase cells. n the metaphase aberration studies, an...

  20. Aberrant immunophenotypes of mantle cell lymphomas.

    PubMed

    Wohlschlaeger, Ch; Lange, K; Merz, H; Feller, A C

    2003-02-01

    Mantle cell lymphomas (MCL) are characterized by cytomorphological criteria, a distinct immunophenotype and a characteristic chromosomal aberration (t(11;14)). In morphological variants of MCL the immunohistochemical constellation with CD5-positivity and CD23-negativity is a helpful and decisive diagnostic aid to differentiate MCL from other B-cell-lymphomas, e.g. lymphocytic lymphomas (B-CLL). In this study the morphological, immunophenotypical, and genetical features of 50 MCL were analysed. Five cases revealed an aberrant immunophenotype with lacking expression of CD5 (n = 3) and positive reactivity to CD23 (n = 2) while cyclin D1 expression could be demonstrated in all 5 cases. These constellations show that there is, besides morphological subgroups, a small group of MCL with aberrant immunophenotypes, which has to be taken into account in the differential diagnosis to lymphocytic lymphoma and other lymphomas. PMID:12688344

  1. Characterization of three de novo derivative chromosomes 16 by [open quotes]Reverse Chromosome Painting[close quotes] and molecular analysis

    SciTech Connect

    Rack, K.A.; Harris, P.C.; MacCarthy, A.B.; Boone, R.; Raynham, H.; Buckle, V.J. )

    1993-05-01

    The authors have analyzed three de novo chromosome 16 rearrangements-two with a 16p+ chromosome and one a 16q+-none of which could be fully characterized by conventional cytogenetics. In each case, flow karyotypes have been produced, and the aberrant chromosome has been isolated by flow sorting. The origin of the additional material has been ascertained by amplifying and labeling the DNA of the abnormal chromosome by degenerate-oligonucleotide-primer-PCR and hybridizing it in situ to normal metaphase spreads (reverse chromosome painting). Both 16p+ chromosomes contain more than 30 Mb of DNA from the short arm of chromosome 9 (9p21.2-pter), while the 16q+ contains approximately 9 Mb of DNA from 2q37. The breakpoints on chromosome 16 have been localized in each case; the two breakpoints on the short arm are at different points within the terminal band, 16p13.3. The breakpoint on the long arm of chromosome 16 is very close to (within 230 kb of) the 16q telomere. Determination of the regions of monosomy and trisomy allowed the observed phenotypes to be compared with other reported cases involving aneuploidy for these regions. 41 refs., 4 figs.

  2. Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

    NASA Technical Reports Server (NTRS)

    George, Kerry; Durante, Marco; Willingham, Veronica; Wu, Honglu; Yang, Tracy C.; Cucinotta, Francis A.

    2003-01-01

    Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

  3. 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 .

    PubMed

    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. PMID:25898552

  4. Cytogenetic evaluation of chromosomal disorders in Down Syndrome

    SciTech Connect

    Shafik, H.M.

    1987-01-01

    Down Syndrome (DS) patients are at high risk to develop leukemia. They are also highly sensitive to the induction of chromosomal aberrations when their GO lymphocytes are irradiated in vitro. The objective of this study was to further investigate the differential radiosensitivity of DS lymphocytes at the different stages of the cell cycle, as damage to proliferating cells is more relevant to health problems than damage to non-dividing cells. In addition, the proliferation kinetics and stage of differentiation of circulating DS lymphocytes was studied in an attempt to understand the mechanism for the enhanced chromosomal radiosensitivity. Moreover, the x-ray induced specific chromosomal breakpoints were identified and correlated with the locations of oncogene and fragile sites in order to investigate cytogenetically the early stages of leukemogenesis.

  5. Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma

    PubMed Central

    Nagel, Stefan; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A.F.

    2015-01-01

    In Hodgkin lymphoma (HL) we recently identified deregulated expression of homeobox genes MSX1 and OTX2 which are physiologically involved in development of the embryonal neural plate border region. Here, we examined in HL homeobox gene SIX1 an additional regulator of this embryonal region mediating differentiation of placodal precursors. SIX1 was aberrantly activated in 12 % of HL patient samples in silico, indicating a pathological role in a subset of this B-cell malignancy. In addition, SIX1 expression was detected in HL cell lines which were used as models to reveal upstream factors and target genes of this basic developmental regulator. We detected increased copy numbers of the SIX1 locus at chromosome 14q23 correlating with enhanced expression while chromosomal translocations were absent. Moreover, comparative expression profiling data and pertinent gene modulation experiments indicated that the WNT-signalling pathway and transcription factor MEF2C regulate SIX1 expression. Genes encoding the transcription factors GATA2, GATA3, MSX1 and SPIB – all basic lymphoid regulators - were identified as targets of SIX1 in HL. In addition, cofactors EYA1 and TLE4, respectively, contrastingly mediated activation and suppression of SIX1 target gene expression. Thus, the protein domain interfaces may represent therapeutic targets in SIX1-positive HL subsets. Collectively, our data reveal a gene regulatory network with SIX1 centrally deregulating lymphoid differentiation and support concordance of lymphopoiesis/lymphomagenesis and developmental processes in the neural plate border region. PMID:26473286

  6. Cytogenetic evidence that DNA topoisomerase II is not involved in radiation induced chromsome-type aberrations.

    PubMed

    Mosesso, P; Pepe, G; Ottavianelli, A; Schinoppi, A; Cinelli, S

    2015-11-01

    ICRF-187 (Cardioxane™, Chiron) is a catalytic inhibitor of DNA topoisomerase II (Topo II), proposed to act by blocking Topo II-mediated DNA cleavage without stabilizing DNA-Topo II-"cleavable complexes". In this study ICRF-187 was used to evaluate the potential involvement of DNA topoisomerase II in the formation of the radiation-induced chromosome-type aberrations in the G0 phase of the cell cycle in human lymphocytes from three healthy male donors. This is based on many evidences that DNA topoisomerases are involved in DNA recombination, mainly of illegitimate type (non-homologous) both in vitro and in vivo. The results obtained clearly indicated that ICRF-187 did not induce per se any chromosomal damage. When challenged with the non-catalytic Topo II poison VP-16 (etoposide), which acts by stabilizing the "cleavable complex" generating "protein concealed" DSB's and thus chromosomal aberrations, it completely abolished the significant induction of chromosome-type aberrations and formation of dicentric chromosomes. This indicates that ICRF-187 acts effectively as catalytic inhibitor of Topo II. On the other hand, when X-ray treatments were challenged with ICRF-187 using experimental conditions as for VP-16 treatments, no modification of the incidence of chromosome-type aberrations and dicentric chromosomes was observed. On this basis, we conclude that Topo II is not involved in the formation of X-ray-induced chromosome-type aberrations and dicentric chromosomes in human lymphocytes in the G0 phase of the cell cycle. PMID:26520368

  7. The Aberration Corrected SEM

    SciTech Connect

    Joy, David C.

    2005-09-09

    The performance of the conventional low-energy CD-SEM is limited by the aberrations inherent in the probe forming lens. Multi-pole correctors are now available which can reduce or eliminate these aberrations. An SEM equipped with such a corrector offers higher spatial resolution and more probe current from a given electron source, and other aspects of the optical performance are also improved, but the much higher numerical aperture associated with an aberration corrected lens results in a reduction in imaging depth of field.

  8. Chromosomal Conditions

    MedlinePlus

    ... 150 babies is born with a chromosomal condition. Down syndrome is an example of a chromosomal condition. Because ... all pregnant women be offered prenatal tests for Down syndrome and other chromosomal conditions. A screening test is ...

  9. Radiation-induced chromosomal inversions in mice. Technical progress report

    SciTech Connect

    Roderick, T.H.

    1986-01-01

    Chromosomal inversions are being produced for the purpose of establishing efficient systems for assessing induced and spontaneous heritable mutations. The inversions and other chromosomal aberrations produced are used to ask basic questions about meiosis and reproductive performance. Chromosomal structure is being studied by identifying the cytological location of genes and break points related to the inversions. 2 tabs.

  10. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damages

    NASA Technical Reports Server (NTRS)

    George, K.; Cucinotta, F. A.

    2006-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from approximately 50 to 174 keV/micrometers and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation (PCC) technique. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 14 to 35. The RBE values increased with LET, reaching a maximum for the 1 GeV/n Fe ions with LET of 150 keV/micrometers, and decreased with further increases in LET. When LET of the primary beam was in the region of increasing RBE (i.e. below approximately 100 keV/micrometers), the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than 150 keV/micrometers.

  11. Direct comparison between genomic constitution and flavonoid contents in Allium multiple alien addition lines reveals chromosomal locations of genes related to biosynthesis from dihydrokaempferol to quercetin glucosides in scaly leaf of shallot (Allium cepa L.).

    PubMed

    Masuzaki, S; Shigyo, M; Yamauchi, N

    2006-02-01

    The extrachromosome 5A of shallot (Allium cepa L., genomes AA) has an important role in flavonoid biosynthesis in the scaly leaf of Allium fistulosum-shallot monosomic addition lines (FF+nA). This study deals with the production and biochemical characterisation of A. fistulosum-shallot multiple alien addition lines carrying at least 5A to determine the chromosomal locations of genes for quercetin formation. The multiple alien additions were selected from the crossing between allotriploid FFA (female symbol) and A. fistulosum (male symbol). The 113 plants obtained from this cross were analysed by a chromosome 5A-specific PGI isozyme marker of shallot. Thirty plants were preliminarily selected for an alien addition carrying 5A. The chromosome numbers of the 30 plants varied from 18 to 23. The other extrachromosomes in 19 plants were completely identified by using seven other chromosome markers of shallot. High-performance liquid chromatography analyses of the 19 multiple additions were conducted to identify the flavonoid compounds produced in the scaly leaves. Direct comparisons between the chromosomal constitution and the flavonoid contents of the multiple alien additions revealed that a flavonoid 3'-hydroxylase (F3'H) gene for the synthesis of quercetin from kaempferol was located on 7A and that an anonymous gene involved in the glucosidation of quercetin was on 3A or 4A. As a result of supplemental SCAR analyses by using genomic DNAs from two complete sets of A. fistulosum-shallot monosomic additions, we have assigned F3'H to 7A and flavonol synthase to 4A. PMID:16411131

  12. Chromosomal analyses of 1510 couples who have experienced recurrent spontaneous abortions.

    PubMed

    Tunç, Erdal; Tanrıverdi, Nilgün; Demirhan, Osman; Süleymanova, Dilara; Çetinel, Nesrin

    2016-04-01

    In this retrospective study, karyotype results of 1510 couples with a history of recurrent spontaneous abortion were evaluated. The study was conducted at Balcalı Hospital in Adana region of Turkey. For all cases, peripheral blood lymphocytes were cultured for chromosome study using the standard method. Chromosome aberrations were detected in 62 couples (4.1% of all couples). At an individual level, chromosome aberrations were found in a total of 65 cases (41 females and 24 male cases), with structural chromosomal aberrations in 58 cases including balanced translocations in 30 cases, Robertsonian translocations in 12 cases, deletions in seven cases, inversions in nine cases and numerical chromosome aberrations in seven cases. The results of the study indicated that structural aberrations, particularly translocations, were the most common type of aberration observed among couples who had experienced recurrent spontaneous abortions and that these couples might benefit from cytogenetic analyses. PMID:26874988

  13. Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.

    PubMed

    Tabach, Yuval; Kogan-Sakin, Ira; Buganim, Yosef; Solomon, Hilla; Goldfinger, Naomi; Hovland, Randi; Ke, Xi-Song; Oyan, Anne M; Kalland, Karl-H; Rotter, Varda; Domany, Eytan

    2011-01-01

    Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification. PMID:21297939

  14. Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

    PubMed Central

    Buganim, Yosef; Solomon, Hilla; Goldfinger, Naomi; Hovland, Randi; Ke, Xi-Song; Oyan, Anne M.; Kalland, Karl-H.; Rotter, Varda; Domany, Eytan

    2011-01-01

    Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification. PMID:21297939

  15. Spherical aberration in electrically thin flat lenses.

    PubMed

    Ruphuy, Miguel; Ramahi, Omar M

    2016-08-01

    We analyze the spherical aberration of a new generation of lenses made of flat electrically thin inhomogeneous media. For such lenses, spherical aberration is analyzed quantitatively and qualitatively, and comparison is made to the classical gradient index rod. Both flat thin and thick lenses are made of gradient index materials, but the physical mechanisms and design equations are different. Using full-wave three-dimensional numerical simulation, we evaluate the spherical aberrations using the Maréchal criterion and show that the thin lens gives significantly better performance than the thick lens (rod). Additionally, based on ray tracing formulation, third-order analysis for longitudinal aberration and optical path difference are presented, showing strong overall performance of thin lenses in comparison to classical rod lenses. PMID:27505651

  16. Synergistic and Additive Effects of Chromosomal and Plasmid-Encoded Hemolysins Contribute to Hemolysis and Virulence in Photobacterium damselae subsp. damselae

    PubMed Central

    Rivas, Amable J.; Balado, Miguel; Lemos, Manuel L.

    2013-01-01

    Photobacterium damselae subsp. damselae causes infections and fatal disease in marine animals and in humans. Highly hemolytic strains produce damselysin (Dly) and plasmid-encoded HlyA (HlyApl). These hemolysins are encoded by plasmid pPHDD1 and contribute to hemolysis and virulence for fish and mice. In this study, we report that all the hemolytic strains produce a hitherto uncharacterized chromosome-encoded HlyA (HlyAch). Hemolysis was completely abolished in a single hlyAch mutant of a plasmidless strain and in a dly hlyApl hlyAch triple mutant. We found that Dly, HlyApl, and HlyAch are needed for full hemolytic values in strains harboring pPHDD1, and these values are the result of the additive effects between HlyApl and HlyAch, on the one hand, and of the synergistic effect of Dly with HlyApl and HlyAch, on the other hand. Interestingly, Dly-producing strains produced synergistic effects with strains lacking Dly production but secreting HlyA, constituting a case of the CAMP (Christie, Atkins, and Munch-Petersen) reaction. Environmental factors such as iron starvation and salt concentration were found to regulate the expression of the three hemolysins. We found that the contributions, in terms of the individual and combined effects, of the three hemolysins to hemolysis and virulence varied depending on the animal species tested. While Dly and HlyApl were found to be main contributors in the virulence for mice, we observed that the contribution of hemolysins to virulence for fish was mainly based on the synergistic effects between Dly and either of the two HlyA hemolysins rather than on their individual effects. PMID:23798530

  17. Pure chromosome-specific PCR libraries from single sorted chromosomes.

    PubMed Central

    VanDevanter, D R; Choongkittaworn, N M; Dyer, K A; Aten, J; Otto, P; Behler, C; Bryant, E M; Rabinovitch, P S

    1994-01-01

    Chromosome-specific DNA libraries can be very useful in molecular and cytogenetic genome mapping studies. We have developed a rapid and simple method for the generation of chromosome-specific DNA sequences that relies on polymerase chain reaction (PCR) amplification of a single flow-sorted chromosome or chromosome fragment. Previously reported methods for the development of chromosome libraries require larger numbers of chromosomes, with preparation of pure chromosomes sorted by flow cytometry, generation of somatic cell hybrids containing targeted chromosomes, or a combination of both procedures. These procedures are labor intensive, especially when hybrid cell lines are not already available, and this has limited the generation of chromosome-specific DNA libraries from nonhuman species. In contrast, a single sorted chromosome is a pure source of DNA for library production even when flow cytometric resolution of chromosome populations is poor. Furthermore, any sorting cytometer may be used with this technique. Using this approach, we demonstrate the generation of PCR libraries suitable for both molecular and fluorescence in situ hybridization studies from individual baboon and canine chromosomes, separate human homologues, and a rearranged marker chromosome from a transformed cell line. PCR libraries specific to subchromosomal regions have also been produced by sorting a small chromosome fragment. This simple and rapid technique will allow generation of nonhuman linkage maps and probes for fluorescence in situ hybridization and the characterization of marker chromosomes from solid tumors. In addition, allele-specific libraries generated by this strategy may also be useful for mapping genetic diseases. Images PMID:8016078

  18. Structure and Stability of Telocentric Chromosomes in Wheat

    PubMed Central

    Koo, Dal-Hoe; Sehgal, Sunish K.; Friebe, Bernd; Gill, Bikram S.

    2015-01-01

    In most eukaryotes, centromeres assemble at a single location per chromosome. Naturally occurring telocentric chromosomes (telosomes) with a terminal centromere are rare but do exist. Telosomes arise through misdivision of centromeres in normal chromosomes, and their cytological stability depends on the structure of their kinetochores. The instability of telosomes may be attributed to the relative centromere size and the degree of completeness of their kinetochore. Here we test this hypothesis by analyzing the cytogenetic structure of wheat telosomes. We used a population of 80 telosomes arising from the misdivision of the 21 chromosomes of wheat that have shown stable inheritance over many generations. We analyzed centromere size by probing with the centromere-specific histone H3 variant, CENH3. Comparing the signal intensity for CENH3 between the intact chromosome and derived telosomes showed that the telosomes had approximately half the signal intensity compared to that of normal chromosomes. Immunofluorescence of CENH3 in a wheat stock with 28 telosomes revealed that none of the telosomes received a complete CENH3 domain. Some of the telosomes lacked centromere specific retrotransposons of wheat in the CENH3 domain, indicating that the stability of telosomes depends on the presence of CENH3 chromatin and not on the presence of CRW repeats. In addition to providing evidence for centromere shift, we also observed chromosomal aberrations including inversions and deletions in the short arm telosomes of double ditelosomic 1D and 6D stocks. The role of centromere-flanking, pericentromeric heterochromatin in mitosis is discussed with respect to genome/chromosome integrity. PMID:26381743

  19. Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation

    PubMed Central

    Kiefer, Yvonne; Schulte, Christoph; Tiemann, Markus; Bullerdiek, Joern

    2012-01-01

    Chronic lymphocytic leukemia is the most common leukemia in adults. By cytogenetic investigations major subgroups of the disease can be identified that reflect different routes of tumor development. Of these chromosomal deviations, trisomy 12 and deletions of parts of either the long arm of chromosome 13, the long arm of chromosome 11, or the short arm of chromosome 17 are most commonly detected. In some of these aberrations the molecular target has been identified as eg, ataxia telangiectasia mutated (ATM) in case of deletions of chromosomal region 11q22~23 and the genes encoding microRNAs miR-15a/16-1 as likely targets of deletions of chromosomal band 13q14.3. Of note, these aberrations do not characterize independent subgroups but often coexist within the metaphases of one tumor. Generally, complex aberrations are associated with a worse prognosis than simple karyotypic alterations. Due to smaller sizes of the missing segment the detection of recurrent deletions is not always possible by means of classical cytogenetics but requires more advanced techniques as in particular fluorescence in situ hybridization (FISH). Nevertheless, at this time it is not recommended to replace classical cytogenetics by FISH because this would miss additional information given by complex or secondary karyotypic alterations. However, the results of cytogenetic analyses allow the stratification of prognostic and predictive groups of the disease. Of these, the group characterized by deletions involving TP53 is clinically most relevant. In the future refined methods as eg, array-based comparative genomic hybridization will supplement the existing techniques to characterize CLL. PMID:23776377

  20. Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines

    PubMed Central

    2011-01-01

    Background Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. Results In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB-siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. Conclusions The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine. PMID:22051105

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

    SciTech Connect

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

    1994-07-15

    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 {open_quotes}adapter{close_quotes} proteins, which are involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as ras, because adaptor protein genes could also, logically, serve as targets of mutation, rearrangement, or other aberration in disease. Therefore, DNAs from panels of rodent-human hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ hybridization. The NCK locus is at chromosome region 3q21, a region involved in neoplasia-associated changes; the SHC cognate locus, SHC1, is at 1q21, and the GRB2 locus is at 17q22-qter telomeric to the HOXB and NGFR loci. Both SHC1 and GRB2 are in chromosome regions that may be duplicated in some tumor types. 41 refs., 4 figs.

  2. Chromosomal Abnormalities Subdivide Ependymal Tumors into Clinically Relevant Groups

    PubMed Central

    Hirose, Yuichi; Aldape, Kenneth; Bollen, Andrew; James, C. David; Brat, Daniel; Lamborn, Kathleen; Berger, Mitchel; Feuerstein, Burt G.

    2001-01-01

    Ependymoma occurs most frequently within the central nervous system of children and young adults. We determined relative chromosomal copy-number aberrations in 44 ependymomas using comparative genomic hybridization. The study included 24 intracranial and 20 spinal cord tumors from pediatric and adult patients. Frequent chromosomal aberrations in intracranial tumors were gain of 1q and losses on 6q, 9, and 13. Gain of 1q and loss on 9 were preferentially associated with histological grade 3 tumors. On the other hand, gain on chromosome 7 was recognized almost exclusively in spinal cord tumors, and was associated with various other chromosomal aberrations including frequent loss of 22q. We conclude that cytogenetic analysis of ependymomas may help to classify these tumors and provide leads concerning their initiation and progression. The relationship of these aberrations to patient outcome needs to be addressed. PMID:11238062

  3. Noninvolvement of the X chromosome in radiation-induced chromosome translocations in the human lymphoblastoid cell line TK6

    SciTech Connect

    Jordan, R.; Schwartz, J.L. )

    1994-03-01

    Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by [sup 60]Co [gamma] rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized autosome chromosome 7. When corrected for DNA content, acentric fragments were induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases in chromosomal interchanges involving chromosome 7 were noted, and the frequencies of balanced translocations and dicentrics produced were approximately equal. Chromosome interchanges involving the X chromosome were rare and showed no apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive to the induction of chromosome breaks, the X chromosome is much less likely to interact with autosomes than chromosome 7. The noninvolvement of the X chromosome in translocations with autosomes may reflect a more peripheral and separate location for the X chromosome in the mammalian nucleus. 20 refs., 2 figs., 1 tab.

  4. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

    NASA Technical Reports Server (NTRS)

    Goeorge, Kerry; Cucinotta, Francis A.

    2007-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from 51 to 184 keV/micron and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected at G2 and mitosis in first division post irradiation after chromosomes were prematurely condensed using calyculin-A. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 9 to 35. The RBE values increased with LET, reaching a maximum for the 600 MeV/n Fe ions with LET of 184 keV/micron. When the LET of the primary beam was below approximately 100 keV/micron, the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of primary beams was higher than 100 keV/micron. The yield of aberrations correlated with the dose-average LET of the beam after traversal through the shielding.

  5. Cytological and molecular studies of chromosomal radiosensitivity in Down Syndrome cells

    SciTech Connect

    MacLaren, R.A.

    1988-01-01

    Molecular, cellular and cytogenetic studies were conducted to determine if altered levels of poly(ADP-ribose) polymerase, a DNA repair-related enzyme, is responsible for the reported formation of excess X-ray induced chromosome aberrations in cells derived from Down Syndrome (DS) patients. Nonstimulated lymphocytes from normal and DS subjects were pretreated with 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase, for 30 minutes before exposure to X-rays and the levels of induced chromosome aberrations were determined in mitotic cells. DS lymphocytes exhibited significantly higher frequencies of chromosome aberrations in the presence of 3-aminobenzamide that normal lymphocytes. No difference was observed in the absence of 3-aminobenzamide. Additional studies were done using normal and DS lymphoblastoid cell lines which exhibited a similar response at the DNA level as the lymphocytes. Analysis of poly(ADP-ribose) polymerase activity based on incorporation of the substrate, NAD{sup +}, into acid insoluble materials, revealed that there was no significant difference in the ability to form poly (ADP-ribose) in the DS or normal cells. 3-aminobenzamide effectively inhibited poly(ADP-ribose) polymerase in both the normal and DS cells.

  6. Chromosomes, conflict, and epigenetics: chromosomal speciation revisited.

    PubMed

    Brown, Judith D; O'Neill, Rachel J

    2010-01-01

    Since Darwin first noted that the process of speciation was indeed the "mystery of mysteries," scientists have tried to develop testable models for the development of reproductive incompatibilities-the first step in the formation of a new species. Early theorists proposed that chromosome rearrangements were implicated in the process of reproductive isolation; however, the chromosomal speciation model has recently been questioned. In addition, recent data from hybrid model systems indicates that simple epistatic interactions, the Dobzhansky-Muller incompatibilities, are more complex. In fact, incompatibilities are quite broad, including interactions among heterochromatin, small RNAs, and distinct, epigenetically defined genomic regions such as the centromere. In this review, we will examine both classical and current models of chromosomal speciation and describe the "evolving" theory of genetic conflict, epigenetics, and chromosomal speciation. PMID:20438362

  7. Chromosomal intrachanges induced by swift iron ions

    NASA Astrophysics Data System (ADS)

    Horstmann, M.; Durante, M.; Johannes, C.; Obe, G.

    We measured the induction of aberrations in human chromosome 5 by iron ions using the novel technique of multicolor banding in situ hybridization (mBAND). Human lymphocytes isolated from whole blood were exposed in vitro to 500 MeV/n (LET=200 keV/μ m, doses 1 or 4 Gy) 56Fe nuclei at the HIMAC accelerator in Chiba (Japan). Chromosomes were prematurely condensed by calyculin A after 48 h in culture, and slides were painted by mBAND (MetaSystems). We found a frequency of 0.11 and 0.57 residual breakpoints per chromosome 5 after 1 Gy and 4 Gy Fe-ions, respectively. The distribution per unit length were similar in the p- and q-arm of chromosome 5, and >50% of the observed fragments measured <30% of the whole chromosome length. Only small fragments (<40% of the chromosome size) were involved in intra-chromosomal exchanges (interstitial deletions or inversions), whereas fragments up to 75% of the whole chromosome 5 were found in inter-chromosomal exchanges. We measured more inter-changes than intra-changes, and more intra-arm than inter-arm exchanges at both doses. No significant differences in the ratios of these aberrations were detected with respect to X-rays. On the other hand, Fe-ions induced a significantly higher fraction of complex-type exchanges when compared to sparsely ionizing radiation. Work supported by DLR, BMBF, INTAS and NIRS-HIMAC.

  8. Aberrant Gene Expression in Humans

    PubMed Central

    Yang, Ence; Ji, Guoli; Brinkmeyer-Langford, Candice L.; Cai, James J.

    2015-01-01

    Gene expression as an intermediate molecular phenotype has been a focus of research interest. In particular, studies of expression quantitative trait loci (eQTL) have offered promise for understanding gene regulation through the discovery of genetic variants that explain variation in gene expression levels. Existing eQTL methods are designed for assessing the effects of common variants, but not rare variants. Here, we address the problem by establishing a novel analytical framework for evaluating the effects of rare or private variants on gene expression. Our method starts from the identification of outlier individuals that show markedly different gene expression from the majority of a population, and then reveals the contributions of private SNPs to the aberrant gene expression in these outliers. Using population-scale mRNA sequencing data, we identify outlier individuals using a multivariate approach. We find that outlier individuals are more readily detected with respect to gene sets that include genes involved in cellular regulation and signal transduction, and less likely to be detected with respect to the gene sets with genes involved in metabolic pathways and other fundamental molecular functions. Analysis of polymorphic data suggests that private SNPs of outlier individuals are enriched in the enhancer and promoter regions of corresponding aberrantly-expressed genes, suggesting a specific regulatory role of private SNPs, while the commonly-occurring regulatory genetic variants (i.e., eQTL SNPs) show little evidence of involvement. Additional data suggest that non-genetic factors may also underlie aberrant gene expression. Taken together, our findings advance a novel viewpoint relevant to situations wherein common eQTLs fail to predict gene expression when heritable, rare inter-individual variation exists. The analytical framework we describe, taking into consideration the reality of differential phenotypic robustness, may be valuable for investigating

  9. Aberrant methylation during cervical carcinogenesis.

    PubMed

    Virmani, A K; Muller, C; Rathi, A; Zoechbauer-Mueller, S; Mathis, M; Gazdar, A F

    2001-03-01

    We studied the pattern of aberrant methylation during the multistage pathogenesis of cervical cancers. We analyzed a total of 73 patient samples and 10 cervical cancer cell lines. In addition, tissue samples [peripheral blood lymphocytes (n = 10) and buccal epithelial cells (n = 12)] were obtained from 22 healthy volunteers. On the basis of the results of preliminary analysis, the cervical samples were grouped into three categories: (a) nondysplasia/low-grade cervical intraepithelial neoplasia (CIN; n = 37); (b) high-grade CIN (n = 17); and (c) invasive cancer (n = 19). The methylation status of six genes was determined (p16, RARbeta, FHIT, GSTP1, MGMT, and hMLH1). Our main findings are as follows: (a) methylation was completely absent in control tissues; (b) the frequencies of methylation for all of the genes except hMLH1 were >20% in cervical cancers; (c) aberrant methylation commenced early during multistage pathogenesis and methylation of at least one gene was noted in 30% of the nondysplasia/low-grade CIN group; (d) an increasing trend for methylation was seen with increasing pathological change; (e) methylation of RARbeta and GSTP1 were early events, p16 and MGMT methylation were intermediate events, and FHIT methylation was a late, tumor-associated event; and (f) methylation occurred independently of other risk factors including papillomavirus infection, smoking history, or hormone use. Although our findings need to be extended to a larger series, they suggest that the pattern of aberrant methylation in women with or without dysplasia may help identify subgroups at increased risk for histological progression or cancer development. PMID:11297252

  10. Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies.

    PubMed

    Wachowicz, Paulina; Fernández-Miranda, Gonzalo; Marugán, Carlos; Escobar, Beatriz; de Cárcer, Guillermo

    2016-07-01

    Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays multiple and essential roles during the cell division cycle. Its inhibition in cultured cells leads to severe mitotic aberrancies and cell death. Whereas previous reports suggested that Plk1 depletion in mice leads to a non-mitotic arrest in early embryos, we show here that the bi-allelic Plk1 depletion in mice certainly results in embryonic lethality due to extensive mitotic aberrations at the morula stage, including multi- and mono-polar spindles, impaired chromosome segregation and cytokinesis failure. In addition, the conditional depletion of Plk1 during mid-gestation leads also to severe mitotic aberrancies. Our data also confirms that Plk1 is completely dispensable for mitotic entry in vivo. On the other hand, Plk1 haploinsufficient mice are viable, and Plk1-heterozygous fibroblasts do not harbor any cell cycle alterations. Plk1 is overexpressed in many human tumors, suggesting a therapeutic benefit of inhibiting Plk1, and specific small-molecule inhibitors for this kinase are now being evaluated in clinical trials. Therefore, the different Plk1 mouse models here presented are a valuable tool to reexamine the relevance of the mitotic kinase Plk1 during mammalian development and animal physiology. PMID:27417127

  11. Comparison of Aberrations After Standard and Customized Refractive Surgery

    NASA Astrophysics Data System (ADS)

    Fang, L.; He, X.; Wang, Y.

    2013-09-01

    To detect possible differences in residual wavefront aberrations between standard and customized laser refractive surgery based onmathematical modeling, the residual optical aberrations after conventional and customized laser refractive surgery were compared accordingto the ablation profile with transition zone. The results indicated that ablation profile has a significant impact on the residual aberrations.The amount of residual aberrations for conventional correction is higher than that for customized correction. Additionally, the residualaberrations for high myopia eyes are markedly larger than those for moderate myopia eyes. For a 5 mm pupil, the main residual aberrationterm is coma and yet it is spherical aberration for a 7 mm pupil. When the pupil diameter is the same as optical zone or greater, themagnitudes of residual aberrations is obviously larger than that for a smaller pupil. In addition, the magnitudes of the residual fifth orsixth order aberrations are relatively large, especially secondary coma in a 6 mm pupil and secondary spherical aberration in a 7 mm pupil.Therefore, the customized ablation profile may be superior to the conventional correction even though the transition zone and treatmentdecentration are taken into account. However, the customized ablation profile will still induce significant amount of residual aberrations.

  12. Characterization of chromosomal architecture in Arabidopsis by chromosome conformation capture

    PubMed Central

    2013-01-01

    Background The packaging of long chromatin fibers in the nucleus poses a major challenge, as it must fulfill both physical and functional requirements. Until recently, insights into the chromosomal architecture of plants were mainly provided by cytogenetic studies. Complementary to these analyses, chromosome conformation capture technologies promise to refine and improve our view on chromosomal architecture and to provide a more generalized description of nuclear organization. Results Employing circular chromosome conformation capture, this study describes chromosomal architecture in Arabidopsis nuclei from a genome-wide perspective. Surprisingly, the linear organization of chromosomes is reflected in the genome-wide interactome. In addition, we study the interplay of the interactome and epigenetic marks and report that the heterochromatic knob on the short arm of chromosome 4 maintains a pericentromere-like interaction profile and interactome despite its euchromatic surrounding. Conclusion Despite the extreme condensation that is necessary to pack the chromosomes into the nucleus, the Arabidopsis genome appears to be packed in a predictive manner, according to the following criteria: heterochromatin and euchromatin represent two distinct interactomes; interactions between chromosomes correlate with the linear position on the chromosome arm; and distal chromosome regions have a higher potential to interact with other chromosomes. PMID:24267747

  13. Cytogenetic heterogeneity and their serial dynamic changes during acquisition of cytogenetic aberrations in cultured mesenchymal stem cells.

    PubMed

    Kim, Jung-Ah; Im, Kyong Ok; Park, Si Nae; Kwon, Ji Seok; Kim, Seon Young; Oh, Keunhee; Lee, Dong-Sup; Kim, Min Kyung; Kim, Seong Who; Jang, Mi; Lee, Gene; Oh, Yeon-Mok; Lee, Sang Do; Lee, Dong Soon

    2015-07-01

    To minimize the risk of tumorigenesis in mesenchymal stem cells (MSCs), G-banding analysis is widely used to detect chromosomal aberrations in MSCs. However, a critical limitation of G-banding is that it only reflects the status of metaphase cells, which can represent as few as 0.01% of tested cells. During routine cytogenetic testing in MSCs, we often detect chromosomal aberrations in minor cell populations. Therefore, we aimed to investigate whether such a minority of cells can expand over time or if they ultimately disappear during MSC passaging. We passaged MSCs serially while monitoring quantitative changes for each aberrant clone among heterogeneous MSCs. To investigate the cytogenetic status of interphase cells, which represent the main population, we also performed interphase FISH analysis, in combination with G-banding and telomere length determination. In human adipose tissue-derived MSCs, 4 types of chromosomal aberrations were found during culturing, and in umbilical cord MSCs, 2 types of chromosomal aberrations were observed. Sequential dynamic changes among heterogeneous aberrant clones during passaging were similar to the dynamic changes observed in cancer stem cells during disease progression. Throughout all passages, the quantitative G-banding results were inconsistent with those of the interphase FISH analysis. Interphase FISH revealed hidden aberrations in stem cell populations with normal karyotypes by G-banding analysis. We found that telomere length gradually decreased during passaging until the point at which cytogenetic aberrations appeared. The present study demonstrates that rare aberrant clones at earlier passages can become predominant clones during later passages. Considering the risk of tumorigenesis due to aberrant MSCs, we believe that our results will help to establish proper safety guidelines for MSC use. In particular, we believe it is critical to test for chromosomal aberrations using both G-banding and FISH to ensure the safety

  14. Chromosomal mosaicism of extraembryonic cells detected by prenatal diagnosis

    SciTech Connect

    Zolotukhina, T.V.; Shilova, N.V.

    1995-09-01

    Data on detection of chromosomal mosaicism in amniotic cells and chorionic villi obtained by prenatal cytogenetic diagnosis are presented. The frequency of chromosomal mosaicism in preparations of amniotic fluid cell culture was 2.6% (6 out of 226), and that in {open_quotes}direct{close_quotes} villus preparations was 1.6% (13 out of 774). The necessity to perform an additional analysis of other fetal cells or neonatal lymphocytes to specify the diagnosis was shown. The analysis of the outcome of pregnancies during which chromosomal mosaicism in the extraembryonic cells was detected indicates that these women form a high-risk group, both genetically and obstetrically; in only 8 out of 19 cases did pregnancies end in normal deliveries at term; in three cases, spontaneous abortions occurred at 16-31 weeks of gestation; in three cases, the pregnancies were terminated due to fetal chromosomal aberrations in nonmosaic form; the outcome of pregnancy in five cases was preterm delivery of an underweight newborn. 26 refs., 1 tab.

  15. X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

    PubMed Central

    Madrigal, I; Rodríguez-Revenga, L; Armengol, L; González, E; Rodriguez, B; Badenas, C; Sánchez, A; Martínez, F; Guitart, M; Fernández, I; Arranz, JA; Tejada, MI; Pérez-Jurado, LA; Estivill, X; Milà, M

    2007-01-01

    Background Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients. PMID:18047645

  16. The ATM kinase signaling induced by the low-energy β-particles emitted by (33)P is essential for the suppression of chromosome aberrations and is greater than that induced by the energetic β-particles emitted by (32)P.

    PubMed

    White, Jason S; Yue, Ning; Hu, Jing; Bakkenist, Christopher J

    2011-03-15

    Ataxia-telangiectasia mutated (ATM) encodes a nuclear serine/threonine protein kinase whose activity is increased in cells exposed to low doses of ionizing radiation (IR). Here we examine ATM kinase activation in cells exposed to either (32)P- or (33)P-orthophosphate under conditions typically employed in metabolic labelling experiments. We calculate that the absorbed dose of IR delivered to a 5cm×5cm monolayer of cells incubated in 2ml media containing 1mCi of the high-energy (1.70MeV) β-particle emitter (32)P-orthophosphate for 30min is ∼1Gy IR. The absorbed dose of IR following an otherwise identical exposure to the low-energy (0.24MeV) β-particle emitter (33)P-orthophosphate is ∼0.18Gy IR. We show that low-energy β-particles emitted by (33)P induce a greater number of ionizing radiation-induced foci (IRIF) and greater ATM kinase signaling than energetic β-particles emitted by (32)P. Hence, we demonstrate that it is inappropriate to use (33)P-orthophosphate as a negative control for (32)P-orthophosphate in experiments investigating DNA damage responses to DNA double-strand breaks (DSBs). Significantly, we show that ATM accumulates in the chromatin fraction when ATM kinase activity is inhibited during exposure to either radionuclide. Finally, we also show that chromosome aberrations accumulate in cells when ATM kinase activity is inhibited during exposure to ∼0.36Gy β-particles emitted by (33)P. We therefore propose that direct cellular exposure to (33)P-orthophosphate is an excellent means to induce and label the IR-induced, ATM kinase-dependent phosphoproteome. PMID:21315088

  17. Characterization of chromosome 1 abnormalities in malignant melanomas.

    PubMed

    Smedley, D; Sidhar, S; Birdsall, S; Bennett, D; Herlyn, M; Cooper, C; Shipley, J

    2000-05-01

    Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanomas. Specific breakpoints are reported for malignant melanomas throughout the chromosome but especially at 1p36 and at several sites throughout 1p22-q21. In addition, partial deletions and loss of heterozygosity have been found on 1p indicating the possible location of tumor suppressor genes. Here we have characterized the involvement of chromosome 1 in a series of seven malignant melanoma cell lines. Initial chromosome painting studies revealed that six of the cell lines had chromosome 1 rearrangements. Deletions involving 1p10-32, 1q11-44, and 1q25-44 were observed. The other rearrangement breakpoints included three in the 1q10-p11 region with the rest at 1p36, 1p34, 1p32, 1p31, 1p12-13, 1q21, and 1q23. The breaks at 1q10-p11 were investigated further using an alpha-satellite 1 centromere probe and yeast artificial chromosomes (YACs) from the region. Two of the 1q10-p11 breaks mapped in the centromeric region, while the others mapped to variable sites. This suggests that the role of these rearrangements in the pathogenesis of melanomas does not involve the alteration of specific oncogenes in the breakpoint region. During the YAC mapping a previously undetected, small (<1 Mbp) del(1)(p10p11) was identified. This deletion lies within minimal overlapping deleted regions reported in head and neck as well as breast carcinomas and it could therefore facilitate the isolation of a carcinoma-associated tumor suppressor gene. PMID:10738310

  18. Ring Chromosome 7 in an Indian Woman

    ERIC Educational Resources Information Center

    Kaur, Anupam; Dhillon, Sumit; Garg, P. D.; Singh, Jai Rup

    2008-01-01

    Background: Ring chromosome 7 [r(7)] is a rare cytogenetic aberration, with only 16 cases (including 3 females) reported in the literature to date. This is the first reported case of r(7) from India. Method: Clinical and cytogenetic investigations were carried out in an adult female with microcephaly and intellectual disability. Results: Ring…

  19. Chromosomes and plant cell division in space

    NASA Technical Reports Server (NTRS)

    Krikorian, A. D.

    1988-01-01

    The objectives were: examination of chromosomal aberrations; development of an experimental system; and engineering design units (EDUs) evaluation. Evaluation criteria are presented. Procedures were developed for shuttle-based investigations which result in the procurement of plant root tips for subsequent cytological examination.

  20. Chromosomal Flexibility

    ERIC Educational Resources Information Center

    Journal of College Science Teaching, 2005

    2005-01-01

    Scientists have shown that a genetic element on one chromosome may direct gene activity on another. Howard Hughes Medical Institute (HHMI) researchers report that a multitasking master-control region appears to over-see both a set of its own genes and a related gene on a nearby chromosome. The findings reinforce the growing importance of location…

  1. Aberration correction of unstable resonators

    NASA Technical Reports Server (NTRS)

    Lang, Robert J. (Inventor)

    1994-01-01

    Construction of aspheric reflectors for unstable resonator lasers to provide an arbitrary laser mode inside the resonator to correct aberrations of an output beam by the construction of the shape of an end reflector opposite the output reflector of the resonator cavity, such as aberrations resulting from refraction of a beam exiting the solid of the resonator having an index of refraction greater than 1 or to produce an aberration in the output beam that will precisely compensate for the aberration of an optical train into which the resonator beam is coupled.

  2. Biological dosimetry by interphase chromosome painting

    NASA Technical Reports Server (NTRS)

    Durante, M.; George, K.; Yang, T. C.

    1996-01-01

    Both fluorescence in situ hybridization of metaphase spreads with whole-chromosome probes and premature chromosome condensation in interphase nuclei have been used in the past to estimate the radiation dose to lymphocytes. We combined these techniques to evaluate the feasibility of using painted interphase chromosomes for biodosimetry. Human peripheral lymphocytes were exposed to gamma rays and fused to mitotic Chinese hamster cells either immediately after irradiation or after 8 h incubation at 37 degrees C. Interphase or metaphase human chromosomes were hybridized with a composite probe specific for human chromosomes 3 and 4. The dose-response curve for fragment induction immediately after irradiation was linear; these results reflected breakage frequency in the total genome in terms of DNA content per chromosome. At 8 h after irradiation, the dose-response curve for chromosome interchanges, the prevalent aberration in interphase chromosomes, was linear-quadratic and similar to that observed for metaphase chromosomes. These results suggest that painting prematurely condensed chromosomes can be useful for biological dosimetry when blood samples are available shortly after the exposure, or when interphase cells are to be scored instead of mitotic cells.

  3. Early and Late Chromosome Damages in Human Lymphocytes Induced by Gamma Rays and Fe Ions

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  4. Genotoxicity studies of the food additive ester gum.

    PubMed

    Mukherjee, A; Agarwal, K; Chakrabarti, J

    1992-07-01

    Ester gum (EG) is used in citrus oil-based beverage flavourings as a weighting or colouring agent. In the present study, concentrations of 50, 100 and 150 mg/kg body weight were administered orally to male Swiss albino mice, and sister chromatid exchange and chromosomal aberration were used as the cytogenetic endpoints to determine the genotoxic and clastogenic potential of the food additive. Although EG was weakly clastogenic and could induce a marginal increase in sister chromatid exchange frequencies, it was not a potential health hazard at the doses tested. PMID:1521837

  5. Aberrant “Barbed-Wire” Nuclear Projections of Neutrophils in Trisomy 18 (Edwards Syndrome)

    PubMed Central

    Kahwash, Basil M.; Nowacki, Nicholas B.; Kahwash, Samir B.

    2015-01-01

    We discuss the significance of neutrophils with increased, aberrant nuclear projections mimicking “barbed-wire” in a newborn child with trisomy 18 (T18). Increased, aberrant nuclear projections have been previously reported in trisomy of the D group of chromosomes (chromosomes 13, 14, and 15), and we report similar findings in a patient with T18. The peripheral blood smear showed relative neutrophilia with the majority (37%) of neutrophils showing two or more thin, rod-shaped or spike-shaped, and often pedunculated aberrant nuclear projections. The number of projections ranged from 2 to 6 per cell, averaged 2 per affected neutrophil, and ranged in length from 0.22 μm to 0.83 μm. This case confirms that the morphologic finding described is not restricted to trisomy of one of the chromosomes in group D, as implied in the literature. PMID:26770846

  6. The chromosome cycle of prokaryotes

    PubMed Central

    Kuzminov, Andrei

    2013-01-01

    Summary In both eukaryotes and prokaryotes, chromosomal DNA undergoes replication, condensation-decondensation and segregation, sequentially, in some fixed order. Other conditions, like sister-chromatid cohesion (SCC), may span several chromosomal events. One set of these chromosomal transactions within a single cell cycle constitutes the “chromosome cycle”. For many years it was generally assumed that the prokaryotic chromosome cycle follows major phases of the eukaryotic one: -replication-condensation-segregation-(cell division)-decondensation-, with SCC of unspecified length. Eventually it became evident that, in contrast to the strictly consecutive chromosome cycle of eukaryotes, all stages of the prokaryotic chromosome cycle run concurrently. Thus, prokaryotes practice “progressive” chromosome segregation separated from replication by a brief SCC, and all three transactions move along the chromosome at the same fast rate. In other words, in addition to replication forks, there are “segregation forks” in prokaryotic chromosomes. Moreover, the bulk of prokaryotic DNA outside the replication-segregation transition stays compacted. I consider possible origins of this concurrent replication-segregation and outline the “nucleoid administration” system that organizes the dynamic part of the prokaryotic chromosome cycle. PMID:23962352

  7. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques

    PubMed Central

    Han, Liangrong; Jing, Xin; Liu, Hailiang; Yang, Chuanchun; Zhang, Fengting; Hu, Yue; Yue, Hongni; Ning, Ying

    2016-01-01

    Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques. PMID:27218255

  8. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

    PubMed

    Pan, Qiong; Hu, Hao; Han, Liangrong; Jing, Xin; Liu, Hailiang; Yang, Chuanchun; Zhang, Fengting; Hu, Yue; Yue, Hongni; Ning, Ying

    2016-01-01

    Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques. PMID:27218255

  9. Adaptive aberration correction using a triode hyperbolic electron mirror.

    PubMed

    Fitzgerald, J P S; Word, R C; Könenkamp, R

    2011-01-01

    A converging electron mirror can be used to compensate spherical and chromatic aberrations in an electron microscope. This paper presents an analytical solution to a novel triode (three electrode) hyperbolic mirror as an improvement to the well-known diode (two electrode) hyperbolic mirror for aberration correction. A weakness of the diode mirror is a lack of flexibility in changing the chromatic and spherical aberration coefficients independently without changes in the mirror geometry. In order to remove this limitation, a third electrode can be added. We calculate the optical properties of the resulting triode mirror analytically on the basis of a simple model field distribution. We present the optical properties-the object/image distance, z(0), and the coefficients of spherical and chromatic aberration, C(s) and C(c), of both mirror types from an analysis of electron trajectories in the mirror field. From this analysis, we demonstrate that while the properties of both designs are similar, the additional parameters in the triode mirror improve the range of aberration that can be corrected. The triode mirror is also able to provide a dynamic adjustment range of chromatic aberration for fixed spherical aberration and focal length, or any permutation of these three parameters. While the dynamic range depends on the values of aberration correction needed, a nominal 10% tuning range is possible for most configurations accompanied by less than 1% change in the other two properties. PMID:21930022

  10. Delayed chromosome changes in gamma-irradiated normal and Li-Fraumeni fibroblasts.

    PubMed

    Boyle, J M; Spreadborough, A R; Greaves, M J; Birch, J M; Varley, J M; Scott, D

    2002-02-01

    Knockout mice with only one Trp53 allele (+/- genotype) are highly susceptible to radiation-induced cancers, possibly through numerical chromosome changes. Patients with the Li-Fraumeni syndrome, having heterozygous TP53 germline mutations (+/mut genotype), are also susceptible to spontaneous and radiogenic cancers. We have investigated the susceptibility of six Li-Fraumeni syndrome +/mut and six normal fibroblast strains to induced numerical and unstable structural aberrations at six population doublings after exposure to 3 or 6 Gy gamma rays. Four of the irradiated Li-Fraumeni syndrome strains showed small increases in both aberration types, similar to those seen in the normal strains. In two irradiated Li-Fraumeni syndrome strains, there were high levels of induced structural changes, and one of these showed a modest increase in hyperploidy. We suggest that enhanced sensitivity to delayed radiation-induced chromosome changes in Li-Fraumeni syndrome cells requires other genetic alterations in addition to TP53 heterozygosity, apparently in contrast to the situation in Trp53 heterozygous null mice. If such additional alterations occur in vivo in Li-Fraumeni syndrome patients, they may predispose them to radiogenic cancers, mainly through enhanced structural rather than numerical chromosome changes. Our findings raise questions about the validity of quantitative extrapolation of cytogenetic data from Trp53-defective mice to radiogenic cancer risk in humans. PMID:11835679

  11. Compendium of aberrant DNA methylation and histone modifications in cancer.

    PubMed

    Hattori, Naoko; Ushijima, Toshikazu

    2014-12-01

    Epigenetics now refers to the study or research field related to DNA methylation and histone modifications. Historically, global DNA hypomethylation was first revealed in 1983, and, after a decade, silencing of a tumor suppressor gene by regional DNA hypermethylation was reported. After the proposal of the histone code in the 2000s, alterations of histone methylation were also identified in cancers. Now, it is established that aberrant epigenetic alterations are involved in cancer development and progression, along with mutations and chromosomal losses. Recent cancer genome analyses have revealed a large number of mutations of epigenetic modifiers, supporting their important roles in cancer pathogenesis. Taking advantage of the reversibility of epigenetic alterations, drugs targeting epigenetic regulators and readers have been developed for restoration of normal pattern of the epigenome, and some have already demonstrated clinical benefits. In addition, DNA methylation of specific marker genes can be used as a biomarker for cancer diagnosis, including risk diagnosis, detection of cancers, and pathophysiological diagnosis. In this paper, we will summarize the major concepts of cancer epigenetics, placing emphasis on history. PMID:25194808

  12. [Chromosomal organization of the genomes of small-chromosome plants].

    PubMed

    Muravenko, O V; Zelenin, A V

    2009-11-01

    An effective approach to study the chromosome organization in genomes of plants with small chromosomes and/or with low-informative C-banding patterns was developed in the course of investigation of the karyotypes of cotton plant, camomile, flax, and pea. To increase the resolving power of chromosome analysis, methods were worked out for revealing early replication patterns on chromosomes and for artificial impairment of mitotic chromosome condensation with the use of a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the patterns of C-banding of small chromosomes on preparations obtained with the use of 9-AMA, it is necessary to choose a length interval that must not exceed three average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA increases the resolution of differential C- and OR-banding and the precision of physical chromosome mapping by the FISH method. Of particular importance in studying small chromosomes is optimization of the computer-aided methods used to obtain and process chromosome images. The complex approach developed for analysis of the chromosome organization in plant genomes was used to study the karyotypes of 24 species of the genus Linum L. It permitted their chromosomes to be identified for the first time, and, in addition, B chromosomes were discovered and studied in the karyotypes of the species of the section Syllinum. By similarity of the karyotypes, the studied flax species were distributed in eight groups in agreement with the clusterization of these species according to the results of RAPD analysis performed in parallel. Systematic positions and phylogenetic relationships of the studied flax species were verified. Out results can serve as an important argument in favour of the proposal to develop a special program for sequencing the genome of cultivated flax (L. usitatissimum L.), which is a major representative of small-chromosome species. PMID:20058798

  13. Advances in understanding paternally transmitted Chromosomal Abnormalities

    SciTech Connect

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate the types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.

  14. Zygotic chromosomal structural aberrations after paternal drug treatment

    PubMed Central

    Downey, Anne Marie; Robaire, Bernard

    2015-01-01

    In recent years, the field of male-mediated reproductive toxicology has received growing attention. It is now well-established that many drugs, chemicals, and environmental factors can harm male germ cells by inducing DNA damage. Male germ cells have extensive repair mechanisms that allow detection and repair of damaged DNA during the early phases of spermatogenesis. However, during the later phase of spermiogenesis, when the haploid spermatids undergo chromatin condensation and become transcriptionally quiescent, their ability to repair damaged DNA is lost.12 It is also thought that the highly compacted chromatin of the sperm can protect DNA against damage.3 Therefore, it is expected that late spermatids will be most susceptible to DNA damaging agents. Unrepaired or misrepaired damage in the germ cells leads to the generation of spermatozoa with DNA damage that can be transmitted to the next generation. Fortunately, the maternal DNA repair machinery is capable of recognizing and repairing, at least to some degree, damaged paternal DNA after fertilization in the zygote. Therefore, the efficiency of the maternal repair machinery will greatly influence the risk of transmitting paternal DNA damage to offspring.4 PMID:25999360

  15. Influence of misalignment and aberrations on antenna received power in free-space laser communications

    NASA Astrophysics Data System (ADS)

    Tan, Liying; Yang, Yuqiang; Ma, Jing; Zheng, Guoxian

    2009-04-01

    To evaluate the influence of wavefront aberrations on antenna received power in free-space laser communications, an aberration attenuation factor is proposed, based on which the power penalty at the receiver due to misalignment and primary aberrations is investigated. It is shown that antenna received power decreases gradually with increasing misalignment and aberrations. A comparison shows that tilt (misalignment) has greater influence than other primary aberrations. When the rms aberration value is 0.1λ, the received power penalties caused by tilt, astigmatism, coma, curvature, and spherical aberrations are about 40%, 36%, 35%, 24%, and 23%, respectively. In addition, the obscuration ratio of the transmitter antenna has a noticeable but relatively minor influence on the aberration attenuation factor.

  16. Comparison of mitotic cell death by chromosome fragmentation to premature chromosome condensation

    PubMed Central

    2010-01-01

    Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused with chromosome fragmentation. In this analysis the phenomena of chromosome fragmentation and PCC are reviewed and their similarities and differences are discussed in order to facilitate differentiation of the similar morphologies. Furthermore, chromosome pulverization, which has been used almost synonymously with PCC, is re-examined. Interestingly, many past reports of chromosome pulverization are identified here as chromosome fragmentation and not PCC. These reports describe broad ranging mechanisms of pulverization induction and agree with recent evidence showing chromosome fragmentation is a cellular response to stress. Finally, biological aspects of chromosome fragmentation are discussed, including its application as one form of non-clonal chromosome aberration (NCCA), the driving force of cancer evolution. PMID:20959006

  17. Chromatic variation of aberration: the role of induced aberrations and raytrace direction

    NASA Astrophysics Data System (ADS)

    Berner, A.; Nobis, T.; Shafer, D.; Gross, H.

    2015-09-01

    The design and optimization process of an optical system contains several first order steps. The definition of the appropriate lens type and the fixation of the raytrace direction are some of them. The latter can be understood as a hidden assumption rather than an aware design step. This is usually followed by the determination of the paraxial lens layout calculated for the primary wavelength. It is obvious, that for this primary wavelength the paraxial calculations are independent of raytrace direction. Today, most of the lens designs are specified not to work only for one wavelength, but in a certain wavelength range. Considering such rays of other wavelengths, one can observe that depending on the direction there will already occur differences in the first order chromatic aberrations and additionally in the chromatic variation of the third-order aberrations. The reason for this effect are induced aberrations emerging from one surface to the following surfaces by perturbed ray heights and ray angles. It can be shown, that the total amount of surface-resolved first order chromatic aberrations and the chromatic variation of the five primary aberrations can be split into an intrinsic part and an induced part. The intrinsic part is independent of the raytrace direction whereas the induced part is not.

  18. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  19. Break Point Distribution on Chromosome 3 of Human Epithelial Cells exposed to Gamma Rays, Neutrons and Fe Ions

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

    Most of the reported studies of break point distribution on the damaged chromosomes from radiation exposure were carried out with the G-banding technique or determined based on the relative length of the broken chromosomal fragments. However, these techniques lack the accuracy in comparison with the later developed multicolor banding in situ hybridization (mBAND) technique that is generally used for analysis of intrachromosomal aberrations such as inversions. Using mBAND, we studied chromosome aberrations in human epithelial cells exposed in vitro to both low or high dose rate gamma rays in Houston, low dose rate secondary neutrons at Los Alamos National Laboratory and high dose rate 600 MeV/u Fe ions at NASA Space Radiation Laboratory. Detailed analysis of the inversion type revealed that all of the three radiation types induced a low incidence of simple inversions. Half of the inversions observed after neutron or Fe ion exposure, and the majority of inversions in gamma-irradiated samples were accompanied by other types of intrachromosomal aberrations. In addition, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosome exchanges. We further compared the distribution of break point on chromosome 3 for the three radiation types. The break points were found to be randomly distributed on chromosome 3 after neutrons or Fe ions exposure, whereas non-random distribution with clustering break points was observed for gamma-rays. The break point distribution may serve as a potential fingerprint of high-LET radiation exposure.

  20. Stella preserves maternal chromosome integrity by inhibiting 5hmC-induced γH2AX accumulation

    PubMed Central

    Nakatani, Tsunetoshi; Yamagata, Kazuo; Kimura, Tohru; Oda, Masaaki; Nakashima, Hiroyuki; Hori, Mayuko; Sekita, Yoichi; Arakawa, Tatsuhiko; Nakamura, Toshinobu; Nakano, Toru

    2015-01-01

    In the mouse zygote, Stella/PGC7 protects 5-methylcytosine (5mC) of the maternal genome from Tet3-mediated oxidation to 5-hydroxymethylcytosine (5hmC). Although ablation of Stella causes early embryonic lethality, the underlying molecular mechanisms remain unknown. In this study, we report impaired DNA replication and abnormal chromosome segregation (ACS) of maternal chromosomes in Stella-null embryos. In addition, phosphorylation of H2AX (γH2AX), which has been reported to inhibit DNA replication, accumulates in the maternal chromatin of Stella-null zygotes in a Tet3-dependent manner. Cell culture assays verified that ectopic appearance of 5hmC induces abnormal accumulation of γH2AX and subsequent growth retardation. Thus, Stella protects maternal chromosomes from aberrant epigenetic modifications to ensure early embryogenesis. PMID:25694116

  1. [The chromosomal radiosensitivity of children whose parents were exposed to antitumor radiochemotherapy].

    PubMed

    Vorobtsova, I E; Vorob'eva, M V

    1992-12-01

    The effect of gamma radiation was studied on routine stained chromosomes from lymphocytes of children born to Hodgkin's disease patients after cancer therapy (CP) in comparison to children from healthy parents (HP). Irradiation (0, 0.25, 0.50, 1.00, 1.50 Gy) of the whole blood was performed in culture medium. Metaphases were obtained from 52-h cultures. Chromosomal aberrations were used as an endpoint. Aberrations of both chromosomal and chromatid types were scored in 150-200 metaphases for estimation of spontaneous level of cytogenetic injuries and in 100 metaphases of induced one. It is found that chromosomes of CP children are more radiosensitive than chromosomes of HP ones, the spontaneous frequency of chromosome aberrations being equal in both groups. PMID:1292705

  2. Structural and numerical changes of chromosome X in patients with esophageal atresia

    PubMed Central

    Brosens, Erwin; de Jong, Elisabeth M; Barakat, Tahsin Stefan; Eussen, Bert H; D'haene, Barbara; De Baere, Elfride; Verdin, Hannah; Poddighe, Pino J; Galjaard, Robert-Jan; Gribnau, Joost; Brooks, Alice S; Tibboel, Dick; de Klein, Annelies

    2014-01-01

    Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a relatively common birth defect often associated with additional congenital anomalies such as vertebral, anal, cardiovascular, renal and limb defects, the so-called VACTERL association. Yet, little is known about the causal genetic factors. Rare case reports of gastrointestinal anomalies in children with triple X syndrome prompted us to survey the incidence of structural and numerical changes of chromosome X in patients with EA/TEF. All available (n=269) karyotypes of our large (321) EA/TEF patient cohort were evaluated for X-chromosome anomalies. If sufficient DNA material was available, we determined genome-wide copy number profiles with SNP array and identified subtelomeric aberrations on the difficult to profile PAR1 region using telomere-multiplex ligation-dependent probe amplification. In addition, we investigated X-chromosome inactivation (XCI) patterns and mode of inheritance of detected aberrations in selected patients. Three EA/TEF patients had an additional maternally inherited X chromosome. These three female patients had normal random XCI patterns. Two male EA/TEF patients had small inherited duplications of the XY-linked SHOX (Short stature HOmeoboX-containing) locus. Patients were small for gestational age at birth (additional, mostly VACTERL associated, anomalies. Triple X syndrome is rarely described in patients with EA/TEF and no duplications of the SHOX gene were reported so far in these patients. As normal patterns of XCI were seen, overexpression of X-linked genes that escape XCI, such as the SHOX gene, could be pathogenic by disturbing developmental pathways. PMID:24398799

  3. Abnormal mitosis in hypertetraploid cells causes aberrant nuclear morphology in association with H2O2-induced premature senescence.

    PubMed

    Ohshima, Susumu

    2008-09-01

    Aberrant nuclear morphology, such as nuclei with irregular shapes or fragmented nuclei, is often observed in senescent cells, but its biological significance is not fully understood. My previous study showed that aberrant nuclear morphology in senescent human fibroblasts is attributable to abnormal mitosis in later passages. In this study, the production of abnormal nuclei in association with premature senescence was investigated. Premature senescence was induced by brief exposure of human fibroblasts to hydrogen peroxide (H(2)O(2)), and mitosis was observed by time-lapse microscopy. In addition, cell cycle and nuclear morphology after exposure to H(2)O(2) were also analyzed using a laser scanning cytometer. Time-lapse analysis revealed that the induction of premature senescence caused abnormal mitoses, such as mitotic slippage or incomplete mitosis, especially in later days after H(2)O(2) exposure and often resulted in abnormal nuclear morphology. Analysis by laser scanning cytometer showed significantly higher frequency of abnormal cells with deformed nuclei and abnormal mitotic cells with misaligned chromosomes in a hypertetraploid subpopulation. These results suggest that unstable hypertetraploid cells, formed in association with H(2)O(2)-induced premature senescence, cause abnormal mitosis that leads to aberrant nuclear morphology. PMID:18618767

  4. Correction of Distributed Optical Aberrations

    SciTech Connect

    Baker, K; Olivier, S; Carrano, C; Phillion, D

    2006-02-12

    The objective of this project was to demonstrate the use of multiple distributed deformable mirrors (DMs) to improve the performance of optical systems with distributed aberrations. This concept is expected to provide dramatic improvement in the optical performance of systems in applications where the aberrations are distributed along the optical path or within the instrument itself. Our approach used multiple actuated DMs distributed to match the aberration distribution. The project developed the algorithms necessary to determine the required corrections and simulate the performance of these multiple DM systems.

  5. Coating-induced wavefront aberrations

    NASA Astrophysics Data System (ADS)

    Reiley, Daniel J.; Chipman, Russell A.

    1992-12-01

    The coatings which are used on telescope mirrors and other optical interfaces can have a profound effect on the image quality formed by an optical system. This paper evaluates the defocus and astigmatism which are caused by the s- and p-phase shifts of coatings. These coating-induced wavefront aberrations are usually insignificant, but can, under certain circumstances, overshadow the geometric wavefront aberrations of the system. The wavefront aberrations induced by reflection-enhanced coatings on an f/1.5 Cassegrain telescope are numerically evaluated as an example.

  6. Use of fluorescence in situ hybridization (fish) to study chromosomal damage induced by radiation and bromodeoxyuridine in human colon cancer cells

    SciTech Connect

    Wilt, S.R.; Burgess, A.C.; Lawrence, T.S.

    1994-11-15

    Although the thymidine analog radiation sensitizer bromodeoxyuridine (BrdUrd) increases radiation-induced chromosomal aberrations, it is not known whether these aberrations are uniformly distributed among chromosomes. Using fluorescence in situ hybridization, we carried out a study to test the hypothesis that BrdUrd-induced radiosensitization may be mediated by nonuniform chromsomal damage. Log phase HT29 human colon cancer cells were exposed to 10 {mu}M BrdUrd (or media alone) for one cell cycle, and the G1 cells were separated by centrifugal elutriation. Half of the control and BrdUrd samples were irradiated with 8 Gy. Cells were then incubated for 24-28 h, and metaphase spreads were prepared. Fluorescence in situ hybridization was performed using paint probes for chromosomes 1 and 4. We found that radiation induced 0.20 aberrations per chromosome in chromosome 4. Based on the ratio of the relative lengths of chromosome 1-4(1.34), it was predicted that chromosome 1 would have {approx}0.26 aberrations per chromosome. However, we observed 0.39 aberrations per chromosome 1, which was significantly greater than the predicted (p<0.001 by chi-square). Incubation with BrdUrd prior to irradiation significantly increased the aberrations found in chromosome 1 (by a factor of 1.4) and chromosome 4 (by a factor of 1.9) compared to radiation alone (p<0.001 for both chromosome 1 and 4). This study demonstrates that individual chromosomes in human colon cancer cells show significantly different rates of aberration after irradiation. Furthermore, the BrdUrd-mediated increase in radiation-induced chromosomal aberrations may not be uniform among chromosomes. 20 refs., 4 figs., 1 tab.

  7. Aberrations of 6q13 Mapped to the COL12A1 Locus in Chondromyxoid Fibroma

    PubMed Central

    Yasuda, Taketoshi; Nishio, Jun; Sumegi, Janos; Kapels, Kayla M.; Althof, Pamela A.; Sawyer, Jeffrey R.; Reith, John D.; Bridge, Julia A.

    2009-01-01

    Chondromyxoid fibroma, a rare benign bone tumor, may be mistaken for chondrosarcoma. Although cytogenetic studies of chondromyxoid fibroma are few, rearrangements of the long arm of chromosome 6 frequently expressed as an inv(6)(p25q13) are prominent. In this study, conventional cytogenetic analysis of 16 chondromyxoid fibroma samples from 14 patients revealed rearrangements of chromosome 6 in ten of eleven clonally abnormal specimens. In addition to 6q13 rearrangements, recurrent 6p25 and 6q25 anomalies were detected. Notably, an identical t(6;9)(q25;q22) translocation was identified in two cases suggesting it represents a distinct translocation of chon