Post-irradiation treatment of human lymphocytes with spermidine reduced frequency of chromatid breaks

International Nuclear Information System (INIS)

Bocian, E.; Rosiek, O.; Ziemba-Zoltowska, B.

1978-01-01

Human lymphocyte cultures were X-irradiated with a single dose of 100 or 200 rad 46 h after phytohemagglutinin stimulation. In dose-fractionation experiments, 2h later the second dose was applied. All the cultures were harvested at 54 h after their initiation. In lymphocytes irradiated with a single dose of 200 rad, 2h post-irradiation contact with 10 -5 M exogeneous spermidine resulted in reduction of chromatid breaks by 34 %. Introduction of spermidine into culture medium for fractionation interval between the 2 doses of 100 rad reduced the frequency of chromatid breaks by 42 %. (author)

Chromatid interchanges at intrachromosomal telomeric DNA sequences

International Nuclear Information System (INIS)

Fernandez, J.L.; Vazquez-Gundin, F.; Bilbao, A.; Gosalvez, J.; Goyanes, V.

1997-01-01

Chinese hamster Don cells were exposed to X-rays, mitomycin C and teniposide (VM-26) to induce chromatid exchanges (quadriradials and triradials). After fluorescence in situ hybridization (FISH) of telomere sequences it was found that interstitial telomere-like DNA sequence arrays presented around five times more breakage-rearrangements than the genome overall. This high recombinogenic capacity was independent of the clastogen, suggesting that this susceptibility is not related to the initial mechanisms of DNA damage. (author)

Abnormal centromere-chromatid apposition (ACCA) and Peters' anomaly.

Science.gov (United States)

Wertelecki, W; Dev, V G; Superneau, D W

1985-08-01

Abnormal centromere-chromatid apposition (ACCA) was noted in a patient with Peters' anomaly. Previous reports of ACCA emphasized its association with tetraphocomelia and other congenital malformations (Roberts, SC Phocomelia, Pseudothalidomide Syndromes). This report expands the array of congenital malformations associated with ACCA and emphasizes the diagnostic importance of ocular defects for the ascertainment of additional cases of ACCA and its possible relationship with abnormal cell division.

Meiotic sister chromatid cohesion and recombination in two filamentous fungi

NARCIS (Netherlands)

Heemst, van D.

2000-01-01

Homologous recombination and sister chromatid cohesion play important roles in the maintenance of genome integrity and the fidelity of chromosome segregation in mitosis and meiosis. Within the living cell, the integrity of the DNA is threatened by various factors that cause DNA-lesions, of

Mechanisms of sister chromatid recombination

International Nuclear Information System (INIS)

Nakai, Sayaka; Machida, Isamu; Tsuji, Satsuki

1985-01-01

Studies using T948 as a model system have been carried out aimed at elucidating the mechanism of sister chromatid recombination (SCR). Characterization of U.V. light- and x-ray-induced SCR, the relationiship between SCR induction and DNA repair using rad mutations, and the relationship between SCR induction and the time of cell division using cdc mutations are presented. It has been supposed that SCR is induced at the phase of S-G 2 following DNA replication, that postreplication break of DNA strands is strongly involved in the induction of SCR, and that induction type of SCR, i.e., conversion type or recombination type, is dependent upon the type of molecular damage of DNA. (Namekawa, K.)

Interchromosomal distribution of gamma ray-induced chromatid aberrations in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Martinez-Lopez, Wilner; Porro, Valentina; Folle, Gustavo A.; Mendez-Acuna, Leticia; Obe, Guenter; Savage, John R.K.

2000-01-01

Inter chromosomal distributions of breakpoints from chromatid-type aberrations induced by gamma rays in Chinese hamster ovary cells were analyzed. In most chromosomes the distribution was as expected from chromosome lengths for simple breaks or the respective relative corrected length in case of exchanges. There were deviations from expectation in a few chromosomes for chromatid breaks, interchanges, intra-arm intra changes and inter-arm intra changes. Especially interesting are the results concerning chromosomes 2 and 8, which were more often involved in exchanges than expected. An 'exchange phenotype' for these chromosomes is proposed and possible explanations for the nonrandom distribution of chromosome breakpoints are presented. (author)

Phospho-H1 Decorates the Inter-chromatid Axis and Is Evicted along with Shugoshin by SET during Mitosis.

Science.gov (United States)

Krishnan, Swathi; Smits, Arne H; Vermeulen, Michiel; Reinberg, Danny

2017-08-17

Precise control of sister chromatid separation during mitosis is pivotal to maintaining genomic integrity. Yet, the regulatory mechanisms involved are not well understood. Remarkably, we discovered that linker histone H1 phosphorylated at S/T18 decorated the inter-chromatid axial DNA on mitotic chromosomes. Sister chromatid resolution during mitosis required the eviction of such H1S/T18ph by the chaperone SET, with this process being independent of and most likely downstream of arm-cohesin dissociation. SET also directed the disassembly of Shugoshins in a polo-like kinase 1-augmented manner, aiding centromere resolution. SET ablation compromised mitotic fidelity as evidenced by unresolved sister chromatids with marked accumulation of H1S/T18ph and centromeric Shugoshin. Thus, chaperone-assisted eviction of linker histones and Shugoshins is a fundamental step in mammalian mitotic progression. Our findings also elucidate the functional implications of the decades-old observation of mitotic linker histone phosphorylation, serving as a paradigm to explore the role of linker histones in bio-signaling processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Possible mechanisms of chromosomal aberrations: VII. Comparative dynamics of sister chromatid disjunction and realization of radiation-induced chromosomal aberrations during mitosis

International Nuclear Information System (INIS)

Lebedeva, L.I.; Akhmamet'eva, E.M.

1994-01-01

An increase in radiation-induced chromosomal aberrations during c-metaphase sister chromatid disjunction was demonstrated in murine bone marrow cells exposed to a total γ-irradiation at 0.5 Gy. Caffeine (Cf) treatment during mitosis partially suppressed the chromatid disjunction rate and increased the number of radiation-induced aberrations in this mitosis. Nalidixic acid (NA) treatment of c-metaphase cells completely suppressed chromatid disjunction and the realization of induced aberrations. Topoisomerase 2 was assumed to be involved during mitosis in both processes

Sister-chromatid exchanges in nuclear fuel workers

International Nuclear Information System (INIS)

Prabhavathi, P. Aruna; Fatima, Shehla K.; Padmavathi, P.; Kumari, C. Kusuma; Reddy, P.P.

1995-01-01

Peripheral blood lymphocyte cultures of 116 smokers and 80 non-smokers who were occupationally exposed to uranyl compounds were analysed for sister-chromatid exchanges (SCEs). Blood samples were collected from 59 non-smokers (control group I) and 47 smokers (control group II) who were not exposed to uranium for control data. A significant increase in SCEs was observed among both smokers and non-smokers exposed to uranyl compounds when compared to their respective controls. In controls, a significant increase in the frequency of SCEs was observed in smokers when compared to non-smokers

Induction and disappearance of G2 chromatid breaks in lymphocytes after low doses of low LET γ - rays and high LET fast neutrons

International Nuclear Information System (INIS)

Vral, Anne; Thierens, Hubert; Baeyens, Ans; De Ridder, Leo

2001-01-01

In view of the potential importance of the G2 assay for detecting chromosomal radiosensitivity and possible predisposition to cancer the need to elucidate the mechanism underlying the formation of chromatid breaks, observed with the G2 assay after low dose irradiation, has been recognised. In this study we irradiated blood samples of 4 healthy donors with low LET γ-rays and high LET neutrons, which initially produce the same number of dsb but of a different quality. By means of the G2 assay, we determined the number of chromatid breaks induced by γ-rays and neutrons and compared the kinetics of chromatid break rejoining for radiations of different quality. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for γ-rays and neutrons with doses ranging between 0.1 and 0.5 Gy. In a second set of experiments the kinetics of chromatid break formation and disappearance was investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 h and 3.5 h. For the highest dose of 0.5 Gy the number of isochromatid breaks were also scored. No significant differences in the number of chromatid breaks were observed between low LET γ-rays and high LET neutrons for the 4 donors at any of the doses given. The dose response curves for the formation of chromatid breaks are linear for both radiation qualities and RBE values equal to one were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high LET neutrons are however more effective at inducing isochromatid breaks (RBE of 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low LET γ-rays or high-LET neutrons are not significantly different. T 1/2 0.92 h for γ-rays and t 1/2 = 0.84 h for neutrons were obtained. In conclusion, our results show that at low doses of radiation the induction as well as the disappearance of G2 chromatid breaks is LET

What are sister chromatid exchanges

International Nuclear Information System (INIS)

Evans, H.J.

1977-01-01

The development of new staining techniques to visualise sister chromatid exchange (SCE) in cells exposed to mutagens has led to a better understanding of the mechanisms involved in the formation of such exchanges. SCE are induced by a wide variety of different physical and chemical agents and their incidence provides a sensitive indicator of DNA damage in proliferating mammalian cells. It is shown that lesions which affect one or both strands of the DNA can result in the development of SCE, but only when damaged DNA undergoes replication. The nature of the lesions, the frequency and distribution of SEC in mammalian cells; the sensitivity of the cells to their induction by X-radiation, ultraviolet radiation and chemical mutagens, are discussed and possible mechanisms involved in the formation of SCE during replication considered. (Auth.)

Non-random intrachromosomal distribution of radiation-induced chromatid aberrations in Vicia faba. [Aberration clustering

Energy Technology Data Exchange (ETDEWEB)

Schubert, I; Rieger, R [Akademie der Wissenschaften der DDR, Gatersleben. Zentralinst. fuer Genetik und Kulturpflanzenforschung

1976-04-01

A reconstructed karyotype of Vicia faba, with all chromosomes individually distinguishable, was treated with X-rays, fast neutrons, (/sup 3/H) uridine (/sup 3/HU). The distribution within metaphase chromosomes of induced chromatid aberrations was non-random for all agents used. Aberration clustering, in part agent specific, occurred in chromosome segments containing heterochromatin as defined by the presence of G bands. The pattern of aberration clustering found after treatment with /sup 3/HU did not allow the recognition of chromosome regions active in transcription during treatment. Furthermore, it was impossible to obtain unambiguous indications of the presence of AT- and GC-base clusters from the patterns of /sup 3/HT- and /sup 3/HC-induced chromatid aberrations, respectively. Possible reasons underlying these observations are discussed.

Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes

Science.gov (United States)

Dorsett, Dale

2006-01-01

The sister chromatid cohesion apparatus mediates physical pairing of duplicated chromosomes. This pairing is essential for appropriate distribution of chromosomes into the daughter cells upon cell division. Recent evidence shows that the cohesion apparatus, which is a significant structural component of chromosomes during interphase, also affects gene expression and development. The Cornelia de Lange (CdLS) and Roberts/SC phocomelia (RBS/SC) genetic syndromes in humans are caused by mutations affecting components of the cohesion apparatus. Studies in Drosophila suggest that effects on gene expression are most likely responsible for developmental alterations in CdLS. Effects on chromatid cohesion are apparent in RBS/SC syndrome, but data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits. PMID:16819604

Biomonitoring of genotoxic risk in radar facility workers: comparison of the comet assay with micronucleus assay and chromatid breakage assay

International Nuclear Information System (INIS)

Garaj-Vrhovac, V.; Kopjar, N.

2003-01-01

Genotoxic risks of occupational exposure in a radar facility were evaluated by using alkaline comet assay, micronucleus assay and chromatid breakage assay on peripheral blood leukocytes in exposed subjects and corresponding controls. Results show that occupational exposure to microwave radiation correlates with an increase of genome damage in somatic cells. The levels of DNA damage in exposed subjects determined by using alkaline comet assay were increased compared to control and showed interindividual variations. Incidence of micronuclei was also significantly increased compared to baseline control values. After short exposure of cultured lymphocytes to bleomycin, cells of occupationally exposed subjects responded with high numbers of chromatid breaks. Although the level of chromosome damage generated by bleomycin varied greatly between individuals, in exposed subjects a significantly elevated number of chromatid breaks was observed. Our results support data reported in literature indicating that microwave radiation represents a potential DNA-damaging hazard. Alkaline comet assay is confirmed as a sensitive and highly reproducible technique for detection of primary DNA damage inflicted in somatic cells. Micronucleus assay was confirmed as reliable bio-markers of effect and chromatid breakage assay as sensitive bio-marker of individual cancer susceptibility. The results obtained also confirm the necessity to improve measures and to perform accurate health surveillance of individuals occupationally exposed to microwave radiation

A CO-FISH assay to assess sister chromatid segregation patterns in mitosis of mouse embryonic stem cells.

Science.gov (United States)

Sauer, Stephan; Burkett, Sandra S; Lewandoski, Mark; Klar, Amar J S

2013-05-01

Sister chromatids contain identical DNA sequence but are chiral with respect to both their helical handedness and their replication history. Emerging evidence from various model organisms suggests that certain stem cells segregate sister chromatids nonrandomly to either maintain genome integrity or to bias cellular differentiation in asymmetric cell divisions. Conventional methods for tracing of old vs. newly synthesized DNA strands generally lack resolution for individual chromosomes and employ halogenated thymidine analogs with profound cytotoxic effects on rapidly dividing cells. Here, we present a modified chromosome orientation fluorescence in situ hybridization (CO-FISH) assay, where identification of individual chromosomes and their replication history is achieved in subsequent hybridization steps with chromosome-specific DNA probes and PNA telomere probes. Importantly, we tackle the issue of BrdU cytotoxicity and show that our method is compatible with normal mouse ES cell biology, unlike a recently published related protocol. Results from our CO-FISH assay show that mitotic segregation of mouse chromosome 7 is random in ES cells, which contrasts previously published results from our laboratory and settles a controversy. Our straightforward protocol represents a useful resource for future studies on chromatid segregation patterns of in vitro-cultured cells from distinct model organisms.

Frequency of sister chromatid exchanges in lymphocyte cultures of human peripheral blood after the combined effect of γ-radiation and caffeine

International Nuclear Information System (INIS)

Nugis, V.Yu.; Pyatkin, E.K.

1986-01-01

Keeping of human peripheral blood lymphocytes, irradiated in vitro with 60 Co-γ-quanta at a dose of 3 Gy at G 0 phase, with caffeine of 16 and 160 μg/ml during cultivation with PHA had no appreciable influence on the fraquency of sister chromatid exchanges. A minor increase in the number of sister chromatid exchanges was only noted when nonirradiated and irradiated lymphocytes were cultured with 160 μg/ml caffeine

Cleavage of cohesin rings coordinates the separation of centrioles and chromatids.

Science.gov (United States)

Schöckel, Laura; Möckel, Martin; Mayer, Bernd; Boos, Dominik; Stemmann, Olaf

2011-07-10

Cohesin pairs sister chromatids by forming a tripartite Scc1-Smc1-Smc3 ring around them. In mitosis, cohesin is removed from chromosome arms by the phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase 2A (Sgo1-PP2A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-chromatid separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.

Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance

NARCIS (Netherlands)

V.C. Seitan (Vlad); P.A. Banks (Peter); S. Laval (Steve); N.A. Majid (Nazia); D. Dorsett (Dale); A. Rana (Amer); J. Smith (Jeremy); A. Bateman (Alex); S. Krpic (Sanja); A. Hostert (Arnd); S.M. Rollins; H. Erdjument-Bromage (Hediye); P. Tempst (Paul); C.Y. Benard (Claire); S. Hekimi (Siegfried); S.F. Newbury (Sarah); T. Strachan (Tom)

2006-01-01

textabstractSaccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside

Influence of irradiation at different stages of mitotic cycle upon production of sister chromatid exchanges in cultured Chinese hamster cells

International Nuclear Information System (INIS)

Antoshina, M.M.; Poryadkova, N.A.; Luchnik, N.V.

1982-01-01

Frequency of sister chromatid exchanges (SCE) and microexchanges in Chinese hamster cells has been studied by means of the method of differential staining of chromatids on irradiation at different stages of the mitotic cycle. It is shown that the irradiation enhances frequency of SCE and microexchanges if it is carried out before the end of DNA replication synthesis. Comparison of frequency depenedence of radiation-induced microexchanges and SCE at different stages of the mitotic cycle results in the conclusion that the microexchanges are none other than small SCE

Photoreactivation of ultraviolet light-induced sister chromatid exchanges in potorous cells

International Nuclear Information System (INIS)

Ishizaki, K.; Nikaido, O.; Takebe, H.

1980-01-01

Exposure to visible light after UV-irradiation showed a remarkable effect on UV-induced sister chromatid exchanges (SCEs). After 6-h exposure to visible light (3 x 10 5 J/m 2 ), two-thirds of the UV-induced SCEs were prevented, confirming Kato's findings. (Nature 249, 552-3, 1974) Exposure to visible light before UV irradiation had no effect. This effect of visible light on UV-induced CSEs was temperature dependent, suggesting the presence of enzymatic photoreactivation. (author)

The frequency of chromatide aberrations as a function of radiation dose estimated by the number of dicentrics found by the cytogenetic analysis of lymphocytes in subjects affected by the Chernobyl accident

International Nuclear Information System (INIS)

Nugis, V.Yu.; Chirkov, A.A.

1990-01-01

A study was made of the frequency of chromatide aberrations in lymphocyte culture of subjects affected by the Chernobyl accident as a function of dose estimated by the incidence of dicentrics. The average number of chromatide aberrations was nearly the same within the dose range from 0 to 5 Gy exhibiting a tendency towards growth with dose. A high individual variability of the chromatide aberration frequency was observed

Biochemical evidence for deficient DNA repair leading to enhanced G2 chromatid radiosensitivity and susceptibility to cancer

International Nuclear Information System (INIS)

Gantt, R.; Parshad, R.; Price, F.M.; Sanford, K.K.

1986-01-01

Human tumor cells and cells from cancer-prone individuals, compared with those from normal individuals, show a significantly higher incidence of chromatid breaks and gaps seen in metaphase cells immediately after G2 X irradiation. Previous studies with DNA repair-deficient mutants and DNA repair inhibitors strongly indicate that the enhancement results from a G2 deficiency(ies) in DNA repair. We report here biochemical evidence for a DNA repair deficiency that correlates with the cytogenetic studies. In the alkaline elution technique, after a pulse label with radioactive thymidine in the presence of 3-acetylaminobenzamide (a G2-phase blocker) and X irradiation, DNA from tumor or cancer-prone cells elutes more rapidly during the postirradiation period than that from normal cells. These results indicate that the DNA of tumor and cancer-prone cells either repairs more slowly or acquires more breaks than that of normal cells; breaks can accumulate during incomplete or deficient repair processes. The kinetic difference between normal and tumor or cancer-prone cells in DNA strand-break repair reaches a maximum within 2 h, and this maximum corresponds to the kinetic difference in chromatid aberration incidence following X irradiation reported previously. These findings support the concept that cells showing enhanced G2 chromatid radiosensitivity are deficient in DNA repair. The findings could also lead to a biochemical assay for cancer susceptibility

Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide

International Nuclear Information System (INIS)

Yamazaki, Etsuo; Fukuda, Hozumi; Shibuya, Hitoshi; Matsubara, Sho

1996-01-01

The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. The increase in frequency of SCE seen after the addition of Gd-DTPA was decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related. 14 refs., 6 tabs

UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells

DEFF Research Database (Denmark)

Oka, Yasuyoshi; Varmark, Hanne; Vitting-Seerup, Kristoffer

2014-01-01

UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficien...

Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells

International Nuclear Information System (INIS)

Sajesh, Babu V; Lichtensztejn, Zelda; McManus, Kirk J

2013-01-01

Chromosome instability manifests as an abnormal chromosome complement and is a pathogenic event in cancer. Although a correlation between abnormal chromosome numbers and cancer exist, the underlying mechanisms that cause chromosome instability are poorly understood. Recent data suggests that aberrant sister chromatid cohesion causes chromosome instability and thus contributes to the development of cancer. Cohesion normally functions by tethering nascently synthesized chromatids together to prevent premature segregation and thus chromosome instability. Although the prevalence of aberrant cohesion has been reported for some solid tumors, its prevalence within liquid tumors is unknown. Consequently, the current study was undertaken to evaluate aberrant cohesion within Hodgkin lymphoma, a lymphoid malignancy that frequently exhibits chromosome instability. Using established cytogenetic techniques, the prevalence of chromosome instability and aberrant cohesion was examined within mitotic spreads generated from five commonly employed Hodgkin lymphoma cell lines (L-1236, KM-H2, L-428, L-540 and HDLM-2) and a lymphocyte control. Indirect immunofluorescence and Western blot analyses were performed to evaluate the localization and expression of six critical proteins involved in the regulation of sister chromatid cohesion. We first confirmed that all five Hodgkin lymphoma cell lines exhibited chromosome instability relative to the lymphocyte control. We then determined that each Hodgkin lymphoma cell line exhibited cohesion defects that were subsequently classified into mild, moderate or severe categories. Surprisingly, ~50% of the mitotic spreads generated from L-540 and HDLM-2 harbored cohesion defects. To gain mechanistic insight into the underlying cause of the aberrant cohesion we examined the localization and expression of six critical proteins involved in cohesion. Although all proteins produced the expected nuclear localization pattern, striking differences in RAD21

Kinetics of chromatid aberrations in G2 ataxia-telangiectasia cells exposed to X-rays and ara A

International Nuclear Information System (INIS)

Mozdarani, Hossein; Bryant, P.E.

1989-01-01

The cytogenetic effects of X-rays alone or in combination with 9-β-D-arabinofuranosyladenine (ara A) were studied in an immortalized fibroblastic line of ataxia-telangiectasia (A-T) cells. It is postulated that the kinetics of disappearance (rejoining) of chromatid deletions with postirradiation incubation time reflects the underlying repair of dsb, and is inhibited by ara A. The rejoining kinetics for deletions in A-T was similar to that found in a previous study of normal human fibroblasts (Mozdarani and Bryant 1987). The number of deletions in X-irradiated A-T cells at 1.5 h before fixation was found to be higher by a factor of approximately 2 than that found previously in normals, indicating that in A-T a higher rate of conversion of dsb into chromatid deletions occurs. The frequency of exchanges induced in G2 A-T cells was similarly enhanced but, unlike the situation in normal cells, ara A was found to cause only a slight increase in this frequency. (author)

A proposal of a standardised nomenclature for terminal minute sister chromatid exchanges

Directory of Open Access Journals (Sweden)

Máximo E. Drets

2006-01-01

Full Text Available We described spontaneous minute sister chromatid exchanges (SCE in telomeric regions of human and Chinese hamster ovary (CHO chromosomes more than 10 years ago. These structures, which we called t-SCE, were detected by means of highly precise quantitative microphotometrical scanning and computer graphic image analysis. Recently, several authors using the CO-FISH method also found small SCEs in telomeric regions and called them T-SCE. The use of different terms for designating the same phenomenon should be avoided. We propose ter SCE as a uniform nomenclature for minute telomeric SCEs.

RPA Mediates Recruitment of MRX to Forks and Double-Strand Breaks to Hold Sister Chromatids Together.

Science.gov (United States)

Seeber, Andrew; Hegnauer, Anna Maria; Hustedt, Nicole; Deshpande, Ishan; Poli, Jérôme; Eglinger, Jan; Pasero, Philippe; Gut, Heinz; Shinohara, Miki; Hopfner, Karl-Peter; Shimada, Kenji; Gasser, Susan M

2016-12-01

The Mre11-Rad50-Xrs2 (MRX) complex is related to SMC complexes that form rings capable of holding two distinct DNA strands together. MRX functions at stalled replication forks and double-strand breaks (DSBs). A mutation in the N-terminal OB fold of the 70 kDa subunit of yeast replication protein A, rfa1-t11, abrogates MRX recruitment to both types of DNA damage. The rfa1 mutation is functionally epistatic with loss of any of the MRX subunits for survival of replication fork stress or DSB recovery, although it does not compromise end-resection. High-resolution imaging shows that either the rfa1-t11 or the rad50Δ mutation lets stalled replication forks collapse and allows the separation not only of opposing ends but of sister chromatids at breaks. Given that cohesin loss does not provoke visible sister separation as long as the RPA-MRX contacts are intact, we conclude that MRX also serves as a structural linchpin holding sister chromatids together at breaks. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma

International Nuclear Information System (INIS)

Roser, M.; Boehm, A.O.; Oldigs, M.; Weichenthal, M.; Reimers, U.; Schmidt-Preuss, U.; Breitbart, E.W.; Ruediger, H.W.

1989-01-01

Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light

Chiasmata promote monopolar attachment of sister chromatids and their co-segregation toward the proper pole during meiosis I.

Directory of Open Access Journals (Sweden)

Yukinobu Hirose

2011-03-01

Full Text Available The chiasma is a structure that forms between a pair of homologous chromosomes by crossover recombination and physically links the homologous chromosomes during meiosis. Chiasmata are essential for the attachment of the homologous chromosomes to opposite spindle poles (bipolar attachment and their subsequent segregation to the opposite poles during meiosis I. However, the overall function of chiasmata during meiosis is not fully understood. Here, we show that chiasmata also play a crucial role in the attachment of sister chromatids to the same spindle pole and in their co-segregation during meiosis I in fission yeast. Analysis of cells lacking chiasmata and the cohesin protector Sgo1 showed that loss of chiasmata causes frequent bipolar attachment of sister chromatids during anaphase. Furthermore, high time-resolution analysis of centromere dynamics in various types of chiasmate and achiasmate cells, including those lacking the DNA replication checkpoint factor Mrc1 or the meiotic centromere protein Moa1, showed the following three outcomes: (i during the pre-anaphase stage, the bipolar attachment of sister chromatids occurs irrespective of chiasma formation; (ii the chiasma contributes to the elimination of the pre-anaphase bipolar attachment; and (iii when the bipolar attachment remains during anaphase, the chiasmata generate a bias toward the proper pole during poleward chromosome pulling that results in appropriate chromosome segregation. Based on these results, we propose that chiasmata play a pivotal role in the selection of proper attachments and provide a backup mechanism that promotes correct chromosome segregation when improper attachments remain during anaphase I.

Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome

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Stefanie M. Percival

2015-08-01

Full Text Available Mutations in ESCO2, one of two establishment of cohesion factors necessary for proper sister chromatid cohesion (SCC, cause a spectrum of developmental defects in the autosomal-recessive disorder Roberts syndrome (RBS, warranting in vivo analysis of the consequence of cohesion dysfunction. Through a genetic screen in zebrafish targeting embryonic-lethal mutants that have increased genomic instability, we have identified an esco2 mutant zebrafish. Utilizing the natural transparency of zebrafish embryos, we have developed a novel technique to observe chromosome dynamics within a single cell during mitosis in a live vertebrate embryo. Within esco2 mutant embryos, we observed premature chromatid separation, a unique chromosome scattering, prolonged mitotic delay, and genomic instability in the form of anaphase bridges and micronuclei formation. Cytogenetic studies indicated complete chromatid separation and high levels of aneuploidy within mutant embryos. Amongst aneuploid spreads, we predominantly observed decreases in chromosome number, suggesting that either cells with micronuclei or micronuclei themselves are eliminated. We also demonstrated that the genomic instability leads to p53-dependent neural tube apoptosis. Surprisingly, although many cells required Esco2 to establish cohesion, 10-20% of cells had only weakened cohesion in the absence of Esco2, suggesting that compensatory cohesion mechanisms exist in these cells that undergo a normal mitotic division. These studies provide a unique in vivo vertebrate view of the mitotic defects and consequences of cohesion establishment loss, and they provide a compensation-based model to explain the RBS phenotypes.

Cell-stage-specific enhancement by caffeine of the frequency of chromatid aberrations induced by X-rays in neutral ganglia of Drosophila melanogaster

International Nuclear Information System (INIS)

De Marco, A.; Polani, S.

1981-01-01

Caffeine (10 -2 M) induced a high level of chromatid aberrations in neural ganglia of third-instar larvae of Drosophila melanogaster only when it was added to cells in late G 2 and mitotic prophase. No aberrations were observed after treatment in late S-middle G 2 or C-mitosis. We observed that, in these stages, caffeine strongly increased X-ray-induced damage (500 R). This potentiation was quantitatively similar. But it involved all types of aberration after treatment in C-mitosis, and essentially isochromatid deletions and chromatid exhanges after treatment in S-G 2 . Some hypotheses are put forth to explain the possible mechanism of action of caffeine in the potentiation of X-ray-induced damage. (orig.)

The MCM-binding protein ETG1 aids sister chromatid cohesion required for postreplicative homologous recombination repair.

Directory of Open Access Journals (Sweden)

Naoki Takahashi

2010-01-01

Full Text Available The DNA replication process represents a source of DNA stress that causes potentially spontaneous genome damage. This effect might be strengthened by mutations in crucial replication factors, requiring the activation of DNA damage checkpoints to enable DNA repair before anaphase onset. Here, we demonstrate that depletion of the evolutionarily conserved minichromosome maintenance helicase-binding protein ETG1 of Arabidopsis thaliana resulted in a stringent late G2 cell cycle arrest. This arrest correlated with a partial loss of sister chromatid cohesion. The lack-of-cohesion phenotype was intensified in plants without functional CTF18, a replication fork factor needed for cohesion establishment. The synergistic effect of the etg1 and ctf18 mutants on sister chromatid cohesion strengthened the impact on plant growth of the replication stress caused by ETG1 deficiency because of inefficient DNA repair. We conclude that the ETG1 replication factor is required for efficient cohesion and that cohesion establishment is essential for proper development of plants suffering from endogenous DNA stress. Cohesion defects observed upon knockdown of its human counterpart suggest an equally important developmental role for the orthologous mammalian ETG1 protein.

Mutagen-induced sister chromatid exchanges in xeroderma pigmentosum and normal lymphocytes

International Nuclear Information System (INIS)

Perry, P.E.; Jager, M.; Evans, H.J.

1978-01-01

The induction of sister chromatid exchanges (SCE), by ultra-violet irradiation and by three chemical mutagens that differ in the type of repair response that they elicit, has been compared in lymphocytes from a control and from an individual suffering from the DNA excision repair deficiency syndrome, xeroderma pigmentosum (XP). The XP lymphocytes were found to be more sensitive in terms of SCE response, not only to UV irradiation, but also to all of the chemicals studied. The results indicate that the abnormality of DNA repair in this XP patient is expressed not only in the defective excision of thymine dimers, or other UV photoproducts, but also in a reduced ability to repair other types of DNA lesion. (author)

The Scc2/Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

Science.gov (United States)

Lopez-Serra, Lidia; Kelly, Gavin; Patel, Harshil; Stewart, Aengus; Uhlmann, Frank

2014-01-01

The cohesin complex is at the heart of many chromosomal activities, including sister chromatid cohesion and transcriptional regulation1-3. Cohesin loading onto chromosomes depends on the Scc2/Scc4 cohesin loader complex4-6, but the chromatin features that form cohesin loading sites remain poorly understood. Here, we show that the RSC chromatin remodeling complex recruits budding yeast Scc2/Scc4 to broad nucleosome-free regions, that the cohesin loader itself helps to maintain. Consequently, inactivation of the cohesin loader or RSC complex have similar effects on nucleosome positioning, gene expression and sister chromatid cohesion. These results reveal an intimate link between local chromatin structure and higher order chromosome architecture. Our findings pertain to the similarities between two severe human disorders, Cornelia de Lange syndrome, caused by mutations in the human cohesin loader, and Coffin-Siris syndrome, resulting from mutations in human RSC complex components7-9. Both could arise from gene misregulation due to related changes in the nucleosome landscape. PMID:25173104

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

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Nagasawa, H.; Little, J.B.

1980-01-01

The repair of X-ray-induced DNA single strand breaks and DNA-protein cross-links was investigated in stationary phase, contact-inhibited mouse cells by the alkaline-elution technique. Approx. 90% of X-ray-induced single strand breaks were rejoined during the first hour of repair, whereas most of the remaining breaks were rejoined more slowly during the next 5 h. At early repair times, the number of residual non-rejoined sungle strand breaks was approx. proportional to the X-ray dose. DNA-protein cross-links were removed at a slower rate (Tsub(1/2) approx. 10-12 h). Cells were held in stationary growth for various periods of time after irradiation before subculture at low density to score for colony survival (potentially lethal damage repair), chromosome aberrations in the first mitosis, and sister-chromatid exchanges in the second mitosis. Both cell killing and the frequency of chromosome aberrations decreased during the first several hours of recovery, reaching a minimum level by 6 h; this decrease correlated temporally with the repair of the slowly rejoining DNA-strand breaks. Relatively few sister-chromatid exchanges were observed when the cells were subcultured immediately after X-ray. The exchange frequency rose to maximum levels after a 4-h recovery interval, and returned to control levels after 12 h of recovery. The possible relationship of DNA repair to these changes in survival, chromosome aberrations, and sister-chromatid exchanges during liquid-holding recovery is discussed. (orig.)

Sister chromatid exchange analysis and chromosoma aberration studies in interventional cardiology laboratory workers. One year follow up study

International Nuclear Information System (INIS)

Erol, M.K.; Oztas, S.; Bozkurt, E.; Karakelleoglu, S.

2002-01-01

Invasive cardiology laboratory workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation has a damaging effect on chromosomes. In present study, we investigated the frequency of sister chromatid exchange (SCE) and chromosomal aberrations in 11 invasive cardiology laboratory workers and 11 healthy controls. After a vacation period, we took blood samples for chromosome analysis in months 0, 4, 8 and 12 (last two month period was the nonradiation time). The SCE frequencies did not change significantly after exposure to ionizing radiation in any worker. Our study has revealed that non-specific structural chromosome aberrations such as gaps, isogaps, acentric chromosomes, chromatids and chromosome breakage could be in the 4th and 8th months after ionizing radiation exposure in the metaphase plaques. All abnormal chromosomal effects had disappeared by the end of the two month non-exposure period in each worker. In conclusion, the results suggest that SCE frequencies are not significantly affected in invasive cardiology laboratory workers who are exposed occupationally to ionizing radiation, although some degree of reversible chromosomal aberrations did appear. (author)

Sister-chromatid exchange induced by X-ray of human lymphocytes and the effect of L-crysteine

International Nuclear Information System (INIS)

Abramovski, I.; Vorsanger, G.; Hirschhorn, K.

1978-01-01

A staining technique that detects sister-chromatid exchanges (SCEs) has been used to examine the response of human lymphocyte chromosomes to various dosages of X-irradiation. The SCE frequency was markedly increased following irradiation. However, the increase was of a significantly smaller magnitude when irradiation occurred in the presence of an antimutagenic agent. Scoring SCEs may provide a useful technique for assaying the mutagenic effects of environmental carcinogens as well as the protective effects of antimutagenic agents. (Auth.)

Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis.

Directory of Open Access Journals (Sweden)

Tamara Goldfarb

2010-10-01

Full Text Available Recombination between homologous chromosomes of different parental origin (homologs is necessary for their accurate segregation during meiosis. It has been suggested that meiotic inter-homolog recombination is promoted by a barrier to inter-sister-chromatid recombination, imposed by meiosis-specific components of the chromosome axis. Consistent with this, measures of Holliday junction-containing recombination intermediates (joint molecules [JMs] show a strong bias towards inter-homolog and against inter-sister JMs. However, recombination between sister chromatids also has an important role in meiosis. The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions, and meiotic double-strand breaks (DSBs that form within such polymorphic regions must be repaired by inter-sister recombination. Efforts to study inter-sister recombination during meiosis, in particular to determine recombination frequencies and mechanisms, have been constrained by the inability to monitor the products of inter-sister recombination. We present here molecular-level studies of inter-sister recombination during budding yeast meiosis. We examined events initiated by DSBs in regions that lack corresponding sequences on the homolog, and show that these DSBs are efficiently repaired by inter-sister recombination. This occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold yields of JMs. Loss of the meiotic-chromosome-axis-associated kinase Mek1 accelerates inter-sister DSB repair and markedly increases inter-sister JM frequencies. Furthermore, inter-sister JMs formed in mek1Δ mutants are preferentially lost, while inter-homolog JMs are maintained. These findings indicate that inter-sister recombination occurs frequently during budding yeast meiosis, with the possibility that up to one-third of all recombination events occur between sister chromatids. We suggest that a Mek1-dependent reduction in

Sister chromatid exchange in children of Seventh-Day Adventists and matched controls.

Science.gov (United States)

Hermansen, R; Waksvik, H; Fønnebø, V

1991-03-01

The low risk of cancer in Seventh-Day Adventists (SDAs) has been suggested to be due to genetic selection. To investigate this claim we examined the sister chromatid exchange (SCE) frequency in peripheral blood lymphocytes in 16 SDA children in Tromsø, all aged 0.5-8 years and 16 controls matched for sex and age. In 12 of 16 pairs, the SDA children had a lower SCE frequency than the controls. The mean difference was 4.06 (95% confidence interval -17.02-8.89, P = 0.51). There was no sex difference, and no correlation between age and SCE frequency. The genetic starting point with regard to SCE frequency seems to be the same for SDA children and controls.

Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

Energy Technology Data Exchange (ETDEWEB)

Sauer, Stephan; Klar, Amar J. S., E-mail: sauers@mail.nih.gov, E-mail: klara@mail.nih.gov [Gene Regulation and Chromosome Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD (United States)

2012-11-16

Ever since cloning the classic iv (inversedviscerum) mutation identified the “left-right dynein” (lrd) gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old “Watson” versus old “Crick” strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical “left-right axis development 1” (“lra1”) gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

International Nuclear Information System (INIS)

Sauer, Stephan; Klar, Amar J. S.

2012-01-01

Ever since cloning the classic iv (inversedviscerum) mutation identified the “left-right dynein” (lrd) gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old “Watson” versus old “Crick” strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical “left-right axis development 1” (“lra1”) gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

Directory of Open Access Journals (Sweden)

Stephan eSauer

2012-11-01

Full Text Available Ever since cloning the classic iv mutation identified the ‘left-right dynein’ (lrd gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old ‘Watson’ vs. old ‘Crick’ strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical ‘left-right axis development 1’ (‘lra1’ gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

Sister chromatid exchange induced by X-irradiation of retinoblastoma lymphocytes

International Nuclear Information System (INIS)

Abramovsky-Kaplan, I.; Jones, I.S.

1984-01-01

Lymphocyte cultures were employed to assess the degree of spontaneous and induced chromosomal fragility in retinoblastoma. Sister chromatid exchange (SCEs) were scored in metaphases. Three unilateral, three bilateral, eleven family members and controls were studied. Retinoblastoma (RB) lymphocytes did not exhibit increased spontaneous fragility. X-irradiation (25-200 rad) did not significantly increase SCE in unilateral retinoblastoma lymphocytes when compared with controls (P greater than 0.50). However, bilaterally affected subjects and three unaffected relatives demonstrated a statistically significant increase in SCE (P less than 0.01). In conclusion, hereditary retinoblastoma lymphocytes appear more radiosensitive than sporadic retinoblastoma, perhaps, reflecting the increased second malignancies in germinal mutation retinoblastoma. In addition, the analysis of radiation-induced SCE in peripheral blood lymphocytes of RB patients and family members may provide a valuable tool increasing the accuracy of genetic counseling for this disorder. Additional studies of RB patients and families are needed to assess the relevance of this approach to genetic counseling

Elevated sister chromatid exchange frequencies in New Zealand Vietnam War veterans.

Science.gov (United States)

Rowland, R E; Edwards, L A; Podd, J V

2007-01-01

From July 1965 until November 1971, New Zealand Defence Force Personnel fought in the Vietnam War. During this time more than 76,500,000 litres of phenoxylic herbicides were sprayed over parts of Southern Vietnam and Laos, the most common being known as 'Agent Orange'. The current study aimed to ascertain whether or not New Zealand Vietnam War veterans show evidence of genetic disturbance arising as a consequence of their now confirmed exposure to these defoliants. A sample group of 24 New Zealand Vietnam War veterans and 23 control volunteers were compared using an SCE (sister chromatid exchange) analysis. The results from the SCE study show a highly significant difference (P Vietnam War veterans studied here were exposed to a clastogenic substance(s) which continues to exert an observable genetic effect today, and suggest that this is attributable to their service in Vietnam. Copyright 2007 S. Karger AG, Basel.

Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fision yeast to humans.

NARCIS (Netherlands)

S. Parisi; M.J. McKay (Michael); M. Molnar; M.A. Thompson (Anne); P.J. van der Spek (Peter); E. van Drunen-Schoenmaker; R. Kanaar (Roland); E. Lehmann; J.H.J. Hoeijmakers (Jan); J. Kohli

1999-01-01

textabstractOur work and that of others defined mitosis-specific (Rad21 subfamily) and meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion in several eukaryotes, including humans. Mutation of the fission yeast Schizosaccharomyces pombe rec8 gene was previously shown to

Use of a ring chromosome and pulsed-field gels to study interhomolog recombination, double-strand DNA breaks and sister-chromatid exchange in yeast

International Nuclear Information System (INIS)

Game, J.C.; Sitney, K.C.; Cook, V.E.; Mortimer, R.K.

1989-01-01

The authors describe a system that uses pulsed-field gels for the physical detection of recombinant DNA molecules, double-strand DNA breaks (DSB) and sister-chromatid exchange in the yeast Saccharomyces cerevisiae. The system makes use of a circular variant of chromosome II (Chr. III). Meiotic recombination between this ring chromosome and a linear homolog produces new molecules of sizes distinguishable on gels from either parental molecule. They demonstrate that these recombinant molecules are not present either in strains with two linear Chr. III molecules or in rad50 mutants, which are defective in meiotic recombination. In conjunction with the molecular endpoints. They present data on the timing of commitment to meiotic recombination scored genetically. They have used x-rays to linearize circular Chr. III, both to develop a sensitive method for measuring frequency of DSB and as a means of detecting double-size circles originating in part from sister-chromatid exchange, which they find to be frequent during meiosis

In vitro and occupational induction of sister-chromatid exchanges in human lymphocytes with furfuryl alcohol and furfural

Energy Technology Data Exchange (ETDEWEB)

Gomez-Arroyo, S.; Souza, V.

1985-06-01

Sister-chromatid exchanges (SCEs) in human lymphocytes were studied using the FPG technique in order to determine the cytogenetic effect of furfural and furfuryl alcohol. The induction of SCEs was also investigated in workers occupationally exposed to these solvents that are commonly used in the manufacture of furoic resins. The results obtained from the in vitro treatments show that furfural increased the number of SCEs, while furfuryl alcohol did not. In exposed workers, neither of these solvents increased the spontaneous frequency of SCEs per metaphase.

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

International Nuclear Information System (INIS)

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 -1 ) or to 60 Co gamma rays delivered at low dose rates (4.8 X 10 -5 to 1.2 X 10 -1 Gy h -1 ). After irradiation, the larvae were exposed to 3 X 10 -5 M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h ( 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 60 Co irradiation showed elevated SCE frequencies; a significant increase in SCE frequency was observed at 0.6 Gy. 49 references, 2 figures

Indirect intergenic suppression of a radiosensitive mutant of Sordaria macrospora defective in sister-chromatid cohesiveness.

Science.gov (United States)

Huynh, A D; Leblon, G; Zickler, D

1986-01-01

Six ultra violet (UV) mutageneses were performed on the spo76 UV-sensitive mutant of Sordaria macrospora. Spo76 shows an early centromere cleavage associated with an arrest at the first meiotic division and therefore does not form ascospores. Moreover, it exhibits altered pairing structure (synaptonemal complex), revealing a defect in the sister-chromatid cohesiveness. From 37 revertants which partially restored sporulation, 34 extragenic suppressors of spo76 were isolated. All suppressors are altered in chromosomal pairing but, unlike spo76, show a wild type centromere cleavage. The 34 suppressors were assigned to six different genes and mapped. Only one of the suppressor genes is involved in repair functions.

Evaluation of the persistence in the induction of Sister Chromatid Exchanges (SCE) by alkylating agents

International Nuclear Information System (INIS)

Rodriguez R, R.; Huerta V, C.; MOrales R, P.R.

2006-01-01

The persistence in the induction of sister chromatid exchanges (SCE) by the alkylating agents methyl and ethyl-methanesulfonates (MMS and EMS) was evaluated. For it, to groups of mice its were administered a dose of these agents and later its were analyzed the induced SCE's in two periods: early and late. Both agents caused high increments of SCE in the early period and small in the late one; however, the caused lately by EMS was significantly bigger. This late induction of SCE by EMS possibly is associated with an epigenetic change or with the presence of etiladucts in the phosphodiester bonds of the DNA. (Author)

Regulation of Centromere Localization of the Drosophila Shugoshin MEI-S332 and Sister-Chromatid Cohesion in Meiosis

Science.gov (United States)

Nogueira, Cristina; Kashevsky, Helena; Pinto, Belinda; Clarke, Astrid; Orr-Weaver, Terry L.

2014-01-01

The Shugoshin (Sgo) protein family helps to ensure proper chromosome segregation by protecting cohesion at the centromere by preventing cleavage of the cohesin complex. Some Sgo proteins also influence other aspects of kinetochore-microtubule attachments. Although many Sgo members require Aurora B kinase to localize to the centromere, factors controlling delocalization are poorly understood and diverse. Moreover, it is not clear how Sgo function is inactivated and whether this is distinct from delocalization. We investigated these questions in Drosophila melanogaster, an organism with superb chromosome cytology to monitor Sgo localization and quantitative assays to test its function in sister-chromatid segregation in meiosis. Previous research showed that in mitosis in cell culture, phosphorylation of the Drosophila Sgo, MEI-S332, by Aurora B promotes centromere localization, whereas Polo phosphorylation promotes delocalization. These studies also suggested that MEI-S332 can be inactivated independently of delocalization, a conclusion supported here by localization and function studies in meiosis. Phosphoresistant and phosphomimetic mutants for the Aurora B and Polo phosphorylation sites were examined for effects on MEI-S332 localization and chromosome segregation in meiosis. Strikingly, MEI-S332 with a phosphomimetic mutation in the Aurora B phosphorylation site prematurely dissociates from the centromeres in meiosis I. Despite the absence of MEI-S332 on meiosis II centromeres in male meiosis, sister chromatids segregate normally, demonstrating that detectable levels of this Sgo are not essential for chromosome congression, kinetochore biorientation, or spindle assembly. PMID:25081981

Sister chromatid exchanges and micronuclei analysis in lymphocytes of men exposed to simazine through drinking water.

Science.gov (United States)

Suárez, Susanna; Rubio, Arantxa; Sueiro, Rosa Ana; Garrido, Joaquín

2003-06-06

In some cities of the autonomous community of Extremadura (south-west of Spain), levels of simazine from 10 to 30 ppm were detected in tap water. To analyse the possible effect of this herbicide, two biomarkers, sister chromatid exchanges (SCE) and micronuclei (MN), were used in peripheral blood lymphocytes from males exposed to simazine through drinking water. SCE and MN analysis failed to detect any statistically significant increase in the people exposed to simazine when compared with the controls. With respect to high frequency cells (HFC), a statistically significant difference was detected between exposed and control groups.

Inhibition of protein synthesis does not antagonize induction of UV-induced sister-chromatid exchange in xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Sono, Akira; Sakaguchi, Kengo.

1988-01-01

Cycloheximide strongly antagonizes the induction of sisterchromatid exchanges by ethyl methanesulfonate or mitomycin C in human skin fibroblast and xeroderma pigmentosum cells (group A). Analogous behavior has been observed in several other species including Chinese hamster and plant cells. This report documents an exception to that pattern: cycloheximide fails to antagonize UV-induced sister chromatid exchange in xeroderma pigmentosum cells, whereas it does in normal human skin fibroblast cells. A genetic defect in these cells is postulated to alter the UV-mediated DNA recombination process. (author)

High frequencies of chromatid aberrations produced during G/sub 2/ in human lymphocytes by very low doses (0. 025-0. 4 Gy) of X-rays in combination with inhibitors of DNA synthesis

Energy Technology Data Exchange (ETDEWEB)

Andersson, H.C.; Kihlman, B.A. (Uppsala Univ. (Sweden). Dept. of Genetics)

1984-09-01

Whole-blood cultures of human lymphocytes were exposed in the G/sub 2/-phase (3.5 h before harvesting) to various doses of X-rays and post-treated for 3 h with inhibitors of DNA synthesis. The inhibitors used were 2'-deoxyadenosine (dAdo), hydroxyurea (HU) and 1-..beta..-D-arabinofuranosylcytosine (ara-C). To prevent deamination of dAdo by adenosine deaminase (ADA), the dAdo treatments were carried out in the presence of the ADA inhibitor coformycin. HU and ara-C were used either alone or in combination. After the 3-h inhibitor treatments, the cultures were harvested and slides prepared and analyzed for chromatid aberrations in metaphase. When the inhibitors were used at concentrations high enough to cause marked chromosome damage by themselves, very low doses of X-rays (0.025-0.2 Gy) were sufficient to produce a dramatic increase in the frequency of chromatid aberrations. High frequencies of chromatid aberrations were also obtained when cultures that had received moderate doses of X-rays (0.4-0.8 Gy) were post-treated with low inhibitor concentrations that produce no or only a few aberrations by themselves.

Sister chromatid exchanges induced in CHO cells by X-rays or 5.5 MeV neutrons

International Nuclear Information System (INIS)

Bocian, E.; Rosiek, O.; Sablinski, J.; Ziemba-Zoltowska, B.

1986-01-01

The induction of sister chromatid exchanges (SCEs) by X-rays (1-9 Gy) and 5.5 MeV neutrons (0.5-4 Gy) was studied in CHO cells. A dose-dependent increase of the frequency of SCE was found for both radiations when cells with BrdUrd substituted DNA were irradiated. The similar doubling dose, approx. 4 Gy, was found for X-rays and neutrons. The increase of the SCE frequency was not clearly dependent on the dose when cells with BrdUrd unsubstituted DNA were irradiated. In this case a dose of 4 Gy enhanced the SCE frequency only by the factor of 1.3. (author)

Increased sister chromatid cohesion and DNA damage response factor localization at an enzyme-induced DNA double-strand break in vertebrate cells.

LENUS (Irish Health Repository)

Dodson, Helen

2009-10-01

The response to DNA damage in vertebrate cells involves successive recruitment of DNA signalling and repair factors. We used light microscopy to monitor the genetic dependencies of such localization to a single, induced DNA double strand break (DSB) in vertebrate cells. We used an inducible version of the rare-cutting I-SceI endonuclease to cut a chromosomally integrated I-SceI site beside a Tet operator array that was visualized by binding a Tet repressor-GFP fusion. Formation of gamma-H2AX foci at a single DSB was independent of ATM or Ku70. ATM-deficient cells showed normal kinetics of 53Bp1 recruitment to DSBs, but Rad51 localization was retarded. 53Bp1 and Rad51 foci formation at a single DSB was greatly reduced in H2AX-null DT40 cells. We also observed decreased inter-sister chromatid distances after DSB induction, suggesting that cohesin loading at DSBs causes elevated sister chromatid cohesion. Loss of ATM reduced DSB-induced cohesion, consistent with cohesin being an ATM target in the DSB response. These data show that the same genetic pathways control how cells respond to single DSBs and to multiple lesions induced by whole-cell DNA damage.

Can consumption of raw vegetables decrease the count of sister chromatid exchange? Results from a cross-sectional study in Krakow, Poland

OpenAIRE

Galas, Aleksander; Cebulska-Wasilewska, Antonina

2014-01-01

Background Sister chromatid exchange (SCE) is a widely used sensitive cytogenetic biomarker of exposure to genotoxic and cancerogenic agents. Results of human monitoring studies and cytogenetic damage have revealed that biological effects of genotoxic exposures are influenced by confounding factors related to life-style. Vegetable and fruit consumption may play a role, but available results are not consistent. The purpose of the study was to investigate the effect of consumption of raw and co...

Amount of sister chromatid exchanges and survival of Chinese hamster V79-4 cells after irradiation with 0,7 MeV neutrons

International Nuclear Information System (INIS)

Lapidus, I.L.; Nasonova, E.A.

1987-01-01

The dependence of the survival and induction of sister chromatid exchanges (SCEs) in Chinese hamster V79-4 cells on the dose of γ-rays and neutrons with average energy 0.7 MeV has been analysed. The value of RBE for neutrons was 5.5. It has been shown that the number of SCE increased with the dose of γ-irradiation and no induction could be detected after neutron irradiation

In vivo persistence of sister chromatid exchanges (SCE) induced by gamma rays in mouse bone marrow cells

International Nuclear Information System (INIS)

Morales-Ramirez, P.; Vallarino-Kelly, T.; Rodriguez-Reyes, R.

1984-01-01

The sister chromatid exchange (SCE) frequencies induced in bone marrow cells by in vivo irradiation with gamma rays before or after bromodeoxyuridine (BrdUrd) incorporation were compared. The frequency of SCE at different postirradiation times was also measured in bone marrow cells in vivo, irradiated before BrdUrd incorporation. Increased sensitivity to SCE induction by radiation was found in cells after BrdUrd incorporation for one cycle when compared with cells irradiated before BrdUrd incorporation. The increased SCE frequency persisted for at least 72 hr after the initial irradiation, implying that the gamma ray-induced lesion(s) capable of eliciting an SCE are persistent and cannot be easily repaired

Acute wood or coal exposure with carbon monoxide intoxication induces sister chromatid exchange

Energy Technology Data Exchange (ETDEWEB)

Ozturk, S.; Vatansever, S.; Cefle, K.; Palanduz, S.; Guler, K.; Erten, N.; Erk, O.; Karan, M.A.; Tascioglu, C. [University of Istanbul, Istanbul (Turkey). Istanbul Faculty of Medicine

2002-07-01

The object of this study was to investigate the genotoxic effect of acute overexposure to combustion products originating from coal or wood stoves in patients presenting with acute carbon monoxide intoxication. The authors analyzed the frequency of sister chromatid exchange and the carboxyhemoglobin concentration in 20 consecutive patients without a history of smoking or drug use who had been treated in the Emergency Care Unit of Istanbul Medical Faculty due to acute carbon monoxide intoxication. All of these cases were domestic accidents due to dysfunctioning coal or wood stoves. The results were compared with a control group of 20 nonsmoking, nondrug-using healthy individuals matched for age, sex, and absence of other chemical exposure. It was concluded that acute exposure to combustion products of wood or coal is genotoxic to DNA. Potential causes of genotoxicity include known mutagenic compounds present in coal or wood smoke and ash, oxygen radicals formed during combustion, as well as hypoxic and reperfusion injury mechanisms initiated by carbon monoxide intoxication.

Very low dose and dose-rate X-ray induced adaptive response in human lymphocytes at various cell cycle stages against bleomycin induced chromatid aberrations

International Nuclear Information System (INIS)

Hossein Mozdarani; Moghadam, R.N.

2007-01-01

Complete text of publication follows. Objective: To study the adaptive response induced by very low doses of X-rays at very low dose rate in human lymphocytes at different cell cycle stages followed by a challenge dose of bleomycin sulphate at G2 phase. Materials and Methods: Human peripheral blood lymphocytes before (G0) and after PHA stimulation (G1 and G2) were exposed to 1 and 5 cGy X-rays generated by a fluoroscopy unit with a dose rate of 5.56 mGy/min and challenged with 5 μg/ml bleomycin sulphate (BLM) 48 hours after culture initiation. Mitotic cells were arrested at metaphase by addition of colcemid in cultures 1.5 h before harvesting. Harvesting and slide preparation was performed using standard method. 100 well spread metaphases were analyzed for the presence of chromatid type aberrations for each sample. Results: Results obtained indicate that there is a linear relationship between the dose of BLM and chromatid aberrations below 5 μg/ml (R=0.93, p<0.0001). The results also show that pretreatment of lymphocytes with low dose X-rays at G0, G1 and G2 phases of the cell cycle significantly reduced the sensitivity of lymphocytes to the clastogenic effects of BLM in G2. Much lower frequencies of chromatid aberrations were observed in X-ray irradiated lymphocytes following BLM treatment (p<0.05). The magnitudes of adaptation induced at different phases of the cell cycle were not significantly different. Furthermore, there was no a significant difference in the magnitude of adaptive response induced by either 1 or 5 cGy X-rays. Conclusion: These observations might indicate that resistance of pre-exposure of lymphocytes to very low doses of X-rays protects them from clastogenic effects of BLM. This effect might be due to initial DNA damage induced in these cells leading to provocation of an active DNA repair mechanism independent of cell cycle stage.

Drosophila TDP-43 RNA-Binding Protein Facilitates Association of Sister Chromatid Cohesion Proteins with Genes, Enhancers and Polycomb Response Elements.

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Amanda Swain

2016-09-01

Full Text Available The cohesin protein complex mediates sister chromatid cohesion and participates in transcriptional control of genes that regulate growth and development. Substantial reduction of cohesin activity alters transcription of many genes without disrupting chromosome segregation. Drosophila Nipped-B protein loads cohesin onto chromosomes, and together Nipped-B and cohesin occupy essentially all active transcriptional enhancers and a large fraction of active genes. It is unknown why some active genes bind high levels of cohesin and some do not. Here we show that the TBPH and Lark RNA-binding proteins influence association of Nipped-B and cohesin with genes and gene regulatory sequences. In vitro, TBPH and Lark proteins specifically bind RNAs produced by genes occupied by Nipped-B and cohesin. By genomic chromatin immunoprecipitation these RNA-binding proteins also bind to chromosomes at cohesin-binding genes, enhancers, and Polycomb response elements (PREs. RNAi depletion reveals that TBPH facilitates association of Nipped-B and cohesin with genes and regulatory sequences. Lark reduces binding of Nipped-B and cohesin at many promoters and aids their association with several large enhancers. Conversely, Nipped-B facilitates TBPH and Lark association with genes and regulatory sequences, and interacts with TBPH and Lark in affinity chromatography and immunoprecipitation experiments. Blocking transcription does not ablate binding of Nipped-B and the RNA-binding proteins to chromosomes, indicating transcription is not required to maintain binding once established. These findings demonstrate that RNA-binding proteins help govern association of sister chromatid cohesion proteins with genes and enhancers.

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

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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 60 Co gamma rays at a low dose rate of from 4.8 x 10 -5 to 1.2 x 10 -1 Gy (0.0048 to 12 rad)/h for 24 h. After irradiation, the larvae were exposed to 3 x 10 -5 M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h ( 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 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

Very low sister-chromatid exchange rate in Seventh-Day Adventists.

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Wulf, H C; Iversen, A S; Husum, B; Niebuhr, E

1986-08-01

42 Seventh-Day Adventists (SDAs) and 42 controls matched for sex, age and occupation had their sister-chromatid exchange (SCE) examined in peripheral blood lymphocytes. This was done to examine if the SCE frequency was lower in this group of people, who are known to have a decreased cancer risk compared to the general population. The average SCE/cell in 30 cells from each person was 5.54 +/- 0.07 (mean +/- standard error of the mean) for the SDAs and 8.00 +/- 0.15 for the controls, the difference being statistically significant (p less than 0.00001). No difference in SCE frequency was found between SDAs eating only an ovo-lacto-vegetarian diet and those eating some fish or meat. The mitotic index (MI) was significantly higher and the replication index (RI) was significantly lower in SDAs than in controls. No correlation was found between gamma (a statistical transformation of SCEs/cell) and MI or RI within the groups of SDAs or controls. In the pooled data there was a negative correlation of gamma and MI and a positive correlation of gamma and RI. Of the interpersonal variation in gamma 8% and 14% could be explained by MI and RI. The finding of a lower SCE frequency in a group of SDAs who have a low risk of cancer might indirectly indicate a relation between SCE and cancer and encourages further studies of SCE and diet.

Role of oxygen free radicals in the induction of sister chromatid exchanges by cigarette smoke

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Lee, C.K.; Brown, B.G.; Rice, W.Y. Jr.; Doolittle, D.J.

1989-01-01

Cigarette smoke has been reported to contain free radicals and free radical generators in both the gas and particulate phases. Studies in our laboratory have shown that both cigarette smoke condensate (CSC) and smoke bubbled through phosphate buffered saline solution (smoke-PBS) increased sister chromatid exchanges (SCE) in Chinese hamster ovary cells in a dose-dependent manner. Since oxygen free radicals have been shown to cause SCEs and other chromosomal damage, we investigated the role of these radicals in the induction of SCEs by CSC and smoke-PBS. Addition of the antioxidant enzymes catalase and superoxide dismutase or the oxygen-radical scavenger ascorbic acid failed to reduce the SCE frequency in the presence of either CSC or smoke-PBS. Additional studies indicated that the quantity of hydrogen peroxide produced in CSC or smoke-PBS is too small to account for the observed SCE induction. It appears, therefore, that SCE induction by CSC or smoke-PBS does not involve the participation of oxygen free radicals

Alkaline DNA fragmentation, DNA disentanglement evaluated viscosimetrically and sister chromatid exchanges, after treatment in vivo with nitrofurantoin.

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Parodi, S; Pala, M; Russo, P; Balbi, C; Abelmoschi, M L; Taningher, M; Zunino, A; Ottaggio, L; de Ferrari, M; Carbone, A; Santi, L

1983-07-01

Nitrofurantoin was not positive as a carcinogen in long term assays. In vitro it was positive in some short term tests and negative in others. We have examined Nitrofurantoin for its capability of inducing DNA damage in vivo. With the alkaline elution technique, Nitrofurantoin appeared clearly positive in all the tissues examined (liver, kidney, lung, spleen and bone marrow). In the liver we also observed some cross-linking effect. In bone marrow cells Nitrofurantoin was also clearly positive in terms of sister chromatid exchanges (SCEs) induction. DNA damage in vivo was also examined with a viscosimetric method, more sensitive than alkaline elution. With this method the results were essentially negative, suggesting that the two methods detect different types of damage. In view of its positivity in many organs and in two short term tests in vivo, the carcinogenic potential of Nitrofurantoin should be reconsidered.

Sister chromatid exchanges and structural chromosome aberrations in lymphocytes in operating room personnel

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Husum, B; Niebuhr, E; Wulf, H C; Norgaard, I

1983-06-01

Information on possible chromosomal damage in humans after long-term exposure to trace concentrations of waste anaesthetic gases is scarce. We examined peripheral lymphocytes in operating room personnel for both chromosome aberrations and sister chromatid exchanges (SCE). Following a standardized procedure of cultivation and staining, 30 cells from each person were scored for SCE and 100 cells from each person were examined for chromosome aberrations. A total of 45 persons were examined, representing anaesthetists (n . 15), operating room nurses assisting the surgeon (n . 10), nurses circulating in the operating room (n . 8) and healthy, unexposed controls (n . 12). The median duration of working in the operating room was 102 months, respectively. Time-weighted concentration levels of 2.5-4.3 p.p.m. of halothane and 25-400 p.p.m. of nitrous oxide were measured in the breathing zones of the anaesthetists during mask anaesthesia. Examination of SCE and chromosome aberrations yielded corresponding qualitative results. With both tests, no statistically significant difference was observed between the four groups of persons. It was concluded that by examination of both SCE and chromosome aberrations in peripheral lymphocytes in operating room personnel, no indication was found of a mutagenic effect of long-term exposure to trace concentrations of waste anaesthetic gases.

Merotelic kinetochore attachment in oocyte meiosis II causes sister chromatids segregation errors in aged mice.

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Cheng, Jin-Mei; Li, Jian; Tang, Ji-Xin; Hao, Xiao-Xia; Wang, Zhi-Peng; Sun, Tie-Cheng; Wang, Xiu-Xia; Zhang, Yan; Chen, Su-Ren; Liu, Yi-Xun

2017-08-03

Mammalian oocyte chromosomes undergo 2 meiotic divisions to generate haploid gametes. The frequency of chromosome segregation errors during meiosis I increase with age. However, little attention has been paid to the question of how aging affects sister chromatid segregation during oocyte meiosis II. More importantly, how aneuploid metaphase II (MII) oocytes from aged mice evade the spindle assembly checkpoint (SAC) mechanism to complete later meiosis II to form aneuploid embryos remains unknown. Here, we report that MII oocytes from naturally aged mice exhibited substantial errors in chromosome arrangement and configuration compared with young MII oocytes. Interestingly, these errors in aged oocytes had no impact on anaphase II onset and completion as well as 2-cell formation after parthenogenetic activation. Further study found that merotelic kinetochore attachment occurred more frequently and could stabilize the kinetochore-microtubule interaction to ensure SAC inactivation and anaphase II onset in aged MII oocytes. This orientation could persist largely during anaphase II in aged oocytes, leading to severe chromosome lagging and trailing as well as delay of anaphase II completion. Therefore, merotelic kinetochore attachment in oocyte meiosis II exacerbates age-related genetic instability and is a key source of age-dependent embryo aneuploidy and dysplasia.

Evidence that cyclophosphamide can to induce exchanges in the sister chromatids (ICH) through secondary injuries

International Nuclear Information System (INIS)

Morales R, P.; Rodriguez R, R.

1997-01-01

By means of the use of destination protocol of ICH inductive injuries (DLI-ICH), it was studied if interchanges in the sister chromatids (ICH) induced by cyclophosphamide (CP), in the second post-treatment division (ICH-2) are produced by secondary injuries or by fresh injuries. For discard between these possibilities it was administered CP at different periods before of the first post-treatment division, taking as reference the administered time for high dose of bromodeoxyuridine (BrdU ) which was approximately at the beginning of this division. The ICH frequencies that occur in the first, the second and the third synthesis stages (S) were determined. It was observed that when the administered CP was four hours before BrdU , the ICH frequencies of the second and the third S were reduced. The frequency of the first ICH increased lightly in relation to those of the normal protocol (0.5 h before BrdU ) and that the supplying of CP six hours before caused almost a total reduction of ICH of second and third S and an important increment of ICH of first S.This was interpreted as evidence that the ICH-2 are product of secondary injuries. (Author)

Enhanced stimulation of chromosomal translocations and sister chromatid exchanges by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces cerevisiae yku70 mutants

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Fasullo, Michael; St Amour, Courtney; Zeng Li

2005-01-01

DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MAT a and MATα inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-Δ5' and his3-Δ3'::HOcs is enhanced in haploids and diploids expressing both MAT a and MATα genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-Δ3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent

Sister chromatid exchanges in X-ray irradiated blood lymphocytes from patients with hereditary diseases with radioresistant DNA synthesis

International Nuclear Information System (INIS)

Pleskach, N.M.; Andriadze, M.I.; Mikhel'son, V.M.; Zhestyanikov, V.D.

1988-01-01

X-ray irradiation induced sister chromatid exchanges (SCE) in blood lymphocytes from patient with Down's syndrome and adult progeria (in both the cases radioresistant DNA synthesis takes place). In normal lymphocytes (in which ionizing radiation inhibits the replicative synthesis of DNA) the rate of SCE rises with the rise of radiation dose. Thus, the rate of SCE in X-ray irradiated lymphocytes is in reverse dependence with radioresistance of replicative synthesis of DNA. The data obtained are explained in accordance with the replicative hypothesis of the SCE nature (Painter, 1980a): in cells of patients with Down's syndrome, xeroderma pigmentosum from 2 and progeria of adults the time of existence of partly replicated clusters of replicons is decreased due to radioresistant replicative synthesis of DNA, but the presence of partly replicated clusters of replicons in necessary for SCE formation. Therefore the rate of SCF in X-irradiated cells of these patients decreases

A comparative investigation of DNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells

International Nuclear Information System (INIS)

Mouron, Silvana Andrea; Grillo, Claudia Alejandra; Dulout, Fernando Noel; Golijow, Carlos Daniel

2004-01-01

Cadmium (Cd) is a toxic heavy metal of continuing occupational and environmental concern with a wide variety of adverse effects. Several studies have shown that cadmium produces DNA strand breaks, DNA-protein cross-links, oxidative DNA damage, chromosomal aberrations, dysregulation of gene expression resulting in enhanced proliferation, depressed apoptosis and/or altered DNA repair. This study was undertaken to investigate the ability of cadmium chloride (CdCl 2 ) and cadmium sulphate (CdSO 4 ) to induce point mutations in codon 12 of the K-ras protooncogene assessed by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and RFLP-enriched PCR methods. Also their genotoxic effects were analyzed by the comet assay and sister chromatid exchanges test. The human lung fibroblast cell line MRC-5 was used for the experiments. Sister chromatid exchanges assay (SCEs) frequencies were significantly increased in cells exposed to cadmium salts in relation to controls (p < 0.001). Despite the slow increment observed in the three comet parameters considered when cells were treated with cadmium chloride, significant differences between groups were only found in the variable comet moment (CM) (p < 0.005). On the other hand, when cells were exposed to cadmium sulphate, the Kruskal-Wallis test showed highly significant differences between groups for migration, tail moment and comet moment parameters (p < 0.001). Nevertheless, a null or weak point mutation induction in K-ras protooncogene was detected using polymerase chain reaction-low ionic strength-single strand conformation polymorphisms (PCR-LIS-SSCP) and RFLP-enriched PCR methods when cells were treated with cadmium salts. Thus, inorganic cadmium produces genotoxicity in human lung fibroblast MRC-5 cells, in the absence of significant point mutation of the K-ras gene

Elastatinal and leupeptin: effects on u.v.-induced mutation and sister-chromatid exchanges in Chinese hamster cells

International Nuclear Information System (INIS)

Paul, P.; Fujiwara, Y.

1981-01-01

Microbial protease inhibitors elastatinal and leupeptin were tested for cytotoxicity and for effects on spontaneous and u.v.-induced 6-thioguanine-resistant (6TGsup(r)) mutation and sister-chromatid exchange (SCE) in V79 Chinese hamster cells. Continuous treatment with elastatinal exhibited marked cytotoxicity, while leupeptin was almost non-cytotoxic. Elastatinal rapidly induced cytotoxic effects as a function of its concentration and time of exposure. Near maximum cytotoxicity was reached after exposures of 6-8 h and this was partially abolished by the presence of 2.5 μg cycloheximide per ml. Concentrations of either protease inhibitor which gave 60-80% survival had no appreciable effects on u.v. survival and frequencies of spontaneous and u.v.-induced 6TGsup(r) mutation and SCE. However, reconstruction experiments revealed that pretreatments of 6TGsup(r) and 6TGsup(s) (wild-type) cells with these inhibitors for 6 days tended to block metabolic co-operation in their co-cultures. Thus, elastatinal and leupeptin are neither clastogenic nor mutagenic by themselves, and do not alter mutation fixation and expression. (author)

Elastatinal and leupeptin: effects on u.v.-induced mutation and sister-chromatid exchanges in Chinese hamster cells

International Nuclear Information System (INIS)

Paul, P.; Fujiwara, Y.

1981-01-01

Microbial protease inhibitors elastatinal and leupeptin were tested for cytotoxicity and for effects on spontaneous and u.v.-induced 6-thioguanine-resistant (6TGr) mutation and sister-chromatid exchange (SCE) in V79 Chinese hamster cells. Continuous treatment with elastatinal exhibited marked cytotoxicity, while leupeptin was almost non-cytotoxic. Elastatinal rapidly induced cytotoxic effects as a function of its concentration and time of exposure. Near maximum cytotoxicity was reached after exposure of 6-8 h and this was partially abolished by the presence of 2.5 micrograms cycloheximide per ml. Concentrations of either protease inhibitor which gave 60-80% survival had no appreciable effects on u.v. survival and frequencies of spontaneous and u.v.-induced 6TGr mutation and SCE. However, reconstruction experiments revealed that pretreatments of 6TGr and 6TGs (wild-type) cells with these inhibitors for 6 days tended to block metabolic co-operation in their co-cultures. Thus, elastatinal and leupeptin are neither clastogenic mutagenic by themselves, and do not alter mutation fixation and expression

Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins.

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Cheri A Schaaf

2009-07-01

Full Text Available The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in which histone H3 is methylated by the Enhancer of zeste [E(z] Polycomb group silencing protein. Here we show that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesin and the E(z-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system. These gene complexes are modestly transcribed, and produce seven of the twelve transcripts that increase the most with cohesin knockdown genome-wide. Cohesin mutations alter eye development in the same manner as increased Enhancer of split activity, suggesting that similar regulation occurs in vivo. We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome.

Perturbation of Incenp function impedes anaphase chromatid movements and chromosomal passenger protein flux at centromeres.

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Ahonen, Leena J; Kukkonen, Anu M; Pouwels, Jeroen; Bolton, Margaret A; Jingle, Christopher D; Stukenberg, P Todd; Kallio, Marko J

2009-02-01

Incenp is an essential mitotic protein that, together with Aurora B, Survivin, and Borealin, forms the core of the chromosomal passenger protein complex (CPC). The CPC regulates various mitotic processes and functions to maintain genomic stability. The proper subcellular localization of the CPC and its full catalytic activity require the presence of each core subunit in the complex. We have investigated the mitotic tasks of the CPC using a function blocking antibody against Incenp microinjected into cells at different mitotic phases. This method allowed temporal analysis of CPC functions without perturbation of complex assembly or activity prior to injection. We have also studied the dynamic properties of Incenp and Aurora B using fusion protein photobleaching. We found that in early mitotic cells, Incenp and Aurora B exhibit dynamic turnover at centromeres, which is prevented by the anti-Incenp antibody. In these cells, the loss of centromeric CPC turnover is accompanied by forced mitotic exit without the execution of cytokinesis. Introduction of anti-Incenp antibody into early anaphase cells causes abnormalities in sister chromatid separation through defects in anaphase spindle functions. In summary, our data uncovers new mitotic roles for the CPC in anaphase and proposes that CPC turnover at centromeres modulates spindle assembly checkpoint signaling.

Effect of chlorophyllin on frequency radiation-induced of sister chromatid exchanges (SCE) and other cytogenetic events in mice bone marrow cells In Vivo

International Nuclear Information System (INIS)

Garcia Rodriguez, M.C.

1992-01-01

The effect of chlorophyllin on gamma radiation induced Sister chromatid exchanges (SCE) and on the mitotic index (IM) and average generation time was determined. Groups of mice were treated in one of the following regimens: (1) untreated, (2) treated with chlorophyllin only, (3) irradiated and (4) treated with chlorophyllin and irradiated intraperitoneal administration of chlorophyllin preceding gamma radiation exposure protected again SCE induction and diminution of IM. However, radioprotection was not reflected in the average generation time for the chlorophyllin per se acceleration the average generation time. The results suggest that, under the experimental conditions of the study the SCE and IM are caused by free radicals produced by radiation and wat the action mechanics of chlorophyllin is scavenger free radicals. (Author)

Health assessment of gasoline and fuel oxygenate vapors: micronucleus and sister chromatid exchange evaluations.

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Schreiner, Ceinwen A; Hoffman, Gary M; Gudi, Ramadevi; Clark, Charles R

2014-11-01

Micronucleus and sister chromatid exchange (SCE) tests were performed for vapor condensate of baseline gasoline (BGVC), or gasoline with oxygenates, methyl tert-butyl ether (G/MTBE), ethyl tert butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), t-butyl alcohol (TBA), or ethanol (G/EtOH). Sprague Dawley rats (the same 5/sex/group for both endpoints) were exposed to 0, 2000, 10,000, or 20,000mg/m(3) of each condensate, 6h/day, 5days/week over 4weeks. Positive controls (5/sex/test) were given cyclophosphamide IP, 24h prior to sacrifice at 5mg/kg (SCE test) and 40mg/kg (micronucleus test). Blood was collected from the abdominal aorta for the SCE test and femurs removed for the micronucleus test. Blood cell cultures were treated with 5μg/ml bromodeoxyuridine (BrdU) for SCE evaluation. No significant increases in micronucleated immature erythrocytes were observed for any test material. Statistically significant increases in SCE were observed in rats given BGVC alone or in female rats given G/MTBE. G/TAME induced increased SCE in both sexes at the highest dose only. Although DNA perturbation was observed for several samples, DNA damage was not expressed as increased micronuclei in bone marrow cells. Inclusion of oxygenates in gasoline did not increase the effects of gasoline alone or produce a cytogenetic hazard. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessment of DNA Damage in Peripheral Blood Lymphocytes of Radiation Workers at Al-Tuwaitha Site by Using the Sister Chromatid Exchange and the Comet Assay

International Nuclear Information System (INIS)

Ali, A.K.; Muttar, A.J.; Khayon, S.K.; Haider, Y.L.; Ali, H.F.; Abdullah, A.K.

2015-01-01

The sister chromatid exchange was performed on peripheral blood lymphocytes obtained from 40 individuals of workers occupationally exposed to low ionizing radiation doses in Al-Tuwaitha site due to decommissioning to radioactive contamination then compared with 40 control individuals living in Baghdad. SCEs were scored in metaphase chromosomes were identified by fluorescent plus Giemsa staining (Figure 2).The mean frequencies of SCEs per cell differed significantly (p≺0 0.05) between individuals of radiation workers and control, being 7.78 0.45 SCE/cells and 6.28 0.22 SCE/cells , respectively. However SCE frequency was statistically significant (P≺0 0.05) among radiation workers as compared to control individuals.

Increased UV-induced sister-chromatid exchange in cultured fibroblasts of first-degree relatives of melanoma patients

International Nuclear Information System (INIS)

Knees-Matzen, S.; Roser, M.; Reimers, U.; Ehlert, U.; Weichenthal, M.; Breitbart, E.W.; Ruediger, H.W.

1991-01-01

Cultured fibroblasts of 17 first-degree relatives of familial melanoma patients and six first-degree relatives of cutaneous melanoma (CMM) patients with multiple CMM primaries were tested for in vitro sensitivity to UV light. Fibroblasts of nine familial CMM patients with a known UV-sensitivity and 19 healthy probands served as a control. Sister chromatid exchange (SCE) was used as a parameter to detect UV-induced genotoxic damage. The authors found significantly (p less than 0.001) increased UV-induced SCE levels in familial melanoma patients, as well as in first-degree relatives of familial melanoma patients (p less than 0.001) after UV-A,B irradiation (375 J/m2), compared to the healthy probands without a family history of CMM. A significant (p less than 0.001) increase of UV-induced SCE was also observed in the relatives of CMM patients with multiple CMM primaries. In addition, the spontaneous SCE were significantly increased (p less than 0.05) in familial CMM patients. This study shows that increased UV sensitivity is a familial phenomenon. It is consistent with the concept of a genetic predisposition to CMM, which is based on increased UV sensitivity and may help to define groups with an elevated risk of developing cutaneous malignant melanoma

The yield of fission neutron-induced chromatid aberrations in G[sub 2]-stage human lymphocytes: effect of caffeine, hydroxyurea and cytosine arabinoside post-irradiation

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Antoccia, A.; Tanzarella, C. (La Sapienza Univ., Rome (Italy)); Palitti, F. (Tuscia Univ., Viterbo (Italy) La Sapienza Univ., Rome (Italy)); Raggi, T. (Tuscia Univ., Viterbo (Italy)); Catena, C. (ENEA, Casaccia (Italy). Centro Ricerche Energia)

1992-11-01

To evaluate the influence of inhibitors of DNA synthesis/repair on the yield of chromosomal aberrations in the G[sub 2] phase of the cell cycle, whole-blood cultures of human lymphocytes were exposed to various doses of fission neutrons or X-rays and treated post-irradiation during the last 2.45 h before harvesting, with 5mM hydroxyurea (HU) and 0.05 mM cytosine arabinoside (ara-C). The presence of caffeine and HU strongly potentiated the yield of chromatid-type aberrations induced by both neutrons and X-rays. No potentiating effect, except at the highest dose of neutrons, was observed when irradiated cells were subsequently treated with ara-C. In addition, neutron-induced mitotic delay was shortened by treatment with caffeine, mainly within the first 2 h after irradiation. (Author).

Effect of chlorophyllin on induction of exchanges in sister chromatids by gamma irradiation in mice spermatogonia in vivo

International Nuclear Information System (INIS)

Mendiola C, M.T.

1994-01-01

Mouse were exposed to different doses of gamma radiation and the effect on Sister Chromatid Exchange (SCE) frequency in spermatogonias was evaluated. The effect was analyzed before and after Bromodeoxyuridine (BrdU) incorporation to determine the interference of such agent with the cellular response induced by radiation. The capacity of chlorophyllin (sodium and Copper salt derivative from chlorophyll) to reduce SCE induction by radiation in normal and BrdU radio sensitized spermatogonia was also determined. The results indicate that there was a significant increase in SCE frequency by gamma radiation exposure in these cells, such effect was higher irradiating after BrdU incorporation than before. This fact confirms previous observations that BrdU sensitizes some cells to SCE induction. With regard to the chlorophyllin effect, it was determined that this salt acts as a radioprotector reducing gamma-rays induced SCE before or after BrdU incorporation Total protection was obtained with 200 μg of chlorophyllin per g of body weight in both protocols. Under the experimental conditions this study there was no evidence of genotoxicity induced by chlorophyllin itself. The results suggest that this agent may act as a radioprotector by scavenging free radicals produced by gamma-radiation which cause DNA lesions that are involved in SCE formation. (Author)

Effects of hyperthermia and x irradiation on sister chromatid exchange (SCE) frequency in Chinese hamster ovary (CHO) cells

International Nuclear Information System (INIS)

Livingston, G.K.; Dethlefsen, L.A.

1979-01-01

The BrdUrd labeling method was used to evaluate the effects of hyperthermia, x irradiation, and the combined treatment on the incidence of sister chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells. Cells cultured in McCoy's 5A media containing 10 μM 5-bromodeoxyuridine were synchronized after one cell cycle by mitotic shake-off. Early-G 1 cells were heated by submerging culture flasks in a 44 +- 0.05 0 C water bath for periods of 20, 40, and 60 min. By the same method, other cultures were x irradiated at doses of 100, 200, 400, and 600 rad. A third protocol involved combined treatment of 20 min at 44 0 C followed immediately by one of the above radiation doses. A fourth protocol reversed the sequence of the combined treatment applying x irradiation (200 or 400 rad) followed immediately by hyperthermia. The data showed that hyperthermia and x irradiation both elevated the frequency of SCEs significantly whether applied separately or together. The combined treatment (heat: 20 min at 44 0 C plus varying x-radiation doses) produced results suggestive of a synergistic interaction. The sequence of the heat and x irradiation did not appear to have a significant effect on the production of SCE

Protection of halogenated DNA from strand breakage and sister-chromatid exchange induced by the topoisomerase I inhibitor camptothecin

International Nuclear Information System (INIS)

Orta, Manuel Luis; Mateos, Santiago; Cantero, Gloria; Wolff, Lisa J.; Cortes, Felipe

2008-01-01

The fundamental nuclear enzyme DNA topoisomerase I (topo I), cleaves the double-stranded DNA molecule at preferred sequences within its recognition/binding sites. We have recently reported that when cells incorporate halogenated nucleosides analogues of thymidine into DNA, it interferes with normal chromosome segregation, as shown by an extraordinarily high yield of endoreduplication, and results in a protection against DNA breakage induced by the topo II poison m-AMSA [F. Cortes, N. Pastor, S. Mateos, I. Dominguez, The nature of DNA plays a role in chromosome segregation: endoreduplication in halogen-substituted chromosomes, DNA Repair 2 (2003) 719-726; G. Cantero, S. Mateos, N. Pastor; F. Cortes, Halogen substitution of DNA protects from poisoning of topoisomerase II that results in DNA double-strand breaks (DSBs), DNA Repair 5 (2006) 667-674]. In the present investigation, we have assessed whether the presence of halogenated nucleosides in DNA diminishes the frequency of interaction of topo I with DNA and thus the frequency with which the stabilisation of cleavage complexes by the topo I poison camptothecin (CPT) takes place, in such a way that it protects from chromosome breakage and sister-chromatid exchange. This protective effect is shown to parallel a loss in halogen-substituted cells of the otherwise CPT-increased catalytic activity bound to DNA

The Relationship between Dioxin Congeners in the Breast Milk of Vietnamese Women and Sister Chromatid Exchange

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Hiroyuki Suzuki

2014-04-01

Full Text Available The aim of this study was to clarify the relationship between dioxin concentrations in breast milk and the sister chromatid exchange (SCE frequency in women from herbicide-sprayed and non sprayed areas. Blood samples were taken from 21 women with high TCDD (tetrachlorodibenzo-p-dioxin levels from sprayed areas, 23 women with moderate TCDD levels from sprayed areas, and 19 women from non sprayed areas to determine their SCE frequency. The SCE frequencies for the high and moderate TCDD groups from the sprayed area and for the non sprayed area group were 2.40, 2.19, and 1.48 per cell, respectively. Multiple regression analysis showed that the standardized β values for 1,2,3,6,7,8-hexaCDD (β = 0.60, 1,2,3,4,6,7,8-heptaCDD (β = 0.64, and octaCDD (β = 0.65 were higher than those for TCDD (β = 0.34 and 1,2,3,7,8-pentaCDD (β = 0.42. The adjusted R2 value for polyCDDs (R2 = 0.38 was higher than that for polyCDD toxic equivalents (TEQ (toxic equivalents; R2 = 0.23. This study therefore shows that levels of hexa-, hepta-, and octaCDD, which were previously regarded as being less toxic than TCDD, are closely related to SCE frequency and that the level of dioxin (pg/g lipid is potentially more useful as an indicator than TEQ value for explaining SCE frequency.

Chromatid repulsion associated with Roberts/SC phocomelia syndrome is reduced in malignant cells and not expressed in interspecies somatic-cell hybrids.

Science.gov (United States)

Krassikoff, N E; Cowan, J M; Parry, D M; Francke, U

1986-01-01

Different cell types from a female patient with Roberts/SC phocomelia syndrome were evaluated quantitatively for the presence of repulsion of heterochromatin and satellite regions of mitotic chromosomes. Whereas EBV-transformed lymphoblasts from an established cell line revealed these phenomena at frequencies equal to those in PHA-stimulated lymphocytes and cultured skin fibroblasts, aneuploid cells from a metastatic melanoma displayed them at 50% lower frequency. Cocultivation of the patient's fibroblasts with either an immortal Chinese hamster cell line or with a human male fibroblast strain carrying a t(4;6)(p14;q21) translocation showed that the phenomenon was not corrected or induced by a diffusible factor or by cell-to-cell contact. In each experiment, only the patient's metaphase spreads revealed chromatid repulsion. In fusion hybrids between the patient's fibroblasts and an established Chinese hamster cell line, the human chromosomes behaved perfectly normally, suggesting that the gene product which is missing or mutant in Roberts/SC phocomelia syndrome is supplied by the Chinese hamster genome. Images Fig. 1 Fig. 2 Fig. 3 PMID:3788975

Evaluation of the persistence in the induction of Sister Chromatid Exchanges (SCE) by alkylating agents; Evaluacion de la persistencia en la induccion de Intercambio en las Cromatidas Hermanas (ICH) por agentes alquilantes

Energy Technology Data Exchange (ETDEWEB)

Rodriguez R, R.; Huerta V, C.; MOrales R, P.R. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

2006-07-01

The persistence in the induction of sister chromatid exchanges (SCE) by the alkylating agents methyl and ethyl-methanesulfonates (MMS and EMS) was evaluated. For it, to groups of mice its were administered a dose of these agents and later its were analyzed the induced SCE's in two periods: early and late. Both agents caused high increments of SCE in the early period and small in the late one; however, the caused lately by EMS was significantly bigger. This late induction of SCE by EMS possibly is associated with an epigenetic change or with the presence of etiladucts in the phosphodiester bonds of the DNA. (Author)

Evaluation of the persistence in the induction of Sister Chromatid Exchanges (SCE) by alkylating agents; Evaluacion de la persistencia en la induccion de Intercambio en las Cromatidas Hermanas (ICH) por agentes alquilantes

Energy Technology Data Exchange (ETDEWEB)

Rodriguez R, R; Huerta V, C; MOrales R, P R [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

2006-07-01

The persistence in the induction of sister chromatid exchanges (SCE) by the alkylating agents methyl and ethyl-methanesulfonates (MMS and EMS) was evaluated. For it, to groups of mice its were administered a dose of these agents and later its were analyzed the induced SCE's in two periods: early and late. Both agents caused high increments of SCE in the early period and small in the late one; however, the caused lately by EMS was significantly bigger. This late induction of SCE by EMS possibly is associated with an epigenetic change or with the presence of etiladucts in the phosphodiester bonds of the DNA. (Author)

Persistence of sister chromatid exchanges and in vitro morphological transformation of Syrian hamster fetal cells by chemical and physical carcinogens

International Nuclear Information System (INIS)

Popescu, N.C.; Amsbaugh, S.C.; DiPaolo, J.A.

1985-01-01

The induction of neoplastic cell transformation is closely associated with DNA alterations which occur shortly after carcinogen exposure. Sister chromatid exchange (SCE) formation is a sensitive indicator of carcinogen-DNA interaction and correlates with the induction of morphological cell transformation. The persistence of lesions generating SCE produced by chemical and physical carcinogens and its relevance to the induction of morphologic transformation was evaluated in coordinated experiments with cultured Syrian hamster fetal cells (HFC). Exponentially growing HFC were exposed for 1 h to benzo[a]pyrene (BP), methyl-methanesulfonate (MMS), cis-platinum (II) diaminedichloride (cis Pt II), N-methyl-N'-nitrosourea (MNU), mitomycin C (MMC), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-acetoxy-2-fluorenyl-acetamide (AcAAF) or u.v. light irradiated. SCE analysis demonstrates that for a period of 48 h after carcinogen exposure, during which time the cells undergo at least four replicative cycles, DNA damage generating SCE induced by all chemical carcinogens either persisted or was partially removed, whereas u.v.-induced lesions were completely removed. An elevated SCE frequency persisted after two additional cell cycles after treatment with BP, AcAAF or MMC without increased cell lethality as compared to other carcinogens whose lesions were completely eliminated during the same period

Micronuclear and sister chromatid exchange analyses in peripheral lymphocytes of patients with oral lichen planus--a pilot study.

Science.gov (United States)

Ergun, S; Warnakulasuriya, S; Duman, N; Saruhanoğlu, A; Sevinç, B; Oztürk, S; Ozel, S; Cefle, K; Palanduz, S; Tanyeri, H

2009-10-01

The purpose of this study was to determine the genetic instability of peripheral blood lymphocytes from patients diagnosed with oral lichen planus (OLP) by investigation of frequencies of micronuclei (MN) and sister chromatid exchange (SCE). A total of 22 newly diagnosed and untreated patients with OLP of same severity scores and twenty healthy controls participated in this study. They were all non-smokers with no previous history or family history of cancer. The periodontal status, flow rate and buffering capacity of whole mouth saliva were recorded. SCE and MN analyses were performed on peripheral blood lymphocytes of OLP patients and healthy controls. The frequencies of MN (50.00 +/- 22.36) and SCE (6.89 +/- 1.48) in OLP patients were found to be significantly elevated compared with that in normal individuals (25.20 +/- 9.52 and 5.93 +/- 1.31; z = 3.946, P = 0.0001; z = 2.346, P = 0.019). There were no significant differences in the MN frequency and SCE between the two subgroups with reticular or erosive types of OLP. These pilot data indicate an increased genomic instability in peripheral blood lymphocytes of a cohort of Turkish patients diagnosed with oral lichen planus as compared with that of healthy individuals. As patients with OLP may have an increased or potential risk for oral malignancy, these assays could be used in translational research to monitor beneficial effects of interventions and long-term prognosis.

Effect of low 60Co dose rates on sister chromatid exchange incidence in the benthic worm. Neanthes arenaceodentata

International Nuclear Information System (INIS)

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

1981-01-01

The usefulness of sister chromatid exchange (SCE) induction as a measure of low-level radiation effect was examined in a benthic marine worm, Neanthes arenaceodentata. Larvae were exposed to 60 Co radiation for 12 to 24 h at total doses ranging from 0.5 to 309 R and at dose rates from 0.04 to 13 R/h. Animals exposed at intermediate dose rates (0.5, 0.6, 1.25, 2.0, and 2.5 R/h) had SCE frequencies per chromosome about twice that of those receiving no radiation (controls), whereas those exposed at the higher dose rates (7.0 and 13 R/h) had SCE frequencies lower than the controls. Animals exposed at the lower dose rates (0.04 and 0.1 R/h) had lower SCE frequencies than those exposed at intermediate dose rates (and higher SCE frequencies than controls). The length of chromosome pair number one differed among metaphase spreads and was used as an index of chromosome condensation in a given metaphase. Because there is a possibility that chromosome morphology may affect the ability to resolve SCEs, morphology will be monitored in future studies. A preliminary experiment was performed to assess the effects of 2.2 and 11.5 R/h for 24 h on growth and development. Larvae observed at 6 and 17 d after irradiation did not have significantly different numbers of abnormal larvae or survival rates

Differences in sensitivity of murine spermatogonia and somatic cells in vivo to sister-chromatid exchange induction by nitrosoureas.

Science.gov (United States)

Morales-Ramírez, P; Cruz-Vallejo, V; Rodríguez-Reyes, R

2001-07-01

Previously published data indicate that spermatogonia (SPG) are less sensitive to a sister-chromatid exchange (SCE) induction for different mutagens. In an earlier study, we have observed that bromodeoxyuridine (BrdU) substituted murine SPG are less sensitive to SCE induction by gamma ray in cells, than bone marrow (BM) and salivary gland (SG) cells in vivo. This was interpreted to mean that SPG are more efficient in DNA repair or are less prone to SCE induction. That the lower induction of SCE could be due to a reduced accessibility of mutagens to the SPG by virtue of a physiological barrier, was discarded by using gamma radiation. The aim of the present study was to establish whether or not there are differences in SCE induction by nitrosoureas among SPG, SG and BM cells with BrdU substituted or unsubstituted DNA. It was observed that SCE induction by methylnitrosourea (MNU) or by ethylnitrosourea (ENU) in SPG was, respectively, five and two times lower than in SG, and ten and three times lower than in BM. In SPG after BrdU incorporation, there was no increase in efficiency of SCE induction; in fact, there was even a slight decrease by exposure to MNU or ENU. BM and SG cells showed an increased efficiency in SCE induction after BrdU incorporation. This implies that SPG are also less sensitive to SCE induction by nitrosoureas, which cause a different kind of damage from previously assayed mutagens.

Trex2 enables spontaneous sister chromatid exchanges without facilitating DNA double-strand break repair.

Science.gov (United States)

Dumitrache, Lavinia C; Hu, Lingchuan; Son, Mi Young; Li, Han; Wesevich, Austin; Scully, Ralph; Stark, Jeremy; Hasty, Paul

2011-08-01

Trex2 is a 3' → 5' exonuclease that removes 3'-mismatched sequences in a biochemical assay; however, its biological function remains unclear. To address biology we previously generated trex2(null) mouse embryonic stem (ES) cells and expressed in these cells wild-type human TREX2 cDNA (Trex2(hTX2)) or cDNA with a single-amino-acid change in the catalytic domain (Trex2(H188A)) or in the DNA-binding domain (Trex2(R167A)). We found the trex2(null) and Trex2(H188A) cells exhibited spontaneous broken chromosomes and trex2(null) cells exhibited spontaneous chromosomal rearrangements. We also found ectopically expressed human TREX2 was active at the 3' ends of I-SceI-induced chromosomal double-strand breaks (DSBs). Therefore, we hypothesized Trex2 participates in DNA DSB repair by modifying 3' ends. This may be especially important for ends with damaged nucleotides. Here we present data that are unexpected and prompt a new model. We found Trex2-altered cells (null, H188A, and R167A) were not hypersensitive to camptothecin, a type-1 topoisomerase inhibitor that induces DSBs at replication forks. In addition, Trex2-altered cells were not hypersensitive to γ-radiation, an agent that causes DSBs throughout the cell cycle. This observation held true even in cells compromised for one of the two major DSB repair pathways: homology-directed repair (HDR) or nonhomologous end joining (NHEJ). Trex2 deletion also enhanced repair of an I-SceI-induced DSB by both HDR and NHEJ without affecting pathway choice. Interestingly, however, trex2(null) cells exhibited reduced spontaneous sister chromatid exchanges (SCEs) but this was not due to a defect in HDR-mediated crossing over. Therefore, reduced spontaneous SCE could be a manifestation of the same defect that caused spontaneous broken chromosomes and spontaneous chromosomal rearrangements. These unexpected data suggest Trex2 does not enable DSB repair and prompt a new model that posits Trex2 suppresses the formation of broken

In vivo study on the replicative model validity of sister chromatid exchanges production

International Nuclear Information System (INIS)

Cruz V, V.L.

1996-01-01

The sister chromatid exchanges (SCE) frequency determination has been used as index of damage to DNA, however the biological meaning of this event is still ignored. Different models in order to explain the mechanism of their formation have been proposed and they could be contained in two categories: a) those that consider that the SCE is produced by means of discreet lesions to the DNA and that they occur in the place of the lesion, and b) those that propose that the SCE is caused by a group of lesions and that therefore the place in which they occur could not be associated with a lesion in particular. The model of Painter (1980) belongs to this last group. It suggests that the region of the DNA where the clusters are united, is the only place in which the exchange of double chain could happen during the synthesis of the DNA and makes the prediction that since the x rays retard the beginning of the duplication, the pretreatment with ionizing radiation would reduce the frequency of SCE induced by agents capable to block the lengthening of the chain of DNA, that are the most efficient SCE inducers. The objective of the present work was to establish the validity of this replicative model for the SCE formation, based in its prediction. The effect of the unilateral preexposition of mouse to gamma radiation was determined on the SCE induction by Mitomycin C (MMC), in cells of the femoral bone marrow In vivo. This strategy allows to determine the effect of the pretreatment in the same organism, minimizing the variability of the response between individuals. There was not a significant variability between the frequencies of SCE, basal and induced by gamma radiation or MMC in the same organism. The animals that received the gamma radiation pretreatment, showed a reduction of approximately the 30 % in the frequency of SCE, assuming an additive effect of the radiation with the MMC. These results coincide with the prediction of the model of Painter, however it is not

Can consumption of raw vegetables decrease the count of sister chromatid exchange? Results from a cross-sectional study in Krakow, Poland.

Science.gov (United States)

Galas, Aleksander; Cebulska-Wasilewska, Antonina

2015-03-01

Sister chromatid exchange (SCE) is a widely used sensitive cytogenetic biomarker of exposure to genotoxic and cancerogenic agents. Results of human monitoring studies and cytogenetic damage have revealed that biological effects of genotoxic exposures are influenced by confounding factors related to life-style. Vegetable and fruit consumption may play a role, but available results are not consistent. The purpose of the study was to investigate the effect of consumption of raw and cooked vegetables and fruits on SCE frequency. A total of 62 participants included colorectal cancer (CRC) patients, hospital-based controls and healthy laboratory workers. SCE frequency was assessed in blood lymphocytes. Frequency of vegetable and fruit consumption was gathered by structured semi-quantitative food frequency questionnaire. SCE frequency was lowest among hospital-based controls (4.4 ± 1.1), a bit higher in CRC patients (4.5 ± 1.0) and highest among laboratory workers (7.4 ± 1.2) (p consumption, but not so for intake of cooked vegetables and fruits. The results of the study have shown the beneficial effect of consumption of raw vegetables on disrupted replication of DNA measured by SCE frequency, implying protection against genotoxic agents. Further effort is required to verify the role of cooked vegetables and fruits.

Chromosomal aberration

International Nuclear Information System (INIS)

Ishii, Yutaka

1988-01-01

Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G 2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G 2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G 2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G 1 phase. (author)

Variation in sister chromatid exchange frequencies between human and pig whole blood, plasma leukocyte, and mononuclear leukocyte cultures

International Nuclear Information System (INIS)

Larramendy, M.L.; Reigosa, M.A.

1986-01-01

Sister chromatid exchange (SCE) induction by ultraviolet (UV) light was studied in both human and pig whole blood cultures (WBC) and plasma leukocyte cultures (PLC). No variation in SCE frequency was observed between pig WBC and PLC in control as well as in treated cells. Conversely, SCE frequencies of human PLC were consistently higher than those of WBC in control and UV-exposed cells. Thus, red blood cells (RBCs) do not influence the sensitivity of lymphocytes to UV LIGHT exposure, and there must be some different culture condition(s) in the inducation of SCEs between human WBC and PLC but not in swine lymphocyte cultures. Since the BrdUrd/lymphocyte ratio of WBC was halved in PLC, the effect of BrdUrd concentration in inducing the SCE baseline frequency of PLC may be ruled out. Neither the cell separation technique nor polymorphonuclear leukocytes had a significant role in the elevated SCE frequency of human PLC or MLC. Experiments where human RBCs were titrated into human PLC showed that the induction of an elevated SCE frequency of PLC was suppressed in a dose-dependent manner by the presence of RBCs in the culture medium. Since the incorporation of pig or human RBCs into human PLC as well as into MLC reduced the SCE frequency to that of WBC, a common component and/or function existing in these cells is suggested. Analysis of different RBC components showed that RBCs, specifically RBC ghosts, release a diffusible but not dialyzable corrective factor into culture medium that is able to reduce the SCE frequencies of PLC

UV-sensitivity of bromodeoxyuridine (BUdR)-substituted chromosomes in Chinese hamster cells

International Nuclear Information System (INIS)

Antoshchina, M.M.; Luchnik, N.V.

1990-01-01

Chinese hamster cells with chromosomes differently substituted for BUdR (TT-TT, TT-TB, TB-TB, TB-BB, where T is thymidine containing chromatid and B is BUdR substituted chromatid) were exposed to UV-light in phase G 2 and chromosome aberrations (mainly chromatid breaks) were analysed. Breaks frequency per chromosome was proportional to BUdR content. No breaks were found in TT-TT chromosomes. The frequency of breaks per TB chromatid was similar with TT-TB and TB-BB chromosomes. In TB-BB chromosomes, however, virtually no breaks occured in TB chromatids whereas in BB chromatids, their frequency was much higher than was expected

Comparison of 6-thioguanine-resistant mutation and sister chromatid exchanges in Chinese hamster V79 cells with forty chemical and physical agents

International Nuclear Information System (INIS)

Nishi, Y.; Hasegawa, M.M.; Taketomi, M.; Ohkawa, Y.; Inui, N.

1984-01-01

The induction of sister chromatid exchanges (SCE) and mutation at the hypoxanthine-guanine phosphoribosyl transferase locus and toxicities of 40 different chemical and physical agents were examined on Chinese hamster V79 cells. These agents included mono-, di-, tri-, and polyfunctional alkylating agents, intercalators, gamma-rays, and UV light irradiation. Mutation was measured as resistance to 6-thioguanine and toxicity as loss of cell-plating efficiency. SCE were examined 29 hr after treatment. With the agents examined, a highly positive correlation existed between SCE-inducing and mutagenic potencies, when expressed as increase in the number per a unit dose over the control values. But the great difference of the ratios of mutagenic potencies versus SCE-inducing potencies among agents was observed, the maximal difference in the ratios being about 200-fold. The agents that showed the higher values of the ratio (agents producing more mutations than SCE) were bleomycin, cobalt-60 gamma-rays, all ethylating agents (N-ethyl-N-nitrosourea, N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and diethylsulfate), N-propyl-N-nitrosourea, N-butyl-N-nitrosourea, isopropyl methanesulfonate, intercalating acridine compounds (2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]-acridine X 2HCl and 2-methoxy-6-chloro-9-[3-(chloroethyl)-aminopropylamino]acridine 2HCl) and UV light at 254 nm

Repairability during G 1 phase of inducting lesions of sister chromatid exchange produced by mitomycin C in salivary gland cells of mice In Vivo

International Nuclear Information System (INIS)

Cruz Vallejo, V.L.

1991-01-01

The repairability of the injuries that lead to the formation of sister chromatid exchange (SCE) produced by mitomycin C (MMC) with a dose of 2.1 mg/g in vivo, during the G 1 phase in the first cycle of cellular division (before the incorporation of BrdU [5-bromo-2 deoxyurine] to the DNA), as well as during the G 1 phase of the second cycle of cellular division (after the incorporation of BrdU) were analyzed. A 35.1% decrease in the frequency of SCE produced by Mitomycin C was observed, in the early G 1 phase of the first division, with respect to the frequency of SCE induced in the later G 1 phase. When Mitomycin C is given to cells whose DNA is substituted with BrdU in only one of the chain's filaments such decrease is not observed. The results suggest that the injuries caused by MMC, which give place to the SCE, in cells of the salivary glands of the mouse in vivo, are partially repaired only when induced in DNA which has not been substituted with BrdU. (Author)

Excision and crosslink repair of DNA and sister chromatid exchanges in cultured human fibroblasts with different repair capacities

Energy Technology Data Exchange (ETDEWEB)

Fujiwara, Y; Kano, Y; Paul, P; Goto, K; Yamamoto, K [Kobe Univ. (Japan). School of Medicine

1981-01-01

Xeroderma pigmentosum (XP) groups A to G lacked the initial stage of ultraviolet (UV) excision repair in the order of A = G > C > D > E asymptotically equals F, while the XP variant was weakly defective in the later repair steps. Killing sensitivities were in the orders of A >= G > D > C > E asymptotically equals F asymptotically equals variant > normal to UV, A = G > D > F > C = E > variant > normal to 4-nitroquinoline-1-oxide (4NQO), and A > C > D = E = F = variant > G = normal to decarbamoyl mitomycin-C(DCMC). The induced sister chromatid exchange (SCE) frequency was unrelated to the extent of repair deficiency. The SCE induction rate was consistently 3 - 6 fold higher by these UV-like mutagens in XP group A cells than in normal cells. However, repair-proficient Cockayne's syndrome (CS) cells showed a higher SCE induction by UV, which was normalized by NAD/sup +/, suggesting that chromatin lesions as well as DNA damage contribute to SCE. Two-step crosslink repair involves a first rapid half-excision and a second slow nucleotide-excision repair. Fanconi's anemia (FA) cells had an impaired first half-excision and were supersensitive to MC, but not to UV and DCMC. The SCE frequency induced by MC (1 hr) was higher in FA cells than in normal cells despite their normal response to DCMC, and vice versa in XP cells. FA cells lacked the first rapid decline and showed higher remaining SCEs. Thus, part of the crosslink seems to lead to SCE formation. Caffeine synergistically elevated UV-induced SCEs, but not UV induced mutations in V79 cells, implying that SCE may not necessarily involve mutation.

Excision and crosslink repair of DNA and sister chromatid exchanges in cultured human fibroblasts with different repair capacities

International Nuclear Information System (INIS)

Fujiwara, Yoshisada; Kano, Yoshio; Paul, P.; Goto, Kaoru; Yamamoto, Kazuo

1981-01-01

Xeroderma pigmentosum (XP) groups A to G lacked the initial stage of ultraviolet (UV) excision repair in the order of A = G > C > D > E asymptotically equals F, while the XP variant was weakly defective in the later repair steps. Killing sensitivities were in the orders of A >= G > D > C > E asymptotically equals F asymptotically equals variant > normal to UV, A = G > D > F > C = E > variant > normal to 4-nitroquinoline-1-oxide (4NQO), and A > C > D = E = F = variant > G = normal to decarbamoyl mitomycin-C(DCMC). The induced sister chromatid exchange (SCE) frequency was unrelated to the extent of repair deficiency. The SCE induction rate was consistently 3 - 6 fold higher by these UV-like mutagens in XP group A cells than in normal cells. However, repair-proficient Cockayne's syndrome (CS) cells showed a higher SCE induction by UV, which was normalized by NAD + , suggesting that chromatin lesions as well as DNA damage contribute to SCE. Two-step crosslink repair involves a first rapid half-excision and a second slow nucleotide-excision repair. Fanconi's anemia (FA) cells had an impaired first half-excision and were supersensitive to MC, but not to UV and DCMC. The SCE frequency induced by MC (1 hr) was higher in FA cells than in normal cells despite their normal response to DCMC, and vice versa in XP cells. FA cells lacked the first rapid decline and showed higher remaining SCEs. Thus, part of the crosslink seems to lead to SCE formation. Caffeine synergistically elevated UV-induced SCEs, but not UV induced mutations in V79 cells, implying that SCE may not necessarily involve mutation. (J.P.N.)

Excision and crosslink repair of DNA and sister chromatid exchanges in cultured human fibroblasts with different repair capacities

Energy Technology Data Exchange (ETDEWEB)

Fujiwara, Y.; Kano, Y.; Paul, P.; Goto, K.; Yamamoto, K. (Kobe Univ. (Japan). School of Medicine)

1981-01-01

Xeroderma pigmentosum (XP) groups A to G lacked the initial stage of ultraviolet (UV) excision repair in the order of A = G > C > D > E asymptotically equals F, while the XP variant was weakly defective in the later repair steps. Killing sensitivities were in the orders of A >= G > D > C > E asymptotically equals F asymptotically equals variant > normal to UV, A = G > D > F > C = E > variant > normal to 4-nitroquinoline-1-oxide (4NQO), and A > C > D = E = F = variant > G = normal to decarbamoyl mitomycin-C(DCMC). The induced sister chromatid exchange (SCE) frequency was unrelated to the extent of repair deficiency. The SCE induction rate was consistently 3 - 6 fold higher by these UV-like mutagens in XP group A cells than in normal cells. However, repair-proficient Cockayne's syndrome (CS) cells showed a higher SCE induction by UV, which was normalized by NAD/sup +/, suggesting that chromatin lesions as well as DNA damage contribute to SCE. Two-step crosslink repair involves a first rapid half-excision and a second slow nucleotide-excision repair. Fanconi's anemia (FA) cells had an impaired first half-excision and were supersensitive to MC, but not to UV and DCMC. The SCE frequency induced by MC (1 hr) was higher in FA cells than in normal cells despite their normal response to DCMC, and vice versa in XP cells. FA cells lacked the first rapid decline and showed higher remaining SCEs. Thus, part of the crosslink seems to lead to SCE formation. Caffeine synergistically elevated UV-induced SCEs, but not UV induced mutations in V79 cells, implying that SCE may not necessarily involve mutation.

Sister chromatid exchanges in the bone marrow cells of in vivo rats induced by gamma radiation and chemical mutagens

International Nuclear Information System (INIS)

Rodriguez R, R.G.

1981-01-01

Sister chromatid exchanges (SCE) in the bone marrow of in vivo rats induced by gamma radiation doses and by the chemical mutagens, mitomycin C (MMC), cyclophosphamide (CP), and sulphonate-methylmethane (SMM), were studied. The purpose was to evaluate the sensitivity and reproducibility of a simplified SCE in vivo detecting system developed in our laboratory and to compare the results obtained with those reported elsewhere. Simplification consisted in administering the amounts of 5-bromo-2'-deoxyuridine (BrdU) necessary to observe the SCE, after first adsorbing the BrdU in activated carbon and then injecting it interperitoneally, into the rats. The results were a longer time in vivo ADN incorporation without convulsions in the rats, and a reduction in the time course as compared to other methods. We observed a basal rate of 3.6+-0.37 SCE/cell and that: 0.44 Gy of gamma radiation induced 7.7+-0.73 SCE/cell; 1.6 μg/g of MMC induced 8.1+-1.20 SCE/cell; 5 μg/g of CP induced 8.25+-1.5 SCE/cell, 40 μg/g of SMM induced 22.0+-5 SCE/cell and 380 μg/g of sulphonate-ethylmethane induced 8.6+-1.2 SCE/cell. This showed that all the agents were capable of inducing SCE in the bone marrow cells of rats in vivo under our conditions. We noted a greater induced efficiency for gamma radiation than the obtained by other investigators and a relatively similar efficiency in the case of chemical mutagens as reported in other studies. (author)

Characterization of the enhancing effect of caffeine on sister-chromatid exchanges induced by ultraviolet radiation in excision-proficient xeroderma pigmentosum lymphoblastoid cells

International Nuclear Information System (INIS)

Thoda, Hiroko; Oikawa, Atsushi

1988-01-01

Cells of some excision-proficient xeroderma pigmentosum (XP) cell lines are highly sensitive to post-UV caffeine treatment in terms of sister-chromatid exchange (SCE) induction as well as cell lethality. In the present study, the authors conducted a detailed investigation of the enhancing effect of caffeine on SCE frequency induced by UV in excision-proficient XP cells, and obtained the following results. (1). Continuous post-UV treatment with 1mM caffeine markedly enhances UV-induced SCEs and such enhanced SCEs occur with similar frequency during either the 1st or the 2nd cell cycle in the presence of caffeine and 5-bromodeoxyuridine (BrdUrd). (2) The high sensitivity of the cells to post-UV caffeine treatment persists for at least 2 days after UV when irradiated cells are held in either the proliferating of the nonproliferating state prior to the addition of BrdUrd. (3) Caffeine exerts its effect on cells in S phase. The most likely explanation for our findings is as follows. In excision-proficient XP cells, the cause of SCE formation such as UV-induced lesions or resulting perturbations of DNA replication persists untill the 2nd round or more of post-UV DNA replication. If caffeine is given as post-UV treatment, such abnormalities may be amplified, resulting in a synergistic increase in SCE frequency. (author). 21 refs.; 4 figs.; 4 tabs

Cytotoxicity and genotoxicity of UVA irradiation in Chinese hamster ovary cells measured by specific locus mutations, sister chromatid exchanges and chromosome aberrations

International Nuclear Information System (INIS)

Lundgren, Karsten; Wulf, H.C.

1988-01-01

The increasing use of artificial UVA (320-400 nm) suntanning devices has brought attention to possible hazardous effects of UVA. In contrast with earlier studies, several groups recently have described that UVA possibly is mutagenic. We evaluate the genotoxic properties of broad band UVA using CHO cells and three different assays: specific locus (HGPRT) mutations, chromosome aberrations, and sister chromatid exchanges (SCEs). The UVA-source was an UVASUN 2000 S (Mutzhas), emitting UVA above 340 nm. The survival curve of the cells exhibited a shoulder up to 200 kJ/m 2 , that was followed by exponential killing at higher fluences. Mutations were induced linearly in the fluence range of 0-200 kJ/m 2 to a level seven fold higher than the spontaneous, followed by a decrease at fluences above 300 kJ/m 2 . Over the total range of tested fluences (0-300 kJ/m 2 ) a linear dose-response relationship was observed for UVA-induced SCEs. A significantly higher percentage of the cells showed chromosomes with aberrations at the higher levels of exposure (200, 300 and 400 kJ/m 2 ), but no dose response was demonstrated. Our results confirm recent findings showing that UVA is mutagenic in mammalian cells and suggest that UVA exposure may contribute to the total burden of genetic damage caused by exposure to ultraviolet light. (author)

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

Science.gov (United States)

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.

Effects of a tumor promoter and an anti-promoter on spontaneous and UV-induced 6-thioguanine-resistant mutations and sister-chromatid exchanges in V79 Chinese hamster cells

International Nuclear Information System (INIS)

Fujiwara, Y.; Kano, Y.; Tatsumi, M.; Paul, P.

1980-01-01

The effects of a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or an anti-promoter antipain (protease inhibitor) on spontaneous and ultraviolet-induced sister-chromatid exchanges (SCEs) and 6-thioguanine-resistant (6TGsup(r)) recessive mutations were examined in V79 Chinese hamster cells in culture. TPA and/or antipain neither significantly altered base-line and UV-induced immediate SCE frequencies, nor decreased the level of delayed SCEs which persisted 6-7 days after irradiation. TPA and/or antipain appeared to enhance the recovery of UV-induced 6TGsup(r) colonies at the plateau expression phase despite non-mutagenicity by themselves and unaltered metabolic cooperation. Thus, the results conceivably imply that the 6TGsup(r)-recessive mutation expression, but not fixation, can be modulated at the cell level by TPA and/or antipain. Our results, together with the recent results of Loveday and Latt, may argue against the notion that TPA enhances the antipain-suppressible SCEs as an index of mitotic recombination in relevance with a tumor-promotion mechanism. (orig.)

Absence of SUN-domain protein Slp1 blocks karyogamy and switches meiotic recombination and synapsis from homologs to sister chromatids

Science.gov (United States)

Vasnier, Christelle; de Muyt, Arnaud; Zhang, Liangran; Tessé, Sophie; Kleckner, Nancy E.; Zickler, Denise; Espagne, Eric

2014-01-01

Karyogamy, the process of nuclear fusion is required for two haploid gamete nuclei to form a zygote. Also, in haplobiontic organisms, karyogamy is required to produce the diploid nucleus/cell that then enters meiosis. We identify sun like protein 1 (Slp1), member of the mid–Sad1p, UNC-84–domain ubiquitous family, as essential for karyogamy in the filamentous fungus Sordaria macrospora, thus uncovering a new function for this protein family. Slp1 is required at the last step, nuclear fusion, not for earlier events including nuclear movements, recognition, and juxtaposition. Correspondingly, like other family members, Slp1 localizes to the endoplasmic reticulum and also to its extensions comprising the nuclear envelope. Remarkably, despite the absence of nuclear fusion in the slp1 null mutant, meiosis proceeds efficiently in the two haploid “twin” nuclei, by the same program and timing as in diploid nuclei with a single dramatic exception: the normal prophase program of recombination and synapsis between homologous chromosomes, including loading of recombination and synaptonemal complex proteins, occurs instead between sister chromatids. Moreover, the numbers of recombination-initiating double-strand breaks (DSBs) and ensuing recombinational interactions, including foci of the essential crossover factor Homo sapiens enhancer of invasion 10 (Hei10), occur at half the diploid level in each haploid nucleus, implying per-chromosome specification of DSB formation. Further, the distribution of Hei10 foci shows interference like in diploid meiosis. Centromere and spindle dynamics, however, still occur in the diploid mode during the two meiotic divisions. These observations imply that the prophase program senses absence of karyogamy and/or absence of a homolog partner and adjusts the interchromosomal interaction program accordingly. PMID:25210014

Suppression of topoisomerase IIα expression and function in human cells decreases chromosomal radiosensitivity

International Nuclear Information System (INIS)

Terry, Samantha Y.A.; Riches, Andrew C.; Bryant, Peter E.

2009-01-01

The mechanism behind chromatid break formation is as yet unclear, although it is known that DNA double-strand breaks (DSBs) are the initiating lesions. Chromatid breaks formed in cells in the G2-phase of the cell-cycle disappear ('rejoin') as a function of time between radiation exposure and cell fixation. However, the kinetics of disappearance of chromatid breaks does not correspond to those of DSB rejoining, leading us to seek alternative models. We have proposed that chromatid breaks could be formed indirectly from DSB and that the mechanism involves topoisomerase IIα. In support of this hypothesis we have recently shown that frequencies of radiation-induced chromatid breaks are lower in two variant human promyelocytic leukaemic cell lines with reduced topoisomerase IIα expression. Here we report that suppression of topoisomerase IIα in human hTERT-RPE1 cells, either by its abrogation using specific siRNA or by inhibition of its catalytic activity with the inhibitor ICRF-193, causes a reduction in frequency of chromatid breaks in radiation-exposed cells. The findings support our hypothesis for the involvement of topoisomerase IIα in the formation of radiation-induced chromatid breaks, and could help explain inter-individual variation in human chromosomal radiosensitivity; elevation of which has been linked with cancer susceptibility.

DNA asymmetry in stem cells - immortal or mortal?

Science.gov (United States)

Yadlapalli, Swathi; Yamashita, Yukiko M

2013-09-15

The immortal strand hypothesis proposes that stem cells retain a template copy of genomic DNA (i.e. an 'immortal strand') to avoid replication-induced mutations. An alternative hypothesis suggests that certain cells segregate sister chromatids non-randomly to transmit distinct epigenetic information. However, this area of research has been highly controversial, with conflicting data even from the same cell types. Moreover, historically, the same term of 'non-random sister chromatid segregation' or 'biased sister chromatid segregation' has been used to indicate distinct biological processes, generating a confusion in the biological significance and potential mechanism of each phenomenon. Here, we discuss the models of non-random sister chromatid segregation, and we explore the strengths and limitations of the various techniques and experimental model systems used to study this question. We also describe our recent study on Drosophila male germline stem cells, where sister chromatids of X and Y chromosomes are segregated non-randomly during cell division. We aim to integrate the existing evidence to speculate on the underlying mechanisms and biological relevance of this long-standing observation on non-random sister chromatid segregation.

Effect of interleukin-2 on cell proliferation, sister-chromatid exchange induction, and nuclear stress protein phosphorylation in PHA-stimulated Fischer 344 rat spleen lymphocytes: Modulation by 2-mercaptoethanol

Energy Technology Data Exchange (ETDEWEB)

Morris, S.M.; Aidoo, A.; Domon, O.E.; McGarrity, L.J.; Kodell, R.L.; Schol, H.M.; Hinson, W.G.; Pipkin, J.L.; Casciano, D.A. (National Center for Toxicological Research, Jefferson, AR (USA))

1990-01-01

The effect of interleukin-2 (IL-2) on cell proliferation, sister-chromatid exchange (SCE) frequency, and the phosphorylation of nuclear stress proteins was evaluated in phytohemagglutinin (PHA)-stimulated spleen lymphocytes isolated from Fischer 344 rats. In addition, the ability of 2-mercaptoethanol (2-ME) to modulate the induction of these biological responses was characterized. Cell proliferation, as measured by the mitotic index, increased significantly. The average generation time (AGT) did not respond to IL-2 in a concentration-dependent manner and decreased significantly. The number of SCE increased significantly from control frequencies, to frequencies of 18.5 to 21.5 SCE per cell as the concentration of IL-2 in the culture medium increased to 50 half-maximal units per ml. A reduction in SCE frequency was observed when cells were cultured with 20 {mu}M 2-ME and IL-2 compared to IL-2 alone. Three nuclear proteins, with relative molecular masses of approximately 13,000-18,000, 20,000, and 80,000, were phosphorylated in IL-2-exposed G{sub 1}-phase nuclei. Elicitation of these nuclear proteins in IL-2-exposed cells was not affected by exposure to 2-ME.

Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo

International Nuclear Information System (INIS)

Toribio E, E.

2005-01-01

The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

Variation in the human lymphocyte sister chromatid exchange frequency as a function of time: results of daily and twice-weekly sampling

Energy Technology Data Exchange (ETDEWEB)

Tucker, J.D.; Christensen, M.L.; Strout, C.L.; McGee, K.A.; Carrano, A.V.

1987-01-01

The variation in lymphocyte sister chromatid exchange (SCE) frequency was investigated in healthy nonsmokers who were not taking any medication. Two separate studies were undertaken. In the first, blood was drawn from four women twice a week for 8 weeks. These donors recorded the onset and termination of menstruation and times of illness. In the second study, blood was obtained from two women and two men for 5 consecutive days on two separate occasions initiated 14 days apart. Analysis of the mean SCE frequencies in each study indicated that significant temporal variation occurred in each donor, and that more variation occurred in the longer study. Some of the variation was found to be associated with the menstrual cycle. In the daily study, most of the variation appeared to be random, but occasional day-to-day changes occurred that were greater than those expected by chance. To determine how well a single SCE sample estimated the pooled mean for each donor in each study, the authors calculated the number of samples that encompassed that donor's pooled mean within 1 or more standard errors. For both studies, about 75% of the samples encompassed the pooled mean within 2 standard errors. An analysis of high-frequency cells (HFCs) was also undertaken. The results for each study indicate that the proportion of HFCs, compared with the use of Fisher's Exact test, is significantly more constant than the means, which were compared by using the t-test. These results coupled with our previous work suggest that HFC analysis may be the method of choice when analyzing data from human population studies.

Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers.

Science.gov (United States)

Kumar, Anil; Yadav, Anita; Giri, Shiv Kumar; Dev, Kapil; Gautam, Sanjeev Kumar; Gupta, Ranjan; Aggarwal, Neeraj

2011-07-01

In the present study, we have investigated the influence of polymorphism of GSTM1 and GSTT1 genes and confounding factors such as age, sex, exposure duration and consumption habits on cytogenetic biomarkers. Frequency of sister chromatid exchanges (SCEs), high frequency cell (HFC) and cytokinesis blocked micronuclei (CBMN) were evaluated in peripheral blood lymphocytes of 115 occupationally exposed road construction workers and 105 unexposed individuals. The distribution of null and positive genotypes of glutathione-S transferase gene was evaluated by multiplex PCR among control and exposed subjects. An increased frequency of CBMN (7.03±2.08); SCE (6.95±1.76) and HFC (6.28±1.69) were found in exposed subjects when compared to referent (CBMN - 3.35±1.10; SCE - 4.13±1.30 and HFC - 3.98±1.56). These results were found statistically significant at p<0.05. When the effect of confounding factors on the frequency of studied biomarkers was evaluated, a strong positive interaction was found. The individuals having GSTM1 and GSTT1 null genotypes had higher frequency of CBMN, SCE and HFC. The association between GSTM1 and GSTT1 genotypes and studied biomarkers was found statistically significant at p<0.05. Our findings suggest that individuals having null type of GST are more susceptible to cytogenetic damage by occupational exposure regardless of confounding factors. There is a significant effect of polymorphism of these genes on cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

As to the clastogenic-, sister-chromatid exchange inducing-and cytotoxic activity of inosine triphosphate in cultures of human peripheral lymphocytes.

Science.gov (United States)

Vormittag, W; Brannath, W

2001-05-09

The influence of commercial inosine triphosphate (ITP) on the chromosome aberration rate, the mitotic rate, sister-chromatid exchange (SCE) frequency, and the proportion of first (X1), second (X2) and third (X3) division metaphases was investigated in 72h cultures of human peripheral lymphocytes. The blood donors had mild inactive arthrosis and a normal health check-up. All cultures of each volunteer were set-up simultaneously. In contrast to a previous report [Arch. Biochem. Biophys. 278 (1990) 238-244], it was demonstrated in two preliminary studies (number of subjects, n=5 each) that ITP at a final concentration of 100 microM does not induce chromosomal aberrations and, furthermore, that not ITP concentrations higher than 100 microM but ITP doses higher than 3.8mM prohibit culture growth. Based on these results, cultures with a final ITP concentration of 3.6mM (max.) and 1.8mM (max./2) were compared with control cultures (number of subjects n=10; three males and seven females, mean age x=57.6 years). Whereas no increase in the chromosomal breakage rate was observed in cultures with an ITP concentration of 1.8mM and only a marginally significant one (P=0.048) for 3.6mM ITP cultures, a highly significant induction of SCEs, not only at an ITP concentration of 3.6mM (Prate from 0 to 1.8mM as well as from 1.8 to 3.6mM in the aberration studies (all P values are equal to smallest possible one for a sample size of 10, namely, 0.002), and in the SCE studies there is a significant decrease in the X3 frequency when ITP is increased (0-1.8mM: P=0.0061 and 1.8-3.6mM: Pchanges significantly only at the second dose step (0-1.8mM ITP: P=0.22 and 1.8-3.6mM ITP: P<0.0001). The results are discussed.

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

International Nuclear Information System (INIS)

Terzoudi, Georgia I.; Hatzi, Vasiliki I.; Donta-Bakoyianni, Catherine; Pantelias, Gabriel E.

2011-01-01

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

Evidence that cyclophosphamide can to induce exchanges in the sister chromatids (ICH) through secondary injuries; Evidencia de que la ciclofosfamida puede inducir intercambios en las cromatidas hermanas (ICH) a traves de lesiones secundarias

Energy Technology Data Exchange (ETDEWEB)

Morales R, P.; Rodriguez R, R. [Instituto Nacional de Investigaciones nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

1997-07-01

By means of the use of destination protocol of ICH inductive injuries (DLI-ICH), it was studied if interchanges in the sister chromatids (ICH) induced by cyclophosphamide (CP), in the second post-treatment division (ICH-2) are produced by secondary injuries or by fresh injuries. For discard between these possibilities it was administered CP at different periods before of the first post-treatment division, taking as reference the administered time for high dose of bromodeoxyuridine (BrdU ) which was approximately at the beginning of this division. The ICH frequencies that occur in the first, the second and the third synthesis stages (S) were determined. It was observed that when the administered CP was four hours before BrdU , the ICH frequencies of the second and the third S were reduced. The frequency of the first ICH increased lightly in relation to those of the normal protocol (0.5 h before BrdU ) and that the supplying of CP six hours before caused almost a total reduction of ICH of second and third S and an important increment of ICH of first S.This was interpreted as evidence that the ICH-2 are product of secondary injuries. (Author)

Chiasmatic and achiasmatic inverted meiosis of plants with holocentric chromosomes

Science.gov (United States)

Cabral, Gabriela; Marques, André; Schubert, Veit; Pedrosa-Harand, Andrea; Schlögelhofer, Peter

2014-01-01

Meiosis is a specialized cell division in sexually reproducing organisms before gamete formation. Following DNA replication, the canonical sequence in species with monocentric chromosomes is characterized by reductional segregation of homologous chromosomes during the first and equational segregation of sister chromatids during the second meiotic division. Species with holocentric chromosomes employ specific adaptations to ensure regular disjunction during meiosis. Here we present the analysis of two closely related plant species with holocentric chromosomes that display an inversion of the canonical meiotic sequence, with the equational division preceding the reductional. In-depth analysis of the meiotic divisions of Rhynchospora pubera and R. tenuis reveals that during meiosis I sister chromatids are bi-oriented, display amphitelic attachment to the spindle and are subsequently separated. During prophase II, chromatids are connected by thin chromatin threads that appear instrumental for the regular disjunction of homologous non-sister chromatids in meiosis II. PMID:25295686

Detection of Ultrafine Anaphase Bridges

DEFF Research Database (Denmark)

Bizard, Anna H; Nielsen, Christian F; Hickson, Ian D

2018-01-01

Ultrafine anaphase bridges (UFBs) are thin DNA threads linking the separating sister chromatids in the anaphase of mitosis. UFBs are thought to form when topological DNA entanglements between two chromatids are not resolved prior to anaphase onset. In contrast to other markers of defective...

Strand-seq : A unifying tool for studies of chromosome segregation

NARCIS (Netherlands)

Falconer, Ester; Lansdorp, Peter M.

2013-01-01

Non random segregation of sister chromatids has been implicated to help specify daughter cell fate (the Silent Sister Hypothesis [1]) or to protect the genome of long-lived stem cells (the Immortal Strand Hypothesis [2]). The idea that sister chromatids are non-randomly segregated into specific

The chromosome damage induced by x-ray radiation doses. Comparison between dicentric chromosomes, micronuclei and Sister Chromatid Exchanges analyses. Valoracion de dao cromosomico originado por una dosis de rayos X. Comparacion de los analisis de cromosomas dicentricos, micronucleos e intercambios entre cromatidas hermanas

Energy Technology Data Exchange (ETDEWEB)

Fernandez, J.L.; Losada, C.; Losada, G.; Veiras, C. (Centro Oncologico de Galicia. La Corua (Spain)); Goyanes, V.J. (Hospital ' ' Teresa Herrera' ' . La Corua (Spain))

1993-01-01

Exposure to ionizing radiations is a well-known source of chromosome damage. Here we present a comparison among three different methodologies employed to recognize cytogenetic damage, after an acute exposure of human lymphocytes to 3 Gy of X-rays (100kVp). Scoring of dicentric chromosomes, present in first mitosis ''in vitro'', was the method of preference as dicentrics increased 937.5 times with respect to background. Micronucleus scoring in binucleated-cytokinesis blocked cells showed an increase of 32.5 times, while it was only of 1.46 times when Sister Chromatid Exchanges (SCEs) were analyzed. The estimated probability of an acentric fragment becoming a micronucleus was around 0.25. Intercellular distribution of dicentrics agree with Poisson, while micronucleus were overdispersed. When analyzed at second cycle after damage induction, the dicentrics yield as well as the level of cells with unstable cromosome aberrations, decreased around a half. Finally, SCEs level was similar in cells with or without unstable structural chromosome aberrations. (Author)

SOLO: a meiotic protein required for centromere cohesion, coorientation, and SMC1 localization in Drosophila melanogaster.

Science.gov (United States)

Yan, Rihui; Thomas, Sharon E; Tsai, Jui-He; Yamada, Yukihiro; McKee, Bruce D

2010-02-08

Sister chromatid cohesion is essential to maintain stable connections between homologues and sister chromatids during meiosis and to establish correct centromere orientation patterns on the meiosis I and II spindles. However, the meiotic cohesion apparatus in Drosophila melanogaster remains largely uncharacterized. We describe a novel protein, sisters on the loose (SOLO), which is essential for meiotic cohesion in Drosophila. In solo mutants, sister centromeres separate before prometaphase I, disrupting meiosis I centromere orientation and causing nondisjunction of both homologous and sister chromatids. Centromeric foci of the cohesin protein SMC1 are absent in solo mutants at all meiotic stages. SOLO and SMC1 colocalize to meiotic centromeres from early prophase I until anaphase II in wild-type males, but both proteins disappear prematurely at anaphase I in mutants for mei-S332, which encodes the Drosophila homologue of the cohesin protector protein shugoshin. The solo mutant phenotypes and the localization patterns of SOLO and SMC1 indicate that they function together to maintain sister chromatid cohesion in Drosophila meiosis.

[The results of a cytogenetic examination of children who were victims of the accident at the Chernobyl Atomic Electric Power Station and who reside in an ecologically unfavorable region].

Science.gov (United States)

Frolov, V M; Baryliak, I R; Peresadin, M O; Khrypko, S V; Kuziuberdina, K M

1994-01-01

It has been detected that children evacuated from the zone with the elevated radioactivity level have the increased number of chromosomal and chromatid aberrations. The frequency of chromatid aberrations is 2.1-fold lower in country-side children than in children from industrial towns. Cytogenetic disturbances in immunocompetent cells correlate with the level of immune imbalance. Children born in families of liquidators of the ChNPP accident in the first year after their return from the accident zone have substantial cytogenetic and immune disturbances. Children living near sources of atmospheric pollution are characterized by the 3-4-fold increase in frequencies of chromatid anomalies and by the development of a pronounced immunodeficiency.

Repair of chromosome damage induced by X-irradiation during G2 phase in a line of normal human fibroblasts and its malignant derivative

International Nuclear Information System (INIS)

Parshad, R.; Gantt, R.; Sanford, K.K.; Jones, G.M.; Tarone, R.E.

1982-01-01

A line of normal human skin fibroblasts (KD) differed from its malignant derivative (HUT-14) in the extent of cytogenetic damage induced by X-irradiation during G2 phase. Malignant cells had significantly more chromatid breaks and gaps after exposure to 25, 50, or 100 rad. The gaps may represent single-strand breaks. Results from alkaline elution of cellular DNA immediately after irradiation showed that the normal and malignant cells in asynchronous population were equally sensitive to DNA single-strand breakage by X-irradiation. Caffeine or beta-cytosine arabinoside (ara-C), inhibitors of DNA repair, when added directly following G2 phase exposure, significantly increased the incidence of radiation-induced chromatid damage in the normal cells. In contrast, similar treatment of the malignant cells had little influence. Ara-C differed from caffeine in its effects; whereas both agents increased the frequency of chromatid breaks and gaps, only ara-C increased the frequency of gaps to the level observed in the irradiated malignant cells. Addition of catalase, a scavenger of the derivative free hydroxyl radical (.OH), to the cultures of malignant cells before, during, and following irradiation significantly reduced the chromatid damage; and catalase prevented formation of chromatid gaps. The DNA damage induced by X-ray during G2 phase in the normal KD cells was apparently repaired by a caffeine- and ara-C-sensitive mechanism(s) that was deficient or absent in their malignant derivatives

Repair of chromosome damage induced by X-irradiation during G2 phase in a line of normal human fibroblasts and its malignant derivative

International Nuclear Information System (INIS)

Parshad, R.; Gantt, R.; Sanford, K.K.; Jones, G.M.; Tarone, R.E.

1982-01-01

A line of normal human skin fibroblasts (KD) differed from its malignant derivative (HUT-14) in the extent of cytogenetic damage induced by X-irradiation during G 2 phase. Malignant cells had significantly more chromatid breaks and gaps after exposure to 25, 50, or 100 rad. Results from alkaline elution of cellular DNA immediately after irradiation showed that the normal and malignant cells in asynchronous population were equally sensitive to DNA single-strand breakage by X-irradiation. Caffeine or #betta#-cytosine arabinoside (ara-C), inhibitors of DNA repair, when added directly following G 2 phase exposure, significantly increased the incidence of radiation-induced chromatid damage in the normal cells. In contrast, similar treatment of the malignant cells had little influence. Ara-C differed from caffeine in its effects; whereas both agents increased the frequency of chromatid breaks and gaps, only ara-C increased the frequency of gaps to the level observed in the irradiated malignant cells. Addition of catalase, which destroys H 2 O 2 , or mannitol, a scavenger of the derivative free hydroxyl radical (.OH), to the cultures of malignant cells before, during, and following irradiation significantly reduced the chromatid damage; and catalase prevented formation of chromatid gaps. The DNA damage induced by X-ray during G 2 phase in the normal KD cells was apparently repaired by a caffeine- and ara-C-sensitive mechanism(s) that was deficient or absent in their malignant derivatives

Characterization of muntjac DNA

International Nuclear Information System (INIS)

Davis, R.C.

1981-01-01

Sister chromatid exchange (SCE) in muntjac chromosomes is generally proportional to the chromosomal DNA content, but the SCE frequency is reduced in the heterochromatic neck region of the X chromosome. The physical properties of muntjac DNA and the kinetics of repair of UV damage in muntjac heterochromatin and euchromatin were examined and compared with the distribution of sister chromatid exchange

Characterization of muntjac DNA

Energy Technology Data Exchange (ETDEWEB)

Davis, R.C.

1981-05-27

Sister chromatid exchange (SCE) in muntjac chromosomes is generally proportional to the chromosomal DNA content, but the SCE frequency is reduced in the heterochromatic neck region of the X chromosome. The physical properties of muntjac DNA and the kinetics of repair of UV damage in muntjac heterochromatin and euchromatin were examined and compared with the distribution of sister chromatid exchange.

Sister chromatid exchanges and high-frequency cells in men environmentally and occupationally exposed to ambient air pollutants. An intergroup comparison with respect to seasonal changes and smoking habit

Energy Technology Data Exchange (ETDEWEB)

Pendzich, Joanna; Motykiewicz, Grazyna; Michalska, Jadwiga; Kostowska, Alina; Chorazy, Mieczyslaw [Department of Tumor Biology, Institute of Oncology, Gliwice (Poland); Wang, Li You [Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei (Taiwan, Province of China)

1997-11-28

Sister chromatid exchanges (SCE) and high-frequency cells (HFC) were measured in peripheral blood lymphocytes from men environmentally and occupationally exposed to a mixture of ambient air pollutants. The environmentally exposed individuals were inhabitants of the industrial region of Upper Silesia; those occupationally exposed were Silesian cokery or steel plant workers, while the control group consisted of rural region residents. A total of 147 males were enrolled in the study. Blood samples were collected in winter (February) and summer (September) seasons. Three major areas were investigated during the study: exposure-based dose dependency, seasonal changes, and influence of smoking habits on the SCE frequencies. The latter is frequently reported as a confounding factor in SCE analyses. In both winter and summer samples, statistically significant increases of SCE were observed in the environmentally and occupationally exposed groups compared to the controls (p<0.001). The difference between both exposed groups was also significant (p<0.001). An intergroup comparison was based on ANOVA after adjustment for smoking status. In all three groups of interest, a seasonal variation was found with higher levels in winter. However, in a part of the study in which each donor served as his own control, statistical differences were only found within the exposed groups. Control region inhabitants did not have significantly higher frequencies of SCE in winter, compared to summer samples. The impact of two major confounders, age of the donor and smoking habit, was investigated by multiple regression analysis. Smoking was a major factor influencing the level of SCE. Nevertheless, the effect was seen in winter samples only, which suggests an additive response and adds new information to this known effect

DNA damage in the kidney tissue cells of the fish Rhamdia quelen after trophic contamination with aluminum sulfate

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Tatiane Klingelfus

2015-01-01

Full Text Available Abstract Even though aluminum is the third most common element present in the earth's crust, information regarding its toxicity remains scarce. It is known that in certain cases, aluminum is neurotoxic, but its effect in other tissues is unknown. The aim of this work was to analyze the genotoxic potential of aluminum sulfate in kidney tissue of the fish Rhamdia quelen after trophic contamination for 60 days. Sixty four fish were subdivided into the following groups: negative control, 5 mg, 50 mg and 500 mg of aluminum sulfate per kg of fish. Samples of the posterior kidney were taken and prepared to obtain mitotic metaphase, as well as the comet assay. The three types of chromosomal abnormalities (CA found were categorized as chromatid breaks, decondensation of telomeric region, and early separation of sister chromatids. The tests for CA showed that the 5 mg/kg and 50 mg/kg doses of aluminum sulfate had genotoxic potential. Under these treatments, early separation of the sister chromatids was observed more frequently and decondensation of the telomeric region tended to increase in frequency. We suggest that structural changes in the proteins involved in DNA compaction may have led to the decondensation of the telomeric region, making the DNA susceptible to breaks. Moreover, early separation of the sister chromatids may have occurred due to changes in the mobility of chromosomes or proteins that keep the sister chromatids together. The comet assay confirmed the genotoxicity of aluminum sulfate in the kidney tissue of Rhamdia quelen at the three doses of exposure.

Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

Science.gov (United States)

Hopkins, Jessica; Hwang, Grace; Jacob, Justin; Sapp, Nicklas; Bedigian, Rick; Oka, Kazuhiro; Overbeek, Paul; Murray, Steve; Jordan, Philip W

2014-07-01

Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3) proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG) protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β), two α-kleisins (RAD21L and REC8) and one STAG protein (STAG3) that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC). From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8) is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis-specific cohesin

Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

Directory of Open Access Journals (Sweden)

Jessica Hopkins

2014-07-01

Full Text Available Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3 proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β, two α-kleisins (RAD21L and REC8 and one STAG protein (STAG3 that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC. From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8 is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis

Sister kinetochores are mechanically fused during meiosis I in yeast.

Science.gov (United States)

Sarangapani, Krishna K; Duro, Eris; Deng, Yi; Alves, Flavia de Lima; Ye, Qiaozhen; Opoku, Kwaku N; Ceto, Steven; Rappsilber, Juri; Corbett, Kevin D; Biggins, Sue; Marston, Adèle L; Asbury, Charles L

2014-10-10

Production of healthy gametes requires a reductional meiosis I division in which replicated sister chromatids comigrate, rather than separate as in mitosis or meiosis II. Fusion of sister kinetochores during meiosis I may underlie sister chromatid comigration in diverse organisms, but direct evidence for such fusion has been lacking. We used laser trapping and quantitative fluorescence microscopy to study native kinetochore particles isolated from yeast. Meiosis I kinetochores formed stronger attachments and carried more microtubule-binding elements than kinetochores isolated from cells in mitosis or meiosis II. The meiosis I-specific monopolin complex was both necessary and sufficient to drive these modifications. Thus, kinetochore fusion directs sister chromatid comigration, a conserved feature of meiosis that is fundamental to Mendelian inheritance. Copyright © 2014, American Association for the Advancement of Science.

The centenary of Janssens's chiasmatype theory.

Science.gov (United States)

Koszul, Romain; Meselson, Matthew; Van Doninck, Karine; Vandenhaute, Jean; Zickler, Denise

2012-06-01

The segregation and random assortment of characters observed by Mendel have their basis in the behavior of chromosomes in meiosis. But showing this actually to be the case requires a correct understanding of the meiotic behavior of chromosomes. This was achieved only gradually, over several decades, with much dispute and confusion along the way. One crucial step in the understanding of meiosis was provided in 1909 by Frans Alfons Janssens who published in La Cellule an article entitled "La théorie de la Chiasmatypie. Nouvelle interprétation des cinèses de maturation," which contains the first description of the chiasma structure. He observed that, of the four chromatids present at the connection sites (chiasmata sites) at diplotene or anaphase of the first meiotic division, two crossed each other and two did not. He therefore postulated that the maternal and paternal chromatids that crossed penetrated the other until they broke and rejoined in maternal and paternal segments new ways; the other two chromatids remained free and thus intact. This allowed him also to propose that the chromatids distributed in the four nuclei issued from the second meiotic division had various combinations of maternal and paternal segments of each chromosome. And conversely, permitted the appreciation that the laws of Mendelian segregation required breakage and joining (crossing over) between homologous non-sister chromatids. Although Janssens's article found a broad appreciative audience and had a large influence on the chromosomal theory at that time, his theory was resisted by both geneticists and cytologists for several decades. This Perspectives aims to highlight the novelty of Janssens's chiasmatype theory by examining the historical background and our actual understanding of meiotic recombination.

Stage specificity and dose-response relationships for chromosome aberrations induced in mouse primary spermatocytes following X-irradiation

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Y.; Tobari, I.; Utsugi, T.

1986-05-01

In this study, dose-response relationships were examined for chromosome aberrations observed at diakinesis-metaphase I of spermatocytes with X-irradiation at various stages of meiosis (diplotene, mid-pachytene, zygotene and leptotene). The frequencies of cells with X-ray-induced chromosome aberrations increased with dose at all stages in the applied range of 0.5-3.0 Gy and tended to increase as the irradiated stages descended after leptotene stage. In three stages, the frequencies increased exponentially with dose, but the rates of induction of chromosome breaks were markedly different depending on the stages at which spermatocytes were irradiated with X-rays. The rate of induction was the highest at diplotene and the lowest at leptotene, suggesting that diplotene spermatocytes had the highest radiosensitivity to the induction of chromosome breaks, followed by pachytene, zygotene and leptotene spermatocytes in that order. The dose-response relationships fitted well to linear equations for deletion-type aberrations at each stage, and to linear-quadratic equations for exchange-type aberrations at all stages except for leptotene. At leptotene, the chromatid exchanges were hardly observed, the aberrations being mainly consisted of iso-chromatid fragments. On the contrary, chromatid exchanges and iso-chromatide deletions were mainly observed at later stages (zygotene-diplotene).

Possible role of protein damages in the origin of UV-induced isochromatid breaks

International Nuclear Information System (INIS)

Lebedeva, L.I.; Ostrovskaya, R.M.; Tsimmerman, V.G.

1978-01-01

Formation of aberrations was studied in the first and second mitosis following UV irradiation with the aim to elucidate the nature of the sensitive target responsible for aberrations formed during the G 2 period. The primary embryonic fibroblast culture from BALB mice was used; UV irradiation was at 254, 265, 280 and 302 nm and 40 and 80 erg/mm 2 doses. The cycle stages and exact times, when fixation was done, were determined from labelled mitosis curves. The frequency of chromosome aberrations after irradiation of cells at the G 2 stage was approximately the same at the wave lengths of 254, 265 and 280 nm, suggesting that DNA and protein are the targets responsible for aberrations.For chromatid aberrations the efficiency spectrum corresponded to the thymine absorption spectrum. Isochromatid break efficiency spectrum was similar to the protein absorption spectra. Caffeine, when applied during S period of the second mitosis, increased the frequency of chromatid breaks and did not affect other aberrations. It is supposed that the formation of chromatid aberrations and isochromatid breaks is underlied by different mechanisms. Chromatid aberrations are initiated by the formation of DNA-DNA cross linkages resulting from thymine dimers. For isochromatid breaks, the presence of a protein chromophore is important

Studies on chromosome aberrations induced in human lymphocytes by very low-dose exposure to tritium

International Nuclear Information System (INIS)

Hori, T.; Moriya, Junko; Nakai, Sayaka

1978-01-01

Assessment of potential hazard from environmental tritium to man becomes very important with increasing the development of nuclear-power industry. However, little data are available as to the determination on the genetic effect of tritium especially at the low levels. The object of the present study is to obtain quantitative data for chromosome aberrations in human lymphocytes, as an indicator for genetic risk estimation, induced by tritium at very low dose levels. Leukocyte cultures of human peripheral blood were chronically exposed for 48h to tritiated water and 3 H-thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and 3 H-thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose-response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extraporation from the linear relation. Partial-hit or partial-target kinetics events appeared at very low dose exposure. (author)

Chromosome fragility in Freemartin cattle

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V. Barbieri

2010-04-01

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

Baseline frequency of chromosomal aberrations and sister chromatid exchanges in peripheral blood lymphocytes of healthy individuals living in Turin (North-Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms on the levels of genomic damage.

Science.gov (United States)

Santovito, Alfredo; Cervella, Piero; Delpero, Massimiliano

2016-05-01

The increased exposure to environmental pollutants has led to the awareness of the necessity for constant monitoring of human populations, especially those living in urban areas. This study evaluated the background levels of genomic damage in a sample of healthy subjects living in the urban area of Turin (Italy). The association between DNA damage with age, sex and GSTs polymorphisms was assessed. One hundred and one individuals were randomly sampled. Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays, as well as genotyping of GSTT1 and GSTM1 genes, were performed. Mean values of SCEs and CAs were 5.137 ± 0.166 and 0.018 ± 0.002, respectively. Results showed age and gender associated with higher frequencies of these two cytogenetic markers. The eldest subjects (51-65 years) showed significantly higher levels of genomic damage than younger individuals. GSTs polymorphisms did not appear to significantly influence the frequencies of either markers. The CAs background frequency observed in this study is one of the highest reported among European populations. Turin is one of the most polluted cities in Europe in terms of air fine PM10 and ozone and the clastogenic potential of these pollutants may explain the high frequencies of chromosomal rearrangements reported here.

Adaptive response to ionizing radiation induced by low doses of gamma rays in human cell lines

International Nuclear Information System (INIS)

Seong, Jinsil; Chang, Ok Suh; Gwi, Eon Kim

1995-01-01

Purpose: The aim of this study was to investigate whether the adaptive response could be induced in human lymphoblastoid cell lines and human tumor cell lines. The time necessary for the expression of the adaptive response was also investigated. Materials and Methods: Three lymphoblastoid cell lines from ataxia telangiectasia (AT) homozygote (GM 1526), AT heterozygote (GM 3382), and normal individual (3402p) and two hepatoma cell lines, Hep G2 and Hep 3B, were used in this study. Experiments were carried out by delivering 0.01 Gy followed by 0.5 Gy of gamma radiation to the exponentially growing cells. The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 to 72 h. In some experiments, 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, was added immediately after the 0.5 Gy exposure. The cultures were fixed 30 min (for the G 2 chromatid) and 6 h (for the S chromatid) after the 0.5 Gy exposure. Metaphase chromosome assay was carried out to score chromatid breaks as an end point. Results: A prior exposure to 0.01 Gy of gamma rays significantly reduced the number of chromatid breaks induced by subsequent higher doses (0.5 Gy) in all the tested cell lines. The magnitude of the adaptive response was similar among the cell lines despite their different radiosensitivities. In the G 2 chromatids, the adaptive response was observed both at short-time intervals, as early as 1 h, and at long-time intervals. In the S chromatids, however, the adaptive response was shown only at long-time intervals. When 3-aminobenzamide was added after the 0.5 Gy, the adaptive responses were abolished in all the experimental groups. Conclusion: The adaptive response was observed in human lymphoblastoid cell lines and hepatoma cell lines. The magnitude of the adaptive response did not seem to be related to the radiosensitivity of the cells. The elimination of the adaptive response with 3

In Vivo Cytogenetic Studies on Aspartame

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Entissar S. AlSuhaibani

2010-01-01

Full Text Available Aspartame (a-Laspartyl-L-phenylalanine 1-methylester is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol was investigated in vivo using chromosomal aberration (CA test and sister chromatid exchange (SCE test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight. Bone marrow cells isolated from femora were analyzed for chromosome aberrations and sister chromatid exchanges. Treatment with aspartame induced dose dependently chromosome aberrations at all concentrations while it did not induce sister chromatid exchanges. On the other hand, aspartame did not decrease the mitotic index (MI. However, statistical analysis of the results show that aspartame is not significantly genotoxic at low concentration.

Genes on chromosomes 1 and 4 in the mouse are associated with repair of radiation-induced chromatin damage.

Science.gov (United States)

Potter, M; Sanford, K K; Parshad, R; Tarone, R E; Price, F M; Mock, B; Huppi, K

1988-04-01

Early-passage skin fibroblasts from different inbred and congenic strains of mice were X-irradiated (1 Gy), and the number of chromatid breaks was determined at 2.0 h after irradiation. The cells from DBA/2N, C3H/HeN, STS/A, C57BL/6N, BALB/cJ, and AKR/N had 25 to 42 chromatid breaks per 100 metaphase cells (efficient repair phenotype). NZB/NJ had greater than 78 and BALB/cAn had 87 to 110 chromatid breaks per 100 cells (inefficient repair phenotype). Differences between BALB/cAn and BALB/c. DBA/2 congenic strains which carry less than 1% of the DBA/2 genome indicate that two genes, one on chromosome 1 linked to bcl-2-Pep-3 and the other on chromosome 4 closely linked to Fv-1, affect the efficiency with which the cells repair radiation-induced chromatin damage.

The Centenary of Janssens’s Chiasmatype Theory

Science.gov (United States)

Koszul, Romain; Meselson, Matthew; Van Doninck, Karine; Vandenhaute, Jean; Zickler, Denise

2012-01-01

The segregation and random assortment of characters observed by Mendel have their basis in the behavior of chromosomes in meiosis. But showing this actually to be the case requires a correct understanding of the meiotic behavior of chromosomes. This was achieved only gradually, over several decades, with much dispute and confusion along the way. One crucial step in the understanding of meiosis was provided in 1909 by Frans Alfons Janssens who published in La Cellule an article entitled “La théorie de la Chiasmatypie. Nouvelle interprétation des cinèses de maturation,” which contains the first description of the chiasma structure. He observed that, of the four chromatids present at the connection sites (chiasmata sites) at diplotene or anaphase of the first meiotic division, two crossed each other and two did not. He therefore postulated that the maternal and paternal chromatids that crossed penetrated the other until they broke and rejoined in maternal and paternal segments new ways; the other two chromatids remained free and thus intact. This allowed him also to propose that the chromatids distributed in the four nuclei issued from the second meiotic division had various combinations of maternal and paternal segments of each chromosome. And conversely, permitted the appreciation that the laws of Mendelian segregation required breakage and joining (crossing over) between homologous non-sister chromatids. Although Janssens’s article found a broad appreciative audience and had a large influence on the chromosomal theory at that time, his theory was resisted by both geneticists and cytologists for several decades. This Perspectives aims to highlight the novelty of Janssens’s chiasmatype theory by examining the historical background and our actual understanding of meiotic recombination. PMID:22701050

Effect of chlorophyllin on induction of exchanges in sister chromatids by gamma irradiation in mice spermatogonia in vivo; Efecto de la clorofilina sobre la induccion de intercambios en las cromatidas hermanas (ICH) por radiacion gamma en espermatogonias de raton In vivo

Energy Technology Data Exchange (ETDEWEB)

Mendiola C, M T

1994-12-31

Mouse were exposed to different doses of gamma radiation and the effect on Sister Chromatid Exchange (SCE) frequency in spermatogonias was evaluated. The effect was analyzed before and after Bromodeoxyuridine (BrdU) incorporation to determine the interference of such agent with the cellular response induced by radiation. The capacity of chlorophyllin (sodium and Copper salt derivative from chlorophyll) to reduce SCE induction by radiation in normal and BrdU radio sensitized spermatogonia was also determined. The results indicate that there was a significant increase in SCE frequency by gamma radiation exposure in these cells, such effect was higher irradiating after BrdU incorporation than before. This fact confirms previous observations that BrdU sensitizes some cells to SCE induction. With regard to the chlorophyllin effect, it was determined that this salt acts as a radioprotector reducing gamma-rays induced SCE before or after BrdU incorporation Total protection was obtained with 200 {mu}g of chlorophyllin per g of body weight in both protocols. Under the experimental conditions this study there was no evidence of genotoxicity induced by chlorophyllin itself. The results suggest that this agent may act as a radioprotector by scavenging free radicals produced by gamma-radiation which cause DNA lesions that are involved in SCE formation. (Author).

Interaction between a pair of gypsy insulators or between heterologous gypsy and Wari insulators modulates Flp site-specific recombination in Drosophila melanogaster.

Science.gov (United States)

Krivega, Margarita; Savitskaya, Ekaterina; Krivega, Ivan; Karakozova, Marina; Parshikov, Aleksander; Golovnin, Anton; Georgiev, Pavel

2010-08-01

Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. An Flp technology was used to examine interactions between Drosophila gypsy and Wari insulators in somatic and germ cells. The gypsy insulator consists of 12 binding sites for the Su(Hw) protein, while the endogenous Wari insulator, located on the 3' side of the white gene, is independent from the Su(Hw) protein. Insertion of the gypsy but not Wari insulator between FRT sites strongly blocks recombination between Flp dimers bound to FRT sites located on the same chromatid (recombination in cis) or in sister chromatids (unequal recombination in trans). At the same time, the interaction between Wari and gypsy insulators regulates the efficiency of Flp-mediated recombination. Thus, insulators may have a role in controlling interactions between distantly located protein complexes (not only those involved in transcriptional gene regulation) on the same chromosome or on sister chromatids in somatic and germ cells. We have also found that the frequency of Flp-mediated recombination between FRT sites is strongly dependent on the relative orientation of gypsy insulators. Taken together, our results indicate that the interactions between insulators can be visualized by Flp technology and that insulators may be involved in blocking undesirable interactions between proteins at the two-chromatid phase of the cell cycle.

Strand-seq: A unifying tool for studies of chromosome segregation

OpenAIRE

Falconer, Ester; Lansdorp, Peter M.

2013-01-01

Non random segregation of sister chromatids has been implicated to help specify daughter cell fate (the Silent Sister Hypothesis [1]) or to protect the genome of long-lived stem cells (the Immortal Strand Hypothesis [2]). The idea that sister chromatids are non-randomly segregated into specific daughter cells is only marginally supported by data in sporadic and often contradictory studies. As a result, the field has moved forward rather slowly. The advent of being able to directly label and d...

Chromosomal aberrations induced by caffeine, 3H-thymidine and by X-rays in two L5178Y sublines of different radiosensitivity. Part 1. Chromosomal aberrations in cells treated with 2mM caffeine and tritiated thymidine

International Nuclear Information System (INIS)

Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B.

1982-01-01

Chromosomal aberrations were studied in two sublines of L5178Y cells with different sensitivity to X-rays. Cells were treated with 2 mM caffeine for 12 h. Then they were examined at various time intervals from 5 to 24 h. Caffeine caused over three times more aberrations, mainly chromatid breaks and gaps, in radiation-sensitive L5178Y-S than in radiation-resistant L5178Y-R cells. The maximum frequency of chromatid breaks in both sublines was found at 8 h and that of chromatid exchanges and isochromatid breaks at 12 h after treatment. A dramatic decrease of the frequency of all types of aberrations at 24 h was observed. In the pulse labelled experiments caffeine enhanced the frequency of aberrations that were induced by 3 H-thymidine at a concentration of 1 μCi/ml. This effect of caffeine was greater in L5178Y-R than in L5178Y-S cells. (author)

The induction of chromosomal aberrations by X irradiation during S-phase in cultured diploid Syrian hamster fibroblasts

International Nuclear Information System (INIS)

Savage, J.R.K.; Bhunya, S.P.

1980-01-01

The induction of chromosomal aberrations by 4.0 Gy of 250 kV X-rays in cell throughout S-phase has been investigated in untransformed diploid Syrian hamster fibroblasts. Using a method of subdividing S into catologically defined stages (on the basis of replication band patterns displayed after brome-deoxyuridine incorporation) it is shown that: (1) This dose does not perturb, measurable, the intracellular programme of synthesis at the chromosome band level, so that the cell classification criteria remain valid after radiation. (2) Mitotic delay and perturbation appears to be less for cells in very early S, but there is no evidence of a massive cell mixing of S cells. (3) S-phase is, in general, much less sensitive to aberration induction at all sub-phases than G 2 . (4) Both chromosome and chromatid-type aberrations are found in pre- S and S cells, but chromatid-types predominate in the latter at all sub-phases. (5) The frequency of chromatid-types, especially interchanges falls in eraly. (orig.)

Ultrastructural analysis of radiation induced chromosome breaks and rearrangements

International Nuclear Information System (INIS)

Fernandez, J.L.; Goyanes, V.J.; Campos, A.; Cajigal, D.

1990-01-01

Chinese Hamster chromosomes R-banded in vitro were gamma-irradiated and chromatid breaks and rearrangements examined by electron microscopy employing whole-mounting technique. Breaks were preferentially located at the point of transition between G- and R-bands where the chromosome showed an average diameter 71.65 % of the wide condensed R-bands. This result was similar to the average diameter of narrow G-bands. Three chromosomes which were thin sectioned presented their broken terminal end organized as a coil constituted by two 23 nm wide chromatin fibers coiling together. Coils diameter was 43.70 % of the mean chromatid diameter. The border of damage-breakage was analyzed in whole-mounted chromosomes where breaks were photoinduced in BrdU-substituted DNA. Measurements of the angle of the sharp border of damage with respect to the chromatid axis showed a tendency to be more perpendicular as condensation progressed. These results clearly correlate with the several levels of chromatin fiber organization of the metaphase chromosome. (author)

Neutrons and X-rays, comparative studies with Drosophila melanogaster. Pt. 2

International Nuclear Information System (INIS)

Leigh, B.; Veerkamp-van Baarle, A.M.A.; Sobels, F.H.; Broese, J.J.

1981-01-01

Losses and duplications of Bsup(S)Y γ + -chromosome markers werde induced by irradiation of spermatozoa with either 0.5-MeV neutrons or 100-kV X-rays. These 2 types of radiation are known to induce significantly different ratios of double:single strand breaks in DNA. Exceptional progeny were grouped into 3 categories; no Y marker, one Y marker, and Y marker duplications + mosaics. The last combination consisted of exceptions derived from only chromatid-type rearrangements. All other classes of exceptions may be derived from either chromatid- or chromosome-type rearrangements. Doses of 15 Gy neutrons and 27 Gy X-rays induced identical frequencies of exceptional progeny, giving an RBE of 1.8. The ratios of the 3 classes of exceptions were similar for both types of radiation. This observation can be interpreted as indicating that, under the conditions used here, chromosome and chromatid rearrangements are not derived directly from double and single DNA strand breaks, respectively. (orig.)

Implications of S-phase exchanges for the mechanisms of radiosensitivity in trisomy 21

International Nuclear Information System (INIS)

Athanasiou, K.; Bartsocas, C.S.

1982-01-01

Human lymphocytes obtained from four patients with Down syndrome and from two normal individuals were irradiated with X-rays during their S phase and examined for chromatid type aberrations. It is suggested that the significantly increased frequency of asymmetrical chromatid interchanges found in trisomic cells is related to an altered DNA repair system. This altered repair system is probably responsible for the increased frequency of chromosome aberrations that can be induced in these cells by x-rays and the increased tendency for leukemia observed in Down syndrome as well

Radiation-cytogenetic study of the mechanism of formation of chromosome aberations in Crepis capillaris cells

International Nuclear Information System (INIS)

Belyaev, I.Ya.; Semakin, A.B.; Grigorova, N.V.; Akif'ev, A.P.; AN SSSR, Moscow. Inst. Khimicheskoj Fiziki)

1986-01-01

Incomplete chromatid exchanges induced by γ-quanta at G 2 stage of Crepis capillaris meristem cells are transformed into complete chromosome exchanges during the second nuclear cycle. After the combined effect of γ-quanta and DNA synthesis inhibitor 5-fluoro-2-deoxyridine, the exchange aberrations disappear. During the second nuclear cycle, the chromatid exchanges, which were not realized in the presence of 5-fluro-2-deoxyuridne and regarded as potential ones, are transformed into chromosome exchanges. The breaks induced by 5-fluoro-2-deoxyuridine at G 2 stage are repaired after one nuclear cycle

Steroid sulfatase gene in XX males.

OpenAIRE

Mohandas, T K; Stern, H J; Meeker, C A; Passage, M B; Müller, U; Page, D C; Yen, P H; Shapiro, L J

1990-01-01

The human X and Y chromosomes pair and recombine at their distal short arms during male meiosis. Recent studies indicate that the majority of XX males arise as a result of an aberrant exchange between X and Y chromosomes such that the testis-determining factor gene (TDF) is transferred from a Y chromatid to an X chromatid. It has been shown that X-specific loci such as that coding for the red cell surface antigen, Xg, are sometimes lost from the X chromosome in this aberrant exchange. The ste...

[Inverted meiosis and its place in the evolution of sexual reproduction pathways].

Science.gov (United States)

Bogdanov, Yu F

2016-05-01

Inverted meiosis is observed in plants (Cyperaceae and Juncaceae) and insects (Coccoidea, Aphididae) with holocentric chromosomes, the centromeres of which occupy from 70 to 90% of the metaphase chromosome length. In the first meiotic division (meiosis I), chiasmata are formed and rodlike bivalents orient equationally, and in anaphase I, sister chromatids segregate to the poles; the diploid chromosome number is maintained. Non-sister chromatids of homologous chromosomes remain in contact during interkinesis and prophase II and segregate in anaphase II, forming haploid chromosome sets. The segregation of sister chromatids in meiosis I was demonstrated by example of three plant species that were heterozygous for chromosomal rearrangements. In these species, sister chromatids, marked with rearrangement, segregated in anaphase I. Using fluorescent antibodies, it was demonstrated that meiotic recombination enzymes Spo11 and Rad5l, typical of canonical meiosis, functioned at the meiotic prophase I of pollen mother cells of Luzula elegance and Rhynchospora pubera. Moreover, antibodies to synaptonemal complexes proteins ASY1 and ZYP1 were visualized as filamentous structures, pointing to probable formation of synaptonemal complexes. In L. elegance, chiasmata are formed by means of chromatin threads containing satellite DNA. According to the hypothesis of the author of this review, equational division of sister chromatids at meiosis I in the organisms with inverted meiosis can be explained by the absence of specific meiotic proteins (shugoshins). These proteins are able to protect cohesins of holocentric centromeres from hydrolysis by separases at meiosis I, as occurs in the organisms with monocentric chromosomes and canonical meiosis. The basic type of inverted meiosis was described in Coccoidea and Aphididae males. In their females, the variants of parthenogenesis were also observed. Until now, the methods of molecular cytogenetics were not applied for the analysis of

Repairability during G1 of the inductor leisure of exchanges in the sister chromatid induced by alkylating agents in DNA substituted and no substituted with BUDR, in cells of the salivary gland of mouse In vivo

International Nuclear Information System (INIS)

Gonzalez B, F.

2004-01-01

In this work you determines the repair of the lesions inductoras of Sister chromatid exchange (ICHs) generated in the cells of the salivary gland of mouse, for the treatment with the N-Methyl-N-Nitrosourea (MNU), the N-Ethyl-N-Nitrosourea (ENU), the Methyl methanesulfonate (MMS) and the Ethyl methanesulfonate (EMS) in early and slow G1 of the first one and the second cellular division, that is to say before and after the cells incorporate 5-bromine-2 -Desoxyuridine (BrdU) in the DNA. Groups witness non treaties were included with mutagen. The cells of the salivary gland repaired the generated lesions partially by the MNU, the MMS and the EMS in the 1st division, and only the lesions induced by the ENU and MMS were repaired partially in the 2nd division. The ENU generates injure that they were not repaired in the 1st division and those taken place by the EMS were little repaired in the 2nd division. The methylating agents generated but ICHs that the ethylating. One observes that the BrdU makes to the molecule of the DNA but susceptible to the damage generated by the alkylating agents that induce the formation of the ICHs. This susceptibility was incremented around 150% for the treatment with the MNU, the ENU and the MMS, on the other hand for the EMS it was 3 times minor. It is proposed that the one electronegative atom of this analog of the timine would to work as a nucleophyllic center with which the electrophyllic compounds react. (Author)

In vivo study on the replicative model validity of sister chromatid exchanges production; Estudio In vivo sobre la validez del modelo replicativo de produccion de intercambios en las cromatidas hermanas

Energy Technology Data Exchange (ETDEWEB)

Cruz V, V L

1997-12-31

The sister chromatid exchanges (SCE) frequency determination has been used as index of damage to DNA, however the biological meaning of this event is still ignored. Different models in order to explain the mechanism of their formation have been proposed and they could be contained in two categories: (a) those that consider that the SCE is produced by means of discrete lesions to the DNA and that they occur in the place of the lesion, and (b) those that propose that the SCE is caused by a group of lesions and that therefore the place in which they occur could not be associated with a lesion in particular. The model of Painter (1980) belongs to this last group. It suggests that the region of the DNA where the clusters are united, is the only place in which the exchange of double chain could happen during the synthesis of the DNA and makes the prediction that since the x rays retard the beginning of the duplication, the pretreatment with ionizing radiation would reduce the frequency of SCE induced by agents capable to block the lengthening of the chain of DNA, that are the most efficient SCE inducers. The objective of the present work was to establish the validity of this replicative model for the SCE formation, based in its prediction. The effect of the unilateral preexposition of mouse to gamma radiation was determined on the SCE induction by Mitomycin C (MMC), in cells of the femoral bone marrow In vivo. This strategy allows to determine the effect of the pretreatment in the same organism, minimizing the variability of the response between individuals. There was not a significant variability between the frequencies of SCE, basal and induced by gamma radiation or MMC in the same organism. The animals that received the gamma radiation pretreatment, showed a reduction of approximately the 30 % in the frequency of SCE, assuming an additive effect of the radiation with the MMC. These results coincide with the prediction of the model of Painter. (Abstract Truncated)

Sequential loading of cohesin subunits during the first meiotic prophase of grasshoppers.

Directory of Open Access Journals (Sweden)

Ana M Valdeolmillos

2007-02-01

Full Text Available The cohesin complexes play a key role in chromosome segregation during both mitosis and meiosis. They establish sister chromatid cohesion between duplicating DNA molecules during S-phase, but they also have an important role during postreplicative double-strand break repair in mitosis, as well as during recombination between homologous chromosomes in meiosis. An additional function in meiosis is related to the sister kinetochore cohesion, so they can be pulled by microtubules to the same pole at anaphase I. Data about the dynamics of cohesin subunits during meiosis are scarce; therefore, it is of great interest to characterize how the formation of the cohesin complexes is achieved in order to understand the roles of the different subunits within them. We have investigated the spatio-temporal distribution of three different cohesin subunits in prophase I grasshopper spermatocytes. We found that structural maintenance of chromosome protein 3 (SMC3 appears as early as preleptotene, and its localization resembles the location of the unsynapsed axial elements, whereas radiation-sensitive mutant 21 (RAD21 (sister chromatid cohesion protein 1, SCC1 and stromal antigen protein 1 (SA1 (sister chromatid cohesion protein 3, SCC3 are not visualized until zygotene, since they are located in the synapsed regions of the bivalents. During pachytene, the distribution of the three cohesin subunits is very similar and all appear along the trajectories of the lateral elements of the autosomal synaptonemal complexes. However, whereas SMC3 also appears over the single and unsynapsed X chromosome, RAD21 and SA1 do not. We conclude that the loading of SMC3 and the non-SMC subunits, RAD21 and SA1, occurs in different steps throughout prophase I grasshopper meiosis. These results strongly suggest the participation of SMC3 in the initial cohesin axis formation as early as preleptotene, thus contributing to sister chromatid cohesion, with a later association of both RAD21

Cytogenetic adaptive response of mouse bone marrow cells to low level HTO

International Nuclear Information System (INIS)

Chen Deqing; Zhang Zhaoyang; Zhou Xiangyan

1993-01-01

Mice were abdominally injected with a adaptive dose of 3.7 x 10 2 -3.7 x 10 5 Bq/gbw HTO, and then exposed to a challenge dose of 1.5 Gy of 6 '0Co γ-rays. In bone marrow cells that received both the adaptive and challenge doses, the chromatid breaks are lower than expected on the basis of additivity of the effects of the individual treatment. The adaptive response induced with 3.7 x 10 3 Bq/gbw HTO is the most remarkable, but at 3.7 x 10 5 Bq/gbw the adaptive response seems to disappear. The adaptive response can be observed by exposing to 1.5 Gy γ-rays from 1 to 5 days after injection of 3.7 x 10 3 Bq/gbw HTO, which is the most obvious one to reduce chromatid breaks to 50% of expected at the 5th day, but at the 7th day to equate to expected. The frequency of chromatid breaks is gradually reduced with time after challenge dose, the maximum index number of adaptive response is 0.50 and appears at 24 hr after challenge dose

The cohesion protein SOLO associates with SMC1 and is required for synapsis, recombination, homolog bias and cohesion and pairing of centromeres in Drosophila Meiosis.

Science.gov (United States)

Yan, Rihui; McKee, Bruce D

2013-01-01

Cohesion between sister chromatids is mediated by cohesin and is essential for proper meiotic segregation of both sister chromatids and homologs. solo encodes a Drosophila meiosis-specific cohesion protein with no apparent sequence homology to cohesins that is required in male meiosis for centromere cohesion, proper orientation of sister centromeres and centromere enrichment of the cohesin subunit SMC1. In this study, we show that solo is involved in multiple aspects of meiosis in female Drosophila. Null mutations in solo caused the following phenotypes: 1) high frequencies of homolog and sister chromatid nondisjunction (NDJ) and sharply reduced frequencies of homolog exchange; 2) reduced transmission of a ring-X chromosome, an indicator of elevated frequencies of sister chromatid exchange (SCE); 3) premature loss of centromere pairing and cohesion during prophase I, as indicated by elevated foci counts of the centromere protein CID; 4) instability of the lateral elements (LE)s and central regions of synaptonemal complexes (SCs), as indicated by fragmented and spotty staining of the chromosome core/LE component SMC1 and the transverse filament protein C(3)G, respectively, at all stages of pachytene. SOLO and SMC1 are both enriched on centromeres throughout prophase I, co-align along the lateral elements of SCs and reciprocally co-immunoprecipitate from ovarian protein extracts. Our studies demonstrate that SOLO is closely associated with meiotic cohesin and required both for enrichment of cohesin on centromeres and stable assembly of cohesin into chromosome cores. These events underlie and are required for stable cohesion of centromeres, synapsis of homologous chromosomes, and a recombination mechanism that suppresses SCE to preferentially generate homolog crossovers (homolog bias). We propose that SOLO is a subunit of a specialized meiotic cohesin complex that mediates both centromeric and axial arm cohesion and promotes homolog bias as a component of chromosome

Essential roles of BCCIP in mouse embryonic development and structural stability of chromosomes.

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Huimei Lu

2011-09-01

Full Text Available BCCIP is a BRCA2- and CDKN1A(p21-interacting protein that has been implicated in the maintenance of genomic integrity. To understand the in vivo functions of BCCIP, we generated a conditional BCCIP knockdown transgenic mouse model using Cre-LoxP mediated RNA interference. The BCCIP knockdown embryos displayed impaired cellular proliferation and apoptosis at day E7.5. Consistent with these results, the in vitro proliferation of blastocysts and mouse embryonic fibroblasts (MEFs of BCCIP knockdown mice were impaired considerably. The BCCIP deficient mouse embryos die before E11.5 day. Deletion of the p53 gene could not rescue the embryonic lethality due to BCCIP deficiency, but partially rescues the growth delay of mouse embryonic fibroblasts in vitro. To further understand the cause of development and proliferation defects in BCCIP-deficient mice, MEFs were subjected to chromosome stability analysis. The BCCIP-deficient MEFs displayed significant spontaneous chromosome structural alterations associated with replication stress, including a 3.5-fold induction of chromatid breaks. Remarkably, the BCCIP-deficient MEFs had a ∼20-fold increase in sister chromatid union (SCU, yet the induction of sister chromatid exchanges (SCE was modestly at 1.5 fold. SCU is a unique type of chromatid aberration that may give rise to chromatin bridges between daughter nuclei in anaphase. In addition, the BCCIP-deficient MEFs have reduced repair of irradiation-induced DNA damage and reductions of Rad51 protein and nuclear foci. Our data suggest a unique function of BCCIP, not only in repair of DNA damage, but also in resolving stalled replication forks and prevention of replication stress. In addition, BCCIP deficiency causes excessive spontaneous chromatin bridges via the formation of SCU, which can subsequently impair chromosome segregations in mitosis and cell division.

Cell killing and chromosomal aberration induced by heavy-ion beams in cultured human tumor cells

International Nuclear Information System (INIS)

Takakura, K.; Funada, A.; Mohri, M.; Lee, R.; Aoki, M.; Furusawa, Y.; Gotoh, E.

2003-01-01

Full text: To clarify the relation between cell death and chromosomal aberration in cultured human tumor cells irradaited with heavy-ion beams. The analyses were carried out on the basis of the linear energy transfer (LET) values of heavy ion beams as radiation source. Exponentially growing human tumor cells, Human Salivary Gland Tumor cells (HSG cells), were irradiated with various high energy heavy ions, such as 13 keV/micrometer carbon (C) ions as low LET charged particle radiation source, 120 keV/ micrometer carbon (C) ions and 440 keV/micrometer iron (Fe) ions as high LET charged particle radiation sources.The cell death was analysed by the colony formation method, and the chromosomal aberration and its repairing kinetics was analysed by prematurely chromosome condensation method (PCC method) using calyculin A. Chromatid-type breaks, isochromatid breaks and exchanges were scored for the samples from the cells keeping with various incubation time after irradiation. The LET dependence of the cell death was similar to that of the chromosome exchange formation after 12 hours incubation. A maximum peak was around 120 keV/micrometer. However it was not similar to the LET dependence of isochromatid breaks or chromatid breaks after 12 hours incubation. These results suggest that the exchanges formed in chromosome after irradiation should be one of essential causes to lead the cell death. The different quality of induced chromosome damage between high-LET and low-LET radiation was also shown. About 89 % and 88 % chromatid breaks induced by X rays and 13 keV/micrometer C ions were rejoined within 12 hours of post-irradiation, though only 71% and 58 % of chromatid breaks induced by 120 keV/micrometer C ions and 440 keV/micrometer Fe ions were rejoined within 12 hours of post-irradiation

Chromosome aberrations in workers of beach sand mineral industries

International Nuclear Information System (INIS)

Meenakshi, C.; Mohankumar, Mary N.

2013-01-01

Beach Sand Mining (BSM) is a profitable industry earning a sizable income for the country by way of foreign exchange. The Indian coast is rich in rare earths such as ilmenite, rutile, leucoxene, zircon, garnet and sillimanite, and is invariably associated with radioactive monazite. Due to the nature of the separation processes involved and the manual handling, workers in these factories are continuously being exposed to suspended particles containing naturally occurring radioactive materials. An attempt was made to estimate DNA damage using a chromosome aberration assay to monitor radiation effects in workers of BSM industries in India. The study group comprised 27 BSM workers and 20 controls. Percentage yields of dicentrics, acentric fragments and chromatid breaks observed in the control group were 0.058 ± 0.017, 0.073 ± 0.03 and 0.22 ± 0.112, respectively. Percentage yields of dicentrics + centric rings, acentric fragments and chromatid breaks observed in the BSM group were 0.029 ± 0.01 (P value 0.19), 0.24 ± 0.06 (P value 0.006) and 0.455 ± 0.06 (P value 0.0004), respectively. Elevated levels of fragments and chromatid aberrations are suggestive of low-dose radiation effects and also chemically-induced DNA damage. (authors)

The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments

Energy Technology Data Exchange (ETDEWEB)

Corbett, Kevin D.; Yip, Calvin K.; Ee, Ly-Sha; Walz, Thomas; Amon, Angelika; Harrison, Stephen C. (Harvard-Med); (MIT)

2010-09-27

The monopolin complex regulates different types of kinetochore-microtubule attachments in fungi, ensuring sister chromatid co-orientation in Saccharomyces cerevisiae meiosis I and inhibiting merotelic attachment in Schizosaccharomyces pombe mitosis. In addition, the monopolin complex maintains the integrity and silencing of ribosomal DNA (rDNA) repeats in the nucleolus. We show here that the S. cerevisiae Csm1/Lrs4 monopolin subcomplex has a distinctive V-shaped structure, with two pairs of protein-protein interaction domains positioned {approx}10 nm apart. Csm1 presents a conserved hydrophobic surface patch that binds two kinetochore proteins: Dsn1, a subunit of the outer-kinetochore MIND/Mis12 complex, and Mif2/CENP-C. Csm1 point-mutations that disrupt kinetochore-subunit binding also disrupt sister chromatid co-orientation in S. cerevisiae meiosis I. We further show that the same Csm1 point-mutations affect rDNA silencing, probably by disrupting binding to the rDNA-associated protein Tof2. We propose that Csm1/Lrs4 functions as a molecular clamp, crosslinking kinetochore components to enforce sister chromatid co-orientation in S. cerevisiae meiosis I and to suppress merotelic attachment in S. pombe mitosis, and crosslinking rDNA repeats to aid rDNA silencing.

Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes

Energy Technology Data Exchange (ETDEWEB)

M' Bemba-Meka, Prosper [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada); University of Louisville, Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine, Louisville, KY (United States); Lemieux, Nicole [Universite de Montreal, Department of Pathology and Cellular Biology, Faculty of Medicine, Main Station, P.O. Box 6128, Montreal, QC (Canada); Chakrabarti, Saroj K. [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada)

2007-02-15

Human peripheral lymphocytes from whole blood cultures were exposed to either soluble form of nickel carbonate hydroxide (NiCH) (0-60 {mu}M), or of nickel subsulfide (Ni{sub 3}S{sub 2}) (0-120 {mu}M), or of nickel oxide (NiO) (0-120 {mu}M), or nickel sulfate (NiSO{sub 4}) (0-120 {mu}M) for a short duration of 2 h. The treatments occurred 46 h after the beginning of the cultures. The cultures were harvested after a total incubation of 72 h, and sister-chromatid exchange (SCE), replication index (RI), and mitotic index (MI) were measured for each nickel compound. The soluble form of NiCH at 30 {mu}M but those of Ni{sub 3}S{sub 2} and NiO at 120 {mu}M produced significant increase in the SCE per cell compared to the control value, whereas NiSO{sub 4} failed to produce any such significant increase. Except NiSO{sub 4}, the soluble forms of NiCH, Ni{sub 3}S{sub 2}, and NiO produced significant cell-cycle delay (as measured by the inhibition of RI) as well as significant inhibition of the MI at respective similar concentrations as mentioned above. Pretreatment of human blood lymphocytes with catalase (H{sub 2}O{sub 2} scavenger), or superoxide dismutase (superoxide anion scavenger), or dimethylthiourea (hydroxyl radical scavenger), or deferoxamine (iron chelator), or N-acetylcysteine (general antioxidant) inhibited NiCH-induced SCE, and changes in RI and MI. This suggests the participation of oxidative stress involving H{sub 2}O{sub 2}, the superoxide anion radical, the hydroxyl radical, and iron in the NiCH-induced genotoxic responses. Cotreatment of NiCH with either verapamil (inhibitor of intracellular calcium ion ([Ca{sup 2+}]{sub i}) movement through plasma membranes), or dantrolene (inhibitor of [Ca{sup 2+}]{sub i} release from sarcoplasmic reticulum), or BAPTA (Ca{sup 2+} chelator) also inhibited the NiCH-induced responses. These results suggest that [Ca{sup 2+}]{sub i} is also implicated in the genotoxicity of NiCH. Overall these data indicate that various types

A critical view to explanations for the maximal value of 50 % of genetic recombination Críticas a las explicaciones del máximo de 50 % de recombinación genética

Directory of Open Access Journals (Sweden)

CARLOS Y VALENZUELA

2001-03-01

Full Text Available The maximal value of 50 % of genetic recombination (RF = recombination fraction between two linked gene loci has been explained by two models: (i the restriction of crossovers to only two of the four chromatids of a tetrad (tetrad model; (ii the limit of the occurrence of an odd number of crossovers between two loci, when the expected number of crossovers tends to infinite (odd-even model. This article shows that (i is wrong. If tetrads were responsible for the maximal 50 % RF, sister chromatid exchanges (SCE should display a maximal 100 % RF. In mammalian CHO cells we found that SCE yield a maximal 50 % recombination. Also, we demonstrated that the maximal 50 % RF for tetrads occurs because the sum of odd order coefficients in the binomial distribution is equal to the sum of even order coefficients. At the end of meiosis the two chromatids of a chromosome that receives K crossovers are separated. Then K breaks should distribute into two chromatids. Thus, the expected number of breaks per chromatid distributes, when K is large, in 50 % of chromatids having an even number of breaks (RF = 0 and 50 % having an odd number (RF = 1, irrespective of tetrads, hexads, octads or more complex meiotic chromosome configurationsEl máximo de 50 % de recombinación genética (RF entre dos loci ligados ha sido explicado por dos modelos. (i la restricción de los entrecruzamientos a dos de las cuatro cromátidas de una tétrada (modelo de tétrada; (ii el límite de la ocurrencia de un número impar de entrecruzamientos entre los dos loci, cuando el número esperado de entrecruzamientos tiende a infinito (modelo par-impar. Este artículo muestra que (i es erróneo, ya que, si la tétrada fuera responsable del máximo de 50 % de RF, el intercambio de cromátidas hermanas (SCE debería alcazar el 100 % de recombinación y esto no se da en células CHO, en las que encontramos un máximo de 50 %. Además, demostramos que el máximo de 50 % RF para las t

UDS and SCE in lymphocytes of persons occupationally exposed to low levels of ionizing radiation

International Nuclear Information System (INIS)

Tuschl, H.; Kovac, R.; Altmann, H.

1983-03-01

Unscheduled DNA synthesis induced by 'in vitro' UV-irradiation was investigated in lymphocytes of persons occupationally exposed to low doses of ionizing radiation (maximum registered radiation dose: 98 mrad/month). For radiation exposures >14 mrad/month, above background level, increased rates of UDS after in vitro UV-irradiation of lymphocytes were found. The bromodeoxyuridine differential chromatid labeling technique was applied to the examination of spontaneous and mytomycin C induced sister chromatid exchanges in the same population. No statistically significant difference could be determined in spontaneously occurring SCEs, while MMC induced SCEs were significantly reduced in persons exposed to radiation doses >14 mrad/month, thus indicating increased repair capability for DNA lesions inflicted by a second insult after protracted low dose irradiation. (Author) [de

Adaptive response induced by occupational exposures to ionizing radiation

International Nuclear Information System (INIS)

Barquinero, J.F.; Caballin, M.R.; Barrios, L.; Murtra, P.; Egozcue, J.; Miro, R.; Ribas, M.

1997-01-01

We have found a significant decreased sensitivity to the cytogenetic effects of ionizing radiation (IR) and bleomycin (BLM) in lymphocytes from individuals occupationally exposed to IR when compared with a control population. These results suggest that occupational exposures to IR can induce adaptive response that can be detected by a subsequent treatment by IR or by BLM. However, no correlation between the results obtained with both treatments was observed. A great heterogeneity in the frequencies of chromatid aberrations induced by BLM was observed. The study of the influence of different harvesting times showed that there was no correlation with the frequencies of chromatid breaks. Our results indicate that the use of BLM to detect adaptive response has several difficulties at the individual level. (author)

Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I.

Science.gov (United States)

El Yakoubi, Warif; Buffin, Eulalie; Cladière, Damien; Gryaznova, Yulia; Berenguer, Inés; Touati, Sandra A; Gómez, Rocío; Suja, José A; van Deursen, Jan M; Wassmann, Katja

2017-09-25

A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H2A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo2 in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo2 at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.

Controlling meiotic recombinational repair - specifying the roles of ZMMs, Sgs1 and Mus81/Mms4 in crossover formation.

Directory of Open Access Journals (Sweden)

Ashwini Oke

2014-10-01

Full Text Available Crossovers (COs play a critical role in ensuring proper alignment and segregation of homologous chromosomes during meiosis. How the cell balances recombination between CO vs. noncrossover (NCO outcomes is not completely understood. Further lacking is what constrains the extent of DNA repair such that multiple events do not arise from a single double-strand break (DSB. Here, by interpreting signatures that result from recombination genome-wide, we find that synaptonemal complex proteins promote crossing over in distinct ways. Our results suggest that Zip3 (RNF212 promotes biased cutting of the double Holliday-junction (dHJ intermediate whereas surprisingly Msh4 does not. Moreover, detailed examination of conversion tracts in sgs1 and mms4-md mutants reveal distinct aberrant recombination events involving multiple chromatid invasions. In sgs1 mutants, these multiple invasions are generally multichromatid involving 3-4 chromatids; in mms4-md mutants the multiple invasions preferentially resolve into one or two chromatids. Our analysis suggests that Mus81/Mms4 (Eme1, rather than just being a minor resolvase for COs is crucial for both COs and NCOs in preventing chromosome entanglements by removing 3'- flaps to promote second-end capture. Together our results force a reevaluation of how key recombination enzymes collaborate to specify the outcome of meiotic DNA repair.

Resolving RAD51C function in late stages of homologous recombination

Directory of Open Access Journals (Sweden)

Kuznetsov Sergey G

2007-06-01

Full Text Available Abstract DNA double strand breaks are efficiently repaired by homologous recombination. One of the last steps of this process is resolution of Holliday junctions that are formed at the sites of genetic exchange between homologous DNA. Although various resolvases with Holliday junctions processing activity have been identified in bacteriophages, bacteria and archaebacteria, eukaryotic resolvases have been elusive. Recent biochemical evidence has revealed that RAD51C and XRCC3, members of the RAD51-like protein family, are involved in Holliday junction resolution in mammalian cells. However, purified recombinant RAD51C and XRCC3 proteins have not shown any Holliday junction resolution activity. In addition, these proteins did not reveal the presence of a nuclease domain, which raises doubts about their ability to function as a resolvase. Furthermore, oocytes from infertile Rad51C mutant mice exhibit precocious separation of sister chromatids at metaphase II, a phenotype that reflects a defect in sister chromatid cohesion, not a lack of Holliday junction resolution. Here we discuss a model to explain how a Holliday junction resolution defect can lead to sister chromatid separation in mouse oocytes. We also describe other recent in vitro and in vivo evidence supporting a late role for RAD51C in homologous recombination in mammalian cells, which is likely to be resolution of the Holliday junction.

The enhancement by caffeine of the frequency of lethal dominant mutation induced by gamma radiation in oocytes of Musca domestica

International Nuclear Information System (INIS)

Targa, H.J.; Rogatko, A.

1982-01-01

The results obtained, when a new technique for feeding insects is employed, on the effects of caffeine of the radiation - induced breaks of oocyte chromatids of Musca domestica are presented. (M.A.) [pt

Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo; Relacion de la desmetilacion del ADN con la induccion de intercambios en las cromatidas hermanas (ICH) In vivo

Energy Technology Data Exchange (ETDEWEB)

Toribio E, E

2005-07-01

The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo; Relacion de la desmetilacion del ADN con la induccion de intercambios en las cromatidas hermanas (ICH) In vivo

Energy Technology Data Exchange (ETDEWEB)

Toribio E, E

2005-07-01

The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

Chromosomal changes in maize induced by hydrogen fluoride gas

Energy Technology Data Exchange (ETDEWEB)

Mohamed, A H

1970-01-01

Maize seedlings were fumigated in growth chambers with hydrogen fluoride at a concentration of about 3 ..mu..g/m/sup 3/. The experiment was run for 10 days, with the first group of treated plants removed from the chambers after 4 days and then at intervals of 2 days. Microsporocyte smears from the treated plants revealed chromosomal aberrations that included asynaptic regions, translocations, inversions, and bridges plus fragments or fragments by themselves. It is believed that these abnormalities were due to the physiological effect of HF causing the chromosomes to become sticky and/or to the occurrence of chromatid breakage followed by reunion to sticky and/or to the occurrence of chromatid breakage followed by reunion to form structural changes. These findings indicate that HF is a mutagenic agent.

Cytogenetic diagnosis of Roberts SC phocomelia syndrome: First report from Kashmir

Directory of Open Access Journals (Sweden)

Tahir M. Malla

2016-01-01

Full Text Available There are several syndromes in which specific mitotic chromosomal abnormalities can be seen, like premature centromere separation, premature (sister chromatid separation, and somatic aneuploidies. Identifications of such specific cytogenetic findings can be the key factor that leads towards the diagnosis of syndromes like Roberts SC phocomelia. The case presented here as Roberts SC phocomelia syndrome was identified as a child with multiple congenital anomalies and dysmorphic features. Conventional cytogenetic analysis of the case revealed premature sister chromatid separation. The premature centromeric separation was also confirmed by C banding analysis of the child. It is the first and the only case of Roberts SC phocomelia diagnosed from this part of the world. The present case report emphasizes the importance of conventional cytogenetics in the diagnosis of such syndromes.

Analysis of structural and numerical chromosomal aberrations at the first and second mitosis after X irradiation of two-cell mouse embryos

International Nuclear Information System (INIS)

Weissenborn, U.; Streffer, C.

1989-01-01

Two-cell mouse embryos were X-irradiated in the late G2 phase in vivo. The first and second postradiation mitoses were analyzed for chromosomal anomalies. The majority of structural aberrations visible at the first mitosis after irradiation were chromatid breaks and chromatid gaps; only a few interchanges and dicentrics were observed. The aberration frequency resulted in a dose-effect relationship which was well described by a linear model. At the second mitosis 29% of the structural aberrations of the first mitosis were counted; the aberration quality changed only slightly. It is discussed whether these aberrations are to be considered new, derived, or unchanged transmitted aberrations. Contrary to the results obtained after irradiation of one-cell embryos, little chromosome loss was induced by radiation in two-cell embryos

Fulltext PDF

Indian Academy of Sciences (India)

Prakash

2010-02-03

Feb 3, 2010 ... proposed as a mechanism for brain hemispheric laterality specification ... By theory, sister chromatids of translocation-containing chromosomes are randomly segregated. ... the left and the other on the right side of the embryo.

INDUCTION OF DNA STRAND BREAKS BY TRIHALOMETHANES IN PRIMARY HUMAN LUNG EPITHELIAL CELLS

Science.gov (United States)

Abstract Trihalomethanes (TEMs) are disinfection by-products and suspected human carcinogens present in chlorinated drinking water. Previous studies have shown that many THMs induce sister chromatid exchanges and DNA strand breaks in human peripheral blood lymphocyte...

The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

Directory of Open Access Journals (Sweden)

Noonan James P

2001-07-01

Full Text Available Abstract Background Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10 or PML (promyelocytic leukemia nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. Results This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. Conclusion The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies.

Localization of two mammalian cyclin dependent kinases during mammalian meiosis

NARCIS (Netherlands)

Ashley, T.; Walpita, D.; de rooij, D. G.

2001-01-01

Mammalian meiotic progression, like mitotic cell cycle progression, is regulated by cyclins and cyclin dependent kinases (CDKs). However, the unique requirements of meiosis (homologous synapsis, reciprocal recombination and the dual divisions that segregate first homologues, then sister chromatids)

Single-cell template strand sequencing by Strand-seq enables the characterization of individual homologs

NARCIS (Netherlands)

Sanders, Ashley D; Falconer, Ester; Hills, Mark; Spierings, Diana C J; Lansdorp, Peter M.

The ability to distinguish between genome sequences of homologous chromosomes in single cells is important for studies of copy-neutral genomic rearrangements (such as inversions and translocations), building chromosome-length haplotypes, refining genome assemblies, mapping sister chromatid exchange

Structure of the Pds5-Scc1 Complex and Implications for Cohesin Function

Directory of Open Access Journals (Sweden)

Kyle W. Muir

2016-03-01

Full Text Available Sister chromatid cohesion is a fundamental prerequisite to faithful genome segregation. Cohesion is precisely regulated by accessory factors that modulate the stability with which the cohesin complex embraces chromosomes. One of these factors, Pds5, engages cohesin through Scc1 and is both a facilitator of cohesion, and, conversely also mediates the release of cohesin from chromatin. We present here the crystal structure of a complex between budding yeast Pds5 and Scc1, thus elucidating the molecular basis of Pds5 function. Pds5 forms an elongated HEAT repeat that binds to Scc1 via a conserved surface patch. We demonstrate that the integrity of the Pds5-Scc1 interface is indispensable for the recruitment of Pds5 to cohesin, and that its abrogation results in loss of sister chromatid cohesion and cell viability.

Triplex configuration in the nick-free DNAs that constitute the chromosomal scaffolds in grasshopper spermatids

Czech Academy of Sciences Publication Activity Database

Černá, Adriana; Lopez-Fernandez, C.; Fernandez, J.L.; de la Espina, S.M.D.; De la Torre, C.; Gosalvez, J.

2008-01-01

Roč. 117, č. 1 (2008), s. 15-24 ISSN 0009-5915 Institutional research plan: CEZ:AV0Z50380511 Keywords : chromatid scaffold * DNA loops * triplex DNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.111, year: 2008

New trends and techniques in chromosome aberration analysis

International Nuclear Information System (INIS)

Bender, M.A.

1978-01-01

The following topics are discussed: automation of chromosome analysis; storage of fixed cells from cultures of lymphocytes obtained routinely during periodic employee medical examinations; analysis of banded chromosomes; identification of first division metaphases; sister chromatid exchange; and patterns of aberration induction

Looping in on Ndc80 - how does a protein loop at the kinetochore control chromosome segregation?

DEFF Research Database (Denmark)

Nilsson, Jakob

2012-01-01

Segregation of chromosomes during mitosis requires the interaction of dynamic microtubules with the kinetochore, a large protein structure established on the centromere region of sister chromatids. The core microtubule-binding activity of the kinetochore resides in the KMN network, an outer...

BLM helicase suppresses recombination at G-quadruplex motifs in transcribed genes

NARCIS (Netherlands)

van Wietmarschen, Niek; Merzouk, Sarra; Halsema, Nancy; Spierings, Diana C J; Guryev, Victor; Lansdorp, Peter M

2018-01-01

Bloom syndrome is a cancer predisposition disorder caused by mutations in the BLM helicase gene. Cells from persons with Bloom syndrome exhibit striking genomic instability characterized by excessive sister chromatid exchange events (SCEs). We applied single-cell DNA template strand sequencing

Characterization of the NTPR and BD1 interacting domains of the human PICH-BEND3 complex

DEFF Research Database (Denmark)

Pitchai, Ganesha P; Hickson, Ian D; Streicher, Werner

2016-01-01

Chromosome integrity depends on DNA structure-specific processing complexes that resolve DNA entanglement between sister chromatids. If left unresolved, these entanglements can generate either chromatin bridging or ultrafine DNA bridging in the anaphase of mitosis. These bridge structures are def...

H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex

DEFF Research Database (Denmark)

Saredi, Giulia; Huang, Hongda; Hammond, Colin M

2016-01-01

After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal...

Sequence Classification: 890748 [

Lifescience Database Archive (English)

Full Text Available in, involved in maintaining sister chromatid cohesion during meiosis I as well as promoting proper attachmen...t of kinetochores to the spindle during meiosis I and meiosis II; Spo13p || http://www.ncbi.nlm.nih.gov/protein/6321802 ...

Terminalia catappa , an anticlastogenic agent against MMS induced ...

African Journals Online (AJOL)

Subjects: Anticarcinogenic potential of methanolic extract of T. catappa has been tested against the carcinogenicity induced by methyl methanesulfonate in the in vitro and in vivo models. Methods: The parameters for evaluation included chromosomal aberrations (CA), sister chromatid exchanges (SCEs) and replication ...

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

NARCIS (Netherlands)

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it

Chromosome-damaging effect of betel leaf.

Science.gov (United States)

Sadasivan, G; Rani, G; Kumari, C K

1978-05-01

The chewing of betel leaf with other ingredients is a widespread addiction in India. The chromosome damaging effect was studied in human leukocyte cultures. There was an increase in the frequency of chromatid aberrations when the leaf extract was added to cultures.

Roberts syndrome: clinical and cytogenetic aspects

OpenAIRE

Mann, N P; Fitzsimmons, J; Fitzsimmons, E; Cooke, P

1982-01-01

Roberts syndrome is reported in two sibs of consanguineous parents. Both infants had severe tetraphocomelia, facial clefting, and other serious malformations. In addition they were found to have an unusual cytogenetic abnormality with distortion of the normal sister chromatid relationship in many chromosomes.

Amphitelic orientation of centromeres at metaphase I is an important ...

Indian Academy of Sciences (India)

2014-07-31

Jul 31, 2014 ... sion of sister chromatids at AI without the second meiotic division (Matsuoka and .... level of chromosome pairing with 0.28 bivalents/PMC was seen in 20% of the ... The union of two such unreduced games could result in the ...

Impact of types of lymphocyte chromosomal aberrations on human cancer risk

DEFF Research Database (Denmark)

Hagmar, Lars; Strömberg, Ulf; Bonassi, Stefano

2004-01-01

The frequency of cells with structural chromosomal aberrations (CAs) in peripheral blood lymphocytes is the first genotoxicity biomarker that has shown an association with cancer risk. CAs are usually divided into chromosome-type (CSAs) and chromatid-type aberrations (CTAs), with different mechan...

Chromatid Painting for Chromosomal Inversion Detection, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

Chromatid Painting for Chromosomal Inversion Detection, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

The radiosensitivity of nile tilapia (Oreochromis niloticus) fingerlings

International Nuclear Information System (INIS)

Reyes, Michael Joseph T.; Velasco, Pia Victoria V.

2000-04-01

The nile tilapia (Oreochromis niloticus), a very popular fish commercially in the Philippines, was studied to determine its radiosensitivity and to see its potential as a biological indicator in aquatic ecosystems. Nile tilapia was seen to be radiosensitive. The fish were exposed to gamma-irradiation and chromosomal aberrations were induced. The various types of aberrations seen were chromatid gaps, chromosome gaps, chromatid fragments, dicentric rings, fusions, despiralizations and translocations. Among the aberrations observed, dicentric rings, fusions and chromosome gaps were strongly correlated with dosage, with only the dicentric rings increasing steadily with increasing dosage. In the course of the study, the lethal dosage 50 for nile tilapia with 18 days was determined and it was observed at 2.0 krad. The modal chromosome number was also established at 2n=44 with a karyotype exhibiting 22 pairs of acrocentric chromosomes with 2 pairs of marker chromosomes present. (Author)

The radiosensitivity of nile tilapia (Oreochromis niloticus) fingerlings

Energy Technology Data Exchange (ETDEWEB)

Reyes, Michael Joseph T; Velasco, Pia Victoria V

2000-04-01

The nile tilapia (Oreochromis niloticus), a very popular fish commercially in the Philippines, was studied to determine its radiosensitivity and to see its potential as a biological indicator in aquatic ecosystems. Nile tilapia was seen to be radiosensitive. The fish were exposed to gamma-irradiation and chromosomal aberrations were induced. The various types of aberrations seen were chromatid gaps, chromosome gaps, chromatid fragments, dicentric rings, fusions, despiralizations and translocations. Among the aberrations observed, dicentric rings, fusions and chromosome gaps were strongly correlated with dosage, with only the dicentric rings increasing steadily with increasing dosage. In the course of the study, the lethal dosage{sub 50} for nile tilapia with 18 days was determined and it was observed at 2.0 krad. The modal chromosome number was also established at 2n=44 with a karyotype exhibiting 22 pairs of acrocentric chromosomes with 2 pairs of marker chromosomes present. (Author)

Certain tryptophan photoproducts are inhibitors of cytochrome P450-dependent mutagenicity

International Nuclear Information System (INIS)

Rannug, U.; Agurell, E.; Cederberg, H.; Rannug, A.

1992-01-01

Two photoproducts, derived from UV-irradiation of the amino acid L-tryptophan and with high Ah (TCDD) receptor binding affinity, were tested for genotoxic and antimutagenic effects. The two indolo[3,2-b]carbazole derivatives, with the molecular weights of 284 and 312, respectively, were tested in Saccharomyces cerevisiae strain D7 for mitotic gene conversion and reverse mutation and in strain RS112 for sister chromatid conversion and gene conversion. No significant (P > 0.05) genotoxic effects were found in strain D7, while strain RS112 showed a small but significant increase in the frequency of sister chromatid conversions. In Chinese hamster ovary (CHO) cells the two compounds induced a statistically significant but less than twofold increase in the frequency of sister chromatid exchanges (SCE). No mutations were detected when the compounds were tested in Salmonella tphimurium strains TA98 and TA100. However, both 284 and 312 acted as antimutagens on strain TA100+S9 in the presence of benzo(a)pyrene. The decrease in mutagenicity by the most potent compound 284 was 20 revertants/nmol. This effect could be explained by an inhibitory effect on the cytochrome P450-dependent ethoxyresorufin O-deethylase (EROD) activity as seen in rat hepatocytes. The two compounds were also tested with hamster cells expressing rat cytochrome P-4501A1. The results support the conclusion that this cytochrome P-450 isozyme is inhibited by the tryptophan photoproducts. Similar results were also seen with two other high affinity Ah receptor ligands the quinazolinocarboline alkaloids rutaecapine and dehydrorutaecarpine. 20 refs., 3 figs., 4 tabs

Thrombopoietin-induced Polyploidization of Bone Marrow Megakaryocytes Is Due to a Unique Regulatory Mechanism in Late Mitosis

Science.gov (United States)

Nagata, Yuka; Muro, Yoshinao; Todokoro, Kazuo

1997-01-01

Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. However, the mechanism underlying this polyploidization remains totally unknown. It has been postulated that polyploidization is due to a skipping of mitosis after each round of DNA replication. We carried out immunohistochemical studies on mouse bone marrow megakaryocytes during thrombopoietin- induced polyploidization and found that during this process megakaryocytes indeed enter mitosis and progress through normal prophase, prometaphase, metaphase, and up to anaphase A, but not to anaphase B, telophase, or cytokinesis. It was clearly observed that multiple spindle poles were formed as the polyploid megakaryocytes entered mitosis; the nuclear membrane broke down during prophase; the sister chromatids were aligned on a multifaced plate, and the centrosomes were symmetrically located on either side of each face of the plate at metaphase; and a set of sister chromatids moved into the multiple centrosomes during anaphase A. We further noted that the pair of spindle poles in anaphase were located in close proximity to each other, probably because of the lack of outward movement of spindle poles during anaphase B. Thus, the reassembling nuclear envelope may enclose all the sister chromatids in a single nucleus at anaphase and then skip telophase and cytokinesis. These observations clearly indicate that polyploidization of megakaryocytes is not simply due to a skipping of mitosis, and that the megakaryocytes must have a unique regulatory mechanism in anaphase, e.g., factors regulating anaphase such as microtubule motor proteins might be involved in this polyploidization process. PMID:9334347

Terminalia arjuna, a herbal remedy against environmental ...

African Journals Online (AJOL)

... 429 due to AFB1 to 141 due to 5th concentration of Terminalia extracts at 32 h of exposure. Conclusion: The ameliorating potential of Terminalia extracts was dose and time dependant. Keywords: Ayurvedic medicine; Carcinogen; Chromosomal aberration; Sister chromatid exchange; Replication index; Terminalia arjuna ...

Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome

DEFF Research Database (Denmark)

Vega, H; Trainer, A H; Gordillo, M

2010-01-01

Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2, which codes for an acetyltransferase involved in the regulation of sister chromatid cohesion. Of 26 mutations described to date, only one missense mutation has been reported and all others are predicted to be truncating...

Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome

NARCIS (Netherlands)

Vega, H.; Trainer, A.H.; Gordillo, M.; Crosier, M.; Kayserili, H.; Skovby, F.; Uzielli, M.L.G.; Schnur, R.E.; Manouvrier, S.; Blair, E.; Hurst, J.A.; Forzano, F.; Meins, M.; Simola, K.O.J.; Raas-Rothschild, A; Hennekam, R.C.M.; Jabs, E.W.

2010-01-01

Background Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2, which codes for an acetyltransferase involved in the regulation of sister chromatid cohesion. Of 26 mutations described to date, only one missense mutation has been reported and all others are predicted to be

DNA Catenation Maintains Structure of Human Metaphase Chromosomes

DEFF Research Database (Denmark)

L. V. Bauer, David; Marie, Rodolphe; Rasmussen, Kristian Hagsted

2012-01-01

Mitotic chromosome structure is pivotal to cell division but difficult to observe in fine detail using conventional methods. DNA catenation has been implicated in both sister chromatid cohesion and chromosome condensation, but has never been observed directly. We have used a lab-on-a-chip microfl...

Assessment of drug induced genotoxicity in gastric cancer patients ...

African Journals Online (AJOL)

Cytogenetic studies were carried out in peripheral blood lymphocytes of study population by adopting standard cytogenetic protocols such as (a) chromosomal aberrations (CA) and (b) sister chromatid exchanges (SCE). Student t- test was adopted to analyze the statistical significance. An increased pattern in the frequency ...

Chromosome aberrations in human lymphocytes exposed to tritiated water in vitro

International Nuclear Information System (INIS)

Bocian, E.; Ziemba-zak, B.; Rosiek, O.; Sablinski, J.

1978-01-01

The induction of chromosome aberrations in human peripheral blood lymphocytes by tritiated water or 180 kV X-rays in vitro was studied. Lymphocytes were exposed to various concentrations of HTO for 2 h or for 53 h. Chromosome and chromatid type aberrations were scored during the first mitotic division after stimulation with phytohaemagglutinin. For the analysis of the dose-response relationship the data were fitted by the method of least-squares to different models. After acute exposure to tritium β-rays and X-rays, the dicentrics + centric rings and terminal + interstitial deletions gave the best fit to the linear-quadratic function. However, data for these types of aberrations after 53 h exposure to HTO gave equally good fit to the linear and linear-quadratic functions. The best description of the dose-response relationship for chromatid aberrations is given by the linear model. In the system studied the RBE of tritium β-rays as compared to 180 KV X-rays was 1.17+-0.02. (Auth.)

Action of cis-dichlorobis (cyclopentylamine) platinum (2) (cis-PAD) on L5178Y cells of two strains inversely cross-sensitive to X-rays and UV-light. Part 1. Cytotoxicity

International Nuclear Information System (INIS)

Szumiel, I.

1977-01-01

The response to cis-PAD, an antitumour platinum complex, was studied in two strains of murine lymphoma L5178Y cross-sensitive to X-rays and UV light. Dose-survival relationship, DNA synthesis, formation of chromatid aberrations, progression through the cell cycle, and growth and viability changes after 1 h cis-PAD treatment at 37 0 C were examined and compared with respective effects of X-rays and UV-light. In both strains studied, cis-PAD causes immediate inhibition of progression through the cell cycle, reduced rate of DNA synthesis, delayed appearance of chromatid aberrations and delayed death. However, there is a marked difference in sensitivity to cis-PAD between L5178Y-S strain (D 0 ca.5.8 μg/ml) and L5178Y-R strain (D 0 ca. 2.5μg/ml). In both strains a close resemblance was found between dose-survival relationship after cis-PAD and UV-light treatment, respectively. (author)

Distinct roles of FANCO/RAD51C in DNA damage signaling and repair: implications for fanconi anemia and breast cancer susceptibility

International Nuclear Information System (INIS)

Nagaraju, G.; Somyajit, K.; Subramanya, S.

2012-01-01

Unrepaired or misrepaired chromosomal double-strand breaks (DSBs) can cause gross chromosomal rearrangements which eventually can lead to tumorigenesis through inactivation of tumor suppressor genes or activation of oncogenes. There are two major mechanisms of DSB repair: non-homologous end joining (NHEJ) and homologous recombination (HR). DSBs that are generated during S and G2 phase of the cell are preferentially repaired by sister chromatid recombination (SCR), an HR pathway that utilizes neighboring sister chromatid as a template. Since the copied information is accurate, SCR is potentially an error-free pathway. HR also plays a critical role in the repair of daughter strand gaps (DSGs) that arise as a result of replication fork stalling and facilitates replication fork recovery. Furthermore, in collaboration with nucleotide excision repair and translesion synthesis, HR is involved in the repair of DNA interstrand cross-links (ICLs). Thus, HR is important for the maintenance of genome integrity and its dysfunction can lead to various genetic disorders and cancer

Restructuring of Holocentric Centromeres During Meiosis in the Plant Rhynchospora pubera.

Science.gov (United States)

Marques, André; Schubert, Veit; Houben, Andreas; Pedrosa-Harand, Andrea

2016-10-01

Centromeres are responsible for the correct segregation of chromosomes during mitosis and meiosis. Holocentric chromosomes, characterized by multiple centromere units along each chromatid, have particular adaptations to ensure regular disjunction during meiosis. Here we show by detecting CENH3, CENP-C, tubulin, and centromeric repeats that holocentromeres may be organized differently in mitosis and meiosis of Rhynchospora pubera Contrasting to the mitotic linear holocentromere organization, meiotic centromeres show several clusters of centromere units (cluster-holocentromeres) during meiosis I. They accumulate along the poleward surface of bivalents where spindle fibers perpendicularly attach. During meiosis II, the cluster-holocentromeres are mostly present in the midregion of each chromatid. A linear holocentromere organization is restored after meiosis during pollen mitosis. Thus, a not yet described case of a cluster-holocentromere organization, showing a clear centromere restructuration between mitosis and meiosis, was identified in a holocentric organism. Copyright © 2016 by the Genetics Society of America.

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.

Science.gov (United States)

Martin, Carol-Anne; Murray, Jennie E; Carroll, Paula; Leitch, Andrea; Mackenzie, Karen J; Halachev, Mihail; Fetit, Ahmed E; Keith, Charlotte; Bicknell, Louise S; Fluteau, Adeline; Gautier, Philippe; Hall, Emma A; Joss, Shelagh; Soares, Gabriela; Silva, João; Bober, Michael B; Duker, Angela; Wise, Carol A; Quigley, Alan J; Phadke, Shubha R; Wood, Andrew J; Vagnarelli, Paola; Jackson, Andrew P

2016-10-01

Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. © 2016 Martin et al.; Published by Cold Spring Harbor Laboratory Press.

Genetic damages in radiation workers of radiology centers in Bushehr port

Directory of Open Access Journals (Sweden)

Gholamreza Khamisipour

2004-09-01

Full Text Available Unstable genetic aberrations might provide a good marker for assessing genetic damage in populations exposed to low levels of ionizing radiation.The frequency of these aberrations was estimated in peripheral lymphocytes from hospital workers in Bushehr Port, occupationally exposed to low levels of ionizing radiation (54 subjects and age and sex matched controls. A total of 34 (23 males & 11 females subjects had unstable genetic aberrations (50 chromosomal-type & 31 chromatid type but only 7 subjects in control group had unstable genetic aberrations. When compared with controls, exposed workers showed a significant increase in structural chromosomal-type aberrations (p<0.001 OR=11 chromosomal exchange being the most frequent alteration. Chromatid deletion (18 cases and ring chromosome (4 cases were seen only in exposed group. There was no association between smoking status, sex, age, level of education or working years. The increased frequencies of chromosomal damage in radiation workers, indicate conducting cytogenetic analysis in parallel to physical dosimetry in the working place.

Adaptive response induced by low concentrations of MMC in human peripheral lymphocytes

International Nuclear Information System (INIS)

Sun Shuqing; Wang Bin; Jiang Jie

1998-01-01

Samples of cultured human peripheral lymphocytes were pre-treated with mitomycin C (MMC) in concentrations of 0.01∼0.1 μg/mL at 34 h of incubation and then exposed to 1.5 Gy of X-rays. Chromosome aberrations, sister chromatid exchanges and micronuclei for these lymphocytes were observed. The results show that the chromosome aberration rates for lymphocytes pre-treated with MMC in concentrations of 0.5 and 0.075 μg/mL and the frequencies of sister chromatid exchanges for lymphocytes pre-treated with MMC in concentrations of 0.01 μg/mL were significantly lower than their own expected values but the rates of micronuclei for lymphocytes pre-treated with MMC in concentrations of 0.05, 0.075 and 0.1 μg/mL were significantly higher than the expected values. Such results suggest that for studying the cross resistance of lymphocytes to chemicals and ionizing radiation, inconsistent conclusions may be obtained if different endpoints are based on

Observations on the radiosensitivity of guppy (Lebistes reticulatus Peters)

International Nuclear Information System (INIS)

Panlaque, C.A.

1982-08-01

The ichthyologically well-known teleostean fish, Lebistes reticulatus Peters commonly known as guppy, found abundant in pools, streams and estuaries was studied to establish its sensitivity to radiation and to explore its possible use as a biological indicator organism of radiation effects in the aquatic system. The guppy, Lebistes reticulatus was found to be radiosensitive. Chromosome aberrations were induced by gamma-irradiation of fish in vivo. Through cytogenetic technique the aberrant chromosomes were evaluated. The aberrant chromosomes observed were of various types such as chromatid gaps and breaks, chromosome gaps and breaks, chromatid and chromosome fragments, polycentrics (dicentrics and tricentrics), fusions and translocations. Of the types seen, it is concluded that dicentrics are the most reliable indicator of radiation effects. In the course of this study, the Lethal Radiation Dose in guppy within thirty days was determined. It was found to lie in the dose of 3 krad (LDsub(50/30)). (author)

Biomonitoring of genotoxic exposure among stainless steel welders

DEFF Research Database (Denmark)

Knudsen, Lisbeth E.; Boisen, T; Christensen, J M

1992-01-01

A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environm......A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G....... A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA...... lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding...

Relative biological efficiency of intermediate energy neutrons and 60Co rays for induction of chromosomal aberrations in Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Sturelid, S.; Bergman, R.

1976-01-01

Intermediate energy neutrons are unique in that a considerable fraction of critical interactions and of dose absorbed is not associated with ionization but with atomic collision. It is still unknown to what extent the qualitative difference in primary damage after atomic collision compared to that of ionization and excitation becomes expressed at biological levels. Chromosomal aberrations were studied in Chinese hamster fibroblasts exposed for 5-8 hours at 22 degree C to intermediate energy neutrons, mean energy 8.5 keV, or to 60 Co-gamma rays. RBE at the 10 per cent aberration frequency level in S-phase were 2.2+-0.6 for total aberrations, 2.1+-0.6 for chromatid breaks and 1.8+-0.5 for exchanges. For each chromatid aberration observed after recovery, about 200 bondbreaking atomic collisions besides 3000 primary iniozations should have occured in DNA. However, the extent to which the aberration response is due to atomic collisions is not clear. (author)

High local carcinogenic activity of 1,3-dimethyl-3-phenyl-1-nitrosourea and its inactivation by intravenous application in rats: comparison of in vivo findings with the in vitro direct and a combined in vivo/in vitro sister chromatid exchange assay in V79-E cells.

Science.gov (United States)

Thust, R; Martin, J; Mendel, J; Schreiber, D

1987-02-01

1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) is a very potent local carcinogen in rats and induces a 100% frequency of forestomach carcinomas when applied i.g. in two different dosages (10 applications of 0.3 or 0.03 mmol/kg body wt, respectively, at 14-day intervals), but it is inactive upon i.v. administration (10 applications of 0.03 mmol/kg body wt at 14-day intervals). By means of the direct sister chromatid exchange (SCE) assay in V79-E cells in the presence of rat blood, serum or plasma, respectively, as well as by a 'host-mediated' SCE assay (in which the agent was given i.v. to rats, and blood taken from the animal was checked for the recovery of genotoxic activity in cell cultures), we tried to elucidate the unexpected lack of carcinogenic activity of i.v. DMPNU. The direct SCE assay revealed a drastic reduction of DMPNU genotoxicity by rat blood, serum or plasma, respectively, which is abolished by the esterase inhibitor diisopropylfluorophosphate. In the 'host-mediated' SCE assay a genotoxic activity of DMPNU was only recoverable after a very high i.v. dose and when the blood added to the cell cultures had been taken from the rat heart within 1 min after DMPNU administration in vivo. 1-Methyl-1-nitrosourea (MNU) and 1-methyl-3-phenyl-1-nitrosourea (MPNU) were used as positive controls in these experiments and also gave a lower response than theoretically expected, but the relative loss of activity with the latter compounds was much lower than with DMPNU. It is assumed that an esterase in rat blood effectively decomposes this trisubstituted nitrosourea. Problems of the novel 'host-mediated' SCE assay are discussed.

Sultana et al., Afr J Tradit Complement Altern Med. (2016) 13(2):185 ...

African Journals Online (AJOL)

Shahid Mahboob

broken anaphase bridges formed due to chromosome rearrangements such as dicentric chromatids, intermingled ring chromosomes or union of sister chromatids‖ (Albertini et al., 2000; Bouraoui et al., 2014). The objective of this study was to assess the indirect effect of radiation in the hospital workers of radiotherapy from ...

The SUMO protease SENP1 is required for cohesion maintenance and mitotic arrest following spindle poison treatment

Energy Technology Data Exchange (ETDEWEB)

Era, Saho [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Abe, Takuya; Arakawa, Hiroshi [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Kobayashi, Shunsuke [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Szakal, Barnabas [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Yoshikawa, Yusuke; Motegi, Akira; Takeda, Shunichi [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Branzei, Dana, E-mail: dana.branzei@ifom.eu [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy)

2012-09-28

Highlights: Black-Right-Pointing-Pointer SENP1 knockout chicken DT40 cells are hypersensitive to spindle poisons. Black-Right-Pointing-Pointer Spindle poison treatment of SENP1{sup -/-} cells leads to increased mitotic slippage. Black-Right-Pointing-Pointer Mitotic slippage in SENP1{sup -/-} cells associates with apoptosis and endoreplication. Black-Right-Pointing-Pointer SENP1 counteracts sister chromatid separation during mitotic arrest. Black-Right-Pointing-Pointer Plk1-mediated cohesion down-regulation is involved in colcemid cytotoxicity. -- Abstract: SUMO conjugation is a reversible posttranslational modification that regulates protein function. SENP1 is one of the six SUMO-specific proteases present in vertebrate cells and its altered expression is observed in several carcinomas. To characterize SENP1 role in genome integrity, we generated Senp1 knockout chicken DT40 cells. SENP1{sup -/-} cells show normal proliferation, but are sensitive to spindle poisons. This hypersensitivity correlates with increased sister chromatid separation, mitotic slippage, and apoptosis. To test whether the cohesion defect had a causal relationship with the observed mitotic events, we restored the cohesive status of sister chromatids by introducing the TOP2{alpha}{sup +/-} mutation, which leads to increased catenation, or by inhibiting Plk1 and Aurora B kinases that promote cohesin release from chromosomes during prolonged mitotic arrest. Although TOP2{alpha} is SUMOylated during mitosis, the TOP2{alpha}{sup +/-} mutation had no obvious effect. By contrast, inhibition of Plk1 or Aurora B rescued the hypersensitivity of SENP1{sup -/-} cells to colcemid. In conclusion, we identify SENP1 as a novel factor required for mitotic arrest and cohesion maintenance during prolonged mitotic arrest induced by spindle poisons.

Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells.

Science.gov (United States)

Slovak, M L; Hoeltge, G A; Ganapathi, R

1986-08-01

B16-BL6 murine melanoma cells were selected for cytogenetic evaluation during the stepwise development of increasing resistance in vitro to the antitumor antibiotic, doxorubicin (DOX). Karyotypic studies demonstrated extensive heteroploidy with both numerical and structural abnormalities which were not present in the parental DOX-sensitive B16-BL6 cells. Trypsin-Giemsa banding revealed the presence of several marker chromosomes containing abnormally banding regions (ABRs) in the 44-fold B16-BL6 DOX-resistant subline. These ABRs appeared to be more homogeneously staining at the higher DOX concentrations. Length measurements (ABR index) in seven banded metaphases indicated a direct correlation with increasing DOX concentration. When the DOX-resistant cells were grown in drug-free medium for 1 yr, the drug-resistant phenotype gradually declined in parallel with the level of resistance and the ABR index. DOX-induced cytogenetic damage examined by sister chromatid exchange methodology in parental B16-BL6 cells indicated a linear sister chromatid exchange:DOX dose-response relationship. However, after continuous treatment of parental B16-BL6 cells with DOX (0.01 microgram/ml) for 30 days, sister chromatid exchange scores were found to return to base-line values. The B16-BL6 resistant cells demonstrated a cross-resistant phenotype with N-trifluoroacetyladriamycin-14-valerate, actinomycin D, and the Vinca alkaloids but not with 1-beta-D-arabinofuranosylcytosine. The results suggest that ABR-containing chromosomes in DOX-resistant sublines may represent cytogenetic alterations of specific amplified genes involved in the expression of DOX resistance. Further studies are required to identify and define the possible gene products and to correlate their relationship to the cytotoxic action of doxorubicin.

The Usefulness Cytogenetic Biomarkers in Assessment of Occupational Exposure to Microwave Radiation

International Nuclear Information System (INIS)

Garaj-Vrhovac, V.; Kopjar, N.

2003-01-01

In recent years there has been growing interest in the health effects of the electromagnetic radiation's designated extremely low frequency (ELF) and radiofrequency radiation (RFR). Available data on cytogenetic consequences of microwave exposure on the induction of chromosome damage are contradictory, mostly because of different experimental conditions of in vitro and in vivo studies. It has been suggested that exposure to radiofrequency radiation may have genetic effects, which predispose to the development of cancer or birth defects. For the detection of early biological effects of DNA-damaging agents, well-established cytogenetic biomarkers are used. Comet assay was also successfully introduced detection of primary DNA damage and micronucleus assay for simultaneous detection of chromosome damage and spindle disfunction. The chromatid breakage assay, allowing selection of persons with a defect in DNA repair, is also an additional marker in human biomonitoring. Susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes may reflect the way a person deals with carcinogenic challenges. The objective of the present study the assessment of primary DNA damage, chromosome and spindle disfunctions as well as the mutagen sensitivity in peripheral blood leukocytes in radar-facility workers daily exposed to microwave radiation and corresponding control. As sensitive biomarkers three endpoints were chosen: the alkaline comet assay, micronucleus assay and chromatid breakage assay (bleomycin sensitivity test). A large number of experimental and epidemiological studies have been carried out to elucidate the possible health hazards associated with human exposure to ELF or RF electromagnetic fields. The results presented here indicate that the alkaline comet assay, as reliable biomarker of exposure, can be successfully applied in study of DNA damaging effects in microwave exposed subjects. The fact that the comet assay is a microdosimetric

Andrographia paniculata a Miracle Herbs for cancer treatment: In ...

African Journals Online (AJOL)

It is extensively used as home remedy for various diseases in Indian traditional system ... Aim: In our present work, extracts of these ayurvedic plants were tested for their ... and anticarcinogenic properties against Aflatoxin B1 induced toxicity. ... (CA), sister chromatid exchanges (SCEs) and cell growth kinetics (RI) both in the ...

Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I

NARCIS (Netherlands)

Yakoubi, W. El; Buffin, E.; Cladiere, D.; Gryaznova, Y.; Berenguer, I.; Touati, S.A.; Gomez, R.; Suja, J.A.; Deursen, J.M.A. van; Wassmann, K.

2017-01-01

A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister

Chromosome variant 1qh− and its influence on the 3D organization ...

Indian Academy of Sciences (India)

2014-04-21

Apr 21, 2014 ... protein for sister chromatid cohesion during S phase, is char- ... tansky in 1860, the mechanisms responsible for the disease ... the Ethics Review Committee on Human Research of the ... somes 1 with equal size of heterochromatic segments in a healthy control subject (A1) .... But, literature reports about the.

4. National Congress on Genetics. Memoirs

International Nuclear Information System (INIS)

1993-01-01

According to INIS coverage were analyzed four free works on Life and Environmental Sciences presented during the Congress which are treating over the effects of external irradiation on animals. Between the main aspects are the sister chromatid exchange, spermatogonia, somatic cells, genotoxicity, DNA, chlorophyll, gamma radiation, bone marrow cells and radiation injuries

Differential response of biochemical parameters to EMS and MMS ...

African Journals Online (AJOL)

(1964) and biochemical estimations from the liver was done by the method of Sinha (1972) for catalase, Van der Vies (1954) for glycogen and Uchiyama and Mihara (1978) for MDA. Results: The study has revealed that EMS and MMS induced a dose dependent increase in chromosomal aberrations of chromatid type in the ...

Andrographia paniculata a Miracle Herbs for cancer treatment: In vivo and in vitro studies against Aflatoxin B1 Toxicity

Directory of Open Access Journals (Sweden)

Md. Sultan Ahmad

2014-04-01

Conclusion: In conclusion A. paniculata extracts significantly reduced the number of aberrant cells and frequencies of aberration per cell at each concentration and duration of exposure in vivo; similarly it reduced chromosomal aberrations and sister chromatid exchanges and replication index was enhanced in vitro that was statistically significant at <0.05 level.

Chl1 DNA helicase regulates Scc2 deposition specifically during DNA-replication in Saccharomyces cerevisiae.

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Soumya Rudra

Full Text Available The conserved family of cohesin proteins that mediate sister chromatid cohesion requires Scc2, Scc4 for chromatin-association and Eco1/Ctf7 for conversion to a tethering competent state. A popular model, based on the notion that cohesins form huge ring-like structures, is that Scc2, Scc4 function is essential only during G1 such that sister chromatid cohesion results simply from DNA replisome passage through pre-loaded cohesin rings. In such a scenario, cohesin deposition during G1 is temporally uncoupled from Eco1-dependent establishment reactions that occur during S-phase. Chl1 DNA helicase (homolog of human ChlR1/DDX11 and BACH1/BRIP1/FANCJ helicases implicated in Fanconi anemia, breast and ovarian cancer and Warsaw Breakage Syndrome plays a critical role in sister chromatid cohesion, however, the mechanism through which Chl1 promotes cohesion remains poorly understood. Here, we report that Chl1 promotes Scc2 loading unto DNA such that both Scc2 and cohesin enrichment to chromatin are defective in chl1 mutant cells. The results further show that both Chl1 expression and chromatin-recruitment are tightly regulated through the cell cycle, peaking during S-phase. Importantly, kinetic ChIP studies reveals that Chl1 is required for Scc2 chromatin-association specifically during S-phase, but not during G1. Despite normal chromatin enrichment of both Scc2 and cohesin during G1, chl1 mutant cells exhibit severe chromosome segregation and cohesion defects--revealing that G1-loaded cohesins is insufficient to promote cohesion. Based on these findings, we propose a new model wherein S-phase cohesin loading occurs during DNA replication and in concert with both cohesion establishment and chromatin assembly reactions--challenging the notion that DNA replication fork navigates through or around pre-loaded cohesin rings.

Cytological and cytochemical effects of sodium benzoate and gamma irradiation on human peripheral lymphocytes

International Nuclear Information System (INIS)

Mohamed, N.A.F.

1981-01-01

In vitro studies of human peripheral lymphocytes were conducted to elucidate and compare the effects of a suspected chemical clastogen, sodium benzoate, widely used in the food industry as an antimicrobial food additive, to that of a well-known physical mutagen, gamma rays. Blood from ten normal donors, five males and five females, was collected and treated with various doses of the two agents independently and in combination during G 0 or G 1 phase. Induction of structural chromosomal aberrations, sister chromatid exchanges (SCEs) and unscheduled DNA synthesis were used as parameters to monitor the effects of the two agents. Sodium benzoate at the same concentrations used in the food industry (0.05% and 0.10%) caused inhibition of mitosis and induced chromatid-type aberrations (gaps and breaks). The frequency of aberrations increased as the concentration of sodium benzoate increased. No increase in SCEs over the control level was observed as either concentration tested. The relative amount of DNA damage inflicted in the treated lymphocytes estimated as 3 H-tritiated thymidine incorporation (unscheduled DNA synthesis) was highly significant. In contrast, blood irradiated with 300, 600, or 900 rad 60 Co gamma rays produced chromatid and chromosome aberrations in cultured lymphocytes, dicentrics being the most frequent exchange event. The aberration yield was found to be dose-dependent and to fit the quadratic model. Unscheduled DNA synthesis as measured by lymphocyte 3 H-TdR incorporation following gamma irradiation was highly significantly increased with the largest uptake occurring during the first hour of incubation. The combined treatment of gamma irradiation plus 0.05% sodium benzoate did not increase the aberration frequencies over the independent irradiation treatments and had no effect on SCEs frequencies

Lack of Bystander Effects From High-LET Radiation For Early Cytogenetic End Points

International Nuclear Information System (INIS)

Groesser, Torsten; Cooper, Brian; Rydberg, Bjorn

2008-01-01

The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, γ-H2AX focus formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronucleus formation using DNA repair-proficient and -deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X rays. Although it was occasionally possible to detect an increase in chromatid break levels using nitrogen ions and to see a higher number of γ-H2AX foci using nitrogen and iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After we pooled all the data, we could not verify a significant bystander effect for any of these end points. Also, we did not detect a significant bystander effect for DSB induction or micronucleus formation in these cell lines or for clonogenic survival in SW48 cells. The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, data in the literature show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it is possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, may be critical for inducing bystander effects.

Lack of Bystander Effects From High LET Radiation For Early Cytogenetic Endpoints.

Energy Technology Data Exchange (ETDEWEB)

Groesser, Torsten; Cooper, Brian; Rydberg, Bjorn

2008-05-07

The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, {gamma}-H2AX focus formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronucleus formation using DNA repair-proficient and -deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X rays. Although it was occasionally possible to detect an increase in chromatid break levels using nitrogen ions and to see a higher number of {gamma}-H2AX foci using nitrogen and iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After we pooled all the data, we could not verify a significant bystander effect for any of these end points. Also, we did not detect a significant bystander effect for DSB induction or micronucleus formation in these cell lines or for clonogenic survival in SW48 cells. The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, data in the literature show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it is possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, may be critical for inducing bystander effects.

Mek1/Mre4 is a master regulator of meiotic recombination in budding yeast

Directory of Open Access Journals (Sweden)

Nancy M. Hollingsworth

2016-02-01

Full Text Available Sexually reproducing organisms create gametes with half the somatic cell chromosome number so that fusion of gametes at fertilization does not change the ploidy of the cell. This reduction in chromosome number occurs by the specialized cell division of meiosis in which two rounds of chromosome segregation follow a single round of chromosome duplication. Meiotic crossovers formed between the non-sister chromatids of homologous chromosomes, combined with sister chromatid cohesion, physically connect homologs, thereby allowing proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs whose repair is highly regulated such that (1 there is a bias for recombination with homologs rather than sister chromatids, (2 crossovers are distributed throughout the genome by a process called interference, (3 crossover homeostasis regulates the balance between crossover and non-crossover repair to maintain a critical number of crossovers and (4 each pair of homologs receives at least one crossover. It was previously known that the imposition of interhomolog bias in budding yeast requires meiosis-specific modifications to the DNA damage response and the local activation of the meiosis-specific Mek1/Mre4 (hereafter Mek1 kinase at DSBs. However, because inactivation of Mek1 results in intersister, rather than interhomolog DSB repair, whether Mek1 had a role in interhomolog pathway choice was unknown. A recent study by Chen et al. (2015 reveals that Mek1 indirectly regulates the crossover/non-crossover decision between homologs as well as genetic interference. It does this by enabling phosphorylation of Zip1, the meiosis-specific transverse filament protein of the synaptonemal complex (SC, by the conserved cell cycle kinase, Cdc7-Dbf4 (DDK. These results suggest that Mek1 is a “master regulator” of meiotic recombination in budding yeast.

Cytotoxic, genotoxic and cell-cycle disruptive effects of thio-dimethylarsinate in cultured human cells and the role of glutathione

Energy Technology Data Exchange (ETDEWEB)

Ochi, Takafumi [Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 229-0195 (Japan); Kita, Kayoko; Suzuki, Toshihide [Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 229-0195 (Japan); Rumpler, Alice; Goessler, Walter; Francesconi, Kevin A [Karl-Franzens University Graz, Institute of Chemistry-Analytical Chemistry, Universitaetsplatz 1, 8010 Graz (Austria)

2008-04-01

Thio-dimethylarsinate (thio-DMA), a recently discovered urine metabolite in humans, was investigated for its cytotoxic, genotoxic and cell-cycle disruptive effects in the cultured human hepatocarcinoma cell line, HepG2, and Syrian hamster embryo cells. In addition, the role of glutathione (GSH) on the cytotoxic effects of thio-DMA was investigated in terms of the effects of GSH depletion and the effects of exogenously added GSH. LC{sub 50} values of arsenicals for cells incubated for 48 h were 0.026 mM for thio-DMA, 0.343 mM for DMA and 3.66 mM for dithio-DMA. Depletion of cell GSH reduced the cytotoxic effects of thio-DMA. The cytotoxic effects of 0.02 mM and 0.05 mM thio-DMA were enhanced markedly when used in combination with 1 to 3 mM GSH, but decreased again when combined with 5 mM GSH. These results suggested that cytotoxic intermediates were generated by the interaction of thio-DMA with GSH, while an excessive amount of GSH suppressed the generation of these intermediates. Flow-cytometry showed that thio-DMA was an inducer of cells with 4N DNA and hypo 2N DNA. The results also demonstrated that cells arrested in the mitotic phase had abnormalities in their spindle organization and centrosome integrity. In addition, cells arrested in mitosis by thio-DMA had chromosome structural aberrations, such as chromatid gaps, chromatid breaks and chromatid exchanges. Moreover, the cytotoxic effects of thio-DMA may in part be associated with an apoptotic mode of cell death that was evaluated by the appearance of nucleosome level DNA fragmentations and an 85-kDa cleavage fragment of poly (ADP-ribose) polymerase. These findings suggest that the presence of thio-DMA in human urine has implications for human health in terms of arsenic metabolism and toxicity.

Differential response of biochemical parameters to EMS and MMS treatments and their dose effect relationship on chromosomes in induced diabetic mouse

Directory of Open Access Journals (Sweden)

B.B.D. Khalandar

2015-10-01

Conclusion: (1 Even though alkylating agents induce chromosomal aberrations in diabetic mice, MMS, a methylating agent is a more potent inducer of chromatid type of aberrations than EMS, an ethylating agent. (2 Diabetic mouse is more resistant than the non diabetic to alkylating agents and (3 the tested agents altered the analyzed biochemical parameters.

Chromosomal aberrations, micronuclei and nuclear buds induced in human lymphocytes by 2,4-dichlorophenoxyacetic acid pesticide formulation

International Nuclear Information System (INIS)

Zeljezic, Davor; Garaj-Vrhovac, Vera

2004-01-01

Pesticides of worldwide application are used in agriculture in vast amounts each year, of which herbicides are the most prominent class. Phenoxyacetic herbicides constitute one of the largest groups of herbicides sold in the world. Among them, for many years 2,4-dichlorophenoxyacetic acid (2,4-D) has been the one most used. In this study we used Deherban A[reg], a commercial formulation of 2,4-D to determine its possible genotoxic effect on human lymphocytes in vitro by chromosomal aberration analysis and micronucleus assay including the scoring of nuclear buds. Two different concentrations of pesticide formulation were used so that final concentrations of 2,4-D were 0.4 and 4 μg/ml, both in the presence and in the absence of the liver microsomal fraction as metabolic activator. Both concentrations of pesticide caused an increase in chromatid and chromosome breaks, number of micronuclei and number of nuclear buds. Presence of the S9 mix additionally elevated the number of chromatid breaks and micronuclei in treated lymphocytes

Interdependence of the rad50 hook and globular domain functions.

Science.gov (United States)

Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

2015-02-05

Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Isolation and characterization of a radiosensitive Chinese hamster ovary cell line

International Nuclear Information System (INIS)

Fuller, L.F.

1987-01-01

A x-ray sensitive Chinese hamster ovary cell line was isolated using a semi-automated procedure in which mutagenized CHO cells were allowed to form colonies on top of agar, x-irradiated, then photographed at two later times. Comparison of the photographs allowed the identification of colonies which displayed significant growth arrest. One of the colonies identified in this manner produced a stable, radiosensitive line. This cell line is normal in x-ray induced inhibition of DNA synthesis, and single- and double-strand break repair, and is moderately sensitive to ethyl methane sulfonate and UV light. The sensitive line performs only half as much x-ray-induced repair replication as the parental line and this deficiency is believed to be the primary cause of its radiosensitivity. The sensitive line produces significantly higher numbers of x-ray-induced chromosome and chromatid aberrations including chromatid aberrations following exposure during the G 1 phase of the cell cycle. The line is hypomutable compared to the parental line with x-ray exposure inducing only one-third as many 6-thioguanine resistant colonies

Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation.

Science.gov (United States)

Asghar, Adeel; Lajeunesse, Audrey; Dulla, Kalyan; Combes, Guillaume; Thebault, Philippe; Nigg, Erich A; Elowe, Sabine

2015-09-24

During mitosis, Bub1 kinase phosphorylates histone H2A-T120 to promote centromere sister chromatid cohesion through recruitment of shugoshin (Sgo) proteins. The regulation and dynamics of H2A-T120 phosphorylation are poorly understood. Using quantitative phosphoproteomics we show that Bub1 is autophosphorylated at numerous sites. We confirm mitosis-specific autophosphorylation of a several residues and show that Bub1 activation is primed in interphase but fully achieved only in mitosis. Mutation of a single autophosphorylation site T589 alters kinetochore turnover of Bub1 and results in uniform H2A-T120 phosphorylation and Sgo recruitment along chromosome arms. Consequently, improper sister chromatid resolution and chromosome segregation errors are observed. Kinetochore tethering of Bub1-T589A refocuses H2A-T120 phosphorylation and Sgo1 to centromeres. Recruitment of the Bub1-Bub3-BubR1 axis to kinetochores has recently been extensively studied. Our data provide novel insight into the regulation and kinetochore residency of Bub1 and indicate that its localization is dynamic and tightly controlled through feedback autophosphorylation.

Study on the accumulation of 147Pm in tissues and its mutagenic effect on bone marrow cells

International Nuclear Information System (INIS)

Zhu Shoupeng; Zheng Siying; Wang Chongdao; Cao Genfa

1987-09-01

The purpose of this study is to ascertain the correlation between the retentive peculiarity of 147 Pm and its possible mutagenic effect in organism administered once or for consecutive 5 days. After 147 Pm was given iv for once to male rats, it was selectively localized in liver in early stage. 5 days later, 147 Pm was located in skeleton predominantly. It caused marked chromosome aberrations on bone marrow cells. There was positive relationship between chromosome aberration rates and the amount of 147 Pm administered. When 147 Pm was administered for consecutive 5 days, it was firstly and chiefly localized in skeleton. The retention data were well described by a two exponential expressions. Retentive T 1/2 ranged from 5.89 d for the first component to 1155 d for the second slow component. Biological T 1/2 in urine for the slow component was 121.58 d. These data pointed out that the excretion of 147 Pm was slow. Among the types of aberration induced by 147 Pm were of chromatid type. Chromatid deletions were predominant, accompanied with a few chromosome aberrations

Loss of heterozygosity in yeast can occur by ultraviolet irradiation during the S phase of the cell cycle

Energy Technology Data Exchange (ETDEWEB)

Daigaku, Yasukazu [Graduate School of Life Sciences, Tohoku University, Sendai 980-8577 (Japan); Mashiko, Satsuki [Graduate School of Life Sciences, Tohoku University, Sendai 980-8577 (Japan); Mishiba, Keiichiro [Iwate Biotechnology Research Center, Kitakami, Iwate 024-0003 (Japan); Yamamura, Saburo [Iwate Biotechnology Research Center, Kitakami, Iwate 024-0003 (Japan); Ui, Ayako [Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 (Japan); Enomoto, Takemi [Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 (Japan); Yamamoto, Kazuo [Graduate School of Life Sciences, Tohoku University, Sendai 980-8577 (Japan)]. E-mail: yamamot@mail.tains.tohoku.ac.jp

2006-08-30

A CAN1/can1{delta} heterozygous allele that determines loss of heterozygosity (LOH) was used to study recombination in Saccharomyces cerevisiae cells exposed to ultraviolet (UV) light at different points in the cell cycle. With this allele, recombination events can be detected as canavanine-resistant mutations after exposure of cells to UV radiation, since a significant fraction of LOH events appear to arise from recombination between homologous chromosomes. The radiation caused a higher level of LOH in cells that were in the S phase of the cell cycle relative to either cells at other points in the cell cycle or unsynchronized cells. In contrast, the inactivation of nucleotide excision repair abolished the cell cycle-specific induction by UV of LOH. We hypothesize that DNA lesions, if not repaired, were converted into double-strand breaks during stalled replication and these breaks could be repaired through recombination using a non-sister chromatid and probably also the sister chromatid. We argue that LOH may be an outcome used by yeast cells to recover from stalled replication at a lesion.

Loss of heterozygosity in yeast can occur by ultraviolet irradiation during the S phase of the cell cycle.

Science.gov (United States)

Daigaku, Yasukazu; Mashiko, Satsuki; Mishiba, Keiichiro; Yamamura, Saburo; Ui, Ayako; Enomoto, Takemi; Yamamoto, Kazuo

2006-08-30

A CAN1/can1Delta heterozygous allele that determines loss of heterozygosity (LOH) was used to study recombination in Saccharomyces cerevisiae cells exposed to ultraviolet (UV) light at different points in the cell cycle. With this allele, recombination events can be detected as canavanine-resistant mutations after exposure of cells to UV radiation, since a significant fraction of LOH events appear to arise from recombination between homologous chromosomes. The radiation caused a higher level of LOH in cells that were in the S phase of the cell cycle relative to either cells at other points in the cell cycle or unsynchronized cells. In contrast, the inactivation of nucleotide excision repair abolished the cell cycle-specific induction by UV of LOH. We hypothesize that DNA lesions, if not repaired, were converted into double-strand breaks during stalled replication and these breaks could be repaired through recombination using a non-sister chromatid and probably also the sister chromatid. We argue that LOH may be an outcome used by yeast cells to recover from stalled replication at a lesion.

Study on radiogenotoxicological effect induced by retention of fission product 147Pm

International Nuclear Information System (INIS)

Zhu Shoupeng; Zheng Siying; Luo Zhongyu; Wang Liuyi; Zhao Xiuying

1988-01-01

Internal contamination of 147 Pm can be induced 4 chromatid breakage in one cell. This phenomenon might be due in part to nonuniform irradiation of bone marrow cells with local deposition of 147 Pm. In addition, among the types of aberrations induced by 147 Pm were predominantly of chromatid type, accompanied with a few chromosome breakage and translocation. A statistically significant elevation of SCEs was observed after 147 Pm injection. The number of SECs per cell in bone marrow cells were always higher in mice when the animals were maintained on the radioactive dose of 0.001 μCi/g level of 147 Pm. The results showed that obvious increase of mincronucleus rates could be induced by 147 Pm with low dose as 0.005 μCi/g. While the peak value appeared at 1.34% after injecting 5 μCu/g of 147 Pm for 24hr. In general, the induction of chromosomal alterations by 147 Pm to induce chromosome aberration was only 0.001 μGi/g. This value was lower than ALI of 147 Pm, as reported by ICRP publication

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

Science.gov (United States)

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.

Further environmental factors causing variations of SCE frequencies

International Nuclear Information System (INIS)

Tuschl, H.; Kovac, R.; Wottawa, A.

1986-12-01

The frequencies of spontaneously occurring sister chromatid exchanges (=SCE) were determined in control persons, persons exposed to very low doses of ionizing radiation and employees of a rubber factory. Besides smoking habits and the usage of oral contraceptives, background ultraviolet (=UV) radiation seems to exert the most pronounced effect on SCE levels in control persons. (Author)

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs

DEFF Research Database (Denmark)

Hagmar, L; Bonassi, S; Strömberg, U

1998-01-01

It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated......, occupational exposures and smoking, will be assessed in a case-referent study within the study base....

Radiogenotoxicological effect of signal nuclide 134Cs on somatic and germ cells

Institute of Scientific and Technical Information of China (English)

ZhuShou－Peng; XiaFen; 等

1997-01-01

Chromosome at aberation rates in bone marrow cells and micronucleus formation in bone marrow polychromatic erythrocytes both rise with increase in radioactivities of 134Cs,and can be fitted to power functions of radioactivities of 134Cs.In spermatogonia 134Cs mainly induced chromatid breakage,and abnormalities in sperm can also be experessed as power functions of radioactivities of 134 Cs.

Cytogenetic studies of blood, experiment M111

Science.gov (United States)

Lockhart, L. H.

1977-01-01

Analysis of the chromosome patterns of Skylab crewmen preflight and postflight recorded two types of defects: minor structural defects including chromatid breaks, chromosome breaks, deletions, and fragments were not significantly increased; structural rearrangements including dicentrics, exchange figures, inversions, and translocations occured more frequently. Data indicate that the flight itself in Skylab missions was not a contributing factor to these abberrations.

Genetical and cytological response of three tomato varieties to gamma rays

Energy Technology Data Exchange (ETDEWEB)

Hassanien, E H; Abdeltawab, F M; Elsouedy, A [Dept., of Genetics, faculty of Agriculture, Ain Shams University, Cairo, (Egypt); Sharabash, M T; Mahmoud, A A [National Center for Research and Radiation Technology, Atomic Energy Agency, Cairo (Egypt)

1995-10-01

Seeds of the tomato varieties, i.e, No. 10, bison and kecskement were irradiated with 12 krad. The abnormalities in the meiotic stages of pollen mother cells in both M1 and M2 were evaluated. The 3 varieties were greatly varied in the percentage of abnormalities occurred. The variety No. 10 showed the maximum percentage of lagging chromosomes. Meanwhile, the variety was super accounted in stickiness or clumping chromosomes, chromatid bridges and micronuclei. Whereas, the highest percentage of disturbed chromosomes and sterility was concerning to the variety kecskement. Different types of abnormalities such as stickiness, disturbed chromosomes, chromatid bridges, micronuclei and pollen sterility highly occurred in M2 than M1. Meanwhile, the percentage of lagging chromosomes reached the maximum in M1 rather than in M2. It could be mentioned that pollen sterility was increased by radiation treatment in tomato varieties. This sterility reached the maximum in M2. This was attributed to the increase in the chromosomal abnormalities in M2. A number of mutants, i.e., dwarf, non-branching, sterile plants and variations in fruit weight, had been occurred in the M2 as a function of gamma irradiation. 13 figs., 1 tab.

Genetical and cytological response of three tomato varieties to gamma rays

International Nuclear Information System (INIS)

Hassanien, E.H.; Abdeltawab, F.M.; Elsouedy, A.; Sharabash, M.T.; Mahmoud, A.A.

1995-01-01

Seeds of the tomato varieties, i.e, No. 10, bison and kecskement were irradiated with 12 krad. The abnormalities in the meiotic stages of pollen mother cells in both M1 and M2 were evaluated. The 3 varieties were greatly varied in the percentage of abnormalities occurred. The variety No. 10 showed the maximum percentage of lagging chromosomes. Meanwhile, the variety was super accounted in stickiness or clumping chromosomes, chromatid bridges and micronuclei. Whereas, the highest percentage of disturbed chromosomes and sterility was concerning to the variety kecskement. Different types of abnormalities such as stickiness, disturbed chromosomes, chromatid bridges, micronuclei and pollen sterility highly occurred in M2 than M1. Meanwhile, the percentage of lagging chromosomes reached the maximum in M1 rather than in M2. It could be mentioned that pollen sterility was increased by radiation treatment in tomato varieties. This sterility reached the maximum in M2. This was attributed to the increase in the chromosomal abnormalities in M2. A number of mutants, i.e., dwarf, non-branching, sterile plants and variations in fruit weight, had been occurred in the M2 as a function of gamma irradiation. 13 figs., 1 tab

Genome-wide high-resolution mapping of UV-induced mitotic recombination events in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Yi Yin

2013-10-01

Full Text Available In the yeast Saccharomyces cerevisiae and most other eukaryotes, mitotic recombination is important for the repair of double-stranded DNA breaks (DSBs. Mitotic recombination between homologous chromosomes can result in loss of heterozygosity (LOH. In this study, LOH events induced by ultraviolet (UV light are mapped throughout the genome to a resolution of about 1 kb using single-nucleotide polymorphism (SNP microarrays. UV doses that have little effect on the viability of diploid cells stimulate crossovers more than 1000-fold in wild-type cells. In addition, UV stimulates recombination in G1-synchronized cells about 10-fold more efficiently than in G2-synchronized cells. Importantly, at high doses of UV, most conversion events reflect the repair of two sister chromatids that are broken at approximately the same position whereas at low doses, most conversion events reflect the repair of a single broken chromatid. Genome-wide mapping of about 380 unselected crossovers, break-induced replication (BIR events, and gene conversions shows that UV-induced recombination events occur throughout the genome without pronounced hotspots, although the ribosomal RNA gene cluster has a significantly lower frequency of crossovers.

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

International Nuclear Information System (INIS)

Ivanov, B.; Mileva, M.; Bulanova, M.; Pantev, T.

1982-01-01

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

No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation

Science.gov (United States)

Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K.

2013-02-01

A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.

The formation and recovery of two-break chromosome rearrangements from irradiated spermatozoa of Drosophila melanogaster

International Nuclear Information System (INIS)

Leigh, B.

1978-01-01

Chromosome and chromatid-type rearrangements can be induced by exposure of spermatozoa of Drosophila to ionising radiation. A model, proposed to explain the formation and recovery of compound autosomes, has been extended to account for the induction of centric fragments capped by a duplication of paternal chromosome material. Three basic assumptions have been used; (1) that the sperm nucleus contains a haploid set of unreplicated chromosomes, (2) that the broken chromosome ends can be joined together before or after replication, and (3) that one of the first two cleavage nuclei may be lost and an adult organism derived from the other. The present paper reports a theoretical application of this combination of aasumptions to the general case of the formation and recovery of two-break rearrangements. This has led to an elucidation of the relation between repeats, compounds, fragments, and deficiencies on the one hand and inversions and translocations on the other hand. Dicentric chromosomes and segmental aneuploidy can be simply explained. A selective screen is formed by the segregation of chromatid rearrangements and the aneuploidy tolerance levels of the early cleavage nuclei. Thus there is an alternative way of explaining observations which might indicate preferential breakage or joining

Comparison of radiosensitivity between human hematopoietic cell lines derived from patients with Down's syndrome and from normal persons

International Nuclear Information System (INIS)

Huang, C.C.; Banerjee, A.; Tan, J.C.; Hou, Y.

1977-01-01

Seven hematopoietic cell lines, four derived from the peripheral blood of patients with Down's syndrome (DS) and three from normal persons, were irradiated with 100, 150, 300, and 500 rads from a 60 Co source and harvested for cell count and chromosome aberration studies every 12 hours for 72 hours post irradiation. Cell growth inhibition and an increase in chromosome aberration were observed in all the cell lines at each dose level and time interval. No significant difference was observed in the effects between DS and normal cell lines. The most common types of aberrations in the 12-hour samples were chromosome and/or chromatid breaks. In the later samples, chromatid exchanges were predominant. The results of the variance analyses on the induced chromosome aberrations in six lines (three DS and three normal lines) showed radiation dosage to be the largest component of total variance, following postirradiation duration and cell lines. The samples harvested 24 and 36 hours post irradiation generally showed greater effects than the samples of other harvest durations. The cell line variance could only be attributed to the differences among and between individual cell lines rather than the difference between DS and normal cell lines

Damage of chromosomes in mouse bone marrow cells after combined treatment with gamma radiation and cyclophosphamide

International Nuclear Information System (INIS)

Rupova, Ivanka

2008-01-01

Full text: Current approaches to successful management of malignancy include combined modalities of treatment with ionizing radiation and anticancer drugs. Together with tumor cells normal tissues and cells are also submitted to the damaging effect of these agents, creating thus a probability for development of secondary neoplastic processes. The aim of the present study was to investigate the rate of chromosome damage at different modalities of combined exposures to gamma irradiation and cyclophosphamide(CY) of mice. Chromosomal aberration frequency in metaphase bone marrow cells was used as a measure to evaluate the effect. Combination treatments with 3 Gy gamma irradiation and 20 mg/kg cyclophosphamide were given at different intervals - simultaneously or at 12 hr interval, in order to establish the conditions and factors influencing the rate of chromosome damage. The distribution of different types of chromosome aberrations, such as chromatid fragments, chromatid exchanges, chromosome fragments and chromosome exchanges was analyzed. The results showed a high synergistic effect at simultaneous treatment with both agents if assessed by the index of aberrations per cell (%). An attempt has been made to suggest a possible explanation of the effects at different combined treatments related to the type of induced chromosomal aberrations. (author)

Cytogenetic effects in children born to participants in the cleanup of the Chernobyl accident consequences - Acute radiation syndrome survivors and children evacuated from Pripyat

International Nuclear Information System (INIS)

Stepanova, E.I.; Misharina, J.A.

1997-01-01

The cytogenetic study of 87 children was held. Age of involved kids ranged from 5 to 14 years old. The I-st study group was presented with 17 kids born in 1987-1988 from the Chernobyl accident consequences cleaning up participants (CACCP) who survived the Acute radiation syndrome (ARS) of I-II severity degree in 1986. The II-nd study group was consisted from the 45 children born in 1983-1985 resident in town Pripyat with thyroid exposure doses from 65 to 616 sZv and total irradiation doses from 0.2 to 13.2 sZv. The 25 children born in 1983-1988 and resident in radiation situation - favourable region of Ukraine constituted the Control (III-rd) group. The aberrant cells number and chromosomal aberrations amount mainly due to chromatide type ones confidential increase compared to that in control was revealed among the children born from CACCP - ARS survivors. In children exposed to ionizing radiation during infant and early childhood age the aberrant cells number and chromosomal aberrations quantity was elevated also but due to both chromosomal (dicentrics and rings) and chromatide types. (author)

Clastogenic effects of different Ureaplasma urealyticum serovars on human chromosomes

Directory of Open Access Journals (Sweden)

R.A.F Cunha

1997-06-01

Full Text Available The possibility that Ureaplasma urealyticum might play an important role in human infertility was first raised more than 20 years ago, but this association remains speculative. Considering the hypothesis that the pathogenicity of Ureaplasma urealyticum may depend on its serotypes, the clastogenic effects of different strains of Ureaplasma urealyticum, at concentrations of 103 CCU (color changing units/ml, 104 CCU/ml and 105 CCU/ml, were evaluated in vitro in short-term cultures of human lymphocytes. Total or partial mitotic inhibition was produced by Ureaplasma urealyticum serotypes 2, 3 and 10 independent of the concentration (103 CCU/ml, 104 CCU/ml or 105 CCU/ml of the microorganisms employed. In contrast, the clastogenic effects observed with serotypes 1, 7 and 12 varied according to the concentration employed in the test. Mitotic alterations were observed in Ureaplasma urealyticum serotypes 5, 6, 7, 8, 9, 11 and 12. Chromatid gaps (53.0% and chromatid breaks (13.9% were the most frequent types of alterations observed. The results of this in vitro assay demonstrated that the clastogenic effects varied with the Ureaplasma urealyticum serotypes evaluated

40 CFR 79.65 - In vivo sister chromatid exchange assay.

Science.gov (United States)

2010-07-01

... PROGRAMS (CONTINUED) REGISTRATION OF FUELS AND FUEL ADDITIVES Testing Requirements for Registration § 79.65... appropriate concentration level, a pilot or trial study may be advisable. Initially, one concentration of the...., “Cytogenetic Studies of Mice Exposed to Styrene by Inhalation.”, Mutation Research, 280:35-43, 1992. (7) Wolff...

Cytogenetic analysis of the combined action of pesticides and radiation on human lymphocytes

International Nuclear Information System (INIS)

Ryabchenko, N.I.; Fesenko, Eh.V.; Antoshchina, M.M.

1995-01-01

The efficiency of the combined action of pesticides and irradiation at the G 0 stage was studied in cultured human lymphocytes. Carbophos (malathion) increased the yield of chromosome and chromatid fragments in irradiated lymphocytes. Herbicide 2,4-D (dichlorophenoxyacetic acid) raised lymphocyte radiosensitivity by increasing the yield of chromosome type aberrations, the radiosensitizing effect of the herbicide decreased as its concentration increased. 4 refs

Microcephaly, mental retardation and chromosomal aberrations in a girl following radiation therapy during late fetal life

Energy Technology Data Exchange (ETDEWEB)

Gustavson, K H; Jagell, S; Blomquist, H K; Nordenson, I [Umeaa Univ. (Sweden)

1981-01-01

A human foetus was heavily irradiated in the thirtieth to the thirty-third week due to carcinoma of the uterine cervix of the mother. Irradiation after 20 weeks of pregnancy is thought not to produce severe abnormalities. However, the child showed microcephaly, mental retardation, stunted growth, microphthalmus, retinal degeneration, cataract and defective dentition. Cytogenetically the frequencies of both chromatid and chromosome breaks were increased.

Microcephaly, mental retardation and chromosomal aberrations in a girl following radiation therapy during late fetal life

International Nuclear Information System (INIS)

Gustavson, K.-H.; Jagell, S.; Blomquist, H.K.; Nordenson, I.

1981-01-01

A human foetus was heavily irradiated in the thirtieth to the thirty-third week due to carcinoma of the uterine cervix of the mother. Irradiation after 20 weeks of pregnancy is thought not to produce severe abnormalities. However, the child showed microcephaly, mental retardation, stunted growth, microphthalmus, retinal degeneration, cataract and defective dentition. Cytogenetically the frequencies of both chromatid and chromosome breaks were increased. (Auth.)

Genome-Wide Analysis of Heteroduplex DNA in Mismatch Repair–Deficient Yeast Cells Reveals Novel Properties of Meiotic Recombination Pathways

Science.gov (United States)

Martini, Emmanuelle; Borde, Valérie; Legendre, Matthieu; Audic, Stéphane; Regnault, Béatrice; Soubigou, Guillaume; Dujon, Bernard; Llorente, Bertrand

2011-01-01

Meiotic DNA double-strand breaks (DSBs) initiate crossover (CO) recombination, which is necessary for accurate chromosome segregation, but DSBs may also repair as non-crossovers (NCOs). Multiple recombination pathways with specific intermediates are expected to lead to COs and NCOs. We revisited the mechanisms of meiotic DSB repair and the regulation of CO formation, by conducting a genome-wide analysis of strand-transfer intermediates associated with recombination events. We performed this analysis in a SK1 × S288C Saccharomyces cerevisiae hybrid lacking the mismatch repair (MMR) protein Msh2, to allow efficient detection of heteroduplex DNAs (hDNAs). First, we observed that the anti-recombinogenic activity of MMR is responsible for a 20% drop in CO number, suggesting that in MMR–proficient cells some DSBs are repaired using the sister chromatid as a template when polymorphisms are present. Second, we observed that a large fraction of NCOs were associated with trans–hDNA tracts constrained to a single chromatid. This unexpected finding is compatible with dissolution of double Holliday junctions (dHJs) during repair, and it suggests the existence of a novel control point for CO formation at the level of the dHJ intermediate, in addition to the previously described control point before the dHJ formation step. Finally, we observed that COs are associated with complex hDNA patterns, confirming that the canonical double-strand break repair model is not sufficient to explain the formation of most COs. We propose that multiple factors contribute to the complexity of recombination intermediates. These factors include repair of nicks and double-stranded gaps, template switches between non-sister and sister chromatids, and HJ branch migration. Finally, the good correlation between the strand transfer properties observed in the absence of and in the presence of Msh2 suggests that the intermediates detected in the absence of Msh2 reflect normal intermediates. PMID

Detection of genomic instability in α-irradiated and bystander human fibroblasts

International Nuclear Information System (INIS)

Ponnaiya, B.; Jenkins-Baker, G.; Bigelow, A.; Marino, S.; Geard, C.R.

2003-01-01

Full text: We have previously demonstrated a radiation induced bystander effect using novel co-culturing techniques where irradiated and bystander cells were cultured on two surfaces of mylar separated by media. Here we present data from experiments designed to investigate the induction of chromosomal aberrations in irradiated and bystander fibroblasts using these co-culturing techniques. Immortalized fibroblasts ((BJ1-tert) were cultured on both mylar surfaces and cells on one side were irradiated with 0.1 or 1 Gy -particles (an average of 1 and 10 particles per cell nucleus respectively), the two sides were separated 1 hour post irradiation and analyzed for chromosomal aberrations using standard Giemsa staining at either immediate or delayed time points. At 24-30 hours post irradiation, frequencies of chromosomal aberrations in irradiated populations were increased in a dose dependent manner as expected. Populations that received 0.1 and 1 Gy had 0.3 and 1.3 aberrations/cell; these aberrations were almost exclusively chromosome type aberrations. In contrast, at these times bystander populations had elevated yields of chromatid-type aberrations. When assayed at later times (15-20 population doublings post irradiation) both irradiated and bystander cells demonstrated elevated frequencies of chromatid-type aberrations. Frequencies in the irradiated populations ranged from 0.07 to 0.09 aberrations/ cell at 15 doublings, and 0.09-0.14/cell at 20 doublings, with no apparent dose response. Aberration frequencies in the bystander populations were between 0.08-0.14 per cell at the delayed time points assayed. Interestingly, the chromatid-type aberrations observed immediately post irradiation in the bystander cells, and at later times in both the irradiated and bystander populations were qualitatively similar to those previously observed at delayed times in neutron irradiated epithelial cells. Furthermore, there was a similar lack of a dose response in those studies as

Genome-wide analysis of heteroduplex DNA in mismatch repair-deficient yeast cells reveals novel properties of meiotic recombination pathways.

Directory of Open Access Journals (Sweden)

Emmanuelle Martini

2011-09-01

Full Text Available Meiotic DNA double-strand breaks (DSBs initiate crossover (CO recombination, which is necessary for accurate chromosome segregation, but DSBs may also repair as non-crossovers (NCOs. Multiple recombination pathways with specific intermediates are expected to lead to COs and NCOs. We revisited the mechanisms of meiotic DSB repair and the regulation of CO formation, by conducting a genome-wide analysis of strand-transfer intermediates associated with recombination events. We performed this analysis in a SK1 × S288C Saccharomyces cerevisiae hybrid lacking the mismatch repair (MMR protein Msh2, to allow efficient detection of heteroduplex DNAs (hDNAs. First, we observed that the anti-recombinogenic activity of MMR is responsible for a 20% drop in CO number, suggesting that in MMR-proficient cells some DSBs are repaired using the sister chromatid as a template when polymorphisms are present. Second, we observed that a large fraction of NCOs were associated with trans-hDNA tracts constrained to a single chromatid. This unexpected finding is compatible with dissolution of double Holliday junctions (dHJs during repair, and it suggests the existence of a novel control point for CO formation at the level of the dHJ intermediate, in addition to the previously described control point before the dHJ formation step. Finally, we observed that COs are associated with complex hDNA patterns, confirming that the canonical double-strand break repair model is not sufficient to explain the formation of most COs. We propose that multiple factors contribute to the complexity of recombination intermediates. These factors include repair of nicks and double-stranded gaps, template switches between non-sister and sister chromatids, and HJ branch migration. Finally, the good correlation between the strand transfer properties observed in the absence of and in the presence of Msh2 suggests that the intermediates detected in the absence of Msh2 reflect normal intermediates.

Chromosomal aberrations induced by X-rays in two mouse lymphoma (L5178Y) sublines of different radiosensitivity

International Nuclear Information System (INIS)

Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B.

1982-01-01

Two mouse lymphoma cell strains, L5178-S and L5178-R, were pulse labelled for 20 min with tritiated thymidine, and then irradiated with 1 Gy of X-rays (180 kV at 0.34 Gy/min). It was found that the cells of the radiation-sensitive subline (S) displayed a higher frequency of chromatid aberrations following radiation exposure, than cells of the radiation-resistant subline (R). (U.K.)

Chromosomal aberrations induced by X-rays in two mouse lymphoma (L5178Y) sublines of different radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B. (Institute of Nuclear Research, Warsaw (Poland))

1982-09-01

Two mouse lymphoma cell strains, L5178-S and L5178-R, were pulse labelled for 20 min with tritiated thymidine, and then irradiated with 1 Gy of X-rays (180 kV at 0.34 Gy/min). It was found that the cells of the radiation-sensitive subline (S) displayed a higher frequency of chromatid aberrations following radiation exposure, than cells of the radiation-resistant subline (R).

Cytogenetic diagnosis of Roberts SC phocomelia syndrome: First report from Kashmir

OpenAIRE

Tahir M. Malla; Arshad A. Pandith; Fayaz A. Dar; Mahrukh H. Zargar

2016-01-01

There are several syndromes in which specific mitotic chromosomal abnormalities can be seen, like premature centromere separation, premature (sister) chromatid separation, and somatic aneuploidies. Identifications of such specific cytogenetic findings can be the key factor that leads towards the diagnosis of syndromes like Roberts SC phocomelia. The case presented here as Roberts SC phocomelia syndrome was identified as a child with multiple congenital anomalies and dysmorphic features. Conve...

Action of the poison of Apis mellifera bee and gamma radiation on bone marrow cells of Wistar rats and on lymphocytes of human peripheral blood

International Nuclear Information System (INIS)

Varanda, E.A.

1987-01-01

''In vivo'' and ''in vitro'' experiments are performed to determine the radioprotective action of the poison of Apis mellifera bees. The frequency of chromosome aberrations, induced by gamma radiation, is studied in two assays: ''in vivo'' in bone marrow cells from Wistar rats and ''in vitro'' in human peripheral blood lymphocyte cultures. The sister chromatid exchanges (SCE) are studied in the ''in vitro'' assays. (M.A.C.) [pt

A comparison of the DNA and chromosome repair kinetics after #betta# irradiation

International Nuclear Information System (INIS)

Hittelman, W.N.; Pollard, M.

1982-01-01

The kinetics of repair at the chromosome and DNA levels were compared after #betta# irradiation of Chinese hamster ovary cells (CHO). Induction and repair of DNA damage were measured by the alkaline and neutral elution techniques, while chromosome damage and repair were determined by the technique of premature chromosome condensation. During and after #betta# irradiation, significant DNA repair occurred within 2 min. This fast repair could be inhibited by EDTA and pyrophosphate and probably reflected polynucleotide ligase activity. A slower component of DNA repair was detected between 15 and 60 min after irradiation, by which time most of the DNA had been repaired. In contrast, chromosome repair was not detectable until 45 min after irradiation, and nearly half of the chromatid breaks were repaired by 60 min. Cycloheximide, an inhibitor of protein synthesis, prevented chromosome break repair, yet had no effect on the immediate formation of chromatid exchanges or DNA repair. These results suggest the following: (1) the rapidly repairing DNA lesions are not important in the repair of chromosomes; (2) chromosome damage involves only a minority of the DNA lesions measured by alkaline and neutral DNA elution; and (3) chromosome repair may involve more than simply the repair of damaged DNA that can be detected by the alkaline and neutral elution assays

Termini of human chromosomes display elevated rates of mitotic recombination.

Science.gov (United States)

Cornforth, M N; Eberle, R L

2001-01-01

The strand-specific in situ hybridization technique of CO-FISH was used to probe telomeres of human mitotic cells in order to determine the spontaneous frequency of crossover. This approach allowed the detection of recombinational crossovers occurring anywhere along the length of individual chromosomes, including reciprocal events taking place between sister chromatids. Although the process of sister chromatid exchange (SCE) is the most prominent type of recombination in somatic mammalian cells, our results show that SCEs accounted for less than a third of the recombinational events revealed by CO-FISH. It is concluded that chromosomal regions near the termini of chromosome arms undergo extraordinarily high rates of spontaneous recombination, producing terminal crossovers whose small size precludes detection by standard cytogenetic methods. That similar results were observed for transformed epithelial cells, as well as primary fibroblasts, suggests that the phenomenon is a common characteristic of human cells. These findings are noteworthy because, although telomeric and subtelomeric DNA is known to be preferentially involved in certain types of recombination, the tips of somatic mammalian chromosomes have not previously been identified as preferred sites for crossover. Implications of these results are discussed in terms of limitations imposed on CO-FISH for its proposed use in directional hybridization mapping.

Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

Science.gov (United States)

Federico, María Belén; Vallerga, María Belén; Radl, Analía; Paviolo, Natalia Soledad; Bocco, José Luis; Di Giorgio, Marina; Soria, Gastón; Gottifredi, Vanesa

2016-01-01

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.

Detection of chromosomal instability in α-irradiated and bystander human fibroblasts

International Nuclear Information System (INIS)

Ponnaiya, Brian; Jenkins-Baker, Gloria; Bigelow, Alan; Marino, Stephen; Geard, Charles R.

2004-01-01

There is increasing evidence biological responses to ionizing radiation are not confined to those cells that are directly hit, but may be seen in the progeny at subsequent generations (genomic instability) and in non-irradiated neighbors of irradiated cells (bystander effects). These so called non-targeted phenomena would have significant contributions to radiation-induced carcinogenesis, especially at low doses where only a limited number of cells in a population are directed hit. Here we present data using a co-culturing protocol examining chromosomal instability in α-irradiated and bystander human fibroblasts BJ1-htert. At the first cell division following exposure to 0.1 and 1 Gy α-particles, irradiated populations demonstrated a dose dependent increase in chromosome-type aberrations. At this time bystander BJ1-htert populations demonstrated elevated chromatid-type aberrations when compared to controls. Irradiated and bystander populations were also analyzed for chromosomal aberrations as a function of time post-irradiation. When considered over 25 doublings, all irradiated and bystander populations had significantly higher frequencies of chromatid aberrations when compared to controls (2-3-fold over controls) and were not dependent on dose. The results presented here support the link between the radiation-induced phenomena of genomic instability and the bystander effect

Selective accumulation of 147Pm in organism on induction of PCE's micronucleus and SCE of bone marrow cells as well as the chromosome aberrations on fetal liver and spleen

International Nuclear Information System (INIS)

Zhu Shoupeng; Zheng Siying; Wang Liuyi; Lu Zhongyan; Yang Shuqin

1989-01-01

Study of accumulation peculiarity of 147 Pm showed that I.V. different doses of 147 Pm were the same selectively localized in skeleton and liver. Retention of 147 Pm in skeleton and liver was elevated when the radioactive doses of 147 Pm were increased. At the same time absorption does of 147 Pm radiation was heightened. The ability of 147 Pm to induce sister chromatid exchanges (SCEs) has been investigated by IdU labelling methods. A statistically significant elevation of SCEs was observed after 147 Pm intake.In mice the number of SCEs per cell in bone marrow cells was always higher when the animals were maintained on the doses of 37 Bq/g. The injurious effects of 147 Pm, using PCE's micronucleus rates in bone marrow cells were observed. 147 Pm was dominantly deposited on maternal liver. Deposition of 147 Pm in maternal spleen was about quandrantal of the maternal liver. Studies indicated that maternal contamination of 147 Pm could induced chromosome aberrations in fetal liver and spleen cells. Among the type of aberrations induced by 147 Pm, chromatid breakage were predominant. The incidence of chromosome aberrations on fetal liver cells induced by 147 Pm was higher on fetal spleen cells

Studies on mutagenic activity of 60Co γ-ray irradiated rape pollen

International Nuclear Information System (INIS)

He Weishun; Liu Aihua; Lin Shiying; Xiong Xikun

1989-01-01

In the present study on disinfection, the rape pollen was irradiated with 2.5 kGy 60 Co γ-ray. Micronuclei, sister chromatid exchanges (SCE) of bone marrow cells and chromosomal aberrations of meiotic cells in mice were used as an indicater of chromosomal damage to study the mutagenicity of irradiated rape pollen. The results are as follows: (1) The frequency of micronuclei in polychromatic erythrocytes is 2.00 per mille; nucleated cells is 0.8 per mille in control group. In the numbers of polychromatic erythrocytes and nucleated cells with micronuclei, there is no obviously difference in irradiated and unirradiated groups. (2) SCE incidence of control group is 2.01 ± 0.12/cell. No significant difference in the frequency of SCE exists between non-irradiated rape pollen and the control groups. But the frequency of SCE in irradiated rape pollen group (3000 mg/kg/day x 7) is 2.36 ± 0.12/cell; high dose group (6000 mg/kg/day x 7) is 2.96 ± 0.14/cell. In comparison with control group, there is a significant difference. (3) The chromatid breaks, fragments, and univalents in primary spermatocytes have been obseved. The frequencies of chromosomal aberration showed no obviously difference among irradiated and non-irradiated rape pollen groups

Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

Science.gov (United States)

Máthé, Csaba; M-Hamvas, Márta; Vasas, Gábor

2013-01-01

Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs), a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN), an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs) are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS) and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization. PMID:24084787

Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

Directory of Open Access Journals (Sweden)

Gábor Vasas

2013-09-01

Full Text Available Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs, a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN, an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization.

Effects of Simultaneous Radiofrequency Radiation and Chemical Exposure of Mammalian Cells. Volume 2

Science.gov (United States)

1988-07-01

chromosome - - - - - - -I aberrations and sister chromatid exchanges (SCE). Yao (1982) exposed rat kangaroo RH5 and RH1l6 cells to 2.45 GHz radiation, and...control was reported in chromosome aberrations. Yac (1982) investigated the cytogenetic consequences of chronic microwave exposure on rat kangaroo RH5...was said to be 280C. The cells were exposed both as conidia, which are "rather inactive metabolically ," and also after DNA replication had been

Repair of O6-(2-chloroethyl)guanine mediates the biological effects of chloroethylnitrosoureas.

OpenAIRE

Bodell, W J; Aida, T; Berger, M S; Rosenblum, M L

1985-01-01

Chloroethylnitrosoureas (CENUs) are alkylating and crosslinking agents used for the treatment of human cancer; they are both mutagenic and carcinogenic. We compared the levels of induction of sister chromatid exchanges (SCEs) and the cytotoxicity of nitrosoureas that alkylate only with CENUs. CENUs are 200-fold more cytotoxic and induce SCEs with 45-fold greater efficiency than agents that do not crosslink; therefore, crosslinking is probably the most important molecular event that leads to c...

Imaging of DNA Ultrafine Bridges in Budding Yeast.

Science.gov (United States)

Quevedo, Oliver; Lisby, Michael

2018-01-01

DNA ultrafine bridges (UFBs) are a type of chromatin-free DNA bridges that connect sister chromatids in anaphase and pose a threat to genome stability. However, little is known about the origin of these structures, and how they are sensed and resolved by the cell. In this chapter, we review tools and methods for studying UFBs by fluorescence microscopy including chemical and genetic approaches to induce UFBs in the model organism Saccharomyces cerevisiae.

Imaging of DNA Ultrafine Bridges in Budding Yeast

DEFF Research Database (Denmark)

Quevedo Rodriguez, Oliver; Lisby, Michael

2018-01-01

DNA ultrafine bridges (UFBs) are a type of chromatin-free DNA bridges that connect sister chromatids in anaphase and pose a threat to genome stability. However, little is known about the origin of these structures, and how they are sensed and resolved by the cell. In this chapter, we review tools...... and methods for studying UFBs by fluorescence microscopy including chemical and genetic approaches to induce UFBs in the model organism Saccharomyces cerevisiae....

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

OpenAIRE

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

2012-01-01

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible. On average, murine embryonic stem (mES) cells exhibit eight SCEs, which are detected at a resolution of up...

Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase

DEFF Research Database (Denmark)

Rosenthal, Andrew S; Dexheimer, Thomas S; Gileadi, Opher

2013-01-01

complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating...... and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome....

In vitro studies on chemoprotective effect of Purnark against benzo(a)pyrene-induced chromosomal damage in human lymphocytes.

Science.gov (United States)

Ghaisas, S D; Bhide, S V

1994-01-01

Human lymphocytes were used as an assay system to test chemopreventive activity of natural products. Purnark, a mixture of extracts of turmeric, betel leaf and catechu, was tested for its chemoprotective activity against BP induced DNA damage. Sister chromatid exchange and micronuclei were used as markers to assess the protective activity of Purnark. Purnark gave 50-60% protection against BP induced SCEs and micronuclei. Purnark at 100 micrograms dose did not show any genotoxicity.

Inhibition of repair activity induced by γ-radiation, UV-rays and radiomimetics in the in vitro cultured cells of patients wiyh schizophrenia

International Nuclear Information System (INIS)

Zasukhina, G.D.; Zharikov, N.M.; L'vova, G.N.; Vasil'eva, I.M.; Chekova, V.V.; Alekhina, N.I.; Ivanova, T.N.

1986-01-01

A study was made of the processes of repair, virus reactivation, and formation of sister chromatid exchages (SCE) in blood cells of patients with schizophrenia after the effect of γ-radiation and 4-nitroquinoline-1-oxide. These processes were estimated by 12 criteria. The mutagen-induced disturbances in the processes of repair and SCE formation were found in cells of patients with schizophrenia and were absent in the control cells of healthy donors

Fanconi anaemia proteins are associated with sister chromatid bridging in mitosis

DEFF Research Database (Denmark)

Ying, Songmin; Hickson, Ian D

2011-01-01

exist in man where a breakdown in genome maintenance is associated with cancer predisposition. Amongst these are Bloom's syndrome (BS) and Fanconi anaemia (FA). The BS and FA gene products co-operate in the repair of damaged DNA. In this review, we focus on interactions between BS and FA proteins...

Homologous recombination, sister chromatid cohesion, and chromosome condensation in mammalian meiosis

NARCIS (Netherlands)

Eijpe, M.

2002-01-01

In the life cycle of sexually reproducing eukaryotes, haploid and diploid generations of cells alternate. Two types of cell division occur in such a life cycle: mitosis and meiosis. They are compared in chapter 1 . Haploid and

Repairability during G1 of the inductor leisure of exchanges in the sister chromatid induced by alkylating agents in DNA substituted and no substituted with BUDR, in cells of the salivary gland of mouse In vivo; Reparabilidad durante G1 de las lesiones inductoras de intercambios en las cromatidas hermanas inducidos por agentes alquilantes en ADN sustituido y no sustituido con BrdU, en celulas de la glandula salival de raton In vivo

Energy Technology Data Exchange (ETDEWEB)

Gonzalez B, F

2004-07-01

In this work you determines the repair of the lesions inductoras of Sister chromatid exchange (ICHs) generated in the cells of the salivary gland of mouse, for the treatment with the N-Methyl-N-Nitrosourea (MNU), the N-Ethyl-N-Nitrosourea (ENU), the Methyl methanesulfonate (MMS) and the Ethyl methanesulfonate (EMS) in early and slow G1 of the first one and the second cellular division, that is to say before and after the cells incorporate 5-bromine-2 -Desoxyuridine (BrdU) in the DNA. Groups witness non treaties were included with mutagen. The cells of the salivary gland repaired the generated lesions partially by the MNU, the MMS and the EMS in the 1st division, and only the lesions induced by the ENU and MMS were repaired partially in the 2nd division. The ENU generates injure that they were not repaired in the 1st division and those taken place by the EMS were little repaired in the 2nd division. The methylating agents generated but ICHs that the ethylating. One observes that the BrdU makes to the molecule of the DNA but susceptible to the damage generated by the alkylating agents that induce the formation of the ICHs. This susceptibility was incremented around 150% for the treatment with the MNU, the ENU and the MMS, on the other hand for the EMS it was 3 times minor. It is proposed that the one electronegative atom of this analog of the timine would to work as a nucleophyllic center with which the electrophyllic compounds react. (Author)

Differential radiosensitivity phenotypes of DNA-PKcs mutations affecting NHEJ and HRR systems following irradiation with gamma-rays or very low fluences of alpha particles.

Science.gov (United States)

Lin, Yu-Fen; Nagasawa, Hatsumi; Little, John B; Kato, Takamitsu A; Shih, Hung-Ying; Xie, Xian-Jin; Wilson, Paul F; Brogan, John R; Kurimasa, Akihiro; Chen, David J; Bedford, Joel S; Chen, Benjamin P C

2014-01-01

We have examined cell-cycle dependence of chromosomal aberration induction and cell killing after high or low dose-rate γ irradiation in cells bearing DNA-PKcs mutations in the S2056 cluster, the T2609 cluster, or the kinase domain. We also compared sister chromatid exchanges (SCE) production by very low fluences of α-particles in DNA-PKcs mutant cells, and in homologous recombination repair (HRR) mutant cells including Rad51C, Rad51D, and Fancg/xrcc9. Generally, chromosomal aberrations and cell killing by γ-rays were similarly affected by mutations in DNA-PKcs, and these mutant cells were more sensitive in G1 than in S/G2 phase. In G1-irradiated DNA-PKcs mutant cells, both chromosome- and chromatid-type breaks and exchanges were in excess than wild-type cells. For cells irradiated in late S/G2 phase, mutant cells showed very high yields of chromatid breaks compared to wild-type cells. Few exchanges were seen in DNA-PKcs-null, Ku80-null, or DNA-PKcs kinase dead mutants, but exchanges in excess were detected in the S2506 or T2609 cluster mutants. SCE induction by very low doses of α-particles is resulted from bystander effects in cells not traversed by α-particles. SCE seen in wild-type cells was completely abolished in Rad51C- or Rad51D-deficient cells, but near normal in Fancg/xrcc9 cells. In marked contrast, very high levels of SCEs were observed in DNA-PKcs-null, DNA-PKcs kinase-dead and Ku80-null mutants. SCE induction was also abolished in T2609 cluster mutant cells, but was only slightly reduced in the S2056 cluster mutant cells. Since both non-homologous end-joining (NHEJ) and HRR systems utilize initial DNA lesions as a substrate, these results suggest the possibility of a competitive interference phenomenon operating between NHEJ and at least the Rad51C/D components of HRR; the level of interaction between damaged DNA and a particular DNA-PK component may determine the level of interaction of such DNA with a relevant HRR component.

Many functions of the meiotic cohesin.

Science.gov (United States)

Bardhan, Amit

2010-12-01

Sister chromatids are held together from the time of their formation in S phase until they segregate in anaphase by the cohesin complex. In meiosis of most organisms, the mitotic Mcd1/Scc1/Rad21 subunit of the cohesin complex is largely replaced by its paralog named Rec8. This article reviews the specialized functions of Rec8 that are crucial for diverse aspects of chromosome dynamics in meiosis, and presents some speculations relating to meiotic chromosome organization.

In Vivo Cytogenetic Studies on Aspartame

OpenAIRE

AlSuhaibani, Entissar S.

2010-01-01

Aspartame (a-Laspartyl-L-phenylalanine 1-methylester) is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol) was investigated in vivo using chromosomal aberration (CA) test and sister chromatid exchange (SCE) test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight)....

Dominant-lethal mutations and heritable translocations in mice

Energy Technology Data Exchange (ETDEWEB)

Generoso, W.M.

1983-01-01

Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

Dominant-lethal mutations and heritable translocations in mice

International Nuclear Information System (INIS)

Generoso, W.M.

1983-01-01

Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

Directory of Open Access Journals (Sweden)

María Belén Federico

2016-01-01

Full Text Available Fanconi Anemia (FA is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs. FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.

APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast.

Science.gov (United States)

Jonak, Katarzyna; Zagoriy, Ievgeniia; Oz, Tugce; Graf, Peter; Rojas, Julie; Mengoli, Valentina; Zachariae, Wolfgang

2017-06-18

Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at meiosis II, it was unclear how and when centromeric Rec8 is liberated from its protector PP2A. One proposal is that bipolar spindle forces separate PP2A from Rec8 as cells enter metaphase II. We show here that sister centromere biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast. Instead, our data suggest that the ubiquitin-ligase APC/C Cdc20 removes PP2A from centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1. This implies that Rec8 remains protected until entry into anaphase II when it is phosphorylated concurrently with the activation of separase. Here, we provide further support for this model and speculate on its relevance to mammalian oocytes.

The mitosis-regulating and protein-protein interaction activities of astrin are controlled by aurora-A-induced phosphorylation.

Science.gov (United States)

Chiu, Shao-Chih; Chen, Jo-Mei Maureen; Wei, Tong-You Wade; Cheng, Tai-Shan; Wang, Ya-Hui Candice; Ku, Chia-Feng; Lian, Chiao-Hsuan; Liu, Chun-Chih Jared; Kuo, Yi-Chun; Yu, Chang-Tze Ricky

2014-09-01

Cells display dramatic morphological changes in mitosis, where numerous factors form regulatory networks to orchestrate the complicated process, resulting in extreme fidelity of the segregation of duplicated chromosomes into two daughter cells. Astrin regulates several aspects of mitosis, such as maintaining the cohesion of sister chromatids by inactivating Separase and stabilizing spindle, aligning and segregating chromosomes, and silencing spindle assembly checkpoint by interacting with Src kinase-associated phosphoprotein (SKAP) and cytoplasmic linker-associated protein-1α (CLASP-1α). To understand how Astrin is regulated in mitosis, we report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser(115). The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. Moreover, S115A fails to bind mitosis regulators, including SKAP and CLASP-1α, which results in the mitotic defects observed in Astrin S115A-transfected cells. In conclusion, Aurora-A phosphorylates Astrin and guides the binding of Astrin to its cellular partners, which ensures proper progression of mitosis. Copyright © 2014 the American Physiological Society.

The kinetochore of the Lepidoptera, (2)

International Nuclear Information System (INIS)

Maeki, Kodo

1980-01-01

The chromosomes of Graphium Sarpedon (n, 20) and Eumeta variegata were examined by the acetoorcein squash method. In the equatorial plate of M-2 metaphase, two sister chromatids (rod-type) appeared in linear arrangement. The spindle fibers then gathered to the chromosomal part toward the cell pole, which condensed longwise on the other side. In the second anaphase, the two sister chromatids moved to the opposite poles, they appeared to move toward the pole ends-first. The M-2 metaphase and anaphase were identified only for the chromosomes equipped with the diffuse kinetochore structure. The male larvae of Graphium Sarpedon at the last-instar were irradiated with 800, 1000, 1500 or 2000 R of 60 Co to induce chromosome fragmentation, and killed 18, 21, 24, 27 and 30 hrs after the irradiation. The chromosomal aberration at the meitotic stage after the irradiation of 1500 R and 2000 R was pronounced. Although the normal haploid chromosome number of G. sarpedon is 20, it was found that the irradiated larvae had 21 or 19 chromosomes at the M-1 metaphase. The aberration resulted from chromosomal fusion as well as from fragmentation during meiosis. It was suggested that the induced fragment chromosomes each carry kinetochore. In general, it is considered that the chromosomes of lepidopteran insects were characterized by holokinetic organization. (Kaihara, S.)

Evaluation of cytogenetic and DNA damage in human lymphocytes treated with adrenaline in vitro.

Science.gov (United States)

Djelić, Ninoslav; Radaković, Milena; Spremo-Potparević, Biljana; Zivković, Lada; Bajić, Vladan; Stevanović, Jevrosima; Stanimirović, Zoran

2015-02-01

Catechol groups can be involved in redox cycling accompanied by generation of reactive oxygen species (ROS) which may lead to oxidative damage of cellular macromolecules including DNA. The objective of this investigation was to evaluate possible genotoxic effects of a natural catecholamine adrenaline in cultured human lymphocytes using cytogenetic (sister chromatid exchange and micronuclei) and the single cell gel electrophoresis (Comet) assay. In cytogenetic tests, six experimental concentrations of adrenaline were used in a range from 0.01-500 μM. There were no indications of genotoxic effects of adrenaline in sister chromatid exchange and micronucleus tests. However, at four highest concentrations of adrenaline (5 μM, 50 μM, 150 μM and 300 μM) we observed a decreased mitotic index and cell-cycle delay. In addition, in the Comet assay we used adrenaline in a range from 0.0005-500 μM, at two treatment times: 15 min or 60 min. In contrast to cytogenetic analysis, there was a dose-dependent increase of DNA damage detected in the Comet assay. These effects were significantly reduced by concomitant treatment with quercetin or catalase. Therefore, the obtained results indicate that adrenaline may exhibit genotoxic effects in cultured human lymphocytes, most likely due to production of reactive oxygen species. Copyright © 2014 Elsevier Ltd. All rights reserved.

An investigation of the genetic toxicology of irradiated foodstuffs using short-term test systems

International Nuclear Information System (INIS)

Phillips, B.J.; Kranz, E.; Elias, P.S.

1980-01-01

As part of a programme of short-term tests used to detect possible genetic toxicity in irradiated foodstuffs, cultured Chinese hamster ovary cells were exposed to extracts and digests of irradiated and unirradiated dates, fish and chicken and subjected to tests for cytotoxicity, sister chromatid exchange induction and mutation to thioguanine resistance. The results showed no evidence of genetic toxicity induced in food by irradiation. The general applicability of cell culture tests to the detection of mutagens in food is discussed. (author)

Zoological aspects of the ecological integrity of a radioactive waste disposal site

International Nuclear Information System (INIS)

Nel, J.A.J.; Picker, M.D.

1986-01-01

The possible effects of nuclear waste disposal at the Vaalputs terrain on the endemic fauna are being monitored by assessing changes in the occurrence of small mammal species, their density, food, reproduction, parasite load, gross abnormalities and longevity, as well as the occurrence of chromosome and chromatid lesions. Interactions between the radiation source and animals are studied by monitoring burrowing activity of arthropods, and the soil they transfer to the surface, as well as the burrowing activity of rodent species

Alteration of gene conversion patterns in Sordaria fimicola by supplementation with DNA bases.

Science.gov (United States)

Kitani, Y; Olive, L S

1970-08-01

Supplementation with DNA bases in crosses of Sordaria fimicola heterozygous for spore color markers (g(1), h(2)) within the gray-spore (g) locus has been found to cause significant alterations in patterns of gene conversion at the two mutant sites. Each base had its own characteristic effect in altering the conversion pattern, and responses of the two mutant sites to the four bases were different in several ways. Also, the responses of the two involved chromatids of the meiotic bivalent were different.

Evaluation of cytogenetic effects of very short laser pulsed radiations

International Nuclear Information System (INIS)

Guedeney, G.; Courant, D.; Malarbet, J.-L.; Dolloy, M.-T.; Court, L.

1992-01-01

The aim of this study is to evaluate the capacity of a laser, delivering very short pulses in the near infrared spectrum with a high pulse ratio frequency, to induce genetic modification on biological tissues. Chromatid exchanges and chromosomal aberrations studies are used to test potential effect on human lymphocytes. The laser irradiation induces a significant increase of acentric fragments but the absence of dicentric suggests that a repetitive very short pulses irradiation has a relatively low capacity to induce genetic abnormalities. (author)

In vitro and in vivo genotoxicity of 1,3-butadiene and metabolites.

OpenAIRE

Arce, G T; Vincent, D R; Cunningham, M J; Choy, W N; Sarrif, A M

1990-01-01

1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange (SCE) and micronucleus induction results indicated 1,3-butadiene was genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats ...

Effect of cysteamine on sister chromatid exchange (SCE) induction by gamma rays

International Nuclear Information System (INIS)

Mendiola Cruz, M.T.

1987-01-01

The effect of different doses of cysteamine (3, 15 and 150 μg/g bw) on gamma ray-induced SCE was evaluated and compared with the responses obtained with regard to frequency of chromosomal aberrations, frequency of proliferating cells and the rate of cellular proliferating kinetics in mouse bone marrow cells in vivo. Groups of mice were either irradiated, treated with cysteamine and irradiated, only treated with cysteamine or left without treatment for determination of these parameters. The intraperitoneal administration of cysteamine preceding 1 Gy of gamma ray exposure, produces a dose dependent radioprotection on SCE-induction obtaining the greatest effect with 150 μg/g bw. However, this effect was not observed in the mitotic index nor in the average generation time. Chromosomic aberrations in animals irradiated after treatment with cysteamine were also detected. It was not observed any citotoxic or genotoxic effect produced by cysteamine per se. The results suggest that, under the experimental conditions of this study, the SCE are caused by free radicals produced by gamma radiation; not so, the additional damage indexes measured. (author)

The Physics of the Metaphase Spindle.

Science.gov (United States)

Oriola, David; Needleman, Daniel J; Brugués, Jan

2018-05-20

The assembly of the mitotic spindle and the subsequent segregation of sister chromatids are based on the self-organized action of microtubule filaments, motor proteins, and other microtubule-associated proteins, which constitute the fundamental force-generating elements in the system. Many of the components in the spindle have been identified, but until recently it remained unclear how their collective behaviors resulted in such a robust bipolar structure. Here, we review the current understanding of the physics of the metaphase spindle that is only now starting to emerge.

Cytogenetic effects of chemotherapy and cranial irradiation on the peripheral blood lymphocytes of children with malignant disease

Energy Technology Data Exchange (ETDEWEB)

Fischer, P; Vetterlein, M; Pohl-Rueling, J; Krepler, P

1977-01-01

Results of a cytogenetic analysis of peripheral blood lymphocytes of children with leukemia after massive chemotherapy and cranial irradiation, and of children with nephrosis after cortisone therapy and cyclophosphamide are presented. Prolonged intensive chemotherapy results in a significant rise in the number of chromatid aberrations after twelve months, and of chromosomal aberrations after 24 months of therapy. After cranial irradiation a sharp rise in chromosome aberrations is present for about three months. This drops after one year to levels present in cases with chemotherapy alone.

Nanoceria have no genotoxic effect on human lens epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Pierscionek, Barbara K; Yasseen, Akeel A [School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA (United Kingdom); Li, Yuebin; Schachar, Ronald A; Chen, Wei [Department of Physics, University of Texas at Arlington, Arlington, TX 76019 (United States); Colhoun, Liza M, E-mail: b.pierscionek@ulster.ac.uk, E-mail: weichen@uta.edu [Centre for Vision and Vascular Sciences, School of Medicine, Dentistry and Biomedical Sciences, Queen' s University Belfast, Grosvenor Road, Belfast, BT12 6BA (United Kingdom)

2010-01-22

There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO{sub 2}) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 {mu}g ml{sup -1} of CeO{sub 2} nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

Resistance to radiation, recombination, repair of DNA and chromosome organisation

Energy Technology Data Exchange (ETDEWEB)

Fletcher, H L [East Anglia Univ., Norwich (UK). School of Biological Sciences

1981-01-01

The model advanced here proposes that death is caused by destructive lesions, mainly double-strand breaks, in all the inter-repairable copies so close together that recombination repair cannot function. Death is related to the exponential of dose where r is the number of copies of the genome. A graph of ln(-ln survival) against ln dose is used to produce a linear dose-survival relationship, the slope of which gives the number of inter-repairable copies of the genome (= number of hits per lethal event). In Ustilago maydis it seems that unless all the chromatids are broken within a few thousand base pairs all ds breaks are repaired. The size of this critical target is similar to the size of a gene. Meiotic pairing in fungi starts outside the genes, and it is therefore suggested that specific pairing sites between genes define the ends of the targets. The model also describes the radiation-induced death of Micrococcus radiodurans and Sacchromyces cerevisiae. Cultured mammalian cells also show a linear ln(-ln survival)/ln dose relationship with a slope of 1.5 showing that both 1st and 2nd order killing occured. Sublethal radiation induces recombination in heterozygous diploid U. maydis proportional to the square of the dose. Sister-chromatid repair is preferred. Polyploid yeast can only use pairs of chromosomes for repair, showing that chromosome pairing is required for recombination repair, and mitotic pairing is restricted to bivalents in the same way that meiotic pairing is.

Arabidopsis thaliana WAPL is essential for the prophase removal of cohesin during meiosis.

Directory of Open Access Journals (Sweden)

Kuntal De

2014-07-01

Full Text Available Sister chromatid cohesion, which is mediated by the cohesin complex, is essential for the proper segregation of chromosomes in mitosis and meiosis. The establishment of stable sister chromatid cohesion occurs during DNA replication and involves acetylation of the complex by the acetyltransferase CTF7. In higher eukaryotes, the majority of cohesin complexes are removed from chromosomes during prophase. Studies in fly and human have shown that this process involves the WAPL mediated opening of the cohesin ring at the junction between the SMC3 ATPase domain and the N-terminal domain of cohesin's α-kleisin subunit. We report here the isolation and detailed characterization of WAPL in Arabidopsis thaliana. We show that Arabidopsis contains two WAPL genes, which share overlapping functions. Plants in which both WAPL genes contain T-DNA insertions show relatively normal growth and development but exhibit a significant reduction in male and female fertility. The removal of cohesin from chromosomes during meiotic prophase is blocked in Atwapl mutants resulting in chromosome bridges, broken chromosomes and uneven chromosome segregation. In contrast, while subtle mitotic alterations are observed in some somatic cells, cohesin complexes appear to be removed normally. Finally, we show that mutations in AtWAPL suppress the lethality associated with inactivation of AtCTF7. Taken together our results demonstrate that WAPL plays a critical role in meiosis and raises the possibility that mechanisms involved in the prophase removal of cohesin may vary between mitosis and meiosis in plants.

Vicia cytogenetic tests for environmental mutagens. A report of the US Environmental Protection Agency gene-tox program

Energy Technology Data Exchange (ETDEWEB)

Ma, T H

1982-01-01

Vicia root-tip mitotic and pollen mother-cell meiotic tests are two major kinds of cytogenetic tests for environmental mutagens. According to the present review, 81 of 85 earlier studies used mitotic tests to determine the frequencies of chromosome or chromatid aberrations and/or sister-chromatid exchange from root-tip meristematic cells; only 4 used meiotic tests to determine the frequencies of chromosome aberration from pollen mother cells. Treatment of root-tip meristem can be done by allowing the newly germinated roots to absorb the chemical mutagens from a water solution. Pollen mother cells can be treated by spraying the solution or pipetting the liquid over the flower buds. After an appropriate recovery time, the samples are fixed and stained, and the slides are prepared for metaphase or anaphase figures for scoring aberration frequencies. Slides for meiotic tests are prepared for metaphase I and/or Anaphase I stages for scoring chromosome aberration frequencies. Results of both cytogenetic tests should be expressed in terms of number of breaks per cell or per 100 cells. Test results of 76 chemicals from 32 classes in this review indicate that the Vicia root-tip mitotic test is reliable, efficient, and relatively inexpensive. These results also reveal that antibiotics are most frequently studied, followed by alkyl sulfones, pyrimidine, and purine derivatives. Of all the agents studied through root-tip mitotic tests, about 90% gave positive responses; antibiotics (phyleomycin and bleomycin) had very high mutagenicity (less than 1 ppM gave positive response).

Centromere separation and association in the nuclei of an interspecific hybrid between Torenia fournieri and T. baillonii (Scrophulariaceae) during mitosis and meiosis.

Science.gov (United States)

Kikuchi, Shinji; Tanaka, Hiroyuki; Wako, Toshiyuki; Tsujimoto, Hisashi

2007-10-01

In the nuclei of some interspecific hybrid and allopolyploid plant species, each genome occupies a separate spatial domain. To analyze this phenomenon, we studied localization of the centromeres in the nuclei of a hybrid between Torenia fournieri and T. baillonii during mitosis and meiosis using three-dimensional fluorescence in situ hybridization (3D-FISH) probed with species-specific centromere repeats. Centromeres of each genome were located separately in undifferentiated cells but not differentiated cells, suggesting that cell division might be the possible force causing centromere separation. However, no remarkable difference of dividing distance was detected between chromatids with different centromeres in anaphase and telophase, indicating that tension of the spindle fiber attached to each chromatid is not the cause of centromere separation in Torenia. In differentiated cells, centromeres in both genomes were not often observed for the expected chromosome number, indicating centromere association. In addition, association of centromeres from the same genome was observed at a higher frequency than between different genomes. This finding suggests that centromeres within one genome are spatially separated from those within the other. This close position may increase possibility of association between centromeres of the same genome. In meiotic prophase, all centromeres irrespective of the genome were associated in a certain portion of the nucleus. Since centromere association in the interspecific hybrid and amphiploid was tighter than that in the diploid parents, it is possible that this phenomenon may be involved in sorting and pairing of homologous chromosomes.

The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities.

Science.gov (United States)

Naim, Valeria; Rosselli, Filippo

2009-06-01

Loss-of-function of caretaker genes characterizes a group of cancer predisposition diseases that feature cellular hypersensitivity to DNA damage and chromosome fragility; this group includes Fanconi anaemia and Bloom syndrome. The products of the 13 FANC genes (mutated in Fanconi anaemia), which constitute the 'FANC' pathway, and BLM (the RecQ helicase mutated in Bloom syndrome) are thought to collaborate during the S phase of the cell cycle, preventing chromosome instability. Recently, BLM has been implicated in the completion of sister chromatid separation during mitosis, a complex process in which precise regulation and execution is crucial to preserve genomic stability. Here we show for the first time a role for the FANC pathway in chromosome segregation during mitotic cell division. FANCD2, a key component of the pathway, localizes to discrete spots on mitotic chromosomes. FANCD2 chromosomal localization is responsive to replicative stress and specifically targets aphidicolin (APH)-induced chromatid gaps and breaks. Our data indicate that the FANC pathway is involved in rescuing abnormal anaphase and telophase (ana-telophase) cells, limiting aneuploidy and reducing chromosome instability in daughter cells. We further address a cooperative role for the FANC pathway and BLM in preventing micronucleation, through FANC-dependent targeting of BLM to non-centromeric abnormal structures induced by replicative stress. We reveal new crosstalk between FANC and BLM proteins, extending their interaction beyond the S-phase rescue of damaged DNA to the safeguarding of chromosome stability during mitosis.

Assessment of adaptability of zebu cattle (Bos indicus) breeds in two different climatic conditions: using cytogenetic techniques on genome integrity.

Science.gov (United States)

Kumar, Anil; Waiz, Syma Ashraf; Sridhar Goud, T; Tonk, R K; Grewal, Anita; Singh, S V; Yadav, B R; Upadhyay, R C

2016-06-01

The aim of this study was to evaluate the genome integrity so as to assess the adaptability of three breeds of indigenous cattle reared under arid and semi-arid regions of Rajasthan (Bikaner) and Haryana (Karnal) India. The cattle were of homogenous group (same age and sex) of indigenous breeds viz. Sahiwal, Tharparkar and Kankrej. A total of 100 animals were selected for this study from both climatic conditions. The sister chromatid exchanges (SCE's), chromosomal gaps and chromatid breaks were observed in metaphase plates of chromosome preparations obtained from in vitro culture of peripheral blood lymphocytes. The mean number of breaks and gaps in Sahiwal and Tharparkar of semi-arid zone were 8.56 ± 3.16, 6.4 ± 3.39 and 8.72 ± 2.04, 3.52 ± 6.29, respectively. Similarly, the mean number of breaks and gaps in Tharparkar and Kankrej cattle of arid zone were 5.26 ± 1.76, 2.74 ± 1.76 and 5.24 ± 1.84, 2.5 ± 1.26, respectively. The frequency of SCEs in chromosomes was found significantly higher (P  0.05) was observed in the same zone. The analysis of frequency of CAs and SCEs revealed significant effects of environmental conditions on the genome integrity of animals, thereby indicating an association with their adaptability.

First-generation physical map of the Culicoides variipennis (Diptera: Ceratopogonidae) genome.

Science.gov (United States)

Nunamaker, R A; Brown, S E; McHolland, L E; Tabachnick, W J; Knudson, D L

1999-11-01

Recombinant cosmids labeled with biotin-11-dUTP or digoxigenin by nick translation were used as in situ hybridization probes to metaphase chromosomes of Culicoides variipennis (Coquillett). Paired fluorescent signals were detected on each arm of sister chromatids and were ordered along the 3 chromosomes. Thirty-three unique probes were mapped to the 3 chromosomes of C. variipennis (2n = 6): 7 to chromosome 1, 20 to chromosome 2, and 6 to chromosome 3. This work represents the first stage in generating a physical map of the genome of C. variipennis.

How unfinished business from S-phase affects mitosis and beyond

DEFF Research Database (Denmark)

Mankouri, H.W.; Huttner, D.; Hickson, I.D.

2013-01-01

The eukaryotic cell cycle is conventionally viewed as comprising several discrete steps, each of which must be completed before the next one is initiated. However, emerging evidence suggests that incompletely replicated, or unresolved, chromosomes from S-phase can persist into mitosis, where...... they present a potential threat to the faithful segregation of sister chromatids. In this review, we provide an overview of the different classes of loci where this 'unfinished S-phase business' can lead to a variety of cytogenetically distinct DNA structures throughout the various steps of mitosis...

STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis

OpenAIRE

Prieto, Ignacio; Pezzi, Nieves; Buesa, José M.; Kremer, Leonor; Barthelemy, Isabel; Carreiro, Candelas; Roncal, Fernando; Martínez, Alicia; Gómez, Lucio; Fernández, Raúl; Martínez-A, Carlos; Barbero, José L.

2002-01-01

STAG/SA proteins are specific cohesin complex subunits that maintain sister chromatid cohesion in mitosis and meiosis. Two members of this family, STAG1/SA1 and STAG2/SA2,‡ are classified as mitotic cohesins, as they are found in human somatic cells and in Xenopus laevis as components of the cohesinSA1 and cohesinSA2 complexes, in which the shared subunits are Rad21/SCC1, SMC1 and SMC3 proteins. A recently reported third family member, STAG3, is germinal cell-specific and is a subunit of the ...

Absence of interference in association with gene conversion in Sordaria fimicola, and presence of interference in association with ordinary recombination.

Science.gov (United States)

Kitani, Y

1978-07-01

From the analysis of large samples of gene conversion asci in the g locus of Sordaria fimicola, it was found that neither the conversion event itself nor conversion-associated recombination of flanking markers cause either chiasma or chromatid interference with crossing over in a neighboring interval. The presence of more than one kind of crossover event, one causing interference the other not, is considered. The existence of two kinds of gene loci, one of single-cistron composition and the other of multiple-cistron composition, is discussed in relation to reciprocal recombination within a locus.

PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

DEFF Research Database (Denmark)

Nielsen, Christian Thomas Friberg; Huttner, Diana; Bizard, Anna H

2015-01-01

PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural......-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis....

Mouse RAD54 affects DNA double-strand break repair and sister chromatid exchange

NARCIS (Netherlands)

H.B. Beverloo (Berna); R.D. Johnson (Roger); M. Jasin (Maria); R. Kanaar (Roland); J.H.J. Hoeijmakers (Jan); M.L.G. Dronkert (Mies)

2000-01-01

textabstractCells can achieve error-free repair of DNA double-strand breaks (DSBs) by homologous recombination through gene conversion with or without crossover. In contrast, an alternative homology-dependent DSB repair pathway, single-strand annealing (SSA), results in deletions. In this study, we

Sister chromatid exchanges (SCEs) in lymphocytes of inhabitants in high background radiation area

International Nuclear Information System (INIS)

Li Jinsheng; Zheng Qiaoling

1985-01-01

Blood samples were taken from 126 students of 15-16 years old, living in the high background radiation area, and from 124 controls of the same age range, living in the normal background radiation area. All students were interviewed for evaluation of their health status. Whole blood cultures were done with RPMI 1640 medium supplemented with 20% fetal calf serum and antibiotics, The culture were incubated for 54-56 h in the presence of BrdU (10 μg/ml). Metaphases were stained for SCE using a modified techniqu of perry and Wolff. From each person 20 second division metaphases were analysed for SCEs. The average frequencies of SCEs observed in the high background group and the control group are presented. More SCEs were observed in the high background group than in the control with a statistically signigicant difference. In regard to the sex factor, it was found that the SCE frequencies in both sexes of the high background group were slightly higher than those in the control group. These findings suggest that continuous low-level irradiation by the high background radiation may induce increased frequency of SCEs

Dysfunctional telomeres in human BRCA2 mutated breast tumors and cell lines

International Nuclear Information System (INIS)

Bodvarsdottir, Sigridur K.; Steinarsdottir, Margret; Bjarnason, Hordur; Eyfjord, Jorunn E.

2012-01-01

In the present study the possible involvement of telomeres in chromosomal instability of breast tumors and cell lines from BRCA2 mutation carriers was examined. Breast tumors from BRCA2 mutation carriers showed significantly higher frequency of chromosome end-to-end fusions (CEFs) than tumors from non-carriers despite normal telomere DNA content. Frequent CEFs were also found in four different BRCA2 heterozygous breast epithelial cell lines, occasionally with telomere signal at the fusion point, indicating telomere capping defects. Extrachromosomal telomeric repeat (ECTR) DNA was frequently found scattered around metaphase chromosomes and interstitial telomere sequences (ITSs) were also common. Telomere sister chromatid exchanges (T-SCEs), characteristic of cells using alternative lengthening of telomeres (ALT), were frequently detected in all heterozygous BRCA2 cell lines as well as the two ALT positive cell lines tested. Even though T-SCE frequency was similar in BRCA2 heterozygous and ALT positive cell lines they differed in single telomere signal loss and ITSs. Chromatid type alterations were more prominent in the BRCA2 heterozygous cell lines that may have propensity for telomere based chromosome healing. Telomere dysfunction-induced foci (TIFs) formation, identified by co-localization of telomeres and γ-H2AX, supported telomere associated DNA damage response in BRCA2 heterozygous cell lines. TIFs were found in interphase nuclei, at chromosome ends, ITSs and ECTR DNA. In conclusion, our results suggest that BRCA2 has an important role in telomere stabilization by repressing CEFs through telomere capping and the prevention of telomere loss by replication stabilization.

Resistance to radiation, recombination, repair of DNA and chromosome organisation

International Nuclear Information System (INIS)

Fletcher, H.L.

1981-01-01

The model advanced here proposes that death is caused by destructive lesions, mainly double-strand breaks, in all the inter-repairable copies so close together that recombination repair cannot function. Death is related to the exponential of dose where r is the number of copies of the genome. A graph of ln(-ln survival) against ln dose is used to produce a linear dose-survival relationship, the slope of which gives the number of inter-repairable copies of the genome (= number of hits per lethal event). In Ustilago maydis it seems that unless all the chromatids are broken within a few thousand base pairs all ds breaks are repaired. The size of this critical target is similar to the size of a gene. Meiotic pairing in fungi starts outside the genes, and it is therefore suggested that specific pairing sites between genes define the ends of the targets. The model also describes the radiation-induced death of Micrococcus radiodurans and Sacchromyces cerevisiae. Cultured mammalian cells also show a linear ln(-ln survival)/ln dose relationship with a slope of 1.5 showing that both 1st and 2nd order killing occured. Sublethal radiation induces recombination in heterozygous diploid U. maydis proportional to the square of the dose. Sister-chromatid repair is preferred. Polyploid yeast can only use pairs of chromosomes for repair, showing that chromosome pairing is required for recombination repair, and mitotic pairing is restricted to bivalents in the same way that meiotic pairing is. (orig./AJ)

Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina

Directory of Open Access Journals (Sweden)

Harris William A

2009-07-01

Full Text Available Abstract Background The condensation of chromosomes and correct sister chromatid segregation during cell division is an essential feature of all proliferative cells. Structural maintenance of chromosomes (SMC and non-SMC proteins form the condensin I complex and regulate chromosome condensation and segregation during mitosis. However, due to the lack of appropriate mutants, the function of the condensin I complex during vertebrate development has not been described. Results Here, we report the positional cloning and detailed characterization of retinal phenotypes of a zebrafish mutation at the cap-g locus. High resolution live imaging reveals that the progression of mitosis between prometa- to telophase is delayed and that sister chromatid segregation is impaired upon loss of CAP-G. CAP-G associates with chromosomes between prometa- and telophase of the cell cycle. Loss of the interaction partners CAP-H and CAP-D2 causes cytoplasmic mislocalization of CAP-G throughout mitosis. DNA content analysis reveals increased genomic imbalances upon loss of non-SMC condensin I subunits. Within the retina, loss of condensin I function causes increased rates of apoptosis among cells within the proliferative ciliary marginal zone (CMZ whereas postmitotic retinal cells are viable. Inhibition of p53-mediated apoptosis partially rescues cell numbers in cap-g mutant retinae and allows normal layering of retinal cell types without alleviating their aberrant nuclear sizes. Conclusion Our findings indicate that the condensin I complex is particularly important within rapidly amplifying progenitor cell populations to ensure faithful chromosome segregation. In contrast, differentiation of postmitotic retinal cells is not impaired upon polyploidization.

Dysfunctional telomeres in human BRCA2 mutated breast tumors and cell lines

Energy Technology Data Exchange (ETDEWEB)

Bodvarsdottir, Sigridur K., E-mail: skb@hi.is [Cancer Research Laboratory, BioMedical Centre, Faculty of Medicine, University of Iceland, Vatnsmyrarvegi 16, 101 Reykjavik (Iceland); Steinarsdottir, Margret [Chromosome Laboratory, Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik (Iceland); Bjarnason, Hordur; Eyfjord, Jorunn E. [Cancer Research Laboratory, BioMedical Centre, Faculty of Medicine, University of Iceland, Vatnsmyrarvegi 16, 101 Reykjavik (Iceland)

2012-01-03

In the present study the possible involvement of telomeres in chromosomal instability of breast tumors and cell lines from BRCA2 mutation carriers was examined. Breast tumors from BRCA2 mutation carriers showed significantly higher frequency of chromosome end-to-end fusions (CEFs) than tumors from non-carriers despite normal telomere DNA content. Frequent CEFs were also found in four different BRCA2 heterozygous breast epithelial cell lines, occasionally with telomere signal at the fusion point, indicating telomere capping defects. Extrachromosomal telomeric repeat (ECTR) DNA was frequently found scattered around metaphase chromosomes and interstitial telomere sequences (ITSs) were also common. Telomere sister chromatid exchanges (T-SCEs), characteristic of cells using alternative lengthening of telomeres (ALT), were frequently detected in all heterozygous BRCA2 cell lines as well as the two ALT positive cell lines tested. Even though T-SCE frequency was similar in BRCA2 heterozygous and ALT positive cell lines they differed in single telomere signal loss and ITSs. Chromatid type alterations were more prominent in the BRCA2 heterozygous cell lines that may have propensity for telomere based chromosome healing. Telomere dysfunction-induced foci (TIFs) formation, identified by co-localization of telomeres and {gamma}-H2AX, supported telomere associated DNA damage response in BRCA2 heterozygous cell lines. TIFs were found in interphase nuclei, at chromosome ends, ITSs and ECTR DNA. In conclusion, our results suggest that BRCA2 has an important role in telomere stabilization by repressing CEFs through telomere capping and the prevention of telomere loss by replication stabilization.

Different radiosensitization effects of the halogenated compounds on the human chromosome in vitro

International Nuclear Information System (INIS)

Kang, Y.S.

1976-01-01

Unscheduled DNA synthesis and chromosome aberrations were compared following X- or UV-irradiation or methyl methanesulfonate treatment in cultures of HeLa S 3 or KB cells or human and rabbit lymphocytes. The sensitization by incorporation of the halouridines BUdR and IUdR was also investigated. Unscheduled DNA synthesis occurred in two established cell lines after irradiation with 0 to 10 kR of X-rays. The rate of unscheduled synthesis was dose dependent and differed for the two cell lines. The unscheduled synthesis was not correlated with the modal chromosome number nor with the number of aberrations produced. UV-irradiated rabbit lymphocytes exhibited unscheduled DNA synthesis which saturated after a dose of 250 ergs/mm 2 . In contrast the incorporation of BUdR or IUdR eliminated this saturation and caused an increasing effect with increasing dose up to 1000 ergs/mm 2 . The degree of sensitization varied between the two halo-uridines, BUdR being more effective at high doses while IUdR was a more potent sensitizer at low doses. Chromosome aberrations were not directly related to unscheduled DNA synthesis but were sensitized by halo-uridine incorporation. In this case IUdR was more potent than BUdR at all doses studied. Methyl methanesulfonate was an effective producer of chromosome aberration in human lymphocytes of both the chromosome and chromatid type. Prior incorporation of BUdR or IUdR did not increase the total aberration produced but did increase the number of chromosome type aberration at the expense of the chromatid type

Effect of SPL (Spent Pot Liner) and its main components on root growth, mitotic activity and phosphorylation of Histone H3 in Lactuca sativa L.

Science.gov (United States)

Freitas, Aline Silva; Fontes Cunha, Isabela Martinez; Andrade-Vieira, Larissa Fonseca; Techio, Vânia Helena

2016-02-01

Spent Pot Liner (SPL) is a solid waste from the aluminum industry frequently disposed of in industrial landfills; it can be leached and contaminate the soil, sources of drinking water and plantations, and thus may pose a risk to human health and to ecosystems. Its composition is high variable, including cyanide, fluoride and aluminum salts, which are highly toxic and environmental pollutants. This study evaluated the effect of SPL and its main components on root growth and the mitosis of Lactuca sativa, by investigating the mechanisms of cellular and chromosomal alterations with the aid of immunolocalization. To this end, newly emerged roots of L. sativa were exposed to SPL and its main components (solutions of cyanide, fluoride and aluminum) and to calcium chloride (control) for 48h. After this, root length was measured and cell cycle was examined by means of conventional cytogenetics and immunolocalization. Root growth was inhibited in the treatments with SPL and aluminum; chromosomal and nuclear alterations were observed in all treatments. The immunolocalization evidenced normal dividing cells with regular temporal and spatial distribution of histone H3 phosphorylation at serine 10 (H3S10ph). However, SPL and its main components inhibited the phosphorylation of histone H3 at serine 10, inactivated pericentromeric regions and affected the cohesion of sister chromatids, thus affecting the arrangement of chromosomes in the metaphase plate and separation of chromatids in anaphase. In addition, these substances induced breaks in pericentromeric regions, characterized as fragile sites. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation Induced G2 Chromatic Break and Repairs Kinetics in Human Lymphoblastoid Cells

International Nuclear Information System (INIS)

Seong, Jin Sil

1993-01-01

In understanding radiosensitivity a new concept of inherent radiosensitivity based on individuality and heterogeneity within a population has recently beer explored. There has been some discussion of possible mechanism underlying differences in radiosensitivity between cells. Ataxia telangiectasia(AT), a rare autosomal recessive genetic disorder, is characterized by hypersensitivity to lonizing radiation and other DNA damaging agents at the cellular level. There have been a lot of efforts to describe the cause of this hypersensitivity to radiation. At the cellular level, chromosome repair kinetics study would be an appropriate approach. The purpose of this study was to better understand radiosensitivity in an approach to investigate kinetics of induction and repair of G2 chromatic breaks using normal, AT heterozygous(ATH), and AT homozygous lymphoblastoid cell lines. In an attempt to estimate initial damage, 9-β-D-arabinosyl-2-fluoroadenine, an inhibitor of DNA synthesis and repair, was used in this study. It was found from this study that radiation induces higher chromatid breaks in AT than in normal and ATH cells. There was no significant differences of initial chromatid breaks between normal and ATH cells. Repair kinetics was the same for all. So the higher level of breaks in AT G2 cells is thought to be a reflection of the increased initial damage. The amount of initial damage correlated well with survival fraction at 2 Gy of cell survival curve following radiation. Therefore, the difference of radiosensitivity in terms of G2 chromosomal sensitivity is thought to result from the difference of initial damage

A study of chromosomal aberrations in amniotic fluid cell cultures.

Science.gov (United States)

Wolstenholme, J; Crocker, M; Jonasson, J

1988-06-01

This paper represents the analysis of 1916 routine amniotic fluid specimens harvested by an in situ fixation technique in a prospective study with regard to cultural chromosome anomalies. Excluding constitutional abnormalities, 2.9 per cent of 19,432 cells analysed showed some form of chromosome anomaly, terminal deletions (57 per cent) and chromatid/chromosome breaks and gaps (18 per cent) being the most frequent, followed by interchange aberrations (13 per cent) and trisomy (5 per cent). No case was found of more than one colony from the same culture showing the same anomaly without it being present in other cultures from the same fluid. The wholly abnormal colonies had a surplus of trisomies and from the mathematical considerations presented one may infer that these are likely to reflect the presence of abnormal cells in the amniotic fluid. Partly abnormal colonies appeared at a frequency that would correspond to virtual absence of selection against chromosomally abnormal cells when cultured in vitro. The aberrations found were similar to those seen as single cell anomalies, except for chromatid breaks and exchanges. The data suggest a basic preferential induction of trisomy for chromosomes 2, 18, 21, and the Y-chromosome. Structural aberrations showed a marked clustering of breakpoints around the centromeres. The frequency of mutant cells was low (1.4 X 10(-3)) before culture was initiated. At harvest, the frequency of abnormal cells was much higher (3 X 10(-2)) corresponding to 3 X 10(-3) mutations per cell per generation accumulating over approximately ten generations in vitro.

[THE INFLUENCE OF THE PREPARATION PRETREATMENT ON IN SITU DETECTION OF 5-METHYLCYTOSINE IN METAPHASE CHROMOSOMES AND IN INTERPHASE NUCLEI].

Science.gov (United States)

Grudinina, N A; Sasina, L K; Noniashvili, E M; Neronova, E G; Pavlinova, L I; Suchkova, I O; Sofronov, G A; Patkin, E L

2015-01-01

Qualitative and quantitate analysis of DNA methylation in situ at the level of cells, chromosomes and chromosomal domains is extremely important for the diagnosis and treatment of various diseases, the study of ageing and the consequences of environmental impacts. An important question arises, whether the revealed in situ methylation pattern reflects DNA methylation per se and (or) availability of the DNA for antibodies, which in turn depends on the peculiarities of chromatin structure and chromosome condensation. These events can lead to an incorrect evaluation of the actual pattern of DNA methylation. To avoid this shortcoming as far as possible, we have modified the most widely used method of revealing 5-methylcytosine in situ with monoclonal antibodies. Here we have shown that the detection of DNA methylation staining of chromosomes including C-heterochromatin, chromosomal arms and sister chromatids is drastically dependent on pretreatment of chromosomal preparations for immunocytochemical study using fluorescent antibodies. Using undifferentiated stem cells of mouse embryonal carcinoma line F9, it has been found that change in preparations storage results in a sharp fluorescence decrease up to complete disappearance of the signal in centromeric heterochromatin. With the help of the method described in the work, we have first revealed the asymmetry of sister chromatids methylation in metaphase chromosomes of F9 cell and lymphocytes of human periphery blood. This may lead to asymmetry of transcriptional signature of daughter cells after division. The proposed here modification of 5-methylcytosine detection in situ provides a more complete characterization of methylation of chromosomes and chromosomal domains, compared to previously published methods.

The reactivity of plant, murine and human genome to electron beam irradiation

International Nuclear Information System (INIS)

Gavrila, L.; Usurelu, D.; Radu, I.; Timus, D.

2005-01-01

A broad spectrum of chromosomal rearrangements is described in plants (Allium cepa), mouse (Mus musculus domestics) and in humans (Homo sapiens sapiens), following in vivo and in vitro beta irradiation. Irradiations were performed at EAL, using a 2.998 GHz traveling-wave electron accelerator. The primary effect of electron beam irradiation is chromosomal breakage followed up by a variety of chromosomal rearrangements i.e. chromosomal aberrations represented mainly by chromatid gaps, deletions, ring chromosomes, dicentrics, translocations, complex chromosomal interchanges, acentric fragments and double minutes (DM). The clastogenic effects were associated in some instances with cell sterilization (i.e. cell death)

DNA strand breakage repair in ataxia telangiectasia fibroblast-like cells

Energy Technology Data Exchange (ETDEWEB)

Vincent, Jr, R A; Sheridan, III, R B; Huang, P C [Johns Hopkins Univ., Baltimore, Md. (USA). Dept. of Environmental and Biophysical Sciences

1975-12-01

Human diploid fibroblast-like cells derived from four patients with the genetic disease ataxia telangiectasia and from two non-mutant donors were examined for the repair of x-ray induced strand breaks in DNA. The ataxia telangiectasia cultures showed no significant differences from the non-mutant cultures in the kinetics and extent of strand repair. This suggests that the increased spontaneous and x-ray induced chromatid aberrations observed in ataxia telangiectasia cells are not caused by a defect in the repair of single strand breaks as might be suspected from a general model of aberration production.

Effect of pretreatment with venom of Apis mellifera bees on the yield of gamma-ray induced chromosome aberrations in human blood lymphocytes

International Nuclear Information System (INIS)

Varanda, E.A.; Takahashi, C.S.

1993-01-01

Venom of the honey bee Apis mellifera induced a protective effect against the induction of dicentric chromosomes by gamma radiation (2.0 Gy) in human peripheral blood lymphocytes when the cultures were treated with 0.00015 μl venom/1 ml medium 6 h before irradiation. In cultures to which the venom was added immediately before irradiation with 0.25, 1.0 and 2.0 Gy, no significant differences in number of dicentric chromosomes induced was observed when compared to cultures submitted to irradiation only. The venom did not induce clastogenic effects nor did it increase the frequency of sister chromatid exchanges. (author)

In situ hybridization of iodinated 5S and 18/25S RNA to Vicia faba metaphase chromosomes

International Nuclear Information System (INIS)

Schubert, I.; Baeumlein, H.; Wobus, U.

1978-01-01

In vitro labelled 125 I ribosomal RNA fractions (18/25S and 5S) were in situ hybridized to metaphase chromosomes of a reconstructed karyotype of Vicia faba (characterized by two translocations and one pericentric inversion, each being present homozygously). The sites of 18S and 25S RNA were found to be confined to the nucleolus organizing secondary constriction. Two loci of 5S RNA were recognized on the satellite of nucleolus bearing chromosome. Possible correlations between the location of ribosomal genes, heterochromatic G-bands and clusters of mutagen induced chromatid aberrations are discussed. (author)

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

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Atidtaya Suttichaiya

2016-01-01

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

Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis

Science.gov (United States)

Marston, Adele L.; Wassmann, Katja

2017-01-01

Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. The less-known meiotic roles of the SAC kinases are described, with a focus on two model systems: yeast and mouse oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. Insights into the molecular signaling pathways that bring about the special chromosome segregation pattern during meiosis will help us understand why human oocytes are so frequently aneuploid. PMID:29322045

Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis

Directory of Open Access Journals (Sweden)

Adele L. Marston

2017-12-01

Full Text Available Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. The less-known meiotic roles of the SAC kinases are described, with a focus on two model systems: yeast and mouse oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3, and Aurora B and C (Ipl1 will be discussed. Insights into the molecular signaling pathways that bring about the special chromosome segregation pattern during meiosis will help us understand why human oocytes are so frequently aneuploid.

FLT3 and JAK2 Mutations in Acute Myeloid Leukemia Promote Interchromosomal Homologous Recombination and the Potential for Copy Neutral Loss of Heterozygosity.

Science.gov (United States)

Gaymes, Terry J; Mohamedali, Azim; Eiliazadeh, Anthony L; Darling, David; Mufti, Ghulam J

2017-04-01

Acquired copy neutral LOH (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here, we show that constitutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F-mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared with wild-type FLT3 NK-AML. HR was harmonized to S phase of the cell cycle to repair broken chromatids and prevent iHR. Increased HR activity in G 0 arrested primary FLT3-ITD NK-AML in contrast to wild-type FLT3 NK-AML. Cells expressing mutated FLT3-ITD demonstrated a relative increase in mutation frequency as detected by thymidine kinase (TK) gene mutation assay. Moreover, resistance was associated with CN-LOH at the TK locus. Treatment of FLT3-ITD- and JAK2V617F-mutant cells with the antioxidant N -acetylcysteine diminished reactive oxygen species (ROS), restoring iHR and HR levels. Our findings show that mutated FLT3-ITD and JAK2 augment ROS production and HR, shifting the cellular milieu toward illegitimate recombination events such as iHR and CN-LOH. Therapeutic reduction of ROS may thus prevent leukemic progression and relapse in myeloid malignancies. Cancer Res; 77(7); 1697-708. ©2017 AACR . ©2017 American Association for Cancer Research.

A role for the budding yeast separase, Esp1, in Ty1 element retrotransposition.

Directory of Open Access Journals (Sweden)

Krystina L Ho

2015-03-01

Full Text Available Separase/Esp1 is a protease required at the onset of anaphase to cleave cohesin and thereby enable sister chromatid separation. Esp1 also promotes release of the Cdc14 phosphatase from the nucleolus to enable mitotic exit. To uncover other potential roles for separase, we performed two complementary genome-wide genetic interaction screens with a strain carrying the budding yeast esp1-1 separase mutation. We identified 161 genes that when mutated aggravate esp1-1 growth and 44 genes that upon increased dosage are detrimental to esp1-1 viability. In addition to the expected cell cycle and sister chromatid segregation genes that were identified, 24% of the genes identified in the esp1-1 genetic screens have a role in Ty1 element retrotransposition. Retrotransposons, like retroviruses, replicate through reverse transcription of an mRNA intermediate and the resultant cDNA product is integrated into the genome by a conserved transposon or retrovirus encoded integrase protein. We purified Esp1 from yeast and identified an interaction between Esp1 and Ty1 integrase using mass spectrometry that was subsequently confirmed by co-immunoprecipitation analysis. Ty1 transposon mobility and insertion upstream of the SUF16 tRNA gene are both reduced in an esp1-1 strain but increased in cohesin mutant strains. Securin/Pds1, which is required for efficient localization of Esp1 to the nucleus, is also required for efficient Ty1 transposition. We propose that Esp1 serves two roles to mediate Ty1 transposition - one to remove cohesin and the second to target Ty1-IN to chromatin.

Associations of polymorphisms in the cytokine genes IL1β (rs16944), IL6 (rs1800795), IL12b (rs3212227) and growth factor VEGFA (rs2010963) with anthracosilicosis in coal miners in Russia and related genotoxic effects.

Science.gov (United States)

Volobaev, Valentin P; Larionov, Aleksey V; Kalyuzhnaya, Ekaterina E; Serdyukova, Ekaterina S; Yakovleva, Svetlana; Druzhinin, Vladimir G; Babich, Olga O; Hill, Elena G; Semenihin, Victor A; Panev, Nikolay I; Minina, Varvara I; Sivanesan, Saravana Devi; Naoghare, Pravin; da Silva, Juliana; Barcelos, Gustavo R M; Prosekov, Alexander Y

2018-04-13

Anthracosilicosis (AS), a prevalent form of pneumoconiosis among coal miners, results from the accumulation of carbon and silica in the lungs from inhaled coal dust. This study investigated genotoxic effects and certain cytokine genes polymorphic variants in Russian coal miners with АS. Peripheral leukocytes were sampled from 129 patients with AS confirmed by X-ray and tissue biopsy and from 164 asymptomatic coal miners. Four single-nucleotide polymorphisms were genotyped in the extracted DNA samples: IL1β T-511C (rs16944), IL6 C-174G (rs1800795), IL12b A1188C (rs3212227) and VEGFA C634G (rs2010963). Genotoxic effects were assessed by the analysis of chromosome aberrations in cultured peripheral lymphocytes. The mean frequency of chromatid-type aberrations and chromosome-type aberrations, namely, chromatid-type breaks and dicentric chromosomes, was found to be higher in AS patients [3.70 (95% confidence interval {CI}, 3.29-4.10) and 0.28 (95% CI, 0.17-0.38)] compared to the control group [2.41 (95% CI, 2.00-2.82) and 0.09 (95% CI, 0.03-0.15)], respectively. IL1β gene T/T genotype (rs16944) was associated with AS [17.83% in AS patients against 4.35% in healthy donors, odds ratio = 4.77 (1.88-12.15), P < 0.01]. A significant increase in the level of certain chromosome interchanges among AS donors is of interest because such effects are typical for radiation damage and caused by acute oxidative stress. IL1β T allele probably may be considered as an AS susceptibility factor among coal miners.

Centromere Locations in Brassica A and C Genomes Revealed Through Half-Tetrad Analysis.

Science.gov (United States)

Mason, Annaliese S; Rousseau-Gueutin, Mathieu; Morice, Jérôme; Bayer, Philipp E; Besharat, Naghmeh; Cousin, Anouska; Pradhan, Aneeta; Parkin, Isobel A P; Chèvre, Anne-Marie; Batley, Jacqueline; Nelson, Matthew N

2016-02-01

Locating centromeres on genome sequences can be challenging. The high density of repetitive elements in these regions makes sequence assembly problematic, especially when using short-read sequencing technologies. It can also be difficult to distinguish between active and recently extinct centromeres through sequence analysis. An effective solution is to identify genetically active centromeres (functional in meiosis) by half-tetrad analysis. This genetic approach involves detecting heterozygosity along chromosomes in segregating populations derived from gametes (half-tetrads). Unreduced gametes produced by first division restitution mechanisms comprise complete sets of nonsister chromatids. Along these chromatids, heterozygosity is maximal at the centromeres, and homologous recombination events result in homozygosity toward the telomeres. We genotyped populations of half-tetrad-derived individuals (from Brassica interspecific hybrids) using a high-density array of physically anchored SNP markers (Illumina Brassica 60K Infinium array). Mapping the distribution of heterozygosity in these half-tetrad individuals allowed the genetic mapping of all 19 centromeres of the Brassica A and C genomes to the reference Brassica napus genome. Gene and transposable element density across the B. napus genome were also assessed and corresponded well to previously reported genetic map positions. Known centromere-specific sequences were located in the reference genome, but mostly matched unanchored sequences, suggesting that the core centromeric regions may not yet be assembled into the pseudochromosomes of the reference genome. The increasing availability of genetic markers physically anchored to reference genomes greatly simplifies the genetic and physical mapping of centromeres using half-tetrad analysis. We discuss possible applications of this approach, including in species where half-tetrads are currently difficult to isolate. Copyright © 2016 by the Genetics Society of America.

Analysis of chromosomal aberrations, micronuclei and hematological disorders among workers of wireless communication instruments and cell phone (Mobile) users

International Nuclear Information System (INIS)

Eldawy, H.A.; Khattab, F.I.; Hassan, N.H.A.; Amin, Y.M.; Mahmoud, M.M.A.

2003-01-01

This study was carried out to investigate the hazardous effect of electromagnetic radiation (EMR) such as chromosomal aberration, disturbed micronucleus formation and hematological disorders that may detected among workers of wireless communication instruments and mobile phone users. Seven individuals ( 3 males and 4 females) of a central workers in the microwave unit of the wireless station and 7 users of Mobil phone (4 males and 3 females ) were volunteered to give blood samples. Chromosomes and micronucleus were prepared for cytogenetic analysis as well as blood film for differential count. The results obtained in the microwave group indicated that, the total summation of all types of aberrations (chromosomes and chromatid aberrations) had a frequency of 6. 14% for the exposed group, whereas, the frequency in the control group amounted to 1.57%. In Mobil phone users, the total summation of all types of aberrations(chromosome and chromatid aberrations) had a frequency of 4.43% for the exposed group and 1.71% for the control group. The incidence of the total number of micronuclei in the exposed microwave group was increased 4.3 folds as compared with those of the control group The incidence of the total number of micronuclei in the exposed mobile phone group was increased 2 fold as compared with those in the control group. On the other hand, normal ranges of total white blood cells counts were determined for mobile phone users but abnormalities in the differential counts of the different types of the white blood cells such as neutropenia, eosinophilia and lymphocytosis were observed in the individuals number 1,2,3,7 in microwave group

[Cytogenetic effect of cyclophosphamide in a culture of human lymphocytes following its activation in the bodies of mice].

Science.gov (United States)

Chebotarev, A N; Telegin, L I; Derzhavets, E M

1976-01-01

Cytogenetic effect of cyclophosphamide in cultured human lymphocytes after its activation in C57BL/6 mice in vivo was investigated. Cyclophosphamide was injected intraperitoneally in mice for 30 min. at doses of 200, 400, 600, 800 and 1000 mg/kg. Blood serum with activated metabolites of cyclophosphamide was added to human lymphocyte culture. The dependence of the part of aberrant metaphases on the concentration of cyclophosphamide after the activation can be presented as equation rho==1-e-(KC+alpha)2 and the total number of breaks as X=e(KC+alpha)2-1, where rho is a part of aberrant metaphases, X is a number of breaks of chromosomes per cell, C is the concentration, K and alpha are coefficients. The part of chromatid breaks from the total number of chromosome damages is constant for all concentrations and the comprises on the average 79,11%. Only the chromatid type of exchanges are observed. Distribution of chromosome breaks in cells corresponds to geometrical, but not to Poisson's distribution. Cyclophosphamide belongs to the group of one-sited mutagens in its cytogenetic chatacteristics. The alkylating activity of cyclophosphamide metabolites, estimated by means of NBP test, increases up to the dose 400 mg/kg and then remains constant for the strain of mice studied, cytogenetic activity increasing. Cyclophosphamide does not produce cytogenetic activity without activation. To test chemical substances for mutagenic activity, it is suggested to activate them in the mouse organism with the following administrating blood serum of these animals with the metabolites of tested (or with primary) substances in the study of their mutagenic activity on human lymphocyte culture.

Treatment of HeLa cells with Giloe (Tinospora cordifolia meirs) increases the radiosensitivity by increasing DNA damage

International Nuclear Information System (INIS)

Varma, Hari Krishna; Jagetia, Ganesh Chandra; Nayak, Vijayashree

2014-01-01

Radiotherapy is an important treatment modality and screening of phytoceuticals may enhance the clinical outcome of radiotherapy, therefore radiosensitizing activity of various guduchi (Tinospora cordifolia) extracts was studied in HeLa cells. Chromosomal aberrations were scored in HeLa cells treated with 10 μg/ml of aqueous, methanol, or methylene chloride guduchi extracts or doxorubicin before exposure to 0, 0.5, 1, 2 or 3 Gy of γ-radiation at 12, 24, 36 or 48 h post-irradiation. Irradiation of HeLa cells caused a dose dependent rise in the chromatid breaks, chromosome breaks, dicentric, centric rings, acentric fragments and total aberrations at all post-irradiation times and the dose response was linear quadratic for all types of aberrations scored. Chromatid breaks increased up to 12 h post-irradiation and declined steadily up to 48 h post-irradiation, whereas chromosome breaks, dicentric, acentric fragments and total aberrations elevated up to 24 h post-irradiation and declined thereafter. However, centric rings continued to rise steadily up to 48 h post-irradiation. Treatment of HeLa cells with aqueous, methanol or methylene chloride guduchi extract or doxorubicin before irradiation significantly enhanced various types of chromosomal aberrations and a maximum rise in the chromosome aberrations was observed in the HeLa cells treated with methylene chloride extract before irradiation when compared to other groups. Various guduchi extracts enhanced the effect of radiation in HeLa cells by increasing the molecular damage to cellular genome and their effect was similar to or even greater than doxorubicin (positive control) pretreatment, depending on the type of guduchi extract used. (author)

From equator to pole: splitting chromosomes in mitosis and meiosis

Science.gov (United States)

Duro, Eris

2015-01-01

During eukaryotic cell division, chromosomes must be precisely partitioned to daughter cells. This relies on a mechanism to move chromosomes in defined directions within the parental cell. While sister chromatids are segregated from one another in mitosis and meiosis II, specific adaptations enable the segregation of homologous chromosomes during meiosis I to reduce ploidy for gamete production. Many of the factors that drive these directed chromosome movements are known, and their molecular mechanism has started to be uncovered. Here we review the mechanisms of eukaryotic chromosome segregation, with a particular emphasis on the modifications that ensure the segregation of homologous chromosomes during meiosis I. PMID:25593304

DNA repair in PHA stimulated human lymphocytes

International Nuclear Information System (INIS)

Catena, C.; Mattoni, A.

1984-01-01

Damage an repair of radiation induced DNA strand breaks were measured by alkaline lysis and hydroxyapatite chromatography. PHA stimulated human lymphocytes show that the rejoining process is complete within the first 50 min., afterwords secondary DNA damage and chromatid aberration. DNA repair, in synchronized culture, allows to evaluate individual repair capacity and this in turn can contribute to the discovery of individual who, although they do not demonstrate apparent clinical signs, are carriers of DNA repair deficiency. Being evident that a correlation exists between DNA repair capacity and carcinogenesis, the possibility of evaluating the existent relationship between DNA repair and survival in tumor cells comes therefore into discussion

Cytogenetic effects of near ultraviolet radiation in normal and systemic lupus erythematosus lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Caporossi, D.; Sebastiani, G.; Nicoletti, B. (Rome 2 University (Italy). Department of Public Health and Cellular Biology); Masala, C. (' La Sapienza' University, rome (Italy). Institute of Infectious and Tropical Diseases)

1990-03-01

The authors conducted a study on the spontaneous and UV-A induced frequency of chromosomal breaks and sister-chromatid exchanges (SCE) in purified lymphocytes from normal donors and from systemic lupus erythematosus (SLE) patients who were in clinical remission at the time of the study. Our results show that although SLE lymphocytes exhibit a higher frequency of spontaneous SCEs than controls, the rate of chromosomal breakage is comparable in the 2-groups. In both controls and patients, irradiation with UV-A (320-400 nm) increases the SCE values but does not significantly affect the frequency of chromosomal aberrations. (author). 14 refs.; 1 fig.; 3 tabs.

Evaluation of chemopreventive effects of betel leaf on the genotoxicity of pan masala.

Science.gov (United States)

Trivedi, A H; Patel, R K; Rawal, U M; Adhvaryu, S G; Balar, D B

1994-01-01

The antigenotoxic effect of the aqueous extract of betel leaf (BL-ext.) against the pan masala was tested with the help of cytogenetic endpoints like chromosome aberration (CA) and sister chromatid exchange (SCE) utilizing Chinese hamster ovary (CHO) cells. Compared to the cultures treated with aqueous extract of pan masala alone, a reduction in CA and SCE frequencies in CHO cells was observed following a combined treatment with pan masala (with or without tobacco) extract and BL-ext. The protective effect of BL-ext. against the genomic damage caused by pan masala was statistically significant only after treating the cells for a longer period.

Cytogenetic effects of near ultraviolet radiation in normal and systemic lupus erythematosus lymphocytes

International Nuclear Information System (INIS)

Caporossi, D.; Sebastiani, G.; Nicoletti, B.; Masala, C.

1990-01-01

The authors conducted a study on the spontaneous and UV-A induced frequency of chromosomal breaks and sister-chromatid exchanges (SCE) in purified lymphocytes from normal donors and from systemic lupus erythematosus (SLE) patients who were in clinical remission at the time of the study. Our results show that although SLE lymphocytes exhibit a higher frequency of spontaneous SCEs than controls, the rate of chromosomal breakage is comparable in the 2-groups. In both controls and patients, irradiation with UV-A (320-400 nm) increases the SCE values but does not significantly affect the frequency of chromosomal aberrations. (author). 14 refs.; 1 fig.; 3 tabs

A comparative study of the potentiating effect of caffeine and poly-D-lysine on chromosome damage induced by X-rays in plant cells

Energy Technology Data Exchange (ETDEWEB)

Mateos, S.; Panneerselvam, N.; Cortes, F. (Sevilla University, Faculty of Biology (Spain). Department of Cell Biology); Mateos, J.C. (Centro Regional de Oncologia ' Duque del Infantado' , Sevilla (Spain))

1992-04-01

X-ray-induced chromosomal aberrations (CA) were potentiated by post-treatments in G{sub 2} with either caffeine (caff) or poly-D-lysine (PDL) in root-tip cells of Allium cepa. The enhancement of the yield of CA was concomittant with an increase in the frequency of mitosis. The results seem to support the idea of a direct relationship between radiation-induced G{sub 2} delay and repair of chromosome damage. Similarities between caff and PDL are reported in both decreasing G{sub 2} delay and enhancing chromatid aberration yield. The possible molecular mechanism(s) of action responsible for the cytogenetic effects observed are discussed. (author). 20 refs.; 2 tabs.

Review of the international symposium, sister chromatid exchanges: twenty-five years of experimental research

International Nuclear Information System (INIS)

Tice, R.R.; Lambert, B.; Morimoto, Kanehisa; Hollaender, A.

1983-01-01

The purpose of this symposium was to honor initial research at Brookhaven by bringing internationally recognized leaders in the fields of genetics, cytogenetics, carcinogenesis, mutagenesis, radiation biology, toxicology, and environmental health together into an open forum to present and discuss: (1) current knowledge of the induction and formation of SCEs and their relationship to other biological endpoints, including carcinogenesis, mutagenesis, transformation, clastogenesis, DNA damage and repair, and cellular toxicity; (2) the optimal strategies for the utilization of SCEs in genetic toxicology testing schemes involving in vitro and in vivo exposure situations; (3) the most valid statistical methods for analyzing SCE data obtained from cells in culture, from cells in intact organisms, and from cells in humans; (4) the relevance of SCEs as an indicator of human disease states, both inherited and acquired, and of progress in disease treatment; and (5) the use of SCEs as an indicator of human exposure to genotoxic agents and their relevance as a prognosticator of future adverse health outcomes. This report summarizes the presentations. 7 references

Probing the mechanism of sister chromatid exchange formation with the fluorescent plus Giemsa technique

International Nuclear Information System (INIS)

Yu, L.C.

1976-01-01

The effects of x rays and light flashes on the SCE formation in BrdUrd-substituted Chinese hamster ovary (CHO) cells are examined using the fluorescent plus Giemsa (FPG) technique, which allows SCE's to be visualized with greater precision than 3 H autoradiography does. Near-diploid cells are selected and scoring SCE from every chromosome of near-diploid cells or from chromosome no. 1 is found to give a more accurate measure of the SCE induction. Double synchronous cells are used for the x ray study and asynchronous cells are used for the light flash study. The results indicate that x rays can induce SCE's throughout the cell cycle with S the most sensitive stage and G 2 the least sensitive stage. Light flashes can induce an appreciable amount of SCE's while no appreciable amount of chromosomal aberrations can be detected under conditions used in this study. For x-ray-induced chromosomal aberrations, G 2 is the most sensitive stage with G 1 being slightly more sensitive than S, which is consistent with other observations. Additionally, aberration induction is shown to be a more sensitive indicator of x-ray-induced cell damage than SCE induction, but SCE induction is a potentially good indicator of mutation induction. This study also suggests that symmetrically reunited isochromatid breaks can not be the sole source of SCE's and SCE induction is a different but not independent radiobiological effect from chromosomal aberration induction. SCE formation is proposed to be a consequence of specific type(s) of single strand breaks in DNA

Effect of tritiated compounds on sister-chromatid exchanges (SCE) in human lymphocytes in vitro

International Nuclear Information System (INIS)

Gong Manli; Rao Yongqing; Chen Guanying; Wu Weiwei; Zhao Zilan; Shen Lei

1990-01-01

Human lymphocytes treated in vitro with various activities of 3 H-TdR and 3 H-UdR were cultured to understand the effects of tritium on the cell cycle and the frequency of SCE. The results of these experiments indicated that both tritiated compounds make the frequency of SCE increase and the cell cycle delay. The frequency of SCE increased markedly with activity of 3 H. With respect to delaying cell cycle, 3 H-UdR was more effective than 3 H-TdR. The average frequencies of SCE for 3 H-UdR were higher than those for 3 H-TdR. With the exception of 3.7 x 10 3 Bq/mL group and differences between other 3 H-UdR groups and corresponding 3 H-TdR group were significant (t test, p < 0.01). These results suggest that tritiated compounds may have the effect on the cell proliferating rate. The cell proliferating rate index (PRI) seems to be related with the frequency of SCE: the higher the frequency of SCE, the lower the PRI is

Review of the international symposium, sister chromatid exchanges: twenty-five years of experimental research

Energy Technology Data Exchange (ETDEWEB)

Tice, R.R.; Lambert, B.; Morimoto, Kanehisa; Hollaender, A.

1983-01-01

The purpose of this symposium was to honor initial research at Brookhaven by bringing internationally recognized leaders in the fields of genetics, cytogenetics, carcinogenesis, mutagenesis, radiation biology, toxicology, and environmental health together into an open forum to present and discuss: (1) current knowledge of the induction and formation of SCEs and their relationship to other biological endpoints, including carcinogenesis, mutagenesis, transformation, clastogenesis, DNA damage and repair, and cellular toxicity; (2) the optimal strategies for the utilization of SCEs in genetic toxicology testing schemes involving in vitro and in vivo exposure situations; (3) the most valid statistical methods for analyzing SCE data obtained from cells in culture, from cells in intact organisms, and from cells in humans; (4) the relevance of SCEs as an indicator of human disease states, both inherited and acquired, and of progress in disease treatment; and (5) the use of SCEs as an indicator of human exposure to genotoxic agents and their relevance as a prognosticator of future adverse health outcomes. This report summarizes the presentations. 7 references. (ACR)

Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

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Simon Gemble

2015-07-01

Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

Science.gov (United States)

Gisselsson, David; Håkanson, Ulf; Stoller, Patrick; Marti, Dominik; Jin, Yuesheng; Rosengren, Anders H; Stewénius, Ylva; Kahl, Fredrik; Panagopoulos, Ioannis

2008-04-02

Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally. Chromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase transition. The multipolar metaphase-anaphase transition was accompanied by a normal reduction of cellular cyclin B levels, but typically occurred before completion of the normal separase activity cycle. Centromeric AURKB and MAD2 foci were observed frequently to remain on the centromeres of multipolar ana-telophase chromosomes, indicating that multipolar mitoses were able to circumvent the spindle assembly checkpoint with some sister chromatids remaining unseparated after anaphase. Accordingly, scoring the distribution of individual chromosomes in multipolar daughter nuclei revealed a high frequency of nondisjunction events, resulting in a near-binomial allotment of sister chromatids to the daughter cells. The capability of multipolar mitoses to circumvent the spindle assembly checkpoint system typically results in a near-random distribution of chromosomes to daughter cells. Spindle multipolarity could thus be a highly efficient generator of genetically diverse minority clones in transformed cell

Mammalian ChlR1 has a role in heterochromatin organization

International Nuclear Information System (INIS)

Inoue, Akira; Hyle, Judith; Lechner, Mark S.; Lahti, Jill M.

2011-01-01

The ChlR1 DNA helicase, encoded by DDX11 gene, which is responsible for Warsaw breakage syndrome (WABS), has a role in sister-chromatid cohesion. In this study, we show that human ChlR1 deficient cells exhibit abnormal heterochromatin organization. While constitutive heterochromatin is discretely localized at perinuclear and perinucleolar regions in control HeLa cells, ChlR1-depleted cells showed dispersed localization of constitutive heterochromatin accompanied by disrupted centromere clustering. Cells isolated from Ddx11 -/- embryos also exhibited diffuse localization of centromeres and heterochromatin foci. Similar abnormalities were found in HeLa cells depleted of combinations of HP1α and HP1β. Immunofluorescence and chromatin immunoprecipitation showed a decreased level of HP1α at pericentric regions in ChlR1-depleted cells. Trimethyl-histone H3 at lysine 9 (H3K9-me3) was also modestly decreased at pericentric sequences. The abnormality in pericentric heterochromatin was further supported by decreased DNA methylation within major satellite repeats of Ddx11 -/- embryos. Furthermore, micrococcal nuclease (MNase) assay revealed a decreased chromatin density at the telomeres. These data suggest that in addition to a role in sister-chromatid cohesion, ChlR1 is also involved in the proper formation of heterochromatin, which in turn contributes to global nuclear organization and pleiotropic effects. -- Highlights: → New role for ChlR1 (DDX11), a cohesinopathy gene, in heterochromatin organization. → Loss of ChlR1 altered heterochromatin localization and centromere clustering. → Reduced ChlR1 levels also reduced HP1α and H3K9-me3 binding to pericentric DNA. → Decreased DNA methylation was found in pericentric repeats of Ddx11 -/- embryos. → These findings will aid in understanding the pathogenesis of Warsaw breakage syndrome.

Niacin deficiency delays DNA excision repair and increases spontaneous and nitrosourea-induced chromosomal instability in rat bone marrow.

Science.gov (United States)

Kostecki, Lisa M; Thomas, Megan; Linford, Geordie; Lizotte, Matthew; Toxopeus, Lori; Bartleman, Anne-Pascale; Kirkland, James B

2007-12-01

We have shown that niacin deficiency impairs poly(ADP-ribose) formation and enhances sister chromatid exchanges and micronuclei formation in rat bone marrow. We designed the current study to investigate the effects of niacin deficiency on the kinetics of DNA repair following ethylation, and the accumulation of double strand breaks, micronuclei (MN) and chromosomal aberrations (CA). Weanling male Long-Evans rats were fed niacin deficient (ND), or pair fed (PF) control diets for 3 weeks. We examined repair kinetics by comet assay in the 36h following a single dose of ethylnitrosourea (ENU) (30mg/kg bw). There was no effect of ND on mean tail moment (MTM) before ENU treatment, or on the development of strand breaks between 0 and 8h after ENU. Repair kinetics between 12 and 30h were significantly delayed by ND, with a doubling of area under the MTM curve during this period. O(6)-ethylation of guanine peaked by 1.5h, was largely repaired by 15h, and was also delayed in bone marrow cells from ND rats. ND significantly enhanced double strand break accumulation at 24h after ENU. ND alone increased chromosome and chromatid breaks (four- and two-fold). ND alone caused a large increase in MN, and this was amplified by ENU treatment. While repair kinetics suggest that ND may be acting by creating catalytically inactive PARP molecules with a dominant-negative effect on repair processes, the effect of ND alone on O(6)-ethylation, MN and CA, in the absence of altered comet results, suggests additional mechanisms are also leading to chromosomal instability. These data support the idea that the bone marrow cells of niacin deficient cancer patients may be more sensitive to the side effects of genotoxic chemotherapy, resulting in acute bone marrow suppression and chronic development of secondary leukemias.

When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

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David Gisselsson

Full Text Available BACKGROUND: Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally. PRINCIPAL FINDINGS: Chromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase transition. The multipolar metaphase-anaphase transition was accompanied by a normal reduction of cellular cyclin B levels, but typically occurred before completion of the normal separase activity cycle. Centromeric AURKB and MAD2 foci were observed frequently to remain on the centromeres of multipolar ana-telophase chromosomes, indicating that multipolar mitoses were able to circumvent the spindle assembly checkpoint with some sister chromatids remaining unseparated after anaphase. Accordingly, scoring the distribution of individual chromosomes in multipolar daughter nuclei revealed a high frequency of nondisjunction events, resulting in a near-binomial allotment of sister chromatids to the daughter cells. CONCLUSION: The capability of multipolar mitoses to circumvent the spindle assembly checkpoint system typically results in a near-random distribution of chromosomes to daughter cells. Spindle multipolarity could thus be a highly efficient

The usefulness of cytogenetic parameters, level of p53 protein and endogenous glutathione as intermediate end-points in raw betel-nut genotoxicity.

Science.gov (United States)

Kumpawat, K; Chatterjee, A

2003-07-01

Betel-nut (BN) chewing related oral mucosal lesions are potential hazards to a large population worldwide. Genotoxicity of betel alkaloids, polyphenol and tannin fractions have been reported. It has been shown earlier that BN ingredients altered the level of endogenous glutathione (GSH) which could modulate the host susceptibility to the action of other chemical carcinogens. The north-east Indian variety of BN, locally known as 'kwai', is raw, wet and consumed unprocessed with betel-leaf and slaked lime and contains higher alkaloids, polyphenol and tannins as compared to the dried one. Therefore, the purpose of this study was to investigate the extent of DNA damage, pattern of cell kinetics, the level of p53-protein and endogenous GSH in kwai chewers in the tribal population of Meghalaya state in the northeastern region of India with an aim to see whether these end-points could serve as biomarkers of genetic damage of relevance for genotoxic/carcinogenic process. The present data show higher DNA damage, delay in cell kinetics, p53 expression and lower GSH-level in heavy chewers (HC) than nonchewers (NC). The influence of bleomycin (BLM) on chromatid break induction in G2-phase of peripheral blood lymphocytes in NC and HC has been analysed to determine individual susceptibility to carcinogenic assaults. HC showed higher induction of chromatid breaks than NC. Risk assessment in this study suggests an interaction between carcinogen exposure and mutagen sensitivity measures, risk estimates being higher in those individuals who both consume kwai and express sensitivity to free radical oxygen damage in vitro. From this study it seems that besides cytogenetical parameters, the level of endogenous GSH and the level of p53 protein could act as effective biomarkers for kwai chewers.

Nitric oxide coordinates development of genomic instability in realization of combined effect with ionizing radiation.

Science.gov (United States)

Mikhailenko, V M; Diomina, E A; Muzalov, I I; Gerashchenko, B I

2013-03-01

The aim of this study was to investigate the ability of environmental nitrogen oxides or natural nitric oxide (NO) donors to modify free radicals ba-lance and development of genomic instability alone or in combination with ionizing radiation. Genotoxicity and cytogenetic abnormalities were assessed in vitro in peripheral blood lymphocytes (PBL) isolated from healthy humans or in vivo in rats PBL. Human PBL were treated with physiologically relevant NO donor - S-Nitrosoglutathione and X-ray irradiation. The inhalation treatment of animals with NO was carried out in chamber with purified gaseous NO mixed inside with air. Levels of S-Nitrosohemoglobin and methemoglobin in the blood were assessed with electron paramagnetic resonance. The total level of reactive oxygen and nitrogen species in PBL was determined fluorometrically, and serum levels of reactive oxygen species was determined by spectrophotometric assay. DNA damages were assessed by alkaline single-cell gel electrophoresis. The frequency of chromosomal aberrations in human PBL measured with the conventional cytogenetic assay in metaphase cells on short-term (52 h) and long-term (72 h) cultures. Environmental nitrogen oxides or release of NO from stable complexes with biomolecules (such as S-Nitrosothiols) intensified generation of free radicals, DNA damage and development of genomic instability alone or in combination with ionizing radiation. Treatment of PBL by S-Nitrosoglutathione caused prevalent induction of chromatid type but irradiation - chromosome aberrations. The dose dependence of chromatid-type aberrations observed in human PBL after combined influence of S-Nitrosoglutathione and ionizing radiation indicates a crucial role of NO in the formation of chromosomal instability. NO can deregulate free radicals balance resulted in genotoxic effect, posttranslational modification of repair enzymes and thus coordinated development of genomic instability and increase of cancer risk.

Evaluation of the genotoxic effects of a folk medicine, Petiveria alliacea (Anamu).

Science.gov (United States)

Hoyos, L S; Au, W W; Heo, M Y; Morris, D L; Legator, M S

1992-07-01

Crude extract from a plant known as Petiveria alliacea (Anamu) is used extensively as folk medicine in developing countries like Colombia, South America. Although the plant is known to contain toxic ingredients potential adverse health effects from its use have not been adequately evaluated. We investigated its genotoxic activities by conducting a sister chromatid exchange (SCE) assay using cells in vitro and in vivo. Lymphocytes from humans were treated at 24 h after initiation of culture for 6 h with alcohol extract from the folk medicine. Concentrations of 0, 10, 100, 250, 275, 500, 750, and 1000 micrograms/ml of the extract were used. Significant dose-dependent increase of SCE (3.7-7.4 SCE per cell) were observed (analysis of variances, p less than 0.01). Delay in cell proliferation but not inhibition of mitosis was also observed. In another experiment, mice were exposed once orally to 1x, 200x, 300x and 400x the human daily consumption dose of Anamu. The induction of sister chromatid exchanges in bone marrow cells were investigated. We observed a significant dose dependent increase of SCE compared with the saline control (2.15-4.53; p less than 0.01) and compared with the solvent control (3.04-4.53; p less than 0.01). Our data suggest, therefore, that the folk medicine contains mutagenic and potentially carcinogenic agents although the medicine is not a potent mutagen. Individuals who consume large amounts of this drug may be at risk for development of health problems. Further studies with cells from exposed individuals and from experimental animals should be conducted to provide a better evaluation of health risk from the use of this drug.

Adaptive Response to ionizing Radiation Induced by Low Doses of Gamma Rays in Human Lymphoblastoid Cell Lines

International Nuclear Information System (INIS)

Seong, Jin Sil; Suh, Chang Ok; Kim, Gwi Eon

1994-01-01

When cells are exposed to low doses of a mutagenic or clastogenic agents, they often become less sensitive to the effects of a higher does administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher does (50 cGy). The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines. Which was first documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism

Research on Spontaneously Emerged Chromosomal Aberrations in the Periphery Blood Lymphocytes in Cattle (‘Buša’ Breed

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Danica Hasanbašić

2007-11-01

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

Nonrandom distribuion of chromosome breaks in cultured lymphocytes of normal subjects

Energy Technology Data Exchange (ETDEWEB)

Ayme, S.; Mattei, J.F.; Mattei, M.G.; Aurran, Y.; Giraud, F.

1976-02-29

Breakpoint distribution was studied from cultured lymphocytes on 7653 metaphases from 524 subjects whose karyotypes were normal. The mean break rate was 5% in both sexes. The frequency increased significantly after 40 years and varied during the year. The location of the breaks was very different from the expected random distribution. The break frequency for each chromosome was different according to the type of break (chromatid, simple chromosomal and chromosomal involving rearrangements). The location of the breaks was also studied according to the type of band and with respect to the centromere. A comparison between spontaneous breaks, x-ray induced breaks, breaks in Fanconi's anemia and in congenital rearrangements, show very significant differences.

Antigenotoxic Effect of Curcumin and Carvacrol against Parathion Induced DNA Damage in Cultured Human Peripheral Blood Lymphocytes and Its Relation to GSTM1 and GSTT1 Polymorphism

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Neeraj Kumar

2014-01-01

Full Text Available In recent years, the use of organophosphorus pesticides has been extensively increased and these compounds signify a major class of agricultural pesticides today. We studied antigenotoxic potential of curcumin and carvacrol against the parathion induced DNA damage in cultured peripheral blood lymphocytes using sister chromatid exchanges as a biomarker of genotoxicity. Heparinised fresh blood from healthy individuals was treated with 2.5 μg/mL concentration of parathion in presence of curcumin and carvacrol in order to observe the antigenotoxic potential of both curcumin and carvacrol. Significant reduction (P0.05 of GSTT1 and GSTM1 polymorphism on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol.

The bystander effect: is reactive oxygen species the driver?

International Nuclear Information System (INIS)

Szumiel, I.

2003-01-01

The paper reviews selected examples of the bystander effect, such as clonogenic survival decrease, chromosomal aberrations and mutations. The similarities and differences between the biological effects in directly targeted and bystander cells are briefly discussed. Also reviewed are the experimental data which support the role of reactive oxygen species (ROS), especially *O 2 - , as mediators of the bystander effect. Endogenously generated ROS, due to activation of NAD(P)H oxidases, play a kay role in the introduction of DNA damage in bystander cells. All the observed effects in bystander cells, such as alteration in gene expression patterns, chromosomal aberrations, sister chromatid exchanges, mutations, genome instability and neoplastic transformation are the consequence of DNA damage. (author)

Chromosome damage and clinical manifestation in a fetus and the mother after accidental 60Co exposure in Xinzhou

International Nuclear Information System (INIS)

Wang Jiajing; Mu Ying; Wang Shanmi

1995-01-01

The authors present the clinical effect and chromosome damage sustained by a fetus and the four months pregnant mother in an accidental 60 Co exposure in November of 1992 in Xinzhou, Shanxi Province. The mother suffered from a moderate acute radiation sickness with ratardation of fetal development. After delivery, the infant's body length, body weight and head circumference were all lowered by three percentiles compared with the normals. Four months after the exposure, the assay of the mother's peripheral lymphocytes showed a chromosome aberration rate of 36%, while concomitant examination of the baby failed to reveal any chromosome abnormality although the sister chromatid exchange rate was remarkably higher than that of the mother and the normal control

Chromosome analyses of nurses handling cytostatic agents

International Nuclear Information System (INIS)

Waksvik, H.; Klepp, O.; Brogger, A.

1981-01-01

A cytogenetic study of ten nurses handling cytostatic agents (average exposure, 2150 hours) and ten female hospital clerks revealed an increased frequency of chromosome gaps and a slight increase in sister chromatid exchange frequency among the nurses. The increase may be due to exposure to cytostatic drugs and points to these agents as a possible occupational health hazard. A second group of 11 nurses handling cytostatic agents for a shorter period of time (average exposure, 1078 hours), and three other groups (eight nurses engaged in therapeutic and diagnostic radiology, nine nurses engaged in anesthesiology, and seven nurses in postoperative ward) did not differ from the office personnel, except for an increased frequency of chromosome gaps in the radiology group

Chromosomes aberations and enviromental factors

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Marković Srđan Z.

2017-01-01

Full Text Available Explanation the topic: Changes in genetic material can lead to aberrant cell in the direction of disorders of cellular regulation, malignant transformation, cell death, or if the adjustment was made at the level of the reproductive cells, to genetic changes in some of the consequent off spring. The topic position in scientific/professional public: Breaking of chromosomes can occur spontaneously or can be induced. Chromatid/chromosome breakings can be induced by different environmental factors: chemicals, biological clastogenic agents, accidentally or intentionally. Conclusions: The authors suggest: - making conditions for strong respect of environmental regulations; - to use higher plants for the early detection of environmental mutagens; - create and orderly update National radionuclide database.

DNA repair in Bloom's syndrome skin fibroblasts after ultraviolet light irradiation

International Nuclear Information System (INIS)

Kurihara, Takayuki; Inoue, Masao; Kawashima, Hiroko; Yagi, Takashi; Takebe, Hiraku.

1981-01-01

Skin fibroblasts from a patient with Bloom's syndrome (86NoKi) were assayed for various DNA repair activities after ultraviolet light (UV) irradiation. Cultured fibroblasts as well as lymphocytes obtained from this patient showed a high frequency of spontaneous sister chromatid exchanges (SCEs). There was no significant difference between 86NoKi fibroblasts and skin fibroblasts from normal donors in the sensitivity to UV as measured by inactivation of colony forming activity, the capacity of host-cell reactivation (HCR) of UV-irradiated virus, and the amount of unscheduled DNA synthesis (UDS) after UV irradiation. However, the yield of UV-induced SCEs in 86NoKi cells was significantly higher than that in normal cells. (author)

Meiosis en mutantes desinápticos con restitución cromosómica en Rhoeo spathacea (Commelinaceae Meiosis in desynaptic-chromosomal restitution mutants in Rhoeo spathacea (Commelinaceae

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Armando García-Velázquez

2008-10-01

Full Text Available El estudio se llevó a cabo en recolectas de Rhoeo spathacea realizadas en Veracruz, Chiapas, Tabasco, Yucatán, Quintana Roo y Michoacán, México. Las plantas presentaron número diploide de cromosomas (2n=12 en mitosis. En meiosis los individuos formaron anillo y/o cadenas en metafase I, con excepción de varios mutantes desinápticos-RSD (separación de cromosomas apareados. En meiosis de Rhoeo no se observan bivalentes ni hay posibilidades de entrecruzamiento, y consecuentemente no habrá quiasmas ya que no hay cuatro cromátidas de las cuales dos deberían ser no-hermanas. Sin embargo, en anafase I hay disyunción altamente regular 6:6 que se presentan como "anillos o donas" con los brazos cortos hacia el interior de esas figuras. De la autofecundación de un mutante desináptico-RSD (GAVA 1.1 se obtuvo una progenie F2 de 123 individuos: 90 diploides-formadores de anillos y 1 acrotrisómico (2n=13. Esto es, 91 individuos "revirtieron" el comportamiento y 29 fueron diploandróginos tetraploides desinápticos (2n=24 y 3 hipertetraploides (2n=25 desinápticos. Este comportamiento diferente entre hermanos confirma que Rhoeo es dicarión: los diploides- con anillo tendrán el subgenoma A, y los tetraploides el B, que incluyen cromatidas hermanas en la restitución en segunda división (2n.This study was carried out with collected material of Rhoeo spathacea in the states of Veracruz, Chiapas, Tabasco, Yucatan, Quintana Roo and Michoacan, Mexico. All material exhibited a diploid chromosome number (2n =12 in mitosis. In meiosis, all individuals showedring and /or chains at metaphase I. Exceptionally several desynaptic mutants resulted desynaptic - SDR (dissociation of paired chromosomes. Therefore, in meiosis Rhoeo did not exhibit synapsis in parallel-fashion instead the chromosomes are united in end-to-end (no chiasmata- fashion. Then, there are not bivalents, no chiasmata-achiasmata- as there are not four chromatids two of which resulted sister-chromatids

Application of mammalian cytogenetics to mutagenicity studies

International Nuclear Information System (INIS)

Brewen, J.G.

1977-01-01

Studies on induction of chromosome damage in germ cells by triethylene melamine (TEM) included determination of frequencies of chromosomal aberrations observed in human leukocytes after treating different stages of the cell cycle with TEM, frequencies of chromatid aberrations in metaphase I oocytes and the female pronuclear chromosomes following treatment of female mice with TEM, and frequencies of labeled diplotene-diakinesis figures and chromosome abberations at various intervals after treatment of primary spermatocytes with TEM and 3 H-thymidine. Studies on effects of low linear energy transfer radiation on mouse oocytes showed that the frequency of aberrations increased as a function of time and remained constant 8 to 9 days post-exposure. It was concluded that cytogenetic procedures were adequate to evaluate certain mutagenic end points

Chromosomal aberrations induced by caffeine, 3H-thymidine and by X-rays in two L5178Y sublines of different radiosensitivity. Part 2. Effect of 2 mM caffeine on the frequency of chromosomal aberrations induced by X-radiation

International Nuclear Information System (INIS)

Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B.

1982-01-01

The effect of 2 mM caffeine on the frequency of X-ray induced chromatid aberrations in two sublines of L5178Y cells with different sensitivity to X-rays was examined. Cells were irradiated with 1 Gy of X-rays and treated with caffeine for 12 h after irradiation. The frequency of aberrations was estimated at time intervals from 5 to 48 h after irradiation. Caffeine increased the frequency of cells with numerous aberrations produced by X radiation in both sublines. Its potentiating effect was greater in the radiation-resistant subline L5178Y-R than in the radiation-sensitive one L5178Y-S. In caffeine-treated L5178Y-S cells chromosomal aberrations were revealed earlier than in the untreated cells. (author)

G2 chromosomal radiosensitivity in Fanconi's anemia

International Nuclear Information System (INIS)

Bigelow, S.B.; Rary, J.M.; Bender, M.A.

1979-01-01

Both the peripheral lymphocytes from 4 patients affected with the inherited disease Fanconi's anemia (FA), and tissue-culture fibroblasts from skin biopsies from 33 patients similarly affected were found to be about twice as sensitive to the induction of chromatid-type chromosomal aberrations by X-rays administered in the G 2 phase of the cell cycle as cells from normal controls. Using tritiated thymidine labelling of peripheral lymphocytes and of cultured fibroblasts, it was determined that 3 affected patients and 3 normal controls all had similar percent labeled mitoses (PLM) curves, so the increased induced aberration yields seen in the FA cells do not appear to be simply a consequence of a longer than normal G 2 phase of the cell cycle. (Auth.)

X ray sensitivity of diploid skin fibroblasts from patients with Fanconi's anemia

Science.gov (United States)

Kale, Ranjini

1989-01-01

Experiments were performed on Fanconi's anemia and normal human fibroblast cell lines growing in culture in an attempt to correlate cell cycle kinetics with genomic damage and determine their bearing on the mechanism of chromosome aberration induction. FA fibroblasts showed a significantly increased susceptibility to chromosomal breakage by x rays in the G2 phase of the cell cycle. No such response was observed in fibroblasts irradiated in the G0 phase. The observed increases in achromatic lesions and in chromatid deletions in FA cells as compared with normal cells appear to indicate that FA cells are deficient in strand break repair and also possibly in base damage excision repair. Experiments are now in progress to further elucidate the mechanisms involved.

Cytomorphological studies in X-ray induced glandless haploids in Gossypium hirsutum L. (cotton)

Energy Technology Data Exchange (ETDEWEB)

Mehetre, S.S.; Thombre, M.V. (Mahatma Phule Krishi Vidyapeeth, Rahuri (India))

1981-08-01

Six haploid plants were obtained in M/sub 2/ generation of the 25 kr. X-ray irradiated Gossypium hirsutum L. cotton variety H.G. 108. The cytomorphological studies on these plants indicated highly irregular meiosis, giving on an average six bivalents, the range being 0-9. Unequal separation of chromosomes and chromatids at anaphase-1 and II respectively led to formation of abnormal tetrads and pollens with high size variations leading to high pollen sterility. These plants were characterized by miniature stature, shorter stem and internodes, smaller leaves, flowers and stomata with fewer chloroplasts, male and female sterility and halving of chromosomes. The reduction in morphological characters was nearly in the proportion of 1:2 as compared to their diploid counterparts. 31 refs.; 5 tables; 12 figures.

The importance of chromosome studies in Roberts syndrome/SC phocomelia and other cohesinopathies.

Science.gov (United States)

Gerkes, Erica H; van der Kevie-Kersemaekers, Anne-Marie F; Yakin, Mariam; Smeets, Dominique F C M; van Ravenswaaij-Arts, Conny M A

2010-01-01

Roberts syndrome/SC phocomelia is a rare, autosomal recessive syndrome characterised by pre- and postnatal growth retardation, microcephaly, craniofacial anomalies, mental retardation, and tetraphocomelia in varying degrees of severity. The clinical diagnosis can be challenging in phenotypically mild cases. In the extremely mild case presented here, specific mitotic abnormalities were detected and proved to be very helpful, since Roberts syndrome/SC phocomelia could be diagnosed after finding premature centromere separation and somatic aneuploidy at routine karyotyping. We discuss these and other mitotic cytogenetic abnormalities that can be of significant diagnostic importance, but which will be missed if only array studies are performed. We also discuss the difference between premature centromere separation and premature (sister) chromatid separation. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

Structural analysis of radiation-induced chromosome aberrations by atomic force microscope (AFM) before and after Giemsa staining

International Nuclear Information System (INIS)

Murakami, M.; Kanda, R.; Minamihisamatsu, M.; Hayata, I.

2003-01-01

Full text: We have studied structures of chromosome aberration induced by ionizing radiation by an atomic force microscope (AFM). The AFM could visualize the fine structure of chromosomes on Giemsa stained or unstained samples, although it was difficult to visualize unstained chromosomes by light microscope. The height data of chromosomes obtained by AFM provided useful information to describe detailed structure of chromatid gaps induced by heavy ion irradiation. A fibrous structure was observed on the unstained chromosome and these structures were considered to be the 30nm fibers on the chromosome. These types of structures were observed in the gaps as well as on surface of the chromosome. Further more, other types of chromosome aberration induced by ionizing radiation visualized by AFM will be presented

Study on germ toxicity of exciting energy resource 147Pm of fluorescent paint

International Nuclear Information System (INIS)

Zhu Shoupeng; Lun Minyue; Tao Feng

1993-02-01

The germ toxicity of exciting energy resource 147 Pm of fluorescent paint was studied. It was shown that the placenta was a barrier for 147 Pm entering into the fetus. The retention T 1/2 was 105 days in testes. The retention value of 147 Pm in testis was high and hardly to excrete. The results showed that 147 Pm can induce abnormal sperms, most of them were non-hock sperms. The chromosome aberrations in germ cells also can be induced. Among the type of chromosome aberrations of spermatogonia, chromatid breakage was predominant. The 147 Pm can cause the chromosome fragment and translocations of primary spermatocytes, and increasing of lethality. The dominant skeletal aberrations in offspring is proportional to the accumulated radioactivity of 147 Pm in tests

Biomonitoring human exposure to environmental carcinogenic chemicals

DEFF Research Database (Denmark)

Farmer, P.B.; Sepai, O.; Lawrence, R.

1996-01-01

A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological...... spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome...... aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical...

Phonic and induced level of mutations and mutagenicity in bioorganisms habitating in the environs of Ignalina APP

International Nuclear Information System (INIS)

Lekevichius, R.; Morkunas, V.; Knabikas, A.

1992-01-01

The investigation of the extracts from the water, mud and hydrobionts of the lake Drukshiai before the construction of the Ignalina atomic power plant (1982-1984) and after its construction enabled to detect the moment of the build-up of mutagens in the hydrobionts (in 1986), when the extracts began to induce spot mutations in Salmonella typhimurium and exchanges of sister chromatids in human leukocytes in vitro. The mutagenicity of rain water, sewerage water and water from the cooler of the atomic power plant to drosophila and Salmonella typhimurium has been detected. The increments of mutations in the populations of Larus ridibundus and Microtus arvalis inhabiting the surroundings of the atomic power plant has not been noticed. (author). 4 figs., 4 refs

The expanding universe of cohesin functions: a new genome stability caretaker involved in human disease and cancer.

Science.gov (United States)

Mannini, Linda; Menga, Stefania; Musio, Antonio

2010-06-01

Cohesin is responsible for sister chromatid cohesion, ensuring the correct chromosome segregation. Beyond this role, cohesin and regulatory cohesin genes seem to play a role in preserving genome stability and gene transcription regulation. DNA damage is thought to be a major culprit for many human diseases, including cancer. Our present knowledge of the molecular basis underlying genome instability is extremely limited. Mutations in cohesin genes cause human diseases such as Cornelia de Lange syndrome and Roberts syndrome/SC phocomelia, and all the cell lines derived from affected patients show genome instability. Cohesin mutations have also been identified in colorectal cancer. Here, we will discuss the human disorders caused by alterations of cohesin function, with emphasis on the emerging role of cohesin as a genome stability caretaker.

Descriptive evaluation of chromosome aberrations in blood lymphocytes due to gamma-irradiation

International Nuclear Information System (INIS)

Medina III, F.S.; Gregorio, J.S.; Vinoya, P.C.; Panlaque, C.A.

1983-01-01

To induce and evaluate the effect of radiation among Filipinos, frequencies and types of ν-ray induced chromosome aberrations were studied with peripheral lymphocytes from 19 donors. Peripheral blood samples were irradiated at 0 Gray, 500 mGy, 1 Gy, 2 Gy, 3 Gy and 4 Gy. Irradiated blood samples were cultured by the same standard technique as that commonly used for human blood lymphocytes. Our observations showed that irradiation causes chromosomal aberration similar to effects observed in Caucasians. Our study confirm that irradiation causes an increase of the chromosome aberrations types normally found in the control (gaps, chromatid breaks and chromosome fragments) and can induce aberrations which are rarely observed in non-exposed individual (deletions, translocations, polycentrics, rings, and despiralizations). (author)

Discovering non-random segregation of sister chromatids: The naïve treatment of a premature discovery

Directory of Open Access Journals (Sweden)

Karl G. Lark

2013-02-01

Full Text Available The discovery of non-random chromosome segregation is discussed from the perspective of what was known in1965 and1966. The distinction between daughter, parent or grandparent strands of DNA was developed in a bacterial system and led to the discovery that multiple copies of DNA elements of bacteria are not distributed randomly with respect to the age of the template strand. Experiments with higher eukaryotic cells demonstrated that during mitosis Mendel’s laws were violated; and the initial serendipitous choice of eukaryotic cell system led to the striking example of non-random segregation of parent and grand-parent DNA template strands in primary cultures of cells derived from mouse embryos. Attempts to extrapolate these findings to established TC lines demonstrated that the property could be lost. Experiments using plant root tips demonstrated that the phenomenon exists in plants and that it was, at some level, under genetic control. Despite publication in major journals and symposia (Lark et al. (1966a; Lark (1967a; 1967b; 1969, 1969a; 1969b the potential implications of these findings were ignored for several decades. Here we explore possible reasons for the pre-maturity (Stent, 1972 of this discovery.

The roles of the Saccharomyces cerevisiae RecQ helicase SGS1 in meiotic genome surveillance.

Directory of Open Access Journals (Sweden)

Amit Dipak Amin

2010-11-01

Full Text Available The Saccharomyces cerevisiae RecQ helicase Sgs1 is essential for mitotic and meiotic genome stability. The stage at which Sgs1 acts during meiosis is subject to debate. Cytological experiments showed that a deletion of SGS1 leads to an increase in synapsis initiation complexes and axial associations leading to the proposal that it has an early role in unwinding surplus strand invasion events. Physical studies of recombination intermediates implicate it in the dissolution of double Holliday junctions between sister chromatids.In this work, we observed an increase in meiotic recombination between diverged sequences (homeologous recombination and an increase in unequal sister chromatid events when SGS1 is deleted. The first of these observations is most consistent with an early role of Sgs1 in unwinding inappropriate strand invasion events while the second is consistent with unwinding or dissolution of recombination intermediates in an Mlh1- and Top3-dependent manner. We also provide data that suggest that Sgs1 is involved in the rejection of 'second strand capture' when sequence divergence is present. Finally, we have identified a novel class of tetrads where non-sister spores (pairs of spores where each contains a centromere marker from a different parent are inviable. We propose a model for this unusual pattern of viability based on the inability of sgs1 mutants to untangle intertwined chromosomes. Our data suggest that this role of Sgs1 is not dependent on its interaction with Top3. We propose that in the absence of SGS1 chromosomes may sometimes remain entangled at the end of pre-meiotic replication. This, combined with reciprocal crossing over, could lead to physical destruction of the recombined and entangled chromosomes. We hypothesise that Sgs1, acting in concert with the topoisomerase Top2, resolves these structures.This work provides evidence that Sgs1 interacts with various partner proteins to maintain genome stability throughout

G2 repair and chromosomal damage in lymphocytes from workers occupationally exposed to low-level ionizing radiation

Directory of Open Access Journals (Sweden)

J PINCHEIRA

1999-01-01

Full Text Available The effect of the G2 repair of chromosomal damage in lymphocytes from workers exposed to low levels of X- or g-rays was evaluated. Samples of peripheral blood were collected from 15 radiation workers, 20 subjects working in radiodiagnostics, and 30 healthy control donors. Chromosomal aberrations (CA were evaluated by scoring the presence of chromatid and isochromatid breaks, dicentric and ring chromosomes in lymphocytes with/without 5mM caffeine plus 3mM-aminobenzamide (3-AB treatment during G2. Our results showed that the mean value of basal aberrations in lymphocytes from exposed workers was higher than in control cells (p< 0.001. The chromosomal damage in G2, detected with caffeine plus 3-AB treatment was higher than the basal damage (untreated conditions, both in control and exposed populations (p< 0.05. In the exposed workers group, the mean value of chromosomal abnormalities in G2 was higher than in the control (p< 0.0001. No correlation was found between the frequency of chromosome type of aberrations (basal or in G2, and the absorbed dose. Nevertheless, significant correlation coefficients (p< 0.05 between absorbed dose and basal aberrations yield (r = 0.430 or in G2 (r = 0.448 were detected when chromatid breaks were included in the total aberrations yield. Under this latter condition no significant effect of age, years of employment or smoking habit on the chromosomal aberrations yield was detected. However, analysis of the relationship between basal aberrations yield and the efficiency of G2 repair mechanisms, defined as the percentage of chromosomal lesions repaired in G2, showed a significant correlation coefficient (r = -0.802; p< 0.001. These results suggest that in addition to the absorbed dose, the individual G2 repair efficiency may be another important factor affecting the chromosomal aberrations yield detected in workers exposed to low-level ionizing radiation

A cytogenetic study of personnel of the Kozloduy NPP with a view to the hazards of late effects

Energy Technology Data Exchange (ETDEWEB)

Bulanova, M; Benova, D; Georgieva, I; Georgieva, V; Yagova, A; Rupova, I; Kusheva, R; Khadzhidekova, V; Topalova, S; Nikolova, T [National Centre of Radiobiology and Radiation Protection, Sofia (Bulgaria)

1996-12-31

Chromosomal analysis of 40 Kozloduy NPP workers has been carried out. Three cytogenetic end-points have been considered: chromosomal aberrations (CA), sister-chromatid exchanges and micro nuclear assays in peripheral blood lymphocytes. A higher incidence of CA has been detected in the investigated group in comparison with a control group. This is attributed to the radiation factor taking into consideration that the highest occurrence is that of dicentric chromosomes induced by radiation exposure. 95% of the workers have been employed for more than 5 years and 60% have received a dose of more than 30 cSv. However no direct relation of CA incidence to the accumulated dose has been observed. Tobacco smoking potentiates additionally the damage of the chromosome structures caused by ionizing radiation. 15 refs., 3 tabs.

Radio-adaptive response

International Nuclear Information System (INIS)

Ikushima, T.

1992-01-01

Knowledge about cellular events in mammalian cells exposed to low doses of ionizing radiation is meager. Recent works showed that human lymphocytes become resistant to radiation-induced chromosomal damage after exposure to low doses of ionizing radiation. Experimental evidence for radio-adaptive response (RAR) in cultured mammalian cells was obtained. Exposure to very low doses of gamma-rays or tritium beta-rays make cells less susceptible to the induction of micronuclei and sister chromatid exchanges by subsequent higher doses. Many important characteristics of the novel response suggest that RAR is a stress response resulting in the enhanced repair of chromosomal DNA damage in cell under restricted conditions. Experiments are still in progress in order to elucidate the molecular basis for RAR processes. (author). 13 refs.; 2 figs., 1 tab

Meiosis in radiation induced triploid and tetraploid plants of pearl millet

International Nuclear Information System (INIS)

Singh, R.B.; Singh, B.D.; Singh, R.M.; Laxmi, V.

1977-01-01

A triploid and a tetraploid plant were isolated from mutagen treated populations of HB3 (Tif23AxJ104) and HBI (Tif23AxBi13B) hybrid pearl millet, respectively. The triploid plant regularly showed univalents (1 to 9 per cell) and trivalents (1 to 6 per cell) at MI. In the case of the tetraploid, only bivalents were observed which showed loose or tight secondary associations at MI; at AI bivalents separated as units (instead of chromosomes) while at AII chromosomes (instead of chromatids) moved to the opposite poles. Although the chromosome behaviour was quite regular, the plant was highly sterile (98%). It is suggested that gamma-rays had induced mutations in a number of genes, including those affecting pairing, concomitant to the induction of tetraploidy. (auth.)

The roles of cohesins in mitosis, meiosis, and human health and disease

Science.gov (United States)

Brooker, Amanda S.; Berkowitz, Karen M.

2015-01-01

Summary Mitosis and meiosis are essential processes that occur during development. Throughout these processes, cohesion is required to keep the sister chromatids together until their separation at anaphase. Cohesion is created by multi-protein subunit complexes called cohesins. Although the subunits differ slightly in mitosis and meiosis, the canonical cohesin complex is composed of four subunits that are quite diverse. The cohesin complexes are also important for DNA repair, gene expression, development, and genome integrity. Here we provide an overview of the roles of cohesins during these different events, as well as their roles in human health and disease, including the cohesinopathies. Although the exact roles and mechanisms of these proteins are still being elucidated, this review will serve as a guide for the current knowledge of cohesins. PMID:24906316

Experimental verification for in vitro technique confirmation of bystander effect induced by gamma radiation in CHO-K1 cell line

International Nuclear Information System (INIS)

Viana, P.H.L.; Goes, A.M.; Gomes, D.A.

2013-01-01

The bystander effect refers to biological responses detected in cells not directly irradiated but influenced, somehow, by signals transmitted from neighboring irradiated cells. These biological responses include sister chromatid exchange, mutations, micronucleus formation, chromosomal aberrations, carcinogenesis, apoptosis and necrosis. Although its existence is unquestionable, the mechanisms involved on triggering the bystander effect are not yet completely elucidated. Previous studies have shown that the bystander effect depends on a large variety of parameters including the radiation dose, the dose rate, the type of radiation and type of cells or tissue. This study aims to confirm the technique previously used in the literature in human cell lines for the bystander effect verification. The results suggest that the working conditions adopted by the group show technical efficiency and enables the reproduction of the bystander effect. (author)

Stem cell identity and template DNA strand segregation.

Science.gov (United States)

Tajbakhsh, Shahragim

2008-12-01

The quest for stem cell properties to distinguish their identity from that of committed daughters has led to a re-investigation of the notion that DNA strands are not equivalent, and 'immortal' DNA strands are retained in stem cells whereas newly replicated DNA strands segregate to the differentiating daughter cell during mitosis. Whether this process occurs only in stem cells, and also in all tissues, remains unclear. That individual chromosomes can be also partitioned non-randomly raises the question if this phenomenon is related to the immortal DNA hypothesis, and it underscores the need for high-resolution techniques to observe these events empirically. Although initially postulated as a mechanism to avoid DNA replication errors, alternative views including epigenetic regulation and sister chromatid silencing may provide insights into this process.

The genetic effects of radio-activity in man and other organisms

International Nuclear Information System (INIS)

Parry, J.M.

1979-01-01

The changes that occur in the chromosomal information and which give rise to observable genetic effects stem from the induction by radiation of a number of lesions within the DNA. The relative frequencies of single and double strand breaks induced in DNA is dependent upon the type of radiation exposure given. Radiation sensitivity of a variety of different species of bacteria irradiated with gamma rays in air are given. The effect of dose rate upon radiation induced genetic damage indicates that at low dose rates the cells are capable of handling or repairing a higher proportion of the radiation induced DNA lesions before they undergo the events leading to chromosome and chromatid aberration. The radiation quality, expressed in terms of LET (linear energy transfer) also influence the induction of genetic damage. (U.K.)

Proteomic analysis of human metaphase chromosomes reveals Topoisomerase II alpha as an Aurora B substrate

DEFF Research Database (Denmark)

Morrison, Ciaran; Henzing, Alexander J; Jensen, Ole Nørregaard

2002-01-01

B in the presence of radioactive ATP. Immunoblot analysis confirmed the HeLa scaffold fraction to be enriched for known chromosomal proteins including CENP-A, CENP-B, CENP-C, ScII and INCENP. Mass spectrometry of bands excised from one-dimensional polyacrylamide gels further defined the protein......The essential Aurora B kinase is a chromosomal passenger protein that is required for mitotic chromosome alignment and segregation. Aurora B function is dependent on the chromosome passenger, INCENP. INCENP, in turn, requires sister chromatid cohesion for its appropriate behaviour. Relatively few...... composition of the extracted chromosome fraction. Cloning, fluorescent tagging and expression in HeLa cells of the putative GTP-binding protein NGB/CRFG demonstrated it to be a novel mitotic chromosome protein, with a perichromosomal localisation. Identi fication of the protein bands corresponding to those...

Experimental verification for in vitro technique confirmation of bystander effect induced by gamma radiation in CHO-K1 cell line; Verificacao experimental para confirmacao da tecnica in vitro do efeito bystander induzido por radiacao gama na linhagem celular CHO-K1

Energy Technology Data Exchange (ETDEWEB)

Viana, P.H.L.; Goes, A.M.; Gomes, D.A., E-mail: pedroleroybio@hotmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento Bioquimica e Imunologia. Lab. de Imunologia Celular e Molecular; Grynberg, S.E., E-mail: seg@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2013-08-15

The bystander effect refers to biological responses detected in cells not directly irradiated but influenced, somehow, by signals transmitted from neighboring irradiated cells. These biological responses include sister chromatid exchange, mutations, micronucleus formation, chromosomal aberrations, carcinogenesis, apoptosis and necrosis. Although its existence is unquestionable, the mechanisms involved on triggering the bystander effect are not yet completely elucidated. Previous studies have shown that the bystander effect depends on a large variety of parameters including the radiation dose, the dose rate, the type of radiation and type of cells or tissue. This study aims to confirm the technique previously used in the literature in human cell lines for the bystander effect verification. The results suggest that the working conditions adopted by the group show technical efficiency and enables the reproduction of the bystander effect. (author)

In vivo mutagenicity studies in rats mice and Chinese hamsters fed irradiated foodstuffs - chicken, fish, dates, pulses, mangoes and cocoa beans

International Nuclear Information System (INIS)

Renner, H.W.

1982-01-01

Three in vivo genetic toxicity tests were performed in rats, mice and Chinese hamsters to detect possible mutagenic effects of irradiated chicken, dried dates, fish, cocoa beans, pulses and mangoes. The tests employed were the micronucleus test and sister-chromatid exchange (SCE) test for irradiated and unirradiated samples of all foodstuffs listed, and the spermatogonia test, (including SCE technique) in mice for irradiated and unirradiated chicken, fish and dates only. In the case of cocoa beans, the mutagenicity tests were performed on an additional test group fed beans fumigated with ethylene oxide. The different mammalian species used for the various experiments are given below. None of the tests provided any evidence of mutagenicity induced by irradiation in any of the foodstuffs studied. Moreover, these tests are currently considered to be the most sensitive in vivo mutagenicity tests in mammals. (orig.)

Human hereditary diseases associated with elevated frequency of chromosome aberrations

International Nuclear Information System (INIS)

Ejima, Yosuke

1988-01-01

Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G 0 or G 1 phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases. (author)

The phenotype of FancB-mutant mouse embryonic stem cells

International Nuclear Information System (INIS)

Kim, Tae Moon; Ko, Jun Ho; Choi, Yong Jun; Hu Lingchuan; Hasty, Paul

2011-01-01

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by bone marrow failure, developmental defects and cancer. There are multiple FA genes that enable the repair of interstrand crosslinks (ICLs) in coordination with a variety of other DNA repair pathways in a way that is poorly understood. Here we present the phenotype of mouse embryonic stem (ES) cells mutated for FancB. We found FancB-mutant cells exhibited reduced cellular proliferation, hypersensitivity to the crosslinking agent mitomycin C (MMC), increased spontaneous and MMC-induced chromosomal abnormalities, reduced spontaneous sister chromatid exchanges (SCEs), reduced gene targeting, reduced MMC-induced Rad51 foci and absent MMC-induced FancD2 foci. Since FancB is on the X chromosome and since ES cells are typically XY, FancB is an excellent target for an epistatic analysis to elucidate FA's role in ICL repair.

Human hereditary diseases associated with elevated frequency of chromosome aberrations

Energy Technology Data Exchange (ETDEWEB)

Ejima, Yosuke; Ikushima, Takaji (ed.)

1988-07-01

Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G/sub 0/ or G/sub 1/ phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases.

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

DEFF Research Database (Denmark)

Hagmar, L; Brøgger, A; Hansteen, I L

1994-01-01

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

Yield of chromosomal aberrations and recoil particle range in Chineses hamster fibroblasts exposed to 8.5 to 500 keV neutrons

International Nuclear Information System (INIS)

Sturelid, S.; Bergman, R.

1976-01-01

Induction of chromatid aberrations in S-phase Chinese hamster fibroblasts has been studied for irradiation by 60 Co gamma rays and neutrons of average energy 8.5, 45, 83, 200 and 500 keV. At 10 per cent aberration level the relative biological afficiency varied between 2.2 +- 0.6 (at 8.5 keV) and a maximum of 47 +- 9 (at 200 keV). The neutron generated recoils have short range in comparison to chromosomal dimensions. The strong variation with neutron energy is therefore not necessarily reflecting variations in the average linear energy transfer. Good agreement between experimental and predicted response was obtained when effects ascribed to range were considered. A critical volume within which primary lesions should occur in order to make chromosomal aberrations probable was derived. The corresponding site radius was estimated to be 1-3 μm. (author)

MUS81 promotes common fragile site expression

DEFF Research Database (Denmark)

Ying, Songmin; Minocherhomji, Sheroy; Chan, Kok Lung

2013-01-01

Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair the fait......Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair...... the faithful disjunction of sister chromatids in mitosis. However, the mechanisms by which CFSs express their fragility, and the cellular factors required to suppress CFS instability, remain largely undefined. Here, we report that the DNA structure-specific nuclease MUS81-EME1 localizes to CFS loci in early...

Antioxidant and antigenotoxic potencies of Sempervivum armenum on human lymphocytes in vitro.

Science.gov (United States)

Sunar, Serap; Anar, Mustafa; Sengul, Meryem; Agar, Guleray

2016-12-01

In this research, the genotoxic and antigenotoxic effects of methanol extract of Sempervivum armenum (MSA) were studied using micronucleus (MN) test and sister chromatid exchange (SCE) test systems in cultured human peripheral blood cells. According to the SCE and MN tests results, MSA reduced the genotoxic effects of aflatoxin B 1 . In order to explain the reason for the antigenotoxic effects of MSA, antioxidants levels were determined. Cotreatments of 5, 10, 20 mg/mL concentrations of MSA with aflatoxin B 1 decreased the frequencies of SCE, MN and the malondialdehyde level and increased the amount of superoxide dismutase, glutathione and glutathione peroxidase which were decreased by aflatoxin. The results of this experiment showed that MSA has strong antioxidative and antigenotoxic effects and this antigenotoxic activities of MSA can be due to the antioxidant activities.

Time/effect after acute gamma irradiation of rats

International Nuclear Information System (INIS)

Georgieva, I.; Mileva, M.; Ivanov, B.

1991-01-01

Sexually mature male Wistar rats has received single acute whole body gamma irradiation with 51.6 mC/kg ( 137 Cs). Samples for cytogenetic investigations of bone-marrow cells have been prepared at 8, 24 and 50 hours, as well as on 3, 7. 15, 30 and 180 days after irradiation. Spontaneous structure aberrations are presented by acentric single and pair chromosomal fragments with occurencies 1.3 and 1.1%. Chromatid exchanges, dicentics and symmetric exchanges have been also found after irradiation. The higher percent of cells with aberrations and bigger number of aberrations per cell have been established in the initial periods (8 and 24 hrs after irradiation), then a statistically reliable reduction of the aberration rates has been observed. After the 15th day both indices are equalized with those of controls. 1 fig., 1 tab., 20 refs

On the genetic effects of low-level tritium

International Nuclear Information System (INIS)

Hori, Tada-aka; Nakai, Sayaka

1976-01-01

Genetic risk assessment for potential hazard from environmental tritium to man becomes important with increasing nuclear-power industry. The purpose of this short review is to discuss the possible genetic effects of tritium from a view of genetic risk estimation. The discussion is based mainly on our experimental results on the chromosome aberrations induced in human lymphocytes by tritium at the very low-level. The types of chromosome aberrations induced by radiation from tritium incorporated into the cells are mostly chromatid types. The most interesting finding is that the dose-response relationship observed in both tritiated-water and tritiated-thymidine is composed of two phases. The examination on the nature of two-phase dose-response relationship is very important not only for the mechanisms of chromosome aberrations, but also for the evaluation of genetic risk from low-level radiation. (auth.)

Estimate of radiation detriment long period after exposure to low doses of ionizing radiation: Chromosomal aberrations in liquidators 6-10 years after the Chernobyl accident

International Nuclear Information System (INIS)

Nikiforov, A.M.; Slozina, N.M.; Neronova, E.G.; Kharchenko, T.V.; Drygina, L.B.; Strukov, E.L.

1997-01-01

The group of 297 liquidators was cytogenetically investigated 6 - 10 years after the Chernobyl accident. The significantly increased level of chromosomal and chromatid types exchange aberrations was shown. For all subjects questionnaires that provide consideration of known and suspected confounding variables were filled in. The participation in recovery works at the Chernobyl nuclear power station was the only reason for dicentrics and rings rise in liquidators. An investigation of the tumor-specific markers (CEA, AFP, CA19-9, PSA, NSE) was carried out in 56 liquidators simultaneously with chromosomal analysis. The increased level of NSE was found in liquidators bearing the chromosomal aberrations of exchange type. The results of this work let us to consider the liquidators who underwent to low doses of ionizing radiation 6-10 years ago as a detrimental group that needs special scientific and medical attention. (author)

Cis-Acting Determinants Affecting Centromere Function, Sister-Chromatid Cohesion and Reciprocal Recombination during Meiosis in Saccharomyces Cerevisiae

OpenAIRE

Sears, D. D.; Hegemann, J. H.; Shero, J. H.; Hieter, P.

1995-01-01

We have employed a system that utilizes homologous pairs of human DNA-derived yeast artificial chromosomes (YACs) as marker chromosomes to assess the specific role (s) of conserved centromere DNA elements (CDEI, CDEII and CDEIII) in meiotic chromosome disjunction fidelity. Thirteen different centromere (CEN) mutations were tested for their effects on meiotic centromere function. YACs containing a wild-type CEN DNA sequence segregate with high fidelity in meiosis I (99% normal segregation) and...

Parallel increases in sister chromatid exchanges at base level and with UV treatment in human opiate users

International Nuclear Information System (INIS)

Shafer, D.A.; Falek, A.; Madden, J.J.; Tadayon, F.; Pline, M.; Kuehnle, J.C.; Mendelson, J.

1983-01-01

The SCE base level frequency and SCE levels induced by far-UV (254 nm) treatment of cells in early G 1 and early S phases of the cell cycle were significantly higher in leukocytes from heroin addicts as compared to controls. The increased SCE levels in addicts was greatest at base level and smallest after UV irradiation of cells in S phase. These results corrobate and extend our previous findings of increased chromosome damage and reduced DNA-repair synthesis in heroin users. Since opiates do not directly damage DNA, the elevated cytogenetic effects associated with opiate use probably arise from secondary promotional effects related to opiate-mediated alterations in leukocyte metabolism. (orig.)

Sister Chromatid Exchanges (=SCEs) in Lymphocytes of persons working at Shlobin (USSR), 150km north of Chernobyl

International Nuclear Information System (INIS)

Tuschl, H.; Kovac, R.

1988-08-01

SCEs are considered to be a sensitive indicator for the DNA damaging effects of mutagenic and carcinogenic agents. In 1986, during the Chernobyl accident, employees of an Austrian company worked at Shlobin, 150km north of Chernobyl. At their return to Austria blood as taken and spontaneously occurring and MMC induced SCEs were studied. Spontaneously occurring SCEs in lymphocytes of 'exposed' and 'unexposed' persons were only insignificantly different when results were summarized for all test persons. A significant influence of smoking could be established. When results were correlated with the time interval between the Chernobyl accident and the date of blood sampling, the increased rate of spontaneous SCEs observed soon after the accident decreased to the normal range during the following months. Irrespective of the molecular mechanism that might be the rationale for the observed decreased induction of SCEs in lymphocytes of exposed persons, the estimation of MMC induced SCEs proved to be the most sensitive test to demonstrate population exposure to low doses of ionizing radiation. 7 refs., 1 fig., 5 tabs. (Author)

The functional polymorphism of NBS1 p.Glu185Gln is associated with an increased risk of lung cancer in Chinese populations: Case–control and a meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Fang, Wenxiang; Qiu, Fuman; Zhang, Lisha [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China); Deng, Jieqiong [Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123 (China); Zhang, Haibo [Department of Cardio-thoracic Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080 (China); Yang, Lei [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China); Zhou, Yifeng [Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123 (China); Lu, Jiachun, E-mail: jcLu@gzhmu.edu.cn [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China)

2014-12-15

Highlights: • NBS1 rs1805794G>C polymorphism conferred an adverse role on lung cancer risk in a two centers case–control study. • Rs1805794C variants had more chromatid breaks and higher DNA damage induced by X-ray radiation. • Meta analysis result confirmed the association between the variant rs1805794G>C and lung cancer risk. - Abstract: NBS1 plays pivotal roles in maintaining genomic stability and cancer development. The exon variant rs1805794G>C (p.Glu185Gln) of NBS1 has been frequently studied in several association studies. However, the results were conflicting. Also, the function of this variant has never been well studied. In the current study, we performed a two centers case–control study and function assays to investigate the effect of the variant rs1805794G>C on lung cancer risk in Chinese, and a meta-analysis to summarize the data on the association between rs1805794G>C and cancer risk. We found that compared with the rs1805794GG genotype, the C genotypes (CG/CC) conferred a significantly increased risk of lung cancer in Chinese (OR = 1.40, 95% CI = 1.21–1.62) and interacted with medical ionizing radiation exposure on increasing cancer risk (P{sub interaction} = 0.015). The lymphocyte cells from the C genotype individuals developed more chromatid breaks than those from the GG genotype carriers after the X-ray radiation (P = 0.036). Moreover, the rs1805794C allele encoding p.185Gln attenuated NBS1's ability to repair DNA damage as the cell lines transfected with NBS1 cDNA expression vector carrying rs1805794C allele had significantly higher DNA breaks than those transfected with NBS1 cDNA expression vector carrying rs1805794G allele (P < 0.05). The meta-analysis further confirmed the association between the variant rs1805794G>C and lung cancer risk, that compared with the GG genotype, the carriers of C genotypes had a 1.30-fold risk of cancer (95% CI = 1.14–1.49, P = 8.49 × 10{sup −5}). These findings suggest that the rs1805794G

Genetic damage in human cells exposed to non-ionizing radiofrequency fields: a meta-analysis of the data from 88 publications (1990-2011).

Science.gov (United States)

Vijayalaxmi; Prihoda, Thomas J

2012-12-12

Based on the 'limited' evidence suggesting an association between exposure to radiofrequency fields (RF) emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as 'possibly carcinogenic to humans' in group 2B. In view of this classification and the positive correlation between increased genetic damage and carcinogenesis, a meta-analysis was conducted to determine whether a significant increase in genetic damage in human cells exposed to RF provides a potential mechanism for its carcinogenic potential. The extent of genetic damage in human cells, assessed from various end-points, viz., single-/double-strand breaks in the DNA, incidence of chromosomal aberrations, micronuclei and sister chromatid exchanges, reported in a total of 88 peer-reviewed scientific publications during 1990-2011 was considered in the meta-analysis. Among the several variables in the experimental protocols used, the influence of five specific variables related to RF exposure characteristics was investigated: (i) frequency, (ii) specific absorption rate, (iii) exposure as continuous wave, pulsed wave and occupationally exposed/mobile phone users, (iv) duration of exposure, and (v) different cell types. The data indicated the following. (1) The magnitude of difference between RF-exposed and sham-/un-exposed controls was small with some exceptions. (2) In certain RF exposure conditions there was a statistically significant increase in genotoxicity assessed from some end-points: the effect was observed in studies with small sample size and was largely influenced by publication bias. Studies conducted within the generally recommended RF exposure guidelines showed a smaller effect. (3) The multiple regression analyses and heterogeneity goodness of fit data indicated that factors other than the above five variables as well as the quality of publications have contributed to the overall results. (4) More

Cell cycle kinetics and in vivo micronuclei induction in rat rhabdomyosarcoma tumors using a monoclonal antibody to BrdUrd and cell sorting

International Nuclear Information System (INIS)

Nuesse, M.; Afzal, S.M.J.; Carr, B.C.; Kavanau, K.S.; Tenforde, T.S.; Curtis, S.B.

1986-01-01

The aim of the experiments reported here was to investigate the applicability of the BrdUrd/DNA technique to a rat rhabdomyosarcoma tumor system growing in vivo and to study radiation-induced changes in the progression of cells through the cell cycle. Details of this technique are described elsewhere. In addition, the induction of micronuclei in tumor cells irradiated in vivo with x-rays or peak neon ions was studied. Micronuclei found in interphase cells after irradiation represent genetic material that is lost from the genome of the cells during mitosis. The formation of micronuclei that can mainly be ascribed to acentric chromosome or chromatid fragments occurs only after cells go through one or more cell divisions. Cycling cells in the tumors were, therefore, continuously labeled with BrdUrd, and micronuclei induction was measured only in tetraploid cycling tumor cells using the flow cytometric cell sorting technique

Sensitivity to ultraviolet radiation in a dominantly inherited form of xeroderma pigmentosum

International Nuclear Information System (INIS)

Imray, F.P.; Relf, W.; Ramsay, R.G.; Kidson, C.; Hockey, A.

1986-01-01

An Australian family is described in which a mild form of xeroderma pigmentosum (XP) is inherited as an autosomal dominant trait. Studies of lymphoblastoid cells and fibroblasts from affected person demonstrated sensitivity to ultraviolet (UV) light as judged by diminished clonogenicity and higher frequencies of UV induced chromosome aberrations compared to normal controls. After UV irradiation of dominant XP cells, replicative DNA synthesis was depressed to a greater extent than normal and the level of UV induced DNA repair synthesis was lower than that in normal cells. The level of sister chromatid exchanges and the numbers of 6-thioguanine resistant mutants induced by UV irradiation were equal to those found in normal controls. Although two subjects in the family had skin cancers, this dominant form of XP is not apparently associated with high risk, or large numbers of skin cancers in affected persons. (author)

Assessment of in vitro genotoxic and cytotoxic effects of flurbiprofen on human cultured lymphocytes.

Science.gov (United States)

Timocin, Taygun; Ila, Hasan Basri; Dordu, Tuba; Husunet, Mehmet Tahir; Tazehkand, Mostafa Norizadeh; Valipour, Ebrahim; Topaktas, Mehmet

2016-01-01

Flurbiprofen is non-steroidal anti-inflammatory drug which is commonly used for its analgesic, antipyretic, and anti-inflammatory effects. The purpose of the study was to explore the genotoxic and cytotoxic effects of flurbiprofen in human cultured lymphocytes by sister chromatid exchange, chromosome aberration, and cytokinesis-blocked micronucleus tests. 10, 20, 30, and 40 μg/mL concentrations of flurbiprofen (solvent is DMSO) were used to treatment of human cultured lymphocytes at two different treatment periods (24 and 48 h). Flurbiprofen had no significant genotoxic effect in any of these tests. But exposing to flurbiprofen for 24 and 48 h led to significant decrease on proliferation index, mitotic index, and nuclear division index (NDI). Also, all decreases were concentration-dependent (except NDI at 24 h treatment period). Consequently, the findings of this research showed that flurbiprofen had cytotoxic effects in human blood lymphocytes.

Effects of 5-fluorouracil on the mitotic activity of onion root tips apical meristem

Directory of Open Access Journals (Sweden)

Waldemar Lechowicz

2015-01-01

Full Text Available The effects of various concentrations of 5-FU on the mitotic activity of onion root tips apical meristem were investigated during 24-hour incubation in 5-FU and postincubation in water. The incubation in 5-FU caused a reversible inhibition of mitotic activity, and waves of the partially synchronised mitoses were observed during the period of postincubation. The most pronounced synchronisation of mitoses was obtained after incubation in 100 mg/l. 5-FU but the mitotic index of the resumed mitotic activity amounted to only one half of the control value. 5-FU was found to cause some cytological changes in meristematic cells such as enlargement of the nucleoli, change in the interphasic nuclei structure, appearance of subchromatid and chromatid aberrations and micronuclei. The effects of 5-FU on nucleic acids and the cell division cycle ace discussed and compared with the effects of 5-FUdR.

Male meiosis in Crustacea: synapsis, recombination, epigenetics and fertility in Daphnia magna.

Science.gov (United States)

Gómez, Rocío; Van Damme, Kay; Gosálvez, Jaime; Morán, Eugenio Sánchez; Colbourne, John K

2016-09-01

We present the first detailed cytological study of male meiosis in Daphnia (Crustacea: Branchiopoda: Cladocera)-an aquatic microcrustacean with a cyclical parthenogenetic life cycle. Using immunostaining of the testes in Daphnia magna for baseline knowledge, we characterized the different stages of meiotic division and spermiogenesis in relation to the distribution of proteins involved in synapsis, early recombination events and sister chromatid cohesion. We also studied post-translational histone modifications in male spermatocytes, in relation to the dynamic chromatin progression of meiosis. Finally, we applied a DNA fragmentation test to measure sperm quality of D. magna, with respect to levels of inbreeding. As a proxy for fertility, this technique may be used to assess the reproductive health of a sentinel species of aquatic ecosystems. Daphnia proves to be a model species for comparative studies of meiosis that is poised to improve our understanding of the cytological basis of sexual and asexual reproduction.

Cytogenetic indices in blood lymphocytes of individuals from the staff working on new confinement constructing in Chornobyl NPP zone

International Nuclear Information System (INIS)

Bezdrobna, L.K.; Tarasenko, L.V.; Tsiganok, T.V.; Mel'nik, T.V.; Nosach, Yu.O.; Sushko, V.O.; Nechajev, S.Yu.; Shvajko, L.Yi.

2014-01-01

In contracting staff mean group frequency of aberrant lymphocytes, chromosome (dicentrics, acentrics, abnormal monocentrics) and chromatide type aberrations is significantly higher than such frequency in the comparison group. Three staff persons had individual frequency of specific markers of exposure - dicentric chromosomes with accompanying fragments significantly higher than their mean population level and the average frequency in the comparison group. It indicates the probability of their excess radiation when working in Chornobyl NPP local zone. Cells with two chromosome exchanges and one multiaberrant cell were registered in staff with the absence of such in control persons. The calculated estimated radiation doses of two staff persons were 87-123 mGy and and one person 210-240 mGy of acute exposure respectively. Calculated by frequency of dicentric chromosomes tentative 'biological' doses of three staff persons show a more significant radiation effect comparing to the data of physical dosimetry

Chromosomal radiosensitivity: a study of the chromosomal G2 assay in human blood lymphocytes indicating significant inter-individual variability

International Nuclear Information System (INIS)

Smart, V.; Curwen, G.B.; Whitehouse, C.A.; Edwards, A.; Tawn, E.J.

2003-01-01

The G 2 chromosomal radiosensitivity assay is a technically demanding assay. To ensure that it is reproducible in our laboratory, we have examined the effects of storage and culture conditions by applying the assay to a group of healthy controls and determined the extent of intra- and inter-individual variations. Nineteen different individuals provided one or more blood samples resulting in a total of 57 successful tests. Multiple cultures from a single blood sample showed no statistically significant difference in the number of chromatid type aberrations between cultures. A 24 h delay prior to culturing the lymphocytes did not significantly affect the induced G 2 score. Intra-individual variation was not statistically significant in seven out of nine individuals. Inter-individual variation was highly statistically significant (P<0.001), indicating that there is a real difference between individuals in the response to radiation using this assay

Familial melanoma associated with dominant ultraviolet radiation sensitivity

International Nuclear Information System (INIS)

Ramsay, R.G.; Chen, P.; Imray, F.P.; Kidson, C.; Lavin, M.F.; Hockey, A.

1982-01-01

Sensitivity to ultraviolet radiation was studied in lymphoblastoid cell lines derived from 32 members of two families with histories of multiple primary melanomas in several generations. As assayed by colony formation in agar or by trypan blue exclusion following irradiation, cellular sensitivity showed a bimodal distribution. All persons with melanoma or multiple moles were in the sensitive group, while some family members exhibited responses similar to those of controls. Cells from four cases of sporadic melanoma showed normal levels of sensitivity. The data are consistent with a dominantly inherited ultraviolet light sensitivity associated with these examples of familial melanoma. Spontaneous and ultraviolet light-induced sister chromatid exchange frequencies were similar to those in control cell lines. No defect in excision repair was detected in any of the above cell lines, but the sensitive group showed postirradiation inhibition of DNA replication intermediate between controls and an excision-deficient xeroderma pigmentosum cell line

Chromosome aberration analysis in peripheral lymphocytes of Gulf war and Balkans war veterans

Energy Technology Data Exchange (ETDEWEB)

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

2003-07-01

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 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 dic 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. The frequency of SCEs was decreased when compared with the laboratory control. (author)

Chromosome aberration analysis in peripheral lymphocytes of Gulf war and Balkans war veterans

International Nuclear Information System (INIS)

Schroeder, 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 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 dic 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. The frequency of SCEs was decreased when compared with the laboratory control. (author)

The phenotype of FancB-mutant mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Tae Moon; Ko, Jun Ho; Choi, Yong Jun; Hu Lingchuan [Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245 (United States)

2011-07-01

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by bone marrow failure, developmental defects and cancer. There are multiple FA genes that enable the repair of interstrand crosslinks (ICLs) in coordination with a variety of other DNA repair pathways in a way that is poorly understood. Here we present the phenotype of mouse embryonic stem (ES) cells mutated for FancB. We found FancB-mutant cells exhibited reduced cellular proliferation, hypersensitivity to the crosslinking agent mitomycin C (MMC), increased spontaneous and MMC-induced chromosomal abnormalities, reduced spontaneous sister chromatid exchanges (SCEs), reduced gene targeting, reduced MMC-induced Rad51 foci and absent MMC-induced FancD2 foci. Since FancB is on the X chromosome and since ES cells are typically XY, FancB is an excellent target for an epistatic analysis to elucidate FA's role in ICL repair.

Initial occupational exposure to lead

Energy Technology Data Exchange (ETDEWEB)

Forni, A.; Cambiaghi, G.; Secchi, G.C.

1976-01-01

Serial chromosome and biochemical studies were carried out in 11 subjects before and during initial occupational exposure to moderate quantities of lead fumes in a storage battery plant. The rate of abnormal metaphases, mostly with chromatid and one-break chromosome aberrations, was approximately doubled after one month of work; it further increased after two months of work; remained in this range up to seven months of exposure; and then tended to decrease somewhat. Blood lead levels increased progressively in the first few months, then reached a steady state. Urinary lead and coproporphyrin levels increased sharply after one month of work, while urinary delta-aminolevulinic acid (ALA) levels increased moderately. The ALA dehydratase (ALAD) activity of red blood cells (RBCs) was reduced to almost 50 percent of the initial values after one month, decreased further in subsequent months, and remained decreased through the remainder of the study.

Study of cell cycle parameters of man lymphocytes irradiated at various stages using differential coloring of sister chromatides

International Nuclear Information System (INIS)

Poryadkova, N.A.

1984-01-01

Parameters of the cell cycle of human lymphocytes are specified, radiation effect applied at various stages of mitotic cycle on the kinetics of cell advance in the cycle is also investigated. It is shown that increasing mitotic index occurs only due to the introduction of cells into the first mitosis. It is not excluded that cells ready to enter the second mitosis died with greater probability as after second synthesis they contained two-fold amount of BDU (5-brominedesoxiuridine) than cells of the first mitosis. In all cases with irradiation of cells of the third mitosis were not found

Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation

NARCIS (Netherlands)

Handyside, Alan H.; Montag, Markus; Magli, M. Cristina; Repping, Sjoerd; Harper, Joyce; Schmutzler, Andreas; Vesela, Katerina; Gianaroli, Luca; Geraedts, Joep

2012-01-01

Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis following natural conception

Differential features of sister-chromatid exchange responses to ultraviolet radiation and caffeine in xeroderma pigmentosum lymphoblastoid cell lines

International Nuclear Information System (INIS)

Tohda, H.; Oikawa, A.

1983-01-01

Sister-chromatic exchange (SCE) induced by ultraviolet (UV) irradiation and viability after UV irradiation were studied in lymphoblastoid cell lines derived from 7 patients with xeroderma pigmentosum (XP) and 6 normal donors. UV irradiation caused significant increases of SCEs in both XP and normal cells. In 3 XP cell lines, which were deficient in unscheduled DNA synthesis (UDS) and sensitive to the killing effect of UV, very high SCE frequencies were observed after UV irradiation. Cells from a patient with the De Sanctis-Cacchione syndrome were the most sensitive to UV in terms of both SCE induction and cell killing. In 2 of 4 UDS-proficient XP cell lines tested, the incidences of UV-induced SCEs were similar to those in normal cell lines, but in 2 other UDS-proficient lines from 2 XP patients with skin cancer, the frequencies of UV-induced SCEs were significantly higher than in normal cells. (orig./AJ)

Effects of bromine on mitosis in root-tips of Allium cepa

Energy Technology Data Exchange (ETDEWEB)

Chury, J; Slouka, V

1949-01-01

The root-tips of Allium cepa, 1.5-2 cm. long, were exposed to pure bromine vapor for five minutes. The root-tips were then washed for ten minutes in water, and kept in fresh-water at a temperature of 20-24/sup 0/C. Squash preparations were made and stained according to the method of Darlington and La Cour. Bromine acting for five minutes on the root-tips of Allium has a specific effect on the cell nucleus in the resting stage. The effects induced are shown thirty-six hours after treatment by spindle abnormalities in metaphase and anaphase, and result in polyploidy in a large number of cells. Bromine produces chromosome and chromatid fragmentation; the latter may be followed by reunion. The effect of the bromine is cumulative and depends on the time which elapses between treatment and fixation. The cytological effects induced by bromine strongly suggest that it is another specific mutafacient chemical.

MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination.

Science.gov (United States)

Bhattacharjee, Sonali; Osman, Fekret; Feeney, Laura; Lorenz, Alexander; Bryer, Claire; Whitby, Matthew C

2013-09-11

The histone-fold proteins Mhf1/CENP-S and Mhf2/CENP-X perform two important functions in vertebrate cells. First, they are components of the constitutive centromere-associated network, aiding kinetochore assembly and function. Second, they work with the FANCM DNA translocase to promote DNA repair. However, it has been unclear whether there is crosstalk between these roles. We show that Mhf1 and Mhf2 in fission yeast, as in vertebrates, serve a dual function, aiding DNA repair/recombination and localizing to centromeres to promote chromosome segregation. Importantly, these functions are distinct, with the former being dependent on their interaction with the FANCM orthologue Fml1 and the latter not. Together with Fml1, they play a second role in aiding chromosome segregation by processing sister chromatid junctions. However, a failure of this activity does not manifest dramatically increased levels of chromosome missegregation due to the Mus81-Eme1 endonuclease, which acts as a failsafe to resolve DNA junctions before the end of mitosis.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides

Science.gov (United States)

Izquierdo-Vega, Jeannett Alejandra; Morales-González, José Antonio; Sánchez-Gutiérrez, Manuel; Betanzos-Cabrera, Gabriel; Sosa-Delgado, Sara M.; Sumaya-Martínez, María Teresa; Morales-González, Ángel; Paniagua-Pérez, Rogelio; Madrigal-Bujaidar, Eduardo; Madrigal-Santillán, Eduardo

2017-01-01

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequently consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay. PMID:28157162

Recent progress in nickel carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Sunderman, F.W. Jr.

1984-01-01

Positive bacterial mutagenesis tests have been obtained with Ni(II) in Corynybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni(II) binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister-chromatid exchanges, (b) DNA strandbreaks and DNA-protein crosslinks, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double-stranded poly(dG-dC) DNA from the right-handed B-helix to the left-handed Z-helix, suggesting a mechanism whereby nickel might modulate oncogene expression. 99 references, 4 tables.

Adaptive response induced by occupational exposures to ionizing radiation

International Nuclear Information System (INIS)

Barquinero, J.F.; Caballin, M.R.; Barrios, L.; Egozcue, J.; Miro, R.; Ribas, M.

1997-01-01

We have found a significant decreased sensitivity to the cytogenetic effects of both ionizing radiation (IR) (2 Gy of γ rays) and bleomycin (BLM, 0,03 U/ml), in lymphocytes from individuals occupationally exposed to IR when compared with controls. These results suggest that occupational exposures to IR can induce adaptive response that can be detected by a subsequent treatment either by IR or by BLM. When a comparison is made between the cytogenetic effects of both treatments, no correlation was observed at the individual level. On the other hand, the individual frequencies of chromosome aberrations induced by a challenge dose of IR were negatively correlated with the occupationally received doses during the last three years. This correlation was not observed after the challenge treatment of BLM. Moreover, the individual frequencies of chromosome aberrations induced by IR treatment were homogeneous. This is not the case of the individual frequencies of chromatid aberrations induced by BLM, where a great heterogeneity was observed. (authors)

Somatic cell chromosome changes in a population exposed to low levels of ionizing radiation

International Nuclear Information System (INIS)

Brandom, W.F.

1982-01-01

The analysis of chromosomes from the cells of 897 plutonium workers is reported. Within three years, the number of controls alone analyzed for this study approximated the largest plutonium cytogenetic studies today including workers plus controls (81 compared to 84 in a 1979 French study and 94 in a 1982 British report). The number of subjects analyzed in the first three years were: new employees - 245; new employees assigned to plutonium work areas - 7; workers with less than 3% of maximum permissible systemic burden (MPSB) - 35; workers with less than 50% MPSB - 274; workers with greater than 50% of MPSB - 65; follow-up familial congenital cytogenetics at worker request (through Medical) - 6; polymorphic/variant chromosome constitutions - 242; re-sampling of workers with elevated aberration yields - 26; cell sample study - 28; sister-chromatid-exchange (SCE) study - 23; beryllium workers at Rocky Flats - 10; Hanford worker analyses - 5). 20 refs., 3 figs., 5 tabs

Effects of cellular non-protein sulfhydryl depletion in radiation induced oncogenic transformation and genotoxicity in mouse C3H 10T1/2 cells

International Nuclear Information System (INIS)

Hei, T.K.; Geard, C.R.; Hall, E.J.

1984-01-01

A study was made of the effects of cellular non-protein sulfhydryl (NPSH) depletion on cytotoxicity, cell cycle kinetics, oncogenic transformation and sister chromatid exchange (SCE) in C 3 H 10T1/2 cells. Using DL-Buthionine S-R-Sulfoximine (BSO) to deplete thiols, it was found spectrophotometrically that less than 5% of control NPSH level remained in the cells after 24-hour treatment under aerated conditions. Such NPSH depleted cells, when subject to a 3 Gy γ-ray treatment, were found to have no radiosensitizing response either in terms of cell survival or oncogenic transformation. In addition, decreased levels of NPSH had no effect on spontaneous or radiation-induced SCE nor were cell cycle kinetics additionally altered. Therefore, the inability of NPSH depletion to alter γ-ray induced cellular transformation was unrelated to any possible effect of BSO on the cell cycle. These results suggest that such depletion may result in little or no additional oncogenic or genotoxic effects on aerated normal tissues

Induction of sustained aberration and SCE in peripheral blood lymphocytes by internal contamination of fragment 147Pm

International Nuclear Information System (INIS)

Zhu Shoupeng; Cao Genfa; Sun Baofu

1994-12-01

The purpose of this study is to ascertain the induction of sustained aberration and SCE in peripheral blood lymphocytes by 147 Pm retention in the body. The retention process of 147 Pm in the body fitted an equation which consists of two components, fast and slow. The half-time of the fast component is T 1 = 4.77 d and that of the slow component is T 2 = 816.3 d. When 147 Pm was accumulated in the body, it caused chromosome aberrations in peripheral blood lymphocytes. Among the different types of aberration induced by 147 Pm, the predominant type was aberration of chromatid, accompanied by a few chromosome breakage and translocation. The experimental results indicated that SCE of peripheral blood lymphocytes increased significantly after different periods of 147 Pm exposures. It should be noted that after exposure for 30 d, a peak elevation of SCE in peripheral blood lymphocytes was observed. (8 figs., 3 tabs.)

Chromosomal radiosensitivity during the G2 cell-cycle period of skin fibroblasts from individuals with familial cancer

International Nuclear Information System (INIS)

Parshad, R.; Sanford, K.K.; Jones, G.M.

1985-01-01

The authors reported previously that human cells after neoplastic transformation in culture had acquired an increased susceptibility to chromatid damage induced by x-irradiation during the G2 phase of the cell cycle. Evidence suggested that this results from deficient DNA repair during G2 phase. Cells derived from human tumors also showed enhanced G2-phase chromosomal radiosensitivity. Furthermore, skin fibroblasts from individuals with genetic diseases predisposing to a high risk of cancer, including ataxia-telangiectasia, Bloom syndrome, Fanconi anemia, and xeroderma pigmentosum exhibited enhanced G2-phase chromosomal radiosensitivity. The present study shows that apparently normal skin fibroblasts from individuals with familial cancer--i.e., from families with a history of neoplastic disease--also exhibit enhanced G2-phase chromosomal radiosensitivity. This radiosensitivity appears, therefore, to be associated with both a genetic predisposition to cancer and a malignant neoplastic state. Furthermore, enhanced G2-phase chromosomal radiosensitivity may provide the basis for an assay to detect genetic susceptibility to cancer

Polo kinase Cdc5 is a central regulator of meiosis I

Science.gov (United States)

Attner, Michelle A.; Miller, Matthew P.; Ee, Ly-sha; Elkin, Sheryl K.; Amon, Angelika

2013-01-01

During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern. PMID:23918381

Meiosis I chromosome segregation is established through regulation of microtubule–kinetochore interactions

Science.gov (United States)

Miller, Matthew P; Ünal, Elçin; Brar, Gloria A; Amon, Angelika

2012-01-01

During meiosis, a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate, while sister chromatids remain together. Determining how this unusual chromosome segregation behavior is established is central to understanding germ cell development. Here we show that preventing microtubule–kinetochore interactions during premeiotic S phase and prophase I is essential for establishing the meiosis I chromosome segregation pattern. Premature interactions of kinetochores with microtubules transform meiosis I into a mitosis-like division by disrupting two key meiosis I events: coorientation of sister kinetochores and protection of centromeric cohesin removal from chromosomes. Furthermore we find that restricting outer kinetochore assembly contributes to preventing premature engagement of microtubules with kinetochores. We propose that inhibition of microtubule–kinetochore interactions during premeiotic S phase and prophase I is central to establishing the unique meiosis I chromosome segregation pattern. DOI: http://dx.doi.org/10.7554/eLife.00117.001 PMID:23275833

Proteomic effects of wet cupping (Al-hijamah).

Science.gov (United States)

Almaiman, Amer A

2018-01-01

Wet cupping (Al-hijamah) is a therapeutic technique practiced worldwide as a part of the Unani system of medicine. It involves bloodletting from acupoints on a patient's skin to produce a therapeutic outcome. A thorough review of research articles on wet cupping with relevance to proteomics field that are indexed by Google Scholar, PubMed, and/or Science Direct databases was performed. Eight original research articles were summarized in this paper. Overall, wet cupping did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid exchanges, and cell replication index. In contrast, wet cupping was found to produce higher oxygen saturation, eliminate lactate from subcutaneous tissues, remove blood containing higher levels of malondialdehyde and nitric oxide, and produce higher activity of myeloperoxidase. The proteomic effects of wet cupping therapy have not been adequately investigated. Thus, future studies on wet cupping that use systemic and sound protocols to avoid bias should be conducted.

Proteomic effects of wet cupping (Al-hijamah

Directory of Open Access Journals (Sweden)

Amer A. Almaiman

2018-01-01

Full Text Available Wet cupping (Al-hijamah is a therapeutic technique practiced worldwide as a part of the Unani system of medicine. It involves bloodletting from acupoints on a patient’s skin to produce a therapeutic outcome. A thorough review of research articles on wet cupping with relevance to proteomics field that are indexed by Google Scholar, PubMed, and/or Science Direct databases was performed. Eight original research articles were summarized in this paper. Overall, wet cupping did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid exchanges, and cell replication index. In contrast, wet cupping was found to produce higher oxygen saturation, eliminate lactate from subcutaneous tissues, remove blood containing higher levels of malondialdehyde and nitric oxide, and produce higher activity of myeloperoxidase. The proteomic effects of wet cupping therapy have not been adequately investigated. Thus, future studies on wet cupping that use systemic and sound protocols to avoid bias should be conducted.

Cytogenetic investigation of subjects professionally exposed to radiofrequency radiation.

Science.gov (United States)

Maes, Annemarie; Van Gorp, Urbain; Verschaeve, Luc

2006-03-01

Nowadays, virtually everybody is exposed to radiofrequency radiation (RFR) from mobile phone base station antennas or other sources. At least according to some scientists, this exposure can have detrimental health effects. We investigated cytogenetic effects in peripheral blood lymphocytes from subjects who were professionally exposed to mobile phone electromagnetic fields in an attempt to demonstrate possible RFR-induced genetic effects. These subjects can be considered well suited for this purpose as their RFR exposure is 'normal' though rather high, and definitely higher than that of the 'general population'. The alkaline comet assay, sister chromatid exchange (SCE) and chromosome aberration tests revealed no evidence of RFR-induced genetic effects. Blood cells were also exposed to the well known chemical mutagen mitomycin C in order to investigate possible combined effects of RFR and the chemical. No cooperative action was found between the electromagnetic field exposure and the mutagen using either the comet assay or SCE test.

Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

Energy Technology Data Exchange (ETDEWEB)

Wiese, Claudia; Dray, Eloise; Groesser, Torsten; San Filippo,Joseph; Shi, Idina; Collins, David W.; Tsai, Miaw-Sheue; Williams,Gareth; Rydberg, Bjorn; Sung, Patrick; Schild, David

2007-04-11

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice

Energy Technology Data Exchange (ETDEWEB)

Leland, Shawn; Nagarajan, Prabakaran; Polyzos, Aris; Thomas, Sharon; Samaan, George; Donnell, Robert; Marchetti, Francesco; Venkatachalam, Sundaresan

2009-06-24

Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice, and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes was sufficient to explain the reduced litter size in matings with Bub1 heterozygous females. No effects were seen in germ cells from heterozygous males. These findings show that Bub1 dysfunction is linked to inherited aneuploidy in female germ cells and may contribute to the maternal age-related increase in aneuploidy and pregnancy loss.

Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.

Directory of Open Access Journals (Sweden)

Damien F Hudson

2016-12-01

Full Text Available Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Cells from homozygous individuals exhibit elevated rates of sister chromatid exchange, anaphase DNA bridges and micronuclei. Similar genome and chromosome instability phenotypes are observed in independently derived RMI2 knockout cells. In both patient and knockout cell lines reduced localisation of BLM to ultra fine DNA bridges and FANCD2 at foci linking bridges are observed. Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome.

TopBP1 associates with NBS1 and is involved in homologous recombination repair

International Nuclear Information System (INIS)

Morishima, Ken-ichi; Sakamoto, Shuichi; Kobayashi, Junya; Izumi, Hideki; Suda, Tetsuji; Matsumoto, Yoshiyuki; Tauchi, Hiroshi; Ide, Hiroshi; Komatsu, Kenshi; Matsuura, Shinya

2007-01-01

TopBP1 is involved in DNA replication and DNA damage checkpoint. Recent studies have demonstrated that TopBP1 is a direct positive effecter of ATR. However, it is not known how TopBP1 recognizes damaged DNA. Here, we show that TopBP1 formed nuclear foci after exposure to ionizing radiation, but such TopBP1 foci were abolished in Nijmegen breakage syndrome cells. We also show that TopBP1 physically associated with NBS1 in vivo. These results suggested that NBS1 might regulate TopBP1 recruitment to the sites of DNA damage. TopBP1-depleted cells showed hypersensitivity to Mitomycin C and ionizing radiation, an increased frequency of sister-chromatid exchange level, and a reduced frequency of DNA double-strand break induced homologous recombination repair. Together, these results suggested that TopBP1 might be a mediator of DNA damage signaling from NBS1 to ATR and promote homologous recombination repair

Repair-induced DNA double strand breaks after ultraviolet-light and either aphidocolin or 1-β-D-arabinofuranosylcytosine/hydroxyurea

International Nuclear Information System (INIS)

Bradley, M.O.; Taylor, V.I.

1983-01-01

A study was performed to determine whether 'repair-induced double strand breaks' (RDSBs) occur in IMR-90 cells at low u.v. doses and whether the RDSBs are themselves repairable by holding open the excision-repair induced gaps by inhibiting nucleotide polymerization after u.v. light with hydroxyurea/ara C or aphidocolin. The results show as little as 2.5 J.m -2 of u.v. light induces RDSBs during repair incubation when repair inhibitors are present. This suggests that 'hot spots' of high lesion frequency occur and the overlapping excision in these areas will produce RDSBs. Removing aphidocolin showed that RDSBs are only partially repairable with between 15 and 40% of the breaks unrepaired at 24 h. Because the lesions are partially repairable they should not always cause toxicity and may be involved in processes such as mutation, transformation, and chromosome or chromatid type aberrations of the sort associated with human tumors. (author)

DNA Amplification by Breakage/Fusion/Bridge Cycles Initiated by Spontaneous Telomere Loss in a Human Cancer Cell Line

Directory of Open Access Journals (Sweden)

Anthony W.l. Lo

2002-01-01

Full Text Available The development of genomic instability is an important step in generatingthe multiple genetic changes required for cancer. One consequence of genomic instability is the overexpression of oncogenes due to gene amplification. One mechanism for gene amplification is the breakagelfusionlbridge (B/F/Bcyclethatinvolvesthe repeated fusion and breakage of chromosomes following the loss of a telomere. B/F/B cycles have been associated with low-copy gene amplification in human cancer cells, and have been proposed to be an initiating event in high-copy gene amplification. We have found that spontaneous telomere loss on a marker chromosome 16 in a human tumor cell line results in sister chromatid fusion and prolonged periods of chromosome instability. The high rate of anaphase bridges involving chromosome 16 demonstrates that this instability results from B/F/B cycles. The amplification of subtelomeric DNA on the marker chromosome provides conclusive evidence that B/F/B cycles initiated by spontaneous telomere loss are a mechanism for gene amplification in human cancer cells.

Bloom syndrome and maternal uniparental disomy for chromosome 15

Energy Technology Data Exchange (ETDEWEB)

Woodage, T.; Prasad, M.; Trent, R.J.; Smith, A. (Children' s Hospital, Camperdown, New South Wales (New Zealand)); Dixon, J.W.; Romain, D.R.; Columbano-Green, L.M.; Selby, R.E. (Wellington Hospital (New Zealand)); Graham, D. (Waikato Hospital, Hamilton (New Zealand)); Rogan, P.K. (Pennsylvania State Univ., Hershey, PA (United States)) (and others)

1994-07-01

Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 37 refs., 3 figs., 2 tabs.

Genetic effects of the flavonols quercetin, kaempferol, and galangin on Chinese hamster ovary cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Carver, J.H. (Lawrence Livermore National Lab., Livermore, CA); Carrano, A.V.; MacGregor, J.T.

1983-01-01

The genotoxicity of selected flavonols was evaluated by multiple endpoints in Chinese hamster ovary (CHO) cells. Chromosomal aberrations, sister-chromatid exchange (SCE), and forward mutation at 4 gene loci were measured in a single population of cells exposed to quercetin, kaempferol, or galangin for 15 h with and without metabolic activation. The incidence of chromosomal aberrations was significantly increased by quercetin in the absence of activation and by kaempferol and galangin with and without activation. Flavanol treatment affected SCE and mutation at the hgprt, aprt, or Na/sup +//K/sup +/-ATPase loci only marginally, but significantly increased mutation frequencies at the tk locus. The response at the tk locus suggests that the CHO cells may behave similarly to L5178Y cells, in which the tk locus is thought to reflect chromosomal lesions in addition to point mutation. These results indicate that, at least under the conditions examined, flavonols induce chromosomal aberrations in CHO cells, but have little effect on point mutation or SCE.

Accuracy of preimplantation genetic diagnosis (PGD) of single gene and chromosomal disorders

Energy Technology Data Exchange (ETDEWEB)

Verlinsky, Y.; Strom, C.; Rechitsky, S. [Reproductive Genetics Institute, Chicage, IL (United States)] [and others

1994-09-01

We have developed a polar body inferred approach for preconception diagnosis of single gene and chromosomal disorders. Preconception PCR or FISH analysis was performed in a total of 310 first polar bodies for the following genetic conditions: cystic fibrosis, hemophilia A, alpha-1-antitrypsin deficiency, Tay Sachs disease, retinitis pigmentosa and common chromosomal trisomies. An important advantage of this approach is the avoidance of sperm (DNA) contamination, which is the major problem of PGD. We are currently applying FISH analysis of biopsied blastomeres, in combination with PCR or separately, and have demonstrated a significant improvement of the accuracy of PGD of X-linked disorders at this stage. Our data have also demonstrated feasibility of the application of FISH technique for PGD of chromosomal disorders. It was possible to detect chromosomal non-disjunctions and chromatid malsegregations in the first meiotic division, as well as to evaluate chromosomal mutations originating from the second meiotic nondisjunction.

Hoechst 33258 dye generates DNA-protein cross-links during ultraviolet light-induced photolysis of bromodeoxyuridine in replicated and repaired DNA

Energy Technology Data Exchange (ETDEWEB)

Guo Xicang; Morgan, W.F.; Cleaver, J.E.

1986-08-01

Substitution of bromodeoxyuridine for thymidine in the DNA of mammalian cells sensitizes them to a range of wavelengths of ultraviolet light. Cells are also sensitized to photochemical reactions involving dyes such as Hoechst 33258, which is used to produce differential staining of chromatids according to their bromodeoxyuridine content. Irradiation with 313 nm light of human and hamster cells containing bromodeoxyuridine in their DNA produced single-strand breaks but no DNA-protein cross-links. Irradiation with 360 nm light in the presence of Hoechst 33258 produced extensive DNA-protein cross-linkage as well as single-strand breaks. These cross-links were observed in DNA containing bromodeoxyuridine incorporated by either semiconservative or repair replication. When the protein was removed with proteinase K, bromodeoxyuridine in repair patches after irradiation by doses of ultraviolet (254 nm) light as low as 0.26 J/m/sup 2/ could readily be detected. Hoechst 33258-mediated photolysis, therefore, provides a sensitive new technique for measuring repair replication after ultraviolet light irradiation.

Cohesinopathies of a feather flock together.

Directory of Open Access Journals (Sweden)

Robert V Skibbens

Full Text Available Roberts Syndrome (RBS and Cornelia de Lange Syndrome (CdLS are severe developmental maladies that present with nearly an identical suite of multi-spectrum birth defects. Not surprisingly, RBS and CdLS arise from mutations within a single pathway--here involving cohesion. Sister chromatid tethering reactions that comprise cohesion are required for high fidelity chromosome segregation, but cohesin tethers also regulate gene transcription, promote DNA repair, and impact DNA replication. Currently, RBS is thought to arise from elevated levels of apoptosis, mitotic failure, and limited progenitor cell proliferation, while CdLS is thought to arise, instead, from transcription dysregulation. Here, we review new information that implicates RBS gene mutations in altered transcription profiles. We propose that cohesin-dependent transcription dysregulation may extend to other developmental maladies; the diagnoses of which are complicated through multi-functional proteins that manifest a sliding scale of diverse and severe phenotypes. We further review evidence that cohesinopathies are more common than currently posited.

Radio-adaptive response

International Nuclear Information System (INIS)

Ikushima, Takaji

1991-01-01

An adaptive response to radiation stress was found in cultured Chinese hamster V79 cells, as a suppressed induction of micronuclei (MNs) and sister chromatid exchanges (SCEs) in the cells conditioned by very low doses. The important characteristics of the novel chromosomal response, called radio-adaptive response (RAR), that have newly emerged in this study are: 1) Low doses of beta-rays from tritiated water (HTO) as well as tritiated thymidine can cause the RAR. 2) Thermal neutrons, a high LET radiation, can not act as tritium beta-rays or gamma-rays. 3) The RAR expression is suppressed by an inhibition of protein synthesis. 4) Several proteins are newly synthesized concurrently with the RAR expression after adapting doses, viewed by two-dimensional electrophoresis of cellular proteins. These results suggest that the RAR is an adaptive chromosomal DNA repair induced by very low doses of low LET radiations under restricted conditions, accompanying the inducible specific gene expression. (author)

LET effects on normal and radiosensitive cell lines

International Nuclear Information System (INIS)

Geard, C.R.; Travisano, M.

1986-01-01

Charged particles in the track segment mode were produced by the RARAF Van de Graaff accelerator and used to irradiate two CHO cell lines, a radiosensitive hypermutable line EM9 and its normal parent AA8. Asynchronous cells were irradiated attached to 6 micrometer thick Mylar with protons, deuterons and helium-3 particles at LETs ranging from 10 to 150 keV per micrometer. A 50 kVp x-ray tube integrated into the track segment facility provided a low LET comparison. Following irradiation cells were monitored for clonogenicity, and in a separate series of experiments frequencies of sister chromatid exchanges. Up to 9 experiments were carried out at each LET, with a total of 8 radiations of different LETs being compared. The optimally effective LET for cell survival was between 80 and 120 keV per micrometer, with the 150 keV per micrometer particles indicating energy wastage. The differential between the normal and radiosensitive cell lines was maintained at all LETs

In vitro studies on chemoprotective effect of borax against aflatoxin B1-induced genetic damage in human lymphocytes.

Science.gov (United States)

Turkez, Hasan; Geyikoğlu, Fatime; Dirican, Ebubekir; Tatar, Abdulgani

2012-12-01

A common dietary contaminant, aflatoxin B1 (AFB1), has been shown to be a potent mutagen and carcinogen in humans and many animal species. Since the eradication of AFB1 contamination in agricultural products has been rare, the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Boron compounds like borax (BX) and boric acid are the major components of industry and their antioxidant role has recently been reported. In the present report, we evaluated the capability of BX to inhibit the rate of micronucleus (MN) and sister chromatid exchange (SCE) formations induced by AFB1. There were significant increases (P Borax gave 30-50 % protection against AFB1 induced SCEs and MNs. In conclusion, the support of borax was especially useful in aflatoxin-toxicated blood tissue. Thus, the risk on target tissues of AFB1 could be reduced and ensured early recovery from its toxicity.

In vitro effect of the antimalarial drug proguanil hydrochloride on viability and DNA damage in human peripheral blood lymphocytes.

Science.gov (United States)

Gajski, Goran; Dinter, Domagoj; Garaj-Vrhovac, Vera

2010-11-01

This study aimed to evaluate the effect of proguanil, a chemical substance used for treatment and prevention of malaria on viability and DNA integrity in human lymphocytes in vitro. Two different concentrations of proguanil obtained from the plasma concentrations were used: 130ng/ml used for prophylactic treatment and 520ng/ml used in treatment of malaria. Testing was done with and without metabolic activation. Viability of lymphocytes decreased in time and dose dependent manner. Comet assay parameters showed similar effects, indicating that some damage to DNA molecule can occur. Frequency of sister chromatid exchanges did not show significant deviation from the control samples. As for the proliferation kinetics no significant changes were noticed. Since majority of DNA damaging effect is induced after metabolic activation it is to be concluded that activity of proguanil is dependent upon the active metabolite cycloguanil and that monitoring should be conducted especially among frequent travellers. Copyright © 2010 Elsevier B.V. All rights reserved.

The development of ideas about the effect of DNA repair on the induction of gene mutations and chromosomal aberrations by radiation and by chemicals

International Nuclear Information System (INIS)

Kimball, R.F.

1987-01-01

An historical overview is given of the development of ideas about chromosomal and DNA repair as they relate to the induction of mutations, chromosomal aberrations, and sister-chromatid exchanges by radiations and chemicals. The genetic and molecular bases of the various repair pathways are reviewed whenever possible. Work on both prokaryotes and eukaryotes is included. Mention is made, when deemed appropriate, of major developments in other areas that served as essential background for the repair work, but no attempt is made to cover these background developments in any detail. Near the end, a brief review is given of factors affecting polymerase fidelity. The history is subdivided into approximately 10-year intervals. For the most part, references are to reviews and symposia in which the ideas of the time were brought together. The implications of these findings for some practical problems in genetic toxicology and for our understanding of the maintenance of the genome are discussed at the end. 147 refs

The ATPases of cohesin interface with regulators to modulate cohesin-mediated DNA tethering

Science.gov (United States)

Çamdere, Gamze; Guacci, Vincent; Stricklin, Jeremiah; Koshland, Douglas

2015-01-01

Cohesin tethers together regions of DNA, thereby mediating higher order chromatin organization that is critical for sister chromatid cohesion, DNA repair and transcriptional regulation. Cohesin contains a heterodimeric ATP-binding Cassette (ABC) ATPase comprised of Smc1 and Smc3 ATPase active sites. These ATPases are required for cohesin to bind DNA. Cohesin’s DNA binding activity is also promoted by the Eco1 acetyltransferase and inhibited by Wpl1. Recently we showed that after cohesin stably binds DNA, a second step is required for DNA tethering. This second step is also controlled by Eco1 acetylation. Here, we use genetic and biochemical analyses to show that this second DNA tethering step is regulated by cohesin ATPase. Furthermore, our results also suggest that Eco1 promotes cohesion by modulating the ATPase cycle of DNA-bound cohesin in a state that is permissive for DNA tethering and refractory to Wpl1 inhibition. DOI: http://dx.doi.org/10.7554/eLife.11315.001 PMID:26583750

Development of ideas about the effect of DNA repair on the induction of gene mutations and chromosomal aberrations by radiation and by chemicals

Energy Technology Data Exchange (ETDEWEB)

Kimball, R F

1987-07-01

An historical overview is given of the development of ideas about chromosomal and DNA repair as they relate to the induction of mutations, chromosomal aberrations, and sister-chromatid exchanges by radiations and chemicals. The genetic and molecular bases of the various repair pathways are reviewed whenever possible. Work on both prokaryotes and eukaryotes is included. Mention is made, when deemed appropriate, of major developments in other areas that served as essential background for the repair work, but no attempt is made to cover these background developments in any detail. Near the end, a brief review is given of factors affecting polymerase fidelity. The history is subdivided into approximately 10-year intervals. For the most part, references are to reviews and symposia in which the ideas of the time were brought together. The implications of these findings for some practical problems in genetic toxicology and for our understanding of the maintenance of the genome are discussed at the end. 147 refs.

DNA damage and chromosome aberration induced by heavy-ion beams

International Nuclear Information System (INIS)

Takakura, Kahoru; Funada, Aya; Aoki, Mizuho; Furusawa, Yoshiya

2003-01-01

The aim of this study is to clarify the relation between cell death and chromosomal aberration in cultured human cells (human salivary gland (HSG) tumor cells and GM05389 human normal fibroblasts) irradiated with heavy ion beams on the basis of linear energy transfer (LET) values. The LET dependences of cell death were observed for the both cells by the method of colony assay. The LET dependences of the chromosomal aberrations, breaks and gaps, isochromatid breaks and exchanges were also observed for the both cells using the premature chromosome condensation (PCC) method. From these results it is suggested that exchange formation is essential for the cell death caused by heavy ion beam irradiation. It is suspected that the densely ionizing track structure of hight LET heavy ions inhibits the effective repair in the chromatid breaks and isochromatid breaks and finally induce much exchange in the cells, which should be essential cause of cell death. (author)

Chromosome aberrations and rogue cells in lymphocytes of Chernobyl clean-up workers

International Nuclear Information System (INIS)

Lazutka, J.R.

1996-01-01

A cytogenetic analysis was performed on peripheral blood lymphocytes from 183 Chernobyl clean-up workers and 27 control individuals. Increased frequencies of chromosome aberrations were associated with exposure to radiation at Chernobyl, alcohol abuse and a history of recent influenza infection. However, only approximately 20% of Chernobyl clean-up workers had an increased frequency of dicentric and ring chromosomes. At the same time, an increased frequency of acentric fragments in lymphocytes of clean-up workers was characteristic. The use of multivitamins as dietary supplement significantly decreased the frequency of chromosome aberrations, especially of chromatid breaks. Rogue cells were found in lymphocytes of 28 clean-up workers and 3 control individuals. The appearance of rogue cells was associated with a recent history of acute respiratory disease (presumably caused by adenoviral infection) and, probably, alcohol abuse. Dicentric chromosomes in rogue cells were distributed according to a negative binomial distribution. Occurrence of rogue cells due to a perturbation of cell cycle control and abnormal apoptosis is suggested

Hypothetical physicochemical mechanisms of some intracellular processes: The hydrate hypothesis of mitosis and DNA replication

International Nuclear Information System (INIS)

Kadyshevich, E.A.; Ostrovskii, V.E.

2007-01-01

A DNA replication, mitosis, and binary fission hydrate hypothesis (MRH hypothesis) allowing non-trivial explanations for the physicochemical mechanisms of some intracellular processes is proposed. The hypothesis has a thermodynamic basis and is initiated by original experimental calorimetric and kinetic studies of the behavior of functional organic polymer and monomer substances in highly concentrated aqueous solutions. Experimental data demonstrating the occurrence of a short-range ordering in concentrated aqueous solutions of such substances are included. Hypothetical simple non-enzymatic unified mechanisms for the natural processes of DNA local unwinding preceding the start of duplication, DNA replication, formation and disappearance of the protein bonds between sister chromatids in the centromere region of eukaryotic DNA and in the centromere-like region of prokaryotic DNA, moving of daughter chromosomes apart to the opposite sides of cells in late anaphase, and formation of the nuclear envelopes in telophase and intracellular membranes between the newly formed nuclei in cytokinesis are formulated. The nature of a number of other intracellular phenomena is discussed

Techniques for imaging human metaphase chromosomes in liquid conditions by atomic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Ushiki, Tatsuo; Hoshi, Osamu [Division of Microscopic Anatomy and Bio-imaging, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510 (Japan); Shigeno, Masatsugu [SII NanoTechnology Incorporated, RBM Tsukiji Building, Shintomi 2-15-5, Chuo-ku, Tokyo 104-0041 (Japan)], E-mail: t-ushiki@med.niigata-u.ac.jp

2008-09-24

The purpose of this study was to obtain three-dimensional images of wet chromosomes by atomic force microscopy (AFM) in liquid conditions. Human metaphase chromosomes-obtained either by chromosome spreads or by an isolation technique-were observed in a dynamic mode by AFM in a buffer solution. Under suitable operating conditions with a soft triangular cantilever (with the spring constant of 0.08-0.4 N m{sup -1}), clear images of fixed chromosomes in the chromosome spread were obtained by AFM. For imaging isolated chromosomes with the height of more than 400 nm, a cantilever with a high aspect ratio probing tip was required. The combination of a Q-control system and the sampling intelligent scan (SIS) system in dynamic force mode AFM was useful for obtaining high-quality images of the isolated chromosomes, in which globular or cord-like structures about 50 nm thick were clearly observed on the surface of each chromatid.

Comparative retention of fission fragment 147Pm in regenerated and fetal liver on induction of chromosome aberrations in these cells

International Nuclear Information System (INIS)

Zhu Shoupeng; Zheng Siying; Wang Liuyi; Yang Shujin

1989-01-01

The purpose of the present study is to ascertain comparative retention of fission fragment 147 Pm in regenerated and fetal liver on induction of chromosome aberrations in these cells. The results indicated that retention of 147 Pm in regenerated liver was about 700 times than in fetal liver. The cumulative absorption dose in regenerated liver was about 2.87 Gy, while in fetal liver-only 0.004 Gy. Under the same conditions, the incidence rate of chromosome aberrations in regenerated liver cells induced by 147 Pm was 50.2%, and in fetal liver cells-about 28.3%. It should be concluded that the radiosensitivity to 147 Pm was not uniform among the regenerated and fetal liver cells. The study suggested that fetal liver cells show to be more radiosensitive to 147 Pm than regenerated liver cells. Among the type of aberrations in both cells induced by 147 Pm, chromatid breakages were predominant, accompanied with a few chromosome breakages

[Effects of oil-refining microbes (genus Acinetobacter) on cytogenetical structures of human lymphocytes in cell cultures].

Science.gov (United States)

Il'inskikh, N N; Il'inskikh, E N; Il'inskikh, I N

2012-01-01

The objective of this study was to assess ability of oil-refining bacteria Acinetobacter calcoaceticus and A. valentis to induce karyopathological abnormalities and chromosomal aberrations in human lymphocyte cultures. It was found that the cultures infected with A. calcoaceticus showed significantly high frequencies of cytogenetical effects and chromosomal aberrant cells as compared to the intact cultures and cultures infected with A. valentis. The most of chromosomal aberrations, mainly chromatid aberrations, were located in 1 and 2 chromosomes. Moreover, the aberrations were detected in some specific chromosome areas. Abnormalities of mitotic cell division and nucleus morphology were determined in lymphocyte cultures infected with A. calcoaceticus. There were found significantly high frequencies of cells with micronuclei, nucleus protrusions, anaphase or metaphase chromosome and chromosomal fragments lagging as well as multipolar and C-mitoses. Thus, the oil-refining bacteria A. calcoaceticus in contrast to A. valentis demonstrated strong genotoxic effects in human lymphocyte cultures in vitro.

The hsSsu72 phosphatase is a cohesin-binding protein that regulates the resolution of sister chromatid arm cohesion

OpenAIRE

Kim, Hyun-Soo; Baek, Kwan-Hyuck; Ha, Geun-Hyoung; Lee, Jae-Chul; Kim, Yu-Na; Lee, Janet; Park, Hye-Young; Lee, Noo Ri; Lee, Ho; Cho, Yunje; Lee, Chang-Woo

2010-01-01

An interplay of phosphorylation, dephosphorylation and protecting factors controls proteolysis-independent cohesin dissociation from chromosomes. The identification of a new phosphatase protecting arm cohesin now adds further complexity to this regulation.

Monitoring of DNA and cytogenetic damage in lymphocytes in patients with skin cancer disease

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Dyga, W.; Krasnowolski, S.; Wierzewska, A.; Budzanowska, E.

1999-01-01

One major oncogenesis process is activation of proto-oncogenes by point mutations or chromosomal translocations. There is substantial evidence that indicates that human carcinogenesis involves loss of heterozygosity of certain chromosomes. Our study aimed at searching the possible association between cancer and DNA and cytogenetic abnormalities induced in lymphocytes of people with various categories of skin cancer cells. Fresh blood was collected by venepuncture from 25 individuals (including nine prior to cancer treatment). All patients were nonsmoking males, however 42.3% of them were former smokers. Blood samples were divided into two parts; in the first part of samples cytogenetic studies were performed immediately, while lymphocytes from the other part were isolated and stored at -70 0C for further studies in vitro. A single cell gel electrophoresis assay (SCGE), known as a Comet assay, was performed on them to study individual susceptibility to the induction of DNA damage by UV or radiation and to estimate variability in cellular repair capabilities. On average 220 good metaphase spreads per sample in the first mitotic division, and 100 spreads per sample in the second division were accepted for analysis of the cytogenetic damage. Chromosome and chromatid type aberrations were scored in the cells in the first mitosis, and expressed as total aberration frequency including and excluding gaps. Sister chromatid exchanges , high frequency cells and proliferating rate index were screened and evaluated in the second mitosis. Each patient showed a level exceeding (in at least one of the cytogenetic biomarker) the biomarker level in a reference group. In order to estimate susceptibility of people to environmentally induced damage, the isolated lymphocytes were irradiated with 2 Gy dose of X-rays or 6 J/m 2 of UV radiation, and the single cell gel electrophoresis (SCGE assay) was performed. To compare various individual capabilities to repair the induced damage

New way to rise estimation objectivity of radiation consequences on human

International Nuclear Information System (INIS)

Akhmatullina, N. B.

2001-01-01

The discussion of negative consequences of radiation on human often leaves without attention the fact that the basic meaning of danger of radiation level rise in environment for human connected with genetic structure defects. Namely changes in genome lead to different negative consequences and not only accompany, but also precede them. However the tendency which appeared in our country to substitute the direct genetic analysis with references to rise of frequency of morbidity on separate nosologic groups, whose area is widen arbitrary, has brought to nonadequateness of methodologic approach, distorted the determination of 'genetic consequence' itself and as the effect of this, distorted the real estimation of consequences of Kazakh Test Sites (TS) and other sources of radiation contamination activity. The question is arising: how can we distinguish observed and discribed effects of other genotoxicants of chemical and biological origin? There are different cytogenetic methods to detect genetic damages. The more widely used - is the estimation of the chromosome anomalies frequency estimation in somatic cells, especially in lymphocytes of peripheral blood. Traditionally researches proceeds from thin mechanisms of mutagenesis, which points that radiation mutagenesis leads primarily to chromosome, and chemical - to chromatide aberrations. In radiation influence chromosome aberrations appears in nondivided lymphocytes (G1-phase) and became easily observed in first metaphase (Browen e.a.1972, Bender e.a.1966). On the contrary the aberrations, induced by chemical factors, appears primarily in the S- phase irrespectively of what is cycle's stage, when the cells were exposed. Therefore the majority of aberrations have chromatide type (Evanse e.a.1980, Preston e.a.1981). Following pointed criteria many original investigations on people exposed to radiation were carried out. Moreover it was proved the application of such method to estimate the absorbed radiation in the

Studies on sister chromatid exchange (SCE) induction by γ-irradiation and protective effect of L-cysteine in HeLa cells

International Nuclear Information System (INIS)

Shah, V.C.; Mittal, S.C.

1987-01-01

Effect of different doses of γ-irradiation on SCE induction in unifiliarly 5-bromo 2-deoxyuridine substituted DNA was studied in various phases of cell cycle. Changes in γ-irradiation induced SCE frequency was measured by post-irradiation treatment with antimutagen L-cysteine. Perturbation in cellular proliferation kinetics due to γ-irradiation and γ-irradiation plus L-cysteine was also studied. It was observed that γ-irradiation is an efficient inducer of SCE and is most effective in S phase. L-cysteine also causes SCE induction which is slightly higher than the spontaneous level of SCEs found in HeLa cells. However, post-irradiation addition of L-cysteine reduces SCE frequency in γ-irradiated cultures and this reduction is maximum in G 1 phase irradiated cells. γ-irradiation delayed the mitosis considerably and this delay continued to increase with increasing doses. L-cysteine reduced the delay in cell cycle caused by γ-irradiation. (orig.) [de

Higher incidence of spontaneous sister-chromatid exchanges (SCEs) and X-ray-induced chromosome aberrations in peripheral blood lymphocytes during pregnancy

International Nuclear Information System (INIS)

Sharma, T.; Das, B.C.

1986-01-01

In vitro cultures of peripheral blood lymphocytes from human and muntjac (barking deer) females who were at an advanced stage of pregnancy (32-37 weeks pregnant women and 20-24 weeks pregnant muntjacs) showed an enhanced frequency of SCEs and X-ray-induced chromosome aberrations when compared with those of nonpregnant females. Lymphocyte cultures of nonpregnant females to which sex hormones progesterone, oestrogen and human chorionic gonadotropin (HCG) were added together exogenously also showed higher frequency of SCEs. The plausible reason(s) for such high incidence of SCEs during pregnancy is discussed. (orig.)

The mutagenic potential of high flash aromatic naphtha.

Science.gov (United States)

Schreiner, C A; Edwards, D A; McKee, R H; Swanson, M; Wong, Z A; Schmitt, S; Beatty, P

1989-06-01

Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--high-flash aromatic naphtha. A program was initiated to assess the toxicological properties of high-flash aromatic naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted partly to assess the potential for mutagenic activity and also to assist in an assessment of carcinogenic potential. The specific tests utilized included the Salmonella/mammalian microsome mutagenicity assay, the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) forward mutation assay in CHO cells, in vitro chromosome aberration and sister chromatid exchange (SCE) assays in CHO cells, and an in vivo chromosome aberration assay in rat bone marrow.

TRITOX: a multiple parameter evaluation of tritium toxicity

International Nuclear Information System (INIS)

Carsten, A.L.

1982-01-01

The increased use of nuclear reactors for power generation will lead to the introduction of tritium into the environment. The need for assessing possible immediate and long-term effects of exposure to this tritium led to the development of a broad program directed towards evaluating the possible somatic and genetic effects of continuous exposure to tritiated water (HTO). Among the parameters measured are the genetic, cytogenetic, reproductive efficiency, growth, nonspecific lifetime shortening, bone marrow cellularity and stem cell content, relative biological effectiveness as compared to 137 Cesium gamma exposure, and related biochemical and microdosimetric evaluations. These parameters have been evaluated on animals maintained on HTO at 10 to 100 times the maximum permissible concentration (0.03 - 3.0 μCi/ml) for HTO. Dominant lethal mutations, chromosome aberrations in regenerating liver, increased sister chromatid exchanges in bone marrow and reduction in bone marrow stem cell content have been observed at the higher concentrations. The relative biological effectiveness for HTO ingestion as compared to external 137 Cesium gamma exposures has been found to be between 1 and 2

Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader

Directory of Open Access Journals (Sweden)

William C.H. Chao

2015-08-01

Full Text Available The remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of Scc4 bound to the N terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped by the core of the Scc4 superhelix. Electron microscopy (EM analysis reveals that the Scc2-Scc4 loader complex comprises three domains: a head, body, and hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head domain, whereas in vitro cohesin loading assays show that the central body and the hook domains are sufficient to catalyze cohesin loading onto circular DNA, but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a chromatin adaptor.

Acute and long-term cytogenetic effects of treatment in childhood cancer

International Nuclear Information System (INIS)

Aronson, M.M.; Miller, R.C.; Hill, R.B.; Nichols, W.W.; Meadows, A.T.

1982-01-01

The incidence of chromosomal aberrations in banded karyotypes and of sister-chromatid exchanges (SCEs) was determined in the lymphocytes of survivors of childhood cancer as 2 parameters which are pertinent in assessing the genetic damage induced by chemotherapy. The proportion of cells with chromosome breakage or structural rearrangement-type aberration was 1 cell in 67 in a control group of 8 untreated cancer patients and 2 parents of cancer patients, 1 cell in 8 in 12 patients currently on therapy, and 1 cell in 50 in 17 patients sampled 6 months to 35 years post-treatment. The range of mean SCE levels per cell was 4.5-6.5 in the untreated cancer patients, 4.0-9.6 in non-cancer controls, 3.3-33.7 in patients on therapy, and 4.6-9.7 in post-therapy survivors. Considerable variability was observed between individuals with both SCE and breakage assays but therapy-induced increases in SCEs were not necessarily correlated with increased levels of aberrations arising from chromosomal breakage. (orig.)

Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.

Science.gov (United States)

Gulten, Tuna; Evke, Elif; Ercan, Ilker; Evrensel, Turkkan; Kurt, Ender; Manavoglu, Osman

2011-01-01

In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

Cytogenetic characteristics of Chironomus balatonicus Devai, Wulker, Scholl (Diptera, Chironomidae) from the Chernobyl region

International Nuclear Information System (INIS)

Michailova, P.; Petrova, N.

1994-01-01

A cytogenetic analysis was carried out on a population of Chironomus balatonicus (Chironomidae, Diptera) from Chernobyl, a highly radioactive area of the Kiev region. Several chromosomal aberrations were established unique to a population of Chironomus balatonicus living in an area contaminated by radioactive waste. Five new heterozygous inversions, deficiencies in arms C, D, E, F and chromatid breaks were found in the irradiated population but not in nonirradiated populations. A pericentric inversion in chromosome AB occurred at a relatively high frequency. Genome aberrations expressed by a heterochromatized 'B' chromosome were evident. In the irradiated and nonirradiated populations common inversions occurred showing variation in their frequency depending on specific environmental conditions. The somatic and also the germ cells were characterized by a number of heteropycnotic nuclei and vacuolized chromosomes. Both the somatic and germ cells showed changes in the structural and functional organization of heterochromatin and this was particularly marked in the telomeric sectors of the chromosomes. The heterochromatin which is extremely sensitive to radioactivity appears to protect euchromatin from adverse environmental conditions

An investigation of the genetic toxicology of irradiated food-stuffs using short-term test systems

International Nuclear Information System (INIS)

Renner, H.W.; Altmann, H.; Asquith, J.C.; Elias, P.S.

1982-01-01

Six in vivo genetic toxicity tests were carried out on irradiated or unirradiated cooked chicken, dried dates and cooked fish. The tests were as follows: sex-linked recessive lethal mutations in Drosophila melanogaster (dried dates only), chromosome aberrations in bone marrow of Chinese hamsters, micronucleus test in rats, mice and Chinese hamsters, sister-chromatid exchange in bone marrow of mice and Chinese hamsters and in spermatogonia of mice, and DNA metabolism in spleen cells of Chinese hamsters. None of the tests provided any evidence of genetic toxicity induced by irradiation. However, dried dates, whether irradiated or not, showed evidence of some genetic toxicity in their effect on DNA metabolism in spleen cells and SCE induction in bone marrow. Feeding irradiated fish affected DNA metabolism in the spleen cells of Chinese hamsters. This effect could be interpreted as an induction of an immunoactive compound, although it could also be explained by the persistence of an immunoactive compound due to the removal by irradiation of spoilage organisms that would normally degrade it. (author)

Fission yeast cells undergo nuclear division in the absence of spindle microtubules.

Directory of Open Access Journals (Sweden)

Stefania Castagnetti

2010-10-01

Full Text Available Mitosis in eukaryotic cells employs spindle microtubules to drive accurate chromosome segregation at cell division. Cells lacking spindle microtubules arrest in mitosis due to a spindle checkpoint that delays mitotic progression until all chromosomes have achieved stable bipolar attachment to spindle microtubules. In fission yeast, mitosis occurs within an intact nuclear membrane with the mitotic spindle elongating between the spindle pole bodies. We show here that in fission yeast interference with mitotic spindle formation delays mitosis only briefly and cells proceed to an unusual nuclear division process we term nuclear fission, during which cells perform some chromosome segregation and efficiently enter S-phase of the next cell cycle. Nuclear fission is blocked if spindle pole body maturation or sister chromatid separation cannot take place or if actin polymerization is inhibited. We suggest that this process exhibits vestiges of a primitive nuclear division process independent of spindle microtubules, possibly reflecting an evolutionary intermediate state between bacterial and Archeal chromosome segregation where the nucleoid divides without a spindle and a microtubule spindle-based eukaryotic mitosis.

Telomere length maintenance--an ALTernative mechanism.

Science.gov (United States)

Royle, N J; Foxon, J; Jeyapalan, J N; Mendez-Bermudez, A; Novo, C L; Williams, J; Cotton, V E

2008-01-01

The Alternative Lengthening of Telomeres (ALT) mechanism is utilised by approximately 10% of human tumours and a higher proportion of some types of sarcomas. ALT+ cell lines and tumours show heterogeneous telomere length, extra-chromosomal circular and linear telomeric DNA, ALT associated promyelocytic bodies (APBs), a high frequency of post-replication exchanges in telomeres (designated as telomere-sister chromatid exchanges, T-SCE) and high instability at a GC-rich minisatellite, MS32 (D1S8). It is clear that there is a link between the minisatellite instability and the mechanism that underpins ALT, however currently the nature of this relationship is uncertain. Single molecule analysis of telomeric DNA from ALT+ cell lines and tumours has revealed complex telomere mutations that have not been seen in cell lines or tumours that express telomerase. These complex telomere mutations cannot be explained by T-SCE but must arise by another inter-molecular process. The break-induced replication (BIR) model that may explain the observed high frequency of T-SCE and the presence of complex telomere mutations is reviewed. Copyright 2008 S. Karger AG, Basel.

DNA Damage in Melania Snail (Semisulcospira libertine) Irradiated with Gamma Radiation

Energy Technology Data Exchange (ETDEWEB)

Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of); An, Kwang Guk [Chungnam National University, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

2010-10-15

Generally radiological protection has focused on human. But International Commission on Radiological Protection (ICRP) requires the effect data of ionizing radiation on nonhuman biota for the radiological protection of the environment. The choice of a melania snail as a model for environmental biomonitoring of radiation genotoxicity took into account that invertebrates represent one of aquatic species. The comet assay or single cell gel electrophoresis (SCGE) assay, first introduced by Ostling and Johanson, was used to detect DNA single strand breaks and to investigate the application of this technique as a tool for aquatic biomonitoring. Comet assay offers considerable advantages over some other assays used in DNA damage detection, such as chromosomal aberrations, sister chromatid Exchange and the micronucleus test, since there is no need for cells to be in a dividing state. Other advantages are its rapidity, relatively low coast, and wide applicability to virtually any nucleated cell type. In this study, we evaluated DNA damage in cells of Semisulcospira libertina after irradiation with {sup 60}Co gamma radiation by using the comet assay

Budding yeast mms4 is epistatic with rad52 and the function of Mms4 can be replaced by a bacterial Holliday junction resolvase.

Science.gov (United States)

Odagiri, Nao; Seki, Masayuki; Onoda, Fumitoshi; Yoshimura, Akari; Watanabe, Sei; Enomoto, Takemi

2003-03-01

MMS4 of Saccharomyces cerevisiae was originally identified as the gene responsible for one of the collection of methyl methanesulfonate (MMS)-sensitive mutants, mms4. Recently it was identified as a synthetic lethal gene with an SGS1 mutation. Epistatic analyses revealed that MMS4 is involved in a pathway leading to homologous recombination requiring Rad52 or in the recombination itself, in which SGS1 is also involved. MMS sensitivity of mms4 but not sgs1, was suppressed by introducing a bacterial Holliday junction (HJ) resolvase, RusA. The frequencies of spontaneously occurring unequal sister chromatid recombination (SCR) and loss of marker in the rDNA in haploid mms4 cells and interchromosomal recombination between heteroalleles in diploid mms4 cells were essentially the same as those of wild-type cells. Although UV- and MMS-induced interchromosomal recombination was defective in sgs1 diploid cells, hyper-induction of interchromosomal recombination was observed in diploid mms4 cells, indicating that the function of Mms4 is dispensable for this type of recombination.