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Sample records for sce sister chromatid

  1. 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)

  2. 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

  3. 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.)

  4. A schedule to demonstrate radiation-induced sister chromatid exchanges in human lymphocytes

    International Nuclear Information System (INIS)

    Chaudhuri, J.P.

    1982-01-01

    The reciprocal interchange between the chromatids of a chromosome, termed sister chromatid exchange (SCE), is considered to be one of the most sensitive and accurate cytogenetic parameters and respond to toxic chemicals at very low doses. But the response of SCE to ionizing radiation is very poor. Human lymphocytes fail to give SCE response when irradiated at G 0 . Probably the primary lesions induced at G 0 do not remain available long enough to find expression as SCEs. Based on this assumption a schedule was developed using caffeine to demonstrate radiation induced SCEs. Following this schedule a dose-dependent increase in the frequency of radiation induced SCEs has been observed. (orig.)

  5. 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)

  6. 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.

  7. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

    OpenAIRE

    Pongsavee Malinee

    2009-01-01

    Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0...

  8. 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

  9. 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

  10. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes.

    Science.gov (United States)

    Pongsavee, Malinee

    2009-10-30

    Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

  11. 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)

  12. 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)

  13. 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)

  14. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

    Directory of Open Access Journals (Sweden)

    Pongsavee Malinee

    2009-10-01

    Full Text Available Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI. The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

  15. 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.

  16. 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

  17. 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)

  18. 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

  19. 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

  20. Mechanics of Sister Chromatids studied with a Polymer Model

    Directory of Open Access Journals (Sweden)

    Yang eZhang

    2013-10-01

    Full Text Available Sister chromatid cohesion denotes the phenomenon that sister chromatids are initially attached to each other in mitosis to guarantee the error-free distribution into the daughter cells. Cohesion is mediated by binding proteins and only resolved after mitotic chromosome condensation is completed. However, the amount of attachement points required to maintain sister chromatid cohesion while still allowing proper chromosome condensation is not known yet. Additionally the impact of cohesion on the mechanical properties of chromosomes also poses an interesting problem. In this work we study the conformational and mechanical properties of sister chromatids by means of computer simulations. We model both protein-mediated cohesion between sister chromatids and chromosome condensation with a dynamic binding mechanisms. We show in a phase diagram that only specific link concentrations lead to connected and fully condensed chromatids that do not intermingle with each other nor separate due to entropic forces. Furthermore we show that dynamic bonding between chromatids decrease the Young's modulus compared to non-bonded chromatids.

  1. 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)

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

    Science.gov (United States)

    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.

  3. 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.

  4. Sister chromatid segregation in meiosis II

    Science.gov (United States)

    Wassmann, Katja

    2013-01-01

    Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed—deprotected”—for sister chromatid segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection. PMID:23574717

  5. 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.

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

    International Nuclear Information System (INIS)

    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

  7. 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)

  8. 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.)

  9. 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)

  10. Splitting the chromosome: cutting the ties that bind sister chromatids.

    Science.gov (United States)

    Nasmyth, K; Peters, J M; Uhlmann, F

    2001-01-01

    In eukaryotic cells, replicated DNA molecules remain physically connected from their synthesis in S phase until they are separated during anaphase. This phenomenon, called sister chromatid cohesion, is essential for the temporal separation of DNA replication and mitosis and for the equal separation of the duplicated genome. Recent work has identified a number of chromosomal proteins required for cohesion. In this review we discuss how these proteins may connect sister chromatids and how they are removed from chromosomes to allow sister chromatid separation at the onset of anaphase.

  11. 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

  12. Epigenetic differences between sister chromatids?

    NARCIS (Netherlands)

    Lansdorp, Peter M.; Falconer, Ester; Tao, Jiang; Brind'Amour, Julie; Naumann, Ulrike; Kanz, L; Fibbe, WE; Lengerke, C; Dick, JE

    2012-01-01

    Semi-conservative replication ensures that the DNA sequence of sister chromatids is identical except for replication errors and variation in the length of telomere repeats resulting from replicative losses and variable end processing. What happens with the various epigenetic marks during DNA

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  15. 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.

  16. 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

  17. 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...

  18. 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

  19. 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)

  20. 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.

  1. 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.

  2. 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

  3. Effect of chloramphenicol on sister chromatid exchange in bovine fibroblasts.

    Science.gov (United States)

    Arruga, M V; Catalan, J; Moreno, C

    1992-03-01

    The genotoxic potential of different chloramphenicol concentrations (5, 20, 40 and 60 micrograms ml-1) was investigated in bovine fibroblast primary lines by sister chromatid exchange assay. Chloramphenicol acted for long enough to ensure similar effects to persistent storage in the kidney. In this experiment 10 micrograms ml-1 of 5-bromodeoxyuridine was added for 60 hours for all doses of chloramphenicol and to the control. When the tissue culture cells were exposed to increasing doses, increased numbers of sister chromatid exchanges developed. Differences were significantly different to the control.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. 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)

  7. 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

  8. 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

  9. Colchicine promotes a change in chromosome structure without loss of sister chromatid cohesion in prometaphase I-arrested bivalents.

    Science.gov (United States)

    Rodríguez, E M; Parra, M T; Rufas, J S; Suja, J A

    2001-12-01

    In somatic cells colchicine promotes the arrest of cell division at prometaphase, and chromosomes show a sequential loss of sister chromatid arm and centromere cohesion. In this study we used colchicine to analyse possible changes in chromosome structure and sister chromatid cohesion in prometaphase I-arrested bivalents of the katydid Pycnogaster cucullata. After silver staining we observed that in colchicine-arrested prometaphase I bivalents, and in contrast to what was found in control bivalents, sister kinetochores appeared individualised and sister chromatid axes were completely separated all along their length. However, this change in chromosome structure occurred without loss of sister chromatid arm cohesion. We also employed the MPM-2 monoclonal antibody against mitotic phosphoproteins on control and colchicine-treated spermatocytes. In control metaphase I bivalents this antibody labelled the tightly associated sister kinetochores and the interchromatid domain. By contrast, in colchicine-treated prometaphase I bivalents individualised sister kinetochores appeared labelled, but the interchromatid domain did not show labelling. These results support the notion that MPM-2 phosphoproteins, probably DNA topoisomerase IIalpha, located in the interchromatid domain act as "chromosomal staples" associating sister chromatid axes in metaphase I bivalents. The disappearance of these chromosomal staples would induce a change in chromosome structure, as reflected by the separation of sister kinetochores and sister axes, but without a concomitant loss of sister chromatid cohesion.

  10. 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)

  11. 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

  12. Genome-wide mapping of sister chromatid exchange events in single yeast cells using Strand-seq

    NARCIS (Netherlands)

    Claussin, Clemence; Porubsky, David; Spierings, Diana C. J.; Halsema, Nancy; Rentas, Stefan; Guryev, Victor; Lansdorp, Peter M.; Chang, Michael

    2017-01-01

    Homologous recombination involving sister chromatids is the most accurate, and thus most frequently used, form of recombination-mediated DNA repair. Despite its importance, sister chromatid recombination is not easily studied because it does not result in a change in DNA sequence, making

  13. 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)

  14. 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)

  15. 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.

  16. 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

  17. 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)

  18. 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

  19. 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.

  20. 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.)

  1. 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.

  2. 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

  3. Sister chromatid exchange in peripheral blood lymphocytes as a ...

    African Journals Online (AJOL)

    Introduction: Sister chromatid exchanges (SCEs) can be induced by various genotoxic treatments, suggesting that SCEs refl ect a DNA repair process and it may be a good index for assessment of genomic instability. However, the occurrence of genetic instability and in particular, of spontaneous SCEs has been strongly ...

  4. 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.

  5. 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)

  6. 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.)

  7. 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

  8. 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

  9. 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

  10. 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.

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

    International Nuclear Information System (INIS)

    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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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)

  18. 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

  19. 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.

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

    International Nuclear Information System (INIS)

    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

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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...

  6. 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)

  7. 12-O-Tetradecanoyl-phorbol-13-acetate and its relationship to SCE induction in Syrian and Chinese hamster cells

    International Nuclear Information System (INIS)

    Popescu, N.C.; Amsbaugh, S.C.; Larramendy, M.L.; DiPaolo

    1982-01-01

    12-O-Tetradecanoyl-phorbol-13-acetate (TPA) in conditions that produce enhancement of ultraviolet light (UV) and x-irradiation Syrian hamster embryo cell (HEC) transformation did not cause further increase in the sister chromatid exchange (SCE) frequency induced by UV and x-irradiation, two physical carcinogens that differ in their mode of DNA interaction and efficiency of SCE induction. Several factors which might influence SCE induction by TPA were studied on HEC and Chinese hamster V79-4 cells. Heat-inactivated serum was used because of the possibility that a serum component may interfere with TPA ability to cause SCE. TPA effect on SCE was determined at the first and second division post treatment on cells exposed to different 5-bromodeoxyuridine (BrdUrd) concentrations. Independent of BrdUrd concentration (1-10μg/ml medium) and the number of cells divisions post treatment, TPA (0.01-2μg/ml medium) was ineffective in inducing SCE in exponentially and stationary HEC cultures cultivated in medium supplemented with heat-inactivated serum. Also, TPA did not increase the SCE frequency in V79-4 Chinese hamster cells cultured in heat-activated or noninactivated serum. Although SCE induction, a cellular response to carcinogen-induced DNA damage, may be important for the induction of transformation by environmental agents, the enhancement of transformation frequency caused by TPA occurs without further DNA alterations involved in SCE formation

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.)

  16. 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

  17. 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)

  18. 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.)

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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)

  6. Detection of a deuterium isotope effect in di- and trisubstituted alkylphenylnitrosoureas. An SCE study in Chinese hamster V79-E cells

    International Nuclear Information System (INIS)

    Thust, R.; Mendel, J.; Bach, B.; Schwarz, H.

    1985-01-01

    The genotoxicity of 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (C1-MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU) and their derivatives substituted by deuterium in different positions was studied using sister chromatid exchange (SCE) induction in Chinese hamster V79-E cells. Deuterium substitution in the 1-methyl group of MPNU (MPNU-d3) and C1-MPNU (C1-MPNU-d3) diminished the SCE-inducing capacity by 20-30% and by 30-40% in DMPNU (DMPNU-d3B). There was no altered SCE activity detected when the phenyl group of MPNU (MPNU-d5) or the 3-methyl group of DMPNU (DMPNU-d3A) was deuterium labeled. No isotope effect was detected in deuterated EPNU derivatives, presumably due to the instability of these compounds. It is surmised that the easier delocalization of the positive charge in the deuterated alkyl diazonium ion causes a diminished reactivity and therefore influences the type and amount of DNA alkylation. Furthermore, the experiments with DMPNU and its derivatives revealed that, in contrast to mono- and disubstituted nitrosoureas, the biological activities of these very stable trisubstituted nitrosoureas are strongly influenced by a serum factor in the culture fluid

  7. Detection of a deuterium isotope effect in di- and trisubstituted alkylphenylnitrosoureas. An SCE study in Chinese hamster V79-E cells.

    Science.gov (United States)

    Thust, R; Mendel, J; Bach, B; Schwarz, H

    1985-06-01

    The genotoxicity of 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (C1-MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU) and their derivatives substituted by deuterium in different positions was studied using sister chromatid exchange (SCE) induction in Chinese hamster V79-E cells. Deuterium substitution in the 1-methyl group of MPNU (MPNU-d3) and C1-MPNU (C1-MPNU-d3) diminished the SCE-inducing capacity by 20-30% and by 30-40% in DMPNU (DMPNU-d3B). There was no altered SCE activity detected when the phenyl group of MPNU (MPNU-d5) or the 3-methyl group of DMPNU (DMPNU-d3A) was deuterium labeled. No isotope effect was detected in deuterated EPNU derivatives, presumably due to the instability of these compounds. It is surmised that the easier delocalization of the positive charge in the deuterated alkyl diazonium ion causes a diminished reactivity and therefore influences the type and amount of DNA alkylation. Furthermore, the experiments with DMPNU and its derivatives revealed that, in contrast to mono- and disubstituted nitrosoureas, the biological activities of these very stable trisubstituted nitrosoureas are strongly influenced by a serum factor in the culture fluid.

  8. 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.

  9. 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...

  10. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Sister chromatoid exchanges in atomic bomb survivors

    International Nuclear Information System (INIS)

    Nakano, Mimako; Awa, Akio

    1980-01-01

    Sister chromatoid exchange (SCE) frequencies in the peripheral lymphocyte with and without mitomycin-C (MMC) were studied, in the age of tens and thirties for an atomic-bomb survivor group and in thirties, fifties, and seventies for an unexposed group. The observation of 100 cells showed no statistically significant difference of SCE frequencies with aging or irradiation. The increasing rates of SCE frequencies by MMC showed no difference among the groups. The average increasing ratio by MMC was 3.6. (Nakanishi, T.)

  16. 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

  17. 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.

  18. Defects in the Fanconi Anemia Pathway and Chromatid Cohesion in Head and Neck Cancer.

    Science.gov (United States)

    Stoepker, Chantal; Ameziane, Najim; van der Lelij, Petra; Kooi, Irsan E; Oostra, Anneke B; Rooimans, Martin A; van Mil, Saskia E; Brink, Arjen; Dietrich, Ralf; Balk, Jesper A; Ylstra, Bauke; Joenje, Hans; Feller, Stephan M; Brakenhoff, Ruud H

    2015-09-01

    Failure to repair DNA damage or defective sister chromatid cohesion, a process essential for correct chromosome segregation, can be causative of chromosomal instability (CIN), which is a hallmark of many types of cancers. We investigated how frequent this occurs in head and neck squamous cell carcinoma (HNSCC) and whether specific mechanisms or genes could be linked to these phenotypes. The genomic instability syndrome Fanconi anemia is caused by mutations in any of at least 16 genes regulating DNA interstrand crosslink (ICL) repair. Since patients with Fanconi anemia have a high risk to develop HNSCC, we investigated whether and to which extent Fanconi anemia pathway inactivation underlies CIN in HNSCC of non-Fanconi anemia individuals. We observed ICL-induced chromosomal breakage in 9 of 17 (53%) HNSCC cell lines derived from patients without Fanconi anemia. In addition, defective sister chromatid cohesion was observed in five HNSCC cell lines. Inactivation of FANCM was responsible for chromosomal breakage in one cell line, whereas in two other cell lines, somatic mutations in PDS5A or STAG2 resulted in inadequate sister chromatid cohesion. In addition, FANCF methylation was found in one cell line by screening an additional panel of 39 HNSCC cell lines. Our data demonstrate that CIN in terms of ICL-induced chromosomal breakage and defective chromatid cohesion is frequently observed in HNSCC. Inactivation of known Fanconi anemia and chromatid cohesion genes does explain CIN in the minority of cases. These findings point to phenotypes that may be highly relevant in treatment response of HNSCC. ©2015 American Association for Cancer Research.

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

    Science.gov (United States)

    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.

  20. In Vivo Cytogenetic Studies on Aspartame

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. 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

  3. 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 ...

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

    Science.gov (United States)

    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.

  5. 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)

  6. X-ray sensitization of chromatids with unifilarly and bifilarly substituted DNA

    International Nuclear Information System (INIS)

    Wolff, S.

    1981-01-01

    When cells are grown for two rounds of DNA replication in the presence of the thymidine analogue 5-bromodeoxyuridine, chromosomes containing one chromatid with unifilarly substituted DNA and one with bifilarly substituted DNA are found. These can be distinguished by harlequin staining techniques that stain one chromatid dark and one light. When the degree of substitution is 60% or greater, 3 times as many X-ray-induced chromatid breaks are produced as in unsubstituted chromatids. This represents maximal sensitization. The unifilarly substituted (dark) chromatid is as sensitive as its bifilarly substituted (light) sister chromatid. If cells are grown in low concentrations of 5-bromodeoxyuridine (BrdUrd), then the amount of substitution is less and the bifilarly substituted chromatic is more sensitive than the unifilarly substituted one. When large numbers of cells are grown in very low concentrations of BrdUrd, the analogue is almost completely depleted during the first round of replication leading to harlequin chromosomes containing one unsubstituted (dark) and one unifilarly substituted (light) chromatid. Under these conditions a maximal sensitization between light-staining and dark-staining chromatids can occur. This can be confused with the differential sensitivity between unifilarly and bifilarly substituted chromatids. The apparent discrepant results obtained by different investigators are most likely caused by the use of very low levels of BrdUrd in some of the experiments. (orig.)

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Cell elongation is an adaptive response for clearing long chromatid arms from the cleavage plane

    Science.gov (United States)

    Kotadia, Shaila; Montembault, Emilie; Sullivan, William

    2012-01-01

    Chromosome segregation must be coordinated with cell cleavage to ensure correct transmission of the genome to daughter cells. Here we identify a novel mechanism by which Drosophila melanogaster neuronal stem cells coordinate sister chromatid segregation with cleavage furrow ingression. Cells adapted to a dramatic increase in chromatid arm length by transiently elongating during anaphase/telophase. The degree of cell elongation correlated with the length of the trailing chromatid arms and was concomitant with a slight increase in spindle length and an enlargement of the zone of cortical myosin distribution. Rho guanine-nucleotide exchange factor (Pebble)–depleted cells failed to elongate during segregation of long chromatids. As a result, Pebble-depleted adult flies exhibited morphological defects likely caused by cell death during development. These studies reveal a novel pathway linking trailing chromatid arms and cortical myosin that ensures the clearance of chromatids from the cleavage plane at the appropriate time during cytokinesis, thus preserving genome integrity. PMID:23185030

  10. 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.)

  11. 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.)

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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)....

  4. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

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

  5. 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.

  6. 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 ...

  7. Separase Is Required for Homolog and Sister Disjunction during Drosophila melanogaster Male Meiosis, but Not for Biorientation of Sister Centromeres.

    Science.gov (United States)

    Blattner, Ariane C; Chaurasia, Soumya; McKee, Bruce D; Lehner, Christian F

    2016-04-01

    Spatially controlled release of sister chromatid cohesion during progression through the meiotic divisions is of paramount importance for error-free chromosome segregation during meiosis. Cohesion is mediated by the cohesin protein complex and cleavage of one of its subunits by the endoprotease separase removes cohesin first from chromosome arms during exit from meiosis I and later from the pericentromeric region during exit from meiosis II. At the onset of the meiotic divisions, cohesin has also been proposed to be present within the centromeric region for the unification of sister centromeres into a single functional entity, allowing bipolar orientation of paired homologs within the meiosis I spindle. Separase-mediated removal of centromeric cohesin during exit from meiosis I might explain sister centromere individualization which is essential for subsequent biorientation of sister centromeres during meiosis II. To characterize a potential involvement of separase in sister centromere individualization before meiosis II, we have studied meiosis in Drosophila melanogaster males where homologs are not paired in the canonical manner. Meiosis does not include meiotic recombination and synaptonemal complex formation in these males. Instead, an alternative homolog conjunction system keeps homologous chromosomes in pairs. Using independent strategies for spermatocyte-specific depletion of separase complex subunits in combination with time-lapse imaging, we demonstrate that separase is required for the inactivation of this alternative conjunction at anaphase I onset. Mutations that abolish alternative homolog conjunction therefore result in random segregation of univalents during meiosis I also after separase depletion. Interestingly, these univalents become bioriented during meiosis II, suggesting that sister centromere individualization before meiosis II does not require separase.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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)

  14. Studies of DNA and chromosome damage in skin fibroblasts and blood lymphocytes from psoriasis patients treated with 8-methoxypsoralen and UVA irradiation

    International Nuclear Information System (INIS)

    Bredberg, A.; Lambert, B.; Lindblad, A.; Swanbeck, G.; Wennersten, G.

    1983-01-01

    Exposure of human lymphocytes and skin fibroblasts in vitro to a single, clinically used dose of PUVA, i.e., 0.1 micrograms/ml of 8-methoxypsoralen (8-MOP) plus 0.9-4 J/cm2 of longwave ultraviolet radiation (UVA), lead to the formation of DNA damage as determined by alkaline elution, and to chromosome aberrations and sister chromatid exchanges (SCE). When lymphocyte-enriched plasma was obtained from psoriasis patients 2 h after oral intake of 8-MOP and then UVA irradiated (1.8-3.6 J/cm2) in vitro, an increased frequency of chromosome aberrations and SCE was observed. Normal levels of chromosome aberrations and SCE were found in lymphocytes of psoriasis patients after 3-30 weeks of PUVA treatment in vivo. A small but statistically significant increase in the SCE frequency was observed in the lymphocytes of psoriasis patients treated for 1-6 years with PUVA (mean 18.0 SCE/cell) as compared with before PUVA (mean 15.8, p less than 0.05). Skin fibroblasts of psoriasis patients analyzed 5 years after the start of PUVA treatment showed a normal number of SCE but a high fraction of filter-retained DNA in the alkaline elution assay, suggesting the presence of cross-linked DNA

  15. Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship.

    Science.gov (United States)

    Erselcan, Taner; Sungu, Selma; Ozdemir, Semra; Turgut, Bulent; Dogan, Derya; Ozdemir, Ozturk

    2004-05-01

    Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of (131)I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and 5.75+/-2.06, respectively, in the whole group, and these values differed significantly from each other ( Pdisappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following (131)I treatment. Further studies are therefore needed to clarify the effect of the negative beta value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of (131)I treatment.

  16. 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

  17. 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.)

  18. 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

  19. Genotoxicity of dill (Anethum graveolens L.), peppermint (Menthaxpiperita L.) and pine (Pinus sylvestris L.) essential oils in human lymphocytes and Drosophila melanogaster.

    Science.gov (United States)

    Lazutka, J R; Mierauskiene, J; Slapsyte, G; Dedonyte, V

    2001-05-01

    Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and seeds, peppermint (Menthaxpiperita L.) herb and pine (Pinus sylvestris L.) needles were studied using chromosome aberration (CA) and sister chromatid exchange (SCE) tests in human lymphocytes in vitro, and Drosophila melanogaster somatic mutation and recombination test (SMART) in vivo. In the CA test, the most active essential oil was from dill seeds, then followed essential oils from dill herb, peppermint herb and pine needles, respectively. In the SCE test, the most active essential oils were from dill herb and seeds followed by essential oils from pine needles and peppermint herb. Essential oils from dill herb and seeds and pine needles induced CA and SCE in a clear dose-dependent manner, while peppermint essential oil induced SCE in a dose-independent manner. All essential oils were cytotoxic for human lymphocytes. In the SMART test, a dose-dependent increase in mutation frequency was observed for essential oils from pine and dill herb. Peppermint essential oil induced mutations in a dose-independent manner. Essential oil from dill seeds was almost inactive in the SMART test.

  20. Summary update of the Brookhaven tritium toxicity program with emphasis on recent cytogenetic and lifetime-shortening studies

    International Nuclear Information System (INIS)

    Carsten, A.L.; Benz, R.D.; Hughes, W.P.; Ichimasa, Yusuke; Ikushima, Takaji; Tezuka, Hideo.

    1988-01-01

    A number of years ago a multiparameter program to evaluate the toxicity of tritiated water (HTO) was undertaken in the Medical Department at Brookhaven National Laboratory. The results of most of these studies have been published and will receive brief attention. Emphasis will be placed on the unpublished studies involving the induction of sister chromatid exchanges (SCE's) in bone marrow of mice, new biochemical information, and preliminary results on lifetime-shortening and carcinogenesis. In brief, male Hale-Stoner Brookhaven (HSB) mice maintained on HTO concentrations ranging from 3.0 to 30.0 μCi/ml exhibited essentially the same number of SCE's per cell throughout their lifetime. Control mice showed a decrease in number of SCE's with age. The lack of a dose-response effect and the constant level of SCE's in HTO mice as compared to controls will be discussed. In the carcinogenesis study C57BL/6J male mice received various x-ray or HTO regimens. Mortality data from these and other studies in which CBA/Ca/BNL mice received single x-ray exposures or equivalent integrated dose exposures by single HTO injections will be discussed. 25 refs., 4 figs

  1. 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.

  2. Provocation and palliation of in vitro cellular aging

    International Nuclear Information System (INIS)

    Schmidt, M.A.

    1983-01-01

    Normal human fibroblast cell lines, obtained from a male neonate, were serially cultivated in vitro in MEM-H medium until senescence. One cell line was irradiated with Co 60 , 400 rad at population doublings of approximately 12, 24, and 32. In addition, one cell line was similarly irradiated after 30 minutes of preconditioning with 5 mM cysteamine and catalase. The cells were maintained to an average of 66 population doublings. Sister chromatid exchanges (SCE) were enumerated at critical periods and growth parameters were continuously evaluated. It as postulated that because the efficiency of DNA repair declines with age, free radical DNA damage may be more harmful to older cells. Also, DNA damage may effectively be retarded by exogenous compounds, in this case, cysteamine. It was demonstrated that the identical free radical insult does indeed cause more DNA damage, as determined by SCE frequency and growth potential, as a cell ages. Radiation-induced SCE-type damage was virtually eliminated by the addition of cysteamine and catalase. Reduction of final population doubling level was commensurate with the growth inhibition discussed

  3. Summary update of the Brookhaven tritium toxicity program with emphasis on recent cytogenetic and lifetime-shortening studies

    Energy Technology Data Exchange (ETDEWEB)

    Carsten, A.L.; Benz, R.D.; Hughes, W.P.; Ichimasa, Yusuke; Ikushima, Takaji; Tezuka, Hideo

    1988-01-01

    A number of years ago a multiparameter program to evaluate the toxicity of tritiated water (HTO) was undertaken in the Medical Department at Brookhaven National Laboratory. The results of most of these studies have been published and will receive brief attention. Emphasis will be placed on the unpublished studies involving the induction of sister chromatid exchanges (SCE's) in bone marrow of mice, new biochemical information, and preliminary results on lifetime-shortening and carcinogenesis. In brief, male Hale-Stoner Brookhaven (HSB) mice maintained on HTO concentrations ranging from 3.0 to 30.0 ..mu..Ci/ml exhibited essentially the same number of SCE's per cell throughout their lifetime. Control mice showed a decrease in number of SCE's with age. The lack of a dose-response effect and the constant level of SCE's in HTO mice as compared to controls will be discussed. In the carcinogenesis study C57BL/6J male mice received various x-ray or HTO regimens. Mortality data from these and other studies in which CBA/Ca/BNL mice received single x-ray exposures or equivalent integrated dose exposures by single HTO injections will be discussed. 25 refs., 4 figs.

  4. Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

    Energy Technology Data Exchange (ETDEWEB)

    Sahin, Ali [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey)], E-mail: alibabam2001@yahoo.com; Tatar, Abdulgani; Oztas, Sitki [Department of Genetics, Faculty of Medicine, Ataturk University, 25240 Erzurum (Turkey); Seven, Bedri; Varoglu, Erhan [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey); Yesilyurt, Ahmet [Department of Genetics, Faculty of Medicine, Ataturk University, 25240 Erzurum (Turkey); Ayan, Arif Kursad [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey)

    2009-07-15

    Introduction: Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN). Methods: The present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period. Results: In nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05). Conclusions: This study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.

  5. Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

    International Nuclear Information System (INIS)

    Sahin, Ali; Tatar, Abdulgani; Oztas, Sitki; Seven, Bedri; Varoglu, Erhan; Yesilyurt, Ahmet; Ayan, Arif Kursad

    2009-01-01

    Introduction: Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN). Methods: The present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period. Results: In nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05). Conclusions: This study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Genotoxic biomonitoring of agricultural workers exposed to pesticides in the north of Sinaloa State, Mexico.

    Science.gov (United States)

    Martínez-Valenzuela, Carmen; Gómez-Arroyo, Sandra; Villalobos-Pietrini, Rafael; Waliszewski, Stefan; Calderón-Segura, María Elena; Félix-Gastélum, Rubén; Alvarez-Torres, Armando

    2009-11-01

    Genotoxic damage was evaluated in 70 agricultural workers, 25 women and 45 men, exposed to pesticides in Las Grullas, Ahome, Sinaloa, Mexico, with an average of 7 years of exposure. The effect was detected through the sister chromatid exchanges (SCE) in lymphocytes of peripheral blood and micronuclei (MN) and other nuclear anomalies (NA) in buccal exfoliated cells. Also, the influence on cellular proliferation kinetics (CPK) was studied by means of the replication index (RI) and the cytotoxic effect was examined with the mitotic index (MI). The non-exposed group consisted of 70 other persons, 21 women and 47 men from the city of Los Mochis, Sinaloa, Mexico. Significant differences between the exposed and the non-exposed groups were observed in SCE, CPK, MI, MN and NA. Analysis of variance revealed that age, gender, smoking and alcohol consumption did not have a significant effect on genetic damage. However, there was a correlation between exposure time to pesticides and SCE frequency. These results could have been due to the exposure of workers to pesticides containing different chemical compounds. This study afforded valuable data to estimate the possible risk to health associated with pesticide exposure.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

  14. 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)

  15. Composition: S.C.E

    DEFF Research Database (Denmark)

    2012-01-01

    S.C.E. is a large collection of open compositions to be realised by improvising musicians. See more about my composition practise in the entry "Composition - General Introduction". This work is licensed under a Creative Commons "by-nc" License. You may for non-commercial purposes use and distribute...

  16. Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors.

    Science.gov (United States)

    Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M

    1992-05-01

    The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha-Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha-Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes.

  17. 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)

  18. 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

  19. Modelling and testing the molecular mechanism of radiation-induced chromatid breaks

    International Nuclear Information System (INIS)

    Bryant, P. E.

    2001-01-01

    Chromatid breaks induced by ionizing radiation in the G2 phase of the cell cycle are considered as markers of individual human radiosensitivity and may indicate the presence of low-penetrance genes regulating susceptibility to breast and other cancers). Together with our own study of Scottish (Tayside) breast cancer patients and a group of normal controls these studies show an overall 10-fold variation in chromatid break frequency (the parameter defining individual chromosomal 'radiosensitivity'). Thus, an understanding of the mechanisms and genes involved in determining these widely different responses should help to clarify the reasons for individual radiosensitivity and may lead us to identify key genes involved in cancer susceptibility. The presence of colour-switches at around 16% of chromatid break points (detected in harlequin-stained chromosomes) indicates that this type of chromatid break is formed by a chromatin rearrangement involving one or more large chromatin domains of the order of 3 - 5 Mbp, possibly representing transcription 'factories'. The signal model of chromatid breaks assumes that all chromatid breaks are the result of chromatin rearrangements, and that the initiating DNA double-strand break (dsb) is itself not involved in the rearrangement but signals its presence (possibly via ATM protein or DNAPK) leading to the initiation of the chromatin rearrangement. Experimental evidence from radiosensitive cell lines (e.g. human AT and hamster irs2) and with the nucleoside analogue araA (9-β-D-arabinofuranosyladenine) demonstrates the lack of correspondence between the rejoining kinetics of dsb and that of disappearance of chromatid breaks, thus supporting the signal model. Coupled with the linear induction of chromatid breaks with dose in both human and rodent cell lines of various types, and the production of chromatid breaks by single dsb in genetically engineered cell lines the classical 'breakage-first' model of chromatid breaks is no longer

  20. NREL/SCE High Penetration PV Integration Project: FY13 Annual Report

    Energy Technology Data Exchange (ETDEWEB)

    Mather, B. A.; Shah, S.; Norris, B. L.; Dise, J. H.; Yu, L.; Paradis, D.; Katiraei, F.; Seguin, R.; Costyk, D.; Woyak, J.; Jung, J.; Russell, K.; Broadwater, R.

    2014-06-01

    In 2010, the National Renewable Energy Laboratory (NREL), Southern California Edison (SCE), Quanta Technology, Satcon Technology Corporation, Electrical Distribution Design (EDD), and Clean Power Research (CPR) teamed to analyze the impacts of high penetration levels of photovoltaic (PV) systems interconnected onto the SCE distribution system. This project was designed specifically to benefit from the experience that SCE and the project team would gain during the installation of 500 megawatts (MW) of utility-scale PV systems (with 1-5 MW typical ratings) starting in 2010 and completing in 2015 within SCE's service territory through a program approved by the California Public Utility Commission (CPUC). This report provides the findings of the research completed under the project to date.

  1. Effects of boric acid and borax on titanium dioxide genotoxicity.

    Science.gov (United States)

    Turkez, Hasan

    2008-07-01

    Titanium dioxide (TiO(2)) is a potential carcinogenic/mutagenic agent although it is used in many areas including medical industries and cosmetics. Boron (as boric acid and borax) has also well-described biological effects and therapeutic benefits. In a previous study, sister-chromatid exchanges (SCEs) and micronuclei (MN) rates were assessed in control and TiO(2)-treated (1, 2, 3, 5, 7.5 and 10 microm) human whole blood cultures. The results showed that the rates of SCE (at 2, 3, 5, 7.5 and 10 microm) and MN (at 5, 7.5 and 10 microm) formation in peripheral lymphocytes were increased significantly by TiO(2) compared with the controls. The present study also investigated the genetic effects of boric acid and borax (2.5, 5 and 10 microm) on cultures with and without TiO(2) addition. No significant increase in SCE and MN frequencies were observed at all concentrations of boron compounds. However, TiO(2)-induced SCE and MN could be reduced significantly by the presence of boric acid and borax. In conclusion, this study indicated for the first time that boric acid and borax led to an increased resistance of DNA to damage induced by TiO(2). 2008 John Wiley & Sons, Ltd

  2. 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.)

  3. Delayed repair of DNA single-strand breaks does not increase cytogenetic damage

    International Nuclear Information System (INIS)

    Morgan, W.F.; Djordjevic, M.C.; Jostes, R.F.; Pantelias, G.E.

    1985-01-01

    DNA damage and cytogenetic effects of ionizing radiation were investigated in Chinese hamster ovary (CHO) cells and unstimulated human peripheral blood lymphocytes. DNA damage and repair were analysed by alkaline elution under conditions that predominantly measured DNA single-strand breaks (ssb). X-radiation (2.5 Gy) induced ssb in both CHO cells and unstimulated lymphocytes, and the breaks were repaired within 30 and 90 min, respectively. This rapid repair was delayed by the poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3AB). The cytogenetic effects of the 3AB-induced delay in DNA repair were examined by analysing sister chromatid exchange (SCE) frequency in CHO cells and fragmentation of prematurely condensed chromosomes (PCC) in unstimulated human lymphocytes after 2.5 Gy of X-rays. Although 3AB delayed the rejoining of DNA ssb, this delay did not result in increased cytogenetic damage manifested as either SCE or fragmentation of PCC. These results indicate that the rapidly rejoining DNA ssb are not important in the production of chromosome damage. (author)

  4. Evaluation of antigenotoxic effects of carotenoids from green algae Chlorococcum humicola using human lymphocytes

    Science.gov (United States)

    Bhagavathy, S; Sumathi, P

    2012-01-01

    Objective To identify the available phytochemicals and carotenoids in the selected green algae and evaluate the potential genotoxic/antigenotoxic effect using lymphocytes. Methods Organic solvent extracts of Chlorococcum humicola (C. humicola) were used for the phytochemical analysis. The available carotenoids were assessed by HPLC, and LC-MS analysis. The genotoxicity was induced by the benzo(a)pyrene in the lymphocyte culture, the genotoxic and antigenotoxic effects of algal carotenoids with and without genotoxic inducer were evaluated by chromosomal aberration (CA), sister chromatid exchange (SCE) and micronucleus assay (MN). Results The results of the analysis showed that the algae were rich in carotenoids and fatty acids. In the total carotenoids lutein, β-carotene and α-carotene were found to be present in higher concentration. The frequency of CA and SCE increased by benzo(a)pyrene were significantly decreased by the carotenoids (Pcarotenoids when compared with the positive controls (Pcarotenoids which effectively fight against environmental genotoxic agents, the carotenoids itself is not a genotoxic substance and should be further considered for its beneficial effects. PMID:23569879

  5. Genotoxicity of water from the Songhua River, China, in 1994-1995 and 2002-2003: Potential risks for human health

    International Nuclear Information System (INIS)

    Liu Jiaren; Dong Hongwei; Tang Xuanle; Sun Xiangrong; Han Xiaohui; Chen Bingqing; Sun Changhao; Yang Baofeng

    2009-01-01

    A previous study showed that the cancer mortalities are higher for residents who lived nearby the Songhua River heavily polluted by organic contamination. It is important to determine its risk of carcinogenic potential. Short-term genotoxic bio-assays using Salmonella, Sister Chromatid Exchange (SCE), and Micronuclei (MN) assays were employed to examine the genotoxic activity of ether extracts of water samples taken from the Songhua River. The results of the Salmonella bioassay indicated that there were indirect frame-shift mutagens in the water samples. A dose-response relationship for the SCE and MN assays was obtained. These results showed that organic extracts of water samples have genotoxic activity and the risk of carcinogenic potential to human health. The mutagenesis of water samples had changed compared to the results in 1994-1995. An increasing trend of risk of carcinogenic potential in the Songhua River after ten years should be noted and needs to be studied further. - Organic extracts of water samples taken from the Songhua River have genotoxic activity and the risk of carcinogenic potential to human health

  6. Application of ANN-SCE model on the evaluation of automatic generation control performance

    Energy Technology Data Exchange (ETDEWEB)

    Chang-Chien, L.R.; Lo, C.S.; Lee, K.S. [National Cheng Kung Univ., Tainan, Taiwan (China)

    2005-07-01

    An accurate evaluation of load frequency control (LFC) performance is needed to balance minute-to-minute electricity generation and demand. In this study, an artificial neural network-based system control error (ANN-SCE) model was used to assess the performance of automatic generation controls (AGC). The model was used to identify system dynamics for control references in supplementing AGC logic. The artificial neural network control error model was used to track a single area's LFC dynamics in Taiwan. The model was used to gauge the impacts of regulation control. Results of the training, evaluating, and projecting processes showed that the ANN-SCE model could be algebraically decomposed into components corresponding to different impact factors. The SCE information obtained from testing of various AGC gains provided data for the creation of a new control approach. The ANN-SCE model was used in conjunction with load forecasting and scheduled generation data to create an ANN-SCE identifier. The model successfully simulated SCE dynamics. 13 refs., 10 figs.

  7. Unique geometry of sister kinetochores in human oocytes during meiosis I may explain maternal age-associated increases in chromosomal abnormalities

    Directory of Open Access Journals (Sweden)

    Jessica Patel

    2016-02-01

    Full Text Available The first meiotic division in human oocytes is highly error-prone and contributes to the uniquely high incidence of aneuploidy observed in human pregnancies. A successful meiosis I (MI division entails separation of homologous chromosome pairs and co-segregation of sister chromatids. For this to happen, sister kinetochores must form attachments to spindle kinetochore-fibres emanating from the same pole. In mouse and budding yeast, sister kinetochores remain closely associated with each other during MI, enabling them to act as a single unified structure. However, whether this arrangement also applies in human meiosis I oocytes was unclear. In this study, we perform high-resolution imaging of over 1900 kinetochores in human oocytes, to examine the geometry and architecture of the human meiotic kinetochore. We reveal that sister kinetochores in MI are not physically fused, and instead individual kinetochores within a pair are capable of forming independent attachments to spindle k-fibres. Notably, with increasing female age, the separation between kinetochores increases, suggesting a degradation of centromeric cohesion and/or changes in kinetochore architecture. Our data suggest that the differential arrangement of sister kinetochores and dual k-fibre attachments may explain the high proportion of unstable attachments that form in MI and thus indicate why human oocytes are prone to aneuploidy, particularly with increasing maternal age.

  8. A correlation between ultraviolet-induced sister chromatid exchanges and ultraviolet-indced mutagenesis in ''Muntiacus muntjak'' (Indian Muntjac) skin fibroblasts in culture

    International Nuclear Information System (INIS)

    Lugo, M.H.

    1983-01-01

    The purpose of this thesis was to develop the capability of simultaneously assaying SCEs and mutations in Indian muntjac cells to determine (1) the relationship between the ultraviolet radiation (UVR) induction of SCEs and the UVR induction of mutations at the (UVR) HGPRT locus in Indian muntjac cells and (2) the possible role of DNA repair in the UVR induction of these two events. Indian muntjac skin fibroblasts were chosen for this study because of a unique karyotype consisting of a diploid chromosome number of 6 in females and 7 in males. An HGPRT mutation assay in Indian muntjac cells was developed by this author since at the time this study was undertaken no mutational assay system utilizing Indian muntjac cells existed. It is concluded from this study that a linear correlation exists betwen the UVR-induction of SCEs and of mutations to 6TG resistance in Indian muntjac cells. As more time is allowed between the UVR-induced DNA damage and onset of DNA replication, more of the lesions leading to both mutations and SCE formation are repaired. The fact that SCE and mutation frequencies are reduced at different rates may indicate that the lesions responsible for SCEs and for mutations are repaired differently

  9. 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.

  10. Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 and GSTT1

    Energy Technology Data Exchange (ETDEWEB)

    Joost H.M. van Delft; Marie-Jose S.T. Steenwinkel; Jeff G. van Asten; Nico de Vogel; Truus C.D.M. Bruijntjes-Rozier; Ton Schouten; Patricia Cramers; Lou Maas; Marcel H. van Herwijnen; Frederik-Jan van Schooten; Piet M.J. Hopmans [TNO Nutrition and Food Research Institute (Netherlands). Toxicology Division

    2001-07-01

    Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. This study aimed to assess whether the current exposure to PAH of coke oven workers in a Dutch plant induced biological effects, and to determine if these effects are influenced by tobacco smoking and by genetic polymorphisms for the glutathione S-transferase genes GSTM1 and GSTT1. Urinary 1-hydroxypyrene (1-OHpyr) levels were used to monitor the internal dose, while the internal effective dose was assessed by monitoring PAH-DNA adducts, DNA strand breaks (Comet assay), sister-chromatid exchanges (SCE) and cells with a high frequency of SCE (HFC) in lymphocytes together with micronuclei (MN) in exfoliated urothelial cells. Occupational exposure to PAH resulted in statistically significant increased 1-OHpyr levels, but it did not cause a significant induction of SCE, HFC, MN, DNA strand breaks or DNA adducts. Smoking caused a significant increase of 1-OHpyr, SCE, HFC and DNA adducts, but not of MN or DNA strand breaks. Following correction for the smoking-related effects, no occupational induction of the effect biomarkers could be discerned. Multi-variate analysis did not show a significant influence of GSTM1 and GSTT1 polymorphisms on any biomarker. Also no significant interactions were observed between the various biomarkers.

  11. 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)

  12. 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

  13. Accelerating the SCE-UA Global Optimization Method Based on Multi-Core CPU and Many-Core GPU

    Directory of Open Access Journals (Sweden)

    Guangyuan Kan

    2016-01-01

    Full Text Available The famous global optimization SCE-UA method, which has been widely used in the field of environmental model parameter calibration, is an effective and robust method. However, the SCE-UA method has a high computational load which prohibits the application of SCE-UA to high dimensional and complex problems. In recent years, the hardware of computer, such as multi-core CPUs and many-core GPUs, improves significantly. These much more powerful new hardware and their software ecosystems provide an opportunity to accelerate the SCE-UA method. In this paper, we proposed two parallel SCE-UA methods and implemented them on Intel multi-core CPU and NVIDIA many-core GPU by OpenMP and CUDA Fortran, respectively. The Griewank benchmark function was adopted in this paper to test and compare the performances of the serial and parallel SCE-UA methods. According to the results of the comparison, some useful advises were given to direct how to properly use the parallel SCE-UA methods.

  14. G2-chromatid breaks and rejoining in HO8910 cells induced by γ-rays

    International Nuclear Information System (INIS)

    Wang Zhuanzi; Liu Bing; Duan Xin

    2006-01-01

    The premature chromosome condensation technique was used to estimate the dosage effect on the G2-chromosome breaks in HO8910 after exposure to γ-rays, and to investigate the time effect on the rejoining of the G2-chromosome breaks. The results show that the number of G2 chromatid-type breaks linearly increased with doses and the number of G2 iso-chromatid breaks increased with dose in a linear-square manner. With the prolongation of culture time, G2 chromatid-type breaks obviously got repaired, and almost 65% chromatid-type breaks got repaired in the early 24 hour post-irradiation, whereas only about 20% iso-chromatid breaks got repaired during the same time. Furthermore, the rejoining of the two types of chromatid breaks occurred mostly in 2 hours after irradiation and from 12 to 24 hours after irradiation, the number of chromatid breaks was found to get stabilized basically, which indicates that the repairing process is over in the early 24 hours of post-irradiation. (authors)

  15. 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

  16. 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...

  17. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs. A report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    Energy Technology Data Exchange (ETDEWEB)

    Hagmar, Lars; Stroemberg, Ulf; Mikoczy, Zoli; Tinnerberg, Hakan; Skerfving, Staffan [Department of Occupational and Environmental Medicine, Lund University, S-221 85 Lund (Sweden); Bonassi, Stefano; Lando, Cecilia [Department of Environmental Epidemiology, Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, I-1016132 Genoa (Italy); Hansteen, Inger-Lise [Department of Occupational Medicine, Telemark Central Hospital, N-3710 Skien (Norway); Montagud, Alicia Huici [Centro Nacional de Condiciones de Trabajo, Instituto Nacional de Seguridad e Higiene en el Trabajo, Dulcet 2-10, ES-08034 Barcelona (Spain); Knudsen, Lisbeth [National Institute of Occupational Health, Lersoe Parkalle 105, DK-2100 Copenhagen (Denmark); Norppa, Hannu [Finnish Institute of Occupational Health, Topeliuksekatu 41 aA, FIN-00250 Helsinki (Finland); Reuterwall, Christina [National Institute of Work Life, S-171 84 Solna (Sweden); Broegger, Anton [Norwegian Radium Hospital, Oslo (Norway); Forni, Alessandra [Istituto di Medicina del Lavoro Clinica del Lavoro `L. Devoto`, Milan (Italy); Hoegstedt, Benkt [Department of Occupational Medicine, Central Hospital, Halmstad (Sweden); Lambert, Bo [Department of Environmental Medicine, Centre for Nutrition and Toxicology, Karolinska Institute, Stockholm (Sweden); Mitelman, Felix [Department of Clinical Genetics, Lund University, Lund (Sweden); Nordenson, Ingrid [National Institute of Work Life, Umea (Sweden); Salomaa, Sisko [Finnish Center for Radiation and Nuclear Safety, Helsinki (Finland)

    1998-09-20

    The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base

  18. Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells

    Energy Technology Data Exchange (ETDEWEB)

    Di Virgilio, A.L. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Diag. 113 y 64, Correo 16, Suc. 4, La Plata (1900) (Argentina); Reigosa, M. [Instituto Multidisciplinario de Biologia Celular (IMBICE), Calle 526 y Camino Gral. Belgrano (entre 10 y 11), La Plata 1900 (Argentina); Arnal, P.M. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Diag. 113 y 64, Correo 16, Suc. 4, La Plata 1900 (Argentina); Fernandez Lorenzo de Mele, M., E-mail: mmele@inifta.unlp.edu.ar [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Diag. 113 y 64, Correo 16, Suc. 4, La Plata 1900 (Argentina)

    2010-05-15

    The aim of this study was to analyze the cytotoxicity and genotoxicity of titanium oxide (TiO{sub 2}) and aluminium oxide (Al{sub 2}O{sub 3}) nanoparticles (NPs) on Chinese hamster ovary (CHO-K1) cells using neutral red (NR), mitochondrial activity (by MTT assay), sister chromatid exchange (SCE), micronucleus (MN) formation, and cell cycle kinetics techniques. Results showed a dose-related cytotoxic effect evidenced after 24 h by changes in lysosomal and mitochondrial dehydrogenase activity. Interestingly, transmission electronic microscopy (TEM) showed the formation of perinuclear vesicles in CHO-K1 cells after treatment with both NPs during 24 h but no NP was detected in the nuclei. Genotoxic effects were shown by MN frequencies which significantly increased at 0.5 and 1 {mu}g/mL TiO{sub 2} and 0.5-10 {mu}g/mL Al{sub 2}O{sub 3}. SCE frequencies were higher for cells treated with 1-5 {mu}g/mL TiO{sub 2}. The absence of metaphases evidenced cytotoxicity for higher concentrations of TiO{sub 2}. No SCE induction was achieved after treatment with 1-25 {mu}g/mL Al{sub 2}O{sub 3}. In conclusion, findings showed cytotoxic and genotoxic effects of TiO{sub 2} and Al{sub 2}O{sub 3} NPs on CHO-K1 cells. Possible causes of controversial reports are discussed further on.

  19. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs. A report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    International Nuclear Information System (INIS)

    Hagmar, Lars; Stroemberg, Ulf; Mikoczy, Zoli; Tinnerberg, Hakan; Skerfving, Staffan; Bonassi, Stefano; Lando, Cecilia; Hansteen, Inger-Lise; Montagud, Alicia Huici; Knudsen, Lisbeth; Norppa, Hannu; Reuterwall, Christina; Broegger, Anton; Forni, Alessandra; Hoegstedt, Benkt; Lambert, Bo; Mitelman, Felix; Nordenson, Ingrid; Salomaa, Sisko

    1998-01-01

    The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base

  20. A heterogeneous computing accelerated SCE-UA global optimization method using OpenMP, OpenCL, CUDA, and OpenACC.

    Science.gov (United States)

    Kan, Guangyuan; He, Xiaoyan; Ding, Liuqian; Li, Jiren; Liang, Ke; Hong, Yang

    2017-10-01

    The shuffled complex evolution optimization developed at the University of Arizona (SCE-UA) has been successfully applied in various kinds of scientific and engineering optimization applications, such as hydrological model parameter calibration, for many years. The algorithm possesses good global optimality, convergence stability and robustness. However, benchmark and real-world applications reveal the poor computational efficiency of the SCE-UA. This research aims at the parallelization and acceleration of the SCE-UA method based on powerful heterogeneous computing technology. The parallel SCE-UA is implemented on Intel Xeon multi-core CPU (by using OpenMP and OpenCL) and NVIDIA Tesla many-core GPU (by using OpenCL, CUDA, and OpenACC). The serial and parallel SCE-UA were tested based on the Griewank benchmark function. Comparison results indicate the parallel SCE-UA significantly improves computational efficiency compared to the original serial version. The OpenCL implementation obtains the best overall acceleration results however, with the most complex source code. The parallel SCE-UA has bright prospects to be applied in real-world applications.

  1. 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.

  2. Genotoxic evaluation of terbinafine in human lymphocytes in vitro.

    Science.gov (United States)

    Tolomeotti, Danielle; de Castro-Prado, Marialba Avezum Alves; de Sant'Anna, Juliane Rocha; Martins, Ana Beatriz Tozzo; Della-Rosa, Valter Augusto

    2015-01-01

    Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0 μg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0 μg/ml, 25.0 μg/ml, 50.0 μg/ml and 100.0 μg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α = 0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.

  3. WRNIP1 functions upstream of DNA polymerase η in the UV-induced DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimura, Akari, E-mail: akari_yo@stu.musashino-u.ac.jp [Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585 (Japan); Kobayashi, Yume [Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585 (Japan); Tada, Shusuke [Department of Medical Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510 (Japan); Seki, Masayuki [Department of Biochemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai-shi, Miyagi 981-8558 (Japan); Enomoto, Takemi [Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585 (Japan)

    2014-09-12

    Highlights: • The UV sensitivity of POLH{sup −/−} cells was suppressed by disruption of WRNIP1. • In WRNIP1{sup −/−/−}/POLH{sup −/−} cells, mutation frequencies and SCE after irradiation reduced. • WRNIP1 defect recovered rate of fork progression after irradiation in POLH{sup −/−} cells. • WRNIP1 functions upstream of Polη in the translesion DNA synthesis pathway. - Abstract: WRNIP1 (WRN-interacting protein 1) was first identified as a factor that interacts with WRN, the protein that is defective in Werner syndrome (WS). WRNIP1 associates with DNA polymerase η (Polη), but the biological significance of this interaction remains unknown. In this study, we analyzed the functional interaction between WRNIP1 and Polη by generating knockouts of both genes in DT40 chicken cells. Disruption of WRNIP1 in Polη-disrupted (POLH{sup −/−}) cells suppressed the phenotypes associated with the loss of Polη: sensitivity to ultraviolet light (UV), delayed repair of cyclobutane pyrimidine dimers (CPD), elevated frequency of mutation, elevated levels of UV-induced sister chromatid exchange (SCE), and reduced rate of fork progression after UV irradiation. These results suggest that WRNIP1 functions upstream of Polη in the response to UV irradiation.

  4. Telomere lengthening early in development.

    Science.gov (United States)

    Liu, Lin; Bailey, Susan M; Okuka, Maja; Muñoz, Purificación; Li, Chao; Zhou, Lingjun; Wu, Chao; Czerwiec, Eva; Sandler, Laurel; Seyfang, Andreas; Blasco, Maria A; Keefe, David L

    2007-12-01

    Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts. How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange (T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.

  5. In vitro evaluation of the genotoxicity of a family of novel MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer and PLGA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    He Lili; Yang Likai; Zhang Zhirong; Gong Tao; Deng Li; Sun Xun [Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China); Gu Zhongwei, E-mail: xunsun22@gmail.co [National Engineering Research Center for Biomaterials, Engineering Research Center of Biomaterials, Sichuan University, Chengdu 610064 (China)

    2009-11-11

    Despite the booming development of nanoparticle materials for pharmaceutical applications, studies on their genotoxicity are few. In our previous efforts to develop an intravenous nanoparticle material, a family of novel monomethoxy(polyethylene glycol)-poly(D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) polymers was synthesized. The cytotoxicity and genotoxicity of nine kinds of selected blank PELGE and PLGA (poly(D,L-lactic and glycolic acid)) nanoparticles were evaluated using methyl thiazolyl tetrazolium (MTT), micronucleus (MN) and sister chromatid exchange (SCE) assays with or without the addition of a metabolic activation system (S9 mix), using Chinese hamster ovary (CHO) cells. The cytotoxicity of nanoparticles exhibited a dose-dependent response, with a concentration of 5 mg ml{sup -1} being the turning point. The frequencies of MN observed in samples treated with various nanoparticles were not statistically different from those seen in the negative controls in the presence or absence of the S9 mix. Also, no cell cycle delay was observed. The numbers of SCE per cell observed in samples treated with five kinds of PELGE nanoparticles were significantly greater than those found in the negative controls with or without the S9 mix. The discrepancies found in the two assays suggest that the five kinds of nanoparticles may produce only a weakly clastogenic response.

  6. Assessment of the radioprotective effects of amifostine and melatonin on human lymphocytes irradiated with gamma-rays in vitro

    International Nuclear Information System (INIS)

    Kopjar, N.; Miocic, S.; Ramic, S.; Milic, M.; Viculin, T.

    2005-01-01

    Radioprotective effects of amifostine and melatonin on human peripheral blood irradiated with g-rays were investigated using the micronucleus (MN) assay and the analysis of sister chromatid exchanges (SCE). Duplicate blood samples were pre-treated with amifostine (7.7 mM), melatonin (2 mM) and their combination for 30 minutes. Negative controls were also included. After treatment with radioprotectors, one blood sample from each experimental group was exposed to g-rays from a 6 0C o source. The radiation dose absorbed was 2 Gy. Pre-treated irradiated blood samples showed a decrease in the total number of MN and in the number of cells with more than one MN. Moreover, they also showed significantly lower mean SCE values. Our results indicate that amifostine, melatonin and their combination in vitro have radioprotective effects on g-irradiated human peripheral blood lymphocytes, with no significant genotoxicity. Therefore, it may be reasonable to use them in combination, adjusting the doses of amifostine to achieve the best radioprotective effect with as few side effects as possible. Before employment, this combination should be extensively tested in vitro and in vivo, using the same and other biomarkers for different radiation dose and concentration ranges of both radioprotectors.(author)

  7. Comprehensive progress report

    International Nuclear Information System (INIS)

    Little, J.B.

    1980-01-01

    The goal of this research project during the past three years has been to characterize the effects of alpha radiation in the induction of malignant transformation in vitro. A 238 PuO 2 source was constructed and mounted in a specially designed chamber which allowed uniform alpha particle irradiation of monolayer cultures in 100 mm plastic Petri dishes at a dose-rate of 24 rads/min. The biologic effects were compared with those observed with 220 Kv x-rays. The induction of sister chromatid exchanges (SCE) and gross chromosomal aberrations by alpha radiation was studied in parallel experiments. The maximally effective dose for the induction of SCE by alpha particles was about 5% of that required for x-rays, though the actual frequencies induced were somewhat lower. As in the case of survival and transformation, no decline occurred in the level of chromosome aberrations in alpha-irradiated cells when they were held in the stationary phase of growth after exposure. Finally, preliminary experiments have been initiated to study transformation induced by incorporated radioisotopes of varying LET. 125 IudR, which emits densely ionizing Auger electrons, appears to be several-fold more effective per decay than 3 H-thymidine. These results generally confirm those obtained for external alpha irradiation

  8. In vitro and in vivo activities of SCE-2787, a new parenteral cephalosporin with a broad antibacterial spectrum.

    Science.gov (United States)

    Iwahi, T; Okonogi, K; Yamazaki, T; Shiki, S; Kondo, M; Miyake, A; Imada, A

    1992-01-01

    SCE-2787, a new cephalosporin having a condensed azolium moiety in the 3 position and an aminothiadiazolyl group in the 7 beta side chain, was evaluated for its in vitro and in vivo activities in comparison with those of ceftazidime, flomoxef, cefpirome, and E1040. Against methicillin-susceptible strains of Staphylococcus aureus and Staphylococcus epidermidis, SCE-2787 was more active than ceftazidime and E1040 and was as active as flomoxef and cefpirome, with MICs for 90% of strains tested (MIC90s) being 1.56 micrograms/ml or less. SCE-2787 was also active against Pseudomonas aeruginosa, for which the MIC90 was 6.25 micrograms/ml, which was lower than that of cefpirome and comparable to that of ceftazidime. SCE-2787 was marginally active against methicillin-resistant strains of staphylococci and Enterococcus faecalis, although its MIC90s were the lowest among those of the antibiotics tested. The activities of SCE-2787 against Streptococcus species, most members of the family Enterobacteriaceae, and Haemophilus influenzae exceeded those of ceftazidime and flomoxef and were comparable to those of cefpirome. Furthermore, MIC90s of SCE-2787 were significantly lower than those of ceftazidime for ceftazidime-resistant isolates of Citrobacter freundii and Enterobacter cloacae. SCE-2787 was resistant to hydrolysis by various types of beta-lactamases, including the Bush group 1 beta-lactamases, and had low affinities for these enzymes, with Km or Ki values of greater than 100 microM. The in vitro activity of SCE-2787 was reflected in its efficacy in mouse protection tests. Thus, SCE-2787 appears to be a promising cephalosporin that should be further evaluated in clinical trials. PMID:1510428

  9. 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

  10. Optimum Parameters for Tuned Mass Damper Using Shuffled Complex Evolution (SCE Algorithm

    Directory of Open Access Journals (Sweden)

    Hessamoddin Meshkat Razavi

    2015-06-01

    Full Text Available This study is investigated the optimum parameters for a tuned mass damper (TMD under the seismic excitation. Shuffled complex evolution (SCE is a meta-heuristic optimization method which is used to find the optimum damping and tuning frequency ratio for a TMD. The efficiency of the TMD is evaluated by decreasing the structural displacement dynamic magnification factor (DDMF and acceleration dynamic magnification factor (ADMF for a specific vibration mode of the structure. The optimum TMD parameters and the corresponding optimized DDMF and ADMF are achieved for two control levels (displacement control and acceleration control, different structural damping ratio and mass ratio of the TMD system. The optimum TMD parameters are checked for a 10-storey building under earthquake excitations. The maximum storey displacement and acceleration obtained by SCE method are compared with the results of other existing approaches. The results show that the peak building response decreased with decreases of about 20% for displacement and 30% for acceleration of the top floor. To show the efficiency of the adopted algorithm (SCE, a comparison is also made between SCE and other meta-heuristic optimization methods such as genetic algorithm (GA, particle swarm optimization (PSO method and harmony search (HS algorithm in terms of success rate and computational processing time. The results show that the proposed algorithm outperforms other meta-heuristic optimization methods.

  11. Sisters Hope

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Worre Hallberg, Gry

    2011-01-01

    Sisters Hope invites young scholars to visit our elite-school for run-away youngsters. Maybe you will be the next one to be collected and accepted?......Sisters Hope invites young scholars to visit our elite-school for run-away youngsters. Maybe you will be the next one to be collected and accepted?...

  12. Similar kinetics of chromatid aberrations in X-irradiated xrs 5 and wild-type Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    MacLeod, R.A.F.; Bryant, P.E.

    1990-01-01

    We have studied the kinetics of chromatid aberrations in cells of the Chinese hamster ovary (CHO-K1) derived, X-ray sensitive cell line xrs 5 irradiated in the G 2 phase at 37 0 C, as well as during a cell cycle extended by transient hypothermia at 33 0 C. While a given X-ray dose was estimated to produce about 4 times as many chromatid break and twice the frequency of exchanges in xrs 5 cells as in the parent line, there was no difference between the lines in the rates of disappearance of chromatid breaks during G 2 at either temperature; and similar patterns of chromatid exchange kinetics were observed in the two lines. Both the frequencies and distributions of chromatid breaks at different times after irradiation are consistent with the view that the disappearance of these during incubation represents a repair process. These results imply that the G 2 chromosomal radiosensitivity of the xrs 5 mutant resides at the level of initial chromatid damage. (author)

  13. 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

  14. 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.

  15. Explosive Infrasonic Events: Sensor Comparison Experiment (SCE)

    Energy Technology Data Exchange (ETDEWEB)

    Schnurr, J. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Garces, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rodgers, A. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-02-06

    SCE (sensor comparison experiment) 1 through 4 consists of a series of four controlled above-ground explosions designed to provide new data for overpressure propagation. Infrasound data were collected by LLNL iPhones and other sensors. Origin times, locations HOB, and yields are not being released at this time and are therefore not included in this report. This preliminary report will be updated as access to additional data changes, or instrument responses are determined.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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)

  18. Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship

    International Nuclear Information System (INIS)

    Erselcan, Taner; Ozdemir, Semra; Turgut, Bulent; Dogan, Derya; Sungu, Selma; Ozdemir, Ozturk

    2004-01-01

    Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of 131 I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean±SD) were 3.19±0.93, 10.83±1.72 and 5.75±2.06, respectively, in the whole group, and these values differed significantly from each other (P 131 I dose in the whole group, but a negative correlation was found between the 131 I dose and the RR at the 6th month (r=-0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x-28.4x 2 +38.1 (R 2 =0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of 131 I and DR and RR were obtained with a linear-quadratic model (Y=αD+βD 2 ) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient β to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following 131 I treatment. Further studies are therefore needed to clarify the effect of the negative β value on the biological dosimetry approach in continuous internal low LET radiation, as in the case

  19. Evaluation of SO{sub 2} control technologies for three SCE&G power stations

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, J.A. Jr. [South Carolina Electric and Gas, Co., Columbia, SC (United States); Wiggins, D.S. [Raytheon Engineers and Constructors, Philadelphia, PA (United States)

    1995-06-01

    South Carolina Electric and Gas, Co. (SCE&G) commissioned a detailed engineering study evaluating flue gas desulphurization (FGD) equipment for three coal fired generating stations in 1993. Raytheon Engineers and Constructors performed the study evaluating wet and dry FGD processes at three of SCE&G`s generating stations. This paper presents the results and conclusions from the study. The following areas are discussed: (1) Station Descriptions; (2) Process Design Criteria; (3) Study Goals and Methodology; (4) Results from the Economic and Kepner-Tregoe Analysis; and (5) Study Recommendations. The paper concludes with a lessons learned section discussing issues which arose during the study.

  20. Sisters Hope - the exposed self

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Hallberg, Gry Worre

    Sisters Hope is an art-educational method and a practice-led research tool, rooted in the construction of a fictional parallel universe revolving around the twin sisters Coco and Coca Pebber. Our work is rooted in the ambition to democratize the aesthetic dimension through ‘affective engineering......’ and the establishment of fictional spaces outside the institutional art context. In the Unfolding Academia-context Sisters Hope investigates new forms of research and (re)presentation through the creation of interactive and affective learning-spaces. At Collective Futures Sisters Hope explored questions such as: How...

  1. A comparison of G2 phase radiation-induced chromatid break kinetics using calyculin-PCC with those obtained using colcemid block.

    Science.gov (United States)

    Bryant, Peter E; Mozdarani, Hossein

    2007-09-01

    To study the possible influence of cell-cycle delay on cells reaching mitosis during conventional radiation-induced chromatid break experiments using colcemid as a blocking agent, we have compared the chromatid break kinetics following a single dose of gamma rays (0.75 Gy) in metaphase CHO cells using calyculin-induced premature chromosome condensation (PCC), with those using colcemid block. Calyculin-induced PCC causes very rapid condensation of G2 cell chromosomes without the need for a cell to progress to mitosis, hence eliminating any effect of cell-cycle checkpoint on chromatid break frequency. We found that the kinetics of the exponential first-order decrease in chromatid breaks with time after irradiation was similar (not significantly different) between the two methods of chromosome condensation. However, use of the calyculin-PCC technique resulted in a slightly increased rate of disappearance of chromatid breaks and thus higher frequencies of breaks at 1.5 and 2.5 h following irradiation. We also report on the effect of the nucleoside analogue ara A on chromatid break kinetics using the two chromosome condensation techniques. Ara A treatment of cells abrogated the decrease in chromatid breaks with time, both using the calyculin-PCC and colcemid methods. We conclude that cell-cycle delay may be a factor determining the absolute frequency of chromatid breaks at various times following irradiation of cells in G2 phase but that the first-order disappearance of chromatid breaks with time and its abrogation by ara A are not significantly influenced by the G2 checkpoint.

  2. 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...

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

    Science.gov (United States)

    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.

  4. Investigations into the molecular mechanism of chromatid breakage in the G2-phase of mammalian cells

    International Nuclear Information System (INIS)

    Bryant, P.E.; Armstrong, G.N.; Gray, L.; Frankenberg, D.; Mozdarani, H.

    2003-01-01

    Chromatid breakage following irradiation of cells in the G2-phase of the cell cycle results from the induction of DNA double-strand breaks (dsb). The conversion of dsb into chromatid breaks (cb) has a genetic basis, seemingly different from that of dsb rejoining. The variation in extent of this conversion is exemplified by the stiking variation in frequency of cb in irradiated cycling T-lymphocytes between different normal individuals. Elevated cb frequency in lymphocytes of around 40% of breast cancer patients and their first-degree relatives suggests the presence of mutations in low penetrance cancer predisposing genes that also affect conversion of dsb to cb. Investigation of the mechanism of chromatid radiosensitivity using genetically engineered rodent cell lines containing unique dsb break sites indicate that a single isolated dsb is sufficient to cause a cb. The single-event nature of chromatid breakage is confirmed by the fact that cb are induced as a linear function of radiation dose. Moreover, we have recently shown that ultrasoft carbon-K X-rays also induce chromatid breakage. In this case the energy of the secondary electrons produced by carbon-K X-rays is too low to span more than one DNA double helix, thus further supporting our conclusion that a single dsb is responsible for the formation of a cb. Chromatid breakage is thought to involve a rearrangement between DNA strands at the crossover points of chromatin loop(s) triggered by the presence of a dsb within the loop structure. The occasional observation of 'looped-out' sections of chromatin at cb sites supports this hypothesis. The occurrence of 'colour-switches' between FPG stained chromatids at a proportion of break sites (e.g. about 16% in CHO cells) shows that a significant proportion of cb definitely result from chromatin rearrangements. Measurements of altered colour-switch ratio (csr) in mutant rodent and human cells (irs1 and AT cells respectively) also indicate a genetic basis for the

  5. [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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. Mutagenic and morphologic impacts of 1.8 GHz radiofrequency radiation on human peripheral blood lymphocytes (hPBLs) and possible protective role of pre-treatment with Ginkgo biloba (EGb 761)

    Energy Technology Data Exchange (ETDEWEB)

    Esmekaya, Meric Arda, E-mail: mericarda@yahoo.com [Department of Biophysics, Gazi University, Faculty of Medicine and Gazi Non-ionizing Radiation, Protection (GNRP) Center, Ankara (Turkey); Aytekin, Ebru [Department of Medical Genetics, Gazi University Faculty of Medicine, Ankara (Turkey); Ozgur, Elcin; Gueler, Goeknur [Department of Biophysics, Gazi University, Faculty of Medicine and Gazi Non-ionizing Radiation, Protection (GNRP) Center, Ankara (Turkey); Ergun, Mehmet Ali [Department of Medical Genetics, Gazi University Faculty of Medicine, Ankara (Turkey); Oemeroglu, Suna [Department of Histology and Embryology, Gazi University, Faculty of Medicine, Ankara (Turkey); Seyhan, Nesrin [Department of Biophysics, Gazi University, Faculty of Medicine and Gazi Non-ionizing Radiation, Protection (GNRP) Center, Ankara (Turkey)

    2011-12-01

    The mutagenic and morphologic effects of 1.8 GHz Global System for Mobile Communications (GSM) modulated RF (radiofrequency) radiation alone and in combination with Ginkgo biloba (EGb 761) pre-treatment in human peripheral blood lymphocytes (hPBLs) were investigated in this study using Sister Chromatid Exchange (SCE) and electron microscopy. Cell viability was assessed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction assay. The lymphocyte cultures were exposed to GSM modulated RF radiation at 1.8 GHz for 6, 8, 24 and 48 h with and without EGb 761. We observed morphological changes in pulse-modulated RF radiated lymphocytes. Longer exposure periods led to destruction of organelle and nucleus structures. Chromatin change and the loss of mitochondrial crista occurred in cells exposed to RF for 8 h and 24 h and were more pronounced in cells exposed for 48 h. Cytoplasmic lysis and destruction of membrane integrity of cells and nuclei were also seen in 48 h RF exposed cells. There was a significant increase (p < 0.05) in SCE frequency in RF exposed lymphocytes compared to sham controls. EGb 761 pre-treatment significantly decreased SCE from RF radiation. RF radiation also inhibited cell viability in a time dependent manner. The inhibitory effects of RF radiation on the growth of lymphoctes were marked in longer exposure periods. EGb 761 pre-treatment significantly increased cell viability in RF + EGb 761 treated groups at 8 and 24 h when compared to RF exposed groups alone. The results of our study showed that RF radiation affects cell morphology, increases SCE and inhibits cell proliferation. However, EGb 761 has a protective role against RF induced mutagenity. We concluded that RF radiation induces chromosomal damage in hPBLs but this damage may be reduced by EGb 761 pre-treatment. - Highlights: Black-Right-Pointing-Pointer RF Radiation inhibits cell proliferation. Black-Right-Pointing-Pointer RF radiation induces chromosomal damage

  12. Evaluation of primary DNA damage, cytogenetic biomarkers and genetic polymorphisms for CYP1A1 and GSTM1 in road tunnel construction workers.

    Science.gov (United States)

    Villarini, M; Moretti, M; Fatigoni, C; Agea, E; Dominici, L; Mattioli, A; Volpi, R; Pasquini, R

    2008-01-01

    In tunnel construction workers, occupational exposure to dust (alpha-quartz and other particles from blasting), gases (nitrogen dioxide, NO(2)), diesel exhausts, and oil mist has been associated with lung function decline, induction of inflammatory reactions in the lungs with release of mediators that may influence blood coagulation, and increased risk of chronic obstructive pulmonary disease. The present molecular epidemiology study was designed to evaluate whether occupational exposure to indoor pollutants during road tunnel construction might result in genotoxic effects. A study group of 39 underground workers and a reference group of 34 unexposed subjects were examined. Primary and oxidative DNA damage, sister-chromatid exchanges (SCE), and micronuclei (MN) were measured in peripheral blood cells. The possible influences of polymorphisms in gene encoding for CYP1A1 and GSTM1 xenobiotic-metabolizing enzymes were also investigated. Exposure assessment was performed with detailed interviews and questionnaires. There were no significant differences in the level of primary and oxidative DNA damage and frequency of SCE between the tunnel workers and controls, whereas the frequency of MN showed a significant increase in exposed subjects compared to controls. No effects of CYP1A1 or GSTM1 variants were observed for the analyzed biomarkers. Since MN in peripheral blood lymphocytes are recognized as a predictive biomarker of cancer risk within a population of healthy subjects, the genotoxic risk of occupational exposure to various indoor environmental pollutants during road tunnel construction cannot be excluded by this biomonitoring study.

  13. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mylonaki, Effie; Manika, Katerina [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Zarogoulidis, Paul, E-mail: pzarog@hotmail.com [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Mourelatos, Dionysios [Biology and Genetics, Medical School, Aristotle University of Thessaloniki (Greece)

    2012-12-15

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p < 0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p < 0.001, NSCLC: p = 0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p < 0.001, NSCLC: p = 0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p > 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

  14. Evaluation of the genotoxic and cytotoxic potential of mainstream whole smoke and smoke condensate from a cigarette containing a novel carbon filter.

    Science.gov (United States)

    Bombick, D W; Bombick, B R; Ayres, P H; Putnam, K; Avalos, J; Borgerding, M F; Doolittle, D J

    1997-09-01

    A novel carbon filter has been developed which primarily reduces the amount of certain vapor phase constituents of tobacco smoke with greater efficiency than the charcoal filters of cigarettes currently in the market. In vitro indicators of genotoxic and cytotoxic potential were used to compare the cigarette smoke condensate (particulate phase) or whole cigarette smoke (vapor phase and particulate phase) from cigarettes containing the novel carbon filter with smoke condensate or whole smoke from commercial or prototype cigarettes not containing the novel carbon filter. Ames bacterial mutagenicity, sister chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells, and neutral red cytotoxicity assays in CHO cells were utilized to assess the genotoxic and cytotoxic potential of the cigarette smoke condensates. SCE and neutral red cytotoxicity assays were utilized to assess the genotoxic and cytotoxic potential of the whole smoke. As expected, the novel carbon filter did not significantly affect the genotoxic or cytotoxic activity of the smoke condensate, although we did observe that the use of low-nitrogen tobacco reduced the mutagenicity of the condensate in Salmonella typhimurium strain TA98. However, the whole smoke from cigarettes containing the novel carbon filter demonstrated significant reductions in genotoxic and cytotoxic potential compared to cigarettes without the novel carbon filter. The toxicity of the smoke was correlated (r = 0.7662 for cytotoxicity and r = 0.7562 for SCE induction) to the aggregate mass of several vapor phase components (acetone, acetaldehyde, acrolein, acrylonitrile, 1,3-butadiene, ammonia, NOx, HCN, benzene, isoprene, and formaldehyde) in the smoke of the cigarettes utilized in this study. In conclusion, this novel carbon filter, which significantly reduced the amount of carbonyls and other volatiles in mainstream cigarette smoke, resulted in significant reductions in the genotoxic and cytotoxic activity of the smoke as measured

  15. Comparison of Performance between Genetic Algorithm and SCE-UA for Calibration of SCS-CN Surface Runoff Simulation

    Directory of Open Access Journals (Sweden)

    Ji-Hong Jeon

    2014-11-01

    Full Text Available Global optimization methods linked with simulation models are widely used for automated calibration and serve as useful tools for searching for cost-effective alternatives for environmental management. A genetic algorithm (GA and shuffled complex evolution (SCE-UA algorithm were linked with the Long-Term Hydrologic Impact Assessment (L-THIA model, which employs the curve number (SCS-CN method. The performance of the two optimization methods was compared by automatically calibrating L-THIA for monthly runoff from 10 watersheds in Indiana. The selected watershed areas ranged from 32.7 to 5844.1 km2. The SCS-CN values and total five-day rainfall for adjustment were optimized, and the objective function used was the Nash-Sutcliffe value (NS value. The GA method rapidly reached the optimal space until the 10th generating population (generation, and after the 10th generation solutions increased dispersion around the optimal space, called a cross hair pattern, because of mutation rate increase. The number of looping executions influenced the performance of model calibration for the SCE-UA and GA method. The GA method performed better for the case of fewer loop executions than the SCE-UA method. For most watersheds, calibration performance using GA was better than for SCE-UA until the 50th generation when the number of model loop executions was around 5150 (one generation has 100 individuals. However, after the 50th generation of the GA method, the SCE-UA method performed better for calibrating monthly runoff compared to the GA method. Optimized SCS-CN values for primary land use types were nearly the same for the two methods, but those for minor land use types and total five-day rainfall for AMC adjustment were somewhat different because those parameters did not significantly influence calculation of the objective function. The GA method is recommended for cases when model simulation takes a long time and the model user does not have sufficient time

  16. Canine adenovirus type 2 vector generation via I-Sce1-mediated intracellular genome release.

    Directory of Open Access Journals (Sweden)

    Sandy Ibanes

    Full Text Available When canine adenovirus type 2 (CAdV-2, or also commonly referred to as CAV-2 vectors are injected into the brain parenchyma they preferentially transduce neurons, are capable of efficient axonal transport to afferent regions, and allow transgene expression for at last >1 yr. Yet, translating these data into a user-friendly vector platform has been limited because CAV-2 vector generation is challenging. Generation of E1-deleted adenovirus vectors often requires transfection of linear DNA fragments of >30 kb containing the vector genome into an E1-transcomplementing cell line. In contrast to human adenovirus type 5 vector generation, CAV-2 vector generation is less efficient due, in part, to a reduced ability to initiate replication and poor transfectibility of canine cells with large, linear DNA fragments. To improve CAV-2 vector generation, we generated an E1-transcomplementing cell line expressing the estrogen receptor (ER fused to I-SceI, a yeast meganuclease, and plasmids containing the I-SceI recognition sites flanking the CAV-2 vector genome. Using transfection of supercoiled plasmid and intracellular genome release via 4-OH-tamoxifen-induced nuclear translocation of I-SceI, we improved CAV-2 vector titers 1,000 fold, and in turn increased the efficacy of CAV-2 vector generation.

  17. Canine Adenovirus Type 2 Vector Generation via I-Sce1-Mediated Intracellular Genome Release

    Science.gov (United States)

    Ibanes, Sandy; Kremer, Eric J.

    2013-01-01

    When canine adenovirus type 2 (CAdV-2, or also commonly referred to as CAV-2) vectors are injected into the brain parenchyma they preferentially transduce neurons, are capable of efficient axonal transport to afferent regions, and allow transgene expression for at last >1 yr. Yet, translating these data into a user-friendly vector platform has been limited because CAV-2 vector generation is challenging. Generation of E1-deleted adenovirus vectors often requires transfection of linear DNA fragments of >30 kb containing the vector genome into an E1-transcomplementing cell line. In contrast to human adenovirus type 5 vector generation, CAV-2 vector generation is less efficient due, in part, to a reduced ability to initiate replication and poor transfectibility of canine cells with large, linear DNA fragments. To improve CAV-2 vector generation, we generated an E1-transcomplementing cell line expressing the estrogen receptor (ER) fused to I-SceI, a yeast meganuclease, and plasmids containing the I-SceI recognition sites flanking the CAV-2 vector genome. Using transfection of supercoiled plasmid and intracellular genome release via 4-OH-tamoxifen-induced nuclear translocation of I-SceI, we improved CAV-2 vector titers 1,000 fold, and in turn increased the efficacy of CAV-2 vector generation. PMID:23936483

  18. 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)

  19. 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)

  20. 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.

  1. Teenage pregnancy: the impact of maternal adolescent childbearing and older sister's teenage pregnancy on a younger sister.

    Science.gov (United States)

    Wall-Wieler, Elizabeth; Roos, Leslie L; Nickel, Nathan C

    2016-05-25

    Risk factors for teenage pregnancy are linked to many factors, including a family history of teenage pregnancy. This research examines whether a mother's teenage childbearing or an older sister's teenage pregnancy more strongly predicts teenage pregnancy. This study used linkable administrative databases housed at the Manitoba Centre for Health Policy (MCHP). The original cohort consisted of 17,115 women born in Manitoba between April 1, 1979 and March 31, 1994, who stayed in the province until at least their 20(th) birthday, had at least one older sister, and had no missing values on key variables. Propensity score matching (1:2) was used to create balanced cohorts for two conditional logistic regression models; one examining the impact of an older sister's teenage pregnancy and the other analyzing the effect of the mother's teenage childbearing. The adjusted odds of becoming pregnant between ages 14 and 19 for teens with at least one older sister having a teenage pregnancy were 3.38 (99 % CI 2.77-4.13) times higher than for women whose older sister(s) did not have a teenage pregnancy. Teenage daughters of mothers who had their first child before age 20 had 1.57 (99 % CI 1.30-1.89) times higher odds of pregnancy than those whose mothers had their first child after age 19. Educational achievement was adjusted for in a sub-population examining the odds of pregnancy between ages 16 and 19. After this adjustment, the odds of teenage pregnancy for teens with at least one older sister who had a teenage pregnancy were reduced to 2.48 (99 % CI 2.01-3.06) and the odds of pregnancy for teen daughters of teenage mothers were reduced to 1.39 (99 % CI 1.15-1.68). Although both were significant, the relationship between an older sister's teenage pregnancy and a younger sister's teenage pregnancy is much stronger than that between a mother's teenage childbearing and a younger daughter's teenage pregnancy. This study contributes to understanding of the broader topic "who is

  2. 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)

  3. Consumerism and the Sister Carrie's American Dream%Consumerism and the Sister Carrie''s American Dream

    Institute of Scientific and Technical Information of China (English)

    卢亚丽

    2017-01-01

    From the aspect of consumerism to this text analyze Sister Carrie's"American dream"destruction. The author wholly and deeply analyzes the embodiment of consumerism in Dreiser's Sister Carrie and Dreiser's outlook and values under the effect of consumerism. To prove that the reason for destruction of Carrie's American dream is consumerism.

  4. Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells.

    Science.gov (United States)

    Lin, Jianfei; Chen, He; Luo, Ling; Lai, Yongrong; Xie, Wei; Kee, Kehkooi

    2015-01-01

    To correct a DNA mutation in the human genome for gene therapy, homology-directed repair (HDR) needs to be specific and have the lowest off-target effects to protect the human genome from deleterious mutations. Zinc finger nucleases, transcription activator-like effector nuclease (TALEN) and CRISPR-CAS9 systems have been engineered and used extensively to recognize and modify specific DNA sequences. Although TALEN and CRISPR/CAS9 could induce high levels of HDR in human cells, their genotoxicity was significantly higher. Here, we report the creation of a monomeric endonuclease that can recognize at least 33 bp by fusing the DNA-recognizing domain of TALEN (TALE) to a re-engineered homing endonuclease I-SceI. After sequentially re-engineering I-SceI to recognize 18 bp of the human β-globin sequence, the re-engineered I-SceI induced HDR in human cells. When the re-engineered I-SceI was fused to TALE (TALE-ISVB2), the chimeric endonuclease induced the same HDR rate at the human β-globin gene locus as that induced by TALEN, but significantly reduced genotoxicity. We further demonstrated that TALE-ISVB2 specifically targeted at the β-globin sequence in human hematopoietic stem cells. Therefore, this monomeric endonuclease has the potential to be used in therapeutic gene targeting in human cells. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. 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

  6. Somatomedin C deficiency in Asian sisters.

    OpenAIRE

    McGraw, M E; Price, D A; Hill, D J

    1986-01-01

    Two sisters of Asian origin showed typical clinical and biochemical features of primary somatomedin C (SM-C) deficiency (Laron dwarfism). Abnormalities of SM-C binding proteins were observed, one sister lacking the high molecular weight (150 Kd) protein.

  7. Enhanced targeted integration mediated by translocated I-SceI during the Agrobacterium mediated transformation of yeast.

    Science.gov (United States)

    Rolloos, Martijn; Hooykaas, Paul J J; van der Zaal, Bert J

    2015-02-09

    Agrobacterium mediated transformation (AMT) has been embraced by biotechnologists as the technology of choice to introduce or alter genetic traits of plants. However, in plants it is virtually impossible to predetermine the integration site of the transferred T-strand unless one is able to generate a double stranded break (DSB) in the DNA at the site of interest. In this study, we used the model organism Saccharomyces cerevisiae to investigate whether the Agrobacterium mediated translocation of site-specific endonucleases via the type IV secretion system (T4SS), concomitantly with T-DNA transfer is possible and whether this can improve the gene targeting efficiency. In addition to that, the effect of different chromatin states on targeted integration, was investigated. It was found that Agrobacterium mediated translocation of the homing endonuclease I-SceI has a positive effect on the integration of T-DNA via the homologous repair (HR) pathway. Furthermore, we obtained evidence that nucleosome removal has a positive effect on I-SceI facilitated T-DNA integration by HR. Reversely; inducing nucleosome formation at the site of integration removes the positive effect of translocated I-SceI on T-DNA integration.

  8. 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.

  9. Eruptive history of South Sister, Oregon Cascades

    Science.gov (United States)

    Fierstein, J.; Hildreth, W.; Calvert, A.T.

    2011-01-01

    South Sister is southernmost and highest of the Three Sisters, three geologically dissimilar stratovolcanoes that together form a spectacular 20km reach along the Cascade crest in Oregon. North Sister is a monotonously mafic edifice as old as middle Pleistocene, Middle Sister a basalt-andesite-dacite cone built between 48 and 14ka, and South Sister is a basalt-free edifice that alternated rhyolitic and intermediate modes from 50ka to 2ka (largely contemporaneous with Middle Sister). Detailed mapping, 330 chemical analyses, and 42 radioisotopic ages show that the oldest exposed South Sister lavas were initially rhyolitic ~50ka. By ~37ka, rhyolitic lava flows and domes (72-74% SiO2) began alternating with radially emplaced dacite (63-68% SiO2) and andesite (59-63% SiO2) lava flows. Construction of a broad cone of silicic andesite-dacite (61-64% SiO2) culminated ~30ka in a dominantly explosive sequence that began with crater-forming andesitic eruptions that left fragmental deposits at least 200m thick. This was followed at ~27ka by growth of a steeply dipping summit cone of agglutinate-dominated andesite (56-60.5% SiO2) and formation of a summit crater ~800m wide. This crater was soon filled and overtopped by a thick dacite lava flow and then by >150m of dacitic pyroclastic ejecta. Small-volume dacite lavas (63-67% SiO2) locally cap the pyroclastic pile. A final sheet of mafic agglutinate (54-56% SiO2) - the most mafic product of South Sister - erupted from and drapes the small (300-m-wide) present-day summit crater, ending a summit-building sequence that lasted until ~22ka. A 20kyr-long-hiatus was broken by rhyolite eruptions that produced (1) the Rock Mesa coulee, tephra, and satellite domelets (73.5% SiO2) and (2) the Devils Chain of ~20 domes and short coulees (72.3-72.8% SiO2) from N-S vent alignments on South Sister's flanks. The compositional reversal from mafic summit agglutinate to recent rhyolites epitomizes the frequently changing compositional modes of the

  10. 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.

  11. 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.

  12. Oxcarbazepine-induced cytotoxicity and genotoxicity in human lymphocyte cultures with or without metabolic activation.

    Science.gov (United States)

    Atlı Şekeroğlu, Zülal; Kefelioğlu, Haluk; Kontaş Yedier, Seval; Şekeroğlu, Vedat; Delmecioğlu, Berrin

    2017-03-01

    There has been considerable debate about the relationship between epilepsy and cancer. Oxcarbazepine (OXC) is used for treating certain types of seizures in patients with epilepsy. There have been no detailed investigations about genotoxicity of OXC and its metabolites. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of OXC and its metabolites on cultured human lymphocytes. The cytotoxicity and genotoxicity of OXC on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberration (CA) and micronucleus (MN) tests. Cultures were treated with 125, 250 and 500 μg/ml of OXC in the presence (3 h treatment) and absence (24 h and 48 h treatment) of a metabolic activator (S9 mix). Dimethyl sulfoxide (DMSO) was used as a solvent control. OXC showed cytotoxic activities due to significant decreases in mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) in the absence of S9 mix when compared with solvent control. Metabolites of OXC also significantly reduced MI and PI in cultures with S9 mix. OXC significantly increased the CAs, aberrant cells, SCE and MN values in the presence and absence of S9 mix. Our results indicated that both OXC and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Further studies are necessary to elucidate the relationship between cytotoxic, cytostatic and genotoxic effects, and to make a possible risk assessment in patients receiving therapy with this drug.

  13. Mycotoxins’ Activity at Toxic and Sub-Toxic Concentrations: Differential Cytotoxic and Genotoxic Effects of Single and Combined Administration of Sterigmatocystin, Ochratoxin A and Citrinin on the Hepatocellular Cancer Cell Line Hep3B

    Directory of Open Access Journals (Sweden)

    Nikolia Αnninou

    2014-02-01

    Full Text Available Food safety organizations indicate the likelihood of constant human and animal exposure to mycotoxin mixtures as a possible negative public health impact. Risk assessment demonstrates that certain mycotoxins of Aspergillus and Penicillium spp. are toxic and hold a significant genotoxic efficacy at nanomolar concentrations. The aim of the current study was to investigate the potential cytogenetic effects of sterigmatocystin (STER, ochratoxin A (OTA and citrinin (CTN alone or in combination, at pM to μΜ concentrations, on the human hepatocellular cancer cell line Hep3B. MTT reduction, mitotic divisions, cell cycle delays and sister chromatid exchange rates (SCE were determined as endpoints of metabolic activity, cytotoxicity, cytostaticity, and genotoxicity, respectively. All mycotoxin treatments induce SCE rates from 10−12 M, while their cytotoxic and cytostatic potential varies. In PRI and MI assays, but not at MTT, STER alone or in combination with OTA + CTN appeared cytostatic and cytotoxic, even at 10−12 M, while CTN alone and all other combinations displayed substantial cellular survival inhibition in doses ≥ 10−8 M. Co-administration of STER + OTA or STER + CTN in concentrations ≤ 10−1 M, increased the MI and MTT activity, while it did not affect the PRI. Mycotoxin co-treatments revealed in general similar-to-additive or antagonistic genotoxic and cytotoxic effects. Our results for the first time describe that STER alone or in combination with OTA and/or CTN share a cytotoxic and cytogenetic potential even at picoMolar concentrations on human hepatoma cells in vitro.

  14. Induction and repair of lethal and oncogenic lesions and their relationship to cytogenetic changes in UV-irradiated mouse 10T1/2 cells

    International Nuclear Information System (INIS)

    Chan, G.L.; Nagasawa, H.; Little, J.B.

    1979-01-01

    While bacterial system is valuable for the pragmatic purpose of screening potential environmental carcinogens, the fundamental difference between prokaryotes and mammalian cells warrant caution against the use of bacterial mutagenic mechanisms to explain the oncogenic process in mammalian cells. The 10 T1/2 cells exposed to UV light in the plateau phase and subcultured immediately to low density to assay for clonogenic survival were extremely resistant to the cytotoxic effect of UV light. Purely physical considerations such as the increased thickness of plateau phase cells and the increased cytoplasmic shielding of UV light from the nuclei were insufficient to account for this unusual resistance. The effect of caffeine on the repair processes in UV-irradiated mammalian cells appears to be exerted during the first DNA synthetic phase after the UV exposure. The daughter DNA synthesized on a UV-irradiated template is of reduced molecular weight. 10 T1/2 cells were exposed in the log phase of growth to UV light, and then they were cultured for the next 48 hours in the complete growth medium containing the specific concentration of caffeine. Parallel experiments were performed, in which cells were exposed for 48 hours to caffeine only with no prior exposure to UV light. It was found that caffeine did not potentiate the transformation by UV light. Caffeine alone induced sister chromatid exchange (SCE), whereas the caffeine given after UV light had no effect. The class of UV-induced lesions which induce SCE also leads to malignant transformation. (Yamashita, S.)

  15. 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

  16. 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.

  17. Co-Emulation of Scan-Chain Based Designs Utilizing SCE-MI Infrastructure

    OpenAIRE

    Tomas, Bill Jason; Jiang, Yingtao; Yang, Mei

    2014-01-01

    As the complexity of the scan algorithm is dependent on the number of design registers, large SoC scan designs can no longer be verified in RTL simulation unless partitioned into smaller sub - blocks. This paper proposes a meth odology to decrease scan - chain verification time utilizing SCE - MI, a widely used communication protocol for emulation, and an FPGA - based emulation platform. A high - level (SystemC) testbench and FPGA synthesizable har...

  18. NOAA Climate Data Record (CDR) of Northern Hemisphere (NH) Snow Cover Extent (SCE), Version 1

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This NOAA Climate Data Record (CDR) is a record for the Northern Hemisphere (NH) Snow Cover Extent (SCE) spanning from October 4, 1966 to present, updated monthly...

  19. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    International Nuclear Information System (INIS)

    Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

    2012-01-01

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer

  20. In vitro potential cytogenetic and oxidative stress effects of roxithromycin.

    Science.gov (United States)

    Arslan, Mehmet; Timocin, Taygun; Ila, Hasan B

    2017-10-01

    Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200 μg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48 h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200 μg/mL) for the 24-h treatment period and at all concentrations (except 25 μg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200 μg/mL) for the 24-h treatment period and at all concentrations (expect 25 μg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes.

  1. Use of a ring chromosome and pulsed-field gels to study recombinational repair

    International Nuclear Information System (INIS)

    Game, J.C.; Arabi, S.; Mortimer, R.K.

    1989-01-01

    In wild type yeast, it is known that x-ray induced DNA double-strand breaks (dsb) are repaired, leading to recovery of high molecular-weight molecules on gradients or pulsed-field gels. There is genetic evidence that some or all of this repair occurs via recombinational mechanisms involving sister-chromatid exchange (SCE) and (in diploids) inter-homologue recombination. However, this evidence is indirect and qualitative. The authors of this paper are attempting to use pulsed-field gels to detect and measure recombinational repair at the physical level in yeast strains with a circular homologue of Chr. III. The authors have previously used such strains to study meiotic recombination. The authors have shown that double-size circular molecules can be detected in log-phase haploid yeast cells carrying a ring chromosome, when such cells are exposed to x-rays and allowed time for subsequent repair. Large circular molecules will not enter our pulsed-field gels, but treatment of the DNA samples with radiation prior to running the gels will linearize a fraction of such molecules with a single dsb. Such linearized molecules will run as a band whose position indicates the size of the original unbroken circles

  2. Effects of combinations of chemotherapy and radiation on the emergence of drug resistant cells in 9L rat brain tumor spheroids

    International Nuclear Information System (INIS)

    Tofilon, P.J.; Arundel, C.; Vines, C.M.

    1987-01-01

    Repeated administration of antineoplastic chemotherapeutic agents is generally considered to induce and/or select for drug resistant cells. The authors recently begun to investigate whether chemotherapy interdigitated with radiation can minimize or eliminate the emergence of drug resiistent cells in 9L rat brain tumor spheroids grown from defined mixtures of cells sensitive (9L) and resistant (R/sub 3/) to BCNU. In this experimental system, the sister chromatid exchange (SCE) assay is used to quantitate the proportions of sensitive and resistant cells within the spheroids. While 9L and R/sub 3/ cell have different sensitivities to BCNU, they are equally sensitive to radiation. Mixed-cell spheroids consisting of 1% R/sub 3/ cells were treated with three doses of BCNU (10 μM) every 72 hr resulting in a shift in the 9L to R/sub 3/ ratio to greater than 50% R/sub 3/ cells. The combined protocols to be investigated will involve γ rays administered either 36 hr before or after each BCNU treatment. By initiating these combined protocols on spheroids of different sizes, the effectiveness of each protocol is evaluated with respect to the number of resistant cells present

  3. 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.

  4. Two Nepali Sisters

    DEFF Research Database (Denmark)

    Hansen, Annette Skovsted

    Diaspora is an expansion of a national or family network that can be activated for the benefit of the family and home nation in multiple ways. The argument is based on two life stories. Two Nepali sisters attended Association of Overseas Technical Scholarships (AOTS) training courses in Japan...... at different times during the 1980s. The training was partly funded by official development assistance provided through the Japanese Ministry of International Trade and Industry (MITI). They used their training very differently, but between the two of them extended a family network from Japan and India...... still pursuing a career in a Japanese company. Their children have or are studying in Japan, India, and the USA. The Nepal-based sister is a key stakeholder in the regional cooperation in South Asia. By engaging network theories of weak ties and scaled networks, the life stories become templates...

  5. Developing skills in clinical leadership for ward sisters.

    Science.gov (United States)

    Fenton, Katherine; Phillips, Natasha

    The Francis report has called for a strengthening of the ward sister's role. It recommends that sisters should operate in a supervisory capacity and should not be office bound. Effective ward leadership has been recognised as being vital to high-quality patient care and experience, resource management and interprofessional working. However, there is evidence that ward sisters are ill equipped to lead effectively and lack confidence in their ability to do so. University College London Hospitals Foundation Trust has recognised that the job has become almost impossible in increasingly large and complex organisations. Ward sisters spend less than 40% of their time on clinical leadership and the trust is undertaking a number of initiatives to support them in this role.

  6. I-SceI-mediated double-strand break does not increase the frequency of homologous recombination at the Dct locus in mouse embryonic stem cells.

    Science.gov (United States)

    Fenina, Myriam; Simon-Chazottes, Dominique; Vandormael-Pournin, Sandrine; Soueid, Jihane; Langa, Francina; Cohen-Tannoudji, Michel; Bernard, Bruno A; Panthier, Jean-Jacques

    2012-01-01

    Targeted induction of double-strand breaks (DSBs) at natural endogenous loci was shown to increase the rate of gene replacement by homologous recombination in mouse embryonic stem cells. The gene encoding dopachrome tautomerase (Dct) is specifically expressed in melanocytes and their precursors. To construct a genetic tool allowing the replacement of Dct gene by any gene of interest, we generated an embryonic stem cell line carrying the recognition site for the yeast I-SceI meganuclease embedded in the Dct genomic segment. The embryonic stem cell line was electroporated with an I-SceI expression plasmid, and a template for the DSB-repair process that carried sequence homologies to the Dct target. The I-SceI meganuclease was indeed able to introduce a DSB at the Dct locus in live embryonic stem cells. However, the level of gene targeting was not improved by the DSB induction, indicating a limited capacity of I-SceI to mediate homologous recombination at the Dct locus. These data suggest that homologous recombination by meganuclease-induced DSB may be locus dependent in mammalian cells.

  7. Role of base damage in aberration formation: interaction of aphidicolin and x-rays

    International Nuclear Information System (INIS)

    Bender, M.A.; Preston, R.J.

    1981-01-01

    The base analog cytosine arabinoside (CA) is an inhibitor of DNA synthesis that is able to induce chromosomal aberrations not only in the DNA synthetic (S) phase of the cell cycle but in cells in the pre- (G 0 or G 1 ) and in the post-DNA-synthetic (G 2 ) phases of the cell cycle as well. Incubation of human peripheral lymphocytes in CA following either G 0 or G 2 x irradiation causes a synergistic increase in chromosomal aberration frequency. CA is believed to preferentially inhibit DNA polymerase α. It is suggested that it is inhibition of the repair of x-ray-induced base damage that is responsible for the synergistic effect on chromosomal aberration production observed with x-ray and CA treatment of human peripheral lymphocytes. It has also been observed that CA induces sister chromatid exchanges (SCE) in mammalian cells when present during normal DNA replication and that it also interacts synergistically with uv in the induction of SCE. A number of other inhibitors of DNA synthesis were also tested, one, aphidicolin (APC), did produce effects similar to CA at the same concentration. Aphidicolin is a tetracyclic diterpinoid that inhibits the growth of eukaryotic cells by inhibition of DNA synthesis. This action has been shown to result from specific inhibition of DNA polymerase α, but not of polymerases β or γ. Unlike CA, it seems likely that APC inhibits by binding to and inactivating the DNA-α polymerase complex. Because both CA and APC are α polymerase inhibitors and because both interact synergistically with uv in the production of SCE, studies were conducted to determine whether APC also shares other cytogenetic properties of CA. Results to date have shown that, like CA, APC is clastogenic in both G 0 and G 2 , and it also interacts synergistically with x rays to increase chromosomal aberration production in both G 0 and G 2

  8. Consumerism and the Sister Carrie's American Dream

    Institute of Scientific and Technical Information of China (English)

    卢亚丽

    2017-01-01

    From the aspect of consumerism to this text analyze Sister Carrie's"American dream"destruction. The author wholly and deeply analyzes the embodiment of consumerism in Dreiser's Sister Carrie and Dreiser's outlook and values under the effect of consumerism. To prove that the reason for destruction of Carrie's American dream is consumerism.

  9. 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.

  10. 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.

  11. Satellite Based Probabilistic Snow Cover Extent Mapping (SCE) at Hydro-Québec

    Science.gov (United States)

    Teasdale, Mylène; De Sève, Danielle; Angers, Jean-François; Perreault, Luc

    2016-04-01

    Over 40% of Canada's water resources are in Quebec and Hydro-Quebec has developed potential to become one of the largest producers of hydroelectricity in the world, with a total installed capacity of 36,643 MW. The Hydro-Québec fleet park includes 27 large reservoirs with a combined storage capacity of 176 TWh, and 668 dams and 98 controls. Thus, over 98% of all electricity used to supply the domestic market comes from water resources and the excess output is sold on the wholesale markets. In this perspective the efficient management of water resources is needed and it is based primarily on a good river flow estimation including appropriate hydrological data. Snow on ground is one of the significant variables representing 30% to 40% of its annual energy reserve. More specifically, information on snow cover extent (SCE) and snow water equivalent (SWE) is crucial for hydrological forecasting, particularly in northern regions since the snowmelt provides the water that fills the reservoirs and is subsequently used for hydropower generation. For several years Hydro Quebec's research institute ( IREQ) developed several algorithms to map SCE and SWE. So far all the methods were deterministic. However, given the need to maximize the efficient use of all resources while ensuring reliability, the electrical systems must now be managed taking into account all risks. Since snow cover estimation is based on limited spatial information, it is important to quantify and handle its uncertainty in the hydrological forecasting system. This paper presents the first results of a probabilistic algorithm for mapping SCE by combining Bayesian mixture of probability distributions and multiple logistic regression models applied to passive microwave data. This approach allows assigning for each grid point, probabilities to the set of the mutually exclusive discrete outcomes: "snow" and "no snow". Its performance was evaluated using the Brier score since it is particularly appropriate to

  12. The effect of γ-irradiation on the toxicity of malathion in V79 hamster cells and Molt-4 human lymphocytes

    International Nuclear Information System (INIS)

    Szekely, J.G.; Goodwin, M.; Delaney, S.

    1992-01-01

    There is a growing interest in irradiation of food and agricultural products for insect disinfestation, sprout inhibition, delayed ripening and the reduction of microbiological loads. Irradiation to a maximum dose of 10 kGy is recognized as safe by national and international regulatory agencies. To address the question, whether irradiation of pesticide residues might produce radiation products that were less or more toxic than the original pesticide, effects were observed of 10 kGy of γ-radiation on malathion as measured by sister-chromatid exchange (SCE), micronuclei formation, cell survival, growth rate and polyploid formation. No significant differences were found between effects of irradiated and unirradiated malathion on any of these end- points. Polyploid formation was the most dramatic effect of both irradiated and control malathion on V79 Chinese hamster cells. Cell survival, polyploid formation and growth rate were slightly better in cells treated with irradiated malathion. In Molt-4 human lymphocyte cell, micronuclei formation was not affected by unirradiated or irradiated malathion. Compared to malathion alone, the lack of such biological effects indicates that none of the presumed radiation-induced breakdown products increased or decreased the endpoints studied. The number of SCE was consistently, but not significantly, higher in cells treated with irradiated malathion. There were no significant differences in cell survival or micronucleus formation in the human lymphocyte cell line Molt-4 treated with irradiated or control malathion. Thus, the irradiation of the pesticide malathion to 10 kGy, a recommended upper dose for most food irradiations, does not significantly alter its toxicity in these in vitro systems. (author). 23 refs.; 4 figs.; 3 tabs

  13. 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

  14. 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.

  15. 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.

  16. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

    Yardimci, Hasan; Loveland, Anna B.; Habuchi, Satoshi; van Oijen, Antoine M.; Walter, Johannes C.

    2010-01-01

    The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes.

  17. little sister: An Afro-Temporal Solo-Play.

    Science.gov (United States)

    De Berry, Misty

    2017-07-03

    little sister: An Afro-Temporal Solo-Play is at once a memory-scape and a mytho-biography set to poetry, movement, and mixed media. A performance poem spanning from the Antebellum South to present-moment Chicago, it tells the story of a nomadic spirit named little-she who shape-shifts through the memories and imaginings of her sister, the narrator. Through the characters little-she and the narrator, the solo-performance explores embodied ways to rupture and relieve the impact of macro forms of violence in the micro realm of the everyday. To this end, little sister witnesses and disrupts the legacy of violence in the lives of queer Black women through a trans-temporal navigation of everyday encounters within familial, small groups and intimate partner spaces.

  18. 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...

  19. 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.

  20. The Lehman Sisters Hypothesis

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2014-01-01

    markdownabstract__Abstract__ This article explores the Lehman Sisters Hypothesis. It reviews empirical literature about gender differences in behavioral, experimental, and neuro-economics as well as in other fields of behavioral research. It discusses gender differences along three dimensions of

  1. Organization of Sisters of Mercy During World War One

    Directory of Open Access Journals (Sweden)

    Sribnaia Anna

    2014-10-01

    Full Text Available The article examines the labour organization of Russian sisters of mercy during World War One. The author indicates two periods which took place before and after the February Revolution. Based on archive documents and offi cial publications the article describes general structure of Russian Red Cross Society institutions and basic principles of sisters of mercy communities’ work. It examines the rules of new sisters’ employment, their training, service assignment and professional duties. The emphasis is put on nurses’ work in wartime. During first years of war sisters’ position was stable. Due to specifi c hierarchy in the managing structure sisters’ work was productive and demanded. After the February Revolution the managing system changed drastically as well as the status of sisters of mercy and their reception in society. The author gives a thorough examination of sisters’ position after reorganization of Russian Red Cross Society. In time of political instability Russian sisters of mercy were able to organize themselves into one big organization thus creating All-Russian Union of Sisters of Mercy. This article for the first time ever implements into scientific research a huge amount of documents which allowed a signifi cant extension of views on Bolsheviks’ political approaches to Russian Red Cross Society and institution of sisters of mercy.

  2. 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)

  3. 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

  4. "Sister to the tailor"

    DEFF Research Database (Denmark)

    Simonton, Deborah

    2017-01-01

    Milliners, and their sisters, mantuamakers, modistes and marchandes de mode, were skilled artisans, businesswomen and tradeswomen. During the eighteenth century, they commandeered the high-class sewing that set fashion and created stars of their most famous, like Rose Bertrand, milliner to Marie...

  5. Building International Relations for Children through Sister Schools.

    Science.gov (United States)

    Pryor, Carolyn B.

    1992-01-01

    Inspired by Sister Cities International and the NASSP's school-to-school exchange program, "sister school" pairings have proved to be workable educational programs with long-range impact on participants. Some post-cold war efforts include U.S.-USSR High School Academic Partnerships, Project Harmony, and Center for U.S.-USSR Initiatives.…

  6. 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.

  7. Mutation induction in repair-deficient strains of Drosophila

    International Nuclear Information System (INIS)

    Wuergler, F.E.; Graf, U.

    1980-01-01

    Experimental evidence indicates a polygenic control of mutagenesis in Drosophila melanogaster. In oocytes chromosome aberrations detected as half-translocations or dominant lethals depend on a repair system which in a number of genetically nonrelated strains shows different repair capacities. Sister chromatid exchanges are easily studied as ring chromosome losses. They develop through a genotype controlled mechanism from, premutational lesions. Stocks with particular pairs of third chromosomes were discovered in which increased sensitivity of larvae to the toxic effects of a monofunctional alkylating agent correlates with high frequencies of x-ray induced SCE's. Sex-linked mutagen-sensitive mutants could be shown to control mutation fixation: pronounced maternal effects were found when sperm carrying particular types of premutational lesions were introduced into different types of mutant oocytes. The mutant mus(1)101D1 was found to be unable to process lesions induced by the crosslinking agent nitrogen mustard into point mutations. Alkylation damage leads to increased point mutation frequencies in the excision repair deficient mutant mei-9L1, but to reduced frequencies in the post-replication repair deficient mutant mei-41D5. It became clear that the study of maternal effects on mutagenized sperm represents an efficient tool to analyze the gentic control of mutagenesis in the eukaryotic genome of Drosophila melanogaster

  8. Biological monitors for low levels of ionising radiation

    International Nuclear Information System (INIS)

    Mohankumar, M.N.; Jeevanram, R.K.

    1995-01-01

    The biological effects of high doses of ionising radiation are well understood and the methods of measurement of these doses well established. However the effects due to extremely low doses remain by and large uncertain. This is because of the fact that at such low doses no gross symptoms are seen. In fact, at these levels the occurrence of double strand breaks leading to the formation of chromosomal aberrations like dicentrics is rare and chances of mutation due to base damage are negligible. Hence neither chromosomal aberration studies nor mutational assays are useful for detecting doses of the order of a few milligray. Results of exhaustive work done by various laboratories indicate that below 20 mGy the chromosomal aberration technique based on scoring of dicentrics cannot distinguish between a linear or a threshold model. However indirect methods like unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs) appear to be promising for the detection of radiation exposures due to low levels of radiation. This report reviews the available literature on the biological effects of low levels of ionising radiation and highlights the merits and demerits of the various methods employed in the measurement of UDS and SCE. The phenomenon of radio-adaptive response (RAR) and its relation to DNA repair is also discussed. (author)

  9. Biomarkers of environmental genotoxicity: comparison of genetic damage induced in Trad-SH cells and human lymphocytes

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1999-01-01

    The report presents some of the results of genotoxicity of the environmental agents studied in somatic cells of Tradescantia and show similarity between responses of the Tradescantia stamen hair cells (Trad-SH) and human blood cells to the physical and chemical mutagens. In the studies in vitro chromosome aberrations (CA) and sister chromatid exchanges (SCE) were applied to evaluate genotoxicity of pesticides. For comparison of genotoxic effectiveness of agrochemicals with other chemicals, there are also presented results of the genotoxicity of well-known mutagens (EMS, X-rays). The results confirm that in the environment a chemical pollution might cause higher genetic risk than radiation. Trad-SH assay was applied for in situ monitoring of the ambient air mutagenicity caused by benzene and petroleum associated compounds. The studies showed that gene mutation frequencies were slightly dependent on the distance from the petroleum work center. Results of measures of the cell cycle factor have shown also that the chemical pollutants in the air played also an important role in physiological cellular processes. The similarity of the Trad-SH and human blood cells responses to the physical and chemical mutagens showed that the gene mutations in Tradescantia present a simple and sensitive model, which can be very useful in biological monitoring

  10. [Two Dutch sisters in analysis with Freud].

    Science.gov (United States)

    Stroeken, Harry

    2010-01-01

    The author provides persuasive or at least plausible data for the identity of two patients recorded by Freud in his working season of 1910/11. They were two sisters, living in The Hague/Leiden, who came from a rich banker's family, the van der Lindens. Whereas the treatment does not seem to have led to any decisive improvement for the older of the two, it may have encouraged the younger sister to seek divorce.

  11. 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

  12. 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...

  13. 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

  14. 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...

  15. 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...

  16. 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

  17. Genotoxic and Cytotoxic Studies of Beta-Sitosterol and Pteropodine in Mouse

    Directory of Open Access Journals (Sweden)

    R. Paniagua-Pérez

    2005-01-01

    Full Text Available Beta-sitosterol (BS and pteropodine (PT are constituents of various plants with pharmacological activities potentially useful to man. The chemicals themselves possess biomedical properties related to the modulation of the immune and the nervous systems, as well as to the inflammatory process. Therefore, safety evaluation of the compounds is necessary in regard to their probable beneficial use in human health. The present study evaluates their genotoxic and cytotoxic potential by determining the capacity of the compounds to induce sister chromatid exchanges (SCE, or to alter cellular proliferation kinetics (CPK and the mitotic index (MI in mouse bone marrow cells. Besides, it also determines their capacity to increase the rate of micronucleated polychromatic erythrocytes (MNPE in peripheral mouse blood, and the relationship polychromatic erythrocytes/normochromatic erythrocytes (PE/NE as an index of cytotoxicity. For the first assay, four doses of each compound were tested: 200, 400, 600, and 1000 mg/kg in case of BS, and 100, 200, 300, and 600 mg/kg for PT. The results in regard to both agents showed no SCE increase induced by any of the tested doses, as well as no alteration in the CPK, or in the MI. With respect to the second assay, the results obtained with the two agents were also negative for both the MNPE and the PE/NE index along the daily evaluation made for four days. In the present study, the highest tested dose corresponded to 80% of the LD50 obtained for BS and to 78% in the case of PT. The results obtained establish that the studied agents have neither genotoxic nor cytotoxic effect on the model used, and therefore they encourage studies on their pharmacological properties.

  18. Efeitos genotóxicos e alterações de enzimas hepáticas em trabalhadores do refino de petróleo Genotoxic effects and hepatic enzymes alterations among petroleum refinery workers

    Directory of Open Access Journals (Sweden)

    Rozana Oliveira Gonçalves

    2005-10-01

    Full Text Available Um estudo de casos e controles, aninhado num estudo de coorte, investigou a associação entre efeitos genotóxicos e alteração de enzimas hepáticas em trabalhadores de uma refinaria de petróleo do Nordeste. Foram examinados todos os dez novos casos de alterações de enzimas hepáticas - gama-glutamil transferase (GGT e alanina aminotransferase (ALT - ocorridos em 2002. Dez trabalhadores sem alterações de GGT ou ALT foram selecionados como controles. Os efeitos do fumo, sexo, idade e consumo de café foram controlados. O efeito genotóxico foi avaliado pela técnica de trocas entre cromátides irmãs (TCI e alterações cromossômicas (AC estruturais. As médias de TCI por célula (3,92 ± 1,04 versus 4,25 ± 1,47 e de ACE (8,85 ± 3,4 versus 9,1 ± 3,7 não diferiram de forma significante entre casos e controles respectivamente.A case-control study, nested in a cohort study, investigated the association between genotoxic effects and hepatic enzymes alterations among workers in a petroleum refinery, Northeast Brazil. Ten cases of hepatic enzymes alterations - gamma-glutamyltransferase (GGT and Alanine aminotransferase (ALT - representing all incident cases occurring in the refinery during 2002, were examined. Ten workers without GGT and ALT alterations were selected as controls. The effects of smoking, sex, age and coffee consumption were controlled. The genotoxic effects were evaluated by the sister chromatid exchange (SCE and by the chromosomal aberrations (CA techniques. Mean SCE per cell (3.92 ± 1.04 versus 4.25 ± 1.47 and CA per cell (8.85 ± 3.4 versus 9.1 ± 3.7 did not differ significantly between cases and controls respectively.

  19. 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 ...

  20. 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 ...

  1. 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

  2. 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.

  3. 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 ...

  4. 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

  5. Sister Mary Emil Penet, I.H.M.: Founder of the Sister Formation Conference

    Science.gov (United States)

    Glisky, Joan

    2006-01-01

    Mary Emil Penet, I.H.M., (1916-2001) used her talents and charisma to shape the first national organization of American women religious, the Sister Formation Conference (SFC; 1954-1964), facilitating the integrated intellectual, spiritual, psychological, and professional development of vowed women religious. In the decade preceding Vatican II, her…

  6. Structure of the I-SceI nuclease complexed with its dsDNA target and three catalytic metal ions

    DEFF Research Database (Denmark)

    Prieto, Jesús; Redondo, Pilar; Merino, Nekane

    2016-01-01

    Homing endonucleases are highly specific DNA-cleaving enzymes that recognize and cleave long stretches of DNA. The engineering of these enzymes provides instruments for genome modification in a wide range of fields, including gene targeting. The homing endonuclease I-SceI from the yeast Saccharom......Homing endonucleases are highly specific DNA-cleaving enzymes that recognize and cleave long stretches of DNA. The engineering of these enzymes provides instruments for genome modification in a wide range of fields, including gene targeting. The homing endonuclease I-SceI from the yeast...... experiments were performed in the presence of Mn(2+), yielding crystals that were suitable for X-ray diffraction analysis. The crystals belonged to the orthorhombic space group P212121, with unit-cell parameters a = 80.11, b = 80.57, c = 130.87 Å, α = β = γ = 90°. The self-rotation function and the Matthews...

  7. 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

  8. Three Sisters Dam modifications and performance

    Energy Technology Data Exchange (ETDEWEB)

    Courage, L.J.R. [Monenco AGRA Inc., Calgary, AB (Canada)

    1995-12-31

    Recent modifications and maintenance carried out at the Three Sisters Dam, in the Alberta Rockies south of the town of Canmore, were described. A detailed account was given of the dam`s geological setting, its abnormally high leakage through the foundation and its sinkhole activity. Results of studies aimed at finding the cause of leakage and sinkhole occurrences were reviewed. Modifications made to the dam since 1951 were detailed, as were modifications to handle probable maximum flood levels. Three approaches for estimating failure probabilities after identification of failure modes were described. The overall conclusion was that based on constant leakage, no settlement in the dam, penstocks, or the powerhouse since construction, the Three Sisters Dam was stable. 1 ref.

  9. Reconstitution of Nucleosomes with Differentially Isotope-labeled Sister Histones.

    Science.gov (United States)

    Liokatis, Stamatios

    2017-03-26

    Asymmetrically modified nucleosomes contain the two copies of a histone (sister histones) decorated with distinct sets of Post-translational Modifications (PTMs). They are newly identified species with unknown means of establishment and functional implications. Current analytical methods are inadequate to detect the copy-specific occurrence of PTMs on the nucleosomal sister histones. This protocol presents a biochemical method for the in vitro reconstitution of nucleosomes containing differentially isotope-labeled sister histones. The generated complex can be also asymmetrically modified, after including a premodified histone pool during refolding of histone subcomplexes. These asymmetric nucleosome preparations can be readily reacted with histone-modifying enzymes to study modification cross-talk mechanisms imposed by the asymmetrically pre-incorporated PTM using nuclear magnetic resonance (NMR) spectroscopy. Particularly, the modification reactions in real-time can be mapped independently on the two sister histones by performing different types of NMR correlation experiments, tailored for the respective isotope type. This methodology provides the means to study crosstalk mechanisms that contribute to the formation and propagation of asymmetric PTM patterns on nucleosomal complexes.

  10. GNE Myopathy in Turkish Sisters with a Novel Homozygous Mutation

    Science.gov (United States)

    Diniz, Gulden; Secil, Yaprak; Ceylaner, Serdar; Tokucoglu, Figen; Türe, Sabiha; Celebisoy, Mehmet; İncesu, Tülay Kurt; Akhan, Galip

    2016-01-01

    Background. Hereditary inclusion body myopathy is caused by biallelic defects in the GNE gene located on chromosome 9p13. It generally affects adults older than 20 years of age. Methods and Results. In this study, we present two Turkish sisters with progressive myopathy and describe a novel mutation in the GNE gene. Both sisters had slightly higher levels of creatine kinase (CK) and muscle weakness. The older sister presented at 38 years of age with an inability to climb steps, weakness, and a steppage gait. Her younger sister was 36 years old and had similar symptoms. The first symptoms of the disorder were seen when the sisters were 30 and 34 years old, respectively. The muscle biopsy showed primary myopathic features and presence of rimmed vacuoles. DNA analysis demonstrated the presence of previously unknown homozygous mutations [c.2152 G>A (p.A718T)] in the GNE genes. Conclusion. Based on our literature survey, we believe that ours is the first confirmed case of primary GNE myopathy with a novel missense mutation in Turkey. These patients illustrate that the muscle biopsy is still an important method for the differential diagnosis of vacuolar myopathies in that the detection of inclusions is required for the definitive diagnosis. PMID:27298745

  11. Geographic variance of cardiovascular risk factors among community women: the national Sister to Sister campaign.

    Science.gov (United States)

    Jarvie, Jennifer L; Johnson, Caitlin E; Wang, Yun; Wan, Yun; Aslam, Farhan; Athanasopoulos, Leonidas V; Pollin, Irene; Foody, JoAnne M

    2011-01-01

    There are substantial variations in cardiovascular disease (CVD) risk and outcomes among women. We sought to determine geographic variation in risk factor prevalence in a contemporary sample of U.S. women. Using 2008-2009 Sister to Sister (STS) free heart screening data from 17 U.S. cities, we compared rates of obesity (body mass index [BMI] ≥30 kg/m(2)), hypertension (HTN ≥140/90 mm Hg), low high-density lipoprotein cholesterol (HDL-C cities had higher rates of hyperglycemia and low HDL-C. In a large, community-based sample of women nationwide, this comprehensive analysis shows remarkable geographic variation in risk factors, which provides opportunities to improve and reduce a woman's CVD risk. Further investigation is required to understand the reasons behind such variation, which will provide insight toward tailoring preventive interventions to narrow gaps in CVD risk reduction in women.

  12. 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 ...

  13. 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...

  14. 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

  15. 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...

  16. 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

  17. 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.

  18. 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

  19. Alkylarylnitrosoureas--stability in aqueous solution, partition coefficient, alkylating activity and its relationship to SCE induction in Chinese hamster V 79-E cells.

    Science.gov (United States)

    Mendel, J; Thust, R; Schwarz, H

    1982-01-01

    The alkylating activity, chemical stability in aqueous solution (pH 7.0; 37 degrees C), and partition coefficient (octanol/water) of the following compounds were determined: 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1-isopropyl-3-phenyl-1-nitrosourea (i-PrPNU), 1-methyl-3-(p-fluorophenyl)-1-nitrosourea (F-MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (Cl-MPNU), 1-methyl-3-(p-bromophenyl)-1-nitrosourea (Br-MPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU), and 1-methyl-3-naphthyl-1-nitrosocarbamate (NCA). 1-Methyl-1-nitrosourea (MNU) and 1-ethyl-1-nitrosourea (ENU) were used for the comparison. THe rate of decomposition in aqueous solution is discussed concerning the influences of the substituents at the 1- and 3-N-atom. The mono- and disubstituted N-nitrosoureas showed a coarse correlation between alkylating activity and SCE induction in Chinese hamster V 79-E cells. On the other hand, this correlation is missing in the case of NCA, which is a potent SCE inducer despite relatively low alkylating activity. DMPNU is the strongest SCE inducer, but this compound shows a high stability in aqueous solution and, consequently, we were not able to detect an alkylating activity.

  20. Dam safety at Seven Sisters Generating Station

    International Nuclear Information System (INIS)

    Carson, R. W.; Gupta, R. C.

    1996-01-01

    A safety surveillance program for all hydraulic structures in Manitoba was first implemented in 1979, and updated in 1988. This contribution describes the current status of the program, and the nature of the issues that the program was designed to address. The Seven Sisters Station's dam on the Winnipeg River, about 90 km northeast of the City of Winnipeg, was used as an example. Extensive reviews of flood risks and downstream inundation potential at Seven Sisters' revealed a number of deficiencies; these findings will be incorporated into a corporate plan of overall remediation. Updating the program will also include efforts to ensure adherence to national dam safety guidelines. 5 figs

  1. Geologic map of Three Sisters volcanic cluster, Cascade Range, Oregon

    Science.gov (United States)

    Hildreth, Wes; Fierstein, Judy; Calvert, Andrew T.

    2012-01-01

    The cluster of glaciated stratovolcanoes called the Three Sisters—South Sister, Middle Sister, and North Sister—forms a spectacular 20-km-long reach along the crest of the Cascade Range in Oregon. The three eponymous stratocones, though contiguous and conventionally lumped sororally, could hardly display less family resemblance. North Sister (10,085 ft), a monotonously mafic edifice at least as old as 120 ka, is a glacially ravaged stratocone that consists of hundreds of thin rubbly lava flows and intercalated falls that dip radially and steeply; remnants of two thick lava flows cap its summit. Middle Sister (10,047 ft), an andesite-basalt-dacite cone built between 48 and 14 ka, is capped by a thick stack of radially dipping, dark-gray, thin mafic lava flows; asymmetrically glaciated, its nearly intact west flank contrasts sharply with its steep east face. Snow and ice-filled South Sister is a bimodal rhyolitic-intermediate edifice that was constructed between 50 ka and 2 ka; its crater (rim at 10,358 ft) was created between 30 and 22 ka, during the most recent of several explosive summit eruptions; the thin oxidized agglutinate that mantles its current crater rim protects a 150-m-thick pyroclastic sequence that helped fill a much larger crater. For each of the three, the eruptive volume is likely to have been in the range of 15 to 25 km³, but such estimates are fairly uncertain, owing to glacial erosion. The map area consists exclusively of Quaternary volcanic rocks and derivative surficial deposits. Although most of the area has been modified by glaciation, the volcanoes are young enough that the landforms remain largely constructional. Furthermore, twelve of the 145 eruptive units on the map are postglacial, younger than the deglaciation that was underway by about 17 ka. The most recent eruptions were of rhyolite near South Sister, about 2,000 years ago, and of mafic magma near McKenzie Pass, about 1,500 years ago. As observed by trailblazing volcanologist

  2. 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 ...

  3. 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...

  4. 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.

  5. 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.

  6. Biological monitors for low levels of ionising radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mohankumar, M N; Jeevanram, R K [Safety Research and Health Physics Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India)

    1996-12-31

    The biological effects of high doses of ionising radiation are well understood and the methods of measurement of these doses well established. However the effects due to extremely low doses remain by and large uncertain. This is because of the fact that at such low doses no gross symptoms are seen. In fact, at these levels the occurrence of double strand breaks leading to the formation of chromosomal aberrations like dicentrics is rare and chances of mutation due to base damage are negligible. Hence neither chromosomal aberration studies nor mutational assays are useful for detecting doses of the order of a few milligray. Results of exhaustive work done by various laboratories indicate that below 20 mGy the chromosomal aberration technique based on scoring of dicentrics cannot distinguish between a linear or a threshold model. However indirect methods like unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs) appear to be promising for the detection of radiation exposures due to low levels of radiation. This report reviews the available literature on the biological effects of low levels of ionising radiation and highlights the merits and demerits of the various methods employed in the measurement of UDS and SCE. The phenomenon of radio-adaptive response (RAR) and its relation to DNA repair is also discussed. (author). 98 refs., 11 figs., 4 tabs.

  7. 20 CFR 725.225 - Determination of dependency; parent, brother, or sister.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Determination of dependency; parent, brother, or sister. 725.225 Section 725.225 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION... Benefits) § 725.225 Determination of dependency; parent, brother, or sister. An individual who is the miner...

  8. 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 ...

  9. 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.

  10. 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)

  11. [Florence Nightingale and charity sisters: revisiting the history].

    Science.gov (United States)

    Padilha, Maria Itayra Coelho de Souza; Mancia, Joel Rolim

    2005-01-01

    This study presents an historical analysis on the links between the nursing practice and the influence received from various religious orders/associations along the times, especially from Saint Vincent Paul's charity sisters. The professional nursing which was pioneered by Florence Nightingale in the XlXth century, was directly influenced by the teachings of love and fraternity. In addition, other contributions from the religious orders/associations were the concepts of altruism, valorization of an adequate environment for the care of patients, and the division of work in nursing. The study shows the influence of Charity Sisters on Florence Nightingale.

  12. Clouston′s Disease in Three Sisters

    Directory of Open Access Journals (Sweden)

    Jayakar Thomas

    1988-01-01

    Full Text Available In a family of four children, all females, three sisters presented with Clouston′s disease or hidrotic ectodermal dysplasia. The case is reported for the rarity of presentation in a single generation with no history of other family members affected.

  13. Friel and his "sisters"

    Directory of Open Access Journals (Sweden)

    Nicholas Grene

    2010-11-01

    Full Text Available This essay, occasioned by a revival of Brian Friel's version of Chekhov's Three Sisters at the Abbey Theatre in 2008, considers the circumstances surrounding its first production by the Field Day Theatre Company in 1981, and the motivation behind the decision to translate Chekhov's text into a specifically Irish dialect of English. It also analyses how Friel's plays since that date, notably the award-winning Dancing at Lughnasa (1990, have changed our perspective on the play.

  14. 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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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.)

  19. Sisters Hope - Protected by the Fiction

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Hallberg, Gry Worre

    2011-01-01

    In this article we will introduce the fictional and art-pedagogical universe of Sisters Hope and describe how it in different ways transcends into contexts beyond the art world and thus functions as a tool to democratize the aesthetic dimension and mode of being within high schools, academia...

  20. Comparison of Performance between Genetic Algorithm and SCE-UA for Calibration of SCS-CN Surface Runoff Simulation

    OpenAIRE

    Jeon, Ji-Hong; Park, Chan-Gi; Engel, Bernard

    2014-01-01

    Global optimization methods linked with simulation models are widely used for automated calibration and serve as useful tools for searching for cost-effective alternatives for environmental management. A genetic algorithm (GA) and shuffled complex evolution (SCE-UA) algorithm were linked with the Long-Term Hydrologic Impact Assessment (L-THIA) model, which employs the curve number (SCS-CN) method. The performance of the two optimization methods was compared by automatically calibrating L-THI...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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....

  6. Comparison of new nitrosoureas esters with modified steroidal nucleus for cytogenetic and antineoplastic activity.

    Science.gov (United States)

    Hussein, A; Mioglou-Kalouptsi, E; Papageorgiou, A; Karapidaki, I; Iakovidou-Kritsi, Z; Lialiaris, T; Xrysogelou, E; Camoutsis, C; Mourelatos, D

    2007-01-01

    Nitrosourea is decomposed under physiological conditions to react with biological macromolecules by two mechanisms: alkylation (with proteins and nucleic acids) and carbamoylation (with proteins but not nucleic acids). It has been suggested that the alkylating action is responsible for the therapeutic effects of nitrosoureas, and that the carbamoylation activity leads to toxicity effects. In order to reduce systemic toxicity and improve specificity and distribution for cancer therapy, 2-haloethyl nitrosourea has been esterified with modified steroids, which are used as biological platforms for transporting the alkylating agent to the tumor site in a specific manner. The cytogenetic and antineoplastic effect were studied of seven newly synthesized esters of N,N-bis(2-chloroethyl)alanyl carboxyl derivatives with a modified steroidal nucleus (compounds 1-7). As a very sensitive indicator of genotoxicity the Sister Chromatid Exchange (SCE) assay was used and as a valuable marker of cytostatic activity the cell Proliferation Rate Index (PRI) in cultures of normal human lymphocytes was used. The order of magnitude of the cytogenetic activity on a molar basis (15, 30, 120 microM) of the compounds was 7>6>3>5>2>4>1. The most active compound 7 has an enlarged (seven carbon atoms) A ring modified with a lactam group (-NHCO-) with the nitrosourea moiety esterified at position 17 In the group of seven substances a correlation was observed between the magnitude of SCE response and the depression in PRI (r=-O, 65, p6>2>5>4>3>1 and on lympocytic P388 leukemia cells is 7>2>6>5>4>3>1. The present results are in agreement with previous suggestions that the effectiveness in cytogenetic activity may well be correlated with antitumor effects [T/C: 248% for the compound 7 in 250 mg/kg b.w.; T/C: mean survival time of drug-treated animals (T) (excluding long term survivals) vs. corn-oil-treated controls (C)].

  7. Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

    International Nuclear Information System (INIS)

    Campos-Nebel, Marcelo de; Larripa, Irene; Gonzalez-Cid, Marcela

    2008-01-01

    Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by γH2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU-induced DSB

  8. Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Campos-Nebel, Marcelo de [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)], E-mail: mnebel@hematologia.anm.edu.ar; Larripa, Irene; Gonzalez-Cid, Marcela [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)

    2008-11-10

    Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by {gamma}H2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU

  9. Novel glyceryl glucoside is a low toxic alternative for cryopreservation agent

    Energy Technology Data Exchange (ETDEWEB)

    Su, Cathy; Allum, Allison J. [Department of Environmental & Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523 (United States); Aizawa, Yasushi [Research and Development Group, Toyo Sugar Refining Co. Ltd., Tokyo 103-0046 (Japan); Kato, Takamitsu A., E-mail: Takamitsu.Kato@Colostate.edu [Department of Environmental & Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523 (United States)

    2016-08-05

    Glyceryl glucoside (GG, α-D-glucosyglycerol) is a natural glycerol derivative found in alcoholic drinks. Recently GG has been used as an alternative for glycerol in cosmetic products. However, the safety of using GG is still unclear. Currently, dimethyl sulfoxide (DMSO) and glycerol are wildly used in cryopreservation. Despite GG being a derivative of glycerol, the ability of GG in cryopreservation is still unknown. By using a system of Chinese Hamster Ovary cells (CHO), A549 cells and AG1522 cells, the study examined the cryoprotective effects of DMSO, glycerol and GG. Cytotoxic and genotoxic responses induced by the three chemicals were also investigated with CHO to determine the safety of GG for cosmetic products. Our data suggests that GG has great cryopresearvation ability in the concentration of 30%–40% (v/v). For cytotoxic studies, DMSO showed the highest cytotoxicity above 3% (v/v) in cell doubling time delay among three chemicals. For the acute cytotoxicity with trypan blue dye exclusion assay, GG showed stronger cell killing effect within 24 h above 4% (v/v). For the continuous cytotoxicity with colony formation assay for 7 days, DMSO showed significantly reduced clonogenic ability above 2%. In genotoxicity studies, CHO treated with glycerol at 2% concentration induced three times higher frequencies of sister chromatid exchange (SCE) than background levels. GG did not induce significant amounts of SCE compared to background. Micronuclei formation was equally observed in the 2% and above concentrations of glycerol and GG. Our data showed that GG has significant effects on cryopreservation compared to DMSO. Glycerol and GG have similar cytotoxicity effects to CHO, but glycerol induced genotoxic responses in the same concentration. Therefore, we conclude that GG may be a safer alternative compound to glycerol in cosmetic products and safer alternative to DMSO in cryopreservation. -- Highlights: •Glyceryl Glucoside is low cytotoxicity and genotoxicity

  10. Radiation Exposure by Nuclear Medicine Imaging Procedures: Case Study

    International Nuclear Information System (INIS)

    Kopjar, N.; Marovic, G.; Prlic, I.; Sencar, J.; Zeljezic, D.; Ramic, S.

    2013-01-01

    Using high-resolution gamma spectrometry, we investigated the activity concentrations of thallium radioisotopes in a urine sample collected during a period of 24 h following nuclear medicine cardiac imaging. As part of a thallium stress test the subject of the study received a radiopharmaceutical preparation with 201Tl (activity 111 MBq). In order to assess whether the cardiac imaging procedure resulted in lymphocyte genome damage, we studied the frequency of sister chromatid exchanges (SCE) and lymphocyte cell kinetics in the blood samples collected before and after the cardiac imaging. The highest activity concentration (538960.9 ± 405.9 Bq/L u rine) was estimated for 201Tl, followed by 1770.54 ± 3.57 Bq/L u rine for 202Tl, and 422.035 ± 2.091 Bq/Lurine for 200Tl. The applied radiopharmaceutical contained 99.595 % of 201Tl, 0.078 % of 200Tl and 0.327 % of 202Tl. The estimated effective dose received through a single exposure to the radiopharmaceutical and calculated for a period of two days was mostly affected by 201Tl (0.0453 mSv). Due to its half-life of 12.2 days, the contribution of 202Tl (0.0008 mSv) to the effective dose was also significant. Results of the cytogenetic analysis indicate that a single diagnostic exposure to thallium caused an increase of SCE frequency and decrease of the proliferation rate index (PRI). Both parameters normalized steadily 14 days after the cardiac imaging procedure, which is also in accord with data obtained in previous studies. Our results indicate the presence of impurities in the radiopharmaceutical which should contain only 201Tl. This calls for a stricter process of quality control for radiopharmaceuticals used in nuclear medical diagnostic procedures. In this particular case, we emphasize 'contamination' with 202Tl, whose contribution to the effective dose cannot be ignored if one takes into account that it has the longest half-life of all three thallium radioisotopes detected in the urine sample.(author)

  11. 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...

  12. 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

  13. Food Yields and Nutrient Analyses of the Three Sisters: A Haudenosaunee Cropping System

    Directory of Open Access Journals (Sweden)

    Jane Mt.Pleasant

    2016-11-01

    Full Text Available Scholars have studied The Three Sisters, a traditional cropping system of the Haudenosaunee (Iroquois, from multiple perspectives. However, there is no research examining food yields, defined as the quantities of energy and protein produced per unit land area, from the cropping system within Iroquoia. This article compares food yields and other nutrient contributions from the Three Sisters, comprised of interplanted maize, bean and pumpkin, with monocultures of these same crops. The Three Sisters yields more energy (12.25 x 106 kcal/ha and more protein (349 kg/ha than any of the crop monocultures or mixtures of monocultures planted to the same area. The Three Sisters supplies 13.42 people/ha/yr. with energy and 15.86 people/ha/yr. with protein. Nutrient contents of the crops are further enhanced by nixtamalization, a traditional processing technique where maize is cooked in a high alkaline solution. This process increases calcium, protein quality, and niacin in maize.

  14. Genetic Damage Induced by Accidental Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Beatriz Pérez-Cadahía

    2006-01-01

    Full Text Available Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC, and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE, micronucleus (MN test, and comet assay. Four groups of individuals were included: volunteers (V, hired manual workers (MW, hired high-pressure cleaner workers (HPW and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate.

  15. The cyto- and genotoxicity of organotin compounds is dependent on the cellular uptake capability

    International Nuclear Information System (INIS)

    Dopp, E.; Hartmann, L.M.; Recklinghausen, U. von; Florea, A.M.; Rabieh, S.; Shokouhi, B.; Hirner, A.V.; Obe, G.; Rettenmeier, A.W.

    2007-01-01

    Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability

  16. [Analysis of genomic copy number variations in two sisters with primary amenorrhea and hyperandrogenism].

    Science.gov (United States)

    Zhang, Yanliang; Xu, Qiuyue; Cai, Xuemei; Li, Yixun; Song, Guibo; Wang, Juan; Zhang, Rongchen; Dai, Yong; Duan, Yong

    2015-12-01

    To analyze genomic copy number variations (CNVs) in two sisters with primary amenorrhea and hyperandrogenism. G-banding was performed for karyotype analysis. The whole genome of the two sisters were scanned and analyzed by array-based comparative genomic hybridization (array-CGH). The results were confirmed with real-time quantitative PCR (RT-qPCR). No abnormality was found by conventional G-banded chromosome analysis. Array-CGH has identified 11 identical CNVs from the sisters which, however, overlapped with CNVs reported by the Database of Genomic Variants (http://projects.tcag.ca/variation/). Therefore, they are likely to be benign. In addition, a -8.44 Mb 9p11.1-p13.1 duplication (38,561,587-47,002,387 bp, hg18) and a -80.9 kb 4q13.2 deletion (70,183,990-70,264,889 bp, hg18) were also detected in the elder and younger sister, respectively. The relationship between such CNVs and primary amenorrhea and hyperandrogenism was however uncertain. RT-qPCR results were in accordance with array-CGH. Two CNVs were detected in two sisters by array-CGH, for which further studies are needed to clarify their correlation with primary amenorrhea and hyperandrogenism.

  17. Three Sisters Dam: Investigations and monitoring

    International Nuclear Information System (INIS)

    Slopek, R.J.; Courage, L.J.R.; Keys, R.A.

    1990-01-01

    The geotechnical investigations, monitoring and interpretation of data associated with the evaluation of the Three Sisters Dam, which has been suffering from excessive seepage and is in need of enhancement, are outlined. The Three Sisters Dam is located in the continental ranges of the Rocky Mountains in Alberta, impounding the Spray Reservoir, and is founded on 60 m of interbedded sand, gravel, silt and clay layers. The computer code PC-SEEP was used to evaluate seepage. Details are provided of drilling, ground-penetrating radar surveys, seismic surveys, penstock inspection, sinkhole activity, piezometer monitoring, silt wells, settlement monuments, and tailrace monitoring. The intensive investigations of the foundations showed that they consist of a complex formation of interfingered stratified layers and leases of talus and glaciofluvial deposits. Due to the depth and nature of these materials drill hole penetration was limited to the use of the Becker hammer. This equipment successfully delineated the major soil horizons of the foundation. The continued information attained from inspection, drilling, testing, radar surveys, seismic work, monitoring of piezometers, leakage, silt wells and settlement monuments indicated that there are no large voids within the foundation of the dam. 2 refs., 12 figs

  18. IMPLEMENTASI SISTER PROVINCE PROVINSI JAWA TENGAH DENGAN NEGARA BAGIAN QUEENSLAND AUSTRALIA DI BIDANG PERTANIAN

    Directory of Open Access Journals (Sweden)

    Reni Windiani

    2016-02-01

    Full Text Available Globalization on national context has insisted the central government to work together and share duties and rights with the local government in order to achieve the national interest.  In Indonesia, UU 32/2004 about local government provide the chance for them to become more active in foreign policy, such as doing the cooperation in sister province/sister city program. The Central Java Province had done many sister province/sister city program with some partners aboard, such as Fujian province (China, Chungchoeng buk-do province (South Korea and the Queensland province (Australia.  The cooperation cover many sectors such as agriculture, city and village development, transportation and tourism, industry, trade and infestation, education, science and technology, and other sectors that will be confer in advance. From all of the cooperation that have been done between Central Java Province and Queensland, the author, is interested to have research on farming, because central government has had many cows imported from Australia.  This research is become important because central java province is one of the major of national fresh meat distributors. This research is using a qualitative method, with descriptive type of research.  This research has three research questions: How effective is the Sister Province program in Central Java with the Queensland in farm sector? What is the obstacle that holds the Sister Province program in Central Java with the Queensland in farm sector? How is the prospect of Sister Province program in Central Java with the Queensland in farm sector? This result of this research is to prove that the implementation of Sister Province program in Central Java with the Queensland in farm sectors is not effective.  Some of the implementation variables of this program have not been fulfilled. Communication, financial resources and bureaucracy structure are some of the variables that have weakness on this program.  Act of

  19. IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister.

    LENUS (Irish Health Repository)

    Sills, Eric Scott

    2010-01-01

    BACKGROUND: Premature ovarian failure (POF) remains a clinically challenging entity because in vitro fertilisation (IVF) with donor oocytes is currently the only treatment known to be effective. METHODS: A 33 year-old nulligravid patient with a normal karyotype was diagnosed with POF; she had a history of failed fertility treatments and had an elevated serum FSH (42 mIU\\/ml). Oocytes donated by her dizygotic twin sister were used for IVF. The donor had already completed a successful pregnancy herself and subsequently produced a total of 10 oocytes after a combined FSH\\/LH superovulation regime. These eggs were fertilised with sperm from the recipient\\'s husband via intracytoplasmic injection and two fresh embryos were transferred to the recipient on day three. RESULTS: A healthy twin pregnancy resulted from IVF; two boys were delivered by caesarean section at 39 weeks\\' gestation. Additionally, four embryos were cryopreserved for the recipient\\'s future use. The sister-donor achieved another natural pregnancy six months after oocyte retrieval, resulting in a healthy singleton delivery. CONCLUSION: POF is believed to affect approximately 1% of reproductive age females, and POF patients with a sister who can be an oocyte donor for IVF are rare. Most such IVF patients will conceive from treatment using oocytes from an anonymous oocyte donor. This is the first report of births following sister-donor oocyte IVF in Ireland. Indeed, while sister-donor IVF has been successfully undertaken by IVF units elsewhere, this is the only known case where oocyte donation involved twin sisters. As with all types of donor gamete therapy, pre-treatment counselling is important in the circumstance of sister oocyte donation.

  20. Catholic nursing sisters and brothers and racial justice in mid-20th-century America.

    Science.gov (United States)

    Wall, Barbra Mann

    2009-01-01

    This historical article considers nursing's work for social justice in the 1960s civil rights movement through the lens of religious sisters and brothers who advocated for racial equality. The article examines Catholic nurses' work with African Americans in the mid-20th century that took place amid the prevailing social conditions of poverty and racial disempowerment, conditions that were linked to serious health consequences. Historical methodology is used within the framework of "bearing witness," a term often used in relation to the civil rights movement and one the sisters themselves employed. Two situations involving nurses in the mid-20th century are examined: the civil rights movement in Selma, Alabama, and the actions for racial justice in Chicago, Illinois. The thoughts and actions of Catholic sister and brother nurses in the mid-20th century are chronicled, including those few sister nurses who stepped outside their ordinary roles in an attempt to change an unjust system entirely.

  1. Living with a brother or sister with epilepsy: siblings' experiences.

    Science.gov (United States)

    Hames, Annette; Appleton, Richard

    2009-12-01

    There is conflicting evidence about the impact of disability upon siblings, and very little research on the siblings of children with epilepsy. There is some evidence that siblings who have less accurate information exhibit more distress. The aim of this study was to assess siblings' response to having a brother or sister with epilepsy and to begin to develop information for them. Parents of children attending paediatric neurology outpatient departments were invited to participate in a pilot study. Parents who consented to take part were asked if they had previously received information for siblings. Parents and siblings participated in a semi-structured interview and siblings were also invited to submit a personal account of living with a brother or sister who had epilepsy. Twenty-five families with a child with epilepsy aged 2.5-15 years initially agreed to take part. None of the families stated that they had ever seen or received any information specifically for siblings. Fourteen siblings from the 25 families, aged 8-25 years, provided a personal account of what it was like living with a brother or sister with epilepsy. Siblings' accounts included both negative and positive feelings, and specifically feelings of care and love for their sibling. This initial study suggests that siblings of children with epilepsy have many positive but also early negative feelings. The results are limited by the size of the study, the fact that most siblings were older sisters, and the mean time since diagnosis was 6 years. Finally, it is hoped that the personal accounts collected in this study will be published for the benefit of other siblings of children with epilepsy.

  2. Spinal involvement in Camptodactyly Arthropathy Coxa-vara Pericarditis (CACP) syndrome in two Yemeni sisters

    NARCIS (Netherlands)

    Emad, Yasser; Ragab, Yasser; Ibrahim, Osama; Khalifa, Maher; Dawood, Ahmed; Rasker, Johannes J.

    2017-01-01

    Aim of the work The objective of this clinical report is to describe the detailed magnetic resonance imaging (MRI) findings of the spine, knee and hip joints in two young sisters with Camptodactyly Arthropathy Coxa-vara Pericarditis (CACP) syndrome. Cases report In two young sisters, both had normal

  3. Brothers and Sisters of Adults with Mental Retardation: Gendered Nature of the Sibling Relationship.

    Science.gov (United States)

    Orsmond, Gael I.; Seltzer, Marsha Mailick

    2000-01-01

    Differences and similarities between 245 brothers and sisters of adults with mental retardation in the sibling relationship were examined. Sisters scored higher in the caregiving, companionship, and positive affect aspects of the sibling relationship. Sibling involvement increased over time, but was dependent upon changes in maternal health.…

  4. Two Sisters with Idiopathic Pulmonary Hemosiderosis

    Directory of Open Access Journals (Sweden)

    Mehmet Gencer

    2007-01-01

    Full Text Available Idiopathic pulmonary hemosiderosis (IPH is a rare cause of diffuse alveolar hemorrhage with unknown etiology. In the present report, the presentations of two sisters are described: one sister had IPH, eosinophilia and a high serum immunoglobulin E (IgE level; and the other had IPH, pneumothorax, eosinophilia and a high serum IgE level. Both cases had quite unusual presentations. The first patient was 23 years of age, and had suffered from dry cough and progressive dyspnea for four years. Her hemoglobin level was 60 g/L, total serum IgE level was 900 U/mL and eosinophilia was 9%. Her chest radiography revealed diffuse infiltration. She died due to respiratory failure. The second patient was 18 years of age. She had also suffered from dry cough and gradually increasing dyspnea for two years. She had partial pneumothorax in the right lung and diffuse infiltration in other pulmonary fields on chest radiography. Her hemoglobin level was 99 g/L, total serum IgE level was 1200 U/mL and eosinophilia was 8%. IPH was diagnosed by open lung biopsy. All these findings suggested that familial or allergic factors, as well as immunological factors, might have contributed to the etiology of IPH.

  5. Identical Twin Primigravid Sisters -Spontaneous Labour and ...

    African Journals Online (AJOL)

    We report 2 cases of identical twin sisters, the older sibling getting married 14 months earlier but both got pregnant for their first child at about the same time and were managed by the same Obstetrician and fell into spontaneous labour within a few hours of each other. Both were delivered by emergency caesarean section ...

  6. Freud on Brothers and Sisters: A Neglected Topic

    Science.gov (United States)

    Sherwin-White, Susan

    2007-01-01

    This paper explores Freud's developing thought on brothers and sisters, and their importance in his psychoanalytical writings and clinical work. Freud's work on sibling psychology has been seriously undervalued. This paper aims to give due recognition to Freud's work in this area. (Contains 1 note.)

  7. 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

  8. 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.

  9. National Report for the Netherlands ‘Study on the implementation of the Regulation 1435/2003 on the Statute for European Cooperative Society (SCE)’

    NARCIS (Netherlands)

    van der Sangen, G.J.H.

    2010-01-01

    This National Report contains an analysis of the implementation of the SCE assessing its attractiveness vis-a-vis the national cooperative business form, based on the legal research and a survey of the cooperative movement in the Netherlands. It will be an integral part of the European Commission's

  10. Broad phylogenomic sampling and the sister lineage of land plants.

    Directory of Open Access Journals (Sweden)

    Ruth E Timme

    Full Text Available The tremendous diversity of land plants all descended from a single charophyte green alga that colonized the land somewhere between 430 and 470 million years ago. Six orders of charophyte green algae, in addition to embryophytes, comprise the Streptophyta s.l. Previous studies have focused on reconstructing the phylogeny of organisms tied to this key colonization event, but wildly conflicting results have sparked a contentious debate over which lineage gave rise to land plants. The dominant view has been that 'stoneworts,' or Charales, are the sister lineage, but an alternative hypothesis supports the Zygnematales (often referred to as "pond scum" as the sister lineage. In this paper, we provide a well-supported, 160-nuclear-gene phylogenomic analysis supporting the Zygnematales as the closest living relative to land plants. Our study makes two key contributions to the field: 1 the use of an unbiased method to collect a large set of orthologs from deeply diverging species and 2 the use of these data in determining the sister lineage to land plants. We anticipate this updated phylogeny not only will hugely impact lesson plans in introductory biology courses, but also will provide a solid phylogenetic tree for future green-lineage research, whether it be related to plants or green algae.

  11. Psychopathology, childhood trauma, and personality traits in patients with borderline personality disorder and their sisters.

    Science.gov (United States)

    Laporte, Lise; Paris, Joel; Guttman, Herta; Russell, Jennifer

    2011-08-01

    The aim of this study was to document and compare adverse childhood experiences, and personality profiles in women with borderline personality disorder (BPD) and their sisters, and to determine how these factors impact current psychopathology. Fifty-six patients with BPD and their sisters were compared on measures assessing psychopathology, personality traits, and childhood adversities. Most sisters showed little evidence of psychopathology. Both groups reported dysfunctional parent-child relationships and a high prevalence of childhood trauma. Subjects with BPD reported experiencing more emotional abuse and intrafamilial sexual abuse, but more similarities than differences between probands and sisters were found. In multilevel analyses, personality traits of affective instability and impulsivity predicted DIB-R scores and SCL-90-R scores, above and beyond trauma. There were few relationships between childhood adversities and other measures of psychopathology. Sensitivity to adverse experiences, as reflected in the development of psychopathology, appears to be influenced by personality trait profiles.

  12. El naturalismo americano: Theodore Dreiser y Sister Carrie

    Directory of Open Access Journals (Sweden)

    Dolores G. ALONSO MULAS

    2009-08-01

    Full Text Available Para situar a un escritor, como Theodore Dreiser, y especialmente su novela Sister Carrie dentro de un movimiento literario y de una etapa determinada de la historia americana, es necesario dar un breve repaso al naturalismo, llegado a América a través de Stephen Crane

  13. "If I only touch her cloak": the Sisters of Charity of St. Joseph in New Orleans hospital, 1834-1860.

    Science.gov (United States)

    Kong, Hyejung Grace; Kim, Ock-Joo

    2015-04-01

    This study is about the Sisters of Charity of St. Joseph in New Orleans' Charity Hospital during the years between 1834 and 1860. The Sisters of Charity of St. Joseph was founded in 1809 by Saint Elizabeth Ann Bailey Seton (first native-born North American canonized in 1975) in Emmitsburg, Maryland. Seton's Sisters of Charity was the first community for religious women to be established in the United States and was later incorporated with the French Daughters of Charity of St. Vincent de Paul in 1850. A call to work in New Orleans' Charity Hospital in the 1830s meant a significant achievement for the Sisters of Charity, since it was the second oldest continuously operating public hospitals in the United States until 2005, bearing the same name over the decades. In 1834, Sister Regina Smith and other sisters were officially called to Charity Hospital, in order to supersede the existing "nurses, attendants, and servants," and take a complete charge of the internal management of Charity Hospital. The existing scholarship on the history of hospitals and Catholic nursing has not integrated the concrete stories of the Sisters of Charity into the broader histories of institutionalized medicine, gender, and religion. Along with a variety of primary sources, this study primarily relies on the Charity Hospital History Folder stored at the Daughters of Charity West Center Province Archives. Located in the "Queen city of the South," Charity Hospital was the center of the southern medical profession and the world's fair of people and diseases. Charity Hospital provided the sisters with a unique situation that religion and medicine became intertwined. The Sisters, as nurses, constructed a new atmosphere of caring for patients and even their families inside and outside the hospital, and built their own separate space within the hospital walls. As hospital managers, the Sisters of Charity were put in complete charge of the hospital, which was never seen in other hospitals. By

  14. 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...

  15. Cellular characterization of cells from the Fanconi anemia complementation group, FA-D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Buul, Paul P.W. van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Jaspers, Nicolaas G.J. [Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam (Netherlands); Elghalbzouri-Maghrani, Elhaam [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Duijn-Goedhart, Annemarie van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N.Copernicus University, Bydgoszcz (Poland)]. E-mail: M.Z.Zdzienicka@LUMC.nl

    2006-10-10

    Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability and hypersensitivity to DNA cross-linking agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane sulfonate (MMS), and like cells derived from other FA complementation groups, not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells were slightly sensitive to UV irradiation. Despite the observed lack of X-ray sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells displayed greatly enhanced levels of spontaneous as well as MMC-induced chromosomal aberrations (Canada), similar to cells deficient in homologous recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, both spontaneous as well as after MMC treatment. Hence, these data indicate that human cells with biallelic BRCA2 mutations display typical features of both FA- and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the integrated FA/BRCA DNA damage response pathway but also controls other functions outside the FA pathway.

  16. Cellular characterization of cells from the Fanconi anemia complementation group, FA-D1/BRCA2

    International Nuclear Information System (INIS)

    Godthelp, Barbara C.; Buul, Paul P.W. van; Jaspers, Nicolaas G.J.; Elghalbzouri-Maghrani, Elhaam; Duijn-Goedhart, Annemarie van; Arwert, Fre; Joenje, Hans; Zdzienicka, Malgorzata Z.

    2006-01-01

    Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability and hypersensitivity to DNA cross-linking agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane sulfonate (MMS), and like cells derived from other FA complementation groups, not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells were slightly sensitive to UV irradiation. Despite the observed lack of X-ray sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells displayed greatly enhanced levels of spontaneous as well as MMC-induced chromosomal aberrations (Canada), similar to cells deficient in homologous recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, both spontaneous as well as after MMC treatment. Hence, these data indicate that human cells with biallelic BRCA2 mutations display typical features of both FA- and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the integrated FA/BRCA DNA damage response pathway but also controls other functions outside the FA pathway

  17. Tritium: a model for low level long-term ionizing radiation exposure

    International Nuclear Information System (INIS)

    Carsten, A.L.

    1984-01-01

    The somatic, cytogenetic and genetic effects of single and chronic tritiated water (HTO) ingestion in mice was investigated. This study serves not only as an evaluation of tritium toxicity (TRITOX) but due to its design involving long-term low concentration ingestion of HTO may serve as a model for low level long-term ionizing radiation exposure in general. Long-term studies involved animals maintained on HTO at concentrations of 0.3 μCi/ml, 1.0 μCi/ml, 3.0 μCi/ml or depth dose equivalent chronic external exposures to 137 Cs gamma rays. Maintenance on 3.0 μCi/ml resulted in no effect on growth, life-time shortening or bone marrow cellularity, but did result in a reduction of bone marrow stem cells, an increase in DLM's in second generation animals maintained on this regimen and cytogenetic effects as indicated by increased sister chromatid exchanges (SCE's) in bone marrow cells, increased chromosome aberrations in the regenerating liver and an increase in micronuclei in red blood cells. Biochemical and microdosimetry studies showed that animals placed on the HTO regimen reached tritium equilibrium in the body water in approximately 17 to 21 days with a more gradual increase in bound tritium. When animals maintained for 180 days on 3.0 μCi/ml HTO were placed on a tap water regimen, the tritium level in tissue dropped from the equilibrium value of 2.02 μCi/ml before withdrawal to 0.001 μCi/ml at 28 days. 18 references

  18. 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)

  19. Sisters in hereditary breast and ovarian cancer families: communal coping, social integration, and psychological well-being.

    Science.gov (United States)

    Koehly, Laura M; Peters, June A; Kuhn, Natalia; Hoskins, Lindsey; Letocha, Anne; Kenen, Regina; Loud, Jennifer; Greene, Mark H

    2008-08-01

    We investigated the association between psychological distress and indices of social integration and communal coping among sisters from hereditary breast and ovarian cancer (HBOC) families. Sixty-five sisters from 31 HBOC families completed the Brief Symptom Inventory-18 and the Colored Eco-Genetic Relationship Map, which identified members of participants' social support networks. Hierarchical linear models were used for all analyses to account for the clustering of sisters within families. Intra-family correlation coefficients suggested that sisters shared perceptions of breast cancer risk and worry, but not ovarian cancer risk and worry. Further, sisters demonstrated shared levels of anxiety and somatization, but not depressive symptoms. Communal coping indices quantifying shared support resources were negatively related to anxiety and somatization. The number of persons with whom cancer risk information was shared exhibited a positive trend with somatization. Social integration, as measured by the size of participants' emotional support network, was negatively associated with anxiety. Lower depression scores were observed among participants with more persons playing multiple support roles and fewer persons providing tangible assistance. Understanding how support relationships impact well-being among persons adjusting to HBOC risk, and the particular role of family in that process, will facilitate developing appropriate management approaches to help cancer-prone families adjust to their cancer risk.

  20. Childhood obsessive-compulsive traits in anorexia nervosa patients, their unaffected sisters and healthy controls: a retrospective study.

    Science.gov (United States)

    Degortes, Daniela; Zanetti, Tatiana; Tenconi, Elena; Santonastaso, Paolo; Favaro, Angela

    2014-07-01

    Although there is evidence that childhood perfectionistic traits predate the onset of eating disorders, few studies to date have examined the prevalence and clinical correlates of these traits in patients with anorexia nervosa (AN) and their unaffected sisters. The aim of this work was to study the prevalence of childhood obsessive-compulsive traits in patients with lifetime AN, their unaffected sisters and healthy women. A total of 116 AN patients, 32 healthy sisters and 119 controls were assessed by the EATATE Interview to assess traits such as perfectionism, inflexibility, rule-bound traits, drive for order and symmetry, and excessive doubt and cautiousness. Both self-report and maternal reports were collected. AN patients reported more childhood obsessive-compulsive traits than their healthy sisters and controls. In contrast, no differences between healthy controls and unaffected sisters emerged. In patients with AN, a dose-response relationship was found between the number of childhood obsessive-compulsive traits and psychopathology, including body image distortion, thus indicating that these traits are an important feature to be considered in assessing and treating eating disorders. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

  1. 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...

  2. 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.

  3. 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....

  4. 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...

  5. 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....

  6. 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.

  7. Site- and strand-specific nicking of DNA by fusion proteins derived from MutH and I-SceI or TALE repeats.

    Science.gov (United States)

    Gabsalilow, Lilia; Schierling, Benno; Friedhoff, Peter; Pingoud, Alfred; Wende, Wolfgang

    2013-04-01

    Targeted genome engineering requires nucleases that introduce a highly specific double-strand break in the genome that is either processed by homology-directed repair in the presence of a homologous repair template or by non-homologous end-joining (NHEJ) that usually results in insertions or deletions. The error-prone NHEJ can be efficiently suppressed by 'nickases' that produce a single-strand break rather than a double-strand break. Highly specific nickases have been produced by engineering of homing endonucleases and more recently by modifying zinc finger nucleases (ZFNs) composed of a zinc finger array and the catalytic domain of the restriction endonuclease FokI. These ZF-nickases work as heterodimers in which one subunit has a catalytically inactive FokI domain. We present two different approaches to engineer highly specific nickases; both rely on the sequence-specific nicking activity of the DNA mismatch repair endonuclease MutH which we fused to a DNA-binding module, either a catalytically inactive variant of the homing endonuclease I-SceI or the DNA-binding domain of the TALE protein AvrBs4. The fusion proteins nick strand specifically a bipartite recognition sequence consisting of the MutH and the I-SceI or TALE recognition sequences, respectively, with a more than 1000-fold preference over a stand-alone MutH site. TALE-MutH is a programmable nickase.

  8. An illness in the family: Dr. Maude Abbott and her sister, Alice Abbott.

    Science.gov (United States)

    Brookes, Barbara

    2011-01-01

    This paper explores Maude Abbott's internationally significant career in medicine and her parallel commitment to caring for her sister, Alice Abbott. An examination of Abbott's life reveals the difficulties faced by an ambitious Canadian woman in medicine from the 1890s to the 1920s; difficulties compounded by caring for a sister with a mental illness. The Abbott archive suggests that it was far more difficult for a woman doctor to make the kind of sharp distinction between public and private life that might be expected of professional men.

  9. Sister chromosome pairing maintains heterozygosity in parthenogenetic lizards.

    Science.gov (United States)

    Lutes, Aracely A; Neaves, William B; Baumann, Diana P; Wiegraebe, Winfried; Baumann, Peter

    2010-03-11

    Although bisexual reproduction has proven to be highly successful, parthenogenetic all-female populations occur frequently in certain taxa, including the whiptail lizards of the genus Aspidoscelis. Allozyme analysis revealed a high degree of fixed heterozygosity in these parthenogenetic species, supporting the view that they originated from hybridization events between related sexual species. It has remained unclear how the meiotic program is altered to produce diploid eggs while maintaining heterozygosity. Here we show that meiosis commences with twice the number of chromosomes in parthenogenetic versus sexual species, a mechanism that provides the basis for generating gametes with unreduced chromosome content without fundamental deviation from the classic meiotic program. Our observation of synaptonemal complexes and chiasmata demonstrate that a typical meiotic program occurs and that heterozygosity is not maintained by bypassing recombination. Instead, fluorescent in situ hybridization probes that distinguish between homologues reveal that bivalents form between sister chromosomes, the genetically identical products of the first of two premeiotic replication cycles. Sister chromosome pairing provides a mechanism for the maintenance of heterozygosity, which is critical for offsetting the reduced fitness associated with the lack of genetic diversity in parthenogenetic species.

  10. Umbilical metastasis (Sister Mary Joseph's nodule diagnosed by fine-needle aspiration

    Directory of Open Access Journals (Sweden)

    Tatomirović Željka

    2004-01-01

    Full Text Available Sister Mary Joseph’s nodule is the eponym for metastatic involvement of the umbilicus. This less common entity is the sign of disseminated malignant disease, mainly of digestive and gynecologic origin, and is associated with a poor prognosis. A case of Sister Mary Joseph’s nodule in a 76-year-old woman in whom the umbilical metastasis was the first sign of malignant disease in presented. The diagnosis of metastatic adenocarcinoma was established by fine needle aspiration cytology of the umbilical nodule. Radiological and ultrasonographic investigation disclosed carcinoma of the gallbladder with pancreas, stomach, and colon invasion as well as peritoneal dissemination. The diagnosis was confirmed by exploratory laparatomy and histological examination of the excised umbilical nodule.

  11. Homing at an extragenic locus mediated by VDE (PI-SceI) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Nogami, Satoru; Fukuda, Tomoyuki; Nagai, Yuri; Yabe, Shizu; Sugiura, Masako; Mizutani, Ryuta; Satow, Yoshinori; Anraku, Yasuhiro; Ohya, Yoshikazu

    2002-06-30

    PI-SceI (VDE), a homing endonuclease with protein splicing activity, is a genomic parasite in the VMA1 gene of Saccharomyces cerevisiae. In a heterozygous diploid of the VDE-less VMA1 allele and a VDE-containing VMA1 allele, VDE specifically cleaves its recognition sequence (VRS) in the VDE-less VMA1 allele at meiosis, followed by 'homing', i.e. a conversion to a VDE-containing allele. We found that upon VDE expression, homing of a marker gene at an extragenic locus occurs only when a 45 bp element containing the VRS is inserted at its allelic site, while mutants of VDE with no endonuclease activity lack authentic extragenic homing activity. Thus, both the VRS and VDE are required for homing. Insertion of the VRS in a homozygous diploid significantly lowered the spore germination ability, indicating that a template for gene repair at its allelic locus is essential for efficient homing and survival of yeast cells. Copyright 2002 John Wiley & Sons, Ltd.

  12. The Lehman Sisters Hypothesis: an exploration of literature and bankers

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2012-01-01

    textabstractAbstract This article tests the Lehman Sisters Hypothesis in two complementary, although incomplete ways. It reviews the diverse empirical literature in behavioral, experimental, and neuroeconomics as well as related fields of behavioral research. And it presents the findings from an

  13. The Lehman Sisters Hypothesis: an exploration of literature and bankers

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2012-01-01

    textabstractThis article tests the Lehman Sisters Hypothesis in two complementary, although incomplete ways. It reviews the diverse empirical literature in behavioural, experimental, and neuroeconomics as well as related fields of behavioural research. And it presents the findings from an

  14. Extensive range overlap between heliconiine sister species: evidence for sympatric speciation in butterflies?

    Science.gov (United States)

    Rosser, Neil; Kozak, Krzysztof M; Phillimore, Albert B; Mallet, James

    2015-06-30

    Sympatric speciation is today generally viewed as plausible, and some well-supported examples exist, but its relative contribution to biodiversity remains to be established. We here quantify geographic overlap of sister species of heliconiine butterflies, and use age-range correlations and spatial simulations of the geography of speciation to infer the frequency of sympatric speciation. We also test whether shifts in mimetic wing colour pattern, host plant use and climate niche play a role in speciation, and whether such shifts are associated with sympatry. Approximately a third of all heliconiine sister species pairs exhibit near complete range overlap, and analyses of the observed patterns of range overlap suggest that sympatric speciation contributes 32%-95% of speciation events. Müllerian mimicry colour patterns and host plant choice are highly labile traits that seem to be associated with speciation, but we find no association between shifts in these traits and range overlap. In contrast, climatic niches of sister species are more conserved. Unlike birds and mammals, sister species of heliconiines are often sympatric and our inferences using the most recent comparative methods suggest that sympatric speciation is common. However, if sister species spread rapidly into sympatry (e.g. due to their similar climatic niches), then assumptions underlying our methods would be violated. Furthermore, although we find some evidence for the role of ecology in speciation, ecological shifts did not show the associations with range overlap expected under sympatric speciation. We delimit species of heliconiines in three different ways, based on "strict and " "relaxed" biological species concepts (BSC), as well as on a surrogate for the widely-used "diagnostic" version of the phylogenetic species concept (PSC). We show that one reason why more sympatric speciation is inferred in heliconiines than in birds may be due to a different culture of species delimitation in the two

  15. Ukrainian and European Baroque in the Context of “Sister Arts” Idea

    Directory of Open Access Journals (Sweden)

    Olga Shikirinskaya

    2015-08-01

    Full Text Available The article deals with the “Sister Arts” tradition as the interrelationship of various art forms (poetry, fiction, painting, theatre, music etc. relative to the Baroque period. “Sister Arts” criticism, based on E.G. Lessing essay “Laocoön…” uses the inter-art analogies to appreciate the importance of literature in the Arts, as well as to comprehend aspects of the modern approach to the synthesis of the arts. The article presents the aesthetic concept of Baroque art and its realization in architecture, sculpture, decorative and applied arts, music and literature on the background of the European and Ukrainian cultural tradition.

  16. 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.

  17. The development of SisterTalk: a cable TV-delivered weight control program for black women.

    Science.gov (United States)

    Gans, Kim M; Kumanyika, Shiriki K; Lovell, H Joan; Risica, Patricia M; Goldman, Roberta; Odoms-Young, Angela; Strolla, Leslie O; Decaille, Donna O; Caron, Colleen; Lasater, Thomas M

    2003-12-01

    Overweight and obesity have reached epidemic proportions in the United States, with black women disproportionately affected. SisterTalk is a weight control program designed specifically for delivery to black women via cable TV. The theoretical and conceptual frameworks and formative research that guided the development and cultural tailoring of SisterTalk are described. Social Action Theory was applied in the development of SisterTalk along with a detailed behavioral analysis of the way that black women view weight and weight loss within the context of their cultural and social realities. The entire intervention development process was framed using this information, rather than by changing only superficial aspects of program delivery. Community networking and both qualitative and quantitative interview techniques from the fields of social marketing and cultural anthropology were used to involve black women from Boston in the design and implementation of a program that would be practical, appealing, and culturally sensitive. Also discussed are strategies for evaluating the program, and lessons learned that might have broader applicability are highlighted. The development of the SisterTalk program could provide a useful starting point for development of successful weight control programs for black women in other parts of the United States as well as for other ethnic and racial groups.

  18. 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.

  19. Happiness matters : exploring the linkages between personality, personal happiness, and work-related psychological health among priests and sisters in Italy

    OpenAIRE

    Francis, Leslie J.; Crea, Giuseppe

    2017-01-01

    This study responds to the challenge posed by Rossetti’s work to explore the antecedents and consequences of individual differences in happiness among priests and religious sisters. The Oxford Happiness Questionnaire was completed together with measures of personality and work-related psychological health by 95 priests and 61 religious sisters. Overall the data demonstrated high levels of personal happiness among priests and religious sisters, but also significant signs of vulnerability. Pers...

  20. Do brothers and sisters of siblings with intelectual disability need the support of social work?

    OpenAIRE

    Cardová, Michaela

    2007-01-01

    This thesis explores the experience and support needs of siblings with a brother or sister with intellectual disability. Through review of what is a quite limited literature and from original qualitative research, involving interviews with siblings, the author examines their social reality, focusing especially on their relationships with their disabled brother or sister and with the wider society. Particular attention is given to identifying to what extent the siblings' lives are influenced b...

  1. 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....

  2. 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

  3. 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.

  4. 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.

  5. 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.)

  6. 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.

  7. 20 CFR 410.340 - Determination of relationship; parent, brother, or sister.

    Science.gov (United States)

    2010-04-01

    ... domiciled (see § 410.392) at the time of his death would find, under the law they would apply in determining..., brother, or sister. Where, under such law, the individual does not bear the relationship to the miner of...

  8. Conditional genomic rearrangement by designed meiotic recombination using VDE (PI-SceI) in yeast.

    Science.gov (United States)

    Fukuda, Tomoyuki; Ohya, Yoshikazu; Ohta, Kunihiro

    2007-10-01

    Meiotic recombination plays critical roles in the acquisition of genetic diversity and has been utilized for conventional breeding of livestock and crops. The frequency of meiotic recombination is normally low, and is extremely low in regions called "recombination cold domains". Here, we describe a new and highly efficient method to modulate yeast meiotic gene rearrangements using VDE (PI-SceI), an intein-encoded endonuclease that causes an efficient unidirectional meiotic gene conversion at its recognition sequence (VRS). We designed universal targeting vectors, by use of which the strain that inserts the VRS at a desired site is acquired. Meiotic induction of the strains provided unidirectional gene conversions and frequent genetic rearrangements of flanking genes with little impact on cell viability. This system thus opens the way for the designed modulation of meiotic gene rearrangements, regardless of recombinational activity of chromosomal domains. Finally, the VDE-VRS system enabled us to conduct meiosis-specific conditional knockout of genes where VDE-initiated gene conversion disrupts the target gene during meiosis, serving as a novel approach to examine the functions of genes during germination of resultant spores.

  9. 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.

  10. Induction of SCE by DNA cross-links in human fibroblasts exposed to 8-MOP and UVA irradiation

    International Nuclear Information System (INIS)

    Bredberg, A.; Lambert, B.

    1983-01-01

    To study the SCE-inducing effect of psoralen cross-links in the DNA of normal, human fibroblasts, cell cultures were exposed to PUVA (0.2-1 μg of 8-MOP per ml, followed by UVA irradiation at 0.04 J/cm 2 ) and carefully washed to remove non-covalently bound psoralen. Some cell cultures were then given a second dose of UVA (1.1 J/cm 2 ), either immediately after PUVA or 1-3 days later. By this type of treatment, cells with different proportions of DNA cross-links are obtained. The initial PUVA treatment will mainly give rise to psoralen monoadducts and only few cross-links in the DNA, and the second UVA irradiation will convert a number of the psoralen monoadducts into cross-links. (orig./AJ)

  11. 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)

  12. Bartter syndrome in two sisters with a novel mutation of the CLCNKB gene, one with deafness.

    Science.gov (United States)

    Robitaille, Pierre; Merouani, Aicha; He, Ning; Pei, York

    2011-09-01

    This article describes two sisters with type III Bartter syndrome (BS) due to a novel missense variant of the CLCNKB gene. The phenotypic expression of the disease was very different in these two siblings. In one sister, the disease followed a very severe course, especially in the neonatal period and as a toddler. Both the classic symptoms and the biochemical features of the syndrome were striking. In addition, she presented with sensorineural deafness, a complication yet unreported in this subtype of BS In contrast, the least affected sister was symptom free and the biochemical features of the disease although present remained discrete throughout the prolonged follow-up. It is suggested that such a difference in the phenotypic expression of the disease is possibly secondary to the modifier effect of a gene and/or results from environmental factor(s).

  13. Evidence for alternative lengthening of telomeres in liposarcomas in the absence of ALT-associated PML bodies.

    Science.gov (United States)

    Jeyapalan, Jennie N; Mendez-Bermudez, Aaron; Zaffaroni, Nadia; Dubrova, Yuri E; Royle, Nicola J

    2008-06-01

    Immortalized and cancer cells maintain their telomeres by activation of a telomere maintenance mechanism (TMM). In approximately 85% of cancers telomerase is activated (TA) but in some tumours, in particular sarcomas, an alternative lengthening of telomeres (ALT) pathway is used. Liposarcomas are the most common soft-tissue sarcoma in adults and they activate ALT or telomerase with equal frequency, however no TMM has been identified in approximately 50% of liposarcomas. In our study, we have shown that instability at the minisatellite MS32, usually associated with ALT activation, aids the identification of liposarcomas that have recombination-like activity at telomeres in absence of ALT associated PML-bodies (APBs). Furthermore, using single molecule telomere analysis, we have detected complex telomere mutations directly in ALT positive liposarcomas and interestingly in some liposarcomas with an unknown TMM but high MS32 instability. We have shown by sequence analysis that some of these complex telomere mutations must arise by an inter-molecular recombination-like process rather than by deletion caused by t-loop excision or by unequal telomere-sister-chromatid-exchange (T-SCE), which is known to be elevated in ALT cell lines. Preliminary evidence also suggests that inter-molecular recombination events may be processed differently in liposarcomas with APBs compared to those without. In conclusion, we have shown for the first time, that some telomerase negative liposarcomas without APBs have other features associated with ALT, indicating that the incidence of ALT in these tumours has previously been under-estimated. This has major implications for the use of cancer treatments targeted at TMMs. (c) 2008 Wiley-Liss, Inc.

  14. Adult Sibling Relationships with Brothers and Sisters with Severe Disabilities

    Science.gov (United States)

    Rossetti, Zach; Hall, Sarah

    2015-01-01

    The purpose of this qualitative study was to examine perceptions of adult sibling relationships with a brother or sister with severe disabilities and the contexts affecting the relationships. Adult siblings without disabilities (N = 79) from 19 to 72 years of age completed an online survey with four open-ended questions about their relationship…

  15. High prevalence of metabolic syndrome in young Hispanic women: findings from the national Sister to Sister campaign.

    Science.gov (United States)

    Rodriguez, Fátima; Naderi, Sahar; Wang, Yun; Johnson, Caitlin E; Foody, JoAnne M

    2013-04-01

    Hispanics are the fastest growing segment of the U.S. population and have a higher prevalence of cardiometabolic risk factors as compared with non-Hispanic whites. Further data suggests that Hispanics have undiagnosed complications of metabolic syndrome, namely diabetes mellitus, at an earlier age. We sought to better understand the epidemiology of metabolic syndrome in Hispanic women using data from a large, community-based health screening program. Using data from the Sister to Sister: The Women's Heart Health Foundation community health fairs from 2008 to 2009 held in 17 U.S. cities, we sought to characterize how cardiometabolic risk profiles vary across age for women by race and ethnicity. Metabolic syndrome was defined using the updated National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, which included three or more of the following: Waist circumference ≥35 inches, triglycerides ≥150 mg/dL, high-density lipoprotein (HDL) <50 mg/dL, systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or a fasting glucose ≥100 mg/dL. A total of 6843 community women were included in the analyses. Metabolic syndrome had a prevalence of 35%. The risk-adjusted odds ratio for metabolic syndrome in Hispanic women versus white women was 1.7 (95% confidence interval, 1.4, 2.0). Dyslipidemia was the strongest predictor of metabolic syndrome among Hispanic women. This disparity appeared most pronounced for younger women. Additional predictors of metabolic syndrome included black race, increasing age, and smoking. In a large, nationally representative sample of women, we found that metabolic syndrome was highly prevalent among young Hispanic women. Efforts specifically targeted to identifying these high-risk women are necessary to prevent the cardiovascular morbidity and mortality associated with metabolic syndrome.

  16. Sister broods in the spruce bark beetle, Ips typographus (L.)

    Czech Academy of Sciences Publication Activity Database

    Davídková, Markéta; Doležal, Petr

    2017-01-01

    Roč. 405, DEC 01 (2017), s. 13-21 ISSN 0378-1127 Grant - others:Lesy ČR(CZ) 08/2009-2015 Institutional support: RVO:60077344 Keywords : re-emergence * sister broods * Ips typographus Subject RIV: EH - Ecology, Behaviour OBOR OECD: Zoology Impact factor: 3.064, year: 2016 http://www.sciencedirect.com/science/article/pii/S0378112717309507

  17. Phylogenetic conservatism of thermal traits explains dispersal limitation and genomic differentiation of Streptomyces sister-taxa.

    Science.gov (United States)

    Choudoir, Mallory J; Buckley, Daniel H

    2018-06-07

    The latitudinal diversity gradient is a pattern of biogeography observed broadly in plants and animals but largely undocumented in terrestrial microbial systems. Although patterns of microbial biogeography across broad taxonomic scales have been described in a range of contexts, the mechanisms that generate biogeographic patterns between closely related taxa remain incompletely characterized. Adaptive processes are a major driver of microbial biogeography, but there is less understanding of how microbial biogeography and diversification are shaped by dispersal limitation and drift. We recently described a latitudinal diversity gradient of species richness and intraspecific genetic diversity in Streptomyces by using a geographically explicit culture collection. Within this geographically explicit culture collection, we have identified Streptomyces sister-taxa whose geographic distribution is delimited by latitude. These sister-taxa differ in geographic distribution, genomic diversity, and ecological traits despite having nearly identical SSU rRNA gene sequences. Comparative genomic analysis reveals genomic differentiation of these sister-taxa consistent with restricted gene flow across latitude. Furthermore, we show phylogenetic conservatism of thermal traits between the sister-taxa suggesting that thermal trait adaptation limits dispersal and gene flow across climate regimes as defined by latitude. Such phylogenetic conservatism of thermal traits is commonly associated with latitudinal diversity gradients for plants and animals. These data provide further support for the hypothesis that the Streptomyces latitudinal diversity gradient was formed as a result of historical demographic processes defined by dispersal limitation and driven by paleoclimate dynamics.

  18. Metabolic syndrome, hypertension, and hyperlipidemia in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Yilmaz, Bulent; Vellanki, Priyathama; Ata, Baris; Yildiz, Bulent Okan

    2018-02-01

    To provide an evidence-based assessment of metabolic syndrome, hypertension, and hyperlipidemia in first-degree relatives of women with polycystic ovary syndrome (PCOS). Systematic review and meta-analysis. Not applicable. Mothers, fathers, sisters, and brothers of women with and without PCOS. An electronic-based search with the use of PubMed from 1960 to June 2015 and cross-checked references of relevant articles. Metabolic syndrome, hypertension and dyslipidemia, and surrogate markers, including systolic blood pressure (BP), diastolic BP, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Fourteen of 3,346 studies were included in the meta-analysis. Prevalence of the following was significantly increased in relatives of women with PCOS: metabolic syndrome (risk ratio [RR] 1.78 [95% confidence interval 1.37, 2.30] in mothers, 1.43 [1.12, 1.81] in fathers, and 1.50 [1.12, 2.00] in sisters), hypertension (RR 1.93 [1.58, 2.35] in fathers, 2.92 [1.92, 4.45] in sisters), and dyslipidemia (RR 3.86 [2.54, 5.85] in brothers and 1.29 [1.11, 1.50] in fathers). Moreover, systolic BP (mothers, sisters, and brothers), total cholesterol (mothers and sisters), low-density lipoprotein cholesterol (sisters), and triglycerides (mothers and sisters) were significantly higher in first-degree relatives of PCOS probands than in controls. Our results show evidence of clustering for metabolic syndrome, hypertension, and dyslipidemia in mothers, fathers, sisters, and brothers of women with PCOS. PROSPERO 2016 CRD42016048557. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. The use of convent archival records in medical research: the School Sisters of Notre Dame archives and the nun study.

    Science.gov (United States)

    Patzwald, Gari-Anne; Wildt, Sister Carol Marie

    2004-01-01

    The School Sisters of Notre Dame (SSND) archives program in a cooperative system for the arrangement and preservation of the records of the SSND provinces in North America, including records of individual sisters. Archival records include autobiographies, school and college transcripts, employment histories, and family socioeconomic data. The Nun Study, a longitudinal study of Alzheimer's disease and aging in 678 SSND sisters, compares data extracted from these records with data on late-life cognitive and physical function and postmortem brain neuropathology to explore early life factor that may affect late-life cognitive function and longevity.

  20. 20 CFR 410.380 - Determination of dependency; parent, brother, or sister.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Determination of dependency; parent, brother... MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Relationship and Dependency § 410.380 Determination of dependency; parent, brother, or sister. An individual who is the miner's...

  1. 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.

  2. 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.

  3. "Brothers and Sisters": A Novel Way to Teach Human Resources Management.

    Science.gov (United States)

    Bumpus, Minnette

    2000-01-01

    The novel "Brothers and Sisters" by Bebe Moore Campbell was used in a management course to explore human resource management issues, concepts, and theories. The course included prereading and postreading surveys, lecture, book review, and examination. Most of the students (92%) felt the novel was an appropriate way to meet course…

  4. Therapeutic effect of cefozopran (SCE-2787), a new parenteral cephalosporin, against experimental infections in mice.

    Science.gov (United States)

    Iizawa, Y; Okonogi, K; Hayashi, R; Iwahi, T; Yamazaki, T; Imada, A

    1993-01-01

    The therapeutic effect of cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Klebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, cefozopran was as effective as ceftazidime. The therapeutic effect of cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, cefozopran was the most effective agent. The potent therapeutic effect of cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram-negative bacteria in humans. PMID:8431004

  5. 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

  6. Cortical Pathology in RRMS: Taking a Cue from Four Sisters

    Directory of Open Access Journals (Sweden)

    Massimiliano Calabrese

    2012-01-01

    Full Text Available Background. Although grey matter pathology is a relevant aspect of multiple sclerosis (MS both with physical and cognitive rebounds, its pathogenesis is still under investigation. To what extent the familial and sporadic cases of MS differ in cortical pathology has not been elucidated yet. Here we present a multiple case report of four sisters affected by MS, all of them having a very high burden of cortical pathology. Methods. The clinical and grey matter MRI parameters of the patients were compared with those of twenty-five-aged matched healthy women and 25 women affected by sporadic MS (matched for age, disease duration, EDSS, and white matter lesion load. Results. Despite their short disease duration (<5 years, the four sisters showed a significant cortical thinning compared to healthy controls ( and sporadic MS ( and higher CLs number ( and volume ( compared to sporadic MS. Discussion. Although limited to a single family, our observation is worth of interest since it suggests that familial factors may account for a peculiar involvement of the cortex in MS pathology. This hypothesis should be further evaluated in a large number of multiplex MS families.

  7. Constraining volcanic inflation at Three Sisters Volcanic Field in Oregon, USA, through microgravity and deformation modeling

    Science.gov (United States)

    Zurek, Jeffrey; William-Jones, Glyn; Johnson, Dan; Eggers, Al

    2012-10-01

    Microgravity data were collected between 2002 and 2009 at the Three Sisters Volcanic Complex, Oregon, to investigate the causes of an ongoing deformation event west of South Sister volcano. Three different conceptual models have been proposed as the causal mechanism for the deformation event: (1) hydraulic uplift due to continual injection of magma at depth, (2) pressurization of hydrothermal systems and (3) viscoelastic response to an initial pressurization at depth. The gravitational effect of continual magma injection was modeled to be 20 to 33 μGal at the center of the deformation field with volumes based on previous deformation studies. The gravity time series, however, did not detect a mass increase suggesting that a viscoelactic response of the crust is the most likely cause for the deformation from 2002 to 2009. The crust, deeper than 3 km, in the Three Sisters region was modeled as a Maxwell viscoelastic material and the results suggest a dynamic viscosity between 1018 to 5 × 1019 Pa s. This low crustal viscosity suggests that magma emplacement or stall depth is controlled by density and not the brittle ductile transition zone. Furthermore, these crustal properties and the observed geochemical composition gaps at Three Sisters can be best explained by different melt sources and limited magma mixing rather than fractional crystallization. More generally, low intrusion rates, low crustal viscosity, and multiple melt sources could also explain the whole rock compositional gaps observed at other arc volcanoes.

  8. Psyche’s Sisters: Ambivalence of Sisterhood in Twentieth-century Irish Women’s Short Stories

    Directory of Open Access Journals (Sweden)

    Ann Wan-lih Chang

    2013-03-01

    Full Text Available This paper examines and evaluates representations of problematic sisterly relationships in twentieth-century Irish women’s stories which display an emphasis on ambivalence and sibling rivalry.  The paper is based primarily on the literary output of Mary Lavin, Clare Boylan, Moy McCrory, Éilís Ní Dhuibhne, Jan Kennedy, Mary Morrissy and Claire Keegan.  The paper seeks, by reference both to feminist studies and Irish women’s short stories, to demonstrate the consequences and causes of a divided sisterhood which itself may be traced back to a suppression of expression of female solidarity embedded in western culture and manifested in western literary heritage.  Typically, such stories depict a conflict sourced in the need to develop self-identity and framed within the constraints imposed by separate social roles.  This kind of conflict results potentially in rivalry, antagonism, ambivalence, and the domination of one sibling by another.  Daughters/sisters are often depicted in these stories both as competing with each other for limited resources and also as seeking a sense of personal identity through mutual polarisation.  There are also stories into which are woven undertones of domination disguised as sisterly closeness, for which the actual motivation seems to be a repressed aspiration for intimacy.

  9. [The work of Moscow communities of Sisters of Charity in own medical institutions].

    Science.gov (United States)

    Zorin, K V

    2011-01-01

    The article analyses the medical activities of Moscow communities of Sisters of Charity in curative and educational institutions organized by the communities themselves. The social ministration of communities on the territory of Moscow is considered.

  10. 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.

  11. 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.

  12. Maria Carolina and Marie Antoinette: Sisters and Queens in the mirror of Jacobin Public Opinion

    Directory of Open Access Journals (Sweden)

    Cinzia Recca

    2014-09-01

    Full Text Available Marie Antoinette of Franceand Maria Carolina of Naples, both consorts, contributed to a flourishing of matronage, reproducing conceptions of royal femininity that embraced both the private and public roles they were expected to fulfil. However, while the political role of the first Queen has been largely reconsidered, her sister Maria Carolina has not yet been adjudicated impartially. This is somewhat curious, because Maria Carolina inherited from her sister the same disregard towards the Revolution and this, as perceived by the Jacobins, was duly proposed in their acrimonious criticism of her political role. This paper aims to focus on this criticism, analysing how the charges against Maria Carolina in the post-French revolutionary period, were a political duplication of the Jacobin attacks on Marie Antoinette from 1791 onwards. From this point of view, the paper will focus on the portrait of Maria Carolina in 1793 revolutionary Parisby Giuseppe Gorani, an Italian Jacobin noble. His Mémoires Secrets – where Maria Carolina was represented as a wicked woman in the same terms previously employed to denounce her sister Marie Antoinette by the French Republicans – was well known across Italy. This subject dominated the main pamphlets and brochures published in Naples in 1799, during the brief duration of the Neapolitan Republic, because it legitimised the rebellion against the monarchy. After the fall of the Neapolitan Republic, the political attacks on Maria Carolina continued likewise in France, where many Neapolitan patriots were obliged to flee. Analysing  Giuseppe Gorani’s Mémoires we gather that the portrait of Marie Antoinette’s sister was painted according to the main stereotypes of  French revolutionary political culture.

  13. Interface and integration of a silicon graphics UNIX computer with the Encore based SCE SONGS 2/3 simulator

    International Nuclear Information System (INIS)

    Olmos, J.; Lio, P.; Chan, K.S.

    1991-01-01

    The SONGS Unit 2/3 simulator was originally implemented in 1983 on a Master/Slave 32/7780 Encore MPX platform by the Singer-Link Company. In 1986, a 32/9780 MPX Encore computer was incorporated into the simulator computer system to provide the additional CPU processing needed to install the PACE plant monitoring system and to enable the upgrade of the NSSS Simulation to the advanced RETACT/STK models. Since the spring of 1990, the SCE SONGS Nuclear Training Division simulator technical staff, in cooperation with Micro Simulation Inc., has undertaken a project to integrate a Silicon Graphics UNIX based computer with the Encore MPX SONGS 2/3 simulation computer system. In this paper the authors review the objectives, advantages to be gained, software and hardware approaches utilized, and the results so far achieved by the authors' project

  14. Synergistic convergence and split pons in horizontal gaze palsy and progressive scoliosis in two sisters

    Directory of Open Access Journals (Sweden)

    Jain Nitin

    2011-01-01

    Full Text Available Synergistic convergence is an ocular motor anomaly where on attempted abduction or on attempted horizontal gaze, both the eyes converge. It has been related to peripheral causes such as congenital fibrosis of extraocular muscles (CFEOM, congenital cranial dysinnervation syndrome, ocular misinnervation or rarely central causes like horizontal gaze palsy with progressive scoliosis, brain stem dysplasia. We hereby report the occurrence of synergistic convergence in two sisters. Both of them also had kyphoscoliosis. Magnetic resonance imaging (MRI brain and spine in both the patients showed signs of brain stem dysplasia (split pons sign differing in degree (younger sister had more marked changes.

  15. Empirical Psycho-Aesthetics and Her Sisters: Substantive and Methodological Issues--Part II

    Science.gov (United States)

    Konecni, Vladimir J.

    2013-01-01

    Empirical psycho-aesthetics is approached in this two-part article from two directions. Part I, which appeared in the Winter 2012 issue of "JAE," addressed definitional and organizational issues, including the field's origins, its relation to "sister" disciplines (experimental philosophy, cognitive neuroscience of art, and neuroaesthetics), and…

  16. 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.

  17. 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...

  18. 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 ...

  19. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde

    International Nuclear Information System (INIS)

    Costa, Solange; Coelho, Patricia; Costa, Carla; Silva, Susana; Mayan, Olga; Silva Santos, Luis; Gaspar, Jorge; Teixeira, Joao Paulo

    2008-01-01

    Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy laboratories as a tissue preservative. Several epidemiological studies of occupational exposure to FA have indicated an increased risk of nasopharyngeal cancers in industrial workers, embalmers and pathology anatomists. There is also a clear evidence of nasal squamous cell carcinomas from inhalation studies in the rat. The postulated mode of action for nasal tumours in rats was considered biologically plausible and considered likely to be relevant to humans. Based on the available data IARC, the International Agency for Research on Cancer, has recently classified FA as a human carcinogen. Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of FA are well documented in mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting thus remains to be more documented. To evaluate the genetic effects of long-term occupational exposure to FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid exchange, SCE) and comet assay. The level of exposure to FA was evaluated near the breathing zone of workers, time weighted average of exposure was calculated for each subject. The association between the biomarkers and polymorphic genes of xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level of exposure was 0.44 ± 0.08 ppm (0.04-1.58 ppm). MN frequency was significantly higher (p = 0.003) in the exposed subjects (5.47 ± 0.76) when compared with controls (3.27 ± 0.69). SCE mean value was significantly higher (p < 0.05) among the exposed group (6.13 ± 0.29) compared with control group (4.49 ± 0.16). Comet assay data showed a significant increase (p < 0.05) of TL in FA-exposed workers (60.00 ± 2.31) with respect to the control group (41.85 ± 1.97). A positive correlation was

  20. Enhanced induction of SCEs in hypoxic mammalian cells by ionizing radiation

    International Nuclear Information System (INIS)

    Tofilon, P.J.; Meyn, R.E.

    1985-01-01

    Ionizing radiation is, in general, a poor inducer of sister chromatoid exchanges (SCEs). However, the authors previously observed an increase in X-ray induced DNA-protein crosslinks in hypoxic cells, as compared to aerated cells, suggesting that in the absence of oxygen, X rays induce a qualitatively different DNA lesion. Therefore, they examined the effect of X-rays on SCE induction under hypoxic conditions. CHO cells were rendered hypoxic by incubation at 37 0 for 3 hr. in evacuated glass ampules and irradiated with graded doses of X-rays. After irradiation, cells were incubated in medium containing BrdUrd and the SCE assay performed. At each dose tested (0-900 rads) the number of SCEs induced by X-rays in hypoxic cells was approximately 2.5 fold the number induced in aerated cells. When a 16-hr. repair-incubation interval was allowed between irradiation and BrdUrd labeling, the number of SCEs returned to background levels. In further experiments, repair-deficient cells, incapable of completely removing crosslinks from their DNA, did not completely restore SCE levels to background within the repair period. These data provide further evidence suggesting that hypoxic cells respond differently to radiation in a qualitative sense, in addition to the well known quantitative sense

  1. Birth weight and fetal growth in infants born to female hairdressers and their sisters.

    Science.gov (United States)

    Axmon, A; Rylander, L

    2009-03-01

    To investigate birth weight and fetal growth in female hairdressers, while controlling for intergenerational effects and effects related to childhood exposures. A cohort of women who had attended vocational schools for hairdressers were compared to their sisters with respect to birth weight and fetal growth (measured as small for gestational age (SGA) or large for gestational age (LGA), respectively) in their infants. In total, 6223 infants born to 3137 hairdressers and 8388 infants born to 3952 hairdressers' sisters were studied. Among the infants born to the hairdressers' sisters, the distribution of birth weights were wider than that among the infants born to the hairdressers. This was also reflected in that hairdresser cohort affiliation tended to be protective against both SGA (odds ratio 0.80; 95% confidence interval 0.49 to 1.31) and LGA (0.77; 0.54 to 1.09). For LGA, this effect was even more pronounced among women who had actually worked as hairdressers during at least one pregnancy (0.60; 0.39 to 0.92). The infants born to these women also had a significantly lower mean birth weight (3387 g vs 3419 g; p = 0.033). The results from the present study suggest that infants born to hairdressers have a decreased risk of being LGA. This is most likely not caused by a shift in birth weight distribution or abnormal glucose metabolism.

  2. 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

  3. 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

  4. Caffeine inhibits homology-directed repair of I-SceI-induced DNA double-strand breaks.

    Science.gov (United States)

    Wang, Huichen; Boecker, Wilfried; Wang, Hongyan; Wang, Xiang; Guan, Jun; Thompson, Larry H; Nickoloff, Jac A; Iliakis, George

    2004-01-22

    We recently reported that two Chinese hamster mutants deficient in the RAD51 paralogs XRCC2 and XRCC3 show reduced radiosensitization after treatment with caffeine, thus implicating homology-directed repair (HDR) of DNA double-strand breaks (DSBs) in the mechanism of caffeine radiosensitization. Here, we investigate directly the effect of caffeine on HDR initiated by DSBs induced by a rare cutting endonuclease (I-SceI) into one of two direct DNA repeats. The results demonstrate a strong inhibition by caffeine of HDR in wild-type cells, and a substantial reduction of this effect in HDR-deficient XRCC3 mutant cells. Inhibition of HDR and cell radiosensitization to killing shows similar dependence on caffeine concentration suggesting a cause-effect relationship between these effects. UCN-01, a kinase inhibitor that effectively abrogates checkpoint activation in irradiated cells, has only a small effect on HDR, indicating that similar to radiosensitization, inhibition of checkpoint signaling is not sufficient for HDR inhibition. Recombination events occurring during treatment with caffeine are characterized by rearrangements reminiscent to those previously reported for the XRCC3 mutant, and immunofluorescence microscopy demonstrates significantly reduced formation of IR-specific RAD51 foci after caffeine treatment. In summary, our results identify inhibition of HDR as a significant contributor to caffeine radiosensitization.

  5. Exploring the transition from\\ud staff nurse to\\ud ward sister/manager –\\ud An exploratory case study

    OpenAIRE

    Enterkin, Judith

    2016-01-01

    Background\\ud The ward sister/manager figure has traditionally been considered the ward based\\ud clinical leader. This role has evolved over time in response to professional and\\ud political demands; despite or because of this, reports of role ambiguity exist and\\ud the ward sister/manager position has become increasingly difficult to recruit to,\\ud with nurses arguably looking to roles perceived to have greater influence and\\ud status, but less onerous managerial responsibility. Understandin...

  6. Familial Churg-Strauss Syndrome in a Sister and Brother.

    Science.gov (United States)

    Alyasin, Soheyla; Khoshkhui, Maryam; Amin, Reza

    2015-06-01

    Churg-Strauss syndrome (CSS) is a granulomatous small vessel vasculitis. It is characterized by asthma, allergic granulomatosis and vasculitis. This syndrome is rare in children. A 5 years old boy was admitted with cough, fever and dyspnea for 2 weeks. On the basis of laboratory data (peripheral eosinophilia), associated with skin biopsy, and history of CSS in his sister, this disease was eventually diagnosed. The patient had good response to corticosteroid. In every asthmatic patient with prolonged fever, eosinophilia and multisystemic involvment, CSS should be considered.

  7. In vitro cytogenetic testing of an organoselenium compound and its sulfur analogue in cultured rat bone marrow cells

    Directory of Open Access Journals (Sweden)

    Jacob Jacob H

    2004-03-01

    Full Text Available Abstract Background Selenium (Se is a non-metal element, occurring in varying degrees in the environment and it has been found to be a component of several enzymes. Different selenium compounds have been associated with carcinogenicity, toxicity, modification of metal toxicity and prevention of cancer. Organoselenium compounds had substantially greater bioavailability and less toxicity than that of inorganic selenium. From a chemical point of view, Se resembles sulfur (S in many of its properties, thus, Se and S may be considered to be isosteric. The ability of a synthetic organoselenium compound; cyclopenta-dienyldicarbonyl ironselenoterephthalic acid (CSe and its sulfur analogue (CS in the range of 10-8 to 10-5 M, to induce sister-chormatid exchanges (SCE and alter cell division expressed as mitotic index (MI as well as cell survival has been investigated. Methods Rat bone marrow cells were cultured in the presence of CSe and CS in the range of 10-8 to 10-5 M with a total exposure time of 4, 16 or 28 h at 37°C. Fluorescence-plus-Giemsa (FPG technique was used to visualize chromosomes for SCE analysis and MI determination. Trypan blue exclusion technique was used to determine cell viability. Results At the three exposure times, cell survival progressively decreased with increasing concentration, but the effect of either chemical was not significant (ANOVA; P -5 M when either chemical was applied for 16 or 28 h. Furthermore, the mean SCE increased with longer exposure times and, in general, CSe had slightly greater effect on cell survival and caused higher frequencies of SCE than CS. The exception was the 10-8 M treatment. However, both CSe and CS failed to induce 2-fold SCE as that of the negative control and therefore they are not considered as mutagens. Conclusion Both CSe and CS in the range of 10-8 to 10-5 M could not double the SCE rate of the negative control and therefore not considered as mutagens at these experimental conditions.

  8. Biomonitoring and biomarkers of organophosphate pesticides exposure - state of the art.

    Science.gov (United States)

    Kapka-Skrzypczak, Lucyna; Cyranka, Małgorzata; Skrzypczak, Maciej; Kruszewski, Marcin

    2011-01-01

    Human biomonitoring provides an efficient and cost-effective way to identify and quantify exposure to chemical substances, including those having deleterious eff ects on human organisms. Once the risk of hazardous exposure has been identified and the mechanism of toxic eff ects has been elucidated, an ultimate decision about how to reduce exposure can be made. A particularly high risk of exposure to hazardous chemicals is associated with the use of pesticides in agriculture, especially the use of organophosphorous pesticides (OP), which are the most widely and commonly used insecticides worldwide. There is some strong evidence that chronic exposure to these compounds may have adverse eff ects on health. Exposure to pesticides has been associated with an increase in the incidence of non-Hodgkin's lymphoma, multiple myeloma, soft tissue sarcoma, lung sarcoma, and cancer of the pancreas, stomach, liver, bladder and gall bladder, Parkinson disease, Alzheimer disease, and reproductive outcomes. In view of these findings, the detection of populations at risk constitutes a very important topic. The biomonitoring studies on individuals exposed to pesticides have shown an elevated level of indicators of DNA damage, such as chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), and recently, single cell gel electrophoresis (SCGE). The cytogenetic markers of DNA damage have become very popular and useful in providing an analytical data for risk assessment, such as internal exposure doses and early biological eff ects of both occupational and environmental exposure to pesticides. The article describes the usefulness and the limitations of these biomarkers in biomonitoring studies of populations exposed to pesticides, with regard to the main routes of uptake and different matrices, which can be used to monitor risk assessment in occupational settings. The article also summarizes the latest reports about biomarkers of susceptibility, and mentions other

  9. Geodetic observations and modeling of magmatic inflation at the Three Sisters volcanic center, central Oregon Cascade Range, USA

    Science.gov (United States)

    Dzurisin, Daniel; Lisowski, Michael; Wicks, Charles W.; Poland, Michael P.; Endo, Elliot T.

    2006-02-01

    Tumescence at the Three Sisters volcanic center began sometime between summer 1996 and summer 1998 and was discovered in April 2001 using interferometric synthetic aperture radar (InSAR). Swelling is centered about 5 km west of the summit of South Sister, a composite basaltic-andesite to rhyolite volcano that last erupted between 2200 and 2000 yr ago, and it affects an area ˜20 km in diameter within the Three Sisters Wilderness. Yearly InSAR observations show that the average maximum displacement rate was 3-5 cm/yr through summer 2001, and the velocity of a continuous GPS station within the deforming area was essentially constant from June 2001 to June 2004. The background level of seismic activity has been low, suggesting that temperatures in the source region are high enough or the strain rate has been low enough to favor plastic deformation over brittle failure. A swarm of about 300 small earthquakes ( Mmax = 1.9) in the northeast quadrant of the deforming area on March 23-26, 2004, was the first notable seismicity in the area for at least two decades. The U.S. Geological Survey (USGS) established tilt-leveling and EDM networks at South Sister in 1985-1986, resurveyed them in 2001, the latter with GPS, and extended them to cover more of the deforming area. The 2001 tilt-leveling results are consistent with the inference drawn from InSAR that the current deformation episode did not start before 1996, i.e., the amount of deformation during 1995-2001 from InSAR fully accounts for the net tilt at South Sister during 1985-2001 from tilt-leveling. Subsequent InSAR, GPS, and leveling observations constrain the source location, geometry, and inflation rate as a function of time. A best-fit source model derived from simultaneous inversion of all three datasets is a dipping sill located 6.5 ± 2.5 km below the surface with a volume increase of 5.0 × 10 6 ± 1.5 × 10 6 m 3/yr (95% confidence limits). The most likely cause of tumescence is a pulse of basaltic magma

  10. The first record of a trans-oceanic sister-group relationship between obligate vertebrate troglobites.

    Directory of Open Access Journals (Sweden)

    Prosanta Chakrabarty

    Full Text Available We show using the most complete phylogeny of one of the most species-rich orders of vertebrates (Gobiiformes, and calibrations from the rich fossil record of teleost fishes, that the genus Typhleotris, endemic to subterranean karst habitats in southwestern Madagascar, is the sister group to Milyeringa, endemic to similar subterranean systems in northwestern Australia. Both groups are eyeless, and our phylogenetic and biogeographic results show that these obligate cave fishes now found on opposite ends of the Indian Ocean (separated by nearly 7,000 km are each others closest relatives and owe their origins to the break up of the southern supercontinent, Gondwana, at the end of the Cretaceous period. Trans-oceanic sister-group relationships are otherwise unknown between blind, cave-adapted vertebrates and our results provide an extraordinary case of Gondwanan vicariance.

  11. X-ray- and TEM-induced mitotic recombination in Drosophila melanogaster: Unequal and sister-strand recombination

    International Nuclear Information System (INIS)

    Becker, H.J.

    1975-01-01

    Twin mosaic spots of dark-apricot and light-apricot ommatidia were found in the eyes of wsup(a)/wsup(a) females, of wsup(a) males, of females homozygous for In(1)sc 4 , wsup(a) and of attached-X females homozygous for wsup(a). The flies were raised from larvae which had been treated with 1,630 R of X-rays at the age of 48-52 hours. An additional group of wsup(a)/wsup(a) females and wsup(a) males came from larvae that had been fed with triethylene melamine (TEM) at the age of 22-24 hours. The twin spots apparently were the result of induced unequal mitotic recombination, i.e. from unequal sister-strand recombination in the males and from unequal sister-strand recombination as well as, possibly, unequal recombination between homologous strands in the females. That is, a duplication resulted in wsup(a)Dpwsup(a)/wsup(a) dark-apricto ommatidia and the corresponding deficiency in an adjacent area of wsup(a)/Dfwsup(a) light-apricot ommatidia. In an additional experiment sister-strand mitotic recombination in the ring-X chromosome of ring-X/rod-X females heterozygous for w and wsup(co) is believed to be the cause for X-ray induced single mosaic spots that show the phenotype of the rod-X marker. (orig.) [de

  12. 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.

  13. [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.

  14. Dealing with conflict - The role of the ward sister

    Directory of Open Access Journals (Sweden)

    L.M. Cremer

    1980-09-01

    Full Text Available In the course of her duties, the ward sister has to contend with many forms of conflict, discord and dissension. These involve conflict of the intrapersonal, interpersonal and intergroup varieties. Conflict is in the main, disruptive and dysfunctional. Skilful management, however, embodying cooperative effort in its reduction can produce constructive and positive results. Conflict management strategies are therefore either restrictive or constructive. Persons in serious conflict suffer varied degrees of personality disequilibrium, which necessitates emotional first aid or crisis intervention. Such primary preventive care is applicable to patients, their relatives, and members of the nursing staff in such need.

  15. [Wolfram syndrome: clinical and genetic analysis in two sisters].

    Science.gov (United States)

    Conart, J-B; Maalouf, T; Jonveaux, P; Guerci, B; Angioi, K

    2011-10-01

    Wolfram syndrome is a severe genetic disorder defined by the association of diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. Two sisters complained of progressive visual loss. Fundus examination evidenced optic atrophy. Their past medical history revealed diabetes mellitus and deafness since childhood. The association of these symptoms made the diagnosis of Wolfram syndrome possible. It was confirmed by molecular analysis, which evidenced composite WFS1 heterozygous mutations inherited from both their mother and father. Ophthalmologists should be aware of the possibility of Wolfram syndrome when diagnosing optic atrophy in diabetic children. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Social Functioning among Girls with Fragile X or Turner Syndrome and Their Sisters.

    Science.gov (United States)

    Mazzocco, Michele M. M.; Baumgardner, Thomas; Freund, Lisa S.; Reiss, Allan L.

    1998-01-01

    Social behaviors among girls (ages 6-16) with fragile X (n=8) or Turner syndrome (n=9) were examined to address the role of family environment versus biological determinants of social dysfunction. Compared to their sisters, subjects had lower IQS and higher rating of social and attention problems. (Author/CR)

  17. Genotoxic action of the sesquiterpene lactone glaucolide B on mammalian cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Regislaine V. Burim

    1999-09-01

    Full Text Available Glaucolide B is a sesquiterpene lactone isolated from Vernonia eremophila Mart. (Vernonieae, Asteraceae and has schistosomicidal, antimicrobial and analgesic activities. This study examined the cytotoxic and clastogenic activities of glaucolide B in human cultured lymphocytes and in bone marrow cells from BALB/c mice. The mitotic index (MI and chromosomal aberrations were analyzed in both of the above systems, whereas sister chromatid exchanges (SCE and the proliferation index (PI were determined only in vitro. In human cultured lymphocytes, glaucolide B concentrations greater than 15 µg/ml of culture medium completely inhibited cell growth. At 4 µg/ml and 8 µg/ml of culture medium, glaucolide B significantly increased the frequency of chromosomal aberrations in lymphocytes and was also cytotoxic at concentrations ³8 µg/ml; there was no increase in the frequency of SCE. Glaucolide B (160-640 mg/kg did not significantly increase the frequency of chromosomal aberrations in mouse bone marrow cells nor did it affect cell division. Since glaucolide B showed no clastogenic action on mammalian cells in vivo but was cytotoxic and clastogenic in vitro, caution is needed in its medicinal use.O glaucolido B é uma lactona sesquiterpênica, g-lactona a,b-insaturada, isolada da Vernonia eremophila Mart. (Vernonieae, Asteraceae; apresenta atividade esquistossomicida e antimicrobiana, além de atividade analgésica. A aceitação de uma substância para uso medicinal também depende de dados sobre sua toxicidade, além de sua eficiência medicinal. Assim, o objetivo deste trabalho foi testar a atividade clastogênica e citotóxica do composto glaucolido B in vitro e in vivo, utilizando linfócitos em cultura temporária e células da medula óssea de camundongos BALB/c, respectivamente. Analisaram-se o índice mitótico (MI e as aberrações cromossômicas nos sistemas in vitro e in vivo, e trocas entre cromátides irmãs (SCE e índice proliferativo (PI

  18. Climate niches of milkweeds with plesiomorphic traits (Secamonoideae; Apocynaceae) and the milkweed sister group link ancient African climates and floral evolution.

    Science.gov (United States)

    Livshultz, Tatyana; Mead, Jerry V; Goyder, David J; Brannin, Michelle

    2011-12-01

    Climate change that increases mortality of plants and pollinators can create mate-finding Allee effects and thus act as a strong selective force on floral morphology. Milkweeds (Secamonoideae and Asclepiadoideae; Apocynaceae) are typically small plants of seasonally dry habitats, with pollinia and high pollen-transfer efficiency. Their sister group (tribe Baisseeae and Dewevrella) is mostly comprised of giant lianas of African rainforests, with pollen in monads. Comparison of the two groups motivated a new hypothesis: milkweeds evolved in the context of African aridification and the shifting of rainforest to dry forest. Pollinia and high pollen-transfer efficiency may have been adaptations that alleviated mate-finding Allee effects generated by high mortality during droughts. We formally tested whether milkweeds have a drier climate niche by comparing milkweeds with plesiomorphic traits (Secamonoideae) and the milkweed sister group in continental Africa. We georeferenced specimens of the milkweed sister group and Secamonoideae in continental Africa, extracted 19 climatic variables from the Worldclim model, conducted factor analysis to identify correlated suites of variables, and compared the frequency distributions of the two lineages relative to each factor. The distributions of Secamonoideae and the milkweed sister group differed significantly relative to four factors, each correlated with a distinct suite of climate parameters: (1) air temperature (Secamonoideae: cooler), (2) total and (3) summer precipitation (Secamonoideae: drier), and (4) temperature seasonality and isothermality (Secamonoideae: more seasonal and less isothermal). Secamonoideae in continental Africa inhabit drier, cooler sites than do the milkweed sister group, consistent with a shift from rainforests to dry forests in a cooling climate.

  19. 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)

  20. In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE2787 and piperacillin plus tazobactam) in comparison with established compounds (cefotaxime, latamoxef and piperacillin).

    Science.gov (United States)

    Bauernfeind, A; Schweighart, S; Eberlein, E; Jungwirth, R

    1991-01-01

    The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of piperacillin plus tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species. Escherichia coli, Klebsiella spp. Enterobacter sakazakii, Proteus spp. and Shigella spp. were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for piperacillin plus tazobactam was between 2 and 16 mg/l. Enterobacter cloacae, Enterobacter aerogenes and Serratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and piperacillin plus tazobactam. For Citrobacter spp., Providencia spp. and Yersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log2 less active against these species but more active than piperacillin plus tazobactam (MIC90: 2 and 8 mg/l). Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and piperacillin plus tazobactam (MIC90: 8 and greater than 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC90: 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species

  1. The roles of the Saccharomyces cerevisiae RecQ helicase SGS1 in meiotic genome surveillance.

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    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

  2. Living with a Brother Who Has an Autism Spectrum Disorder: A Sister's Perspective

    Science.gov (United States)

    Connell, Zara O.; Halloran, Maeve O.; Doody, Owen

    2016-01-01

    People with Autism Spectrum Disorder (ASD) are born into families and influence family functioning both positively and negatively. One of the most enduring relationships a person with ASD will have is their relationship with a brother or sister. Services for people with ASD should provide effective support to families, which include brothers,…

  3. Arts, Crafts, and Rural Rehabilitation: the Sisters of Charity, Halifax, and Vocational Education in Terence Bay, Nova Scotia, 1938-1942

    Directory of Open Access Journals (Sweden)

    Sasha MULLALLY

    2018-01-01

    Full Text Available Responding to rural poverty associated with the declining fishery, the rise of industrial capitalism, and the impact of the Great Depression, the Sisters of Charity, Halifax, implemented a vocational training program in weaving and carpentry in the small community of Terence Bay, Nova Scotia in 1938. Senator William Dennis, a proponent of the New Democracy Movement, financed the program. Because the Sisters based their claims to success on observed behavioural changes among the residents of Terence Bay, the program can be seen as an example of liberal therapeutics in education, a model that placed emphasis on achieving social goals rather than transferring discrete skills and capacities to pupils. Focusing on the years 1938-43, this paper outlines the rehabilitation efforts at Terence Bay, describes the programs the Sisters implemented, and evaluates the definitions of success ascribed to their training school just a few years later.

  4. 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

  5. Subcortical laminar heterotopia in two sisters and their mother : MRI, clinical findings and pathogenesis

    NARCIS (Netherlands)

    van der Valk, PHM; Snoeck, [No Value; Meiners, LC; des Portes, [No Value; Chelly, J; Pinard, JM; Ippel, PF; van Nieuwenhuizen, O

    MR imaging, clinical data and underlying pathogenesis of subcortical laminar heterotopia (SCLH), also known as band heterotopia, in two sisters and their mother are presented. On MR imaging a different degree of SCLH was found in all three affected family-members. The inversion recovery sequence was

  6. Teaching Sisters and Transnational Networks: Recruitment and Education Expansion in the Long Nineteenth Century

    Science.gov (United States)

    Raftery, Deirdre

    2015-01-01

    This article examines the management of the education enterprise of teaching Sisters, with reference to their transnational networking. The article suggests that orders of women religious were the first all-female transnational networks, engaged constantly in work that was characterised by "movement, ebb and circulation". The mobility of…

  7. Live and let die - the B(sister MADS-box gene OsMADS29 controls the degeneration of cells in maternal tissues during seed development of rice (Oryza sativa.

    Directory of Open Access Journals (Sweden)

    Xuelian Yang

    Full Text Available B(sister genes have been identified as the closest relatives of class B floral homeotic genes. Previous studies have shown that B(sister genes from eudicots are involved in cell differentiation during ovule and seed development. However, the complete function of B(sister genes in eudicots is masked by redundancy with other genes and little is known about the function of B(sister genes in monocots, and about the evolution of B(sister gene functions. Here we characterize OsMADS29, one of three MADS-box B(sister genes in rice. Our analyses show that OsMADS29 is expressed in female reproductive organs including the ovule, ovule vasculature, and the whole seed except for the outer layer cells of the pericarp. Knock-down of OsMADS29 by double-stranded RNA-mediated interference (RNAi results in shriveled and/or aborted seeds. Histological analyses of the abnormal seeds at 7 days after pollination (DAP indicate that the symplastic continuity, including the ovular vascular trace and the nucellar projection, which is the nutrient source for the filial tissue at early development stages, is affected. Moreover, degeneration of all the maternal tissues in the transgenic seeds, including the pericarp, ovular vascular trace, integuments, nucellar epidermis and nucellar projection, is blocked as compared to control plants. Our results suggest that OsMADS29 has important functions in seed development of rice by regulating cell degeneration of maternal tissues. Our findings provide important insights into the ancestral function of B(sister genes.

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

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    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.

  9. 99mTc-DMSA Uptake in a Sister Mary Joseph's Nodule From Ovarian Cancer.

    Science.gov (United States)

    Naddaf, Sleiman; Azzumeea, Fahad; Fahad Alzayed, Mohammed

    2016-12-01

    A 50-year-old woman with ovarian cancer underwent Tc-DMSA scan to evaluate the functional status of the right hydronephrotic kidney. The images incidentally revealed a well-defined focus of mild radiotracer uptake at the midanterior abdominal wall, which correlated with a metastatic Sister Mary Joseph's nodule seen on CT performed a week earlier.

  10. [Sense of coherence and ways of coping in the relationship with brother or sister in healthy siblings of mentally ill persons].

    Science.gov (United States)

    Osuchowska-Kościjańska, Anna; Charzyńska, Katarzyna; Chadzyńska, Małgorzata; Drozdzyńska, Anna; Kasperek-Zimowska, Beata; Bednarek, Agata; Sawicka, Maryla

    2014-01-01

    The aim of the present study was to investigate sense of coherence in healthy siblings of persons suffering from schizophrenia as well as their ways of coping in the relationship with ill brother or sister. 40 healthy brothers and sisters of persons with ICD- 10 diagnosis of F20 to F29 participated in the present study. Orientation to Life Scale (SOC- 29) was used to assess sense of coherence and Ways of Coping with Stress questionnaire (SRSS) was used to examine stress coping strategies. Mean global score of siblings of persons with schizophrenia was 111 points. Subjects used coping strategies focused on problem significantly more often than those focused on emotions. Therapeutic work with healthy siblings should focus on strengthening sense of personal competence, development of personal resources and different ways of coping with stress, investigation of emotions that healthy siblings experience in the relationship with ill brother or sister as well as supporting the process of accepting changes in the relationship with the ill sibling.

  11. On Brothers and Sisters: South Asian and Japanese Idea Systems and their Consequences

    OpenAIRE

    Lyon, Stephen M.

    2017-01-01

    The role expectations of cross siblings varies across culture. Such expectations, while not rigidly prescribing actual behaviors nevertheless influences relations between brothers and sisters in observable ways. In South Asia, a cultural rhetoric of sororal sacrifice and support coupled with fraternal protection are commonplace. While such noble sibling roles are regularly transgressed they remain powerful idioms of the relationship and transgressions require appropriate cultural justificatio...

  12. Mentoring in Schools: An Impact Study of Big Brothers Big Sisters School-Based Mentoring

    Science.gov (United States)

    Herrera, Carla; Grossman, Jean Baldwin; Kauh, Tina J.; McMaken, Jennifer

    2011-01-01

    This random assignment impact study of Big Brothers Big Sisters School-Based Mentoring involved 1,139 9- to 16-year-old students in 10 cities nationwide. Youth were randomly assigned to either a treatment group (receiving mentoring) or a control group (receiving no mentoring) and were followed for 1.5 school years. At the end of the first school…

  13. 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

  14. Two Cases of Endometrial Cancer in Twin Sisters with Myotonic Dystrophy

    Directory of Open Access Journals (Sweden)

    Ezra Y. Koh

    2016-01-01

    Full Text Available We describe two cases of endometrial cancer (EC occurring in nulligravid twin sisters with myotonic dystrophy. Both tested negative for Lynch syndrome and both were treated with laparoscopic hysterectomy with bilateral salpingooophorectomy and adjuvant radiotherapy. Although EC tends to run in families, the diagnosis in itself is not considered sufficient cause for screening or prophylactic measures in close relatives. However, the presence of additional risk factors, such as nulligravidity and myotonic dystrophy in the underlying cases, may call for extra vigilance in first-degree family members.

  15. Getting SaaS-y. Why the sisters of Mercy Health System opted for on-demand portfolio management.

    Science.gov (United States)

    Carter, Jay

    2011-03-01

    Sisters of Mercy Health System chose the SaaS model as a simpler way to plan, execute, and monitor strategic business initiatives. It also provided something that was easy to use and offered quick time to value.

  16. Linking Shorebird Conservation and Education Along Flyways: An Overview of the Shorebird Sister Schools Program

    Science.gov (United States)

    Hillary Chapman; Heather Johnson

    2005-01-01

    The Shorebird Sister Schools Program (SSSP) is an internet-based environmental education program that provides a forum for students, biologists, and shorebird enthusiasts to track shorebird migration and share observations along flyways. The program?s vision is to engage public participation in the conservation of shorebirds and their wetland, grassland, and shoreline...

  17. 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.

  18. 20 CFR 222.40 - When determinations of relationship are made for parent, grandchild, brother or sister.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When determinations of relationship are made... RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT FAMILY RELATIONSHIPS Relationship as Parent..., brother or sister. (a) Parent. The claimant's relationship as a parent of the employee is determined when...

  19. 'For Good, God, and the Empire': French Franciscan Sisters in Ethiopia 1896-1937

    Science.gov (United States)

    Guidi, Pierre

    2018-01-01

    In 1897, four French Franciscan sisters arrived in Ethiopia, having been summoned there by the Capuchin missionaries. In 1925, they ran an orphanage, a dispensary, a leper colony and 10 schools with 350 girl students. The students were freed slaves, orphans and upper-class Ethiopian and European girls. After providing a brief background to the…

  20. Discovering non-random segregation of sister chromatids: The naïve treatment of a premature discovery

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    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.

  1. Crystal Structure of the Cohesin Gatekeeper Pds5 and in Complex with Kleisin Scc1

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    Byung-Gil Lee

    2016-03-01

    Full Text Available Sister chromatid cohesion is mediated by cohesin, whose Smc1, Smc3, and kleisin (Scc1 subunits form a ring structure that entraps sister DNAs. The ring is opened either by separase, which cleaves Scc1 during anaphase, or by a releasing activity involving Wapl, Scc3, and Pds5, which bind to Scc1 and open its interface with Smc3. We present crystal structures of Pds5 from the yeast L. thermotolerans in the presence and absence of the conserved Scc1 region that interacts with Pds5. Scc1 binds along the spine of the Pds5 HEAT repeat fold and is wedged between the spine and C-terminal hook of Pds5. We have isolated mutants that confirm the observed binding mode of Scc1 and verified their effect on cohesin by immunoprecipitation and calibrated ChIP-seq. The Pds5 structure also reveals architectural similarities to Scc3, the other large HEAT repeat protein of cohesin and, most likely, Scc2.

  2. Improving Emotion Regulation and Sibling Relationship Quality: The More Fun with Sisters and Brothers Program

    Science.gov (United States)

    Kennedy, Denise E.; Kramer, Laurie

    2008-01-01

    We examined the role of emotion regulation (ER) in improving sibling relationship quality (SRQ) by evaluating the More Fun With Sisters and Brothers Program where 4- to 8-year-old siblings from 95 families were taught emotional and social competencies. Parents reported on SRQ and ER, and sibling interactions were observed in homes. SRQ and ER…

  3. 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.

  4. 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

  5. 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.

  6. When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

    Directory of Open Access Journals (Sweden)

    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

  7. 77 FR 48993 - Proposed Collection; Comment Request; The Sister Study: A Prospective Study of the Genetic and...

    Science.gov (United States)

    2012-08-15

    ... Genetic and Environmental Risk Factors for Breast Cancer SUMMARY: In compliance with the requirement of... proposed data collection projects, the National Institute of Environmental Health Sciences (NIEHS), the... Sister Study: A Prospective Study of the Genetic and Environmental Risk Factors for Breast Cancer. Type...

  8. Coordination of the Ser2056 and Thr2609 Clusters of DNA-PKcs in Regulating Gamma Rays and Extremely Low Fluencies of Alpha-Particle Irradiation to G0/G1 Phase Cells.

    Science.gov (United States)

    Nagasawa, Hatsumi; Lin, Yu-Fen; Kato, Takamitsu A; Brogan, John R; Shih, Hung-Ying; Kurimasa, Akihiro; Bedford, Joel S; Chen, Benjamin P C; Little, John B

    2017-02-01

    The catalytic subunit of DNA dependent protein kinase (DNA-PKcs) and its kinase activity are critical for mediation of non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSB) in mammalian cells after gamma-ray irradiation. Additionally, DNA-PKcs phosphorylations at the T2609 cluster and the S2056 cluster also affect DSB repair and cellular sensitivity to gamma radiation. Previously we reported that phosphorylations within these two regions affect not only NHEJ but also homologous recombination repair (HRR) dependent DSB repair. In this study, we further examine phenotypic effects on cells bearing various combinations of mutations within either or both regions. Effects studied included cell killing as well as chromosomal aberration induction after 0.5-8 Gy gamma-ray irradiation delivered to synchronized cells during the G 0 /G 1 phase of the cell cycle. Blocking phosphorylation within the T2609 cluster was most critical regarding sensitization and depended on the number of available phosphorylation sites. It was also especially interesting that only one substitution of alanine in each of the two clusters separately abolished the restoration of wild-type sensitivity by DNA-PKcs. Similar patterns were seen for induction of chromosomal aberrations, reflecting their connection to cell killing. To study possible change in coordination between HRR and NHEJ directed repair in these DNA-PKcs mutant cell lines, we compared the induction of sister chromatid exchanges (SCEs) by very low fluencies of alpha particles with mutant cells defective in the HRR pathway that is required for induction of SCEs. Levels of true SCEs induced by very low fluence of alpha-particle irradiation normally seen in wild-type cells were only slightly decreased in the S2056 cluster mutants, but were completely abolished in the T2609 cluster mutants and were indistinguishable from levels seen in HRR deficient cells. Again, a single substitution in the S2056 together with a single

  9. The role of natural indigo dye in alleviation of genotoxicity of sodium dithionite as a reducing agent.

    Science.gov (United States)

    Bektaş, İdris; Karaman, Şengül; Dıraz, Emel; Çelik, Mustafa

    2016-12-01

    Indigo blue is a natural dye used for thousands of years by civilizations to dye fabric blue and it is naturally obtained from Isatis tinctoria. I. tinctoria is not only used for extraction of indigo blue color but also used medicinally in Traditional Chinese Medicine because of its active compounds. Sodium dithionite (Na 2 S 2 O 4 ) is used in dye bath for indigo blue extraction, but this reducing agent and its derivatives are major pollutants of textile industry and subsequently have hazardous influences on public health. Herein, the present study was designed to obtain the high yield of natural indigo dye but with low possible toxic effect. In this context, genotoxic effects of particular combinations of natural dye solutions obtained from Isatis tinctoria subsp. tomentolla with Na 2 S 2 O 4 as reducing agent were investigated. Dye solutions were obtained using two different pH levels (pH 9 and 11) and three different concentrations of Na 2 S 2 O 4 (2.5, 5 and 10 mg/ml). In addition to the dye solutions and reducing agent, aqueous extracts of I. tinctoria were assessed for their genotoxicity on human lymphocytes. For in vitro testing of genotoxicity, chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and mitotic indexes (MI) assays were used. Accordingly, Na 2 S 2 O 4 caused significant increases in CA and SCE as well decrease in MI but the genotoxic effects of sodium dithionite were reduced with natural indigo dye. As a result, aqueous extracts of Isatis leaves removed the toxic effects of sodium dithionite and showed anti-genotoxic effect. For the optimal and desired quality but with less toxic effects of natural dye, 2.5 mg/ml (for wool yarn) and 5 mg/ml (for cotton yarn) of Na 2 S 2 O 4 doses were found to be the best doses for reduction in the dye bath at Ph 9.

  10. Genotoxic and cytotoxic effects of different types of dental cement on normal cultured human lymphocytes.

    Science.gov (United States)

    Bakopoulou, A; Mourelatos, D; Tsiftsoglou, A S; Giassin, N P; Mioglou, E; Garefis, P

    2009-01-31

    In this study we have investigated the genotoxic and cytotoxic effects of eluates derived from different types of commercially available dental cements, including glass ionomer cements (GICs) (Ketac Cem/3M ESPE and GC Fuji I/GC Corp), resin-modified glass ionomer cements (RM-GICs) (RelyX Luting/3M ESPE and Vitrebond/3M ESPE) and dual-cure resin cements (RCs) (Variolink II/ Ivoclar-Vivadent and Panavia F 2.0/Kuraray) on normal cultured human lymphocytes. Lymphocyte primary cultures obtained from blood samples of three healthy donors were exposed to serial dilutions of eluates derived from specimens of each material tested. Metaphases were induced with phytohaemagglutinin, collected after 72h treatment by use of colchicine and stained according to the fluorescence plus giemsa (FPG) procedure. Preparations were scored for sister chromatid exchange (SCE) and chromosomal aberrations (CAs), while the proliferation rate index (PRI) was also calculated. Our results show that eluates derived from the RM-GICs and RCs caused severe genotoxic effects by significantly increasing the frequencies of SCEs and CAs in cultures of peripheral blood lymphocytes and by decreasing the relevant PRI values in a dose-dependent manner, whereas the two GICs caused only minor cytogenetic effects. Eluates of the two RM-GICs (Vitrebond and RelyX) were also very cytotoxic, as the first serial dilutions of both materials caused a complete mitotic arrest in lymphocyte cultures. Overall, the degree of genotoxicity and cytotoxicity caused by dental cements decreased as follows: Viterbond>Rely X>Panavia F 2.0>Variolink II>Ketac Cem=GC Fuji I. These results indicate that different types of dental cement differ extensively in their genotoxic and cytotoxic potential and their ability to affect chromosomal integrity, cell-cycle progression, DNA replication and repair. Although these results cannot be directly extrapolated to the clinical situation, the potential occurrence of adverse effects caused by the

  11. Differences in mycorrhizal communities between Epipactis palustris, E. helleborine and its presumed sister species E. neerlandica

    OpenAIRE

    Jacquemyn, Hans; Waud, Michael; Lievens, Bart; Brys, Rein

    2016-01-01

    Background and Aims In orchid species that have populations occurring in strongly contrasting habitats, mycorrhizal divergence and other habitat-specific adaptations may lead to the formation of reproductively isolated taxa and ultimately to species formation. However, little is known about the mycorrhizal communities associated with recently diverged sister taxa that occupy different habitats.

  12. Mercury poisoning in two 13-year-old twin sisters

    Directory of Open Access Journals (Sweden)

    Ezzat Khodashenas

    2015-01-01

    Full Text Available Mercury (Hg is a toxic agent that evaporates in room temperature and its inhalation may cause poisoning. Due to the nonspecific symptoms, diagnosis is difficult in special circumstances with no initial history of Hg exposure. We report two such cases of Hg poisoning. The patients were two sisters, presenting with pain in extremities, itchy rashes, sweating, salivation, weakness, and mood changes. They have used a compound that contains mercury, for treatment of pedicullosis three months before admission. This compound was purchased from a herbal shop and was applied locally on the scalps for 2 days. Their urinary mercury concentrations were 50 and 70 mg/L. They were successfully treated by D-penicillamine and gabapentin. In a patient with any kind of bone and joint pain, skin rash erythema and peripheral neuropathy, mercury poisoning should be considered as a differential diagnosis.

  13. 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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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)

  15. 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

  16. 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

  17. 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)

  18. Historical biogeography and diversification of truffles in the Tuberaceae and their newly identified Southern hemisphere sister lineage

    Science.gov (United States)

    Gregory Bonito; Matthew E. Smith; Michael Nowak; Rosanne A. Healy; Gonzalo Guevara; Efren Cazares; Akihiko Kinoshita; Eduardo R. Nouhra; Laura S. Dominguez; Leho Tedersoo; Claude Murat; Yun Wang; Baldomero Arroyo Moreno; Donald H. Pfister; Kazuhide Nara; Alessandra Zambonelli; James M. Trappe; Rytas. Vilgalys

    2013-01-01

    In this study we reassessed the biogeography and origin of the Tuberaceae and their relatives using multiple loci and a global sampling of taxa. Multiple independent transitions from an aboveground to a belowground truffie fruiting body form have occurred in the Tuberaceae and in its newly recognized sister lineage...

  19. Novel Familial Variant of the Desert Hedgehog Gene: Clinical Findings in Two Sisters with 46,XY Gonadal Dysgenesis or 46,XX Karyotype and Literature Review.

    Science.gov (United States)

    Baldinotti, Fulvia; Cavallaro, Tiziana; Dati, Eleonora; Baroncelli, Giampiero I; Bertini, Veronica; Valetto, Angelo; Massart, Francesco; Fabrizi, Gian Maria; Zanette, Giampietro; Peroni, Diego; Bertelloni, Silvano

    2018-01-01

    In humans, Desert Hedgehog (DHH) gene mutations are a very rare cause of 46,XY gonadal dysgenesis (GD), eventually associated with peripheral neuropathy. Clinical records of 12 patients with 46,XY GD and unknown genetic background were reviewed and a 46,XY woman with peripheral neuropathy was individuated. Her 46,XX sister affected by similar neuropathy was also investigated. Genomic DNA was extracted and DHH exons sequenced and analyzed. A comparative genomic hybridization array was also performed. In both the 46,XY and 46,XX sisters, a homozygous c.554C>A mutation in exon 2 of the DHH gene was found, determining a premature termination codon (p.Ser 185*). Heterozygous consanguineous carrier parents showed neither reproductive problems nor peripheral neuropathy. In the proband and her sister, a 499-kb duplication in 9p22.1 was also found. A 46,XY European woman with 46,XY GD and a novel homozygous DHH pathogenic variant is reported, confirming that this gene plays a key role in male gonadal development. Her 46,XX sister, harboring the same mutation, showed normal internal and external female phenotype. Thus, DHH seems not to be involved in the ovarian development pathway or its postpubertal function. Homozygous DHH mutations cause a specific peripheral neuropathy in humans with both 46,XY and 46,XX karyotypes. © 2018 S. Karger AG, Basel.

  20. Interview: Tatyana Lipovskaya, Sisters Sexual Assault Recovery Centre, Moscow, Russia.

    Science.gov (United States)

    1998-11-01

    The Sisters' Sexual Assault Recovery Center was established in Moscow, Russia, in 1993, to address the needs of victims of sexual violence. The Center's help-line received 4029 crisis calls in 1994-97. Most clients are seeking information about medical services or legal aid. Others call about employment, HIV/AIDS, alcoholism, and drug abuse. Services are available without regard to age, sex, occupation, or sexual orientation. Program funding has come entirely from Western foundations and organizations. Although Russia has not passed a law on domestic violence, the post-Communism government is reluctantly starting to acknowledge that rape and domestic violence are serious social problems. The Center runs an educational program for law enforcement officers to increase their sensitivity and create an environment of safety for women who report sexual violence.