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Sample records for radiation-induced g1 arrest

  1. Radiosensitization of NSCLC cells by EGFR inhibition is the result of an enhanced p53-dependent G1 arrest

    International Nuclear Information System (INIS)

    Kriegs, Malte; Gurtner, Kristin; Can, Yildiz; Brammer, Ingo; Rieckmann, Thorsten; Oertel, Reinhard; Wysocki, Marek; Dorniok, Franziska; Gal, Andreas; Grob, Tobias J.; Laban, Simon; Kasten-Pisula, Ulla; Petersen, Cordula; Baumann, Michael; Krause, Mechthild; Dikomey, Ekkehard

    2015-01-01

    Purpose: How EGF receptor (EGFR) inhibition induces cellular radiosensitization and with that increase in tumor control is still a matter of discussion. Since EGFR predominantly regulates cell cycle and proliferation, we studied whether a G1-arrest caused by EGFR inhibition may contribute to these effects. Materials and methods: We analyzed human non-small cell lung cancer (NSCLC) cell lines either wild type (wt) or mutated in p53 (A549, H460, vs. H1299, H3122) and HCT116 cells (p21 wt and negative). EGFR was inhibited by BIBX1382BS, erlotinib or cetuximab; p21 was knocked down by siRNA. Functional endpoints analyzed were cell signaling, proliferation, G1-arrest, cell survival as well as tumor control using an A549 tumor model. Results: When combined with IR, EGFR inhibition enhances the radiation-induced permanent G1 arrest, though solely in cells with intact p53/p21 signaling. This increase in G1-arrest was always associated with enhanced cellular radiosensitivity. Strikingly, this effect was abrogated when cells were re-stimulated, suggesting the initiation of dormancy. In line with this, only a small non-significant increase in tumor control was observed for A549 tumors treated with fractionated RT and EGFR inhibition. Conclusion: For NSCLC cells increase in radiosensitivity by EGFR inhibition results from enhanced G1-arrest. However, this effect does not lead to improved tumor control because cells can be released from this arrest by re-stimulation

  2. Abnormal G1 arrest in the cell lines from LEC strain rats after X-irradiation

    International Nuclear Information System (INIS)

    Hayashi, M.; Uehara, K.; Kirisawa, R.; Endoh, D.; Arai, S.; Okui, T.

    1997-01-01

    The effect of X-irradiation of cell lines from LEC and WKAH strain rats on a progression o cell cycle was investigated. When WKAH rat ells were exposed to 5 Gy of X-rays and their cell cycle distribution was determined by a flow cytometer, the proportion of S-phase cells decrease and that of G2/M-phase cells in creased at 8 hr post-irradiation. At 18 and 24 hr post-irradiation, approximately 80% of the cells appeared in the G1 phase. On the contrary, the proportion of S-phase cells increased and that of G1-phase cells decreased in LEC rats during 8-24 hr post-irradiation, compared with that at 0 hr post-irradiation. Thus, radiation-induced delay in the progression from the G1 phase to S phase (G1 arrest) was observed inWKAH rat cells but not in LEC rat cells. In the case of WKAH rat cells, the intensities of the bands of p53 protein increased at 1 and 2 hr after X-irradiation at 5 Gy, compared with those of un-irradiated cells and at 0 hr post-irradiation. In contrast, the intensities of the bands were faint and did not significantly increase in LEC rat ells during 0-6 hr incubation after X-irradiation. Present results suggested that the radioresistant DNA synthesis in LEC rat cells is thought to be due to the abnormal G1 arrest following X-irradiation

  3. Analysis of the G1 arrest position of senescent WI38 cells by quinacrine dihydrochloride nuclear fluorescence: evidence for a late G1 arrest

    International Nuclear Information System (INIS)

    Gorman, S.D.; Cristofalo, V.J.

    1986-01-01

    Senescence of the human diploid fibroblast-like cell line, W138, is characterized by a loss of proliferative activity and an arrest of cells with a 2C DNA content (G1 or G0). To examine the specific region within G1 in which senescent cells arrest, senescent cells were stained with quinacrine dihydrochloride (QDH) and their nuclear fluorescence was compared with that of young cultures arrested in early and late G1 by serum deprivation and hydroxyurea exposure, respectively. Release of these G1-arrested young cultures from their blocking conditions and timing the kinetics of their entry into the S phase by autoradiographic detection of [ 3 H]thymidine incorporation revealed that serum-deprived cells entered the S phase within 15-18h, whereas hydroxyurea-exposed cells entered the S phase within 1.5h, thus confirming their relative G1-arrest positions. QDH-stained, serum-deprived and hydroxyurea-exposed young cells exhibited relative nuclear fluorescence intensities of 51.7 and 23.9, respectively. Senescent cells exhibited a relative nuclear fluorescence intensity of 17.4, closely resembling the fluorescence of young cultures arrested in late G1 by hydroxyurea exposure. These data support the concept that senescent cells are arrested from further progression in the cell cycle in late G1

  4. F-box protein FBXO31 is a dedicated checkpoint protein to facilitate cell cycle arrest through activation of regulators in radiation induced DNA damage

    International Nuclear Information System (INIS)

    Santra, Manas Kumar

    2017-01-01

    In response to radiation-induced DNA damage, eukaryotic cells initiate a complex signalling pathway, termed the DNA damage response (DDR), which coordinates cell cycle arrest with DNA repair. Previous study showed that induction of G1 arrest in response to radiation induced DNA damage is minimally a two-step process: a fast p53-independent initiation of G1 arrest mediated by cyclin D1 proteolysis and a slower maintenance of arrest resulting from increased p53 stability. We elucidated the molecular mechanism of slow and fast response of radiation induced DDR. We showed that FBXO31, a member of F-box family proteins, plays important role in DDR induced by ionizing radiation. We show that FBXO31 is responsible for promoting MDM2 degradation following radiation. FBXO31 interacts with and directs the degradation of MDM2 in ATM dependent phosphorylation of MDM2. FBXO31-mediated loss of MDM2 leads to elevated levels of p53, resulting in growth arrest. In cells depleted of FBXO31, MDM2 is not degraded and p53 levels do not increase following genotoxic stress. Thus, FBXO31 is essential for the classic robust increase in p53 levels following DNA damage

  5. Influence of novobiocin on mitotic events and radiation-induced G2-arrest

    International Nuclear Information System (INIS)

    Rowley, R.

    1987-01-01

    Novobiocin was used in CHO cells to test for an involvement of topoisomerase II activity in; 1) the induction of, and recovery from, radiation-induced G 2 -arrest and 2) progression through mitosis. Novobiocin blocked recovery from G 2 -arrest with a concentration dependency which suggested that this effect resulted from protein synthesis inhibition. Novobiocin alone, at concentrations above 500 μgml, blocked cell progression in early mitosis. The transition point was distinct from that of protein and RNA synthesis inhibitors and was the only arrest point in mitosis. A similar block was imposed by coumermycin. While this may indicate a requirement for topoisomerase II activity during chromosome condensation, it was also associated with inhibition of histone phosphorylation. Histone H3 phosphorylation is believed to be necessary for chromosome condensation and, when inhibited by novobiocin, correlates with a block in premature chromatin condensation in tsBN2 cells. The authors' data thus unite these two findings, provide an opportunity to analyse the temporal relationship between histone phosphorylation and mitotic events and suggest that topological reorganization of the chromatin is not involved in radiation-induced G 2 arrest

  6. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    International Nuclear Information System (INIS)

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun; Zheng, Lemin; Zhou, Boda; Zhang, Wei; Lv, He; Yuan, Yun

    2014-01-01

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21

  7. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Zheng, Lemin [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing 100191 (China); Zhou, Boda [The Department of Cardiology, Peking University Third Hospital, Beijing 100191 (China); Zhang, Wei; Lv, He [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Yuan, Yun, E-mail: yuanyun2002@sohu.com [Department of Neurology, Peking University First Hospital, Beijing 100034 (China)

    2014-03-28

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21.

  8. Cell cycle age dependence for radiation-induced G2 arrest: evidence for time-dependent repair

    International Nuclear Information System (INIS)

    Rowley, R.

    1985-01-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G 2 . The sensitivity of Chinese hamster ovary cells to G 2 arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G 2 . This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G 2 arrest and/or by changes in capability for postirradiation recovery from G 2 arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G 2 arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G 2 arrest, while inhibiting repair of G 2 arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G 2 arrest was expressed. The duration of G 2 arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G 2 arrest induction is present throughout the cell cycle and that the level of G 2 arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G 2 arrest

  9. Cell cycle arrest in plants: what distinguishes quiescence, dormancy and differentiated G1?

    Science.gov (United States)

    Velappan, Yazhini; Signorelli, Santiago; Considine, Michael J

    2017-10-17

    Quiescence is a fundamental feature of plant life, which enables plasticity, renewal and fidelity of the somatic cell line. Cellular quiescence is defined by arrest in a particular phase of the cell cycle, typically G1 or G2; however, the regulation of quiescence and proliferation can also be considered across wider scales in space and time. As such, quiescence is a defining feature of plant development and phenology, from meristematic stem cell progenitors to terminally differentiated cells, as well as dormant or suppressed seeds and buds. While the physiology of each of these states differs considerably, each is referred to as 'cell cycle arrest' or 'G1 arrest'. Here the physiology and molecular regulation of (1) meristematic quiescence, (2) dormancy and (3) terminal differentiation (cell cycle exit) are considered in order to determine whether and how the molecular decisions guiding these nuclear states are distinct. A brief overview of the canonical cell cycle regulators is provided, and the genetic and genomic, as well as physiological, evidence is considered regarding two primary questions: (1) Are the canonical cell cycle regulators superior or subordinate in the regulation of quiescence? (2) Are these three modes of quiescence governed by distinct molecular controls? Meristematic quiescence, dormancy and terminal differentiation are each predominantly characterized by G1 arrest but regulated distinctly, at a level largely superior to the canonical cell cycle. Meristematic quiescence is intrinsically linked to non-cell-autonomous regulation of meristem cell identity, and particularly through the influence of ubiquitin-dependent proteolysis, in partnership with reactive oxygen species, abscisic acid and auxin. The regulation of terminal differentiation shares analogous features with meristematic quiescence, albeit with specific activators and a greater role for cytokinin signalling. Dormancy meanwhile appears to be regulated at the level of chromatin

  10. Identification of herpesvirus proteins that contribute to G1/S arrest.

    Science.gov (United States)

    Paladino, Patrick; Marcon, Edyta; Greenblatt, Jack; Frappier, Lori

    2014-04-01

    Lytic infection by herpesviruses induces cell cycle arrest at the G1/S transition. This appears to be a function of multiple herpesvirus proteins, but only a minority of herpesvirus proteins have been examined for cell cycle effects. To gain a more comprehensive understanding of the viral proteins that contribute to G1/S arrest, we screened a library of over 200 proteins from herpes simplex virus type 1, human cytomegalovirus, and Epstein-Barr virus (EBV) for effects on the G1/S interface, using HeLa fluorescent, ubiquitination-based cell cycle indicator (Fucci) cells in which G1/S can be detected colorimetrically. Proteins from each virus were identified that induce accumulation of G1/S cells, predominantly tegument, early, and capsid proteins. The identification of several capsid proteins in this screen suggests that incoming viral capsids may function to modulate cellular processes. The cell cycle effects of selected EBV proteins were further verified and examined for effects on p53 and p21 as regulators of the G1/S transition. Two EBV replication proteins (BORF2 and BMRF1) were found to induce p53 but not p21, while a previously uncharacterized tegument protein (BGLF2) was found to induce p21 protein levels in a p53-independent manner. Proteomic analyses of BGLF2-interacting proteins identified interactions with the NIMA-related protein kinase (NEK9) and GEM-interacting protein (GMIP). Silencing of either NEK9 or GMIP induced p21 without affecting p53 and abrogated the ability of BGLF2 to further induce p21. Collectively, these results suggest multiple viral proteins contribute to G1/S arrest, including BGLF2, which induces p21 levels likely by interfering with the functions of NEK9 and GMIP. Most people are infected with multiple herpesviruses, whose proteins alter the infected cells in several ways. During lytic infection, the viral proteins block cell proliferation just before the cellular DNA replicates. We used a novel screening method to identify proteins

  11. Parafibromin inhibits cancer cell growth and causes G1 phase arrest

    International Nuclear Information System (INIS)

    Zhang Chun; Kong Dong; Tan, M.-H.; Pappas, Donald L.; Wang, P.-F.; Chen, Jindong; Farber, Leslie; Zhang Nian; Koo, H.-M.; Weinreich, Michael; Williams, Bart O.; Teh, B.T.

    2006-01-01

    The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation of parafibromin predisposes one to the development of HPT-JT syndrome. To date, the role of parafibromin in tumorigenesis is largely unknown. Here, we report that parafibromin is a nuclear protein that possesses anti-proliferative properties. We show that overexpression of parafibromin inhibits colony formation and cellular proliferation, and induces cell cycle arrest in the G1 phase. Moreover, HPT-JT syndrome-derived mutations in HRPT2 behave in a dominant-negative manner by abolishing the ability of parafibromin to suppress cell proliferation. These findings suggest that parafibromin has a critical role in cell growth, and mutations in HRPT2 can directly inhibit this role

  12. Inhibition of G1-phase arrest induced by ionizing radiation in hematopoietic cells by overexpression of genes involved in the G1/S-phase transition

    International Nuclear Information System (INIS)

    Epperly, M.; Berry, L.; Halloran, A.; Greenberger, J.S.

    1995-01-01

    D-type cyclins and cyclin-dependent kinase (cdk-4) are likely involved in regulating passage of cells through the G 1 phase of the cell cycle. A decrease in the proportion of cells in G 1 , a relatively radiation-sensitive phase of the cell cycle, should result in increased resistance to ionizing radiation; however, the effect of such overexpression on X-ray-induced G 1 -phase arrest is not known. Radiation survival curves were obtained at a dose rate of either 8 cGy/min or 1 Gy/min for subclones of the IL-3-dependent hematopoietic progenitor cell line 32D cl 3 expressing transgenes for either cyclin-D1, D2 or D3 or cdk-4. We compared the results to those with overexpression of the transgene for Bcl-2, whose expression enhances radiation survival and delays apoptosis. Cells overexpressing transgenes for each D-type cyclin or Bcl-2 had an increased number of cells in S phase compared to parent line 32D cl 3; however, overexpression of cdk-4 had no effect on cell cycle distribution. Cell death resulting from withdrawal of IL-3 was not affected by overexpression of D2, cdk-4 or Bcl-2. Flow cytometry 24 h after 5 Gy irradiation demonstrated that overexpression of each G 1 -phase regulatory transgene decreased the proportion of cells at the G 1 /S-phase border. Western analysis revealed induction of cyclin-D protein levels by irradiation, but no change in the D O , but a significant increase in the rvec n for cyclin-D or cdk-4 transgene-overexpressing clones at 1 Gy/min (P 1 /S-phase arrest. 31 refs., 4 figs., 4 tabs

  13. Radiation-induced G/sub 2/-arrest is reduced by inhibitors of poly(adenosine diphosphoribose) synthetase

    International Nuclear Information System (INIS)

    Rowley, R.

    1985-01-01

    Experiments are in progress to test whether poly(adenosine diphosphoribose) synthesis is required for the induction of G/sub 2/-arrest in growing mammalian cells following X-irradiation. A variety of poly(ADPR) synthetase inhibitors have been tested to determine: 1) whether addition of an inhibitor to X-irradiated CHO cells reduces G/sub 2/-arrest; 2) whether compounds structurally similar to poly-(ADPR) synthetase inhibitors but inactive against this enzyme affect radiation-induced G/sub 2/-arrest and 3) whether the concentration dependence for poly(ADPR) synthetase inhibition matches that for G/sub 2/-arrest reduction. G/sub 2/-arrest was measured in X-irradiated (1.5 Gy) CHO cells using the mitotic cell selection technique. Poly(ADPR) synthetase activity was measured in permeabilized cells by /sup 3/H-NAD incorporation. The synthetase inhibitors used were 3-aminobenzamide, benzamide, nicotinamide, 4-acetyl pyridine, caffeine and theophylline. The inactive compounds used were 3-aminobenzoic acid, benzoic acid, nicotinic acid, adenine, adenosine and 3'-deoxyadenosine. Inhibitors of poly(ADPR) synthetase reduced G/sub 2/-arrest while related compounds which produced no enzyme inhibition did not. The concentration dependencies for G/sub 2/-arrest reduction and enzyme inhibition were similar only for methyl xanthines. Further analysis awaits the determination of intracellular drug concentrations

  14. Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.

    Directory of Open Access Journals (Sweden)

    Neel M Fofaria

    Full Text Available In this study, we determined the cytotoxic effects of piperine, a major constituent of black and long pepper in melanoma cells. Piperine treatment inhibited the growth of SK MEL 28 and B16 F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine correlated with the down-regulation of cyclin D1 and induction of p21. Furthermore, this growth arrest by piperine treatment was associated with DNA damage as indicated by phosphorylation of H2AX at Ser139, activation of ataxia telangiectasia and rad3-related protein (ATR and checkpoint kinase 1 (Chk1. Pretreatment with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Similarly, transfection of cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine. Piperine treatment caused down-regulation of E2F1 and phosphorylation of retinoblastoma protein (Rb. Apoptosis induced by piperine was associated with down-regulation of XIAP, Bid (full length and cleavage of Caspase-3 and PARP. Furthermore, our results showed that piperine treatment generated ROS in melanoma cells. Blocking ROS by tiron protected the cells from piperine mediated cell cycle arrest and apoptosis. These results suggest that piperine mediated ROS played a critical role in inducing DNA damage and activation of Chk1 leading to G1 cell cycle arrest and apoptosis.

  15. The effect of modulators of radiation-induced G2 arrest on the repair of radiation-induced DNA damage detectable by neutral filter elution

    International Nuclear Information System (INIS)

    Rowley, R.; Kort, L.

    1988-01-01

    The influence of cycloheximide (50 μg/ml), caffeine (5 mM) and cordycepin (0.15 mM) on the repair of the damage detectable in DNA by neutral filter elution was determined. Chinese hamster ovary cells (CHO) were irradiated with X-ray doses of 20, 60 and 100 Gy then allowed to repair without drug treatment or in the presence of each drug for intervals up to 6 h. DNA damage repair proceeded in two phases. The fast component of the repair process (t 1/2 approx. 7 min) was not modified by drug treatment; the slow component (t 1/2 170 min) was unaffected by cycloheximide or cordycepin, but appeared to be inhibited by caffeine. It was concluded that: (a) the lesion which results in radiation-induced G 2 arrest is not the lesion which is detectable by neutral filter elution, and (b) the influence of caffeine on dsb repair is specific to caffeine and is not mediated by a reduction in the duration of G 2 arrest. (author)

  16. SUN1 silencing inhibits cell growth through G0/G1 phase arrest in lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Huang W

    2017-06-01

    Full Text Available Weiyi Huang,* Haihua Huang,* Lei Wang, Jiong Hu, Weifeng Song Department of Oncology, The First People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Cytoskeleton is critical for carcinoma cell proliferation, migration, and invasion. Sad-1 and UNC-84 domain containing 1 (SUN1 is one of the core linkers of nucleoskeleton and cytoskeleton. However, the functions of SUN1 in lung adenocarcinoma are largely unknown.Methods: In this study, we first transduced the lentivirus delivering the short hairpin RNA (shRNA against SUN1 to lung adenocarcinoma cells (A549 and 95D cells with high efficiency. After lentivirus infection, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expressions of SUN1 mRNA and protein. The cell proliferation and colony formation were detected by MTT assay and colony formation assay, respectively. The cell distribution in the cell cycle was analyzed by flow cytometry.Results: Both mRNA and protein levels of SUN1 were significantly decreased in A549 and 95D cells after lentivirus infection, as indicated by quantitative real-time polymerase chain reaction and Western blot. Next, we found that cell proliferation and colony formation were markedly reduced in SUN1 silenced cells. Moreover, suppression of SUN1 led to cell cycle arrest at G0/G1 phase. Furthermore, Cyclin D1, CDK6, and CDK2 expressions were obviously reduced in A549 cells after SUN1 silencing.Conclusion: These results suggest that SUN1 plays an essential role in proliferation of lung adenocarcinoma cells in vitro and may be used as a potential therapeutic target for the treatment of lung adenocarcinoma in the future. Keywords: SUN1, lung cancer, proliferation

  17. Effects of Chk1 inhibition on the temporal duration of radiation-induced G2 arrest in HeLa cells

    International Nuclear Information System (INIS)

    Nahar, Kamrun; Goto, Tatsuaki; Kaida, Atsushi; Deguchi, Shifumi; Miura, Masahiko

    2014-01-01

    Chk1 inhibitor acts as a potent radiosensitizer in p53-deficient tumor cells by abrogating the G2/M check-point. However, the effects of Chk1 inhibitor on the duration of G2 arrest have not been precisely analyzed. To address this issue, we utilized a cell-cycle visualization system, fluorescent ubiquitination-based cell-cycle indicator (Fucci), to analyze the change in the first green phase duration (FGPD) after irradiation. In the Fucci system, G1 and S/G2/M cells emit red and green fluorescence, respectively; therefore, G2 arrest is reflected by an elongated FGPD. The system also allowed us to differentially analyze cells that received irradiation in the red or green phase. Cells irradiated in the green phase exhibited a significantly elongated FGPD relative to cells irradiated in the red phase. In cells irradiated in either phase, Chk1 inhibitor reduced FGPD almost to control levels. The results of this study provide the first clear information regarding the effects of Chk1 inhibition on radiation-induced G2 arrest, with special focus on the time dimension. (author)

  18. Chromosome condensation and radiation-induced G2 arrest studied by the induction of premature chromosome condensation following cell fusion

    International Nuclear Information System (INIS)

    Mitchell, J.B.; Bedford, J.S.

    1978-01-01

    When mitotic and interphase cells are fused together, the chromosomes of the interphase cell sometimes condense prematurely. The phenomenon of premature chromosome condensation (PCC) was utilized in investigating the problem of whether the chromosomes of cells suffering a radiation-induced G 2 delay are capable of condensation. Colcemide-arrested mitotic cells were fused with synchronized G 2 cells, and with irradiated cells suffering a G 2 delay. The frequency of PCC in mitotic X G 2 binucleate cells was determined. This was compared to the PCC frequency in an unirradiated synchronized population rich in G 2 cells after fusion with mitotic cells. Flash-labelling with 3 HTdR and autoradiography allowed S-phase cells to be eliminated. The frequency of G 2 PCCs was not significantly different for the irradiated G 2 -delayed or unirradiated cells. From these results it was concluded that the chromosomes of cells suffering a G 2 arrest are capable of condensation, although the involvement of the condensation process in radiation-induced G 2 delay could not be ruled out. (author)

  19. A novel peptide sansalvamide analogue inhibits pancreatic cancer cell growth through G0/G1 cell-cycle arrest

    International Nuclear Information System (INIS)

    Ujiki, Michael B.; Milam, Ben; Ding Xianzhong; Roginsky, Alexandra B.; Salabat, M. Reza; Talamonti, Mark S.; Bell, Richard H.; Gu Wenxin; Silverman, Richard B.; Adrian, Thomas E.

    2006-01-01

    Patients with pancreatic cancer have little hope for cure because no effective therapies are available. Sansalvamide A is a cyclic depsipeptide produced by a marine fungus. We investigated the effect of a novel sansalvamide A analogue on growth, cell-cycle phases, and induction of apoptosis in human pancreatic cancer cells in vitro. The sansalvamide analogue caused marked time- and concentration-dependent inhibition of DNA synthesis and cell proliferation of two human pancreatic cancer cell lines (AsPC-1 and S2-013). The analogue induced G0/G1 phase cell-cycle arrest and morphological changes suggesting induction of apoptosis. Apoptosis was confirmed by annexin V binding. This novel sansalvamide analogue inhibits growth of pancreatic cancer cells through G0/G1 arrest and induces apoptosis. Sansalvamide analogues may be valuable for the treatment of pancreatic cancer

  20. An inhibitor of polyamine synthesis arrests cells at an earlier stage of G1 than does calcium deprivation.

    OpenAIRE

    Cheetham, B F

    1983-01-01

    Methylglyoxal bis(guanylhydrazone) completely inhibits the induction of thymidine kinase after serum stimulation of quiescent fibroblasts only if added within 3 h after serum, whereas calcium deprivation blocks this induction up to 12 h after serum stimulation. Experiments in which one of these blocks was imposed as the other was released confirmed that cells blocked by methylglyoxal bis(guanylhydrazone) are arrested at an earlier stage in G1 than cells blocked by calcium deprivation.

  1. An inhibitor of polyamine synthesis arrests cells at an earlier stage of G1 than does calcium deprivation.

    Science.gov (United States)

    Cheetham, B F

    1983-01-01

    Methylglyoxal bis(guanylhydrazone) completely inhibits the induction of thymidine kinase after serum stimulation of quiescent fibroblasts only if added within 3 h after serum, whereas calcium deprivation blocks this induction up to 12 h after serum stimulation. Experiments in which one of these blocks was imposed as the other was released confirmed that cells blocked by methylglyoxal bis(guanylhydrazone) are arrested at an earlier stage in G1 than cells blocked by calcium deprivation. PMID:6843551

  2. Porcine epidemic diarrhea virus through p53-dependent pathway causes cell cycle arrest in the G0/G1 phase.

    Science.gov (United States)

    Sun, Pei; Wu, Haoyang; Huang, Jiali; Xu, Ying; Yang, Feng; Zhang, Qi; Xu, Xingang

    2018-05-22

    Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest. PEDV infection up-regulates the levels of p21, cdc2, cdk2, cdk4, Cyclin A protein and down-regulates Cyclin E protein. Further research results showed that inhibition of p53 signaling pathway can reverse the cell cycle arrest in G0/G1 phase induced by PEDV infection and cancel out the up-regulation of p21 and corresponding Cyclin/cdk mentioned above. In addition, PEDV infection of the cells synchronized in various stages of cell cycle showed that viral subgenomic RNA and virus titer were higher in the cells released from G0/G1 phase synchronized cells than that in the cells released from the G1/S phase and G2/M phase synchronized or asynchronous cells after 18 h p.i.. This is the first report to demonstrate that the p53-dependent pathway plays an important role in PEDV induced cell cycle arrest and beneficially contributes to viral infection. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Protein synthetic requirements for caffeine amelioration of radiation-induced G/sub 2/-arrest

    International Nuclear Information System (INIS)

    Rowley, R.; Colkitt, D.

    1984-01-01

    Irradiated cells are arrested in G/sub 2/ (transition point [TP] = 32 min before cell selection in mitosis). Irradiated cells do not recover from G/sub 2/ arrest in the presence of cycloheximide (CHM) indicating dependence of recovery on protein synthesis. Irradiated cells in the presence of caffeine progress to mitosis without arrest. The authors investigate whether irradiated cells in the presence of caffeine require protein synthesis to progress to mitosis. Mitotic cell selection was used to monitor the progression of irradiated CHO cells (150 rad) during exposure to 5 mM caffeine and/or 50 μg/ml CHM. Protein synthesis inhibition was confirmed using /sup 3/H-leucine incorporation. Cells exposed to CHM alone are arrested in G/sub 2/ (TP=49 min), thus cells beyond this point have synthesized all proteins necessary for entry into mitosis. In the presence of caffeine, unirradiated cells exposed to CHM are not arrested at all in G/sub 2/, instead arrest occurs near the S/G/sub 2/ boundary (TP=95 min) indicating that caffeine alleviates the dependence of G/sub 2/ cell progression on protein synthesis. However, irradiated cells exposed to both caffeine and CHM are only able to progress to mitosis if beyond the CHM-TP. Irradiated cells in the presence of caffeine thus behave as untreated cells and require protein synthesis for progression to mitosis when prior to the CHM-TP

  4. Effect of caffeine on radiation-induced mitotic delay: delayed expression of G2 arrest

    International Nuclear Information System (INIS)

    Rowley, R.; Zorch, M.; Leeper, D.B.

    1984-01-01

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G 2 cells progressed to mitosis in register and without arrest in G 2 . Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G 2 arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G 2 phases

  5. TEAD4-YAP interaction regulates tumoral growth by controlling cell-cycle arrest at the G1 phase

    International Nuclear Information System (INIS)

    Takeuchi, Shin; Kasamatsu, Atsushi; Yamatoji, Masanobu; Nakashima, Dai; Endo-Sakamoto, Yosuke; Koide, Nao; Takahara, Toshikazu; Shimizu, Toshihiro; Iyoda, Manabu; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2017-01-01

    TEA domain transcription factor 4 (TEAD4), which has critical functions in the process of embryonic development, is expressed in various cancers. However, the important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain unclear. Here we investigated the TEAD4 expression level and the functional mechanism in OSCC using quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4 knockdown model was used to evaluate cellular proliferation, cell-cycle analysis, and the interaction between TEAD4 and Yes-associated protein (YAP) which was reported to be a transcription coactivator of cellular proliferation. In the current study, we found that TEAD4 expression increased significantly in vitro and in vivo and correlated with tumoral size in OSCC patients. TEAD4 knockdown OSCC cells showed decreased cellular proliferation resulting from cell-cycle arrest in the G1 phase by down-regulation of cyclins, cyclin-dependent kinases (CDKs), and up-regulation of CDK inhibitors. We also found that the TEAD4-YAP complex in the nuclei may be related closely to transcriptions of G1 arrest-related genes. Taken together, we concluded that TEAD4 might play an important role in tumoral growth and have potential to be a therapeutic target in OSCCs. - Highlights: • TEAD4 contributes to tumor progression in OSCCs. • TEAD4 knockdown results in cell-cycle arrest at the G1phase in OSCC cells. • In TEAD4 knockdown cells, the amount of YAP in the nucleus decreases. • Activation of the TEAD4-YAP complex is an important factor in OSCC tumor growth. • TEAD4 might be a critical biomarker and a therapeutic target for OSCCs.

  6. ABT-263 induces G1/G0-phase arrest, apoptosis and autophagy in human esophageal cancer cells in vitro.

    Science.gov (United States)

    Lin, Qing-Huan; Que, Fu-Chang; Gu, Chun-Ping; Zhong, De-Sheng; Zhou, Dan; Kong, Yi; Yu, Le; Liu, Shu-Wen

    2017-12-01

    Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms. Treatment with ABT-263 dose-dependently suppressed the viability of 3 human esophageal cancer cells with IC 50 values of 10.7±1.4, 7.1±1.5 and 8.2±1.6 μmol/L, in EC109, HKESC-2 and CaES-17 cells, respectively. ABT-263 (5-20 μmol/L) dose-dependently induced G 1 /G 0 -phase arrest in the 3 cancer cell lines and induced apoptosis evidenced by increased the Annexin V-positive cell population and elevated levels of cleaved caspase 3, cleaved caspase 9 and PARP. We further demonstrated that ABT-263 treatment markedly increased the expression of p21 Waf1/Cip1 and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G 1 /G 0 -phase arrest. Knockdown of p21 Waf1/Cip1 attenuated ABT-263-induced G 1 /G 0 -phase arrest. Moreover, ABT-263 treatment enhanced pro-survival autophagy, shown as the increased LC3-II levels and decreased p62 levels, which counteracted its anticancer activity. Our results suggest that ABT-263 exerts cytostatic and cytotoxic effects on human esophageal cancer cells in vitro and enhances pro-survival autophagy, which counteracts its anticancer activity.

  7. Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells.

    Science.gov (United States)

    Hashimoto, Takashi; He, Zhiwei; Ma, Wei-Ya; Schmid, Patricia C; Bode, Ann M; Yang, Chung S; Dong, Zigang

    2004-05-01

    Caffeine is a major biologically active constituent in coffee and tea. Because caffeine has been reported to inhibit carcinogenesis in UVB-exposed mice, the cancer-preventing effect of caffeine has attracted considerable attention. In the present study, the effect of caffeine in quiescent (G0 phase) cells was investigated. Pretreatment with caffeine suppressed cell proliferation in a dose-dependent manner 36 h after addition of fetal bovine serum as a cell growth stimulator. Analysis by flow cytometry showed that caffeine suppressed cell cycle progression at the G0/G1 phase, i.e., 18 h after addition of fetal bovine serum, the percentages of cells in G0/G1 phase in 1 mM caffeine-treated cells and in caffeine-untreated cells were 61.7 and 29.0, respectively. The percentage of cells in G0/G1 phase at 0 h was 75.5. Caffeine inhibited phosphorylation of retinoblastoma protein at Ser780 and Ser807/Ser811, the sites where retinoblastoma protein has been reported to be phosphorylated by cyclin-dependent kinase 4 (cdk4). Furthermore, caffeine inhibited the activation of the cyclin D1-cdk4 complex in a dose-dependent manner. However this compound did not directly inhibit the activity of this complex. In addition, caffeine did not affect p16INK4 or p27Kip1 protein levels, but inhibited the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase 3beta. Our results showed that caffeine suppressed the progression of quiescent cells into the cell cycle. The inhibitory mechanism may be due to the inhibition of cell growth signal-induced activation of cdk4, which may be involved in the inhibition of carcinogenesis in vivo.

  8. Arrest of irradiated G1, S, or G2 cells at mitosis using nocodazole promotes repair of potentially lethal damage

    International Nuclear Information System (INIS)

    Iliakis, G.; Nuesse, M.

    1984-01-01

    The ability of synchronized Ehrlich ascites tumor cells, irradiated in G1, S, and G2 phases, to repair potentially lethal damage when arrested at mitosis by using 0.4 μg/ml nocodazole, a specific inhibitor of microtubule polymerization, has been studied. Cells irradiated in these phases were found to repair potentially lethal damage at mitosis. The extent of this repair was similar to that observed for cells irradiated at the same stages in the cell cycle but allowed to repair potentially lethal damage by incubating in balanced salt solution for 6 hr after X irradiation

  9. Middle infrared radiation induces G2/M cell cycle arrest in A549 lung cancer cells.

    Science.gov (United States)

    Chang, Hsin-Yi; Shih, Meng-Her; Huang, Hsuan-Cheng; Tsai, Shang-Ru; Juan, Hsueh-Fen; Lee, Si-Chen

    2013-01-01

    There were studies investigating the effects of broadband infrared radiation (IR) on cancer cell, while the influences of middle-infrared radiation (MIR) are still unknown. In this study, a MIR emitter with emission wavelength band in the 3-5 µm region was developed to irradiate A549 lung adenocarcinoma cells. It was found that MIR exposure inhibited cell proliferation and induced morphological changes by altering the cellular distribution of cytoskeletal components. Using quantitative PCR, we found that MIR promoted the expression levels of ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related and Rad3-related), TP53 (tumor protein p53), p21 (CDKN1A, cyclin-dependent kinase inhibitor 1A) and GADD45 (growth arrest and DNA-damage inducible), but decreased the expression levels of cyclin B coding genes, CCNB1 and CCNB2, as well as CDK1 (Cyclin-dependent kinase 1). The reduction of protein expression levels of CDC25C, cyclin B1 and the phosphorylation of CDK1 at Thr-161 altogether suggest G(2)/M arrest occurred in A549 cells by MIR. DNA repair foci formation of DNA double-strand breaks (DSB) marker γ-H2AX and sensor 53BP1 was induced by MIR treatment, it implies the MIR induced G(2)/M cell cycle arrest resulted from DSB. This study illustrates a potential role for the use of MIR in lung cancer therapy by initiating DSB and blocking cell cycle progression.

  10. Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro by Inducing G1 Arrest and Apoptosis

    Directory of Open Access Journals (Sweden)

    Raja Kumar Vadivelu

    2012-01-01

    Full Text Available Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8 μg/mL significantly (P<0.05. Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC.

  11. p27Kip1 Is Required to Mediate a G1 Cell Cycle Arrest Downstream of ATM following Genotoxic Stress.

    Directory of Open Access Journals (Sweden)

    Erica K Cassimere

    Full Text Available The DNA damage response (DDR is a coordinated signaling network that ensures the maintenance of genome stability under DNA damaging stress. In response to DNA lesions, activation of the DDR leads to the establishment of cell cycle checkpoints that delay cell-cycle progression and allow repair of the defects. The tumor suppressor p27Kip1 is a cyclin-CDK inhibitor that plays an important role in regulating quiescence in a variety of tissues. Several studies have suggested that p27Kip1 also plays a role in the maintenance of genomic integrity. Here we demonstrate that p27Kip1 is essential for the establishment of a G1 checkpoint arrest after DNA damage. We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140, which leads to its stabilization after induction of DNA double-strand breaks. Inhibition of this stabilization by replacing endogenous p27Kip1 with a Ser-140 phospho-mutant (S140A significantly sensitized cells to IR treatments. Our findings reveal a novel role for p27Kip1 in the DNA damage response pathway and suggest that part of its tumor suppressing functions relies in its ability to mediate a G1 arrest after the induction of DNA double strand breaks.

  12. BDE-47 and BDE-209 inhibit proliferation of Neuro-2a cells via inducing G1-phase arrest.

    Science.gov (United States)

    Chen, Hongmei; Tang, Xuexi; Zhou, Bin; Xu, Ningning; Zhou, Zhongyuan; Fang, Kuan; Wang, You

    2017-03-01

    Cell proliferation is closely related to cell cycle which is strictly regulated by genes and regulatory proteins. In the present study, we comparatively analyzed the toxic effects of BDE-47 and BDE-209 on cell proliferation of Neuro-2a cells, and the possible mechanism was discussed. The results indicated that BDE-47 significantly inhibited the cell proliferation and the cell cycle were arrest at G1 phase, while BDE-209 had little effects on either cell proliferation or cell cycle. qRT-PCR and Western blot assay presented that BDE-47 up-regulated the gene expressions of p53 and p21, which down-regulated the expresseion of cyclinD1 and CDK2, and inhibited retinoblastoma protein (pRb) phosphorylation. This process could effectively arrest the cell cycle at G1 phase, which finally caused the inhibition on Neuro-2a cell proliferation. However, BDE-209 was only up-regulated the gene expressions of p53, also suggested to be involved in the inhibition on Neuro-2a cell proliferation. Copyright © 2016. Published by Elsevier B.V.

  13. Inhibition of PI3K by ZSTK474 suppressed tumor growth not via apoptosis but G0/G1 arrest

    International Nuclear Information System (INIS)

    Dan, Shingo; Yoshimi, Hisashi; Okamura, Mutsumi; Mukai, Yumiko; Yamori, Takao

    2009-01-01

    Phosphoinositide 3-kinase (PI3K) is a potential target in cancer therapy. Inhibition of PI3K is believed to induce apoptosis. We recently developed a novel PI3K inhibitor ZSTK474 with antitumor efficacy. In this study, we have examined the underlying mode of action by which ZSTK474 exerts its antitumor efficacy. In vivo, ZSTK474 effectively inhibited the growth of human cancer xenografts. In parallel, ZSTK474 treatment suppressed the expression of phospho-Akt, suggesting effective PI3K inhibition, and also suppressed the expression of nuclear cyclin D1 and Ki67, both of which are hallmarks of proliferation. However, ZSTK474 treatment did not increase TUNEL-positive apoptotic cells. In vitro, ZSTK474 induced marked G 0 /G 1 arrest, but did not increase the subdiploid cells or activate caspase, both of which are hallmarks of apoptosis. These results clearly indicated that inhibition of PI3K by ZSTK474 did not induce apoptosis but rather induced strong G 0 /G 1 arrest, which might cause its efficacy in tumor cells.

  14. Iso-suillin isolated from Suillus luteus, induces G1 phase arrest and apoptosis in human hepatoma SMMC-7721 cells.

    Science.gov (United States)

    Jia, Zhi-Qiang; Chen, Ying; Yan, Yong-Xin; Zhao, Jun-Xia

    2014-01-01

    Iso-suillin, a natural product isolated from Suillus luteus, has been shown to inhibit the growth of some cancer cell lines. However, the molecular mechanisms of action of this compound are poorly understood. The purpose of this study was to investigate how iso-suillin inhibits proliferation and induces apoptosis in a human hepatoma cell line (SMMC-7721). We demonstrated the effects of iso-suillin on cell proliferation and apoptosis in SMMC-7721 cells, with no apparent toxicity in normal human lymphocytes, using colony formation assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Western blotting was used to examine the expression of G1 phase-regulated and apoptosis-associated protein levels in iso-suillin treated SMMC-7721 cells. The results indicated that iso-suillin significantly decreased viability, induced G1 phase arrest and triggered apoptosis in SMMC-7721cells. Taken together, these results suggest the potential of iso-suillin as a candidate for liver cancer treatment.

  15. NBPF1, a tumor suppressor candidate in neuroblastoma, exerts growth inhibitory effects by inducing a G1 cell cycle arrest

    International Nuclear Information System (INIS)

    Andries, Vanessa; Vandepoele, Karl; Staes, Katrien; Berx, Geert; Bogaert, Pieter; Van Isterdael, Gert; Ginneberge, Daisy; Parthoens, Eef; Vandenbussche, Jonathan; Gevaert, Kris; Roy, Frans van

    2015-01-01

    NBPF1 (Neuroblastoma Breakpoint Family, member 1) was originally identified in a neuroblastoma patient on the basis of its disruption by a chromosomal translocation t(1;17)(p36.2;q11.2). Considering this genetic defect and the frequent genomic alterations of the NBPF1 locus in several cancer types, we hypothesized that NBPF1 is a tumor suppressor. Decreased expression of NBPF1 in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor suppressor. However, little is known about the mechanisms involved. Expression of NBPF was analyzed in human skin and human cervix by immunohistochemistry. The effects of NBPF1 on the cell cycle were evaluated by flow cytometry. We investigated by real-time quantitative RT-PCR the expression profile of a panel of genes important in cell cycle regulation. Protein levels of CDKN1A-encoded p21 CIP1/WAF1 were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-of-function approach. LC-MS/MS analysis was used to investigate the proteome of DLD1 colon cancer cells with induced NBPF1 expression. Possible biological interactions between the differentially regulated proteins were investigated with the Ingenuity Pathway Analysis tool. We show that NBPF is expressed in the non-proliferative suprabasal layers of squamous stratified epithelia of human skin and cervix. Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 in a p53-dependent manner. Additionally, forced expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a G1 cell cycle arrest and CDKN1A upregulation. However, CDKN1A upregulation by NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts cell

  16. Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

    Science.gov (United States)

    Maimaitili, Aisha; Shu, Zunhua; Cheng, Xiaojiang; Kaheerman, Kadeer; Sikandeer, Alifu; Li, Weimin

    2017-02-01

    The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60-75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G 0 /G 1 phase and reduced the number of cells in the S phase, as compared with the control group (Parctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G 0 /G 1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

  17. Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann cells.

    Science.gov (United States)

    Petrilli, Alejandra M; Garcia, Jeanine; Bott, Marga; Klingeman Plati, Stephani; Dinh, Christine T; Bracho, Olena R; Yan, Denise; Zou, Bing; Mittal, Rahul; Telischi, Fred F; Liu, Xue-Zhong; Chang, Long-Sheng; Welling, D Bradley; Copik, Alicja J; Fernández-Valle, Cristina

    2017-05-09

    Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC). Merlin-deficient HSC had higher levels of phosphorylated PDGFRα/β, and SRC than merlin-expressing HSC. A similar phosphorylation pattern was observed in phospho-protein arrays of human vestibular schwannoma samples compared to normal HSC. Ponatinib reduced merlin-deficient HSC viability in a dose-dependent manner by decreasing phosphorylation of PDGFRα/β, AKT, p70S6K, MEK1/2, ERK1/2 and STAT3. These changes were associated with decreased cyclin D1 and increased p27Kip1levels, leading to a G1 cell-cycle arrest as assessed by Western blotting and flow cytometry. Ponatinib did not modulate ABL, SRC, focal adhesion kinase (FAK), or paxillin phosphorylation levels. These results suggest that ponatinib is a potential therapeutic agent for NF2-associated schwannomas and warrants further in vivo investigation.

  18. The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling.

    Science.gov (United States)

    Martins, Torcato; Meghini, Francesco; Florio, Francesca; Kimata, Yuu

    2017-01-09

    The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, Drosophila Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. X-ray induction of 6-thioguanine-resistant mutants in division arrested, G0/G1 phase Chinese hamster ovary cells

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, J.P.; Flint, K.B.

    The cytotoxic and mutagenic effect of X-irradiation was determined with Chinese hamster ovary cells arrested in the G0/G1 phase of the cell cycle through 9 days incubation in serum-free medium. In comparison with exponential phase cultures, the arrested cells showed increased cytotoxicity and mutation induction over the dose range of 50-800 rad. Exponential cultures showed a linear mutant frequency-survival relationship while the arrested cells showed a biphasic linear relationship. A post irradiation holding period 24 h does not result in any change in the mutant frequency. The increased sensitivity of the arrested cells to the mutagenic effects of X-rays appears to be a cell-cycle phase phenomenon. Upon readdition of serum, the arrested cells re-enter the cell cycle in a synchronous manner, reaching S phase at 10-12 h. Cells irradiated at 5 h after serum addition, i.e. in G1, show a similar dose response for mutant frequency, while those irradiated at 10 h or later, i.e. in late G1, S or G2, show lower mutation induction. These observations are consistent with a chromosome interchange mechanism of mutation induction by X-rays, possibly through interactions between repairing regions of the DNA. Irradiation of cells in the G0/G1 phase allow more time for such interactions in the absence of semiconservative DNA replication. (orig.).

  20. Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells

    Directory of Open Access Journals (Sweden)

    Li HF

    2015-06-01

    Full Text Available Huai-Feng Li,1–3,* Xu-An Wang,1–3,* Shan-Shan Xiang,1–3,* Yun-Ping Hu,1–3 Lin Jiang,1–3 Yi-Jun Shu,1–3 Mao-Lan Li,1–3 Xiang-Song Wu,1–3 Fei Zhang,1–3 Yuan-Yuan Ye,1–3 Hao Weng,1–3 Run-Fa Bao,1–3 Yang Cao,1–3 Wei Lu,1–3 Qian Dong,1–3 Ying-Bin Liu1–3 1Department of General Surgery, 2Laboratory of General Surgery, 3Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Oleanolic acid (OA, a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma. Keywords: oleanolic acid, gallbladder carcinoma, apoptosis, cell cycle arrest, mitochondrial pathway

  1. Selumetinib suppresses cell proliferation, migration and trigger apoptosis, G1 arrest in triple-negative breast cancer cells.

    Science.gov (United States)

    Zhou, Yan; Lin, Shuchen; Tseng, Kuo-Fu; Han, Kun; Wang, Yaling; Gan, Zhi-Hua; Min, Da-Liu; Hu, Hai-Yan

    2016-10-21

    Triple-negative breast cancer (TNBC) has aggressive progression with poor prognosis and ineffective treatments. Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors. We hypothesized that Selumetinib might be potential drug for TNBC and explore the mechanism. After treated with Selumetinib, the viability and mobility of HCC1937 and MDA-MB-231 were detected by MTT, tunnel, wound-healing assay, transwell assay and FCM methods. MiR array was used to analysis the change of miRs. We predicted and verified CUL1 is the target of miR-302a using Luciferase reporter assay. We also silenced the CUL1 by siRNA, to clarify whether CUL1 take part in the cell proliferation, migration and regulated its substrate TIMP1 and TRAF2. Moreover, after transfection, the antagomir of miR-302a and CUL1 over-expressed plasmid into HCC1937 and MDA-MB-231 cell accompanied with the Selumetinib treatment, we detected the proliferation and migration again. Selumetinib reduce the proliferation, migration, triggered apoptosis and G1 arrest in TNBC cell lines. In this process, the miR-302a was up-regulated and inhibited the CUL1 expression. The later negatively regulated the TIMP1 and TRAF2. As soon as we knockdown miR-302a and over-expression CUL1 in TNBC cells, the cytotoxicity of Selumetinib was reversed. MiR-302a targeted regulated the CUL1 expression and mediated the Selumetinib-induced cytotoxicity of triple-negative breast cancer.

  2. Wogonin induced G1 cell cycle arrest by regulating Wnt/β-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells

    International Nuclear Information System (INIS)

    He, Licheng; Lu, Na; Dai, Qinsheng; Zhao, Yue; Zhao, Li; Wang, Hu; Li, Zhiyu; You, Qidong; Guo, Qinglong

    2013-01-01

    Highlights: • Wogonin inhibited HCT116 cells growth and arrested at G1 phase of the cell cycle. • Wogonin down-regulated the canonical Wnt/β-catenin signaling pathway. • Wogonin interfered in the combination of β-catenin and TCF/Lef. • Wogonin limited the kinase activity of CDK8. - Abstract: Wogonin, a naturally occurring mono-flavonoid, has been reported to have tumor therapeutic potential and good selectivity both in vitro and in vivo. Herein, we investigated the anti-proliferation effects and associated mechanisms of wogonin in human colorectal cancer in vitro. The flow-cytometric analysis showed that wogonin induced a G1 phase cell cycle arrest in HCT116 cells in a concentration- and time-dependent manner. Meanwhile, the cell cycle-related proteins, such as cyclin A, E, D1, and CDK2, 4 were down-regulated in wogonin-induced G1 cell cycle arrest. Furthermore, we showed that the anti-proliferation and G1 arrest effect of wogonin on HCT116 cells was associated with deregulation of Wnt/β-catenin signaling pathway. Wogonin-treated cells showed decreased intracellular levels of Wnt proteins, and activated degradation complex to phosphorylated and targeted β-catenin for proteasomal degradation. Wogonin inhibited β-catenin-mediated transcription by interfering in the transcriptional activity of TCF/Lef, and repressing the kinase activity of CDK8 which has been considered as an oncogene involving in the development of colorectal cancers. Moreover, CDK8 siRNA-transfected HCT116 cells showed similar results to wogonin treated cells. Thus, our data suggested that wogonin induced anti-proliferation and G1 arrest via Wnt/β-catenin signaling pathway and it can be developed as a therapeutic agent against human colorectal cancer

  3. Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during ionization radiation induced DNA damage response in human cells

    International Nuclear Information System (INIS)

    Sharma, Ajit K.; Bhattacharya, Saikat; Khan, Shafqat A.; Khade, Bharat; Gupta, Sanjay

    2015-01-01

    Highlights: • Loss of H3S10P in response to DNA damage is a universal phenomenon from G1 cells. • The loss happens predominantly from histone H3.3, a transcription activation mark. • Compaction of chromatin occurs during repair stage of DDR. • The alteration of H3S10P shows an inverse correlation with γH2AX. - Abstract: Chromatin acts as a natural barrier in DNA-damage recognition and repair. Histones undergo differential post-translational modification(s) to facilitate DNA damage response (DDR). Importance of modifications like phosphorylation of histone variant H2A.X in DNA repair is very well understood, however, ambiguous results exist in literature regarding the levels of certain histone modifications and their possible role in repair. In the present study, we have investigated in depth the alteration in the level of the highly dynamic histone mark H3S10P as it plays a dual role in different phases of the cell cycle. We show here that H3S10P decreases specifically from irradiated G1-enriched cells irrespective of the damaging agent or the cell line used in the study. Interestingly, the loss occurs predominantly from H3.3 variant which is a transcription activation mark like H3S10P itself, suggesting that the alteration might be implicated in transcription repression. The decrease in other transcription marks like H3K9Ac, H3K14Ac, H3K56Ac and H3S28P along with the occurrence of chromatin condensation in response to DNA damage in G1 phase strengthens the hypothesis. In addition, the alteration in the level of H3S10P shows an inverse correlation with that of γH2AX in a dose-dependent manner and probably occurs from the same mononucleosome. We propose that the drop in the levels of histone H3S10 phosphorylation is a universal phenomenon in response to DNA damage and is a trigger to induce transcription repressive state to facilitate repair

  4. Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during ionization radiation induced DNA damage response in human cells

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    Sharma, Ajit K.; Bhattacharya, Saikat; Khan, Shafqat A.; Khade, Bharat; Gupta, Sanjay, E-mail: sgupta@actrec.gov.in

    2015-03-15

    Highlights: • Loss of H3S10P in response to DNA damage is a universal phenomenon from G1 cells. • The loss happens predominantly from histone H3.3, a transcription activation mark. • Compaction of chromatin occurs during repair stage of DDR. • The alteration of H3S10P shows an inverse correlation with γH2AX. - Abstract: Chromatin acts as a natural barrier in DNA-damage recognition and repair. Histones undergo differential post-translational modification(s) to facilitate DNA damage response (DDR). Importance of modifications like phosphorylation of histone variant H2A.X in DNA repair is very well understood, however, ambiguous results exist in literature regarding the levels of certain histone modifications and their possible role in repair. In the present study, we have investigated in depth the alteration in the level of the highly dynamic histone mark H3S10P as it plays a dual role in different phases of the cell cycle. We show here that H3S10P decreases specifically from irradiated G1-enriched cells irrespective of the damaging agent or the cell line used in the study. Interestingly, the loss occurs predominantly from H3.3 variant which is a transcription activation mark like H3S10P itself, suggesting that the alteration might be implicated in transcription repression. The decrease in other transcription marks like H3K9Ac, H3K14Ac, H3K56Ac and H3S28P along with the occurrence of chromatin condensation in response to DNA damage in G1 phase strengthens the hypothesis. In addition, the alteration in the level of H3S10P shows an inverse correlation with that of γH2AX in a dose-dependent manner and probably occurs from the same mononucleosome. We propose that the drop in the levels of histone H3S10 phosphorylation is a universal phenomenon in response to DNA damage and is a trigger to induce transcription repressive state to facilitate repair.

  5. β2-adrenoceptor blockage induces G1/S phase arrest and apoptosis in pancreatic cancer cells via Ras/Akt/NFκB pathway

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    Zhang Dong

    2011-11-01

    Full Text Available Abstract Background Smoking and stress, pancreatic cancer (PanCa risk factors, stimulate nitrosamine 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK and catecholamines production respectively. NNK and catecholamine bind the β-adrenoceptors and induce PanCa cell proliferation; and we have previously suggested that β-adrenergic antagonists may suppress proliferation and invasion and stimulate apoptosis in PanCa. To clarify the mechanism of apoptosis induced by β2-adrenergic antagonist, we hypothesize that blockage of the β2-adrenoceptor could induce G1/S phase arrest and apoptosis and Ras may be a key player in PanCa cells. Results The β1 and β2-adrenoceptor proteins were detected on the cell surface of PanCa cells from pancreatic carcinoma specimen samples by immunohistochemistry. The β2-adrenergic antagonist ICI118,551 significantly induced G1/S phase arrest and apoptosis compared with the β1-adrenergic antagonist metoprolol, which was determined by the flow cytometry assay. β2-adrenergic antagonist therapy significantly suppressed the expression of extracellular signal-regulated kinase, Akt, Bcl-2, cyclin D1, and cyclin E and induced the activation of caspase-3, caspase-9 and Bax by Western blotting. Additionally, the β2-adrenergic antagonist reduced the activation of NFκB in vitro cultured PanCa cells. Conclusions The blockage of β2-adrenoceptor markedly induced PanCa cells to arrest at G1/S phase and consequently resulted in cell death, which is possibly due to that the blockage of β2-adrenoceptor inhibited NFκB, extracellular signal-regulated kinase, and Akt pathways. Therefore, their upstream molecule Ras may be a key factor in the β2-adrenoceptor antagonist induced G1/S phase arrest and apoptosis in PanCa cells. The new pathway discovered in this study may provide an effective therapeutic strategy for PanCa.

  6. Prolonged early G1 arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle–coupled loss of IRF4

    Science.gov (United States)

    Huang, Xiangao; Di Liberto, Maurizio; Jayabalan, David; Liang, Jun; Ely, Scott; Bretz, Jamieson; Shaffer, Arthur L.; Louie, Tracey; Chen, Isan; Randolph, Sophia; Hahn, William C.; Staudt, Louis M.; Niesvizky, Ruben; Moore, Malcolm A. S.

    2012-01-01

    Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G1 arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G1 and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G1 block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy. PMID:22718837

  7. Prolonged early G(1) arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle-coupled loss of IRF4.

    Science.gov (United States)

    Huang, Xiangao; Di Liberto, Maurizio; Jayabalan, David; Liang, Jun; Ely, Scott; Bretz, Jamieson; Shaffer, Arthur L; Louie, Tracey; Chen, Isan; Randolph, Sophia; Hahn, William C; Staudt, Louis M; Niesvizky, Ruben; Moore, Malcolm A S; Chen-Kiang, Selina

    2012-08-02

    Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G(1) arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G(1) and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G(1) block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy.

  8. Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA Stability.

    Science.gov (United States)

    Gao, Guangxun; Chen, Liang; Li, Jingxia; Zhang, Dongyun; Fang, Yong; Huang, Haishan; Chen, Xiequn; Huang, Chuanshu

    2014-05-15

    The cancer chemopreventive property of Chinese herb new isolate isorhapontigenin (ISO) and mechanisms underlying its activity have never been explored. Here we demonstrated that ISO treatment with various concentrations for 3 weeks could dramatically inhibit TPA/EGF-induced cell transformation of Cl41 cells in Soft Agar assay, whereas co-incubation of cells with ISO at the same concentrations could elicit G0/G1 cell-cycle arrest without redundant cytotoxic effects on non-transformed cells. Further studies showed that ISO treatment resulted in cyclin D1 downregulation in dose- and time-dependent manner. Our results indicated that ISO regulated cyclin D1 at transcription level via targeting JNK/C-Jun/AP-1 activation. Moreover, we found that ISO-inhibited JNK/C-Jun/AP-1 activation was mediated by both upregulation of MKP-1 expression through increasing its mRNA stability and deactivating MKK7. Most importantly, MKP-1 knockdown could attenuate ISO-mediated suppression of JNK/C-Jun activation and cyclin D1 expression, as well as G0/G1 cell cycle arrest and cell transformation inhibition, while ectopic expression of FLAG-cyclin D1 T286A mutant also reversed ISO-induced G0/G1 cell-cycle arrest and inhibition of cell transformation. Our results demonstrated that ISO is a promising chemopreventive agent via upregulating mkp-1 mRNA stability, which is distinct from its cancer therapeutic effect with downregulation of XIAP and cyclin D1 expression.

  9. Inhibition of Rac1 activity induces G1/S phase arrest through the GSK3/cyclin D1 pathway in human cancer cells.

    Science.gov (United States)

    Liu, Linna; Zhang, Hongmei; Shi, Lei; Zhang, Wenjuan; Yuan, Juanli; Chen, Xiang; Liu, Juanjuan; Zhang, Yan; Wang, Zhipeng

    2014-10-01

    Rac1 has been shown to regulate the cell cycle in cancer cells. Yet, the related mechanism remains unclear. Thus, the present study aimed to investigate the mechanism involved in the regulation of G1/S phase transition by Rac1 in cancer cells. Inhibition of Rac1 by inhibitor NSC23766 induced G1/S phase arrest and inhibited the proliferation of A431, SW480 and U2-OS cells. Suppression of GSK3 by shRNA partially rescued G1/S phase arrest and inhibition of proliferation. Incubation of cells with NSC23766 reduced p-AKT and inactivated p-GSK3α and p-GSK3β, increased p-cyclin D1 expression and decreased the level of cyclin D1 protein. Consequently, cyclin D1 targeting transcriptional factor E2F1 expression, which promotes G1 to S phase transition, was also reduced. In contrast, constitutive active Rac1 resulted in increased p-AKT and inactivated p-GSK3α and p-GSK3β, decreased p-cyclin D1 expression and enhanced levels of cyclin D1 and E2F1 expression. Moreover, suppression of GSK3 did not alter p-AKT or Rac1 activity, but decreased p-cyclin D1 and increased total cyclin D1 protein. However, neither Rac1 nor GSK3 inhibition altered cyclin D1 at the RNA level. Moreover, after inhibition of Rac1 or GSK3 following proteasome inhibitor MG132 treatment, cyclin D1 expression at the protein level remained constant, indicating that Rac1 and GSK3 may regulate cyclin D1 turnover through phosphorylation and degradation. Therefore, our findings suggest that inhibition of Rac1 induces cell cycle G1/S arrest in cancer cells by regulation of the GSK3/cyclin D1 pathway.

  10. Caffeine-mediated release of alpha-radiation-induced G2 arrest increases the yield of chromosome aberrations

    International Nuclear Information System (INIS)

    Luecke-Huhle, C.; Hieber, L.; Wegner, R.D.

    1983-01-01

    Severe and partly irreversible G2 arrest caused by americium-241 alpha-particles in Chinese hamster V79 cells acted as a competing process to the yield of detectable aberrant mitoses at metaphase. With increasing dose of alpha-radiation an increasing fraction of cells was irreversibly arrested in G2 with the consequence of interphase death before the first post-irradiation mitosis. This irreversible G2 arrest (demonstrated by flow cytofluorometry and mitotic indices) could be overcome by adding caffeine 8 hours after irradiation, the time point of maximum G2 arrest (80-90 per cent of all cells). Within 3.5 hours the number of aberrant mitoses increased by this treatment from 54 to 96 per cent and from 65 to 99.9 per cent for doses of 1.75 and 4.38 Gy of alpha-particles, respectively. The aberration frequency per mitotic cell, scored as chromatid and isochromatid breaks, rings, interchanges and dicentrics increased by a factor of about 3 after releasing G2 arrested cells. The frequency distribution of aberrations per cell revealed that, after 4.38 Gy, 58 per cent of the formerly G2-arrested cells had more than five aberrations per cell compared to only 8 per cent without the interaction of caffeine. (author)

  11. Mouse one-cell embryos undergoing a radiation-induced G2 arrest may re-enter S-phase in the absence of cytokinesis

    International Nuclear Information System (INIS)

    Jacquet, P.; Buset, J.; Vankerkom, J.; Baatout, S.; De Saint-Georges, L.; Schoonjans, W.; Desaintes, C.

    2002-01-01

    PCC (premature chromosome condensation) can be used for visualizing and scoring damage induced by radiation in the chromatin of cells undergoing a G1 or G2 arrest. A method involving the fusion of irradiated single embryonic cells with single MI oocytes was used to induce PCC in mouse zygotes of the BALB/c strain, which suffer a drastic G2 arrest after X-irradiation (dose used 2.5 Gy). Other G2-arrested embryos were exposed in vitro to the phosphatase inhibitor calyculin A. Both methods furnished excellent chromosome preparations of the G2-arrested embryos. The mean number of chromosome fragments did not change significantly during G2 arrest, suggesting that zygotes of this strain are unable to repair DNA damage leading to such aberrations. Forty to fifty percent of the irradiated embryos were unable to cleave after G2 arrest and remained blocked at the one-cell stage for a few days before dying. PCC preparations obtained from such embryos suggested that about 30% of them had undergone a late mitosis not followed by cytokinesis and had entered a new DNA synthesis. These results are discussed in the light of recent observations in irradiated human cells deficient in the p53/14-3-3σ pathway. (author)

  12. MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.

    Directory of Open Access Journals (Sweden)

    Noelia Sanchez

    Full Text Available MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27(KIP and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress.

  13. Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

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    Harrison David J

    2007-11-01

    Full Text Available Abstract Background TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how Rb-deficiency would affect responses to TGFβ-induced cell cycle arrest. Results Primary hepatocytes isolated from Rb-floxed mice were infected with an adenovirus expressing CRE-recombinase to delete the Rb gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16INK4A and P21Cip and reduction of E2F activity. In Rb-null hepatocytes, cMYC activity decreased slightly but P16INK4A was not activated and the great majority of cells continued cycling. Rb is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some Rb-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21Cip1 and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of p53 and p21Cip1. Hepatocytes deficient in p53 or p21Cip1 showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21Cip and P53 work through the same pathway to regulate G1/S in response to TGFβ. In Rb-deficient cells however, p53 but not p21Cip deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity. Conclusion The present results show that otherwise genetically normal hepatocytes with disabled p53, p21Cip1 or Rb genes respond less well to the antiproliferative effects of TGFβ. As the function of

  14. Folate deprivation induces cell cycle arrest at G0/G1 phase and apoptosis in hippocampal neuron cells through down-regulation of IGF-1 signaling pathway.

    Science.gov (United States)

    Yang, Yang; Li, Xi; Sun, Qinwei; He, Bin; Jia, Yimin; Cai, Demin; Zhao, Ruqian

    2016-10-01

    Folate deficiency contributes to impaired adult hippocampal neurogenesis, yet the mechanisms remain unclear. Here we use HT-22 hippocampal neuron cells as model to investigate the effect of folate deprivation (FD) on cell proliferation and apoptosis, and to elucidate the underlying mechanism. FD caused cell cycle arrest at G0/G1 phase and increased the rate of apoptosis, which was associated with disrupted expression of folate transport and methyl transfer genes. FOLR1 and SLC46A1 were (Pmethyl transfer pathway and hypermethylation of IGF-1 gene promoter. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Hung, Chein-Hui [Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Puizi City, Chiayi 613, Taiwan, ROC (China); Chang, Nai Wen [Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan, ROC (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China)

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  16. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

    Science.gov (United States)

    Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

    2017-02-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21 CIP/WAF1 )-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21 CIP/WAF1 )-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21 CIP/WAF1 )-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21 CIP/WAF1 )-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

  17. A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C. [College of Life Science, Hebei University, Baoding (China); Yang, R.L. [Key Laboratory of Microbial Diversity Research and Application of Hebei Province, Baoding, China, Key Laboratory of Microbial Diversity Research and Application of Hebei Province, Baoding (China)

    2013-07-30

    MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27{sup KIP1} protein and p21{sup CIP1} mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21{sup CIP1}, p16{sup INK4a} and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.

  18. A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells

    International Nuclear Information System (INIS)

    Chen, C.; Yang, R.L.

    2013-01-01

    MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27 KIP1 protein and p21 CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21 CIP1 , p16 INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer

  19. Indole-3-carbinol induces G1 cell cycle arrest and apoptosis through aryl hydrocarbon receptor in THP-1 monocytic cell line.

    Science.gov (United States)

    Mohammadi, Saeed; Seyedhosseini, Fakhri Sadat; Behnampour, Nasser; Yazdani, Yaghoub

    2017-10-01

    The role of aryl hydrocarbon receptor (AhR) in carcinogenesis has been studied recently. Indole-3-carbinol (I3C) is an AhR agonist and a potential anticancer agent. Here, we investigated the effects of I3C on cell cycle progression and apoptosis through activation of AhR on THP-1 acute myeloid leukemia (AML) cell line. MTT viability assay was used to measure the cytotoxic effects of I3C on THP-1 cells. Apoptosis and cell cycle assays were investigated using flow cytometry. Real time RT-PCR was conducted to measure the alterations in the expression of AhR gene, key genes associated with AhR activation (IL1β and CYP1A1) and major genes involved in cell cycle regulation and apoptosis including P27, P21, CDK2, P53, BCL2 and FasR. Our findings revealed that I3C inhibits the proliferation of THP-1 cells in a dose- and time-dependent manner with minimal toxicity over normal monocytes. The AhR target genes (CYP1A1, IL1β) were overexpressed upon I3C treatment (p cycle arrest was also observed using flow cytometry. G1-acting cell cycle genes (P21, P27 and P53) were overexpressed (p cycle arrest in a dose- and time-dependent manner. Therefore, AhR could be targeted as a novel treatment possibility in AML.

  20. Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G1 arrest and apoptosis

    Science.gov (United States)

    Jada, S R; Matthews, C; Saad, M S; Hamzah, A S; Lajis, N H; Stevens, M F G; Stanslas, J

    2008-01-01

    Background and purpose: Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death. Experimental approach: Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry. Key results: Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G1 arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis. Conclusion and implications: The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G1 phase cell cycle arrest, coupled with induction of apoptosis. PMID:18806812

  1. The ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer.

    Directory of Open Access Journals (Sweden)

    Tingxiu Xiang

    Full Text Available Breast cancer (BrCa is a complex disease driven by aberrant gene alterations and environmental factors. Recent studies reveal that abnormal epigenetic gene regulation also plays an important role in its pathogenesis. Ubiquitin carboxyl- terminal esterase L1 (UCHL1 is a tumor suppressor silenced by promoter methylation in multiple cancers, but its role and alterations in breast tumorigenesis remain unclear.We found that UCHL1 was frequently downregulated or silenced in breast cancer cell lines and tumor tissues, but readily expressed in normal breast tissues and mammary epithelial cells. Promoter methylation of UCHL1 was detected in 9 of 10 breast cancer cell lines (90% and 53 of 66 (80% primary tumors, but rarely in normal breast tissues, which was statistically correlated with advanced clinical stage and progesterone receptor status. Pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. Ectopic expression of UCHL1 significantly suppressed the colony formation and proliferation of breast tumor cells, through inducing G0/G1 cell cycle arrest and apoptosis. Subcellular localization study showed that UCHL1 increased cytoplasmic abundance of p53. We further found that UCHL1 induced p53 accumulation and reduced MDM2 protein level, and subsequently upregulated the expression of p21, as well as cleavage of caspase3 and PARP, but not in catalytic mutant UCHL1 C90S-expressed cells.UCHL1 exerts its tumor suppressive functions by inducing G0/G1cell cycle arrest and apoptosis in breast tumorigenesis, requiring its deubiquitinase activity. Its frequent silencing by promoter CpG methylation may serve as a potential tumor marker for breast cancer.

  2. Induction of cell cycle arrest at G1 and S phases and cAMP-dependent differentiation in C6 glioma by low concentration of cycloheximide

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    Zhang Samuel S

    2010-12-01

    Full Text Available Abstract Background Differentiation therapy has been shown effective in treatment of several types of cancer cells and may prove to be effective in treatment of glioblastoma multiforme, the most common and most aggressive primary brain tumor. Although extensively used as a reagent to inhibit protein synthesis in mammalian cells, whether cycloheximide treatment leads to glioma cell differentiation has not been reported. Methods C6 glioma cell was treated with or without cycloheximide at low concentrations (0.5-1 μg/ml for 1, 2 and 3 days. Cell proliferation rate was assessed by direct cell counting and colony formation assays. Apoptosis was assessed by Hoechst 33258 staining and FACS analysis. Changes in several cell cycle regulators such as Cyclins D1 and E, PCNA and Ki67, and several apoptosis-related regulators such as p53, p-JNK, p-AKT, and PARP were determined by Western blot analysis. C6 glioma differentiation was determined by morphological characterization, immunostaining and Western blot analysis on upregulation of GFAP and o p-STAT3 expression, and upregulation of intracellular cAMP. Results Treatment of C6 cell with low concentration of cycloheximide inhibited cell proliferation and depleted cells at both G2 and M phases, suggesting blockade at G1 and S phases. While no cell death was observed, cells underwent profound morphological transformation that indicated cell differentiation. Western blotting and immunostaining analyses further indicated that changes in expression of several cell cycle regulators and the differentiation marker GFAP were accompanied with cycloheximide-induced cell cycle arrest and cell differentiation. Increase in intracellular cAMP, a known promoter for C6 cell differentiation, was found to be elevated and required for cycloheximide-promoted C6 cell differentiation. Conclusion Our results suggest that partial inhibition of protein synthesis in C6 glioma by low concentration of cycloheximide induces cell cycle

  3. Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

    International Nuclear Information System (INIS)

    Uchida, Fumihiko; Uzawa, Katsuhiro; Kasamatsu, Atsushi; Takatori, Hiroaki; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Bukawa, Hiroki

    2012-01-01

    Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC. We evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system. The CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21 Cip1 , p27 Kip1 , p15 INK4B , and p16 INK4A ) in the knockdown cells. The current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors

  4. Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia (T-ALL cells

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    Aslı Tetik Vardarlı

    2018-05-01

    Full Text Available Matrine, a natural product extracted from the root of Sophora flavescens, is a promising alternative drug in different types of cancer. Here, we aimed to investigate the therapeutic effects and underlying molecular mechanisms of matrine on human acute lymphoblastic leukemia (ALL cell line, CCRF-CEM. Cell viability and IC50 values were determined by WST-1 cell cytotoxicity assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Expression patterns of 44 selected miRNAs and 44 RNAs were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR using the Applied Biosystems 7500 Fast Real-Time PCR System. Matrine inhibited cell viability and induced apoptosis of CCRF-CEM cells in a dose-dependent manner. Cell cycle analysis demonstrated that matrine-treated CCRF-CEM cells significantly accumulated in the G0/G1 phase compared with the untreated control cells. hsa-miR-376b-3p (-37.09 fold, p = 0.008 and hsa-miR-106b-3p (-16.67 fold, p = 0.028 expressions were decreased, whereas IL6 (95.47 fold, p = 0.000011 and CDKN1A (140.03 fold, p = 0.000159 expressions were increased after matrine treatment. Our results suggest that the downregulation of hsa-miR-106b-3p leads to the upregulation of target p21 gene, CDKN1A, and plays a critical role in the cell cycle progression by arresting matrine-treated cells in the G0/G1 phase.

  5. Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells

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    Choi Hyun

    2009-05-01

    Full Text Available Abstract Background 3,3'-Diindolylmethane (DIM, an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both in vivo and in vitro models. We have previously determined that DIM (0 – 30 μmol/L inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells. Methods HT-29 cells were cultured with various concentrations of DIM (0 – 30 μmol/L and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and in vitro kinase assays for cyclin-dependent kinase (CDK and cell division cycle (CDC2 were conducted. Results The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1 and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1. Conclusion Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.

  6. Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells.

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    Choi, Hyun Ju; Lim, Do Young; Park, Jung Han Yoon

    2009-05-29

    3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both in vivo and in vitro models. We have previously determined that DIM (0 - 30 micromol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells. HT-29 cells were cultured with various concentrations of DIM (0 - 30 micromol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and in vitro kinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted. The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1 and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1. Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.

  7. Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.

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    Chen, Jun-Feng; Yu, Bi-Xia; Yu, Rui; Ma, Liang; Lv, Xiu-Yi; Cheng, Yue; Ma, Qi

    2017-02-01

    Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

  8. Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells.

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    Ando, Shotaro; Kawada, Jun-Ichi; Watanabe, Takahiro; Suzuki, Michio; Sato, Yoshitaka; Torii, Yuka; Asai, Masato; Goshima, Fumi; Murata, Takayuki; Shimizu, Norio; Ito, Yoshinori; Kimura, Hiroshi

    2016-11-22

    Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model. We found that all EBV-positive T and NK cell lines and patient samples tested displayed activation of the JAK3/STAT5 pathway. Treatment of these cell lines with tofacitinib reduced the levels of phospho-STAT5, suppressed proliferation, induced G1 cell-cycle arrest and decreased EBV LMP1 and EBNA1 expression. An EBV-negative NK cell line was also sensitive to tofacitinib, whereas an EBV-infected NK cell line was more sensitive to tofacitinib than its parental line. Tofacitinib significantly inhibited the growth of established tumors in NOG mice. These findings suggest that tofacitinib may represent a useful therapeutic agent for patients with EBV-associated T and NK cell lymphoma.

  9. Human cytochrome c enters murine J774 cells and causes G1 and G2/M cell cycle arrest and induction of apoptosis

    International Nuclear Information System (INIS)

    Hiraoka, Yoshinori; Granja, Ana Teresa; Fialho, Arsenio M.; Schlarb-Ridley, Beatrix G.; Das Gupta, Tapas K.; Chakrabarty, Ananda M.; Yamada, Tohru

    2005-01-01

    Cytochrome c is well known as a carrier of electrons during respiration. Current evidence indicates that cytochrome c also functions as a major component of apoptosomes to induce apoptosis in eukaryotic cells as well as an antioxidant. More recently, a prokaryotic cytochrome c, cytochrome c 551 from Pseudomonas aeruginosa, has been shown to enter in mammalian cells such as the murine macrophage-like J774 cells and causes inhibition of cell cycle progression. Much less is known about such functions by mammalian cytochromes c, particularly the human cytochrome c. We now report that similar to P. aeruginosa cytochrome c 551 , the purified human cytochrome c protein can enter J774 cells and induce cell cycle arrest at the G 1 to S phase, as well as at the G 2 /M phase at higher concentrations. Unlike P. aeruginosa cytochrome c 551 which had no effect on the induction of apoptosis, human cytochrome c induces significant apoptosis and cell death in J774 cells, presumably through inhibition of the cell cycle at the G 2 /M phase. When incubated with human breast cancer MCF-7 and normal mammary epithelial cell line MCF-10A1 cells, human cytochrome c entered in both types of cells but induced cell death only in the normal MCF-10A1 cells. The ability of human cytochrome c to enter J774 cells was greatly reduced at 4 deg. C, suggesting energy requirement in the entry process

  10. Umbelliferone arrest cell cycle at G0/G1 phase and induces apoptosis in human oral carcinoma (KB) cells possibly via oxidative DNA damage.

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    Vijayalakshmi, Annamalai; Sindhu, Ganapathy

    2017-08-01

    Umbelliferone (UMB) has widespread pharmacological activity, comprising anti-inflammatory, anti-oxidant, anti-genotoxic and anti-immunomodulatory but the anticancer activity remains unknown in human oral carcinoma (HOC) KB cells. MTT assay determinations was revealed that treatment of KB cells with UMB, prevent and reduce the cell proliferation with the IC 50 - 200μM as well as induces loss of cell viability, morphology change and internucleosomal DNA fragmentation in a concentration dependent manner. Acridine orange and ethidium bromide dual staining assay established that UMB induced apoptosis in KB cells in a dose dependent manner. Alkaline comet assay determination revealed UMB has the potential to increase oxidative DNA damage in KB cells through DNA tail formation significantly (pKB cells. Similarly, we observed increased DNA damage stimulated apoptotic morphological changes in UMB treated cells. Taken together, the present study suggests that UMB exhibits anticancer effect on KB cell line with the increased generation of intracellular ROS, triggered oxidative stress mediated depolarization of mitochondria, which contributes cell death via DNA damage as well as cell cycle arrest at G0/G1 phase. The results have also provided us insight in the pharmacological backgrounds for the potential use of UMB, to target divergent pathways of cell survival and cell death. To conclude UMB could develop as a novel candidate for cancer chemoprevention and therapy, which is our future focus and to develop a connectivity map between in vivo and in vitro activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

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    Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

    2017-02-01

    Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.

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    Nan Hua

    Full Text Available Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs. In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC.

  13. AZD2014 Radiosensitizes Oral Squamous Cell Carcinoma by Inhibiting AKT/mTOR Axis and Inducing G1/G2/M Cell Cycle Arrest.

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    Chih-Chia Yu

    Full Text Available Oral squamous cell carcinoma (OSCC is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models.We isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression.Combination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells.These findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma.

  14. Ethanol extract of Kilkyung-baeksan, a traditional herbal formula, induces G0/G1 cell cycle arrest in human lung cancer cell lines

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    Jinhee Kim

    2015-09-01

    Conclusion: EE-KKBS exerted its cytostatic activity through regulating G1 cell cycle checkpoint in lung cancer cells, and this activity is mainly mediated by one of its component herbs, seeds of Croton tiglium. Collectively, our data suggest that EE-KKBS could be a novel candidate for adjuvant therapy for lung cancer.

  15. NF-κB and JNK mediated apoptosis and G0/G1 arrest of HeLa cells induced by rubiarbonol G, an arborinane-type triterpenoid from Rubia yunnanensis.

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    Zeng, Guang-Zhi; Wang, Zhe; Zhao, Li-Mei; Fan, Jun-Ting; Tan, Ning-Hua

    2018-06-28

    Rubia yunnanensis is a medicinal plant mainly grown in Yunnan province in Southwest China, and its root named "Xiaohongshen" has been used as a herb in Yunnan for the treatment of cancers. Three major types of chemical components, Rubiaceae-type cyclopeptides, quinones, and triterpenoids, were identified from R. yunnanensis, in which some of compounds including rubiarbonol G (RG), a unique arboriane-type triterpenoid, showed cytotoxicity on cancer cells. But the cytotoxic mechanism of RG has not been reported. To investigate the cytotoxic mechanism of RG on cancer cells. RG was evaluated its cytotoxicity on 7 cancer cell lines by the SRB assay, and detected the effect on apoptosis and cell cycle arrest by Annexin V-FITC/PI apoptosis assay and DNA contents analysis. The expression and activity of apoptosis and cell cycle related proteins were also investigated by western blot and caspase activity assay. Furthermore, the effect of RG on NF-κB signaling was also tested by luciferase assay, western blot, and immunofluorescence staining. RG showed potent cytotoxicity on 7 human cancer cell lines, whose activity was attributed to apoptosis induction and G 0 /G 1 arrest in HeLa cells. Results from the mechanism study showed that RG promoted the activation of ERK1/2 and JNK pathway in MAPK family, which in turn increased the expression of p53, thereby triggering the G 0 /G 1 arrest through p53/p21/cyclin D1 signaling. Moreover, RG-mediated JNK activation down-regulated the expression of the anti-apoptotic protein Bcl-2, which caused the release of cytochrome c to the cytosol and activated the cleavage of caspase cascade and poly(ADP-ribose) polymerase, thereby inducing apoptosis in HeLa cells. In addition, RG was also found to inhibit the activation of NF-κB signaling by down-regulating the expression and attenuating the translocation to nucleus of NF-κB p65, by which the down-stream p53, cyclin D1, Bcl-2, and caspases were regulated, thereby triggering apoptosis and G

  16. An Ingenol Derived from Euphorbia kansui Induces Hepatocyte Cytotoxicity by Triggering G0/G1 Cell Cycle Arrest and Regulating the Mitochondrial Apoptosis Pathway in Vitro

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    Xiaojing Yan

    2016-06-01

    Full Text Available Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8, inverted phase contrast microscope and flow cytometry were used to demonstrate that lingenol significantly inhibited L-O2 cells proliferation, and induced cell cycle arrest and apoptosis. Moreover, the results investigated that lingenol markedly disrupted mitochondrial functions by high content screening (HCS. In addition, the up-regulation of cytochrome c, AIF and Apaf-1 and activation of caspases were found in L-O2 cells detected by Western blotting and ELISA assay, which was required for lingenol activation of cytochrome c-mediated caspase cascades and AIF-mediated DNA damage. Mechanistic investigations revealed that lingenol significantly down-regulated the Bcl-2/Bax ratio and enhanced the reactive oxygen species (ROS in L-O2 cells. These data collectively indicated that lingenol modulation of ROS and Bcl-2/Bax ratio led to cell cycle arrest and mitochondrial-mediated apoptosis in L-O2 cells in vitro. All of these results will be helpful to reveal the hepatotoxicity mechanism of Euphorbia kansui and to effectively guide safer and better clinical application of this herb.

  17. SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis.

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    Zhang, Jing; Jiang, Huawei; Shao, Jiaofang; Mao, Ruifang; Liu, Jie; Ma, Yingying; Fang, Xuefeng; Zhao, Na; Zheng, Shu; Lin, Biaoyang

    2014-11-01

    SOX4 is a transcription factor required for tissue development and differentiation in vertebrates. Overexpression of SOX4 has been reported in many cancers including glioblastoma multiforme (GBM), however, the underlying mechanism of actions has not been studied. In this study, we investigated the role of SOX4 in GBM. Kaplan-Meier analysis was performed to assess the association between SOX4 expression levels and survival times in primary GBM samples. Cre/lox P system was used to generate gain or loss of SOX4 in GBM cells, and microarray analysis uncovered the regulation network of SOX4 in GBM cells. High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1. Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways. Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.

  18. A Novel Polysaccharide Conjugate from Bullacta exarata Induces G1-Phase Arrest and Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells.

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    Liao, Ningbo; Sun, Liang; Chen, Jiang; Zhong, Jianjun; Zhang, Yanjun; Zhang, Ronghua

    2017-03-01

    Bullacta exarata has been consumed in Asia, not only as a part of the normal diet, but also as a traditional Chinese medicine with liver- and kidney-benefitting functions. Several scientific investigations involving extraction of biomolecules from this mollusk and pharmacological studies on their biological activities have been carried out. However, little is known regarding the antitumor properties of polysaccharides from B. exarata , hence the polysaccharides from B. exarata have been investigated here. One polysaccharide conjugate BEPS-IA was isolated and purified from B. exarata . It mainly consisted of mannose and glucose in a molar ratio of 1:2, with an average molecular weight of 127 kDa. Thirteen general amino acids were identified to be components of the protein-bound polysaccharide. Methylation and NMR studies revealed that BEPS-IA is a heteropolysaccharide consisting of 1,4-linked-α-d-Glc, 1,6-linked-α-d-Man, 1,3,6-linked-α-d-Man, and 1-linked-α-d-Man residue, in a molar ratio of 6:1:1:1. In order to test the antitumor activity of BEPS-IA, we investigated its effect against the growth of human hepatocellular carcinoma cells HepG2 in vitro. The result showed that BEPS-IA dose-dependently exhibited an effective HepG2 cells growth inhibition with an IC 50 of 112.4 μg/mL. Flow cytometry analysis showed that BEPS-IA increased the populations of both apoptotic sub-G1 and G1 phase. The result obtained from TUNEL assay corroborated apoptosis which was shown in flow cytometry. Western blot analysis suggested that BEPS-IA induced apoptosis and growth inhibition were associated with up-regulation of p53, p21 and Bax, down-regulation of Bcl-2. These findings suggest that BEPS-IA may serve as a potential novel dietary agent for hepatocellular carcinoma.

  19. Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction.

    Science.gov (United States)

    Zhu, Yongxia; Wei, Wei; Ye, Tinghong; Liu, Zhihao; Liu, Li; Luo, Yong; Zhang, Lidan; Gao, Chao; Wang, Ningyu; Yu, Luoting

    2016-01-01

    Cancer is still a major public health issue worldwide, and new therapeutics with anti-tumor activity are still urgently needed. The anti-tumor activity of TH-39, which shows potent anti-proliferative activity against K562 cells with an IC50 of 0.78 µM, was investigated using immunoblot, co-immunoprecipitation, the MTT assay, and flow cytometry. Mechanistically, TH-39 may disrupt the interaction between Hec1 and Nek2 in K562 cells. Moreover, TH-39 inhibited cell proliferation in a concentration- and time-dependent manner by influencing the morphology of K562 cells and inducing G0/G1 phase arrest. G0/G1 phase arrest was associated with down-regulation of CDK2-cyclin E complex and CDK4/6-cyclin D complex activities. Furthermore, TH-39 also induced cell apoptosis, which was associated with activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax. TH-39 could also decrease mitochondrial membrane potential (Δψm) and increase reactive oxygen species (ROS) accumulation in K562 cells. The results indicated that TH-39 might induce apoptosis via the ROS-mitochondrial apoptotic pathway. This study highlights the potential therapeutic efficacy of the anti-cancer compound TH-39 in treatment-resistant chronic myeloid leukemia. © 2016 The Author(s) Published by S. Karger AG, Basel.

  20. A Novel Polysaccharide Conjugate from Bullacta exarata Induces G1-Phase Arrest and Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

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    Ningbo Liao

    2017-03-01

    Full Text Available Bullacta exarata has been consumed in Asia, not only as a part of the normal diet, but also as a traditional Chinese medicine with liver- and kidney-benefitting functions. Several scientific investigations involving extraction of biomolecules from this mollusk and pharmacological studies on their biological activities have been carried out. However, little is known regarding the antitumor properties of polysaccharides from B. exarata, hence the polysaccharides from B. exarata have been investigated here. One polysaccharide conjugate BEPS-IA was isolated and purified from B. exarata. It mainly consisted of mannose and glucose in a molar ratio of 1:2, with an average molecular weight of 127 kDa. Thirteen general amino acids were identified to be components of the protein-bound polysaccharide. Methylation and NMR studies revealed that BEPS-IA is a heteropolysaccharide consisting of 1,4-linked-α-d-Glc, 1,6-linked-α-d-Man, 1,3,6-linked-α-d-Man, and 1-linked-α-d-Man residue, in a molar ratio of 6:1:1:1. In order to test the antitumor activity of BEPS-IA, we investigated its effect against the growth of human hepatocellular carcinoma cells HepG2 in vitro. The result showed that BEPS-IA dose-dependently exhibited an effective HepG2 cells growth inhibition with an IC50 of 112.4 μg/mL. Flow cytometry analysis showed that BEPS-IA increased the populations of both apoptotic sub-G1 and G1 phase. The result obtained from TUNEL assay corroborated apoptosis which was shown in flow cytometry. Western blot analysis suggested that BEPS-IA induced apoptosis and growth inhibition were associated with up-regulation of p53, p21 and Bax, down-regulation of Bcl-2. These findings suggest that BEPS-IA may serve as a potential novel dietary agent for hepatocellular carcinoma.

  1. The inhibition of activated hepatic stellate cells proliferation by arctigenin through G0/G1 phase cell cycle arrest: persistent p27(Kip1) induction by interfering with PI3K/Akt/FOXO3a signaling pathway.

    Science.gov (United States)

    Li, Ao; Wang, Jun; Wu, Mingjun; Zhang, Xiaoxun; Zhang, Hongzhi

    2015-01-15

    Proliferation of hepatic stellate cells (HSCs) is vital for the development of fibrosis during liver injury. In this study, we describe that arctigenin (ATG), a major bioactive component of Fructus Arctii, exhibited selective cytotoxic activity via inhibiting platelet-derived growth factor-BB (PDGF-BB)-activated HSCs proliferation and arrested cell cycle at G0/G1 phase, which could not be observed in normal human hepatocytes in vitro. The cyclin-dependent kinase (CDK) 4/6 activities could be strongly inhibited by ATG through down-regulation of cyclin D1 and CDK4/6 expression in early G1 phase arrest. In the ATG-treated HSCs, the expression level of p27(Kip1) and the formation of CDK2-p27(Kip1) complex were also increased. p27(Kip1) silencing significantly attenuated the effect of ATG, including cell cycle arrest and suppression of proliferation in activated HSCs. We also found that ATG suppressed PDGF-BB-induced phosphorylation of Akt and its downstream transcription factor Forkhead box O 3a (FOXO3a), decreased binding of FOXO3a to 14-3-3 protein, and stimulated nuclear translocation of FOXO3a in activated HSCs. Furthermore, knockdown of FOXO3a expression by FOXO3a siRNA attenuated ATG-induced up-regulation of p27(Kip1) in activated HSCs. All the above findings suggested that ATG could increase the levels of p27(Kip1) protein through inhibition of Akt and improvement of FOXO3a activity, in turn inhibited the CDK2 kinase activity, and eventually caused an overall inhibition of HSCs proliferation. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.

    Science.gov (United States)

    Martineti, Valentina; Tognarini, Isabella; Azzari, Chiara; Carbonell Sala, Silvia; Clematis, Francesca; Dolci, Marcello; Lanzotti, Virginia; Tonelli, Francesco; Brandi, Maria Luisa; Curir, Paolo

    2010-09-01

    The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications. Copyright 2010 John Wiley & Sons, Ltd.

  3. Rare sugar D-allose induces specific up-regulation of TXNIP and subsequent G1 cell cycle arrest in hepatocellular carcinoma cells by stabilization of p27kip1.

    Science.gov (United States)

    Yamaguchi, Fuminori; Takata, Maki; Kamitori, Kazuyo; Nonaka, Machiko; Dong, Youyi; Sui, Li; Tokuda, Masaaki

    2008-02-01

    'Rare sugars' are defined as monosaccharides that exist in nature but are only present in limited quantities. The development of mass production method of rare sugars revealed some interesting physiological effects of these on animal cells, but the mechanisms have not been well studied. We examined the effect of D-allose on the proliferation of cancer cells and the underlying molecular mechanism of the action. The HuH-7 hepatocellular carcinoma cells were treated with various monosaccharides for 48 h and D-allose was shown to inhibit cell growth by 40% in a dose-dependent manner. D-allose induced G1 cell cycle arrest but not apoptosis. The microarray analysis revealed that D-allose significantly up-regulated thioredoxin interacting protein (TXNIP) gene expression, which is often suppressed in tumor cells and western blot analysis confirmed its increase at protein level. The overexpression of TXNIP also induced G1 cell cycle arrest. Analysis of cell cycle regulatory genes showed p27kip1, a key regulator of G1/S cell cycle transition, to be increased at the protein but not the transcriptional level. Protein interaction between TXNIP and jab1, and p27kip1 and jab1, was observed, suggesting stabilization of p27kip1 protein by the competitive inhibition of jab1-mediated nuclear export of p27kip1 by TXNIP. In addition, increased interaction and nuclear localization of TXNIP and p27kip1 were apparent after D-allose treatment. Our findings surprisingly suggest that D-allose, a simple monosaccharide, may act as a novel anticancer agent via unique TXNIP induction and p27kip1 protein stabilization.

  4. Inhibition of SOX2 induces cell apoptosis and G1/S arrest in Ewing's sarcoma through the PI3K/Akt pathway.

    Science.gov (United States)

    Ren, Chongmin; Ren, Tingting; Yang, Kang; Wang, Shidong; Bao, Xing; Zhang, Fan; Guo, Wei

    2016-03-11

    Ewing's sarcoma is an aggressive bone and soft tissue tumor with a high incidence in children and adolescents. Due to its high malignancy and poor prognosis, identification of novel biomarkers for intervention therapies is necessary to improve outcome. The EWS/FLI1 fusion gene is a characteristic of Ewing's sarcoma in most cases. Sex determining region Y-box 2 (SOX2) is a primary target of EWS/FLI1. It has been identified as an oncogene and linked to apoptotic resistance in several types of cancer. However, its role and regulatory mechanisms in Ewing's sarcoma are largely unknown. We systematically investigated the role of SOX2 in Ewing's sarcoma cell lines, human tissue samples and xenograft models. The expression of SOX2 was detected in Ewing's sarcoma samples by WB and IHC. siRNAs were used to knockdown EWS/FLI1 and SOX2 in A673 and RD-ES cell lines with the efficiencies tested by qRT-PCR and WB. The effect of SOX2 on cell cycle and apoptosis was determined by Flow cytometric and TUNEL assays. Akt overexpression was performed with plasmid. The protein expression of the corresponding factors was examined by WB analysis. Inhibition of SOX2 in vivo was performed by siRNA against SOX2 in xenograft models, and the protein expression of the regulators testified in vitro was examined in xenograft tumors by IHC and WB. The results confirmed that SOX2 was highly expressed in Ewing's sarcoma and was the target of EWS/FLI1. SOX2 advanced Ewing's sarcoma cell survival and proliferation by regulating p21, p27 and cyclin-E to facilitate G1/S phase transition and mediating caspase-3, PARP via both extrinsic (Fas and caspase-8) and intrinsic (caspase-9, Bad, Bcl-2 and XIAP) apoptotic pathways to restrain cell apoptosis. Additionally, SOX2 regulated the cell-cycle progression and apoptosis via activation of the PI3K/Akt signaling pathway. The mechanisms were proved both in vitro and in vivo. The results demonstrate that SOX2 played a central role in promoting Ewing's sarcoma

  5. Persea declinata (Bl. Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation

    Directory of Open Access Journals (Sweden)

    Putri Narrima

    2014-01-01

    Full Text Available Persea declinata (Bl. Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill, which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl. Kosterm bark methanolic crude extract (PDM. PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

  6. Acute dose and low dose-rate irradiation of carcinoma cells expressing human papillomavirus E6 and E7 oncoproteins - the significance of p53, Rb and G1 arrest status

    International Nuclear Information System (INIS)

    DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Shao, Y.; Kessis, Theodore D.; Cho, Kathleen R.; Nelson, William G.

    1995-01-01

    Purpose: The development of carcinomas in a number of sites including the cervix, vulva and anus have been associated with cellular infection by human papillomaviruses (HPV), including HPV 16 and HPV 18. The mechanism by which these viruses contribute to tumor development or progression seems in part to be related to the integration of the viral genome into the host cells DNA, and the binding of p53 protein by the HPV E6 oncoprotein as well as the binding of the retinoblastoma (Rb) protein and Rb-like proteins by the HPV E7 oncoprotein. These interactions lead to loss of p53 and Rb function including loss of the G 1 cell cycle checkpoint. Although it is believed that both p53 and Rb play a role in the radiosensitivity of the cell, whether alteration in either protein enhances or diminishes cellular radiation response is not clear from the literature. Because HPV-associated tumors such as cervical cancer are often treated with acute dose and/or low dose-rate radiation, we set out to evaluate the radiation response of several carcinoma cell sublines expressing either oncogenic E6 or E7 to both types of radiation, and to determine if p53/Rb dependent G 1 arrest is an important determinant of cell fate after irradiation. Materials and Methods: We have previously developed a series of RKO colorectal carcinoma cell sublines expressing both low-risk (HPV 11) and high-risk (HPV 16) E6 and E7 genes. p53-dependent G 1 arrest is intact in RKO parental cells and cells expressing low-risk E6 proteins, while the G 1 arrest is abrogated in cells expressing high-risk E6 or E7. Clonogenic survival was assessed after exposure to acute dose (1 Gy/min) and low dose-rate (0.25 Gy/hour) radiation. The radiobiologic parameters α, β and the surviving fraction at 2 Gy (SF2) were determined. SDS-PAGE/immunoblotting was carried out to assess both p53 and p21 WAF1/CIP1 levels after exposure to radiation. Flow cytometry was performed before and after exposure to low dose-rate radiation to

  7. Ubiquitin ligase Cbl-b is involved in icotinib (BPI-2009H)-induced apoptosis and G1 phase arrest of EGFR mutation-positive non-small-cell lung cancer.

    Science.gov (United States)

    Mu, Xiaodong; Zhang, Ye; Qu, Xiujuan; Hou, Kezuo; Kang, Jian; Hu, Xuejun; Liu, Yunpeng

    2013-01-01

    Epidermal growth factor receptor (EGFR) is one of the most promising targets for non-small-cell lung cancer (NSCLC). Icotinib, a highly selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has shown promising clinical efficacy and safety in patients with NSCLC. The exact molecular mechanism of icotinib remains unclear. In this study, we first investigated the antiproliferative effect of icotinib on NSCLC cells. Icotinib significantly inhibited proliferation of the EGFR-mutated lung cancer HCC827 cells. The IC50 values at 48 and 72 h were 0.67 and 0.07 μ M, respectively. Flow cytometric analysis showed that icotinib caused the G1 phase arrest and increased the rate of apoptosis in HCC827 cells. The levels of cyclin D1 and cyclin A2 were decreased. The apoptotic process was associated with activation of caspase-3, -8, and poly(ADP-ribose) polymerase (PARP). Further study revealed that icotinib inhibited phosphorylation of EGFR, Akt, and extracellular signal-regulated kinase. In addition, icotinib upregulated ubiquitin ligase Cbl-b expression. These observations suggest that icotinib-induced upregulation of Cbl-b is responsible, at least in part, for the antitumor effect of icotinib via the inhibition of phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase pathways in EGFR-mutated NSCLC cells.

  8. Ubiquitin Ligase Cbl-b Is Involved in Icotinib (BPI-2009H-Induced Apoptosis and G1 Phase Arrest of EGFR Mutation-Positive Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2013-01-01

    Full Text Available Epidermal growth factor receptor (EGFR is one of the most promising targets for non-small-cell lung cancer (NSCLC. Icotinib, a highly selective EGFR tyrosine kinase inhibitor (EGFR-TKI, has shown promising clinical efficacy and safety in patients with NSCLC. The exact molecular mechanism of icotinib remains unclear. In this study, we first investigated the antiproliferative effect of icotinib on NSCLC cells. Icotinib significantly inhibited proliferation of the EGFR-mutated lung cancer HCC827 cells. The IC50 values at 48 and 72 h were 0.67 and 0.07 μM, respectively. Flow cytometric analysis showed that icotinib caused the G1 phase arrest and increased the rate of apoptosis in HCC827 cells. The levels of cyclin D1 and cyclin A2 were decreased. The apoptotic process was associated with activation of caspase-3, -8, and poly(ADP-ribose polymerase (PARP. Further study revealed that icotinib inhibited phosphorylation of EGFR, Akt, and extracellular signal-regulated kinase. In addition, icotinib upregulated ubiquitin ligase Cbl-b expression. These observations suggest that icotinib-induced upregulation of Cbl-b is responsible, at least in part, for the antitumor effect of icotinib via the inhibition of phosphoinositide 3-kinase (PI3K/Akt and mitogen-activated protein kinase pathways in EGFR-mutated NSCLC cells.

  9. Ferulago angulata activates intrinsic pathway of apoptosis in MCF-7 cells associated with G1 cell cycle arrest via involvement of p21/p27

    Directory of Open Access Journals (Sweden)

    Karimian H

    2014-09-01

    Full Text Available Hamed Karimian,1 Soheil Zorofchian Moghadamtousi,2 Mehran Fadaeinasab,3 Shahram Golbabapour,2 Mahboubeh Razavi,1 Maryam Hajrezaie,2 Aditya Arya,1 Mahmood Ameen Abdulla,4 Syam Mohan,5 Hapipah Mohd Ali,2 Mohamad Ibrahim Noordin1 1Department of Pharmacy, Faculty of Medicine, 2Institute of Biological Sciences, Faculty of Science, 3Department of Chemistry, 4Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 5Medical Research Centre, Jazan University, Jazan, Saudi Arabia Abstract: Ferulago angulata is a medicinal plant that is traditionally known for its ­anti-inflammatory and antiulcer properties. The present study was aimed to evaluate its anticancer activity and the possible mechanism of action using MCF-7 as an in vitro model. F. angulata leaf extracts were prepared using solvents in the order of increasing polarity. As determined by MTT assay, F. angulata leaves hexane extract (FALHE revealed the strongest cytotoxicity against MCF-7 cells with the half maximal inhibitory concentration (IC50 value of 5.3±0.82 µg/mL. The acute toxicity study of FALHE provided evidence of the safety of the plant extract. Microscopic and flow cytometric analysis using annexin-V probe showed an induction of apoptosis in MCF-7 by FALHE. Treatment of MCF-7 cells with FALHE encouraged the intrinsic pathway of apoptosis, with cell death transducing signals that reduced the mitochondrial membrane potential with cytochrome c release from mitochondria to cytosol. The released cytochrome c triggered the activation of caspase-9. Meanwhile, the overexpression of caspase-8 suggested the involvement of an extrinsic pathway in the induced apoptosis at the late stage of treatment. Moreover, flow cytometric analysis showed that FALHE treatment significantly arrested MCF-7 cells in the G1 phase, which was associated with upregulation of p21 and p27 assessed by quantitative polymerase chain reaction. Immunofluorescence

  10. Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest.

    Science.gov (United States)

    Omer, Fatima Abdelmutaal Ahmed; Hashim, Najihah Binti Mohd; Ibrahim, Mohamed Yousif; Dehghan, Firouzeh; Yahayu, Maizatulakmal; Karimian, Hamed; Salim, Landa Zeenelabdin Ali; Mohan, Syam

    2017-11-01

    Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G 0 /G 1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G 0 /G 1 phase and prompted the intrinsic apoptosis pathway.

  11. 1-(2,6-Dihydroxy-4-methoxyphenyl-2-(4-hydroxyphenyl Ethanone-Induced Cell Cycle Arrest in G1/G0 in HT-29 Cells Human Colon Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ma Ma Lay

    2014-01-01

    Full Text Available 1-(2,6-Dihydroxy-4-methoxyphenyl-2-(4-hydroxyphenyl ethanone (DMHE was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff. Boerl fruits and the structure confirmed by GC-MS (gas chromatography-mass spectrometry and NMR (nuclear magnetic resonance analysis. This compound was tested on the HT-29 human colon adenocarcinoma cell line using MTT (method of transcriptional and translational cell proliferation assay. The results of MTT assay showed that DMHE exhibited good cytotoxic effect on HT-29 cells in a dose- and time-dependent manner but no cytotoxic effect on the MRC-5 cell line after 72 h incubation. Morphological features of apoptotic cells upon treatment by DMHE, e.g., cell shrinkage and membrane blebbing, were examined by an inverted and phase microscope. Other features, such as chromatin condension and nuclear fragmentation were studied using acridine orange and propidium iodide staining under the fluorescence microscope. Future evidence of apoptosis/necrosis was provided by result fromannexin V-FITC/PI (fluorescein-isothiocyanate/propidium iodide staining revealed the percentage of early apoptotic, late apoptotic, necrotic and live cells in a dose- and time-dependent manner using flow cytometry. Cell cycle analysis showed G0/G1 arrest in a time-dependent manner. A western blot analysis indicated that cell death might be associated with the up-regulation of the pro-apoptotic proteins Bax PUMA. However, the anit-apotptic proteins Bcl-2, Bcl-xL, and Mcl-1 were also found to increase in a time-dependent manner. The expression of the pro-apoptotic protein Bak was not observed.

  12. Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ryoichi Tanaka

    Full Text Available Although many chemotherapeutic strategies against cancer have been developed, pancreatic cancer is one of the most aggressive and intractable types of malignancies. Therefore, new strategies and anti-cancer agents are necessary to treat this disease. Metformin is a widely used drug for type-2 diabetes, and is also known as a promising candidate anti-cancer agent from recent studies in vitro and in vivo. However, the mechanisms of metformin's anti-cancer effects have not been elucidated. We demonstrated that metformin suppressed the expression of miR-221, one of the most well-known oncogenic microRNAs, in human pancreatic cancer PANC-1 cells. Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is also a promising agent for cancer treatment. While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL. Metformin induced the expressions of death receptor 5 (DR5, a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway. We suggest that the up-regulation of these proteins may contribute to sensitization of TRAIL-induced apoptosis. The combination therapy of metformin and TRAIL could therefore be effective in the treatment of pancreatic cancer.

  13. Methylselenol, a selenium metabolite, induces cell cycle arrest in G1 phase and apoptosis via the extracellular-regulated kinase 1/2 pathway and other cancer signaling genes.

    Science.gov (United States)

    Zeng, Huawei; Wu, Min; Botnen, James H

    2009-09-01

    Methylselenol has been hypothesized to be a critical selenium (Se) metabolite for anticancer activity in vivo, and our previous study demonstrated that submicromolar methylselenol generated by incubating methionase with seleno-l-methionine inhibits the migration and invasive potential of HT1080 tumor cells. However, little is known about the association between cancer signal pathways and methylselenol's inhibition of tumor cell invasion. In this study, we demonstrated that methylselenol exposure inhibited cell growth and we used a cancer signal pathway-specific array containing 15 different signal transduction pathways involved in oncogenesis to study the effect of methylselenol on cellular signaling. Using real-time RT-PCR, we confirmed that cellular mRNA levels of cyclin-dependent kinase inhibitor 1C (CDKN1C), heme oxygenase 1, platelet/endothelial cell adhesion molecule, and PPARgamma genes were upregulated to 2.8- to 5.7-fold of the control. BCL2-related protein A1, hedgehog interacting protein, and p53 target zinc finger protein genes were downregulated to 26-52% of the control, because of methylselenol exposure. These genes are directly related to the regulation of cell cycle and apoptosis. Methylselenol increased apoptotic cells up to 3.4-fold of the control and inhibited the extracellular-regulated kinase 1/2 (ERK1/2) signaling and cellular myelocytomatosis oncogene (c-Myc) expression. Taken together, our studies identify 7 novel methylselenol responsive genes and demonstrate that methylselenol inhibits ERK1/2 pathway activation and c-Myc expression. The regulation of these genes is likely to play a key role in G1 cell cycle arrest and apoptosis, which may contribute to the inhibition of tumor cell invasion.

  14. Methylglyoxal-bis(guanylhydrazone), a polyamine analogue, sensitized γ-radiation-induced cell death in HL-60 leukemia cells Sensitizing effect of MGBG on γ-radiation-induced cell death.

    Science.gov (United States)

    Kim, Jin Sik; Lee, Jin; Chung, Hai Won; Choi, Han; Paik, Sang Gi; Kim, In Gyu

    2006-09-01

    Methylglyoxal-bis(guanylhydrazone) (MGBG), a polyamine analogue, has been known to inhibit the biosynthesis of polyamines, which are important in cell proliferation. We showed that MGBG treatment significantly affected γ-radiation-induced cell cycle transition (G(1)/G(0)→S→G(2)/M) and thus γ-radiation-induced cell death. As determined by micronuclei and comet assay, we showed that it sensitized the cytotoxic effect induced by γ-radiation. One of the reasons is that polyamine depletion by MGBG treatment did not effectively protect against the chemical (OH) or physical damage to DNA caused by γ-radiation. Through in vitro experiment, we confirmed that DNA strand breaks induced by γ-radiation was prevented more effectively in the presence of polyamines (spermine and spermidine) than in the absence of polyamines. MGBG also blocks the cell cycle transition caused by γ-radiation (G(2) arrest), which helps protect cells by allowing time for DNA repair before entry into mitosis or apoptosis, via the down regulation of cyclin D1, which mediates the transition from G(1) to S phase of cell cycle, and ataxia telangiectasia mutated, which is involved in the DNA sensing, repair and cell cycle check point. Therefore, the abrogation of G(2) arrest sensitizes cells to the effect of γ-radiation. As a result, γ-radiation-induced cell death increased by about 2.5-3.0-fold in cells treated with MGBG. However, exogenous spermidine supplement partially relieved this γ-radiation-induced cytotoxicity and cell death. These findings suggest a potentially therapeutic strategy for increasing the cytotoxic efficacy of γ-radiation.

  15. Cell cycle arrest induced by radiation

    International Nuclear Information System (INIS)

    Okaichi, Yasuo; Matsumoto, Hideki; Ohnishi, Takeo

    1994-01-01

    It is known that various chemical reactions, such as cell cycle arrest, DNA repair and cell killing, can occur within the cells when exposed to ionizing radiation and ultraviolet radiation. Thus protein dynamics involved in such chemical reactions has received considerable attention. In this article, cell cycle regulation is first discussed in terms of the G2/M-phase and the G1/S-phase. Then, radiation-induced cell cycle arrest is reviewed. Cell cycle regulation mechanism involved in the G2 arrest, which is well known to occur when exposed to radiation, has recently been investigated using yeasts. In addition, recent study has yielded a noticeable finding that the G1 arrest can occur with intracellular accumulation of p53 product following ionization radiation. p53 is also shown to play an extremely important role in both DNA repair and cell killing due to DNA damage. Studies on the role of genes in protein groups induced by radiation will hold promise for the elucidation of cell cycle mechanism. (N.K.) 57 refs

  16. Preferential radiosensitization of G1 checkpoint--deficient cells by methylxanthines

    International Nuclear Information System (INIS)

    Russell, Kenneth J.; Wiens, Linda W.; Demers, G. William; Galloway, Denise A.; Le, Tiep; Rice, Glenn C.; Bianco, James A.; Singer, Jack W.; Groudine, Mark

    1996-01-01

    Purpose: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. Methods and Materials: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. Results: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. Conclusions: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues

  17. Radiation-induced pneumothorax

    International Nuclear Information System (INIS)

    Epstein, D.M.; Littman, P.; Gefter, W.B.; Miller, W.T.; Raney, R.B. Jr.

    1983-01-01

    Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis

  18. Platelet-derived growth factor (PDGF)-signaling mediates radiation-induced apoptosis in human prostate cancer cells with loss of p53 function

    International Nuclear Information System (INIS)

    Kim, Harold E.; Han, Sue J.; Kasza, Thomas; Han, Richard; Choi, Hyeong-Seon; Palmer, Kenneth C.; Kim, Hyeong-Reh C.

    1997-01-01

    Platelet-derived growth factor (PDGF) signals a diversity of cellular responses in vitro, including cell proliferation, survival, transformation, and chemotaxis. PDGF functions as a 'competence factor' to induce a set of early response genes expressed in G 1 including p21 WAF1/CIP1 , a functional mediator of the tumor suppressor gene p53 in G 1 /S checkpoint. For PDGF-stimulated cells to progress beyond G 1 and transit the cell cycle completely, progression factors in serum such as insulin and IGF-1 are required. We have recently shown a novel role of PDGF in inducing apoptosis in growth-arrested murine fibroblasts. The PDGF-induced apoptosis is rescued by insulin, suggesting that G 1 /S checkpoint is a critical determinant for PDGF-induced apoptosis. Because recent studies suggest that radiation-induced signal transduction pathways interact with growth factor-mediated signaling pathways, we have investigated whether activation of the PDGF-signaling facilitates the radiation-induced apoptosis in the absence of functional p53. For this study we have used the 125-IL cell line, a mutant p53-containing, highly metastatic, and hormone-unresponsive human prostate carcinoma cell line. PDGF signaling is constitutively activated by transfection with a p28 v-sis expression vector, which was previously shown to activate PDGF α- and β- receptors. Although the basal level of p21 WAF1/CIP1 expression and radiation-induced apoptosis were not detectable in control 125-IL cells as would be predicted in mutant p53-containing cells, activation of PDGF-signaling induced expression of p21 WAF1/CIP1 and radiation-induced apoptosis. Our study suggests that the level of 'competence' growth factors including PDGF may be one of the critical determinants for radiation-induced apoptosis, especially in cells with loss of p53 function at the site of radiotherapy in vivo

  19. Radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Ohyama, Harumi

    1995-01-01

    Apoptosis is an active process of gene-directed cellular self-destruction that can be induced in many cell types via numerous physiological and pathological stimuli. We found that interphasedeath of thymocytes is a typical apoptosis showing the characteristic features of apoptosis including cell shrinkage, chromatin condensation and DNA degradation. Moderate dose of radiation induces extensive apoptosis in rapidly proliferating cell population such as the epithelium of intestinal crypt. Recent reports indicate that the ultimate form of radiation-induced mitotic death in several cells is also apoptosis. One of the hallmarks of apoptosis is the enzymatic internucleosomal degradation of chromatin DNA. We identified an endonuclease responsible for the radiation-induced DNA degradation in rat thymocytes. The death-sparing effects of interrupting RNA and protein synthesis suggested a cell genetic program for apoptosis. Apoptosis of thymocytes initiated by DNA damage, such as radiation and radio mimetic substance, absolutely requires the protein of p53 cancer suppresser gene. The cell death induced by glucocorticoid, or aging, has no such requirement. Expression of oncogene bcl-2 rescues cells from the apoptosis. Massive apoptosis in radiosensitive cells induced by higher dose radiation may be fatal. It is suggested that selective apoptotic elimination of cells would play an important role for protection against carcinogenesis and malformation through removal of cells with unrepaired radiation-induced DNA damages. Data to evaluate the significance of apoptosis in the radiation risk are still poor. Further research should be done in order to clarify the roles of the cell death on the acute and late effects of irradiation. (author)

  20. Radiation-induced myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gaenshirt, H [Heidelberg Univ. (F.R. Germany). Neurologische Klinik

    1975-10-01

    12 cases of radiation-induced myelopathy after /sup 60/Co teletherapy are reported on. Among these were 10 thoracal lesions, one cerviothoracal lesion, and one lesion of the medulla oblongata. In 9 cases, Hodgkin's disease had been the primary disease, tow patients had been irradiated because of suspected vertebral metastases of cancer of the breast, and one patient had suffered from a glomus tumour of the petrous bone. The spinal doses had exceeded the tolerance doses recommended in the relevant literature. There was no close correlation between the radiation dose and the course of the disease. The latency periods between the end of the radiotherapy and the onset of the neurological symptons varied from 6 to 16 mouths and were very constant in 7 cases with 6 to 9 months. The segmental height of the lesion corresponded to the level of irradiation. The presenting symptons of radiation-induced myelopathy are buruing dysaesthesias and Brown-Sequard's paralysis which may develop into transverse lesion of the cord with paraplegia still accompanied by dissociated perception disorders. The disease developed intermittently. Disturbances of the bladder function are frequent. The fluid is normal in most cases. Myelographic examinations were made in 8 cases. 3 cases developed into stationary cases exhibiting. Brown-Sequard syndrome, while 9 patients developed transverse lesion of the cord with paraplegia. 3 patients have died; antopsy findings are given for two of these. In the pathogenesis of radiation-induced myelopathy, the vascular factor is assumed to be of decisive importance.

  1. Protective effects of L-selenomethionine on space radiation induced changes in gene expression.

    Science.gov (United States)

    Stewart, J; Ko, Y-H; Kennedy, A R

    2007-06-01

    Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of L-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 microM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have

  2. DNA of HeLa cells during caffeine-promoted recovery from X-ray induced G2 arrest

    International Nuclear Information System (INIS)

    Bases, R.; Mendez, F.; Liebeskind, D.; Elequin, F.; Neubort, S.

    1980-01-01

    Progression of X-irradiated HeLa cells from G2 arrest through mitosis was promoted by 1mM caffeine. Caffeine promoted the return from abnormally high levels of radiation-induced immunoreactivity to antinucleoside antibodies, which indicates persistent DNA strand separation, to the low levels normally found in G2. With caffeine, the irradiated cells progressed through mitosis, producing daughter cells with the normal G1 content of DNA. Without caffeine, the DNA content of individual radiation-arrested cells retained G2 values and the abnormally high levels of immunoreactivity to antinucleoside antibodies. (author)

  3. Radioprotection against radiation induced bone marrow syndrome by a semi-synthetic derivative of chlorophyll

    International Nuclear Information System (INIS)

    Suryavanshi, Shweta; Sharma, Deepak; Checker, Rahul; Santosh Kumar, S.; Sainis, Krishna B.

    2014-01-01

    A plethora of biological properties have been attributed to chlorophyllin (CHL), the water soluble derivative of the green plant pigment chlorophyll. Several studies are available describing its ability to modify genotoxic effects. It has been shown that administration CHL to human lymphopenic individuals led to the recovery and restoration of the immune system and also inhibited aflatoxin B1-DNA binding in individuals residing in high risk exposure to this liver carcinogen. The present study is aimed at establishing radioprotective efficacy of CHL against ionizing radiation induced hematopoietic syndrome. CHL offered complete protection against whole body irradiation (WBI, 7 Gy) induced mortality in mice. This observation was supported by increase in the number of macroscopic endogenous colonies enumerated on the surface of the spleens taken from CHL+WBI group as compared to WBI group. Radioprotection by CHL was found to be mediated by increasing the frequency of hematopoietic stem cells (HSCs) as evaluated by side population assay. Administration of CHL induced G1 arrest in bone marrow cells, increased number of granulocytes and neutrophils in the peripheral blood. At the molecular level, activation of ERK was observed in bone marrow cells obtained from CHL administered mice. In conclusion, CHL mediated radioprotection was attributed to increased stem cell numbers, G1 arrest in bone marrow cells, increased neutrophil numbers and ERK activation. (author)

  4. Radiation-induced cancer

    International Nuclear Information System (INIS)

    Dutrillaux, B.; CEA Fontenay-aux-Roses, 92

    1998-01-01

    The induction of malignant diseases is one of the most concerning late effects of ionising radiation. A large amount of information has been collected form atomic bomb survivors, patients after therapeutic irradiation, occupational follow-up and accidentally exposed populations. Major uncertainties persist in the (very) low range i.e, population and workers radioprotection. A review of the biological mechanisms leading to cancer strongly suggests that the vast majority of radiation-induced malignancies arise as a consequence of recessive mutations can be unveiled by ageing, this process being possibly furthered by constitutional or acquired genomic instability. The individual risk is likely to be very low, probably because of the usual dose level. However, the magnitude of medical exposure and the reliance of our societies on nuclear industry are so high that irreproachable decision-making processes and standards for practice are inescapable. (author)

  5. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  6. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants.

  7. Radiation induced pesticidal microbes

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S.

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants

  8. Radiation-induced cerebrovasculopathy

    International Nuclear Information System (INIS)

    Ikeyama, Yukihide; Abiko, Seisho; Kurokawa, Yasushi; Okamura, Tomomi; Watanabe, Kohsaku; Inoue, Shinichi; Fujii, Yasuhiro.

    1993-01-01

    We reported a patient who suffered from cerebrovasculopathy after irradiation therapy for astrocytoma located at the left temporal lobe. An eleven year-old boy who presented with headache and vomiting received partial removal of a tumor. Histological diagnosis of the tumor was astrocytoma (grade II). His preoperative cerebral angiograms showed mass sign solely, without stenosis or occlusion of the cerebral vessel. Postoperatively, he was treated with irradiation therapy involving the whole brain with a total of 30 Gy, and gamma knife therapy. Six months after irradiation, he started suffering from frequent cerebral ischemic attacks, but there was no regrowth of the tumor visible on CT scans. Cerebral angiograms were made again, and revealed multifocal stenoses in the bilateral internal carotid arteries, middle cerebral arteries, and the anterior cerebral artery. His symptoms did not improve after conservative treatment with steroids, calcium antagonist, or low molecular weight dextran. Although he received a superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses bilaterally, multiple cerebral infarctions appeared. Although irradiation therapy is acceptable in patients with brain tumor, cerebrovasculopathy after irradiation should be considered as one of the most important complications, and the risk incurred by irradiation therapy should lead to more careful consideration and caution when treating intracranial brain tumors, especially in children. From our experience, the usefulness of bypass surgery for radiation-induced cerebrovasculopathy is still controversial. (author)

  9. Radiation induced nano structures

    International Nuclear Information System (INIS)

    Ibragimova, E.M.; Kalanov, M.U.; Khakimov, Z.

    2006-01-01

    Full text: Nanometer-size silicon clusters have been attracting much attention due to their technological importance, in particular, as promising building blocks for nano electronic and nano photonic systems. Particularly, silicon wires are of great of interest since they have potential for use in one-dimensional quantum wire high-speed field effect transistors and light-emitting devices with extremely low power consumption. Carbon and metal nano structures are studied very intensely due to wide possible applications. Radiation material sciences have been dealing with sub-micron objects for a long time. Under interaction of high energy particles and ionizing radiation with solids by elastic and inelastic mechanisms, at first point defects are created, then they form clusters, column defects, disordered regions (amorphous colloids) and finally precipitates of another crystal phase in the matrix. Such irradiation induced evolution of structure defects and phase transformations was observed by X-diffraction techniques in dielectric crystals of quartz and corundum, which exist in and crystal modifications. If there is no polymorphism, like in alkali halide crystals, then due to radiolysis halogen atoms are evaporated from the surface that results in non-stoichiometry or accumulated in the pores formed by metal vacancies in the sub-surface layer. Nano-pores are created by intensive high energy particles irradiation at first chaotically and then they are ordered and in part filled by inert gas. It is well-known mechanism of radiation induced swelling and embrittlement of metals and alloys, which is undesirable for construction materials for nuclear reactors. Possible solution of this problem may come from nano-structured materials, where there is neither swelling nor embrittlement at gas absorption due to very low density of the structure, while strength keeps high. This review considers experimental observations of radiation induced nano-inclusions in insulating

  10. Radiation-induced genetic instability: no association with changes in radiosensitivity or cell cycle checkpoints in C3H 10T1/2 mouse fibroblasts

    International Nuclear Information System (INIS)

    Crompton, N.E.A.; Emery, G.C.; Shi Yuquan; Sigg, M.; Blattmann, H.

    1998-01-01

    We investigated various phenotypic characteristics of radiation-induced morphologically transformed C3H 10T1/2 mouse fibroblasts. The cells were treated with 8 Gy x-rays, and type II/III foci were isolated. Cell lines were developed from these foci, and subsequently clones were established from these focal lines. The clones were examined for DNA content, radiosensitivity and inducible cell cycle arrests. Besides the morphological changes associated with the transformed state, the major difference between the isolated focal lines or derived clones and the parental C3H 10T1/2 line was one of ploidy. The transformed cells often displayed aneuploid and multiple polyploid populations. No change in the radiosensitivity of the transformed cells was observed. Furthermore, the two major radiation- and staurosporine-induced G1 and G2 cell cycle arrests observed in the parental cell line were also observed in the morphological transformants, suggesting that checkpoint function was normal. (orig.)

  11. Radiation-induced radical ions in calcium sulfite

    Science.gov (United States)

    Bogushevich, S. E.

    2006-07-01

    We have used EPR to study the effect of γ radiation on calcium sulfite. We have observed and identified the radiation-induced radical ions SO 2 - (iso) with g = 2.0055 and SO 2 - (orth-1) with g1 = 2.0093, g2 = 2.0051, g3 = 2.0020, identical to the initial and thermally induced SO 2 - respectively, SO 3 - (iso) with g = 2.0031 and SO 3 - (axial) with g⊥ = 2.0040, g∥ = 2.0023, identical to mechanically induced SO 3 - . We have established the participation of radiation-induced radical ions SO 3 - in formation of post-radiation SO 2 - .

  12. SN-38 Acts as a Radiosensitizer for Colorectal Cancer by Inhibiting the Radiation-induced Up-regulation of HIF-1α.

    Science.gov (United States)

    Okuno, Takayuki; Kawai, Kazushige; Hata, Keisuke; Murono, Koji; Emoto, Shigenobu; Kaneko, Manabu; Sasaki, Kazuhito; Nishikawa, Takeshi; Tanaka, Toshiaki; Nozawa, Hiroaki

    2018-06-01

    Hypoxia offers resistance to therapy in human solid tumors. The aim of the study was to investigate whether SN-38, the active metabolite of irinotecan, acts as a radiosensitizer through inhibition of hypoxia-inducible factor (HIF)-1α in the human colorectal cancer (CRC) cells. HT29 and SW480 cells were cultured with SN-38 (0-4 μM) immediately after irradiation (0-8 Gy). HIF-1α expression was assessed using flow-cytometry and western blot analysis. Cell proliferation was evaluated by the calcein assay. Apoptosis and cell cycle were determined by flow-cytometry. Radiation up-regulated HIF-1α, and SN-38 inhibited the radiation-induced HIF-1α. The combination of radiation and SN-38 inhibited cell proliferation more than radiation alone; treatment with SN-38 after radiation exposure did not increase the number of apoptotic cells, whereas, it enhanced the S and G 2 /M cell-cycle arrest and decreased the population of cells in G 1 Conclusion: SN-38 inhibits the radiation-induced up-regulation of HIF-1α and acts as a radiosensitizer by inducing cell-cycle arrest in CRC cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Radiation induced crosslinking of polytetrafluoroethylene

    International Nuclear Information System (INIS)

    Oshima, Akihiro; Tabata, Yoneho; Ikeda, Shigetoshi; Otsuhata, Kazushige; Kudoh, Hisaaki; Seguchi, Tadao.

    1995-01-01

    The Irradiation temperature effect on polytetrafluoroethylene (PTFE) from room temperature to 380degC was investigated by tensile test and thermal analysis. The behavior of tensile properties and changes of crystallinity on irradiation indicated the formation of a network structure in PTFE by radiation induced crosslinking in inert gas in the molten state just above the melting temperature of PTFE (327degC). The crosslinked PTFE showed a much improved radiation resistance in an atmospheric radiation field. (author)

  14. Specitic gene alterations in radiation-induced tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Joo Mee; Kang, Chang Mo; Lee, Seung Sook; Cho, Chul Koo; Bae, Sang Woo; Lee, Su Jae; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    To identify a set of genes involved in the development of radiation-induced tumorigenesis, we used DNA microarrays consisting of 1,176 mouse genes and compared expression profiles of radioresistant cells, designated NIH3T3-R1 and -R4. These cells were tumorigenic in a nude mouse grafting system, as compared to the parental NIH3T3 cells. Expressions of MDM2, CDK6 and CDC25B were found to increase more than 3-fold. Entactin protein levels were downregulated in NIH3T3-R1 and -R4 cells. Changes in expression genes were confirmed by reverse transcription-PCR or western blotting. When these genes were transfected to NIH3T3 cells, the CDC25B and MDM2 overexpressing NIH3T3 cells showed radioresistance, while 2 CDK6 overexpressing cells did not. In the case of entactin overexpressing NIH3T3-R1 or R-4 cells were still radioresistant. Furthermore, the CDC25B and MDM2 overexpressing cells grafted to nude mice, were tumorigenic. NIH3T3-R1 and R4 cells showed increased radiation-induced apoptosis, accompanied by faster growth rate, rather than and earlier radiation-induced G2/M phase arrest, suggesting that the radioresistance of NIH3T3-R1 and R4 cells was due to faster growth rate, rather than induction of apoptosis. In the case of MDM2 and CDC25B overexpressing cells, similar phenomena, such as increased apoptosis and faster growth rate, were shown. The above results, therefore, demonstrate involvement of CDC25B and MDM2 overexpression in radiation-induced tumorigenesis and provide novel targets for detection of radiation-induced carcinogenesis.

  15. Radiation-induced chromosomal instability

    International Nuclear Information System (INIS)

    Ritter, S.

    1999-01-01

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/μm) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  16. Radiation-induced heart injury

    International Nuclear Information System (INIS)

    Suzuki, Yoshihiko; Niibe, Hideo

    1975-01-01

    In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the internal between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue. (Evans, G.)

  17. Modulation of radiation-induced apoptosis and G{sub 2}/M block in murine T-lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N. [Harvard Medical School, Boston, MA (United States)

    1995-03-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to {sup 137}Cs {gamma} irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of {gamma} radiation. We studied the effect of several pharmacological agents on the radiation-induced G{sub 2}/M block and DNA fragmentation. The agents which reduced the radiation-induced G{sub 2}/M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G{sub 2}/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G{sub 2}/M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G{sub 2}/M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs.

  18. Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells

    International Nuclear Information System (INIS)

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N.

    1995-01-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to 137 Cs γ irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of γ radiation. We studied the effect of several pharmacological agents on the radiation-induced G 2 /M block and DNA fragmentation. The agents which reduced the radiation-induced G 2 /M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G 2 /M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G 2 /M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G 2 /M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs

  19. Radiation-induced thermoacoustic imaging

    International Nuclear Information System (INIS)

    Bowen, T.

    1984-01-01

    This invention provides a new technique for obtaining information non-invasively on the composition and structures of a material or body by detecting radiation-induced thermoacoustic image features. This is accomplished by utilizing the acoustic wave generated by sudden thermal stress. The sudden thermal stress is induced by a pulse of radiation which deposits energy causing a rapid, but very small, rise of temperature (typically, ΔT approximately 10sup(-6) - 10sup(-5) deg C). The radiation may be ionizing radiation, such as high energy electrons, photons (x-rays), neutrons, or other charged particles or it may be non-ionizing radiation, such as R.F. and microwave electromagnetic radiation and ultrasonic radiation. The choice of radiation depends on the nature of the body to be imaged and the type of information desired

  20. Functional analysis of molecular mechanisms of radiation induced apoptosis, that are not mediated by DNA damages

    International Nuclear Information System (INIS)

    Angermeier, Marita; Moertl, Simone

    2012-01-01

    The effects of low-dose irradiation pose new challenges on the radiation protection efforts. Enhanced cellular radiation sensitivity is displayed by disturbed cellular reactions and resulting damage like cell cycle arrest, DNA repair and apoptosis. Apoptosis serves as genetically determinate parameter for the individual radiation sensitivity. In the frame of the project the radiation-induced apoptosis was mechanistically investigated. Since ionizing radiation induced direct DNA damage and generates a reactive oxygen species, the main focus of the research was the differentiation and weighting of DNA damage mediated apoptosis and apoptosis caused by the reactive oxygen species (ROS).

  1. Radiation induced sulfur dioxide removal

    International Nuclear Information System (INIS)

    Chmielewski, A.G.

    2000-01-01

    The biggest source of air pollution is the combustion of fossil fuels, were pollutants such as particulate, sulfur dioxide (SO 2 ), nitrogen oxides (NO x ), and volatile organic compounds (VOC) are emitted. Among these pollutants, sulfur dioxide plays the main role in acidification of the environment. The mechanism of sulfur dioxide transformation in the environment is partly photochemical. This is not direct photooxidation, however, but oxidation through formed radicals. Heterogenic reactions play an important role in this transformation as well; therefore, observations from environmental chemistry can be used in air pollution control engineering. One of the most promising technologies for desulfurization of the flue gases (and simultaneous denitrification) is radiation technology with an electron accelerator application. Contrary to the nitrogen oxides (NO x ) removal processes, which is based on pure radiation induced reactions, sulfur dioxide removal depends on two pathways: a thermochemical reaction in the presence of ammonia/water vapor and a radiation set of radiochemical reactions. The mechanism of these reactions and the consequent technological parameters of the process are discussed in this paper. The industrial application of this radiation technology is being implemented in an industrial pilot plant operated by INCT at EPS Kaweczyn. A full-scale industrial plant is currently in operation in China, and two others are under development in Japan and Poland. (author)

  2. Live-Cell Imaging Visualizes Frequent Mitotic Skipping During Senescence-Like Growth Arrest in Mammary Carcinoma Cells Exposed to Ionizing Radiation

    International Nuclear Information System (INIS)

    Suzuki, Masatoshi; Yamauchi, Motohiro; Oka, Yasuyoshi; Suzuki, Keiji; Yamashita, Shunichi

    2012-01-01

    Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO 2 -hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ß-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.

  3. Live-Cell Imaging Visualizes Frequent Mitotic Skipping During Senescence-Like Growth Arrest in Mammary Carcinoma Cells Exposed to Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masatoshi, E-mail: msuzuki@nagasaki-u.ac.jp [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan); Yamauchi, Motohiro; Oka, Yasuyoshi; Suzuki, Keiji; Yamashita, Shunichi [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan)

    2012-06-01

    Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO{sub 2}-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ss-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.

  4. Radiation-induced apoptosis in different pH environments in vitro

    International Nuclear Information System (INIS)

    Lee, Hyung-Sik; Park, Heon J.; Lyons, John C.; Griffin, Robert J.; Auger, Elizabeth A.; Song, Chang W.

    1997-01-01

    Purpose: The effect of environmental pH on the radiation-induced apoptosis in tumor cells in vitro was investigated. Methods and Materials: Mammary adenocarcinoma cells of A/J mice (SCK cells) were irradiated with γ-rays using a 137 Cs irradiator and incubated in media of different pHs. After incubation at 37 deg. C for 24-120 h the extent of apoptosis was determined using agarose gel electrophoresis, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, flow cytometry, and release of 3 H from 3 H-thymidine labeled cells. The clonogenicity of the cells irradiated in different pH medium was determined, and the progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Results: Irradiation with 2-12 Gy of γ-rays induced apoptosis in SCK cells in pH 7.5 medium within 48 h as judged from the results of four different assays mentioned. Radiation-induced apoptosis declined as the medium pH was lowered from 7.5 to 6.4. Specifically, the radiation-induced degradation of DNA including the early DNA breaks, as determined with the TUNEL method, progressively declined as the medium pH was lowered so that little DNA fragmentation occurred 48 h after irradiation with 12 Gy in pH 6.6 medium. When the cells were irradiated and incubated for 48 h in pH 6.6 medium and the medium was replaced with pH 7.5 medium, DNA fragmentation promptly occurred. DNA fragmentation also occurred even in pH 6.6 medium when the cells were irradiated and maintained in pH 7.5 medium for 8 h or longer post-irradiation before incubation in pH 6.6 medium. The radiation-induced G 2 arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Conclusion: Radiation-induced apoptosis in SCK cells in vitro is reversibly suppressed in an acidic environment. Taking the results of four different assays together, it was concluded that early step(s) in the apoptotic pathway, probably the DNA break or upstream of DNA break, is

  5. Radiation-induced instability of human genome

    International Nuclear Information System (INIS)

    Ryabchenko, N.N.; Demina, Eh.A.

    2014-01-01

    A brief review is dedicated to the phenomenon of radiation-induced genomic instability where the increased level of genomic changes in the offspring of irradiated cells is characteristic. Particular attention is paid to the problems of genomic instability induced by the low-dose radiation, role of the bystander effect in formation of radiation-induced instability, and its relationship with individual radiosensitivity. We believe that in accordance with the paradigm of modern radiobiology the increased human individual radiosensitivity can be formed due to the genome instability onset and is a significant risk factor for radiation-induced cancer

  6. Better flocculants by radiation induced polymerization

    International Nuclear Information System (INIS)

    Laizier, J.; Gaussens, G.

    1978-01-01

    The use of radiation induced polymerization should theoritically allow to prepare better flocculants. The testings of several products prepared by such a process shows that better properties are indeed obtained: better efficiencies, lower amounts needed, better overall properties [fr

  7. Study on the protective effect of MgSO4 on the radiation-induced neural stem cell injury

    International Nuclear Information System (INIS)

    Liu Ping; Tu Yu

    2010-01-01

    Objective: To explore the neuroprotective effect of magnesium sulfate on radiation induced neural stem cell injury. Methods: Brain tissue was obtained from new-born sprague-dawley rats within 24 hours, and the cerebral hemisphere was dissociated to culture the neural stem cells. After being identified by immunofluorescence method, the neural stem cells were randomly divided into 3 groups as blank control group, experimental control group and experimental group. The neural stem cells of experimental control group and experimental group were irradiated with 2 or 4 Gy of gamma rays. The proliferation and the cell cycle of neural stem cells were detected at different time-points ranging from 24 h,48 h, 72 h after irradiation with CCK-8 and FCM. Results: Compared with the blank control group, the proliferation rate of experimental control group was significantly reduced (t=5.33-8.44, P<0.05 ), and the G 1 phase arrest of experimental control group was significantly enhanced (t=30.60-71.22, P<0.05).Compared with the experimental control group, the proliferation of experimental group significantly increased excluding that of 24 h (t=2.45-4.71, P<0.05), the apoptosis rate of experimental group significantly decreased (t=6.73-41.12, P<0.05), which was closer to the blank control group.Conclusion: Magnesium sulfate can alleviate the injury of proliferation and decrease the cell apoptosis in the early stage after irradiation. (authors)

  8. Effect of caffeine on gamma-ray induced G2 arrest in well-synchronized Chinese hamster ovary cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Keng, P.C.

    1996-11-01

    G1-rich cells were separated from exponentially growing asynchronous cultured Chinese hamster ovary (CHO-K1) cells by centrifugal elutriation and a Coulter Counter. The G1-rich cells were incubated in medium that contained hydroxyurea (HU) to kill S phase cells and obtain the purest G1/S boundary cells possible. The HU-treated cells were washed, and were again incubated, in medium without HU, to allow these well-synchronized G1/S boundary cells to progress to S and G2/M phases. At various times after release from G1/S boundary, 4 Gy of gamma-ray and/or caffeine was administered to the cells. Eight hours after the removal of HU, cell-cycle analysis was performed with a flow cytometer. G2 arrest induced by gamma-rays was clearly shown when radiation was given earlier than 6.5 hours after HU removal. G2 arrest induced by radiation given 0.5-6.5 hours after HU removal was reduced by caffeine treatment given 6.0-6.5 hours after HU removal. Caffeine released radiation-induced G2 arrest when the radiation was given before the cultured cells entered G2/M phase and when caffeine was applied to the irradiated cells at the time when G1/S boundary cells not treated by radiation or with caffeine entered G2/M phase. Our method of centrifugal elutriation combined with incubation with HU was useful for isolating pure G1/S boundary cells from in vitro asynchronous cultures. (author)

  9. Effect of caffeine on gamma-ray induced G2 arrest in well-synchronized Chinese hamster ovary cells in vitro

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Keng, P.C.

    1996-01-01

    G1-rich cells were separated from exponentially growing asynchronous cultured Chinese hamster ovary (CHO-K1) cells by centrifugal elutriation and a Coulter Counter. The G1-rich cells were incubated in medium that contained hydroxyurea (HU) to kill S phase cells and obtain the purest G1/S boundary cells possible. The HU-treated cells were washed, and were again incubated, in medium without HU, to allow these well-synchronized G1/S boundary cells to progress to S and G2/M phases. At various times after release from G1/S boundary, 4 Gy of gamma-ray and/or caffeine was administered to the cells. Eight hours after the removal of HU, cell-cycle analysis was performed with a flow cytometer. G2 arrest induced by gamma-rays was clearly shown when radiation was given earlier than 6.5 hours after HU removal. G2 arrest induced by radiation given 0.5-6.5 hours after HU removal was reduced by caffeine treatment given 6.0-6.5 hours after HU removal. Caffeine released radiation-induced G2 arrest when the radiation was given before the cultured cells entered G2/M phase and when caffeine was applied to the irradiated cells at the time when G1/S boundary cells not treated by radiation or with caffeine entered G2/M phase. Our method of centrifugal elutriation combined with incubation with HU was useful for isolating pure G1/S boundary cells from in vitro asynchronous cultures. (author)

  10. 3 cases of radiation-induced sarcoma

    International Nuclear Information System (INIS)

    Shiba, Keiichiro; Fukuma, Hisatoshi; Beppu, Yasuo; Hirota, Teruyuki; Shinohara, Norio.

    1982-01-01

    Criteria for the diagnosis of radiation-induced sarcoma have been previously described. All cases must have a history of irradiation and the second neoplasm must have arisen in the area of the radiation field. A latent period of several years must have elapsed after irradiation before clinical evidence of a second malignant neoplasm. Most important thing is that, all suspected cases must have been proved histologically. We have experienced 3 cases of radiation-induced sarcoma, they were 42-years-old man who developed an osteosarcoma of the lumbar spine at the field of postoperative irradiation for seminoma 7 years previously, 69-years-old woman who developed a malignant fibrous histiocytoma of the buttock at the field of radical radiation for uterine carcinoma 7 years previously and 59-years-old woman who developed an extraskeletal osteosarcoma of the abdominal wall at the field of postoperative irradiation for uterine sarcoma 7 years previously. The last case is very rare and only 8 cases of radiation-induced extraskeletal osteosarcoma have been reported. Since there has been a definite trend in the treatment of cancer toward employing radiation for more favorable cases, in addition to technical improvements in the administration of radiotherapy and more modern equipment, survival data may have been altered considerably in many malignant tumors. Accordingly, more radiation-induced tumors may be encountered in the future. The clinical presentation and histopathology of these radiation-induced sarcomas are presented with a review of the literature. (author)

  11. Daily Arrests

    Data.gov (United States)

    Montgomery County of Maryland — This dataset provides the public with arrest information from the Montgomery County Central Processing Unit (CPU) systems. The data presented is derived from every...

  12. Cardiac arrest

    Science.gov (United States)

    ... magnesium. These minerals help your heart's electrical system work. Abnormally high or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your ...

  13. Radiation-induced centers in inorganic glasses

    International Nuclear Information System (INIS)

    Brekhovskikh, S.M.; Tyul'nin, V.A.

    1988-01-01

    The nature, structure and formation mechanisms of radiation-induced colour centers, EPR, luminescence, generated ionizing radiation in nonorganic oxide glasses are considered. Experimental material covering both fundamental aspects of radiation physics and glass chemistry, and aspects intimately connected with the creation of new materials with the given radiation-spectral characteristics, with possibilities to prepare radiation-stable and radiation-sensitive glasses is systematized and generalized. Considerable attention is paid to the detection of radiation-induced center binding with composition, glass structures redox conditions for their synthesis. Some new possibilities of practical application of glasses with radiation-induced centers, in particular, to record optical information are reflected in the paper

  14. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    Michael eRobbins

    2012-07-01

    Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain

  15. Visualizing the effect of tumor microenvironments on radiation-induced cell kinetics in multicellular spheroids consisting of HeLa cells

    International Nuclear Information System (INIS)

    Kaida, Atsushi; Miura, Masahiko

    2013-01-01

    Highlights: •We visualized radiation-induced cell kinetics in spheroids. •HeLa-Fucci cells were used for detection of cell-cycle changes. •Radiation-induced G2 arrest was prolonged in the spheroid. •The inner and outer cell fractions behaved differently. -- Abstract: In this study, we visualized the effect of tumor microenvironments on radiation-induced tumor cell kinetics. For this purpose, we utilized a multicellular spheroid model, with a diameter of ∼500 μm, consisting of HeLa cells expressing the fluorescent ubiquitination-based cell-cycle indicator (Fucci). In live spheroids, a confocal laser scanning microscope allowed us to clearly monitor cell kinetics at depths of up to 60 μm. Surprisingly, a remarkable prolongation of G2 arrest was observed in the outer region of the spheroid relative to monolayer-cultured cells. Scale, an aqueous reagent that renders tissues optically transparent, allowed visualization deeper inside spheroids. About 16 h after irradiation, a red fluorescent cell fraction, presumably a quiescent G0 cell fraction, became distinct from the outer fraction consisting of proliferating cells, most of which exhibited green fluorescence indicative of G2 arrest. Thereafter, the red cell fraction began to emit green fluorescence and remained in prolonged G2 arrest. Thus, for the first time, we visualized the prolongation of radiation-induced G2 arrest in spheroids and the differences in cell kinetics between the outer and inner fractions

  16. Radiation-induced linking reactions in polyethylene

    International Nuclear Information System (INIS)

    Zoepfl, F.J.

    1983-01-01

    Three types of measurements are reported relating to chemical reactions in polyethylene induced by ionizing radiation: 1) viscometric and low-angle laser light scattering measurements to determine the effect of a radical scavenger on the yield of links; 2) calorimetric measurements to determine the effect of radiation-induced linking on the melting behavior of polyethylene; and 3) high-resolution solution carbon 13 nuclear magnetic resonance (NMR) spectrometry measurements to determine the nature of the links and the method of their formation. The NMR results present the first direct detection of radiation-induced long-chain branching (Y links) in polyethylene, and place an apparent upper limit on the yield of H-shaped crosslinks that are formed when polyethylene is irradiated to low absorbed doses. The effect of radiation-induced linking on the melting behavior of polyethylene was examined using differential scanning calorimetry (DSC). It was found that radiation-induced links do not change the heat of fusion of polythylene crystals, but decrease the melt entropy and increase the fold surface free energy per unit area of the crystals. The carbon 13 NMR results demonstrate that long-chain branches (Y links) are formed much more frequently than H-shaped crosslinks at low absorbed doses. The Y links are produced by reactions of alkyl free radicals with terminal vinyl groups in polyethylene

  17. Mechanisms of transient radiation-induced creep

    International Nuclear Information System (INIS)

    Pyatiletov, Yu.S.

    1981-01-01

    Radiation-induced creep at the transient stage is investigated for metals. The situation, when several possible creep mechanisms operate simultaneously is studied. Among them revealed are those which give the main contribution and determine thereby the creep behaviour. The time dependence of creep rate and its relation to the smelling rate is obtained. The results satisfactorily agree with the available experimental data [ru

  18. Reducing radiation induced emesis in abdominal radiotherapy

    International Nuclear Information System (INIS)

    Griffin, K.

    1994-01-01

    In patients with seminoma testes, a comparison was made between radiation induced emesis suffered by patients receiving 'dogleg' radiotherapy with those suffered by patients who received para-aortic radiotherapy. The same comparisons were made between the effects suffered by those patients who received the anti-emetic, Ondansetron, and those suffered by patients who received conventional anti-emetics. (UK)

  19. The regulation of ras-raf signaling pathway on G1 phase of the irradiated cells

    International Nuclear Information System (INIS)

    Guo Dehuang; Dong Bo; Liu Nongle; Wen Gengyun; Luo Qingliang; Mao Bingzhi

    2000-01-01

    Objective: To investigate the way of ras-raf signaling pathway which regulate the G 1 phase in irradiated KG-1 cells. Methods: Blocked the GM-CSF signaling pathway by transfected DN-ras and then momentary transfected cyclin D1 into irradiated KG-1 cells, the effects of cyclin D1 on G 1 phase was examined. Results: The irradiated KG-1 cells transfected DN-ras can't recover form G 1 phase arrest even though the GM-CSF was given,momentary transfected cyclin D1 promote the irradiated KG-1 cells from G 1 arrest. Conclusion: Activation of ras-raf signaling pathway regulate the cell cycle of the irradiated KG-1 cells through promotion the expression of the cyclin D1

  20. Radiation-induced brain injury: A review

    Energy Technology Data Exchange (ETDEWEB)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Wheeler, Kenneth T. [Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Department of Radiology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Chan, Michael D., E-mail: mrobbins@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States)

    2012-07-19

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  1. Radiation-induced brain injury: A review

    International Nuclear Information System (INIS)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  2. Bile acids in radiation-induced diarrhea

    International Nuclear Information System (INIS)

    Arlow, F.L.; Dekovich, A.A.; Priest, R.J.; Beher, W.T.

    1987-01-01

    Radiation-induced bowel disease manifested by debilitating diarrhea is an unfortunate consequence of therapeutic irradiation for pelvic malignancies. Although the mechanism for this diarrhea is not well understood, many believe it is the result of damage to small bowel mucosa and subsequent bile acid malabsorption. Excess amounts of bile acids, especially the dihydroxy components, are known to induce water and electrolyte secretion and increase bowel motility. We have directly measured individual and total bile acids in the stool samples of 11 patients with radiation-induced diarrhea and have found bile acids elevated two to six times normal in eight of them. Our patients with diarrhea and increased bile acids in their stools had prompt improvement when given cholestyramine. They had fewer stools and returned to a more normal life-style

  3. Radiation-induced meningiomas in pediatric patients

    International Nuclear Information System (INIS)

    Moss, S.D.; Rockswold, G.L.; Chou, S.N.; Yock, D.; Berger, M.S.

    1988-01-01

    Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature

  4. Radiation-induced conductivity of polynaphthoyl benzimidazole

    Energy Technology Data Exchange (ETDEWEB)

    Tiutnev, A P; Berlin, A M; Saenko, V S; Rusanov, A L; Korshak, V V

    1985-01-01

    The nonstationary radiation-induced conductivity of polynaphthoyl benzimidazole, synthesized by single-stage high-temperature catalytic polycondensation, is investigated experimentally. It is shown that the radiation-induced conductivity of this material is characterized by an anomalous (non-Gaussian) transfer of excess charge carriers. The activation energy of the delayed component (0.1 ms after pulse termination) is determined to be 0.12 eV; the volt-ampere characteristic of this component is nonlinear, with the coefficient of nonlinearity increasing with the intensity of the external electric field. Experimental results are interpreted on the basis of the phenomenological theory of jump conductivity proposed by Zviagin. 15 references.

  5. Ionizing radiation induced malignancies in man

    International Nuclear Information System (INIS)

    Dutrillaux, B.

    1997-01-01

    Using data on gene and chromosome alterations in human cancers, it is proposed that most radiation induced cancers are a consequence of recessive mutations of tumor suppressor genes. This explains the long delay between radiation exposure and the cancer onset. As a consequence, radiation induced cancers belong to groups of tumors where no specific translocations (forming or activating oncogenes) but multiple unbalanced chromosome rearrangements (deletions unmasking recessive mutations) exist. This explains why osteosarcomas, malignant fibrous histiocytoma, chondrosarcomas are frequently induced, but not liposarcoma, Ewing sarcomas and rhabdomyosarcomas, among others. A single exception confirms this rule: papillary thyroid cancer, frequently induced in exposed children, in which structural rearrangements frequently form a RET/PTC3 fusion gene. This fusion gene is the results of the inversion of a short segment of chromosome 10, and it is assumed that such rearrangement (small para-centric inversion) can easily occur after exposure to radiations, at contrast with translocations between to genes belonging to different chromosomes. (author)

  6. Radiation-induced degradation of pollutants

    International Nuclear Information System (INIS)

    Proksch, E.

    1988-01-01

    This article outlines the fundamentals of radiation-induced degradation of noxious substances in drinking water and waste water and discusses the relevant literature. Radiation methods present a number of advantages and disadvantages, which should carefully be considered in each case. In many cases, there seems to be merit in combining the radiation method with other techniques, as e.g. ozone treatement and biodegradation. 30 refs., 3 figs. (Author)

  7. Radiation induced glioblastoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Naoki; Kayama, Takamasa; Sakurada, Kaori; Saino, Makoto; Kuroki, Akira [Yamagata Univ. (Japan). School of Medicine

    2000-05-01

    We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. A autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and secondary glioblastoma. (author)

  8. Radiation-induced cancers in man

    International Nuclear Information System (INIS)

    Hirose, Fumio

    1978-01-01

    Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer. (Ichikawa, K.)

  9. Radiation-induced heart injury. Radiopathological study

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Y; Niibe, H [Gunma Univ., Maebashi (Japan). School of Medicine

    1975-11-01

    In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the interval between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue.

  10. Genetic alterations during radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Kodama, Seiji

    1995-01-01

    This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

  11. Radiation-induced cancers in man

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, F [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1978-07-01

    Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer.

  12. Alpha radiation-induced alterations of the proliferation kinetics, chromatin structure and gene expression in mammalian cells

    International Nuclear Information System (INIS)

    Hieber, L.

    1983-01-01

    Exponentially growing mammalian cells were exposed to 3.4 MeV alpha particles. The chromatin of cells arrested in G2 by alpha irradiation was severely damaged, though all cells were still capable to condensate their chromatin after fusion with mitotic cells. In addition to the common types of aberrations (breaks, gaps, dicentrics and exchanges) cells were found possessing one or more chromosomes with long stretches of undercondensed chromatin. Repair of these lesions was indicated by site specific unscheduled DNA synthesis and by the observation that condensation of these regions improved during G2 arrest. Furthermore, during G2 arrest the synthesis of two cellular proteins was stimulated. This was studied by two-dimensional gel electrophoresis of 35 S-methionine labeled cellular proteins. All these findings provided evidence that radiation-induced G2 arrest is caused by chromatin damage, which prevents regular chromosome condensation for mitosis. (orig./MG) [de

  13. The nature and principles of the radiation-induced cancerogenesis

    International Nuclear Information System (INIS)

    Lips'ka, A.YI.; Serkyiz, Ya.Yi.

    2004-01-01

    The paper represents the analysis of the authors and literary data concerning the nature and principles of the radiation-induced neoplasms. The mechanisms of the radiation-induced cancerogenesis development are not clear understood. The experimental data altogether do not allow developing the mathematical model of the radiation-induced cancerogenesis at the molecular level. This model has to take into account all necessary indices including radiation factor and the state of the organism. The general principles of the radiation-induced cancerogenesis have been formulated in the present review. It is possible to use these principles in order to predict and calculate the risks of the radiation-induced neoplasms

  14. Hesperidin as radioprotector against radiation-induced lung damage in rat: A histopathological study

    Directory of Open Access Journals (Sweden)

    Gholam Hassan Haddadi

    2017-01-01

    Full Text Available Reactive oxygen species (ROS are generated by ionizing radiation, and one of the organs commonly affected by ROS is the lung. Radiation-induced lung injury including pneumonia and lung fibrosis is a dose-limiting factor in radiotherapy (RT of patients with thorax irradiation. Administration of antioxidants has been proved to protect against ROS. The present study was aimed to assess the protective effect of hesperidin (HES against radiation-induced lung injury of male rats. Fifty rats were divided into three groups. G1: Received no HES and radiation (sham. G2: Underwent γ-irradiation to the thorax. G3: Received HES and underwent γ-irradiation. The rats were exposed to a single dose of 18 Gy using cobalt-60 unit and were administered HES (100 mg/kg for 7 days before irradiation. Histopathological analysis was performed 24 h and 8 weeks after RT. Histopathological results in 24 h showed radiation-induced inflammation and presence of more inflammatory cells as compared to G1 (P < 0.05. Administration of HES significantly decreased such an effect when compared to G2 (P < 0.05. Histopathological evaluation in 8 weeks showed a significant increase in mast cells, inflammation, inflammatory cells, alveolar thickness, vascular thickness, pulmonary edema, and fibrosis in G2 when compared to G1 (P < 0.05. HES significantly decreased inflammatory response, fibrosis, and mast cells when compared to G2 (P < 0.05. Administration of HES resulted in decreased radiation pneumonitis and radiation fibrosis in the lung tissue. Thus, the present study showed HES to be an efficient radioprotector against radiation-induced damage in the lung of tissue rats.

  15. Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Børresen-Dale, Anne-Lise; Alsner, Jan

    2008-01-01

    BACKGROUND AND PURPOSE: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last...... years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients. MATERIALS AND METHODS: Fibroblast cell lines from 31 individuals......-treated fibroblasts. Transcriptional differences in basal and radiation-induced gene expression profiles were investigated using 15K cDNA microarrays, and results analyzed by both SAM and PAM. RESULTS: Sixty differentially expressed genes were identified by applying SAM on 10 patients with the highest risk of RIF...

  16. Radiation-induced cerebrovascular disease in children

    International Nuclear Information System (INIS)

    Wright, T.L.; Bresnan, M.J.

    1976-01-01

    Radiation-induced internal carotid artery occlusion has not been well recognized previously as a cause of childhood cerebrovascular disease. A child who had received radiation as a neonate for a hemangioma involving the left orbit at the age of 6 years experienced a recurrent right-sided paresis, vascular headaches, and speech difficulties. Angiography showed a hypoplastic left carotid artery with occlusion of both the anterior and middle cerebral arteries. Collateral vessels bypassed the occluded-stenotic segments. Review of the literature showed two additional cases of large vessel occlusion in childhood associated with anastomatic telangiectatic vessel development following early radiation therapy of facial hemangioma

  17. Radiation induced peroxidation in model lipid systems

    International Nuclear Information System (INIS)

    Dahlan, K.Z.B.H.M.

    1981-08-01

    In the studies of radiation induced lipid peroxidation, lecithin-liposomes and aqueous micellar solutions of sodium linoleate (or linoleic acid) have been used as models of lipid membrane systems. The liposomes and aqueous linoleate micelles were irradiated in the presence of O 2 and N 2 O/O 2 (80/20 v/v). The peroxidation was initiated using gamma radiation from 60 Co radiation source and was monitored by measuring the increase in absorbance of conjugated diene at 232 nm and by the thiobarbituric acid (TBA) test. The oxidation products were also identified by GLC and GLC-MS analysis. (author)

  18. Radiation-induced damage of membranes

    International Nuclear Information System (INIS)

    Yonei, Shuji

    1977-01-01

    An outline of membranous structure was stated, and radiation-induced damage of membranes were surveyed. By irradiation, permeability of membranes, especially passive transportation mechanism, was damaged, and glycoprotein in the surface layers of cells and the surface layer structures were changed. The intramembranous damage was induced by decrease of electrophoresis of nuclear mambranes and a quantitative change of cytochrome P450 of microsomal membranes of the liver, and peroxidation of membranous lipid and SH substitute damage of membranous protein were mentioned as the mechanism of membranous damage. Recovery of membranous damage depends on radiation dose and temperature, and membranous damage participates largely in proliferation death. (tsunoda, M.)

  19. Radiation-induced sensitisation of stainless steels

    International Nuclear Information System (INIS)

    Norris, D.I.R.

    1987-01-01

    The book contains the proceedings of a symposium on radiation-induced sensitization of stainless steels, which took place at Berkeley, United Kingdom, 1986. The purpose of the symposium was to examine the mechanism leading to inter-granular corrosion of 20%Cr/25% Ni/Nb stainless steel cladding of AGR fuel following irradiation. Nine papers are presented, of which three are theoretical, two papers are based upon corrosion studies of 20%Cr/25%Ni/Nb steel, and the remaining are concerned with compositional redistribution and its measurement. (U.K.)

  20. A report on radiation-induced gliomas

    International Nuclear Information System (INIS)

    Salvati, M.; Artico, M.; Caruso, R.; Rocchi, G.; Orlando, E.R.; Nucci, F.

    1991-01-01

    Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy.56 references

  1. Radiation-induced diploid spermatids in mice

    International Nuclear Information System (INIS)

    Hacker-Klom, U.; Heiden, Th.; Otto, F.J.; Goehde, W.; Mauro, F.

    1989-01-01

    Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute 60 Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author)

  2. Radiation induced liver disease: A clinical update

    International Nuclear Information System (INIS)

    Benson, R.; Madan, R.; Chander, S.; Kilambi, R.

    2016-01-01

    Radiation-induced liver disease (RILD) or radiation hepatitis is a sub-acute form of liver injury due to radiation. It is one of the most dreaded complications of radiation which prevents radiation dose escalation and re irradiation for hepatobiliary or upper gastrointestinal malignancies. This complication should be kept in mind whenever a patient is planned for irradiation of these malignancies. Although, incidence of RILD is decreasing due to better knowledge of liver tolerance, improved investigation modalities and modern radiation delivery techniques, treatment options are still limited. In this review article, we have focussed on pathophysiology, risk factors, prevention and management of RILD

  3. Radiation-induced diploid spermatids in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hacker-Klom, U; Heiden, Th; Otto, F J; Goehde, W; Mauro, F

    1989-05-01

    Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute /sup 60/Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author).

  4. Injection profiles with radiation induced copolymers

    International Nuclear Information System (INIS)

    Knight, B.L.; Rhudy, J.S.; Gogarty, W.B.

    1976-01-01

    The injectivity profile of a heterogeneous formation and/or vertical conformance is improved by injecting an aqueous solution into the formation, the solution containing a polymer obtained as a product of radiation-induced polymerization of acrylamide and/or methacrylamide and acrylic acid, methacrylic acid, and/or alkali metal salts thereof. The polymerization is preferably carried out in a 10 to 60 percent aqueous solution with gamma radiation; the aqueous monomer solution preferably contains 25 to 99 percent acrylamide and 1 to 75 percent sodium acrylate. Immiscible, miscible, or miscible-like displacing processes can be used in conjunction with this invention. 20 claims

  5. Study on radiation-inducible genes

    International Nuclear Information System (INIS)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Song, Hyu Npa

    2012-01-01

    Transcription of previously identified radiation-inducible genes, uscA and cyoA, was examined responding to radiation. The putative promoter regions of both genes were cloned into pRS415 vector containing lacZ, and the core promoter region necessary for radiation response were determined through promoter deletion method. To investigate the role of uscA, which is assumed to be small RNA related with radiation response, a deletion mutant strain of uscA was constructed. However, uscA deletion did not affect bacterial survival against radiation exposure. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. For outward secretion of anticancer protein produced inside bacteria, the N-terminal 140 amino acid of SspH1 was found to function as a secretion signal peptide. To create an attenuated tumor-targeting bacteria, Salmonella ptsI mutant strain was constructed, and we found that its virulence decreased. Finally, the tumor-targeting ability of ptsI mutant was verified by the use of in-vivo imaging analysis

  6. Study on radiation-inducible genes

    International Nuclear Information System (INIS)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

    2012-01-01

    Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy

  7. Study of radiation-induced chromosomal aberrations

    International Nuclear Information System (INIS)

    Wolfring, E.

    2004-06-01

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

  8. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    Tease, C.

    1989-01-01

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  9. Study on radiation-inducible genes

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

    2012-01-15

    Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy.

  10. Study on radiation-inducible genes

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Song, Hyu Npa

    2012-01-15

    Transcription of previously identified radiation-inducible genes, uscA and cyoA, was examined responding to radiation. The putative promoter regions of both genes were cloned into pRS415 vector containing lacZ, and the core promoter region necessary for radiation response were determined through promoter deletion method. To investigate the role of uscA, which is assumed to be small RNA related with radiation response, a deletion mutant strain of uscA was constructed. However, uscA deletion did not affect bacterial survival against radiation exposure. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. For outward secretion of anticancer protein produced inside bacteria, the N-terminal 140 amino acid of SspH1 was found to function as a secretion signal peptide. To create an attenuated tumor-targeting bacteria, Salmonella ptsI mutant strain was constructed, and we found that its virulence decreased. Finally, the tumor-targeting ability of ptsI mutant was verified by the use of in-vivo imaging analysis.

  11. Cell kinetic studies on radiation induced leukemogenesis

    International Nuclear Information System (INIS)

    Nakao, Isamu; Suzuki, Gen; Imai, Yasufumi; Kawase, Yoshiko; Nose, Masako; Hirashima, Kunitake; Bessho, Masami

    1989-01-01

    The purpose of this study was threefold: (1) to determine the clonal origin of radiation-induced thymic lymphoma in mice with cellular mosaicism for phosphoglycerate kinase; (2) to determine the incidence and latent period of myeloid leukemia and thymic lymphoma induced by whole-body exposure to median doses (3.0 Gy or less) in RFM/MsNrs-2 mice; and (3) to examine the influence of human recombinant interleukin-2 (hrIL-2). Thymic lymphoma was of a single cell origin. The incidence of radiation-induced myeloid leukemia and thymic lymphoma in RFM mice increased in a dose dependent fashion. Mean latent periods of both myeloid leukemia and thymic lymphoma after irradiation became shorter in proportion to radiation doses. When hrIL-2 was injected to RFM mice receiving 3.0 Gy, mean survivals were shorter in thymoma-bearing mice than the control mice. This suggested that hrIL-2 shortens the promotion step of thymoma. Administration of hrIL-2 failed to alter the incidence of myeloid leukemia or the mean survival of mice having myeloid leukemia, indicating that the protocol of hrIL-2 administration was not so sufficient as to alter the myeloid leukemogenesis. (Namekawa, K)

  12. Radiation induced genetic damage in Aspergillus nidulans

    International Nuclear Information System (INIS)

    Georgiou, J.T.

    1984-01-01

    The mechanism by which ionizing radiation induces genetic damage in haploid and diploid conidia of Aspergillus nidulans was investigated. Although the linear dose-response curves obtained following low LET irradiation implied a 'single-hit' action of radiation, high LET radiations were much more efficient than low LET radiations, which suggests the involvement of a multiple target system. It was found that the RBE values for non-disjunction and mitotic crossing-over were very different. Unlike mitotic crossing-over, the RBE values for non-disjunction were much greater than for cell killing. This suggests that non-disjunction is a particularly sensitive genetical endpoint that is brought about by damage to a small, probably non-DNA target. Radiosensitisers were used to study whether radiation acts at the level of the DNA or some other cellular component. The sensitisation to electrons and/or X-rays by oxygen, and two nitroimidazoles (metronidazole and misonidazole) was examined for radiation induced non-disjunction, mitotic crossing-over, gene conversion, point mutation and cell killing. It was found that these compounds sensitised the cells considerably more to genetic damage than to cell killing. (author)

  13. Radiation-induced brain damage in children

    International Nuclear Information System (INIS)

    Oi, Shizuo; Kokunai, Takashi; Ijichi, Akihiro; Matsumoto, Satoshi; Raimondi, A.J.

    1990-01-01

    The nature and sequence of the radiation-induced changes in the brain were studied postmortem in 34 children with glioma, 22 of whom underwent central nervous system radiation therapy. Twenty received whole-brain or whole-neuroaxis radiation at a total mean dosage of 4063 cGy. Brain tissue alternations were analyzed histologically by means of various staining methods, including immunohistochemical techniques. The histological features of irradiated brains were compared with those of non-irradiated brains. Microscopic findings included demyelination (seven cases), focal necrosis (six cases), cortical atrophy (four cases), endothelial proliferation (four cases), and telangiectatic vascular proliferation with vascular thickening and oozing of a thick fluid (one case). Such findings were rare in non-irradiated patients. Demyelination was observed earliest in a patient who died 5 months after radiation therapy and was more common after 9 months. Focal necrosis was first observed 9 months post-irradiation but was more advanced and extensive after 1 year. Calcified foci were found only after 60 months. Various vascular changes such as vascular thickening and thrombosis suggested ischemic insult to the brain as a late effect of radiation injury. The results of this study suggest that the immature brain may be more sensitive to radiation than is the adult brain, and that the manifestations of radiation-induced injury depend on the time elapsed after irradiation. (author)

  14. Three cases of radiation-induced cancer in oral regions

    International Nuclear Information System (INIS)

    Kawamura, Hiroshi; Shinoki, Kunihiko; Endo, Yoshitaka; Fujita, Yasushi; Hayashi, Susumu

    1985-01-01

    Three cases of radiation-induced cancer in the oral regions were reported with relation to radiation therapy. One was the general radiation-induced cancer following radiotherapy for the hemangioma. The other two cases, which belonged in the B-1 group of Sakai and his coworker's diagnostic criteria for radiation-induced cancer, were those occurring after radiotherapy for the malignant tumors. Due to the relatively high dosage exposure by the patient in the radiotherapy it is necessary to look out the latency of the radiation-induced cancer. After radiotherapy, careful and periodical observation is important for immediate treatment in an early stage for the radiation-induced cancer to have a favorable prognosis. In addition careful observation of the changes after radiotherapy helps in discovering the precancerous lesions from the therapy. For the radiation-induced cancer, surgical treatment would be the best, however, radiation therapy is also effective in certain cases. (author)

  15. Role of neurotensin in radiation-induced hypothermia in rats

    International Nuclear Information System (INIS)

    Kandasamy, S.B.; Hunt, W.A.; Harris, A.H.

    1991-01-01

    The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin

  16. Radiation induced dry eye: problem and potential remedies

    International Nuclear Information System (INIS)

    Vemuganti, Geeta K.; Tiwari, Shubha

    2016-01-01

    Advances in orbital radiotherapy have significantly increased therapeutic efficiency and reduced the side effects but a significant proportion of patients are still seen with ophthalmic complication like dry eye syndrome (DES). The treatment of DES involves temporary palliative therapies like ocular surface lubrication and rehydration. We aimed at establishing the human lacrimal gland cultures and evaluating for the presence of stem cells and secretory potential. Using human lacrimal gland tissues obtained from samples of therapeutic exenteration post-radiotherapy, we established a monolayer as well as 3D lacrispheres that show evidence of stem cells, secretory acinar cells, duct like formation and other cells like myoepithelial cells and duct like cells. The stem cells were identified as CD 117 positive that co-segregated with G0/G1 phase, ALDH high, label retaining cells and high clone forming ability. The most promising evidence of its secretory function was seen in the presence of tear substances like lysosymes, lactiferrin, and scIg A in the conditioned media of the lacrimal gland cultures. This novel development would pave way for development of a functionally competent 3D construct for potential clinical application in severe cases of radiation induced dry eye. (author)

  17. Radiation-induced bone neoplasma in facial cranium

    Energy Technology Data Exchange (ETDEWEB)

    Zomer-Drozda, J; Buraczewska-Lipinska, H; Buraczewski, J [Instytut Onkologii, Warsaw (Poland)

    1976-01-01

    Radiation-induced bone neoplasms in the region of facial cranium account for about 40% of all radiation-induced tumours of bones, although the number of cases with lesions irradiated in this area is proportionally much lower than the number of cases treated with radiotherapy in other parts of the body. Four personal cases of radiation-induced tumours with complicated course are reported. Attention is called to the value of radiological investigations in the diagnosis of bone diseases and in differential diagnosis of radiation-induced tumours of bones.

  18. Radiation-induced creep and swelling

    International Nuclear Information System (INIS)

    Heald, P.T.

    1977-01-01

    The physical basis for radiation induced creep and swelling is reviewed. The interactions between the point defects and dislocations are recalled since these interactions are ultimately responsible for the observable deformation phenomena. Both the size misfit interaction and the induced inhomogeneity interaction are considered since the former gives rise to irradiation swelling while the latter, which depends on both internal and external stresses, results in irradiation creep. The defect kinetics leading to the deformation processes are discussed in terms of chemical rate theory. The rate equations for the spatially averaged interstitial and vacancy concentrations are expressed in terms of the microstructural sink strengths and the solution of these equations leads to general expressions for the deformation rates

  19. Studies on radiation-induced graft polymerization

    International Nuclear Information System (INIS)

    Omichi, Hideki

    1978-09-01

    Radiation-induced graft polymerization is used extensively to improve physical properties of polymers, but few processes are now commercialized. The reason for this is partly inadequate basic research on the reaction and partly the difficulty in developing the grafting process with large radiation source. Firstly, new techniques are proposed of studying kinetics of the graft polymerization in heterogeneous system. Based on the grafting yield, the molecular weight of graft chains, and the amount of radicals given by ESR and activation analysis, kinetic parameters are obtained and the reaction mechanism of grafting process is discussed. Secondly, the development of grafting process of poly (vinyl chloride)-butadiene is described. By study of the reaction, process design, construction and operation of the pilot plant, and economic analysis of the process, this process with 60 Co gamma ray sources is shown to be industrially promising. (author)

  20. Radiation-induced lesions of the aorta

    Energy Technology Data Exchange (ETDEWEB)

    Doessing, M; Rasmussen, S [Medical Department C, Diakonissestiftelsen, Copenhagen (Denmark); Fischer-Hansen, B; Walbom-Joergensen, S

    1977-04-09

    A description is given of pathological changes detected in the aortic arch of a 21-year-old man. The patient died from an acute myocardial infarction 16 months after a dose of 3696 rads to a mantle field for Hodgkin's disease confined to the midcervical lymph nodes on the left side of the neck. Histological examination of the exposed part of the aortic arch showed the wall to be focally thickened owing to a pronounced fibrosis of the luminal third of the wall. The elastic lamellae in this area were reduced in number, broken up, and haphazardly arranged. The intima appeared normal. There was no leucocytic infiltration, no proliferation of vasa vasorum and no significant adventitial fibrosis. It is suggested that these noncharacteristic changes may have been early radiation-induced lesions which later might induce fibrotic scarring with perhaps clinically evident disease.

  1. Radiation-induced emulsion polymerization of tetrafluoroethylene

    International Nuclear Information System (INIS)

    Suwa, Takeshi

    1979-10-01

    The radiation-induced emulsifier-free emulsion polymerization of tetrafluoroethylene (TFE) has been studied at initial pressure 2 - 25 kg/cm 2 and temperature 30 0 - 110 0 C for dose rate 0.57 x 10 4 - 3.0 x 10 4 rad/hr. Polytetrafluoroethylene (PTFE), a hydrophobic polymer, forms as a stable latex in the absence of an emulsifier. Stability of the latex is governed by the dose rate/TFE pressure ratio; it increases with sufficient TFE monomer. PTFE particles produced in this polymerization system are stable due to the carboxyl end groups and adsorption of OH - and HF on the particles. PTFE latex of molecular weight higher than 2 x 10 7 is obtained by addition of a radical scavenger such as hydroquinone. The molecular weight of PTFE can be measured from the heat of crystallization conveniently with high reliability, which was found in the course of study on the melting and crystallization behavior. (author)

  2. Radiation-induced mutations and plant breeding

    International Nuclear Information System (INIS)

    Naqvi, S.H.M.

    1985-01-01

    Ionizing radiation could cause genetic changes in an organism and could modify gene linkages. The induction of mutation through radiation is random and the probability of getting the desired genetic change is low but can be increased by manipulating different parameters such as dose rate, physical conditions under which the material has been irradiated, etc. Induced mutations have been used as a supplement to conventional plant breeding, particularly for creating genetic variability for specific characters such as improved plant structure, pest and disease resistance, and desired changes in maturity period; more than 200 varieties of crop plants have been developed by this technique. The Pakistan Atomic Energy Commission has used this technique fruitfully to evolve better germplasm in cotton, rice, chickpea, wheat and mungbean; some of the mutants have become popular commercial varieties. This paper describes some uses of radiation induced mutations and the results achieved in Pakistan so far

  3. Radiation-induced mutations in mammals

    International Nuclear Information System (INIS)

    Ehling, U.H.

    1993-01-01

    The aims of the proposed project are to provide a better basis for extrapolation of animal data to man. Genetic endpoint, strain and species comparisons are made, which will provide critical experimental data regarding strategies in extrapolating laboratory animal data to man. Experiments were conducted to systematically compare the spontaneous and radiation-induced mutation rates for recessive specific-locus, dominant cataract and enzyme activity alleles in the mouse as well as a comparison of the mutation rate in the mouse and hamster for dominant cataract and enzyme activity alleles. The comparison of the radiation-dose response for recessive specific-locus and dominant cataract mutations are extended. Selected mutations are characterized at the genetic, biochemical and molecular levels. (R.P.) 5 refs., 3 tabs

  4. Radiation-induced mutation at minisatellite loci

    International Nuclear Information System (INIS)

    Dubrova, Y.E.; Nesterov, V.N.; Krouchinsky, N.G.

    1997-01-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of γ-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure 137 Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed

  5. Ionizing radiation-induced cell death

    International Nuclear Information System (INIS)

    Szumiel, I.

    1994-01-01

    Selected aspects of radiation-induced cell death, connected with signal transduction pathways are reviewed. Cell death is defined as insufficiency of the cellular signal transducing system to maintain the cell's physiological functions. The insufficiency may be due to impaired signal reception and/or transduction, lack or erroneous transcription activation, and eventual cellular ''misexpression'' of the signal. The molecular basis of this insufficiency would be damage to genomic (but also other cellular) structures and closing of specific signalling pathways or opening of others (like those leading to apoptosis). I describe experimental data that suggest an important role of RAS/NFI and p53/p105 Rb proteins in cell cycle control-coupled responses to DNA damage. (Author)

  6. An integrated model for radiation induced cancer

    International Nuclear Information System (INIS)

    Hall, E.J.; Varma, M.

    1994-01-01

    Risk estimates for radiation induced cancer are based on epidemiological data, principally the Japanese A bomb survivors. These estimates for radiation are better known than for any other environmental pollutant, but they do not relate directly to exposure to low doses and low dose rate. Recent rapid advances in molecular genetics, coupled with steady gains in cellular biology, radiation physics and chemistry led to the notion that the time may not be far off when it may be possible to arrive at human cancer risk estimates entirely from laboratory data. Whether risk estimates based on laboratory data will ever replace estimates based on epidemiological studies is an open question. What is clear is that laboratory data can supplement the present risk estimates by providing information on the relative effectiveness of high LET radiations, the importance of dose rate and dose protraction, and by identifying subpopulations which are unusually sensitive or resistant to radiation carcinogenesis. (author)

  7. Radiation-induced segregation in model alloys

    Science.gov (United States)

    Ezawa, T.; Wakai, E.; Oshima, R.

    2000-12-01

    The dependence of the size factor of solutes on radiation-induced segregation (RIS) was studied. Ni-Si, Ni-Co, Ni-Cu, Ni-Mn, Ni-Pd, and Ni-Nb binary solid solution alloys were irradiated with electrons in a high voltage electron microscope at the same irradiation conditions. A focused beam and a grain boundary were utilized to generate a flow of point defects to cause RIS. From the concentration profile obtained by an energy dispersive X-ray analysis, the amount of RIS was calculated. The amount of RIS decreased as the size of the solute increased up to about 10%. However, as the size increased further, the amount of RIS increased. This result shows that RIS is not simply determined by the size effect rule.

  8. Radiation-induced grafting onto wool

    International Nuclear Information System (INIS)

    Muller-Schulte, D.

    1979-10-01

    Radiation-induced grafting tests were done on single wool fibres. Different vinyl monomers were used for this purpose and they were grafted in twenty different solvents which were selected for their swelling effiency and solvent parameters. The tests were done once with and once without the addition of water. The presence of water causes the polymer uptake to increase considerably. Formic acid/methanol and methanol were found to be the most suitable solvent systems, as they have the highest hydrogen-bond interaction effiency. The moisture uptake of wool depends on the hydrophily and hydrophoby of the grafted polymers. The single-fibre tests serve as a basis for analogous grafting tests on wool fabrics. The permanent- press was improved by graftng with hydrophoric polymers and polymers with a high glass-transition temperature [af

  9. Radiation-induced electron migration along DNA

    International Nuclear Information System (INIS)

    Fuciarelli, A.F.; Sisk, E.C.; Miller, J.H.; Zimbrick, J.D.

    1994-04-01

    Radiation-induced electron migration along DNA is a mechanism by which randomly produced stochastic energy deposition events can lead to nonrandom types of damage along DNA manifested distal to the sites of the initial energy deposition. Electron migration along DNA is significantly influenced by the DNA base sequence and DNA conformation. Migration along 7 base pairs in oligonucleotides containing guanine bases was observed for oligonucleotides irradiated in solution which compares to average migration distances of 6 to 10 bases for Escherichia coli DNA irradiated in solution and 5.5 base pairs for Escherichia coli DNA irradiated in cells. Evidence also suggests that electron migration can occur preferentially in the 5' to 3' direction along DNA. Our continued efforts will provide information regarding the contribution of electron transfer along DNA to formation of locally multiply damaged sites created in DNA by exposure to ionizing radiation

  10. Radiation-induced premature menopause: a misconception

    International Nuclear Information System (INIS)

    Madsen, Berit L.; Giudice, Linda; Donaldson, Sarah S.

    1995-01-01

    Purpose: To disprove the common view that women who have undergone irradiation to fields excluding the pelvis are at risk for radiation-induced premature menopause, we reviewed menstrual function and fertility among women treated with subtotal lymphoid irradiation for Hodgkin's Disease. Methods and Materials: Treatment and follow-up records of all women less than age 50 at the time of diagnosis of Stage I or II supradiaphragmatic Hodgkin's Disease, treated with subtotal lymphoid irradiation alone and enrolled in radiotherapy trials from 1967 to 1985, were reviewed. In addition, patients were surveyed regarding their menstrual status and fertility history. Results: Thirty-six women, aged 10 to 40 years, with normal menstrual function at the time of Hodgkin's diagnosis, were identified. Mean follow-up was 14 years, with a range of 1.25-22.75 years. The average radiation dose to mantle and paraaortic fields was 40-44 Gy; the calculated scatter radiation dose to the pelvis at the ovaries was 3.2 Gy. There were 38 pregnancies in 18 women; all offspring are normal. One of 36 women (2.7%) experienced premature menopause. The reported rate of premature menopause in women who have not undergone irradiation is 1-3%; not significantly different than the rate in our study. There is a syndrome whereby antibodies to several endocrine organs occur (including the ovary), which is associated with premature ovarian failure. This syndrome may be associated with prior radiation to the thyroid, such as that given by mantle-irradiation for Hodgkin's Disease. We report such a case. Conclusion: There is little risk of premature menopause in women treated with radiation fields that exclude the pelvis. Women with presumed radiation-induced premature menopause warrant an evaluation to exclude other causes of ovarian failure, such as autoimmune disorders

  11. Scopolamine methylbromide mitigates radiation induced damage and lethality in zebrafish

    International Nuclear Information System (INIS)

    Shrivastava, Nitisha; Joshi, Jayadev; Ghosh, Subhajit; Dimri, Manali; Prem Kumar, Indracanti; Sehgal, Neeta

    2014-01-01

    In view of the strategic importance radiation countermeasures hold, the present study was undertaken to screen a collection of small molecule clinical compounds for possible radioprotective action using zebrafish as a model system. Preliminary screening in developing zebrafish embryos (24 hour post fertilization, (hpf)) using damage manifestations and survival as end point identified scopolamine methylbromide (SMB), a muscarinic receptor antagonist, as a potential radiomitigator. It was found to be optimal (60% survival advantage after 6 th post irradiation day) at a dose of 80 μM when added 3 h post 20 Gy exposure. Mechanistic studies suggested that SMB though exhibited no significant antioxidant potential, but was found to limit radiation induced apoptosis (pre G1 population) quantified through flow cytometry (6 and 5% reduction after 8 or 24 h after treatments) and annexin V staining (8% reduction). Further, quantitative analysis, using caspase 3 assay, revealed a 2.46 fold increase in apoptosis in irradiated group and treatment of irradiated zebrafish embryos with SMB led to a significant reduction in global apoptosis (1.7 fold; p<0.05) when compared to irradiated group. In silico studies based on structural and functional similarity with known radioprotectors suggested similarities with atropine, a known anti-inflammatory agent with muscarinic antagonism and radioprotective potential. In view of this SMB was tested, in silico, for possible anti-inflammatory action. Molecular docking studies revealed that SMB interacts (B.E-8.0 Kcal/mole) with cycloxygenase-2 (COX-2). In lieu of this, anti-inflammation activity was assessed through ChIN (chemically induced inflammation) method in 3 dpf (days post fertilization) embryos and SMB was found to significantly inhibit inflammation at all doses studied from 20-200 μM at 3 and 6 hpi (hours post inflammation). Overall the result suggests that scopolamine methylbromide mitigates radiation induced injury and lethality in

  12. p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis.

    Science.gov (United States)

    Zhang, Xu Rui; Liu, Yong Ai; Sun, Fang; Li, He; Lei, Su Wen; Wang, Ju Fang

    2016-07-01

    To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest. Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence- associated-β-galactosidase (SA-β-gal) staining combined with Ki67 staining, a cell proliferation marker. Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells. Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  13. Measurements of reactivity of reactor G1

    International Nuclear Information System (INIS)

    Bernot, J.; Koechlin, J.C.; Portes, L.; Teste du Bailler, A.

    1957-01-01

    The various methods used during the physical study of the reactor G1 to determine the variations of the effective multiplication factor consecutive to a given change in the geometry of the multiplying medium, are presented and discussed. The comparison of the results obtained by these various methods has allowed their validity to be tested and precise conditions of use to be given. In the first part are presented the principles used and their ranges of validity. In the second part the experimental results are given, together with some indications on their comparison with theoretical estimations. (author) [fr

  14. Radiation induced diffusion as a method to protect surface

    International Nuclear Information System (INIS)

    Baumvol, I.J.R.

    1980-01-01

    Radiation induced diffusion forms a coating adeherent and without interface on the surface of metalic substrates. This coating improves the behaviour of metal to corrosion and abrasion. The effect of radiation induced diffusion of tin and calcium on pure iron surface is described and analyzed in this work. (author) [pt

  15. Radiation induced changes in the airway - anaesthetic implications ...

    African Journals Online (AJOL)

    Radiation induced changes in the airway - anaesthetic implications: case report. Mallika Balakrishnan, Renju Kuriakose, Rachel Cherian Koshy. Abstract. Radiation induces a variety of changes in the airway that can potentially lead to difficult intubation. Osteoradionecrosis (ORN) of the mandible, a severe consequence of ...

  16. Radiation-induced xerostomia in a patient with nasopharyngeal ...

    African Journals Online (AJOL)

    OBJECTIVE: This study reports a case of radiation-induced xerstomia in a patient with nasopharyngeal cancer, to emphasize the need for prompt oral care to prevent untoward effects of xerostomia and to improve patients' quality of life. CASE REPORT: A 60 year old man diagnosed of radiation-induced xerostomia, after 6 ...

  17. Protection of Normal Cells Against Toxic Effects of Chemotherapy by Reversible G1 Arrest

    National Research Council Canada - National Science Library

    Keyomarsi, Khandan

    2002-01-01

    Treatment of cancer with chemotherapy and radiation therapy has severe side effects that damage healthy proliferating cells such as hematopoietic precursors, hair follicle, cells and the epithelial...

  18. Radiation-induced cancer in Japan

    International Nuclear Information System (INIS)

    Yamashita, Shoji; Sekizuka, Eiichi; Yamashita, Hisao; Takami, Akira; Kubo, Atsushi

    2001-01-01

    Results of two questionnaire surveys on radiation-induced malignant tumors conducted in 1977 and 1984 in Japan are briefly summarized. A total of 234 universities and general hospitals (139 in 1977, and 95 in 1984) responded and provided data from 1945 to 1977 and from 1978 to 1984. The number of patients with benign disease who developed secondary malignant tumors following radiation therapy was 150 in the first survey (1977) and 86 in the second survey (1984). The underlying benign diseases of these patients included tuberculous lymphadenitis, skin disease, hemangioma, and thyroid disease, and the most frequent radiation-induced malignant tumors in these patients were malignant tumors of the pharynx (80), cancer of the larynx (26), malignant tumors of the thyroid gland (22), cancer of the esophagus (219), and skin cancer (21). In patients with head and neck diseases the highest correlation between underlying benign disease and radiation-induced malignant tumors was between cervical tuberculous lymphadenitis and tumors of the pharynx (67 patients), followed by cancer of the larynx (19), and malignant tumors of the thyroid gland (11). There were also correlations between thyroid disease and malignant tumors of the thyroid gland (8 patients), hemangioma and skin cancer (7), and skin disease and skin cancer (8). The ratio of the observed values to predicted values (O/E ratio) in these patients was highest for cancer of the pharynx (118), followed by cancer of the parotid gland (42), skin cancer (31), cancer of the esophagus (22), malignant tumors of the thyroid gland (21), and cancer of the larynx (16). The number of patients with malignant tumors who developed secondary malignant tumors following radiation therapy was 140 in 1977 and 108 in 1984, and the underlying malignant tumors in these patients included tumors of the uterus (106), breast (32), and head and neck (80). The most frequent secondary malignant tumors were soft tissue tumors, followed by leukemia, and

  19. Gamma Radiation-Induced Template Polymerization Technique

    International Nuclear Information System (INIS)

    Siyam, T.

    2005-01-01

    Gamma radiation induced copolymerization of acrylamide sodiumacrylate (AM-AANa) in the presence and absence of the polymer additive was studied at low monomer concentration(1.4M/l). The results showed that the exponents of the dose rate for the polymerization rate was found to be 1.3 and 1.4 in the absence and in the presence of the polymer additive respectively. The molecular weight of the formed polymer increased by addition of the polymer to the system. In the presence of the polymer the comonomers polymerize on the added polymer. In the absence of the added polymer the comonomers polymerize according to the copolymerization process at the initial stage of the copolymerization. While at high conversion the residual comonomers polymerize on the formed macromolecular chains of the produced polymer. These studies showed that the copolymerization in the presence of added polymer is completely template copolymerization while in the absence of the polymer the copolymerization process is only template process with a high conversion

  20. Radiation-Induced Mutation and Crop Improvement

    International Nuclear Information System (INIS)

    Lee, Y. I.; Song, H. S.; Kim, J. S.; Shin, I. C.; Lee, S. J.

    1987-01-01

    Radiation induced mutations have not only been used directly as a cultivar in crop plants, but also indirectly as a genetic resource that is essential to conventional plant breeding. M 1 plant survivals of three rice cultivars treated with gamma rays of 200-350 Gy varied from 30-40%. The survival of the Sawing variety was less sensitive to radiation, but its fertility was more sensitive in comparison with Seomjin and Sponging. Various dwarf or semi-dwarf mutants and early=matured mutants have been selected in the M 2 and M 3 generations of the three rice cultivars irradiated with gamma rays. Other desirable mutants also have been selected, such as high-yielding, high-tailoring and disease-resistant. The genetic nature of most of the selected short calm and earliness mutants was fixed in M 2 or M 3 generations. Dwarfism of IEAR 308 and Monogynol 10 were found to have a single recessive gene. However, the dwarf of IEAR 308 has a recessive deficit phenomenon. The highest genetic heritability of plant height was observed in the cross combination of Monogynol 10 Χ Pawling

  1. Radiation induced mutations for breeding of sorghum

    Energy Technology Data Exchange (ETDEWEB)

    Bretaudeau, A [Rural Polytechnic Inst., Katibougou, Koulikoro (Mali)

    1997-07-01

    Several sorghum cultivars of Mali were irradiated with different doses of gamma rays and compared with the Caudatum types. Radio-sensitivity studies suggested that the local types were less sensitive to radiation than the introduced types. Whereas the local varieties survived dose of 300 Gy, in Caudatum types, seed germination and growth were significantly reduced at 200 Gy. Several agronomically important mutants were obtained among the progeny of the local types. Some of the mutants were shorter and had improved panicle characteristics. Radiation-induced variation was observed in several characters such as plant height, resistance to lodging, plant architecture, drought tolerance, panicle length and compactness, seed size and color, seed quality (viterous or floury) and protein content, glume color and structure, flowering data (early and late maturity), and tillering capacity. One mutant was drought tolerant. Promising mutants were selected and are presently under evaluation in the National List Trials to confirm their potential and future release. Selected variants have been also crossed with local types to obtain promising material. (author). 8 refs, 2 tabs.

  2. Operative treatment of radiation-induced fistulae

    International Nuclear Information System (INIS)

    Balslev, I.; Harling, H.

    1987-01-01

    Out of 136 patients with radiation-induced intestinal complications, 45 had fistulae. Twenty-eight patients had rectovaginal fistulae while the remainder had a total of 13 different types of fistulae. Thirty-seven patients were treated operatively and eight were treated conservatively. Thirty-three patients were submitted to operation for rectal fistulae. Of these, 28 were treated by defunctioning colostomy, three were treated by Hartmann's method and resection and primary anastomosis was carried out in two patients. In the course of the period of observation, 35% of the patients developed new radiation damage. The frequency in the basic material without fistulae was 21% (0.05< p<0.10). Following establishment of defunctioning colostomy on account of rectovaginal fistulae in 25 patients, eight patients developed new fistulae, Significantly more patients with fistulae died of recurrence as compared with patients with other lesions (p<0.01). Defunctioning colostomy in the treatment of rectal fistula is a reasonable form of treatment in elderly patients and in case of recurrence. Younger patients should be assessed in a special department in view of the possibility of a sphincter-preserving procedure following resection of the rectum and restorative anastomosis. (author)

  3. Operative treatment of radiation-induced fistulae

    Energy Technology Data Exchange (ETDEWEB)

    Balslev, I.; Harling, H.

    1987-01-01

    Out of 136 patients with radiation-induced intestinal complications, 45 had fistulae. Twenty-eight patients had rectovaginal fistulae while the remainder had a total of 13 different types of fistulae. Thirty-seven patients were treated operatively and eight were treated conservatively. Thirty-three patients were submitted to operation for rectal fistulae. Of these, 28 were treated by defunctioning colostomy, three were treated by Hartmann's method and resection and primary anastomosis was carried out in two patients. In the course of the period of observation, 35% of the patients developed new radiation damage. The frequency in the basic material without fistulae was 21% (0.05

  4. Radiation-induced cancer in laryngectomized patients

    International Nuclear Information System (INIS)

    Miyahara, Hiroshi; Tsuruta, Yoshihiro; Sato, Takeo; Yoshino, Kunitoshi; Umatani, Katunori

    1991-01-01

    Three patients developed hypopharyngo-cervical esophageal carcinoma, 6.5, 13, and 12 years after total laryngectomy. The first patient had received irradiation (60 Gy) for hypopharyngeal carcinoma. The recurrent tumor was removed with total pharyngolaryngoesophagectomy and reconstruction was performed with a local skin flap. After 6 years and 6 months, she developed progressive dysphagia. A new cervical esophageal skin cancer was diagnosed by pharyngoesophagography and treated. The second patient had had total laryngectomy for laryngeal carcinoma and received irradiation (100 Gy) post-operatively. After 13 years, he developed progressive dysphagia. Pharyngoesophagography revealed cervical esophageal carcinoma. The third patient had received irradiation for laryngeal carcinoma (60 Gy) and underwent total laryngectomy because of recurrence. After 12 years she developed dysphagia, and was treated for hypopharyngeal carcinoma. These three patients seemed to have radiation-induced carcinoma. Patients treated with total laryngectomy and irradiation who later complain of progressive dysphagia should be examined carefully to differentiate between postoperative stenosis due to scarring and a new carcinoma. (author)

  5. Radiation induced mutations for breeding of sorghum

    International Nuclear Information System (INIS)

    Bretaudeau, A.

    1997-01-01

    Several sorghum cultivars of Mali were irradiated with different doses of gamma rays and compared with the Caudatum types. Radio-sensitivity studies suggested that the local types were less sensitive to radiation than the introduced types. Whereas the local varieties survived dose of 300 Gy, in Caudatum types, seed germination and growth were significantly reduced at 200 Gy. Several agronomically important mutants were obtained among the progeny of the local types. Some of the mutants were shorter and had improved panicle characteristics. Radiation-induced variation was observed in several characters such as plant height, resistance to lodging, plant architecture, drought tolerance, panicle length and compactness, seed size and color, seed quality (viterous or floury) and protein content, glume color and structure, flowering data (early and late maturity), and tillering capacity. One mutant was drought tolerant. Promising mutants were selected and are presently under evaluation in the National List Trials to confirm their potential and future release. Selected variants have been also crossed with local types to obtain promising material. (author). 8 refs, 2 tabs

  6. Radiation-induced cranial nerve palsy

    International Nuclear Information System (INIS)

    Berger, P.S.; Bataini, J.P.

    1977-01-01

    Twenty-five patients with 35 cranial nerve palsies were seen at the Fondation Curie during follow-up after radical radiotherapy for head and neck tumors. The twelfth nerve was involved in 19 cases, the tenth in nine, and the eleventh in five; the fifth and second nerves were involved once each and in the same patient. The twelfth nerve was involved alone in 16 patients and the tenth nerve alone in three, with multiple nerves involved in the remaining six patients. The palsy was noted from 12 to 145 months after diagnosis of the tumor. The latency period could be correlated with dose so that the least square fit equation representing NSD vs delay is NSD = 2598--Delay (in months) x 4.6, with a correlation coefficient of -0.58. The distinction between tumor recurrence and radiation-induced nerve palsy is critical. It can often be inferred from the latency period but must be confirmed by observation over a period of time

  7. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  8. Radiation-induced valvular heart disease.

    Science.gov (United States)

    Gujral, Dorothy M; Lloyd, Guy; Bhattacharyya, Sanjeev

    2016-02-15

    Radiation to the mediastinum is a key component of treatment with curative intent for a range of cancers including Hodgkin's lymphoma and breast cancer. Exposure to radiation is associated with a risk of radiation-induced heart valve damage characterised by valve fibrosis and calcification. There is a latent interval of 10-20 years between radiation exposure and development of clinically significant heart valve disease. Risk is related to radiation dose received, interval from exposure and use of concomitant chemotherapy. Long-term outlook and the risk of valve surgery are related to the effects of radiation on mediastinal structures including pulmonary fibrosis and pericardial constriction. Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed. Surveillance strategies for this cohort of cancer survivors at risk of developing significant heart valve complications are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Pathology of radiation induced lung damage

    International Nuclear Information System (INIS)

    Kawabata, Yoshinori; Murata, Yoshihiko; Ogata, Hideo; Katagiri, Shiro; Sugita, Hironobu; Iwai, Kazuo; Sakurai, Isamu.

    1985-01-01

    We examined pathological findings of radiation induced lung damage. Twenty-three cases are chosen from our hospital autopsy cases for 9 years, which fulfil strict criteria of radiation lung damage. Lung damage could be classified into 3 groups : 1) interstitial pneumonia type (9 cases), 2) intermediate pneumonia type (8 cases), and 3) alveolar pneumonia type (6 cases), according to the degree of intra-luminal exudation. These classification is well correlated with clinical findings. Pathological alveolar pneumonia type corresponds to symptomatic, radiologic ground glass pneumonic shadow. And pathologic interstitial type corresponds to clinical asymptomatic, radiologic reticulo-nodular shadow. From the clinico-pathological view point these classification is reasonable one. Radiation affects many lung structures and showed characteristic feature of repair. Elastofibrosis of the alveolar wall is observed in every cases, obstructive bronchiolitis are observed in 5 cases, and obstructive bronchiolitis in 9 cases. They are remarkable additional findings. Thickening of the interlobular septum, broncho-vascular connective tissue, and pleural layer are observed in every cases together with vascular lesions. (author)

  10. Radiation-induced ηe-modes

    International Nuclear Information System (INIS)

    Shukla, P.K.; Yu, M.Y.

    1990-01-01

    Impurity radiation in a plasma can cause not only static instabilities, but also dynamic instabilities related to the drift and acoustic waves. Radiative instabilities are of much interest because they are associated with relatively high frequency and short wavelength fluctuations, which have been suspected to be responsible for anomalous electron energy transport in tokamak edge plasmas. In this paper, we consider radiation-induced η e instabilities, taking into account electrostatic effects as well as density and temperature inhomogeneities. Also included are the effects of finite gyroradius and dissipation. It is found that the latter can cause strong linear coupling between the modes of interest. The resulting instabilities can have larger growth rates than the static radiative instability. Analytical expressions for the growth rates and instability regimes are given for the limiting cases of practical interest. In particular, it is shown that the η e -mode can couple to both radiation and dissipation to cause resistive instabilities. The parameter regimes of the original radiative as well as the dissipative modes are thereby broadened and shifted because of the interaction. (author) 3 refs

  11. Circulatory Arrest, Brain Arrest and Death Determination

    Directory of Open Access Journals (Sweden)

    Sam David Shemie

    2018-03-01

    Full Text Available Technological advances, particularly in the capacity to support, replace or transplant failing organs, continue to challenge and refine our understanding of human death. Given the ability to reanimate organs before and after death, both inside and outside of the body, through reinstitution of oxygenated circulation, concepts related to death of organs (e.g. cardiac death are no longer valid. This paper advances the rationale for a single conceptual determination of death related to permanent brain arrest, resulting from primary brain injury or secondary to circulatory arrest. The clinical characteristics of brain arrest are the permanent loss of capacity for consciousness and loss of all brainstem functions. In the setting of circulatory arrest, death occurs after the arrest of circulation to the brain rather than death of the heart. Correspondingly, any intervention that resumes oxygenated circulation to the brain after circulatory arrest would invalidate the determination of death.

  12. Radiation-Induced Alopecia after Endovascular Embolization under Fluoroscopy

    Directory of Open Access Journals (Sweden)

    Vipawee Ounsakul

    2016-01-01

    Full Text Available Radiation-induced alopecia after fluoroscopically guided procedures is becoming more common due to an increasing use of endovascular procedures. It is characterized by geometric shapes of nonscarring alopecia related to the area of radiation. We report a case of a 46-year-old man presenting with asymptomatic, sharply demarcated rectangular, nonscarring alopecic patch on the occipital scalp following cerebral angiography with fistula embolization under fluoroscopy. His presentations were compatible with radiation-induced alopecia. Herein, we also report a novel scalp dermoscopic finding of blue-grey dots in a target pattern around yellow dots and follicles, which we detected in the lesion of radiation-induced alopecia.

  13. Delayed Radiation-Induced Vasculitic Leukoencephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Rauch, Philipp J. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Faculty of Medicine, University of Heidelberg, Heidelberg (Germany); Park, Henry S. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Knisely, Jonathan P.S. [Department of Radiation Medicine, North Shore University Hospital, Manhasset, New York (United States); Chiang, Veronica L. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Vortmeyer, Alexander O., E-mail: alexander.vortmeyer@yale.edu [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States)

    2012-05-01

    Purpose: Recently, single-fraction, high-dosed focused radiation therapy such as that administered by Gamma Knife radiosurgery has been used increasingly for the treatment of metastatic brain cancer. Radiation therapy to the brain can cause delayed leukoencephalopathy, which carries its own significant morbidity and mortality. While radiosurgery-induced leukoencephalopathy is known to be clinically different from that following fractionated radiation, pathological differences are not well characterized. In this study, we aimed to integrate novel radiographic and histopathologic observations to gain a conceptual understanding of radiosurgery-induced leukoencephalopathy. Methods and Materials: We examined resected tissues of 10 patients treated at Yale New Haven Hospital between January 1, 2009, and June 30, 2010, for brain metastases that had been previously treated with Gamma Knife radiosurgery, who subsequently required surgical management of a symptomatic regrowing lesion. None of the patients showed pathological evidence of tumor recurrence. Clinical and magnetic resonance imaging data for each of the 10 patients were then studied retrospectively. Results: We provide evidence to show that radiosurgery-induced leukoencephalopathy may present as an advancing process that extends beyond the original high-dose radiation field. Neuropathologic examination of the resected tissue revealed traditionally known leukoencephalopathic changes including demyelination, coagulation necrosis, and vascular sclerosis. Unexpectedly, small and medium-sized vessels revealed transmural T-cell infiltration indicative of active vasculitis. Conclusions: We propose that the presence of a vasculitic component in association with radiation-induced leukoencephalopathy may facilitate the progressive nature of the condition. It may also explain the resemblance of delayed leukoencephalopathy with recurring tumor on virtually all imaging modalities used for posttreatment follow-up.

  14. A case of radiation induced cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ozawa, Kazuyoshi; Tsuchikawa, Kohzo; Sato, Akira; Kato, Joji (Nippon Dental Univ., Niigata (Japan). School of Dentistry at Niigata)

    1994-06-01

    A case of carcinoma on the right buccal mucosa is presented. The case was suspected to have been induced by irradiation therapy for a carcinoma on the left buccal mucosa. An external radiotherapy, 6-MeV Linac, had been done for the carcinoma on the left buccal mucosa in a 55-year-old female, with single lateral direction from the left to the right in 1977. In 1985, a papillary lesion on the right buccal mucosa was detected, and histological examination revealed a papilloma without atypism. In 1991, as an ulcer on the right upper buccal fold as well as three papillary lesions in the central portion of the right buccal mucosa were found, the patient was referred to our clinic. Microscopical findings were consistent with the early invasive carcinomas. A surgical excision of these whole lesions and skin graft were completed. The criteria of this case for the suspicion of radiation-induced carcinoma were as follows. There was a long latent period of 14 years. The previous dose of irradiation, 60 Gy, was sufficient. The right buccal mucosa was involved in the radiation field. A severe scar on the left cheek resulted from the previous irradiation. Anatomically, there is no evidence of the secondary carcinoma on the right buccal mucosa with the primary carcinoma on the left buccal mucosa. No evidence for recurrence of the tumors on both sides of buccal mucosa has been detected so far. Further observations will be necessary to detect other tumors in the irradiated field later on. (author).

  15. Radiation-induced carotid artery atherosclerosis

    International Nuclear Information System (INIS)

    Gujral, Dorothy M.; Chahal, Navtej; Senior, Roxy; Harrington, Kevin J.; Nutting, Christopher M.

    2014-01-01

    Purpose: Carotid arteries frequently receive significant doses of radiation as collateral structures in the treatment of malignant diseases. Vascular injury following treatment may result in carotid artery stenosis (CAS) and increased risk of stroke and transient ischaemic attack (TIA). This systematic review examines the effect of radiotherapy (RT) on the carotid arteries, looking at the incidence of stroke in patients receiving neck radiotherapy. In addition, we consider possible surrogate endpoints such as CAS and carotid intima-medial thickness (CIMT) and summarise the evidence for radiation-induced carotid atherosclerosis. Materials and methods: From 853 references, 34 articles met the criteria for inclusion in this systematic review. These papers described 9 studies investigating the incidence of stroke/TIA in irradiated patients, 11 looking at CAS, and 14 examining CIMT. Results: The majority of studies utilised suboptimally-matched controls for each endpoint. The relative risk of stroke in irradiated patients ranged from 1.12 in patients with breast cancer to 5.6 in patients treated for head and neck cancer. The prevalence of CAS was increased by 16–55%, with the more modest increase seen in a study using matched controls. CIMT was increased in irradiated carotid arteries by 18–40%. Only two matched-control studies demonstrated a significant increase in CIMT of 36% and 22% (p = 0.003 and <0.001, respectively). Early prospective data demonstrated a significant increase in CIMT in irradiated arteries at 1 and 2 years after RT (p < 0.001 and <0.01, respectively). Conclusions: The incidence of stroke was significantly increased in patients receiving RT to the neck. There was a consistent difference in CAS and CIMT between irradiated and unirradiated carotid arteries. Future studies should optimise control groups

  16. Hazard of the radiation induced thyroid cancer

    International Nuclear Information System (INIS)

    Buglova, Ye.Ye.

    2001-01-01

    The level of thyroid cancer in Belarus before Chernobyl accident was low and made in different age and sex groups 0,03-2,5 (male) and 0,1-3,9 (female) per 100000 correspondingly. Different risk factors, which can influence the thyroid cancer development, are being taken into account. They are the factors of environment (strong external irradiation, long-time irradiation for medical purposes or in result of disaster), endo gen factors (hormonal, reproductive, genetic predisposition), some medicinal preparations and other. The protective effect of vegetable and fish consumption was found out. Among the factors of thyroid cancer development one of the most important is radiation. There is a point of view, which assumes that one of the reasons of thyroid cancer cases increase among the population of developed countries is increase of radiation induced thyroid cancer. The results of first research testify the influence of radiation factor on thyroid cancer development. During the period 1920 -1960 in the USA X-ray therapy was applied for the treatment of different good-quality diseases. Thyroid got in the zone of irradiation during the complex treatment with using of radiation. The results of the research of 1970 revealed that 70% of children with thyroid cancer were exposed to radiation in children's age. The subsequent researches of by-effects from the side of a thyroid at beam therapy of various diseases alongside with the results of the estimation of consequences of inhabitants of Hiroshima and Nagasaki irradiation owing to nuclear bombardment have shown the influence of irradiation of a thyroid on cancer development. High quantity of radio-epidemiological researches was directed to the studying of the consequences of thyroid external irradiation at young age. In all carried out researches the quantity of observed thyroid cancer cases among irradiated people has exceeded number of expected. The influence of thyroid internal irradiation by I-131 at young age was

  17. Indomethacin attenuation of radiation-induced hyperthermia does not modify radiation-induced motor hypoactivity

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, J.L.; Kandasamy, S.B.; Harris, A.H.; Davis, H.D.; Landauer, M.R. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)

    1996-09-01

    Exposure of rats to 5-10 Gy of ionizing radiation produces hyperthermia and reduces motor activity. Previous studies suggested that radiation-induced hyperthermia results from a relatively direct action on the brain and is mediated by prostaglandins. To test the hypothesis that hypoactivity may be, in part, a thermoregulatory response to this elevation in body temperature, adult male rats were given indomethacin (0.0, 0.5, 1.0, and 3.0 mg/kg, intraperitoneally), a blocker of prostaglandin synthesis, and were either irradiated (LINAC 18.6 MeV (nominal) high-energy electrons, 10 Gy at 10 Gy/min, 2.8 {mu}sec pulses at 2 Hz) or sham-irradiated. The locomotor activity of all rats was then measured for 30 min in a photocell monitor for distance traveled and number of vertical movements. Rectal temperatures of irradiated rats administered vehicle only were elevated by 0.9{+-}0.2degC at the beginning and the end of the activity session. Although indomethacin, at the two higher doses tested, attenuated the hyperthermia in irradiated rats by 52-75%, it did not attenuate radiation-induced reductions in motor activity. These results indicate that motor hypoactivity after exposure to 10 Gy of high-energy electrons is not due to elevated body temperature or to the increased synthesis of prostaglandins. (author)

  18. Indomethacin attenuation of radiation-induced hyperthermia does not modify radiation-induced motor hypoactivity

    International Nuclear Information System (INIS)

    Ferguson, J.L.; Kandasamy, S.B.; Harris, A.H.; Davis, H.D.; Landauer, M.R.

    1996-01-01

    Exposure of rats to 5-10 Gy of ionizing radiation produces hyperthermia and reduces motor activity. Previous studies suggested that radiation-induced hyperthermia results from a relatively direct action on the brain and is mediated by prostaglandins. To test the hypothesis that hypoactivity may be, in part, a thermoregulatory response to this elevation in body temperature, adult male rats were given indomethacin (0.0, 0.5, 1.0, and 3.0 mg/kg, intraperitoneally), a blocker of prostaglandin synthesis, and were either irradiated (LINAC 18.6 MeV (nominal) high-energy electrons, 10 Gy at 10 Gy/min, 2.8 μsec pulses at 2 Hz) or sham-irradiated. The locomotor activity of all rats was then measured for 30 min in a photocell monitor for distance traveled and number of vertical movements. Rectal temperatures of irradiated rats administered vehicle only were elevated by 0.9±0.2degC at the beginning and the end of the activity session. Although indomethacin, at the two higher doses tested, attenuated the hyperthermia in irradiated rats by 52-75%, it did not attenuate radiation-induced reductions in motor activity. These results indicate that motor hypoactivity after exposure to 10 Gy of high-energy electrons is not due to elevated body temperature or to the increased synthesis of prostaglandins. (author)

  19. Novel features of radiation-induced segregation and radiation-induced precipitation in austenitic stainless steels

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Z., E-mail: zjiao@umich.edu [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109 (United States); Was, G.S. [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109 (United States)

    2011-02-15

    Three stainless steel alloys, high-purity 304 (HP304), high-purity 304 with high Si (HP304 + Si) and commercial purity 304 (CP304), were irradiated with 2 MeV protons to a dose of 5 dpa at 360 deg. C and subsequently examined using atom probe tomography (APT) and scanning transmission electron microscopy-energy dispersive X-ray spectrometry (STEM-EDS). Several novel features of radiation-induced segregation and radiation-induced precipitation were observed. There is a significant variation in the composition of enriched and depleted elements in the grain boundary plane and along the dislocation loop core. Boron segregation to the grain boundary prior to irradiation is not affected by the irradiation. Phosphorus segregation is enhanced by irradiation. Carbon depletes at the grain boundary and may be affected by co-segregation with Cr. APT and STEM-EDS measurements are in excellent agreement for almost all the elements studied. The segregation behavior of elements at dislocations mirrors that at the grain boundary, but at a lower magnitude, except for Si. Ni/Si-rich clusters formed in irradiated HP304 + Si and CP304 are probably the precursors of {gamma}' or other Si- and Ni-rich phases. Copper depletion was observed at both the grain boundary and the dislocation loops. Regions adjacent to the depleted zones were sites for Cu cluster formation, which were also spatially correlated with Ni/Si-rich clusters.

  20. Characterization of a Novel Radiation-Induced Sarcoma Cell Line

    Czech Academy of Sciences Publication Activity Database

    Lang, J.; Zhu, W.Z.; Nokes, B.; Sheth, S.G.; Novák, Petr; Fuchs, L.; Watts, G.; Futscher, B. W.; Mineyev, N.; Ring, A.

    2015-01-01

    Roč. 111, č. 6 (2015), s. 669-682 ISSN 0022-4790 Institutional support: RVO:60077344 Keywords : Sarcoma * radiation-induced * breast * cancer Subject RIV: FD - Oncology ; Hematology Impact factor: 3.151, year: 2015

  1. Radiation induced changes in the airway - anaesthetic implications

    African Journals Online (AJOL)

    Adele

    CASE REPORT. Southern African Journal of Anaesthesia & Analgesia - May 2004. 19. Radiation ... Summary: Radiation induces a variety of changes in the airway that can potentially lead to difficult intubation. ... Mask holding and ventilation is.

  2. Image Guidance and Assessment of Radiation Induced Gene Therapy

    National Research Council Canada - National Science Library

    Pelizzari, Charles

    2004-01-01

    Image guidance and assessment techniques are being developed for combined radiation/gene therapy, which utilizes a radiation-inducible gene promoter to cause expression of tumor necrosis factor alpha...

  3. A case of radiation-induced osteosarcoma of the maxilla

    International Nuclear Information System (INIS)

    Tanaka, Rie; Asato, Ryo; Tanaka, Shinzo; Hiratsuka, Yasuyuki; Ito, Juichi

    2003-01-01

    Radiation-induced osteosarcoma in the head and neck region is very rare. A 68-year-old female, who had been treated with radiation for malignant lymphoma of the right maxillary sinus, presented with right cheek swelling. Imaging examinations demonstrated a huge mass occupying the right nasal cavity and paranasal sinuses. Total maxillectomy was performed, and the tumor was histologically diagnosed as osteosarcoma. Diagnosis and treatment for radiation-induced osteosarcoma in the head and neck is discussed. (author)

  4. A case of radiation-induced osteosarcoma of the maxilla

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Rie [Shimada City Hospital, Shizuoka (Japan); Asato, Ryo; Tanaka, Shinzo; Hiratsuka, Yasuyuki; Ito, Juichi [Kyoto Univ. (Japan). Faculty of Medicine

    2003-02-01

    Radiation-induced osteosarcoma in the head and neck region is very rare. A 68-year-old female, who had been treated with radiation for malignant lymphoma of the right maxillary sinus, presented with right cheek swelling. Imaging examinations demonstrated a huge mass occupying the right nasal cavity and paranasal sinuses. Total maxillectomy was performed, and the tumor was histologically diagnosed as osteosarcoma. Diagnosis and treatment for radiation-induced osteosarcoma in the head and neck is discussed. (author)

  5. Radiation-induced neuropathies: collateral damage of improved cancer prognosis

    International Nuclear Information System (INIS)

    Pradat, Pierre-Francois; Maisonobe, Thierry; Psimaras, Dimitri; Lenglet, Timothee; Porcher, Raphael; Lefaix, J.L.; Delenian, S.

    2012-01-01

    Because of the improvement of cancer prognosis, long-term damages of treatments become a medical and public health problem. Among the iatrogenic complications, neurological impairment is crucial to consider since motor disability and pain have a considerable impact on quality of life of long cancer survivors. However, radiation-induced neuropathies have not been the focus of great attention. The objective of this paper is to provide an updated review about the radiation-induced lesions of the peripheral nerve system. Radiation-induced neuropathies are characterized by their heterogeneity in both symptoms and disease course. Signs and symptoms depend on the affected structures of the peripheral nerve system (nerve roots, nerve plexus or nerve trunks). Early-onset complications are often transient and late complications are usually progressive and associated with a poor prognosis. The most frequent and well known is delayed radiation-induced brachial plexopathy, which may follow breast cancer irradiation. Radiation-induced lumbosacral radiculoplexopathy is characterized by pure or predominant lower motor neuron signs. They can be misdiagnosed, confused with amyotrophic lateral sclerosis (ALS) or with leptomeningeal metastases since nodular MRI enhancement of the nerve roots of the cauda equina and increased cerebrospinal fluid protein content can be observed. In the absence of specific markers of the link with radiotherapy, the diagnosis of post-radiation neuropathy may be difficult. Recently, a posteriori conformal radiotherapy with 3D dosimetric reconstitution has been developed to link a precise anatomical site to unexpected excess irradiation. The importance of early diagnosis of radiation-induced neuropathies is underscored by the emergence of new disease-modifying treatments. Although the pathophysiology is not fully understood, it is already possible to target radiation-induced fibrosis but also associated factors such as ischemia, oxidative stress and

  6. Reactor G1: high power experiments

    International Nuclear Information System (INIS)

    Laage, F. de; Teste du Baillet, A.; Veyssiere, A.; Wanner, G.

    1957-01-01

    The experiments carried out in the starting-up programme of the reactor G1 comprised a series of tests at high power, which allowed the following points to be studied: 1- Effect of poisoning by Xenon (absolute value, evolution). 2- Temperature coefficients of the uranium and graphite for a temperature distribution corresponding to heating by fission. 3- Effect of the pressure (due to the coiling system) on the reactivity. 4- Calibration of the security rods as a function of their position in the pile (1). 5- Temperature distribution of the graphite, the sheathing, the uranium and the air leaving the canals, in a pile running normally at high power. 6- Neutron flux distribution in a pile running normally at high power. 7- Determination of the power by nuclear and thermodynamic methods. These experiments have been carried out under two very different pile conditions. From the 1. to the 15. of August 1956, a series of power increases, followed by periods of stabilisation, were induced in a pile containing uranium only, in 457 canals, amounting to about 34 tons of fuel. A knowledge of the efficiency of the control rods in such a pile has made it possible to measure with good accuracy the principal effects at high temperatures, that is, to deal with points 1, 2, 3, 5. Flux charts giving information on the variations of the material Laplacian and extrapolation lengths in the reflector have been drawn up. Finally the thermodynamic power has been measured under good conditions, in spite of some installation difficulties. On September 16, the pile had its final charge of 100 tons. All the canals were loaded, 1,234 with uranium and 53 (i.e. exactly 4 per cent of the total number) with thorium uniformly distributed in a square lattice of 100 cm side. Since technical difficulties prevented the calibration of the control rods, the measurements were limited to the determination of the thermodynamic power and the temperature distributions (points 5 and 7). This report will

  7. Radiation-Induced Second Cancer Risk Estimates From Radionuclide Therapy

    Science.gov (United States)

    Bednarz, Bryan; Besemer, Abigail

    2017-09-01

    The use of radionuclide therapy in the clinical setting is expected to increase significantly over the next decade. There is an important need to understand the radiation-induced second cancer risk associated with these procedures. In this study the radiation-induced cancer risk in five radionuclide therapy patients was investigated. These patients underwent serial SPECT imaging scans following injection as part of a clinical trial testing the efficacy of a 131Iodine-labeled radiopharmaceutical. Using these datasets the committed absorbed doses to multiple sensitive structures were calculated using RAPID, which is a novel Monte Carlo-based 3D dosimetry platform developed for personalized dosimetry. The excess relative risk (ERR) for radiation-induced cancer in these structures was then derived from these dose estimates following the recommendations set forth in the BEIR VII report. The radiation-induced leukemia ERR was highest among all sites considered reaching a maximum value of approximately 4.5. The radiation-induced cancer risk in the kidneys, liver and spleen ranged between 0.3 and 1.3. The lifetime attributable risks (LARs) were also calculated, which ranged from 30 to 1700 cancers per 100,000 persons and were highest for leukemia and the liver for both males and females followed by radiation-induced spleen and kidney cancer. The risks associated with radionuclide therapy are similar to the risk associated with external beam radiation therapy.

  8. Characterization of radiation-induced Apoptosis in rodent cell lines

    International Nuclear Information System (INIS)

    Guo, Min; Chen, Changhu; Ling, C.C.

    1997-01-01

    For REC:myc(ch1), Rat1 and Rat1:myc b cells, we determined the events in the development of radiation-induced apoptosis to be in the following order: cell division followed by chromatin condensation, membrane blebbing, loss of adhesion and the uptake of vital dye. Experimental data which were obtained using 4 He ions of well defined energies and which compared the dependence of apoptosis and clonogenic survival on 4 He range strongly suggested that in our cells both apoptosis and loss of clonogenic survival resulted from radiation damage to the cell nucleus. Corroboratory evidence was that BrdU incorporation sensitized these cells to radiation-induced apoptosis. Comparing the dose response for apoptosis and the clonogenic survival curves for Rat1 and Rat1:myc b cells, we concluded that radiation-induced cell inactivation as assayed by clonogenic survival, and that a modified linear-quadratic model, proposed previously, modeled such a contribution effectively. In the same context, the selective increase in radiation-induced apoptosis. Comparing the dose response for apoptosis and the clonogenic survival curves for Rat1 and Rat1:myc b cells, we concluded that radiation-induced apoptosis contributed to the overall radiation-induced cell inactivation as assayed by clonogenic survival, and that a modified linear-quadratic model, proposed previously, modeled such a contribution effectively. In the same context, the selective increase in radiation-induced apoptosis during late S and G 2 phases reduced the relative radioresistance observed for clonogenic survival during late S and G 2 phases. 30 refs., 8 figs

  9. Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks

    International Nuclear Information System (INIS)

    Turney, Benjamin W.; Kerr, Martin; Chitnis, Meenali M.; Lodhia, Kunal; Wang, Yong; Riedemann, Johann; Rochester, Mark; Protheroe, Andrew S.; Brewster, Simon F.; Macaulay, Valentine M.

    2012-01-01

    Background and purpose: IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNA-damaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair. Methods: We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for γH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry. Results: We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30–40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses. Conclusions: These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments.

  10. Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks.

    Science.gov (United States)

    Turney, Benjamin W; Kerr, Martin; Chitnis, Meenali M; Lodhia, Kunal; Wang, Yong; Riedemann, Johann; Rochester, Mark; Protheroe, Andrew S; Brewster, Simon F; Macaulay, Valentine M

    2012-06-01

    IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNA-damaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair. We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for γH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry. We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30-40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses. These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  12. Radiation-induced camptocormia and dropped head syndrome. Review and case report of radiation-induced movement disorders

    International Nuclear Information System (INIS)

    Seidel, Clemens; Kuhnt, Thomas; Kortmann, Rolf-Dieter; Hering, Kathrin

    2015-01-01

    In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a ''chin to chest position.'' Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords ''camptocormia,'' ''dropped head syndrome,'' ''radiation-induced myopathy,'' ''radiation-induced neuropathy,'' and ''radiation-induced movement disorder'' was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and - including our case - three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable. (orig.) [de

  13. Selection of G1 Phase Yeast Cells for Synchronous Meiosis and Sporulation.

    Science.gov (United States)

    Stuart, David T

    2017-01-01

    Centrifugal elutriation is a procedure that allows the fractionation of cell populations based upon their size and shape. This allows cells in distinct cell cycle stages can be captured from an asynchronous population. The technique is particularly helpful when performing an experiment to monitor the progression of cells through the cell cycle or meiosis. Yeast sporulation like gametogenesis in other eukaryotes initiates from the G1 phase of the cell cycle. Conveniently, S. cerevisiae arrest in G1 phase when starved for nutrients and so withdrawal of nitrogen and glucose allows cells to abandon vegetative growth in G1 phase before initiating the sporulation program. This simple starvation protocol yields a partial synchronization that has been used extensively in studies of progression through meiosis and sporulation. By using centrifugal elutriation it is possible to isolate a homogeneous population of G1 phase cells and induce them to sporulate synchronously, which is beneficial for investigating progression through meiosis and sporulation. An additionally benefit of this protocol is that cell populations can be isolated based upon size and both large and small cell populations can be tested for progression through meiosis and sporulation. Here we present a protocol for purification of G1 phase diploid cells for examining synchronous progression through meiosis and sporulation.

  14. Measurements of reactivity of reactor G1; Mesures de reactivite sur reacteur G1

    Energy Technology Data Exchange (ETDEWEB)

    Bernot, J; Koechlin, J C; Portes, L; Teste du Bailler, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1957-07-01

    The various methods used during the physical study of the reactor G1 to determine the variations of the effective multiplication factor consecutive to a given change in the geometry of the multiplying medium, are presented and discussed. The comparison of the results obtained by these various methods has allowed their validity to be tested and precise conditions of use to be given. In the first part are presented the principles used and their ranges of validity. In the second part the experimental results are given, together with some indications on their comparison with theoretical estimations. (author) [French] Nous exposons et discutons diverses methodes utilisees, lors de l'etude physique du reacteur G1, pour determiner les variations du facteur de multiplication effectif consecutives a un changement donne dans la geometrie du milieu multiplicateur. La comparaison des resultats obtenus par diverses methodes nous a permis de tester leur validite et d'en preciser les conditions d'emploi. Dans une premiere partie, nous exposons les principes utilises et leurs domaines de validite. Dans une seconde partie nous donnons les resultats experimentaux obtenus avec quelques indications sur leur comparaison avec les estimations theoriques. (auteur)

  15. Control of radiation-induced diarrhea with cholestyramine

    International Nuclear Information System (INIS)

    Heusinkveld, R.S.; Manning, M.R.; Aristizabal, S.A.

    1978-01-01

    Cholestyramine is a non-absorbable ion-exchange resin which specifically binds bile salts. We have treated seven patients with acute or chronic radiation-induced diarrhea that was refractory to the usual methods of control with cholestyramine. In each case, the diarrhea was controlled with cholestyramine. This observation supports previous experimental work with animals which indicated that bile salts contribute to the genesis of radiation-induced diarrhea. Cholestyramine is well-tolerated, but should not be administered with certain oral medications. The results of this small series are preliminary, but point the way toward a more extensive clinical trial to define the usefulness of cholestyramine in the treatment of refractory acute or chronic radiation-induced diarrhea

  16. Effect of dose on radiation-induced conductivity in polymers

    International Nuclear Information System (INIS)

    Tyutnev, A.P.; Saenko, V.S.; Pozhidaev, E.D.; Ikhsanov, R.Sh.

    2007-01-01

    Numerical simulation of radiation-induced conductivity in polymers upon long-term irradiation on the basis of the generalized Rose-Fowler-Vaisberg model, which allows for both dipolar carrier transport and generation of radiation traps during irradiation, was performed. The unusual properties of radiation-induced conductivity, such as the appearance of a maximum on current transients, the absence of a steady state, and a substantial difference between these curves for the first and subsequent irradiation, are rationalized in terms of the formation of free radicals, the major feature of radiolysis in the chemical aspect. This interpretation does not require the involvement of degradation or crosslinking processes, unlike other interpretations that appear in the literature. With the use of low-density polyethylene as an example, it was shown that radiation-induced conductivity both upon pulse and continuous irradiation can satisfactorily be described with the unified set of parameters of the generalized Rose-Fowler-Vaisberg model [ru

  17. Membrane phospholipids and radiation-induced death of mammalian cells

    International Nuclear Information System (INIS)

    Wolters, H.

    1987-01-01

    Radiation-induced cell killing is generally believed to be a consequence of residual DNA damage or damage that is mis-repaired. However, besides this DNA damage, damage to other molecules or structures of the cell may be involved in the killing. Especially membranes have been suggested as a determinant in cellular radiosensitivity. In this thesis experiments are described, dealing with the possible involvement of membranes in radiation-induced killing of mammalian cells. A general treatise of membrane structure is followed by information concerning deleterious effects of radiation on membranes. Consequences of damage to structure and function of membranes are reviewed. Thereafter evidence relating to the possible involvement of membranes in radiation-induced cell killing is presented. (Auth.)

  18. Radiation-induced loss of unsaturation in 1,2-polybutadiene

    International Nuclear Information System (INIS)

    Golub, M.A.; Cormia, R.D.

    1982-01-01

    The radiation induced loss of unsaturation and methyl production in 1,2-polybutadiene (VB) was studied using IR spectroscopy. It was found that G(-1,2), which depends on the initial vinyl content, decreased from approximately 550 for VB with 98.5% 1,2 initially, to approximately 270 for VB with 85% 1,2 initially. G(-trans-1,4) ranged from approximately 21 for VB with 14% trans-1,4 to nearly zero for VB with less than 1% trans-1,4 initially. Methyl production was found to equal one methyl group formed for every 4-5 vinyl units consumed in the radiation-cyclized VB, in contrast to one methyl formed for every two vinyls reacted during cationic cyclization to give monocyclic structures. The IR spectra of gamma-irradiated VB were very similar to the spectra of UV-irradiated or thermally-treated VB at the same residual vinyl contents. It is suggested that the radiation-induced cyclization of VB occurs by a nonionic, nonradical 'energy chain' mechanism, which apparently holds for the cyclization of VB, whether induced by gamma-rays, UV radiation, or heat

  19. Mechanistic issues for modeling radiation-induced segregation

    International Nuclear Information System (INIS)

    Simonen, E.P.; Bruemmer, S.M.

    1993-03-01

    Model calculations of radiation-induced chromium depletion and radiation-induced nickel enrichment at grain boundaries are compared to measured depletions and enrichments. The model is calibrated to fit chromium depletion in commercial purity 304 stainless steel irradiated in boiling water reactor (BWR) environments. Predicted chromium depletion profiles and the dose dependence of chromium concentration at grain boundaries are in accord with measured trends. Evaluation of chromium and nickel profiles in three neutron, and two ion, irradiation environments reveal significant inconsistencies between measurements and predictions

  20. Radiation induced ionic polymerisation and grafting of vinyl monomers

    International Nuclear Information System (INIS)

    Stannett, V.T.

    1981-01-01

    Some special aspects of the radiation induced ionic polymerisation and grafting of vinyl monomers will be described. In particular the effects of solvents on the cationic polymerisation of the vinyl ethers will be discussed in detail. The unequivocal free ion nature of the polymerisation makes such information of considerable general interest. Estimates of the propagation rate constants with free cation polymerisation in solvents of different dielectric constants and solvation powers will be presented. Finally, some observations on the radiation induced graft polymerisation of ethyl vinyl ether to poly(vinyl chloride) and to polypropylene will be presented. (author)

  1. Radiation-induced osteosarcoma of the calvaria; Case report

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Yasuo; Shigemori, Minoru; Miyagi, Jun; Ochiai, Satoshi; Lee, Souichi; Watanabe, Toshinori; Abe, Hitoshi; Morimatsu, Minoru [Kurume Univ., Fukuoka (Japan). School of Medicine

    1992-01-01

    The authors report a case of radiation-induced calvarial osteosarcoma. A 58-year-old female received subtotal removal of the pituitary adenoma and 5000 rads postoperative irradiation. Seven years later, an osteoblastic osteosarcoma occurred in the frontotemporal region. She received total tumor removal and chemotherapy. However, computed tomography subsequently revealed multiple small lesions at the margin of the bone flap. A chest x-ray film demonstrated lung metastasis. Local recurrence and lung metastasis require careful attention in radiation-induced osteosarcoma patients. (author).

  2. Radiation induced mitotic delay and stimulation of growth

    International Nuclear Information System (INIS)

    Feldmann, A.

    1974-01-01

    The mechanisms responsible for the radiation induced mitotic delay and stimulation of growth are discussed in connection with the results of studies in Lemna minor and Lepidium sativum. The action of temperature seems to be of major importance. As many authors suggest that various chemical agents and slight intoxications also affect mitosis in a way similar to that induced by ionizing radiation, the radiation induced stimulation has lost its specific character and approaches might be found for further investigations of this phenomenon. (MG) [de

  3. Radiation-induced void swelling in metals and alloys

    International Nuclear Information System (INIS)

    Zelinskij, V.F.; Neklyudov, I.M.; Ozhigov, L.S.; Reznichenko, Eh.A.; Rozhkov, V.V.; Chernyaeva, T.T.

    1979-01-01

    Main regularities in the development of radiation-induced void swelling are considered. Special attention is paid to consideration of a possibility to obtain information on material behaviour under conditions of reactor irradiation proceeding from the data of simulation experiments and to methods of rate control, for the processes which occur in material during irradiation and further annealing by the way of rationalized alloying, of thermomechanical treatment and programmed change of irradiation conditions under operation. Problems of initiation and growth of voids in irradiated materials are discussed as well as the ways to decrease the rate of radiation-induced void swelling

  4. Reduced hepatic tumor incidence in cyclin G1-deficient mice

    DEFF Research Database (Denmark)

    Jensen, Michael Rugaard; Factor, Valentina M; Fantozzi, Anna

    2003-01-01

    found that the p53 levels in the cyclin G1-deficient mice are 2-fold higher that in wild-type mice. Moreover, we showed that treatment of mice with the alkylating agent 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin), followed by partial hepatectomy, decreased G1-S transition in cyclin G1-null...

  5. 26 CFR 301.6503(g)-1 - Suspension pending correction.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Suspension pending correction. 301.6503(g)-1 Section 301.6503(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Collection § 301.6503(g)-1 Suspension pending correction. The running of the periods of limitations provided...

  6. G2 phase arrest of cell cycle induced by ionizing radiation

    International Nuclear Information System (INIS)

    Liu Guangwei; Gong Shouliang

    2002-01-01

    The exposure of mammalian cells to X rays results in the prolongation of the cell cycle, including the delay or the arrest in G 1 , S and G 2 phase. The major function of G 1 arrest may be to eliminate the cells containing DNA damage and only occurs in the cells with wild type p53 function whereas G 2 arrest following ionizing radiation has been shown to be important in protecting the cells from death and occurs in all cells regardless of p53 status. So the study on G 2 phase arrest of the cell cycle induced by ionizing radiation has currently become a focus at radiobiological fields

  7. Poor outcome in radiation-induced constrictive pericarditis

    International Nuclear Information System (INIS)

    Karram, T.; Rinkevitch, D.; Markiewicz, W.

    1993-01-01

    The purpose was to compare the outcome of patients with radiation-induced constrictive pericarditis versus patients with constiction due to another etiology. Twenty patients with constrictive pericarditis were seen during 1975-1986 at a single medical center. Six had radiation-induced constrictive pericarditis (Group A). The etiology was idiopathic in ten subjects and secondary to carcinomatous encasement, chronic renal failure, purulent infection and tuberculosis in one patient each (Group B, N = 14). Meang age was 53.4 ± 15.5 years. Extensive pericardiectomy was performed in 3/6 Group A and 13/14 Group B patients. All Group A patients died, 4 weeks - 11 years post-diagnosis (median = 10 months). Two Group A patients died suddenly, one died post-operatively of respiratory failure, another of pneumonia and two of recurrent carcinoma. Thirteen Group B patients are alive (median follow-up = 72 months). The only death in this group was due to metastatic cancer. The poor outcome with radiation-induced constriction is probably multi-factorial. Poor surgical outcome is to be expected in patients with evidence of recurrent tumor, high-dose irradiation, pulmonary fibrosis or associated radiation-induced myocardinal, valvular or coronary damage

  8. Homoeologous chromatin exchange in a radiation-induced gene transfer

    International Nuclear Information System (INIS)

    Dvorak, J.; Knott, D.R.

    1977-01-01

    Some of the ionizing-radiation-induced translocations between alien and wheat chromosomes show no deleterious effects and are transmitted normally through the pollen. Translocations of this type will be called ''compensating''. In one such compensating translocation, designated T4, it was found that chromatin in the long arm of wheat chromosome 7D was replaced with homoeologous chromatin of the Agropyron chromosome

  9. Radiation-induced vascular lesions of the skin: an overview

    NARCIS (Netherlands)

    Flucke, U.E.; Requena, L.; Mentzel, T.

    2013-01-01

    Radiation-induced cutaneous vascular neoplasms occur infrequently and comprise benign, so-called atypical vascular lesions (AVL) and angiosarcomas (AS), often being high-grade malignant tumors. Both arise most frequently within previously irradiated skin in breast-conserving-treated mammary cancer

  10. Radiation-induced nitration of organic compounds in aqueous solutions

    International Nuclear Information System (INIS)

    Ershov, B.G.; Gordeev, A.V.; Bykov, G.L.

    2009-01-01

    Radiation-induced nitration of organic compounds in aqueous solutions was studied. It was found that γ-irradiation of solutions containing acetic and nitric acid and/or their salts gives nitromethane. Dependences of the product yield on the absorbed dose and the contents of components were established. The mechanism of radiation nitration involving radicals is discussed. (author)

  11. Seven cases of radiation-induced cutaneous squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sugita, Kazunari; Yamamoto, Osamu; Suenaga, Yoshinori

    2000-01-01

    We report 7 cases of radiation-induced skin cancer. The diagnosis was based on the history of radiotherapy for benign skin diseases (5 cases) and of occupational exposures to medical doctors (2 cases). All cases were squamous cell carcinomas which arose from chronic radiodermatitis. The estimated latent period of these tumors ranged from 6 to 64 years, with an average of 29.9 years. After surgical treatments of the lesions, no local recurrences were observed in all cases. Benign skin diseases had sometimes been treated with low-energy radiation before the 1960s. Considering the estimated latent period, the peak time point of developing risk of radiation-induced skin cancer by such treatment has been already passed, however, the danger of it should not be ignored in future. In association with multiplicity of radiation usage, occupational exposure of radiation may develop the risk of occurrence of skin cancer in future. Therefore, we should recognize that radiation-induced skin cancer is not in the past. In the cases of chronic skin diseases showing warty keratotic growth, erosion and ulcer, we should include chronic radio-dermatitis in the differential diagnosis. It is necessary to recall all patients about the history of radiotherapy or radiation exposure. Rapid histopathological examination is mandatory because of the suspicion of radiation-induced skin cancer. (author)

  12. Radiation-induced hondrosarcoma - a clinical case from our practice

    International Nuclear Information System (INIS)

    Marinova, L.; Georgiev, R.; Mihaylova, I.

    2013-01-01

    We present a clinical case of radiation - induced occipital extracerebral chondrosarcoma in 36 years old young man. The patient had undergone two brain operations 8 years ago due to oligodendroglioma in the left temporo - parietal area. These surgical interventions were partial and subtotal tumor extirpation, followed by local radiotherapy to the brain to a total dose of 56Gy. The necessity of immunohistochemistry (IHH) analysis for pathologic differential diagnosis in high grade brain and peripheral tumors was discussed. In this particular case a precise differential diagnosis between peripheral chondrosarcoma and Ewing sarcoma/pPNET is needed. important risk factors for the development of radiation-induced brain tumors and chondrosarcoma, extremely rarely diagnosed, was discussed. A very accurate precising of the treatment radiation dose is needed in young patients with malignant brain tumors, not only in the surrounding healthy brain tissues, but also in other tissues, such as skin, subcutaneous layer and bone. The exceeding of the radiation dose in the bone above 45-50 Gy, increases the risk of radiation - induced sarcoma with latent period over 8 years. Key words: Hondrosarcoma. Radiotherapy. Radiation-induced Sarcoma. Complex Treatment. Immunohistochemistry

  13. Dose rate effectiveness in radiation-induced teratogenesis in mice

    International Nuclear Information System (INIS)

    Kato, F.; Ootsuyama, A.; Norimura, T.

    2000-01-01

    To investigate the role of p53 gene in tissue repair of teratogenic injury, we compared incidence of radiation-induced malformations in homozygous p53(-/-) mice, heterozygous p53(+/-) mice and wild-type p53(+/+) mice. After X-irradiation with 2 Gy at high dose rate on 9.5 days of gestation, p53(-/-) mice showed higher incidences of anomalies and higher resistance to prenatal deaths than p53(+/+) mice. This reciprocal relationship of radiosensitivity to anomalies and deaths supports the notion that embryos or fetuses have a p53-dependent 'guardian' that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of apoptotic cells was greatly increased in p53(+/+) fetuses but not in p53(-/-) fetuses. The same dose of γ-ray exposure at low dose rate on 9.5-10.5 day of gestation produced significant reduction of radiation-induced malformation in p53(+/+) and p53(+/-) mice, remained teratogenic for p53(-/-) mice. These results suggest that complete elimination of teratogenic damage from irradiated tissues requires the concerted cooperation of two mechanisms; proficient DNA repair and the p53-dependent apoptotic tissue repair. When concerted DNA repair and apoptosis functions efficiently, there is a threshold dose-rate for radiation-induced malformations. (author)

  14. Kinetics of radiation-induced segregation in ternary alloys

    International Nuclear Information System (INIS)

    Lam, N.O.; Kumar, A.; Wiedersich, H.

    1982-01-01

    Model calculations of radiation-induced segregation in ternary alloys have been performed, using a simple theory. The theoretical model describes the coupling between the fluxes of radiation-induced defects and alloying elements in an alloy A-B-C by partitioning the defect fluxes into those occurring via A-, B-, and C-atoms, and the atom fluxes into those taking place via vacancies and interstitials. The defect and atom fluxes can be expressed in terms of concentrations and concentration gradients of all the species present. With reasonable simplifications, the radiation-induced segregation problem can be cast into a system of four coupled partial-differential equations, which can be solved numerically for appropriate initial and boundary conditions. Model calculations have been performed for ternary solid solutions intended to be representative of Fe-Cr-Ni and Ni-Al-Si alloys under various irradiation conditions. The dependence of segregation on both the alloy properties and the irradiation variables, e.g., temperature and displacement rate, was calculated. The sample calculations are in good qualitative agreement with the general trends of radiation-induced segregation observed experimentally

  15. Seven cases of radiation-induced cutaneous squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Kazunari; Yamamoto, Osamu; Suenaga, Yoshinori [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

    2000-09-01

    We report 7 cases of radiation-induced skin cancer. The diagnosis was based on the history of radiotherapy for benign skin diseases (5 cases) and of occupational exposures to medical doctors (2 cases). All cases were squamous cell carcinomas which arose from chronic radiodermatitis. The estimated latent period of these tumors ranged from 6 to 64 years, with an average of 29.9 years. After surgical treatments of the lesions, no local recurrences were observed in all cases. Benign skin diseases had sometimes been treated with low-energy radiation before the 1960s. Considering the estimated latent period, the peak time point of developing risk of radiation-induced skin cancer by such treatment has been already passed, however, the danger of it should not be ignored in future. In association with multiplicity of radiation usage, occupational exposure of radiation may develop the risk of occurrence of skin cancer in future. Therefore, we should recognize that radiation-induced skin cancer is not in the past. In the cases of chronic skin diseases showing warty keratotic growth, erosion and ulcer, we should include chronic radio-dermatitis in the differential diagnosis. It is necessary to recall all patients about the history of radiotherapy or radiation exposure. Rapid histopathological examination is mandatory because of the suspicion of radiation-induced skin cancer. (author)

  16. Poor outcome in radiation-induced constrictive pericarditis

    Energy Technology Data Exchange (ETDEWEB)

    Karram, T.; Rinkevitch, D.; Markiewicz, W. (Technion Medical School, Haifa (Israel))

    1993-01-15

    The purpose was to compare the outcome of patients with radiation-induced constrictive pericarditis versus patients with constiction due to another etiology. Twenty patients with constrictive pericarditis were seen during 1975-1986 at a single medical center. Six had radiation-induced constrictive pericarditis (Group A). The etiology was idiopathic in ten subjects and secondary to carcinomatous encasement, chronic renal failure, purulent infection and tuberculosis in one patient each (Group B, N = 14). Meang age was 53.4 [+-] 15.5 years. Extensive pericardiectomy was performed in 3/6 Group A and 13/14 Group B patients. All Group A patients died, 4 weeks - 11 years post-diagnosis (median = 10 months). Two Group A patients died suddenly, one died post-operatively of respiratory failure, another of pneumonia and two of recurrent carcinoma. Thirteen Group B patients are alive (median follow-up = 72 months). The only death in this group was due to metastatic cancer. The poor outcome with radiation-induced constriction is probably multi-factorial. Poor surgical outcome is to be expected in patients with evidence of recurrent tumor, high-dose irradiation, pulmonary fibrosis or associated radiation-induced myocardinal, valvular or coronary damage.

  17. Homoeologous chromatin exchange in a radiation-induced gene transfer

    Energy Technology Data Exchange (ETDEWEB)

    Dvorak, J; Knott, D R [Department of Crop Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    1977-03-01

    Some of the ionizing-radiation-induced translocations between alien and wheat chromosomes show no deleterious effects and are transmitted normally through the pollen. Translocations of this type will be called ''compensating''. In one such compensating translocation, designated T4, it was found that chromatin in the long arm of wheat chromosome 7D was replaced with homologous chromatin of the Agropyron chromosome.

  18. Radiation-induced augmentation of the immune response

    International Nuclear Information System (INIS)

    Anderson, R.E.; Lefkovits, I.; Troup, G.M.

    1980-01-01

    Radiation-induced augmentation of the immune response has been shown to occur both in vivo and in vitro. Evidence is presented to implicate injury to an extremely radiosensitive T cell in the expression of this phenomenon. Experiments are outlined which could be employed to support or reflect this hypothesis

  19. Preparation of polymer microspheres by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Naka, Y.; Yamamoto, Y.; Yoshida, Y.; Tagawa, S.

    1995-01-01

    Cross-liking monomer, diethylene glycol dimethacrylate gives microspheres from organic solution by radiation-induced polymerization. /One of the remarkable result is that the number of the microspheres is not changing during the polymerization. Ethyl methacrylate, maleic anhydride, styrene and acrylamide are used as comonomers. These comonomers give the microspheres in the range of 0 to 0.4 as mol fractions. (author)

  20. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  1. The effects of cysteamine on the radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Choi, Young Min; Cho, Heung Lae; Park, Chang Gyo; Lee, Hyung Sik; Hur, Won Joo

    2000-01-01

    To investigate the pathways of radiation induced apoptosis and the effect of cysteamine (β-mercaptoethylamine), as a radioprotector, on it. HL-60 cells were assigned to control, irradiated, and cysteamine (1 mM, 10 mM) pretreated groups. Irradiation was given in a single fraction of 10 Gy (6 MV x-ray) and cysteamine was administered 1 hour before irradiation. The activities of caspase-8 were measured in control and irradiated group to evaiuate its relation to the radiation induced apoptosis. To evaluate the role of cysteamine in radiation induced apoptosis, the number of viable cells, the expression and activity or caspase-3, and the expression of poly (ADP-ribose) polymerase (PARP) were measured and compared after irradiating the HL cells with cysteamine pretreatment or not. The intracellular caspase-8 activity, known to be related to the death receptor induced apoptosis, was not affected by irradiation( p>0.05). The number of viable cells began to decrease from 6 hours after irradiation (p>0.05), but the number of viable cells in 1 mM cysteamine pretreated group was not decreased after irradiation and was similar to those in the control group. In caspase-3 analyses, known as apoptosis executioner, its expression was not different but its activity was increased by irradialion(p>0.05). However, this increase of activity was suppressed by the pretreatment of 1 mM cysteamine. The cleavage of PARP, thought to be resulted from caspase-3 activation, occurred, after irradiation, which was attenuated by the pretreatment of 1 mM cysteamine. These results show that radiation induced apoptotic process is somewhat different from death receptor induced one and the pretreatment of 1 mM cysteamine has a tendency to decrease the radiation-induced apoptosis in HL-60 cells

  2. Radiation-induced cancers of the head and neck, (3)

    International Nuclear Information System (INIS)

    Umatani, Katsunori; Satoh, Takeo; Yoshino, Kunitoshi; Takagi, Tadashi; Fujii, Takashi; Hatta, Chihiro; Maetani, Chikahide; Lu, Bo

    1989-01-01

    This paper discusses twenty patients with radiation-induced cancers of the head and neck treated in the Department of Otorhinolaryngology, the Center for Adult Diseases, Osaka, from January 1979 to December 1985. The most common site of radiation-induced cancers was the hypopharynx and cervical esophagus (70%). We found synchronous double cancers in 2 out of the 20 patients (10%). One patient had hypopharyngeal cancer and thyroid cancer, and the other had oropharyngeal cancer and thyroid cancer. All of the laryngeal cancers were in the supraglottic area. Cancer of the hypopharynx and cervical esophagus occurred more frequently in females (1:3.7 males-females ratio). Half of the patients (10/20) had received irradiation for tuberculous cervical adenitis and 8 patients had been irradiated for malignant tumors. The averaged latent period in the patients who had irradiated for benign conditions was 37.4 years, and that for malignant diseases was 16.0 years. Therefore the latent period of the former was 2.3 times as long as that of the latter. The incidence of radiation-induced cancers in all the patients who had the cancer of the hypopharynx and cervical esophagus was 9% and that of the laryngeal cancer was 0.7%. The incidence of radiation-induced cancers in the hypopharynx and cervical esophagus remarkably differed from that in the larynx. However, it was suggested that the larynx was as resistant to radiation induction as the hypopharynx. Six of the 20 patients (30%) had radiation-induced thyroid tumors. Among them, the incidence of cancers was 33%. (author)

  3. Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

    International Nuclear Information System (INIS)

    Ahmed, M.

    2003-01-01

    Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

  4. Radiation-induced camptocormia and dropped head syndrome. Review and case report of radiation-induced movement disorders

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, Clemens; Kuhnt, Thomas; Kortmann, Rolf-Dieter; Hering, Kathrin [Leipzig University, Department of Radiotherapy and Radiation Oncology, Leipzig (Germany)

    2015-10-15

    In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a ''chin to chest position.'' Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords ''camptocormia,'' ''dropped head syndrome,'' ''radiation-induced myopathy,'' ''radiation-induced neuropathy,'' and ''radiation-induced movement disorder'' was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and - including our case - three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable. (orig.) [German] In den letzten Jahren haben Bewegungsstoerungen von Wirbelsaeule und paraspinaler Muskulatur in

  5. A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

    Directory of Open Access Journals (Sweden)

    Jianhong Ye

    Full Text Available To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC patients.Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs, internal carotid arteries (ICAs and basal artery (BA were estimated through Transcranial Color Doppler (TCD. The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals.Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05. IMT had positive correlation with post radiation interval (p = 0.049. Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001. Plaques were more common in patients with TLN than patients without TLN (p = 0.038. In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001. Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001.Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

  6. Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    El-Missiry, M.A.; Shehata, G.; Roushdy, H.M; Fayed, Th.A.

    1999-01-01

    Preventing the propagation of radiation induced oxidative damage has been a subject of considerable investigations. The ultimate goal of the present study is to use bone marrow cells to ameliorate or to treat the radiation sickness. Transplantation of bone marrow cell has shown promising results in the present experimental radiation treatment. In this report, suspension of bone marrow cells was injected into rats 12 h. after exposure to 4.5 Gy whole body gamma irradiation. Significant results were recorded on the successful control of the radiation induced disorders in a number of biochemical parameters including certain enzymatic and nonenzymatic antioxidants (superoxide dismutase and glutathione) and certain parameters related to kidney function including creatinine, urea as well as Atpase Activity in blood serum, urine and kidney tissue

  7. A case of radiation-induced cancer of the hypopharynx

    International Nuclear Information System (INIS)

    Miyamoto, Kouji; Shimizu, Yukio; Yura, Jirou; Itoh, Yasufumi; Ikeda, Tsuneko; Outsubo, Toshio; Saitou, Hitoshi

    2001-01-01

    We report a case of radiation-induced cancer of the hypopharynx in a 65-year-old woman. The patient had received radiation treatment for Basedow's disease for several years starting at the age of 10 years. On June 26, 1993, she was examined at our hospital because of hoarseness and dysphagia. On July 22, right lobectomy was performed for suspected thyroid cancer. During this operation, endoscopy revealed hypopharyngeal cancer. Twenty-two days after surgery, total pharyngolaryngectomy and total esophagectomy were performed and a pharyngogastrostomy and a permanent tracheostomy were created. Histologic examination revealed moderately differentiated squamous cell cancer. This case was diagnosed as radiation-induced caner according to the diagnostic criteria of Sakai. (author)

  8. Radiation Induced Color Centers in a La Doped PWO Crystal

    CERN Document Server

    Deng, Qun

    1998-01-01

    This report presents result of a study on radiation induced color center densities in a La doped lead tungstate ( PWO) crystal. The creation and annihilation constants of radiation induced color centers were determined by using transmittance data measured for a PWO sample before and during Co-60 gamma ray irradiation at a dose rate of 15 rad/hr. Following a model of color center kinetics, these constants were used to calculate color center densities under irradiations at 100 rad/hr. The result was found to be in a good agreement with experimental data, indicating that this model of color center kinetics can be used to predict behavior of PWO crystals under irradiation.

  9. Depleted uranium and radiation - induced lung cancer and leukaemia

    International Nuclear Information System (INIS)

    Mould, R.F.

    2002-01-01

    Reports of leukaemias and other cancers among servicemen who took part in the 1991 Gulf war or in the more recent operations in the Balkans are of continuing interest, as is the possibility, however slight, that depleted uranium (DU) is one of the causative factors. This commentary includes the results of a UK epidemiological study on the mortality of Gulf war veterans and , although not containing information on DU exposure, gives data on overall levels of mortality and therefore carries more weight than anecdotal reports. Also included are brief summaries on radiation-induced lung cancer in uranium workers as well as radiation-induced leukaemia in Japanese atomic bomb survivors and patients ankylosing spondylitis treated using x-rays. This commentary concludes with a critique of Iraqi cancer statistics as well as giving information on environmental contamination in Kosovo and the use of DU ammunition. (author)

  10. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    International Nuclear Information System (INIS)

    Jiang Erkang; Wu Lijun

    2009-01-01

    In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy α-particle irradiated and non-irradiated bystander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensitive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)- 4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose α-particle radiation-induced damage in irradiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE). (ion beam bioengineering)

  11. Computer modelling of radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Khvostunov, Igor K.; Nikjoo, Hooshang

    2002-01-01

    Radiation-induced genomic instability and bystander effects are now well established consequences of exposure of living cells to ionising radiation. It has been observed that cells not directly hit by radiation tracks may still exhibit radiation effects. We present a quantitative modelling of the radiation-induced bystander effect based on a diffusion model of spreading the bystander signal. The model assumes the bystander factor to be a protein of low molecular weight, given out by the hit cell, diffusing in the medium and reacting with non-hit cells. The model calculations successfully predict the results of cell survival in an irradiated conditioned medium. The model predicts the shape of dose-effect relationship for cell survival and oncogenic transformation induced by broad-beam and micro-beam irradiation by alpha-particles. (author)

  12. Radiation induced sarcomas of bone following therapeutic radiation

    International Nuclear Information System (INIS)

    Kim, J.H.; Chu, F.C.H.; Woodward, H.Q.; Huvos, A.

    1983-01-01

    Because of new therapeutic trends of multi-modality and the importance of late effects, we have updated our series of radiation induced bone sarcomas seen at Memorial Sloan-Kettering Cancer Center over the past four decades. A total of 37 cases of bone sarcoma arising from normal bone in the irradiated field was analyzed. The median for latent period from irradiation to diagnosis of bone sarcoma was 11 years with a minimum latent period of four years. The median radiation dose for the bone sarcoma was 6000 rad in 6 weeks with a minimum total radiation dose of 3000 rad in 3 weeks. We have found nine patients who developed bone sarcomas in the radiation field after successful treatment of Hodgkin's disease. Criteria for radiation induced bone sarcomas and the magnitude of the risk of bone sarcomas are briefly discussed

  13. Radiation-induced soft-tissue and bone sarcoma

    International Nuclear Information System (INIS)

    Kim, J.H.; Chu, F.C.; Woodard, H.Q.; Melamed, R.; Huvos, A.; Cantin, J.

    1978-01-01

    From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed

  14. Radiation-induced tritium labelling and product analysis

    Energy Technology Data Exchange (ETDEWEB)

    Peng, C.T. (California Univ., San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry)

    1993-05-01

    By-products formed in radiation-induced tritium labelling are identified by co-chromatography with authentic samples or by structure prediction using a quantitative structure-retention index relationship. The by-products, formed from labelling of steroids, polynuclear aromatic hydrocarbons, 7-membered heterocyclic ring structures, 1,4-benzodiazepines, 1-haloalkanes, etc. with activated tritium and adsorbed tritium, are shown to be specifically labelled and anticipated products from known chemical reactions. From analyses of the by-products, one can conclude that the hydrogen abstraction by tritium atoms and the substitution by tritium ions are the mechanisms of labelling. Classification of the tritium labelling methods, on the basis of the type of tritium reagent, clearly shows the active role played by tritium atoms and ions in radiation-induced methods. (author).

  15. Radiation induced graft copolymerization of acrylamide onto poly (3-hydroxybutyrate)

    International Nuclear Information System (INIS)

    Gonzalez Torres, Maykel; Rapado Paneque, Manuel; Paredes Zaldivar, Mayte; Altanes Valentin, Sonia; Barrera Gonzalez, Gisela

    2008-01-01

    The graft copolymer poly (3-hydroxybutyrate)-g- polyacrylamide [P (HB-g-AAm)] was synthesized by radiation induced graft copolymerization of acrylamide onto poly (3-hydroxybutyrate). The study was conducted by the simultaneous irradiation method. The structure of [P (HB-g-AAm)] was identified by Fourier Transform Infrared (FTIR) spectroscopy. Thermal behavior of the graft copolymer was also studied by Thermal Gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). From the results it was found that FTIR studies showed new signals (stretching -N-H) as strong evidence of grafting. The grafting degree was found to be 10 % and the thermodynamic parameter obtained from the DSC thermogram of plain PHB and the graft copolymer varied showing decrease in the material crystallinity and increase in the glass transition temperature. These results demonstrate that the radiation induced graft copolymerization reaction of acrylamide onto PHB was successively achieved. (Author)

  16. A case of radiation-induced cancer of the hypopharynx

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Kouji; Shimizu, Yukio; Yura, Jirou; Itoh, Yasufumi; Ikeda, Tsuneko [Matsunami General Hospital, Kasamatsu, Gifu (Japan); Outsubo, Toshio; Saitou, Hitoshi

    2001-06-01

    We report a case of radiation-induced cancer of the hypopharynx in a 65-year-old woman. The patient had received radiation treatment for Basedow's disease for several years starting at the age of 10 years. On June 26, 1993, she was examined at our hospital because of hoarseness and dysphagia. On July 22, right lobectomy was performed for suspected thyroid cancer. During this operation, endoscopy revealed hypopharyngeal cancer. Twenty-two days after surgery, total pharyngolaryngectomy and total esophagectomy were performed and a pharyngogastrostomy and a permanent tracheostomy were created. Histologic examination revealed moderately differentiated squamous cell cancer. This case was diagnosed as radiation-induced caner according to the diagnostic criteria of Sakai. (author)

  17. Radiation-induced malignant tumours: a specific cytogenetic profile?

    International Nuclear Information System (INIS)

    Chauveinc, L.; Gaboriaux, G.; Dutrillaux, A. M.; Dutrillaux, B.; Chauveinc, L.; Ricoul, M.; Sabatier, L.; Dutrillaux, B.

    1997-01-01

    To date, there is no criterion enabling to determine the spontaneous or radio-induced origin of malignant tumour occurring in a previously irradiated patient. Biological studies are rare. The cytogenetic data which could be found in the literature for eleven radio-induced tumours suggest that aneuploidies and polyclonality are frequent events. We studied, by R-Banding cytogenetic technique, five patients with short-term cultures (3 cases), short and long-term cultures (1 case) and xeno-grafting on nude pattern a high rate of balanced translocations, numerous random break points and a polyclonal evolution (10 clones). All other tumours, including the xeno-grafting sarcoma, had a monoclonal profile with complex karyotypes, hypo-diploid formulas and many deletions. These results show that the mechanism of radiation-induced tumours frequently involves chromosomes losses and deletions. The most likely explanation is that these alterations unmask radiation induced recessive mutations of tumour suppressor genes. (authors)

  18. Radiation induced DNA damage and repair in mutagenesis

    International Nuclear Information System (INIS)

    Strniste, G.F.; Chen, D.J.; Okinaka, R.T.

    1987-01-01

    The central theme in cellular radiobiological research has been the mechanisms of radiation action and the physiological response of cells to this action. Considerable effort has been directed toward the characterization of radiation-induced DNA damage and the correlation of this damage to cellular genetic change that is expressed as mutation or initiating events leading to cellular transformation and ultimately carcinogenesis. In addition, there has been a significant advancement in their understanding of the role of DNA repair in the process of mutation leading to genetic change in cells. There is extensive literature concerning studies that address radiation action in both procaryotic and eucaryotic systems. This brief report will make no attempt to summarize this voluminous data but will focus on recent results from their laboratory of experiments in which they have examined, at both the cellular and molecular levels, the process of ionizing radiation-induced mutagenesis in cultured human cells

  19. Ubiquitin-dependent system controls radiation induced apoptosis

    International Nuclear Information System (INIS)

    Delic, J.; Magdelenat, H.; Glaisner, S.; Magdelenat, H.; Maciorowski, Z.

    1997-01-01

    The selective proteolytic pathway, dependent upon 'N-end rule' protein recognition/ubiquitination and on the subsequent proteasome dependent processing of ubiquitin conjugates, operates in apoptosis induced by γ-irradiation. The proteasome inhibitor peptide aldehyde, MG132, efficiently induced apoptosis and was also able (at doses lower than those required for apoptosis induction) to potentiate apoptosis induced by DNA damage. Its specificity is suggested by the induction of the ubiquitin (UbB and UbC) and E1 (ubiquitin activating enzyme) genes and by an altered ubiquitination pattern. More selectively, a di-peptide competitor of the 'N-end rule' of ubiquitin dependent protein processing inhibited radiation induced apoptosis. This inhibition is also followed by an altered ubiquitination pattern and by activation of Poly (ADP-ribose) polymerase (PARP). These data strongly suggest that early apoptosis radiation induced events are controlled by ubiquitin-dependent proteolytic processing. (author)

  20. Radiation-induced gene amplification in rodent and human cells

    International Nuclear Information System (INIS)

    Luecke-Huhle, C.; Gloss, B.; Herrlich, P.

    1990-01-01

    Ionizing and UV radiations induce amplification of SV40 DNA sequences integrated in the genome of Chinese hamster cells and increase amplification of the dihydrofolate reductase (DHFR) gene during methotrexate selection in human skin fibroblasts of a patient with ataxia telangiectasia. Various types of external (60-Co-γ-rays, 241-Am-α-particles, UV) or internal radiation (caused by the decay of 125 I incorporated into DNA in form of I-UdR) were applied. By cell fusion experiments it could be shown that SV40 gene amplification is mediated by one or several diffusible trans-acting factors induced or activated in a dose dependent manner by all types of radiation. One of these factors binds to a 10 bp sequence within the minimal origin of replication of SV40. In vivo competition with an excess of a synthetic oligonucleotide comprising this sequence blocks radiation-induced amplification. (author) 25 refs.; 8 figs

  1. 26 CFR 1.514(g)-1 - Business lease indebtedness.

    Science.gov (United States)

    2010-04-01

    ....514(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(g)-1... to cases such as the following: Example 1. A university pledges some of its investment securities...

  2. Prevention of radiation-induced salivary gland dysfunction utilizing a CDK inhibitor in a mouse model.

    Directory of Open Access Journals (Sweden)

    Katie L Martin

    Full Text Available Treatment of head and neck cancer with radiation often results in damage to surrounding normal tissues such as salivary glands. Permanent loss of function in the salivary glands often leads patients to discontinue treatment due to incapacitating side effects. It has previously been shown that IGF-1 suppresses radiation-induced apoptosis and enhances G2/M arrest leading to preservation of salivary gland function. In an effort to recapitulate the effects of IGF-1, as well as increase the likelihood of translating these findings to the clinic, the small molecule therapeutic Roscovitine, is being tested. Roscovitine is a cyclin-dependent kinase inhibitor that acts to transiently inhibit cell cycle progression and allow for DNA repair in damaged tissues.Treatment with Roscovitine prior to irradiation induced a significant increase in the percentage of cells in the G(2/M phase, as demonstrated by flow cytometry. In contrast, mice treated with radiation exhibit no differences in the percentage of cells in G(2/M when compared to unirradiated controls. Similar to previous studies utilizing IGF-1, pretreatment with Roscovitine leads to a significant up-regulation of p21 expression and a significant decrease in the number of PCNA positive cells. Radiation treatment leads to a significant increase in activated caspase-3 positive salivary acinar cells, which is suppressed by pretreatment with Roscovitine. Administration of Roscovitine prior to targeted head and neck irradiation preserves normal tissue function in mouse parotid salivary glands, both acutely and chronically, as measured by salivary output.These studies suggest that induction of transient G(2/M cell cycle arrest by Roscovitine allows for suppression of apoptosis, thus preserving normal salivary function following targeted head and neck irradiation. This could have an important clinical impact by preventing the negative side effects of radiation therapy in surrounding normal tissues.

  3. Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

    2006-01-01

    Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

  4. Study of radiation induced structural changes in nitrile rubber

    International Nuclear Information System (INIS)

    Cardona, F.; Hill, D.J.T.; Pomery, P.J.; Whittaker, A.K.

    1996-01-01

    Full text: Copolymers of butadiene (BD) and acrylonitrile (AN) (NBR rubber), have become important commercial material. NBR rubbers are part of a larger classification of products often referred to as special-purpose rubbers. Oil resistance is the most important property of nitrile rubbers, and refer to the ability of the vulcanised product to retain its original physical properties such as modulus, tensile strength, abrasion resistance and dimensions, while in contact with oils and fuels. Despite these reported advantages very few studies have been conducted on the radiation yields and structural changes in nitrile rubbers during exposure to high energy radiation. In this study we are investigating the stability against gamma and UV radiation, to different doses in vacuum, of butadiene, acrylonitrile and NBR copolymers with different composition ratio BD/AN. The mechanism of radiation induced structural changes is being investigated using experimental techniques such as ESR, NMR (Solid-state), FT-IR, RAMAN and UV spectroscopy. Also is being investigated the effect of irradiation on the mechanical properties of stressed and unstressed samples by TGA, DSC, DMA, Instron and Creep Test measurements. So far the main effect have been a marked radiation-induced loss of unsaturation in the butadiene units, cis to trans isomerization and formation of crosslink structures (intermolecular and intramolecular). One of the main challenges in the studies of NBR polymers is to observe directly the crosslinks produces by the radiation induced chemical reactions. IR spectroscopy is unsuitable because of the low molar absorbity of the peaks related to intermolecular crosslinking and the overlapping of the peaks (1630-1670 cm-1) related to intramolecular crosslinking (cyclization), with conjugated and nonconjugated (-C=C-; -C=N-) double bonds. A. K. Whittaker has shown that crosslink structures in PBD can be detected and measured directly using solid-state 13 C NMR. This technique

  5. Heavy-ion radiation induced bystander effect in mice

    Science.gov (United States)

    Liang, Shujian; Sun, Yeqing; Zhang, Meng; Wang, Wei; Cui, Changna

    2012-07-01

    Radiation-induced bystander effect is defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, Low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic, metabolomics and proteomics play significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male mice head were exposed to 2000mGy dose of 12C heavy-ion radiation and the distant organ liver was detected on 1h, 6h, 12h and 24h after radiation, respectively. MSAP was used to monitor the level of polymorphic DNA methylation changes. The results show that heavy-ion irradiate mouse head can induce liver DNA methylation changes significantly. The percent of DNA methylation changes are time-dependent and highest at 6h after radiation. We also prove that the hypo-methylation changes on 1h and 6h after irradiation. But the expression level of DNA methyltransferase DNMT3a is not changed. UPLC/Synapt HDMS G2 was employed to detect the proteomics of bystander liver 1h after irradiation. 64 proteins are found significantly different between treatment and control group. GO process show that six of 64 which were unique in irradiation group are associated with apoptosis and DNA damage response. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo.

  6. [The occupational radiation-induced cataract in five industrial radiographers].

    Science.gov (United States)

    Benzarti Mezni, A; Loukil, I; Hriz, N; Kallel, K; Mlaiki, N; Ben Jemaâ, A

    2012-04-01

    The industrial uses of ionizing radiation in Tunisia are expanding, especially in industry and most particularly in the nondestructive testing of welds. Thus workers operating in the non-destructive testing of welds may develop a radiation-induced cataract varying in time to onset depending on the dose. To describe the characteristics of the radiation-induced cataract in patients exposed to ionizing radiation, determine the risk factors of radiation-induced cataracts. This was an anamnestic, clinical, and environmental study of five cases of radiation-induced cataract in workers employed in non-destructive testing of welds. This series of five cases had a mean age of 30.2 years and 5.53 years of work experience, ranging from 14 months to 15 years. All the patients were male and industrial radiographers specialized in nondestructive testing of welds. The average duration of exposure to ionizing radiation was 5.53 years. None of the patients had worn protective gear such as eye goggles. The ophthalmic check-up for the five special industrial radiographers showed punctuate opacities in three cases, punctiform opacities in one eye in one case, and phacosclerosis with bilateral lens multiple crystalline stromal opacities in a case of micro-lens opacities in both eyes with opalescence of both eyes in one case. These cataracts had been declared as occupational diseases. The value of a specialized ophthalmologic surveillance among these workers and the early diagnosis of lens opacities must be emphasized. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  7. Radiation-induced transient absorption in single mode optical fibers

    International Nuclear Information System (INIS)

    Looney, L.D.; Lyons, P.B.

    1988-01-01

    This paper reviews the measurements conducted by the Los Alamos National Laboratory in support of these NATO efforts wherein radiation-induced transient absorption was measured over time ranges from a few ns to several μs for two single mode fibers. Experimental conditions were varied to provide data for future development of standarized test conditions for single mode fibers. 8 refs., 11 figs

  8. Radiation-induced morphea of the breast: a case report

    Directory of Open Access Journals (Sweden)

    Cheah Nellie LC

    2008-04-01

    Full Text Available Abstract Radiation-induced morphea (RIM of the breast is a rare complication of radiotherapy. It is disfiguring, painful and defeats the purpose of achieving a good cosmesis in breast-conservation surgery. This report describes a severe case of RIM in a breast cancer patient together with photographic illustrations of the serial changes over time and histopathology slides. A review of the literature is provided.

  9. Radiation-induced trioxane postpolymerization in the liquid phase

    International Nuclear Information System (INIS)

    Kapustina, I.B.; Starchenko, T.V.

    1979-01-01

    Radiation-induced trioxane postpolymerization in the presence of maleic anhydride and different solvents in the liquid phase has been studied. It has been found that addition of small quantities of different solvents inhibits the trioxane polymerization process both in the presence of maleic anhydride and in the absence of it. Trioxane postpolymerization in a solvent-nonsolvent mixture gives fibrous polyoxymethylene with high molecular mass and high yield

  10. Pittsburgh Police Arrest Data

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Arrest data contains information on people taken into custody by City of Pittsburgh police officers. More serious crimes such as felony offenses are more likely to...

  11. Radiation induced structural changes in alpha-copper-zinc alloys

    International Nuclear Information System (INIS)

    Schuele, W.; Gieb, M.

    1991-01-01

    During irradiation of alpha-copper-zinc alloys with high energy electrons and protons a decrease of the electrical resistivity due to an increase of the degree of short range order is observed through radiation enhanced diffusion followed by an increase of the electrical resistivity through the formation of radiation induced interstitial clusters. The initial formation rate of interstitial clusters increases about linearly with the displacement rate for electron and proton irradiation. The largest initial formation rate is found between 60 and 130 0 C becoming negligibly small above 158 0 C and decreases drastically below 60 0 C. The dynamic steady state interstitial cluster concentration increases with decreasing irradiation temperature in the investigated temperature range between 158 and 40 0 C. Above 158 0 C the formation rate of interstitial clusters is negligibly small. Thus the transition temperature for radiation induced interstitial cluster formation is 158 0 C, depending mainly on the migration activation energy of vacancies. The radiation induced interstitial clusters are precipitates in those alloys in which the diffusion rate of the undersized component atoms via an interstitialcy diffusion mechanism is larger than that of the other atoms

  12. Protection against radiation-induced performance decrement in mice

    International Nuclear Information System (INIS)

    Mukherjee, S.K.; Pant, Kanchan; Goel, H.C.; Jain, Viney

    1997-01-01

    Recognizing that there is lack of information on the effects of low-level ionizing radiations and the modifying role of radioprotectors, an attempt has been made in this study to explore the relationship between impairment of spatial learning and low level of radiation exposure. A radial arm maze was utilised to evaluate radiation-induced behavioural alterations and performance decrement in mice. Immediately after whole body exposure to gamma radiation (absorbed dose, 1 Gy) significant perturbations in the learned behaviour of the animals were observed. The regular control movement became irregular and the food consumption time was reduced appreciably (40%). Recovery took place in four days. If diltiazem (7 mg/kg b.w.), a Ca 2+ channel blocker and a radioprotector, was administered i.p. 20-30 min prior to irradiation, radiation-induced behavioural abnormalities were reduced. Mechanisms underlying protection by diltiazem against radiation-induced performance decrement observed in the present study need to be investigated. (author). 23 refs., 2 figs

  13. Radiation-induced grain boundary segregation in austenitic stainless steels

    International Nuclear Information System (INIS)

    Bruemmer, S.M.; Charlot, L.A.; Vetrano, J.S.; Simonen, E.P.

    1994-11-01

    Radiation-induced segregation (RIS) to grain boundaries in Fe-Ni-Cr-Si stainless alloys has been measured as a function of irradiation temperature and dose. Heavy-ion irradiation was used to produce damage levels from 1 to 20 displacements per atom (dpa) at temperatures from 175 to 550 degrees C. Measured Fe, Ni, and Cr segregation increased sharply with irradiation dose (from G to 5 dpa) and temperature (from 175 to about 350 degrees C). However, grain boundary concentrations did not change significantly as dose or temperatures were further increased. Although interfacial compositions were similar, the width of radiation-induced enrichment or depletion profiles increased consistently with increasing dose or temperature. Impurity segregation (Si and P) was also measured, but only Si enrichment appeared to be radiation-induced. Grain boundary Si peaked at levels approaching 10 at% after irradiation doses to 10 dpa at an intermediate temperature of 325 degrees C. No evidence of grain boundary silicide precipitation was detected after irradiation at any temperature. Equilibrium segregation of P was measured in the high-P alloys, but interfacial concentration did not increase with irradiation exposure. Comparisons to reported RIS in neutron-irradiated stainless steels revealed similar grain boundary compositional changes for both major alloying and impurity elements

  14. Radiation-Induced Differentiation in Human Lung Fibroblast

    International Nuclear Information System (INIS)

    Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young

    2007-01-01

    One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of α-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-β), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-β with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-β but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90

  15. Radiation-induced tumors of the nervous system

    International Nuclear Information System (INIS)

    Bernstein, M.; Laperriere, N.

    1991-01-01

    Therapeutic and nontherapeutic ionizing radiation has long been recognized as a putative carcinogenic agent, but the evidence that radiation causes tumors is circumstantial at worst and statistically significant at best. There are no distinct histological, biochemical, cytogenetic, or clinical criteria that can be used to determine if an individual tumor was caused directly by previous irradiation of the anatomic area. Additional supportive evidence for radiation-induced tumors includes a position correlation between radiation dose and tumor incidence (usually in the low dose range) and experimental induction of the same neoplasm in appropriate animal models. even if these criteria are fulfilled, coincidental development of a second tumor can never be discounted in an individual patient, particularly if there is an underlying diathesis to develop multiple tumors of different histology, such as in Recklinghausen's disease, or if there is an strong family history for the development of neoplastic disease. In this paper, the authors critically evaluate the available evidence to support the hypothesis that radiation induces tumors in the nervous system. The current concepts of radiation carcinogenesis are discussed and are followed by a discussion of animal data and clinical experience in humans. Finally, a brief discussion on treatment of radiation-induced nervous system tumors is presented

  16. Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced apoptosis of mouse L5178Y lymphoma cells

    International Nuclear Information System (INIS)

    Aoki, Mizuho; Furusawa, Yoshiya; Shibamoto, Yuta

    2002-01-01

    We investigated the sensitizing effect of the 2-nitroimidazole analogue doranidazole, a new hypoxic radiosensitizer, on radiation-induced apoptosis in L5178Y cells. Apoptosis was assessed by checking DNA ladder formation, the presence of sub-G1 peaks in flow cytometry, and chromation condensation. A radiosensitizing effect of doranidazole was also confirmed by a soft-agar colony assay of surviving cells. In the assay of DNA ladder formation, DNA fragmentation was observed following irradiation under an aerobic or hypoxic condition with or without doranidazole. The proportions of the cells at the sub-G1 peak in a flow cytometric measurement was not very different among the irradiations at 5 Gy under the aerobic condition, 15 Gy under hypoxia, and 10 Gy with 1 mM doranidazole under hypoxia. The fraction of cells with chromatin condensation was found to be significantly increased with doranidazole up to 3 mM when applied under hypoxic irradiation, but did not increase even at 10 mM. The sensitizer enhancement ratio was estimated to be about 1.7 with a concentration of 1 mM. This enhancement ratio was not different from that observed by assaying cell survivals. On the other hand, doranidazole showed no radiosensitizing effect under aerobic conditions with 1 mM. In conclusion, the radiation-induced apoptosis of L5178Y cells was enhanced by doranidazole under hypoxia. (author)

  17. Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A.

    Science.gov (United States)

    Dong, X; Zavitz, K H; Thomas, B J; Lin, M; Campbell, S; Zipursky, S L

    1997-01-01

    In the developing eye of Drosophila melanogaster, cells become synchronized in the G1 phase of the cell cycle just prior to the onset of cellular differentiation and morphogenesis. In roughex (rux) mutants, cells enter S phase precociously because of ectopic activation of a Cyclin A/Cdk complex in early G1. This leads to defects in cell fate and pattern formation, and results in abnormalities in the morphology of the adult eye. A screen for dominant suppressors of the rux eye phenotype led to the identification of mutations in cyclin A, string (cdc25), and new cell cycle genes. One of these genes, regulator of cyclin A (rca1), encodes a novel protein required for both mitotic and meiotic cell cycle progression. rca1 mutants arrest in G2 of embryonic cell cycle 16 with a phenotype very similar to cyclin A loss of function mutants. Expression of rca1 transgenes in G1 or in postmitotic neurons promotes Cyclin A protein accumulation and drives cells into S phase in a Cyclin A-dependent fashion.

  18. Identification of Secreted Proteins from Ionizing Radiation-Induced Senescent MCF7 Cells Using Comparative Proteomics

    International Nuclear Information System (INIS)

    Han, Na Kyung; Kim, Han Na; Hong, Mi Na; Park, Su Min; Lee, Jae Seon; Chi, Seong Gil

    2010-01-01

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated β-galactosidase positivity and over the years a large number of molecular phenotypes have been described, such as changes in gene expression, protein processing and chromatin organization. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence-associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence

  19. Identification and characterization of secretory proteins during ionizing radiation-induced premature senescence

    International Nuclear Information System (INIS)

    Han, Na Kyung; Hong, Mi Na; Jung, Seung Hee; Kang, Kyoung Ah; Lee, Jae Seon; Chi, Seong Gil

    2011-01-01

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated β alactosidase positivity. Recently a large number of molecular phenotypes such as changes in gene expression, protein processing and chromatin organization have been also described. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence. Here, we show that senescent human breast cancer MCF7 cells promote the proliferation, invasion and migration of neighboring cells

  20. Identification and characterization of secretory proteins during ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Han, Na Kyung; Hong, Mi Na; Jung, Seung Hee; Kang, Kyoung Ah; Lee, Jae Seon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chi, Seong Gil [Korea University, Seoul (Korea, Republic of)

    2011-05-15

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated {beta} alactosidase positivity. Recently a large number of molecular phenotypes such as changes in gene expression, protein processing and chromatin organization have been also described. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence. Here, we show that senescent human breast cancer MCF7 cells promote the proliferation, invasion and migration of neighboring cells

  1. Radiation-induced apoptosis of chicken lymphocyte B-cell line DT40

    International Nuclear Information System (INIS)

    Furusawa, Y.; Aoki, M.; Takakura, K.

    2003-01-01

    Full text: Ionizing radiation causes lesions of DNA, cell cycle arrest, induced cell death, and apoptosis in the irradiated cells. Then it is easy to expect that those events would be increased in a cell line which is defective in DNA repair system. However, induction of apoptosis by irradiation takes so complicated process when the cells are defective of DNA repair system. Indeed by many recent studies it has been clarified that DNA repair gene is also concerned with apoptotic event and some study shows the contrary data. Thus, the relationship between the genetics of apoptosis and that of DNA repair is still unclear. In this study two kinds of DNA repair proteins, Rad54 and Ku70, were focused. Proteins of Rad54 and Ku70 have important role at two type of DNA repair systems called homologous recombination repair and non-homologous end joining repair, respectively. 4 phenotypes of DT40, parent type, ku70-/-, rad54-/- and ku70-/-/rad54-/- were used to study the radiation-induced apoptosis (Previous study shows that survival fraction of 4 phenotypes of DT40 is decreased in the cell line, in which DNA repair gene is defective). From the results in this study, two things are clarifies. One is that the dependence of apoptotic index on phenotypes is so different between at low dose and at high dose irradiation. The other is that Ku70 has effective role to induce apoptosis in DT40 irradiated with high dose X-rays

  2. Identification of Secreted Proteins from Ionizing Radiation-Induced Senescent MCF7 Cells Using Comparative Proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Han, Na Kyung; Kim, Han Na; Hong, Mi Na; Park, Su Min; Lee, Jae Seon [Korea Institue of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chi, Seong Gil [Korea University, Seoul (Korea, Republic of)

    2010-05-15

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated beta-galactosidase positivity and over the years a large number of molecular phenotypes have been described, such as changes in gene expression, protein processing and chromatin organization. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence-associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence

  3. Radiation-induced pseudotumor following therapy for soft tissue sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Lacey F.; Kransdorf, Mark J. [Mayo Clinic, Department of Radiology, Jacksonville, FL (United States); Buskirk, Steven J. [Mayo Clinic, Department of Radiation Oncology, Jacksonville, FL (United States); O' Connor, Mary I. [Mayo Clinic, Department of Orthopedic Surgery, Jacksonville, FL (United States); Menke, David M. [Mayo Clinic, Department of Pathology, Jacksonville, FL (United States)

    2009-06-15

    The purpose of this study was to describe the prevalence and imaging appearance of radiation induced pseudotumors in patients following radiation therapy for extremity soft tissue sarcomas. We retrospectively reviewed the serial magnetic resonance (MR) images of 24 patients following radiation therapy for extremity soft tissue sarcomas. A total of 208 exams were reviewed (mean, 8.7 exams per patient) and included all available studies following the start of radiation therapy. Exams were analyzed for the identification of focal signal abnormalities within the surgical bed suggesting local tumor recurrence. Histopathologic correlation was available in nine patients suspected of having local tumor recurrence. Additional information recorded included patient demographics, tumor type and location, radiation type, and dose. The study group consisted of 12 men and 12 women, having an average age of 63 years (range, 39-88 years). Primary tumors were malignant fibrous histiocytoma (n = 13), leiomyosarcoma (n = 6), liposarcoma (n = 3), synovial sarcoma (n = 1), and extraskeletal chondrosarcoma (n = 1). All lesions were high-grade sarcomas, except for two myxoid liposarcomas. Average patient radiation dose was 5,658 cGy (range, 4,500-8,040 cGy). Average follow-up time was 63 months (range, 3-204 months). Focal signal abnormalities suggesting local recurrence were seen in nine (38%) patients. Three of the nine patients with these signal abnormalities were surgically proven to have radiation-induced pseudotumor. The pseudotumors developed between 11 and 61 months following the initiation of radiation therapy (mean, 38 months), with an average radiation dose of 5,527 cGy (range, 5,040-6,500 cGy). MR imaging demonstrated a relatively ill-defined ovoid focus of abnormal signal and intense heterogeneous enhancement with little or no associated mass effect. MR imaging of radiation-induced pseudotumor typically demonstrates a relatively ill-defined ovoid mass-like focus of intense

  4. Bla g 1 allergen levels in Zagreb area household dust.

    Science.gov (United States)

    Prester, Ljerka; Macan, Jelena

    2011-03-01

    Cockroach allergy is a health problem in many parts of the world. In urban environments, indoor exposure to cockroach allergens involves a risk of asthma. The aim of this study was to measure the mass fraction of Bla g 1, a major allergen of the German cockroach (Blatella germanica) in 30 house samples, collected at random from Zagreb area households, Croatia. Dust samples were collected on cellulose filters by vacuuming living rooms floors. After extraction, Bla g 1 was detected using the commercial enzyme-linked immunosorbent assay (ELISA). Only four of the thirty households had detectable Bla g 1 levels, and only in one was its concentration higher than 2.0 U g(-1), the threshold associated with sensitisation. The Bla g 1 ELISA proved highly sensitive, with the detection limit of 0.12 U g(-1). The within- and between-assay imprecision was 8.9 % and 14.4 %, respectively, and accuracy 85 % to 120 %. Low Bla g 1 levels in the household dust support previously reported low prevalence of skin sensitisation to B. germanica among Zagreb residents. Further monitoring should reveal if there are differences in cockroach allergen exposure and sensitisation between households from other geographic areas in Croatia.

  5. Rapid biodegradation of organophosphorus pesticides by Stenotrophomonas sp. G1

    International Nuclear Information System (INIS)

    Deng, Shuyan; Chen, Yao; Wang, Daosheng; Shi, Taozhong; Wu, Xiangwei; Ma, Xin; Li, Xiangqiong; Hua, Rimao; Tang, Xinyun; Li, Qing X.

    2015-01-01

    Highlights: • Stenotrophomonas sp. G1 was isolated from chlorpyrifos contaminated sludge. • Strain G1 is closest to Stenotrophomonas acidaminiphila. • Strain G1 can efficiently degrade 8 organophosphorus pesticides (OPs). • Intracellular methyl parathion hydrolase is responsible for the OP degradation. • Three factors were orthogonally optimized for degradation of methyl parathion. - Abstract: Organophosphorus insecticides have been widely used, which are highly poisonous and cause serious concerns over food safety and environmental pollution. A bacterial strain being capable of degrading O,O-dialkyl phosphorothioate and O,O-dialkyl phosphate insecticides, designated as G1, was isolated from sludge collected at the drain outlet of a chlorpyrifos manufacture plant. Physiological and biochemical characteristics and 16S rDNA gene sequence analysis suggested that strain G1 belongs to the genus Stenotrophomonas. At an initial concentration of 50 mg/L, strain G1 degraded 100% of methyl parathion, methyl paraoxon, diazinon, and phoxim, 95% of parathion, 63% of chlorpyrifos, 38% of profenofos, and 34% of triazophos in 24 h. Orthogonal experiments showed that the optimum conditions were an inoculum volume of 20% (v/v), a substrate concentration of 50 mg/L, and an incubation temperature in 40 °C. p-Nitrophenol was detected as the metabolite of methyl parathion, for which intracellular methyl parathion hydrolase was responsible. Strain G1 can efficiently degrade eight organophosphorus pesticides (OPs) and is a very excellent candidate for applications in OP pollution remediation

  6. Rapid biodegradation of organophosphorus pesticides by Stenotrophomonas sp. G1

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Shuyan; Chen, Yao [Key Laboratory of Agri-food Safety of Anhui Province, Lab of Quality & Safety and Risk Assessment for Agro-products on Storage and Preservation (Hefei), Ministry of Agriculture, School of Resource and Environment, Anhui Agricultural University, Hefei 230036 (China); Wang, Daosheng [School of Life Science, Anhui Agricultural University, Hefei 230036 (China); Shi, Taozhong; Wu, Xiangwei; Ma, Xin; Li, Xiangqiong [Key Laboratory of Agri-food Safety of Anhui Province, Lab of Quality & Safety and Risk Assessment for Agro-products on Storage and Preservation (Hefei), Ministry of Agriculture, School of Resource and Environment, Anhui Agricultural University, Hefei 230036 (China); Hua, Rimao, E-mail: rimaohua@ahau.edu.cn [Key Laboratory of Agri-food Safety of Anhui Province, Lab of Quality & Safety and Risk Assessment for Agro-products on Storage and Preservation (Hefei), Ministry of Agriculture, School of Resource and Environment, Anhui Agricultural University, Hefei 230036 (China); Tang, Xinyun [School of Life Science, Anhui Agricultural University, Hefei 230036 (China); Li, Qing X. [Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 1955 East–West Road, Honolulu, HI 957822 (United States)

    2015-10-30

    Highlights: • Stenotrophomonas sp. G1 was isolated from chlorpyrifos contaminated sludge. • Strain G1 is closest to Stenotrophomonas acidaminiphila. • Strain G1 can efficiently degrade 8 organophosphorus pesticides (OPs). • Intracellular methyl parathion hydrolase is responsible for the OP degradation. • Three factors were orthogonally optimized for degradation of methyl parathion. - Abstract: Organophosphorus insecticides have been widely used, which are highly poisonous and cause serious concerns over food safety and environmental pollution. A bacterial strain being capable of degrading O,O-dialkyl phosphorothioate and O,O-dialkyl phosphate insecticides, designated as G1, was isolated from sludge collected at the drain outlet of a chlorpyrifos manufacture plant. Physiological and biochemical characteristics and 16S rDNA gene sequence analysis suggested that strain G1 belongs to the genus Stenotrophomonas. At an initial concentration of 50 mg/L, strain G1 degraded 100% of methyl parathion, methyl paraoxon, diazinon, and phoxim, 95% of parathion, 63% of chlorpyrifos, 38% of profenofos, and 34% of triazophos in 24 h. Orthogonal experiments showed that the optimum conditions were an inoculum volume of 20% (v/v), a substrate concentration of 50 mg/L, and an incubation temperature in 40 °C. p-Nitrophenol was detected as the metabolite of methyl parathion, for which intracellular methyl parathion hydrolase was responsible. Strain G1 can efficiently degrade eight organophosphorus pesticides (OPs) and is a very excellent candidate for applications in OP pollution remediation.

  7. Relationship between radiation induced activation of DNA repair genes and radiation induced apoptosis in human cell line A431

    International Nuclear Information System (INIS)

    Bom, Hee Seung; Min, Jung Jun; Kim, Kyung Keun; Choi, Keun Hee

    2000-01-01

    The purpose of this study was to evaluate the relationship between radiation-induced acivation of DNA repair genes and radiation induced apoptosis in A431 cell line. Five and 25 Gys of gamma radiation were given to A431 cells by a Cs-137 cell irradiator. Apoptosis was evaluated by flow cytometry using annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression of DNA repair genes was evaluated by both Northern and Western blot analyses. The number of apoptotic cells increased with the increased radiation dose. It increased most significantly at 12 hours after irradiation. Expression of p53, p21, and ℎRAD50 reached the highest level at 12 hours after 5 Gy irradiation. In response to 25 Gy irradiation, ℎRAD50 and p21 were expressed maximally at 12 hours, but p53 and GADD45 genes showed the highest expression level after 12 hours. Induction of apoptosis and DNA repair by ionizing radiation were closely correlated. The peak time of inducing apoptosis and DNA repair was 12 hours in this study model. ℎRAD50, a recently discovered DNA repair gene, was also associated with radiation-induced apoptosis.=20

  8. Semigroup Method on a MX/G/1 Queueing Model

    Directory of Open Access Journals (Sweden)

    Alim Mijit

    2013-01-01

    Full Text Available By using the Hille-Yosida theorem, Phillips theorem, and Fattorini theorem in functional analysis we prove that the MX/G/1 queueing model with vacation times has a unique nonnegative time-dependent solution.

  9. Modifying effect of 5-fluoro-2-deoxyuridine and thymidine at G1 phase on radiation and chemically induced chromosome rearrangement

    International Nuclear Information System (INIS)

    Azatyan, R.A.; Voskanyan, A.Z.; Avakyan, V.A.; Akif'ev, A.P.

    1978-01-01

    The yield of structural chromosome mutations induced in Crepis capillaris seeds by X-rays and nitrogen mustard was studied as a function of treatment (at G 1 phase) with an inhibitor of unscheduled DNA synthesis, 5-fluoro-2-deoxyuridine (FdU), and its antagonist, thymidine. Air-dry seeds were irradiated at 10 krad and immediately placed in aqueous solutions of FdU, thymidine, or FdU + thymidine. Ionizing radiation induced only chromosome exchanges in the seeds. When EdU was used, the number of chromosome exchanges was the same although the fraction of simple and isolocus deletions was significantly greater than additive. The effect of FdU was manifested only after 10-hour incubation of the cells. Thymidine alone did not appreciably alter the frequency of radiation-induced aberrations. At the same time, the FdU + thymidine combination decreased the mutation yield i.e. was protective. Frequencies of the chromosome aberration in this experiment were the same as in the control

  10. Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle progression in hepatocytes

    International Nuclear Information System (INIS)

    Bhadriraju, Kiran; Hansen, Linda K.

    2004-01-01

    Cell spreading and proliferation are tightly coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require an intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation

  11. Construction of radiation - induced metastasis model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; Jang, Su Jin; Kang, Sung Wook; Kim, Jae Sung; Hwang, Sang Gu; Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-05-15

    In treatment of cancer, distant metastases are important limiting factor because an estimated 50% of all cancer patients will develop metastases, and the metastases are major causing of cancer treatment failure. Recently a few reports indicated {gamma}-radiation induced an increase of invasiveness of several cancer cells. In this study, we had tried to show the possibility that radiation could also induce metastasis in vivo system. To prove our hypothesis, we constructed primary tumor by using C6-TL transfectant cell line expressing HSV1-tk and firefly luciferase (fLuc), and then {gamma}-radiation was treated to xenografts locally. Treatment of {gamma}-radiation to primary C6-TL xenografts of mice reduced size of xenografts and elongated survival of mice than those of mock control mice. But we also show that {gamma}-radiation treatment was followed by the growth of dormant metastases in various organs including lung and intestine after 2-4 weeks of {gamma}-radiation treatment. When bioluminescence imaging indicated growth of tumor in organs in mice, we sacrificed the mice and repeat acquired bioluminescence imaging after repeatedly. These images presented tumor growth locations exactly in organs. Because metastatic tumor candidates have morphology of foci, biopsies were performed for histological analysis or PCR analysis to confirm metastases. In most foci, histological analysis indicated several features of typical cancer tissue and PCR analysis showed present of fLuc gene in metastases. Detection of fLuc gene in metastases indicated these foci were originated from primary C6-TL xenografts, and the results suggest that {gamma}-radiation could promote metastasis in vivo as well as in vitro system. Although we need to understand changes of intracellular signaling or physiological phenomena of the radiation-induced metastasis yet, these results also imply that {gamma}-radiation treatment only to cancer patients need to pay attention carefully, and development of new

  12. Radioprotective effects of melatonin on radiation-induced cataract

    International Nuclear Information System (INIS)

    Karslioglu, Ie.; Ertekin, M.V.; Taysi, S.; Kocer, Ie.; Sezen, O.; Koc, M.; Bakan, N.; Gepdiremen, A.

    2005-01-01

    One of the mechanisms proposed to explain lens opacification is the oxidation of crystallins, either by radiation or reactive oxygen species (ROS). It has been shown that melatonin has both an anti-peroxidative effect on several tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant role of melatonin (5 mg/kg/day) against radiation-induced cataract in the lens after total-cranium irradiation of rats with a single dose of 5 Gy. Sprague-Dawley rats were divided into four groups. Control group received neither melatonin nor irradiation. Irradiated rats (IR) and melatonin+irradiated rats (IR+Mel) groups were exposed to total cranium irradiation of 5 Gy in a single dose by using a cobalt-60 teletherapy unit. IR+Mel and melatonin (Mel) groups were administered 5 mg/kg melatonin daily by intraperitoneal injections during ten days. Chylack's cataract classification was used in this study. At the end of the 10 th day, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes i.e. the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation level (malondialdehyde (MDA)). Irradiation significantly increased the MDA level, as an end product of lipid peroxidation, and also significantly decreased SOD and GSH-Px activity, emphasizing the generation of increased oxidative stress. Rats injected with melatonin only did not cause cataract formation. Melatonin supplementation with irradiation significantly increased the activity of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a single dose enhanced cataract formation, and melatonin supplementation protected the lenses from radiation-induced cataract formation. Our results suggest that supplementing cancer patients with adjuvant therapy of melatonin may reduce patients suffering from toxic therapeutic regimens such as chemotherapy and/or radiotherapy and may provide

  13. Radiation-induced erectile dysfunction: Recent advances and future directions

    Directory of Open Access Journals (Sweden)

    Javed Mahmood, PhD

    2016-07-01

    Full Text Available Prostate cancer is one of the most prevalent cancers and the second leading cause of cancer-related deaths in men in the United States. A large number of patients undergo radiation therapy (RT as a standard care of treatment; however, RT causes erectile dysfunction (radiation-induced erectile dysfunction; RiED because of late side effects after RT that significantly affects quality of life of prostate cancer patients. Within 5 years of RT, approximately 50% of patients could develop RiED. Based on the past and current research findings and number of publications from our group, the precise mechanism of RiED is under exploration in detail. Recent investigations have shown prostate RT induces significant morphologic arterial damage with aberrant alterations in internal pudendal arterial tone. Prostatic RT also reduces motor function in the cavernous nerve which may attribute to axonal degeneration may contributing to RiED. Furthermore, the advances in radiogenomics such as radiation induced somatic mutation identification, copy number variation and genome-wide association studies has significantly facilitated identification of biomarkers that could be used to monitoring radiation-induced late toxicity and damage to the nerves; thus, genomic- and proteomic-based biomarkers could greatly improve treatment and minimize arterial tissue and nerve damage. Further, advanced technologies such as proton beam therapy that precisely target tumor and significantly reduce off-target damage to vital organs and healthy tissues. In this review, we summarize recent advances in RiED research and novel treatment modalities for RiED. We also discuss the possible molecular mechanism involved in the development of RiED in prostate cancer patients. Further, we discuss various readily available methods as well as novel strategies such as stem cell therapies, shockwave therapy, nerve grafting with tissue engineering, and nutritional supplementations might be used to

  14. Effect of Flavopiridol on Radiation-induced Apoptosis of Human Laryngeal and Lung Cancer Cells

    International Nuclear Information System (INIS)

    Kim, Suzy; Kwon, Eun Kyung; Lee, B. S.; Lee, Seung Hee; Park, B. S.; Wu, Hong Gyun

    2007-01-01

    Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin D1 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according

  15. Radiation-induced rhabdomyosarcomatous transformation of a recurrent meningeal haemangiopericytoma

    International Nuclear Information System (INIS)

    Ka Kit Leung, G.; Chun Kit Lee, W.; Nicholls, J.M.

    2007-01-01

    A 53-year-old woman presented in 1979 with a posterior fossa meningeal haemangiopericytoma (HPC) for which she underwent surgical resection and post-operative radiotherapy. Repeated tumor recurrences occurred 18 years afterwards which were treated with resections and stereotactic radiotherapy. Surgery for tumor recurrence in 2005 revealed features of rhabdomyosarcomatous transformation. To our knowledge, this is the first reported case of rhabdomyosarcomatous transformation within a HPC which was likely to be radiation-induced, and was associated with relentless disease progression more than 20 years after the initial presentation. (author)

  16. Segregation effect of radiation induced crosslinking of HDPE: morphology change

    International Nuclear Information System (INIS)

    Deng Pengyang; Zhong Xiaoguang

    2000-01-01

    Scanning Electronic Microscopy has been used to study morphology of pure gel; sol-gel blend and sol-gel segregation samples of radiation induced crosslinking of HDPE. The results show that the morphology of segregation sample is the same as that of pure gel and different from that of sol-gel blend. This kind of morphology change proves that the sol-gel blend have occurred a liquid---solid phase segregation in the melting state. The liquid phase (sol) will naturally immersed in the network of the gel. (author)

  17. Radiation-induced hyperprolactinaemia in a treated acromegalic

    International Nuclear Information System (INIS)

    Shalet, S.M.; MacFarlane, I.A.; Beardwell, C.G.

    1979-01-01

    A 31-year-old acromegalic was normoprolactinaemic after partial removal of her pituitary tumour. The post-operative external pituitary irradiation lowered the mean growth hormone (GH) level from 75 mU/l to less than 1 mU/l within 2 years. However, at the same time hyperprolactinaemia developed. These changes in the GH and prolactin levels were confirmed 3 and 4 years after irradiation. The cause of the hyperprolactinaemia was radiation-induced hypothalamic damage. Therefore it is suggested that similar damage may occur in patients receiving external pituitary irradiation for 'prolactinomas' and that this mechanism may contribute to the persistent hyperprolactinaemia observed in such patients. (author)

  18. The effect of caffeine on radiation-induced division delay

    International Nuclear Information System (INIS)

    Snyder, M.H.; Kimler, B.F.; Leeper, D.B.

    1977-01-01

    Caffeine (100 μg/ml) was added to monolayer cultures of Chinese hamster ovary cells coincident with 60 Co γ-irradiation (75 to 300 rad). The results indicated that caffeine (at concentrations that did not perturb cell-cycle progression as monitored by the mitotic selection technique) exerted a protective effect against radiation-induced division delay. This protection consisted of an increase in the number of cells that were refractory to the radiation insult, as well as a decrease in the average time that non-refractory cells were delayed before they recovered their ability to progress through the cell cycle. (U.K.)

  19. Tissue culture regeneration and radiation induced mutagenesis in banana

    International Nuclear Information System (INIS)

    Kulkarni, V.M.; Ganapathi, T.R.

    2009-01-01

    Radiation induced mutagenesis is an important tool for banana genetic improvement. At BARC, protocols for shoo-tip multiplication of commercial banana varieties have been developed and transferred to user agencies for commercial production. Excellent embryogenic cell suspensions were established in banana cvs. Rasthali and Rajeli, and were maintained at low temperatures for long-term storage. Normal plantlets were successfully regenerated from these cell suspensions. The cell suspensions and shoot-tip cultures were gamma-irradiated for mutagenesis. The mutagenized populations were field screened and a few interesting mutants have been isolated. The existence of genetic variation was confirmed using DNA markers. Further evaluation of these mutants is in progress. (author)

  20. Radiation-induced glycoside bond breaking in cellulose methyl ethers

    International Nuclear Information System (INIS)

    Petryaev, E.P.; Boltromeyuk, V.V.; Kovalenko, N.I.; Shadyro, O.I.

    1988-01-01

    Radiation-induced destruction of cellulose methyl ethers of different degree of esterification in aqueous solutions with and without acceptors: (N 2 O, O 2 , H 2 O + , Co(2), Cu(2)) is investigated. It is established that OH radicals make main contribution into radiolytic transformations of cellulose ethers in aqueous solutions. Reactions of radicals with free valency on carbon atoms containing secondary nonsubstituted hydroxyl groups lead also to glycoside bond breaking besides the reaction of β-fragmentation and hydrolysis of radicals with an unpaired electron localized near C 1 , C 4 , C 5 aroms

  1. Management of radiation-induced accelerated carotid atherosclerosis

    International Nuclear Information System (INIS)

    Loftus, C.M.; Biller, J.; Hart, M.N.; Cornell, S.H.; Hiratzka, L.F.

    1987-01-01

    Patients with long survival following cervical irradiation are at risk for accelerated carotid atherosclerosis. The neurologic presentation in these patients mimics naturally occurring atheromatous disease, but patients often present at younger ages and with less concurrent coronary or systemic vascular disease. Hypercholesterolemia also contributes to this accelerated arteriosclerosis. Angiographic findings in this disorder include disproportionate involvement of the distal common carotid artery and unusually long carotid lesions. Pathologic findings include destruction of the internal elastic lamina and replacement of the normal intima and media with fibrous tissue. This article describes two surgical patients with radiation-induced accelerated carotid atherosclerosis who typify the presentation and characteristics of this disease

  2. Effect of electrodes in the radiation induced conductivity for polymers

    International Nuclear Information System (INIS)

    Gregorio Filho, R.; Gross, B.

    1988-01-01

    Samples of PET with 23 μm thickness were exposed to continuous X-rays and the radiation-induced conductivity (RIC) as a function of time were measured, using electrodes of evaporated aluminum and gold. The results showed that the use of higher atomic number metal electrodes increase the received dose rate by sample, without almost modifying the time evolution of the RIC or its dependence with the applied electric field intensity. It is also showed that this increase is caused by the electrode placed in the face of the sample where the radiation strikes, as well as by the one placed in the oposite face. (author) [pt

  3. Radiation-induced attenuation in integrated optical materials

    International Nuclear Information System (INIS)

    Evans, B.D.

    1989-01-01

    This paper reports that three materials commonly employed in opto-electronic integrated circuits evaluated for radiation-induced optical attenuation in the range 300 nm to 3000 nm. These include optically clear epoxy and crystalline lithium niobate after Co-60 exposure and crystalline tellurium dioxide after mixed gamma/fast-neutron exposure. In all these materials, however, induced loss was restricted to shorter wavelengths; attenuation induced at the telecommunications windows near 850, 1300 and 1550 nm was <0.1 dB/cm

  4. Radiation-induced cationic curing of vinyl ethers

    International Nuclear Information System (INIS)

    Lapin, S.C.

    1992-01-01

    Recently there has been an increasing interest in nonacrylate radiation-curable coatings. Vinyl ethers are particularly reactive under cationic polymerization reaction conditions. The high efficiency of the photoacid initiators combined with the high reactivity of vinyl ether monomers makes this a potentially very useful system. This chapter discusses the preparation of vinyl ethers, introduces vinyl ether-functional monomers and oligomers, describes radiation-induced cationic polymerization of vinyl ethers, and discusses various coating systems. Throughout the chapter, an emphasis is placed on radiation-curable coating applications. 64 refs., 5 figs., 11 tabs

  5. Immobilization of yeast cells by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Fujimura, T.; Kaetsu, I.

    1982-01-01

    Radiation-induced polymerization method was applied to the immobilization of yeast cells. The effects of irradiation, cooling and monomer, which are neccessary for polymerization, were recovered completely by subsequent aerobical incubation of yeast cells. The ethanol productive in immobilized yeast cells increased with the increase of aerobical incubation period. The growth of yeast cells in immobilized yeast cells was indicated. The maximum ethanol productivity in immobilized yeast cell system was around three times as much as that in free yeast cell system. (orig.)

  6. Radiation-induced life-shortening and premature aging

    International Nuclear Information System (INIS)

    Walburg, H.E. Jr.

    1975-01-01

    Data from a number of studies on irradiated laboratory animals showed that almost none of the characteristic lesions associated with senescence that were studied adequately reflects a radiation effect analogous to premature aging. In fact, most of the age-related changes showed no effect of radiation at all, and many of those that did (for example, graying of hair, sterility, cataract formation) did not appear to be due to similar mechanisms. It is concluded that, in the light of more recent information, the hypothesis of radiation-induced premature aging requires reassessment. (80 references) (CH)

  7. Delayed radiation-induced necrosis of the brain stem

    International Nuclear Information System (INIS)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi; Uozumi, Toru.

    1993-01-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author)

  8. Facial reconstruction for radiation-induced skin cancer

    International Nuclear Information System (INIS)

    Panje, W.R.; Dobleman, T.J.

    1990-01-01

    Radiation-induced skin cancers can be difficult to diagnose and treat. Typically, a patient who has received orthovoltage radiotherapy for disorders such as acne, eczema, tinea capitis, skin tuberculosis, and skin cancer can expect that aggressive skin cancers and chronic radiodermatitis may develop subsequently. Cryptic facial cancers can lead to metastases and death. Prophylactic widefield excision of previously irradiated facial skin that has been subject to multiple recurrent skin cancers is suggested as a method of deterring future cutaneous malignancy and metastases. The use of tissue expanders and full-thickness skin grafts offers an expedient and successful method of subsequent reconstruction

  9. Radiation-induced invagination of the nuclear envelope

    International Nuclear Information System (INIS)

    Szekely, J.G.; Copps, T.P.; Morash, B.D.

    1980-01-01

    Using electron microscopy, we have measured radiation-induced invagination of the nuclear envelope of Chinese hamster V-79 and mouse L cells to produce a quantifiable radiation endpoint on a membrane system. In the dose ranges measured (800 to 3000 rad in L cells and 1270 to 5700 rad in V-79 cells), the amount of invagination increased with dose and continued to develop in intact cells for up to 72 hr after the original population was irradiated. Small vacuoles, which sometimes appeared in the nuclei of L cells, were also more numerous in irradiated cells and increased with dose and incubation time in a similar fashion to invagination development

  10. Weak-beam electron microscopy of radiation-induced segregation

    International Nuclear Information System (INIS)

    Saka, H.

    1983-01-01

    The segregation of solute atoms to dislocations during irradiation by 1 MeV electrons in a HVEM was studied by measuring the dissociation width of extended dislocations in Cu-5.1 at.%Si, Cu-5.3 at.%Ge, Ag-9.4 at.% In and Ag-9.6 at.%Al alloys. 'Weak-beam' electron microscopy was used. In Cu-Si (oversized solute), Cu-Ge (oversize) and Ag-Al (undersize), solute enrichment was observed near dislocations, while in Ag-In (oversize) solute depletion was observed. The results are discussed in terms of current mechanisms for radiation-induced segregation. (author)

  11. Use of radiation-induced polymers in cement slurries

    International Nuclear Information System (INIS)

    Knight, B.L.; Rhudy, J.S.; Gogarty, W.B.

    1976-01-01

    Water loss from cement slurries is reduced by incorporating within a cement slurry a polymer obtained as a product of radiation-induced polymerization of acrylamide and/or methacrylamide and acrylic acid, methacrylic acid, and/or alkali metal salts thereof. The polymerization is preferably carried out in 10-60 percent aqueous monomer solution with gamma radiation. The aqueous monomer solution preferably contains 25-99 percent acrylamide and 75-1 percent sodium acrylate. The polymer can be present in concentration of about 0.001 to about 3.0 weight percent, based on the aqueous phase of the slurry

  12. Radiation-induced O-glycoside bond scission in carbohydrates

    International Nuclear Information System (INIS)

    Kisel', R.M.

    2005-01-01

    Regularities in formation of products resulting from O-glycoside bond cleavage on radiolysis of aqueous solutions of (-methyl-D-glucopyranoside (I), 3-O-methylglucopyranose (II), maltose and lactose were studied. Oxygen and quinones were shown to inhibit radiation-induced homolytic destruction processes taking place in glycosides. The data obtained in this study enabled the authors to demonstrate an important role played by fragmentation reaction of C-2 radicals generated from the starting substances in formation of final radiolysis products. (authors)

  13. 'Like new': plastic wastes regeneration by radiation induced grafting

    International Nuclear Information System (INIS)

    Laizier, J.; Gaussens, G.; Lemaire, F.

    1978-01-01

    The reclaiming and the recycling of plastic wastes is made especially difficult when those wastes are a mixture of various plastics; this is due to the incompatibility of the polymers. The radiation induced grafting allows to overcome this incompatibility. Results are given which shows that, for various mixtures of reclaimed polyethylene, PVC and polystyrene, an improvement of the properties of the processed blends is obtained by grafting the mixtures of wastes by a suitable polymer; the obtained properties of those regenerated plastic blends are enough attractive from the technical point of view to open a market to those products with a reasonable economical value [fr

  14. Enhanced micronucleus formation in the descendants of {gamma}-ray-irradiated tobacco cells: Evidence for radiation-induced genomic instability in plant cells

    Energy Technology Data Exchange (ETDEWEB)

    Yokota, Yuichiro, E-mail: yokota.yuichiro@jaea.go.jp [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Funayama, Tomoo; Hase, Yoshihiro [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Hamada, Nobuyuki [Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, 2-11-1 Iwado-kita, Komae, Tokyo 201-8511 (Japan); Kobayashi, Yasuhiko; Tanaka, Atsushi; Narumi, Issay [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan)

    2010-09-10

    Ionizing radiation-induced genomic instability has been documented in various end points such as chromosomal aberrations and mutations, which arises in the descendants of irradiated mammalian or yeast cells many generations after the initial insult. This study aimed at addressing radiation-induced genomic instability in higher plant tobacco cells. We thus investigated micronucleus (MN) formation and cell proliferation in tobacco cells irradiated with {gamma}-rays and their descendants. In {gamma}-irradiated cells, cell cycle was arrested at G{sub 2}/M phase at around 24 h post-irradiation but released afterward. In contrast, MN frequency peaked at 48 h post-irradiation. Almost half of 40 Gy-irradiated cells had MN at 48 h post-irradiation, but proliferated as actively as sham-irradiated cells up to 120 h post-irradiation. Moreover, the descendants that have undergone at least 22 generations after irradiation still showed a two-fold MN frequency compared to sham-irradiated cells. This is the direct evidence for radiation-induced genomic instability in tobacco cells.

  15. Radiation-induced apoptosis and cell cycle checkpoints in human colorectal tumour cell lines

    International Nuclear Information System (INIS)

    Playle, L.C.

    2001-03-01

    The p53 tumour suppressor gene is mutated in 75% of colorectal carcinomas and is critical for DNA damage-induced G1 cell cycle arrest. Data presented in this thesis demonstrate that after treatment with Ionizing Radiation (IR), colorectal tumour cell lines with mutant p53 are unable to arrest at G1 and undergo cell cycle arrest at G2. The staurosporine derivative, UCN-01, was shown to abrogate the IR-induced G2 checkpoint in colorectal tumour cell lines. Furthermore, in some cell lines, abrogation of the G2 checkpoint was associated with radiosensitisation. Data presented in this study demonstrate that 2 out of 5 cell lines with mutant p53 were sensitised to IR by UCN-01. In order to determine whether radiosensitisation correlated with lack of functional p53, transfected derivatives of an adenoma-derived cell line were studied, in which endogenous wild type p53 was disrupted by expression of a dominant negative p53 mutant protein (and with a vector control). In both these cell lines UCN-01 abrogated the G2 arrest however this was not associated with radiosensitisation, indicating that radiosensitisation is a cell type-specific phenomenon. Although 2 colorectal carcinoma cell lines, with mutant p53, were sensitised to IR by UCN-01, the mechanisms of p53-independent IR-induced apoptosis in the colon are essentially unknown. The mitogen-activated protein kinase (MAPK) pathways (that is the JNK, p38 and ERK pathways) have been implicated in apoptosis in a range of cell systems and in IR-induced apoptosis in some cell types. Data presented in this study show that, although the MAPKs can be activated by the known activator anisomycin, there is no evidence of a role for MAPKs in IR-induced apoptosis in colorectal tumour cell lines, regardless of p53 status. In summary, some colorectal tumour cell lines with mutant p53 can be sensitised to IR-induced cell death by G2 checkpoint abrogation and this may be an important treatment strategy, however mechanisms of IR-induced p53

  16. Sestrin2 protects the myocardium against radiation-induced damage

    International Nuclear Information System (INIS)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong; Zeng, Jing; Wang, Hong-Mei

    2016-01-01

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  17. Radiation-induced segregation in Cu-Au alloys

    International Nuclear Information System (INIS)

    Hashimoto, T.; Rehn, L.E.; Okamoto, P.R.

    1987-01-01

    Radiation-induced segregation in a Cu-lat.% Au alloy was investigated using in-situ Rutherford backscattering spectrometry. Irradiation with 1.8-MeV helium produced nonequilibrium gold atom depletion in the near surface region. The amount of segregation was measured as a function of dose, dose rate, and temperature. Segregation was observed in the temperature range between about 300 and 500 0 C. For a calculated dose rate of 3.9 x 10/sup -5/ dpa/s, the radiation-induced segregation rate peaked near 400 0 C. Theoretical analysis based on the Johnson-Lam model predicted that the amount of segregation would be directly proportional to dose at the early stage of irradiation, would deviate from linearity with a continuously decreasing slope of intermediate doses, and finally approach a constant value after high doses. The analysis also predicted that the segregation rate would vary as the - 1/4th power of the dose rate at constant dose in the low temperature region. These predictions were all verified experimentally. A procedure for extracting relative defect production efficiencies from similar measurements is discussed

  18. Radiation-induced electron migration in nucleic acids

    International Nuclear Information System (INIS)

    Fuciarelli, A.F.; Sisk, E.C.; Miller, J.H.; Zimbrick, J.D.

    1994-01-01

    Radiation-induced electron migration along DNA is a mechanism by which randomly produced stochastic energy deposition events can lead to non-random types of damage along DNA manifested distal to the sites of the initial energy deposition. Radiation-induced electron migration in nucleic acids has been examined using oligonucleotides containing 5-bromouracil (5-BrU). Interaction of 5-BrU with solvated electrons results in release of bromide ions and formation of uracil-5-yl radicals. Monitoring either bromide ion release or uracil formation provides an opportunity to study electron migration processes in model nucleic acid systems. Using this approach we have discovered that electron migration along oligonucleotides is significantly influenced by the base sequence and strandedness. Migration along 7 base pairs in oligonucleotides containing guanine bases was observed for oligonucleotides irradiated in solution, which compares with mean migration distances of 6-10 bp for Escherichia coli DNA irradiated in solution and 5.5 bp for E. coli DNA irradiated in cells. Evidence also suggests that electron migration can occur preferentially in the 5' to 3' direction along a double-stranded oligonucleotide containing a region of purine bases adjacent to the 5-BrU moiety. Our continued efforts will provide information regarding the contribution of electron transfer along DNA to formation of locally multiply damaged sites created in DNA by exposure to ionizing radiation. (Author)

  19. Improvement of boiling heat transfer by radiation induced boiling enhancement

    International Nuclear Information System (INIS)

    Imai, Yasuyuki; Okamoto, Koji; Madarame, Haruki; Takamasa, Tomoji

    2003-01-01

    For nuclear reactor systems, the critical heat flux (CHF) data is very important because it limits reactor efficiency. Improvement of CHF requires that the cooling liquid can contact the heating surface, or a high-wettability, highly hydrophilic heating surface, even if a vapor bubble layer is generated on the surface. In our previous study, we confirmed that the surface wettability changed significantly or that highly hydrophilic conditions were achieved, after irradiation of 60 Co gamma ray, by the Radiation Induced Surface Activation (RISA) phenomenon. To delineate the effect of RISA on boiling phenomena, surface wettability in a high-temperature environment and critical heat flux (CHF) of metal oxides irradiated by gamma rays were investigated. A CHF experiment in the pool boiling condition was carried out under atmospheric pressure. The heating test section made of titanium was 0.2 mm in thickness, 3 mm in height, and 60 mm in length. Oxidation of the surface was carried out by plasma jetting for 40 seconds. The test section was irradiated by 60 Co gamma ray with predetermined radiation intensity and period. The CHF of oxidized titanium was improved up to 100 percent after 800 kGy 60 Co gamma ray irradiation. We call this effect Radiation Induced Boiling Enhancement (RIBE). Before we conducted the CHF experiment, contact angles of the test pieces were measured to show the relationship between wettability and CHF. The CHF in the present experiment increases will surface wettability in the same manner as shown by Liaw and Dhir's results. (author)

  20. Ionizing radiation induced conductivity in Mylar (PET) and Kapton (Polyimide)

    International Nuclear Information System (INIS)

    Gregorio Filho, R.

    1986-01-01

    The extensive results of measurements of the prompt and delayed radiation-induced conductivity of samples of PET and Kapton are presented. Experimental parameters, such as the effective energy of the radiation, the exposure rate, the total dose, the value of the applied electric field, the nature of the electrodes, and the ambiental conditions were changed within wide limits. We also report measurement of thermally stimulated currents for non-irradiated and for irradiated samples which allowed us to investigate the trap-structure of the materials. Measurements of photo-Compton currents with different electrode materials and sample thicknesses gave information about the relation between the nature of the electrodes and the amplitudes of the currents. Based on the generalized rate theory of radiation-induced conduction we developed a theoretical model which includes the effect of the applied electric field on the carrier generation yield (geminate recombination, Onsager effect). Comparison of experimental and theoretical curves allowed us to determine the values of the main conduction parameters, such as carrier mobility, recombination coefficient, trap densities, for the materials under investigation. (Author) [pt

  1. Allopurinol gel mitigates radiation-induced mucositis and dermatitis

    International Nuclear Information System (INIS)

    Kitagawa, Junichi; Nasu, Masanori; Okumura, Hayato; Matsumoto, Shigeji; Shibata, Akihiko; Makino, Kimiko; Terada, Hiroshi

    2008-01-01

    It has not been verified whether allopurinol application is beneficial in decreasing the severity of radiation-induced oral mucositis and dermatitis. Rats were divided into 4 groups and received 15 Gy irradiation on the left whisker pad. Group 1 received only irradiation. Group 2 was maintained by applying allopurinol/carrageenan-mixed gel (allopurinol gel) continuously from 2 days before to 20 days after irradiation. Group 3 had allopurinol gel applied for 20 days after radiation. Group 4 was maintained by applying carrageenan gel continuously from 2 days before to 20 days after irradiation. The intra oral mucosal and acute skin reactions were assessed daily using mucositis and skin score systems. The escape thresholds for mechanical stimulation to the left whisker pad were measured daily. In addition, the irradiated tissues at the endpoint of this study were compared with naive tissue. Escape threshold in group 2 was significantly higher than that in group 1, and mucositis and skin scores were much improved compared with those of group 1. Concerning escape threshold, mucositis and skin scores in group 3 began to improve 10 days after irradiation. Group 4 showed severe symptoms of mucositis and dermatitis to the same extent as that observed in group 1. In the histopathological study, the tissues of group 1 showed severe inflammatory reactions, compared with those of group 2. These results suggest that allopurinol gel application can mitigate inflammation reactions associated with radiation-induced oral mucositis and dermatitis. (author)

  2. Radiation-induced mucositis pain in laryngeal cancer

    International Nuclear Information System (INIS)

    Takahashi, Atsuhito; Shoji, Kazuhiko; Iki, Takehiro; Mizuta, Masanobu; Matsubara, Mami

    2009-01-01

    Radiation therapy in those with head and neck malignancies often triggers painful mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). To better understand how radiation-induced pain develops over time, we studied the numerical rating scale (NRS 0-5) pain scores from 32 persons undergoing radiation therapy of 60-72 Gy for newly diagnosed laryngeal cancer. The degree of mucositis was evaluated using Common Terminology Criteria for Adverse Events version3.0 (CTCAE v3.0). We divided the 32 into a conventional fractionation (CF) group of 14 and a hyperfractionation (HF) group of 18, and further divided laryngeal cancer into a small-field group of 23 and a large-field group of 9. The mucositis pain course was similar in CF and HF, but mucositis pain was severer in the HF group, which also required more NSAIDs. Those in the large-field group had severer pain and mucositis and required more NSAIDs than those in the small-field group. We therefore concluded that small/large-field radiation therapy, rather fractionation type, was related to the incidence of radiation-induced mucositis pain. (author)

  3. Protection from ionizing radiation induced damages by phytoceuticals and nutraceuticals

    International Nuclear Information System (INIS)

    Nair, C.K.K.

    2012-01-01

    Exposure of living systems to ionizing radiation cause a variety of damages to DNA and membranes due to generation of free radicals and reactive oxygen species. The radiation induced lesions in the cellular DNA are mainly strand breaks, damage to sugar moiety, alterations and elimination of bases, cross links of the intra and inter strand type and cross links to proteins while peroxidation of the lipids and oxidation of proteins constitute the major lesions in the membranes. The radioprotectors elicit their action by various mechanisms such as i) by suppressing the formation of reactive species, ii) detoxification of radiation induced species, iii) target stabilization and iv) enhancing the repair and recovery processes. The radioprotective compounds are of importance in medical, industrial, environmental, military and space science applications. Radiation protection might offer a tactical advantage on the battlefield in the event of a nuclear warfare. Radioprotectors might reduce the cancer risk to populations exposed to radiations directly or indirectly through industrial and military applications. The antioxidant and radioprotective properties a few of these agents under in vitro and in vivo conditions in animal models will be discussed

  4. Sestrin2 protects the myocardium against radiation-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong [Shengjing Hospital of China Medical University, Department of Medical Oncology, Cancer Center, Shenyang (China); Zeng, Jing [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); Wang, Hong-Mei [Nanfang Hospital of Southern Medical University, Department of Radiation Oncology, Guangzhou (China)

    2016-05-15

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  5. Radiation-induced segregation in binary and ternary alloys

    International Nuclear Information System (INIS)

    Okamoto, P.R.; Rehn, L.E.

    1979-01-01

    A review is given of our current knowledge of radiation-induced segregation of major and minor elements in simple binary and ternary alloys as derived from experimental techniques such as Auger electron spectroscopy, secondary-ion mass spectroscopy, ion-backscattering, infrared emissivity measurements and transmission electron microscopy. Measurements of the temperature, dose and dose-rate dependences as well as of the effects of such materials variables as solute solubility, solute misfit and initial solute concentration has proved particularly valuable in understanding the mechanisms of segregation. The interpretation of these data in terms of current theoretical models which link solute segregation behavior to defect-solute binding interactions and/or to the relative diffusion rates of solute and solvent atoms the interstitial and vacancy migration mechanisms has, in general, been fairly successful and has provided considerable insight into the highly interrelated phenomena of solute-defect trapping, solute segregation, phase stability and void swelling. Specific examples in selected fcc, bcc and hcp alloy systems are discussed with particular emphasis given to the effects of radiation-induced segregation on the phase stability of single-phase and two-phase binary alloys and simple Fe-Cr-Ni alloys. (Auth.)

  6. Neurolysis and myocutaneous flap for radiation induced brachial plexus neuropathy

    International Nuclear Information System (INIS)

    Hirachi, Kazuhiko; Minami, Akio; Kato, Hiroyuki; Nishio, Yasuhiko; Ohnishi, Nobuki

    1998-01-01

    Surgical treatment for radiation induced brachial plexus neuropathy is difficult. We followed 9 patients of radiation induced brachial plexus neuropathy who were surgically treated with neurolysis and myocutaneous flap coverage. Their ages ranged from 29 to 72 years old. Their diagnoses were breast cancer in 6 patients, lingual cancer in 1, thyroid cancer in 1 and malignant lymphoma in 1. Total dose of radiation ranged from 44 to 240 Gy. Interval from radiation therapy to our surgery ranged from 1 to 18 years (mean 6.7 years). Chief complaints were dysesthesia in 9 patients, motor weakness in 7 patients and dullach in scar formation of radiated skin in 7 patients. Preoperative neural functions were slight palsy in 1, moderate palsy in 5 and complete palsy in 3. In surgical treatment, neurolysis of the brachial plexus was done and it was covered by latissimus dorsi myocutaneous flap. We evaluated about dysesthesia and motor recovery after treatment for neuropathy. Follow up periods ranged from 1 to 11 years (average in 5 years). Dysesthesia improved in 6 patients and got worse in 3 patients. Motor weakness recovered in only 2 patients and got worse in 7 patients. From our results, intolerable dysesthesia which was first complaint of these patients improved. But motor function had not recovered. Our treatment was thought to be effective for extraneural factor like an compression neuropathy by scar formation and poor vascularity. But it was not effective for intraneural damage by radiation therapy. (author)

  7. Treatment of a radiation-induced brachial plexopathy

    International Nuclear Information System (INIS)

    Tanaka, Ichirou; Harashina, Takao; Inoue, Takeo; Ueda, Kouichi; Hatoko, Mituo; Shidara, Yukinobu; Ito, Yoshiyasu.

    1990-01-01

    A radiation-induced brachial plexopathy after a mastectomy causes severe pain and numbness, as well as motor and sensory disorders. Severe pain is often resistant to analgesic blocks, and in most instances, the effect of neurolysis is only temporary. We have treated two such patients with microsurgical neurolysis and then have covered the nerve by transferred muscles. In one case, the exposed brachial plexus was covered with a pedicled latissimus dorsi muscle flap, and in the other, with a free rectus abdominis muscle flap. Pain and numbness were markedly improved in these two patients soon after the surgery, and the improvement in the sensory function also was relatively satisfactory. In one case, the motor function also improved. These patients have had no recurrence of pain or numbness for 4 years and 2 months and 4 years and 7 months after surgery, respectively. Further, their sensory and motor disorders did not advance. Surgical indications for a radiation-induced brachial plexopathy remain controversial, since the operation does not always ensure a marked improvement in the sensory and motor functions. Further, the operation is ineffective for patients with advanced nerve degeneration. Taking these factors into consideration, the preoperative predication of beneficial effects from this surgery is difficult. Despite our limited experience, however, our surgical method has been thought to be effective because it achieves a marked improvement in the numbness and pain experienced in the arms, which are usually the patients' chief complaints. (author)

  8. Improvement of boiling heat transfer by radiation induced boiling enhancement

    International Nuclear Information System (INIS)

    Imai, Y.; Okamoto, K.; Madarame, H.; Takamasa, T.

    2003-01-01

    For nuclear reactor systems, the Critical Heat Flux (CHF) data is very important because it limits reactor efficiency. Improvement of CHF requires that the cooling liquid can contact the heating surface, or a high-wettability, highly hydrophilic heating surface, even if a vapor bubble layer is generated on the surface. In our previous study, we confirmed that the surface wettability changed significantly or that highly hydrophilic conditions were achieved, after irradiation of 60Co gamma ray, by the Radiation Induced Surface Activation (RISA) phenomenon. To delineate the effect of RISA on boiling phenomena, surface wettability in a high-temperature environment and Critical Heat Flux (CHF) of metal oxides irradiated by gamma rays were investigated. A CHF experiment in the pool boiling condition was carried out under atmospheric pressure. The heating test section made of titanium was 0.2mm in thickness, 3mm in height, and 60mm in length. Oxidation of the surfaces was carried out by plasma jetting for 40 seconds. The test section was irradiated by 60Co gamma ray with predetermined radiation intensity and period. The CHF of oxidized titanium was improved up to 100 percent after 800kGy 60Co gamma ray irradiation. We call this effect Radiation Induced Boiling Enhancement (RIBE). Before we conducted the CHF experiment, contact angles of the test pieces were measured to show the relationship between wettability and CHF. The CHF in the present experiment increases with surface wettability in the same manner as shown by Liaw and Dhir's results

  9. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-03-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor.

  10. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    International Nuclear Information System (INIS)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-01-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor

  11. Radiation-Induced Correlation between Molecules Nearby Metallic Antenna Array

    Directory of Open Access Journals (Sweden)

    Yoshiki Osaka

    2015-01-01

    Full Text Available We theoretically investigate optical absorption of molecules embedded nearby metallic antennas by using discrete dipole approximation method. It is found that the spectral peak of the absorption is shifted due to the radiation-induced correlation between the molecules. The most distinguishing feature of our work is to show that the shift is largely enhanced even when the individual molecules couple with localized surface plasmons near the different antennas. Specifically, we first consider the case that two sets of dimeric gold blocks with a spacing of a few nanometers are arranged and reveal that the intensity and spectral peak of the optical absorption strongly depend on the position of the molecules. In addition, when the dimeric blocks and the molecules are periodically arranged, the peak shift is found to increase up to ~1.2 meV (300 GHz. Because the radiation-induced correlation is essential for collective photon emission, our result implies the possibility of plasmon-assisted superfluorescence in designed antenna-molecule complex systems.

  12. Radiation-induced skin carcinomas of the head and neck

    International Nuclear Information System (INIS)

    Ron, E.; Modan, B.; Preston, D.; Alfandary, E.; Stovall, M.; Boice, J.D. Jr.

    1991-01-01

    Radiation exposures to the scalp during childhood for tinea capitis were associated with a fourfold increase in skin cancer, primarily basal cell carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma, however, was not significantly elevated. Overall, 80 neoplasms were identified from an extensive search of the pathology logs of all major hospitals in Israel and computer linkage with the national cancer registry. Radiation dose to the scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy), and incidence rates were contrasted with those observed in 16,000 matched comparison subjects. The relative risk of radiogenic skin cancer did not differ significantly between men or women or by time since exposure; however, risk was greatest following exposures in early childhood. After adjusting for sex, ethnic origin, and attained age, the estimated excess relative risk was 0.7 per Gy and the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk per Gy of radiation-induced skin cancer was intermediate between the high risk found among whites and no risk found among blacks in a similar study conducted in New York City. This finding suggests the role that subsequent exposure to uv radiation likely plays in the expression of a potential radiation-induced skin malignancy

  13. [Biomarkers of radiation-induced DNA repair processes].

    Science.gov (United States)

    Vallard, Alexis; Rancoule, Chloé; Guy, Jean-Baptiste; Espenel, Sophie; Sauvaigo, Sylvie; Rodriguez-Lafrasse, Claire; Magné, Nicolas

    2017-11-01

    The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death. The most important DNA repair biomarkers are DNA damage signaling proteins, with ATM, DNA-PKcs, 53BP1 and γ-H2AX. They can be analyzed either using immunostaining, or using lived cell imaging. However, to date, these techniques are still time and money consuming. The development of "omics" technologies should lead the way to new (and usable in daily routine) DNA repair biomarkers. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  14. Radiation-induced recurrent intestinal pseudo-obstruction

    International Nuclear Information System (INIS)

    Conklin, J.L.; Anuras, S.

    1981-01-01

    The syndrome of intestinal pseudo-obstruction is a complex of signs and symptoms of intestinal obstruction without evidence of mechanical obstruction of the intestinal lumen. A patient with radiation-induced intestinal pseudoobstruction is described. The patient is a 74-year old woman with a history of chronic diarrhea, recurrent episodes of crampy abdominal pain, nausea and vomiting since receiving a 13,000 rad radiation dose to the pelvis in 1954. She has been hospitalized on many occasions for symptoms and signs of bowel obstruction. Upper gastrointestinal contrast roentgenograms with small bowel follow-through done during these episodes revealed multiple dilated loops of small bowel with no obstructing lesion. Barium enemas revealed no obstructing lesion. Each episode resolved with conservative therapy. Other secondary causes for intestinal pseudo-obstruction were ruled out in our patient. She gave no history of familial gastrointestinal disorders. Although postirradiation motility abnormalities have been demonstrated experimentally this is the first report of radiation induced intestinal pseudo-obstruction

  15. Radiation induced effects in the developing central nervous system

    International Nuclear Information System (INIS)

    Gisone, P.; Dubner, D.; Michelin, S.C.; Perez, M.R. Del

    1997-01-01

    The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed

  16. Radiation-induced grafting of styrene on polypropylene pellets

    International Nuclear Information System (INIS)

    Souza, Camila P.; Ferreira, Henrique P.; Parra, Duclerc F.; Lugao, Ademar B.

    2009-01-01

    The changes of radiation-induced in polypropylene (PP) pellets exposed to gamma irradiation in inert atmosphere were investigated in correlation with the applied doses (10 and 50 kGy). Also, results from the grafting of styrene onto PP pellets using simultaneous irradiation at the same doses are presented. The grafting reaction was carried out using toluene as solvent, under nitrogen atmosphere and at room temperature. The properties of the irradiated and grafted PP pellets were studied using Melt Flow Index, thermal analysis (TG and DSC), and ATR-IR. The degree of grafting (DOG) for the grafted pellets was gravimetrically determined. The results showed that radiation-induced graft polymerization on pellets were successfully obtained and the influence of dose irradiated did not change the thermal properties in spite of the increase in the MFI and consequently this increase in the viscosity results an decrease the molecular mass. The MFI for grafted pellets was not achievable because the high degree of viscosity of polymer, even arising the test temperature, the polymer was not flow enough. (author)

  17. Radiation-induced polymerization and radiation effect on polymers

    International Nuclear Information System (INIS)

    Seguchi, Tadao

    1977-12-01

    The processes of radiation-induced polymerization of monomers and also radiation effects on polymers have been studied by instrumental analyses of electron spin resonance (ESR), nuclear magnetic resonance (NMR) and electron microscopy. In radiation-induced polymerization, graft-copolymerization and absorbed state polymerization were taken up. For graft-copolymerization, monomers such as methylmethacrylate and butadiene were made to react with irradiated polyethylene, and behaviors of the initiating radicals and propagating radicals were followed under the reaction by ESR. For absorbed state polymerization, acrylonitrile/zeolite and methylmethacrylate/zeolite were chosen. Absorbed monomers were irradiated at 77 0 K and polymerized at room temperature. Active species and the concentrations were measured by ESR and the yields of polymer were observed by NMR. In radiation effect on polymers, polyvinylfluoride, polyvinylidenfluoride and polytetrafluoroethylene were taken up. Active species trapped in the polymer matrixes were identified and decay and reactivity of the species were also studied. On the basis of information from the electron microscopy and x-ray analysis, radiation effects on these polymers are described. In polytetrafluoroethylene produced by radiation polymerization, the relation between morphology and polymerization conditions and also the process of crystallization during polymerization were studied. (auth.)

  18. Characterization of radiation-induced emesis in the ferret

    International Nuclear Information System (INIS)

    King, G.L.

    1988-01-01

    Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral 60 Co gamma radiation at 100 cGy min-1 at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED50 was calculated at 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously or subcutaneously with 30 to 300 micrograms/kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n = 4) or 401 (n = 4) cGy radiation and their emetic responses were compared with NaCl-injected-irradiated controls (n = 8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species

  19. ROS Mediates Radiation-Induced Differentiation in Human Lung Fibroblast

    International Nuclear Information System (INIS)

    Park, Sa Rah; Ahn, Ji Yeon; Kim, Mi Hyeung; Lim, Min Jin; Yun, Yeon Sook; Song, Jie Young

    2009-01-01

    One of the most common tumors worldwide is lung cancer and the number of patients with lung cancer received radiotherapy is increasing rapidly. Although radiotherapy may have lots of advantages, it can also induce serious adverse effects such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of smooth muscle actin-alpha (a-SMA) and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-b), tumor necrosis factor (TNF), IL-6, platelet-derived growth factor (PDGF) and reactive oxygen species are related to fibrosis. It is also reported that reactive oxygen species (ROS) can be induced by radiation and can act as a second messenger in various signaling pathways. Therefore we focused on the role of ROS in radiation induced fibrosis. Here, we suggest that irradiation generate ROS mainly through NOX4, result in differentiation of lung fibroblast into myofibroblast

  20. Origin of specific chromosome aberration in radiation-induced leukemia

    International Nuclear Information System (INIS)

    Ban, Nobuhiko; Kai, Michiaki; Masuno, Yoko

    2005-01-01

    The theme in the title is discussed from the four aspects of specific chromosome aberration (sAb) patterns in radiation-induced leukemia (RIL), possibility for radiation to induce the sAb in RIL, any evidence for participation of delayed aberration to form sAb and the proportion of such healthy humans as having the specifically rearranged genome. Data of sAb observed in leukemia of 25 A-bomb survivors and of 38 patients post radiotherapy of cancers give a rather common pattern. However, many inconsistent results are obtained for sAb in patients post radiotherapy, A-bomb survivors, residents living in radio-contaminated houses in Taipei, in vitro exposure, and Chernobyl residents. At present, any clear evidence is available neither for sAb derived from the delayed aberration nor for estimating the proportion with the specifically rearranged gene. As above, it is unlikely that radiation induces such a translocation abnormality as BCR-ABL specifically seen in leukemia, and this aspect will be important for studies on the genesis of RIL and its risk assessment. (S.I.)

  1. Radiation induced segregation and point defects in binary copper alloys

    International Nuclear Information System (INIS)

    Monteiro, W.A.

    1984-01-01

    Considerable progress, both theoretical and experimental, has been made in establishing and understanding the influence of factors such as temperature, time, displacement rate dependence and the effect of initial solute misfit on radiation induced solute diffusion and segregation. During irradiation, the composition of the alloy changes locally, due to defect flux driven non-equilibrium segregation near sinks such as voids, external surfaces and grain boundaries. This change in composition could influence properties and phenomena such as ductility, corrosion resistance, stress corrosion cracking, sputtering and blistering of materials used in thermo-nuclear reactors. In this work, the effect of 1 MeV electron irradiation on the initiation and development of segregation and defect diffusion in binary copper alloys has been studied in situ, with the aid of a high voltage electron microscope. The binary copper alloys had Be, Pt and Sn as alloying elements which had atomic radii less than, similar and greater than that of copper, respectively. It has been observed that in a wide irradiation temperature range, stabilization and growth of dislocation loops took place in Cu-Sn and Cu-Pt alloys. Whereas in the Cu-Be alloy, radiation induced precipitates formed and transformed to the stable γ phase. (Author) [pt

  2. International Activities in Radiation-Induced Carcinogenesis. Survey Paper

    Energy Technology Data Exchange (ETDEWEB)

    Komarov, E. [World Health Organization, Geneva (Switzerland)

    1969-11-15

    During the past 10 years special attention has been paid to the problem of late effects of radiation and in particular to radiation-induced carcinogenesis and leukaemogenesis. In the UNSCEAR report of 1958-1962 this.problem was mentioned as being of considerable importance from the point of view of estimation of risk to the population from environmental radiation. In 1964 a special report was prepared by UNSCEAR on radiation- induced carcinogenesis. In the ICRP publication No. 8, a chapter dealing with assessment of somatic risks discussed the problem of leukaemia and other neoplasms and particularly stressed the problem of thyroid carcinoma-and bone sarcoma. WHO panels of experts discussed the problem in 1960-1966 and made some recommendations for international activity in this field. In spite of the amount of scientific attention that has been given in recent years to experimental radiobiology in animals and lower forms, it has become abundantly clear that information directly applicable to humans is woefully inadequate and that there is a desperate need for carefully collected data from man on which to base public health planning and day to day work in radiation protection. This has long been recognized in the technical program of WHO in the emphasis given to the practical importance of epidemiology in human radiobiology and the degree to which it depends upon international collaboration.

  3. Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

    OpenAIRE

    Maimaitili, Aisha; Shu, Zunhua; Cheng, Xiaojiang; Kaheerman, Kadeer; Sikandeer, Alifu; Li, Weimin

    2016-01-01

    The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphen...

  4. Knock-down of ABCE1 gene induces G1/S arrest in human oral cancer cells

    OpenAIRE

    Wang, Lei; Zhang, Mei; Liu, Dong-Xu

    2014-01-01

    Purpose: This study aims to explore the clinical characteristics of ATP binding cassette E1 (ABCE1) in oral squamous cell carcinomas (OSCC) and its roles in the proliferation, invasiveness, migration and apoptosis of the human oral squamous cell carcinoma cells CAL-27. Methods: The expression of ABCE1 and its target protein-RNase L, were first studied in tumor tissues of OSCC and adjacent non-tumor tissues. Moreover, CAL-27cells were transfected by ABCE1-specific shRNA, then MTT assay, the tr...

  5. Mutations in cyr1 and pat1 reveal pheromone-induced G1 arrest in the fission yeast Schizosaccharomyces pombe

    DEFF Research Database (Denmark)

    Davey, William John; Nielsen, O; Nielsen, Olaf

    1994-01-01

    Investigations into sexual differentiation and pheromone response in the fission yeast Schizosaccharomyces pombe are complicated by the need to first starve the cells of nitrogen. Most mating-related experiments are therefore performed on non-dividing cells. Here we overcome this problem by using...

  6. The transcription factor Swi4 is target for PKA regulation of cell size at the G1 to S transition in Saccharomyces cerevisiae.

    Science.gov (United States)

    Amigoni, Loredana; Colombo, Sonia; Belotti, Fiorella; Alberghina, Lilia; Martegani, Enzo

    2015-08-03

    To investigate the specific target of PKA in the regulation of cell cycle progression and cell size we developed a new approach using the yeast strain GG104 bearing a deletion in adenylate cyclase gene and permeable to cAMP ( cyr1Δ, pde2Δ, msn2Δ, msn4Δ). In this strain the PKA activity is absent and can be activated by addition of cAMP in the medium, without any other change of the growth conditions. In the present work we show that the activation of PKA by exogenous cAMP in the GG104 strain exponentially growing in glucose medium caused a marked increase of cell size and perturbation of cell cycle with a transient arrest of cells in G1, followed by an accumulation of cells in G2/M phase with a minimal change in the growth rate. Deletion of CLN1 gene, but not of CLN2, abolished the transient G1 phase arrest. Consistently we found that PKA activation caused a transcriptional repression of CLN1 gene. Transcription of CLN1 is controlled by SBF and MBF dual-regulated promoter. We found that also the deletion of SWI4 gene abolished the transient G1 arrest suggesting that Swi4 is a target responsible for PKA modulation of G1/S phase transition. We generated a SWI4 allele mutated in the consensus site for PKA (Swi4(S159A)) and we found that expression of Swi4(S159A) protein in the GG104-Swi4Δ strain did not restore the transient G1 arrest induced by PKA activation, suggesting that Swi4 phosphorylation by PKA regulates CLN1 gene expression and G1/S phase transition.

  7. Runway Arrested Landing Site (RALS)

    Data.gov (United States)

    Federal Laboratory Consortium — The Runway Arrested Landing Site includes an underground complex located on a Mod 2, Mod 3, and Mod 3+ arresting gear and are located under the runway and accurately...

  8. The M/G/1 queue with permanent customers

    NARCIS (Netherlands)

    Boxma, O.J.; Cohen, J.W.

    1991-01-01

    The authors examine an M/G/1 FCFS (first come, first served) queue with two types of customers: ordinary customers, who arrive according to a Poisson process, and permanent customers, who immediately return to the end of the queue after having received a service. The influence of the permanent

  9. Nonparametric inference from the M/G/1 workload

    DEFF Research Database (Denmark)

    Hansen, Martin Bøgsted; Pitts, Susan M.

    2006-01-01

    Consider an M/G/1 queue with unknown service-time distribution and unknown traffic intensity ρ. Given systematically sampled observations of the workload, we construct estimators of ρ and of the service-time distribution function, and we study asymptotoic properties of these estimators....

  10. Nonparametric inference from the M/G/1 workload

    DEFF Research Database (Denmark)

    Hansen, Martin Bøgsted; Pitts, Susan M.

    Consider an M/G/1 queue with unknown service-time distribution and unknown traffic intensity $\\rho$. Given systematically sampled observations of the workload, we construct estimators of $\\rho$ and of the service-time distribution function, and we study asymptotic properties of these estimators....

  11. 26 CFR 1.167(g)-1 - Basis for depreciation.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Basis for depreciation. 1.167(g)-1 Section 1.167... for depreciation. The basis upon which the allowance for depreciation is to be computed with respect... property at that time, is the basis for computing depreciation. [T.D. 6500, 25 FR 11402, Nov. 26, 1960...

  12. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    Science.gov (United States)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  13. Effectiveness of the herbal medicine daikenchuto for radiation-induced enteritis.

    Science.gov (United States)

    Takeda, Takashi; Kamiura, Shouji; Kimura, Tadashi

    2008-07-01

    Radiation-induced enteritis is a serious clinical problem for which there is currently no recommended standard management. Daikenchuto (DKT) is a Japanese herbal medicine that has been used to treat adhesive bowel obstruction in Japan. This report describes a patient with radiation-induced enteritis whose clinical symptoms were much improved by treatment with DKT. The patient was administered DKT, a traditional Japanese herbal formula, orally (2.5 g 3 times daily). Abdominal distention was evaluated objectively with computed tomography. Gastrointestinal symptoms associated with radiation-induced enteritis were controlled successfully with DKT treatment. DKT treatment may be useful for the management of radiation-induced enteritis.

  14. Radiation-induced Pulmonary Damage in Lung Cancer Patients

    International Nuclear Information System (INIS)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Mi Mun; Kim, In Ah; Shinn, Kyung Sub

    1993-01-01

    Purpose: A retrospective analysis was performed to evaluate the incidence of radiation induced lung damage after the radiation therapy for the patients with carcinoma of the lung. Method and Materials: Sixty-six patients with lung cancer (squamous cell carcinoma 27, adenocarcinoma 14, large cell carcinoma 2, small cell carcinoma 13, unknown 10) were treated with definitive, postoperative or palliative radiation therapy with or without chemotherapy between July 1987 and December 1991. There were 50 males and 16 females with median age of 63 years(range: 33-80 years). Total lung doses ranged from 500 to 6,660 cGy (median 3960 cGy) given in 2 to 38 fractions (median 20) over a range of 2 to 150 days (median 40 days) using 6 MV or 15 MV linear accelerator. To represent different fractionation schedules of equivalent biological effect, the estimated single dose(ED) model, ED=D·N-0.377·T-0.058 was used in which D was the lung dose in cGy, N was the number of fractions, and T was the overall treatment time in days. The range of ED was 370 to 1357. The endpoint was a visible increase in lung density within the irradiated volume on chest X-ray as observed independently by three diagnostic radiologists. Patients were grouped according to ED, treatment duration, treatment modality and age, and the percent incidence of pulmonary damage for each group was determined. Result: In 40 of 66 patients, radiation induced change was seen on chest radiographs between 11 days and 314 days after initiation of radiation therapy. The incidence of radiation pneumonitis was increased according to increased ED, which was statistically significant (p=0.001). Roentgenographic charges consistent with radiation pneumonitis were seen in 100% of patients receiving radiotherapy after lobectomy or pneumonectomy, which was not statistically significant. In 32 patients who also received chemotherapy, there was no difference in the incidence of radiation induced charge between the group with radiation

  15. Hereditary Factors Involved in Radiation-Induced Leukaemogenesis

    International Nuclear Information System (INIS)

    Duplan, J.F.

    1969-01-01

    The hereditary factors involved in radiation-induced leukaemogenesis were studied in pure AKR and C57BL strains, their first-generation hybrids and their back-crosses. It is known that the heredity of spontaneous lymphoid leukaemias is attributable to hereditary factors, of which only some are chromosomal, and the same situation can be considered to exist as regards the heredity of radiation-induced leukoses. In order to identify the various chromosomal and non-chromosomal factors concerned, three types of experiment were conducted with the pure strains and with each of the crosses, intended to evaluate (a) the incidence of spontaneous lymphoid leukoses, (b) the incidence of radiation-induced leukoses and (c) the inhibition of radioleukaemo- genesis by the injection of isogenic haematopoietic cells. The results show that the main non-chromosomal factor is the leukaemogenic Gross virus (VG) in the case of the AKR strain and the radioleukaemia virus (VRL) in that of the C57BL strain; these two agents are transmitted by the mother to her progeny. The VG may be responsible for radioleukaemias as well as for spontaneous leukoses, but the VRL does not produce spontaneous leukaemias even in back-crosses possessing a substantial fraction of the AKR genome, which is particularly conducive to leukaemogenesis. Restoration using C57BL bone marrow brings about a distinct inhibition of leukaemogenesis in all animals deriving from crossings for which this material is histocompatible; AKR marrow, however, never exhibits any restorative activity. Three hypotheses may be put forward to explain these results. The first is that C57BL bone marrow contains many more precursor elements than AKR marrow, these cells being necessary for inhibition of the leukaemogenic process. The second hypothesis is that the AKR strain lacks a factor which is essential for the utilization of these precursors. Finally the third hypothesis, which seems the least probable, is that AKR cells are much more

  16. Effect of pH on radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Chang, W. Song; Park, Heon J.; Lyons, John C.; Auger, Elizabeth A.; Lee, Hyung-Sik

    1996-01-01

    Purpose/Objective: The effect of environmental pH on the radiation-induced apoptosis in tumor cells in vitro was investigated. Materials and Methods: SCK mammary adenocarcinoma cells of A/J mice were irradiated with γ-rays using a 137 Cs irradiator and incubated in media of different pHs. After incubation at 37 degree sign C for 24-120 hrs., the extent of apoptosis was determined using agarose gel electrophoresis of DNA, in situ TUNEL staining, flow cytometry, and release of 3 H from 3 H-thymidine labeled cells. The membrane integrity, using the trypan blue exclusion method, and the clonogenicity of the cells were also determined. Results: Irradiation with 2-12 Gy of γ-rays induced apoptosis in pH 7.5 medium within 48 hrs. The radiation-induced apoptosis progressively declined as the medium pH was lowered so that little apoptosis occurred in 48 hrs. after irradiation with 12 Gy in pH 6.6 medium. However, when the cells were irradiated and incubated for 48 hrs. in pH 6.6 medium and then medium was replaced with pH 7.5 medium, apoptosis promptly occurred. Apoptosis also occurred even in pH 6.6 medium when the cells were irradiated and maintained in pH 7.5 medium for 8 hrs. or longer post-irradiation before incubation in pH 6.6 medium. Conclusion: An acidic environment markedly suppresses radiation-induced apoptosis probably by suppressing the expression of initial signals responsible for irradiation-induced apoptosis. Indications are that the signals persist in an acidic environment and trigger apoptosis when the environmental acidity is eased. Our results suggest that the acidic environment in human tumors may inhibit the apoptosis after irradiation. However, apoptosis may be triggered when reoxygenation occurs after irradiation, and thus, the intratumor environment becomes less acidic after irradiation. Not only the change in pO 2 but the change in pH during the course of fractionated radiotherapy may greatly influence the outcome of the treatment

  17. Sequential activation of proteases in radiation induced apoptosis

    International Nuclear Information System (INIS)

    Watters, D.; Waterhouse, N.

    1997-01-01

    Full text: Significant advances have been made in recent years in unraveling the molecular mechanisms of apoptosis particularly in relation to Fas- and TNF-mediated cell death, however there are considerable gaps in our knowledge of the processes involved in apoptosis induced by ionizing radiation. We have used the degradation of specific proteolytic targets in a pair of isogenic Burkitt's Iymphoma cells lines (BL30A, sensitive and BL30K resistant) to study the sequence of events in the execution of radiation-induced apoptosis. Fodrin can be cleaved to fragments of 150 kDa and 120 kDa. In the case of Fas-mediated apoptosis both cleavages are inhibited by the caspase inhibitor zVAD-fmk at 10 μM, a concentration which inhibits all the hallmarks of apoptosis. However in radiation-induced apoptosis, inhibition of the clevage of fodrin to the 150 kDa fragment requires 100 μM zVAD-fink while apoptosis itself is inhibited at 10 μM. This suggests that different enzymes are responsible for the generation of the 150 kDa fragment in the two models of apoptosis. Fodrin has been reported to be cleaved by μ-calpain to a 150 kDa fragment however, the involvement of μ-calpain in apoptosis has not yet been established. In murine fodrin there is a caspase cleavage site within 1 kDa of the calpain cleavage site. In vitro studies using purified enzymes showed that only caspase-3 and μ-calpain could cleave fodrin in untreated cell extracts to the same sized fragments as seen during apoptosis in vivo. We provide evidence for the early activation of μ-calpain after ionizing radiation in the sensitive BL30A cell line, and show that the time course of μ-calpain activation parallels that of the appearance of the 150 kDa fragment. Caspase-3 is activated much later and is likely to be responsible for the generation of the 120 kDa fragment. μ-Calpain was not activated in the resistant cell line. Based on these results we propose a model for the proteolytic cascade in radiation-induced

  18. Ionizing radiation induced transcriptional changes in the developing mouse brain. Doctoral Thesis Prepared at SCK-CEN and Defended in 2006

    International Nuclear Information System (INIS)

    Verheyde, J.

    2007-01-01

    radiation exposure. The Trp53 null mutants at this stage exhibited a decreased expression profile for various Cyclins and Cyclin-dependent kinases, suggesting the induction of a Trp53 independent cell cycle arrest. The observed absence of high levels of apoptosis is in concordance with the described phenotype of Trp53 null mutant mice that show an increased risk for tumour formation. Next, we questioned if the developing brain is characterized by a regional dependent differences on radiation sensitivity. Therefore, additional transcriptional analyses of the different regions (hippocampus, pallidal neuroepithelium and cortex of control and irradiated brain embryos) of the ventral wild type brain at E15 were performed. In these three regions of the developing brain, the differential expression of Trp53inp1 and Ccng1 by in situ hybridization suggested that the ventral brain shows a specific regional dependent expression pattern. This was further evidenced by real time qPCR, by which it also became clear that the strongest radiation induced effect can be observed in the cerebral cortex. However, this experiment didn't allow making a distinction between neural cells in this experiment, and different cell types contribute to correct neural network formation. Detailed analysis of cultured and irradiated neural cell types indicated that the expression of the Trp53inp1/Hipk2 and Ccng1/Mdm2/P19Arf signalling pathways are activated in a cell-type dependent matter. From this data it appears that, depending on the cell type and the stage of differentiation, two possible mechanisms for the induction of apoptosis are activated. In one hand cell cycle arrest occurs via P21 (Cdkn1a) induction and to certain extends via P19ARF in the mitotic astrocytes, while in short-term neurons this mechanism seems to be preferentially induced by Cyclin G1. This arrest is then followed by the induction of the mitochondrial proapoptotic pathway. Interestingly, long term cultured neurons show also an

  19. Dose-dependent and gender-related radiation-induced transcription alterations of Gadd45a and Ier5 in human lymphocytes exposed to gamma ray emitted by 60Co

    International Nuclear Information System (INIS)

    Tavakoli, H.; Manoochehri, M.; Mosalla, S. M. M.; Ghafori, M.; Karimi, A. A.

    2013-01-01

    Growth arrest DNA damage-inducible 45a gene (Gadd45a) and immediate early response gene 5 (Ier5) have been emphasised as ideal radiation bio-markers in several reports. However, some aspects of radiation-induced transcriptional alterations of these genes are unknown. In this study, gender-dependency and dose-dependency as two factors that may affect radiation induced transcription of Gadd45a and Ier5 genes were investigated. Human lymphocyte cells from six healthy voluntary blood donors (three women and three men) were irradiated in vitro with doses of 0.5-4.0 Gy from a 60 Co source and RNA isolated 4 h later using the High Pure RNA Isolation Kit. Dose and gender dependency of radiation-induced transcriptional alterations of Gadd45a and Ier5 genes were studied by quantitative real-time polymerase chain reaction. The results showed that as a whole, Gadd45a and Ier5 gave responses to gamma rays, while the responses were independent of radiation doses. Therefore, regardless of radiation dose, Gadd45a and Ier5 can be considered potential radiation bio-markers. Besides, although radiation-induced transcriptional alterations of Gadd45a in female and male lymphocyte samples were insignificant at 0.5 Gy, at other doses, their quantities in female samples were at a significantly higher level than in male samples. Radiation induced transcription of Ier5 of females samples had a reduction in comparison with male samples at 1 and 2 Gy, but at doses of 0.5 and 4 Gy, females were significantly more susceptible to radiation-induced transcriptional alteration of Ier5. (authors)

  20. γ-radiation induces cellular sensitivity and aberrant methylation in human tumor cell lines.

    Science.gov (United States)

    Kumar, Ashok; Rai, Padmalatha S; Upadhya, Raghavendra; Vishwanatha; Prasada, K Shama; Rao, B S Satish; Satyamoorthy, Kapettu

    2011-11-01

    Ionizing radiation induces cellular damage through both direct and indirect mechanisms, which may include effects from epigenetic changes. The purpose of this study was to determine the effect of ionizing radiation on DNA methylation patterns that may be associated with altered gene expression. Sixteen human tumor cell lines originating from various cancers were initially tested for radiation sensitivity by irradiating them with γ-radiation in vitro and subsequently, radiation sensitive and resistant cell lines were treated with different doses of a demethylating agent, 5-Aza-2'-Deoxycytidine (5-aza-dC) and a chromatin modifier, Trichostatin-A (TSA). Survival of these cell lines was measured using 3-(4, 5-Dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium (MTT) and clonogenic assays. The effect of radiation on global DNA methylation was measured using reverse phase high performance liquid chromatography (RP-HPLC). The transcription response of methylated gene promoters, from cyclin-dependent kinase inhibitor 2A (p16(INK4a)) and ataxia telangiectasia mutated (ATM) genes, to radiation was measured using a luciferase reporter assay. γ-radiation resistant (SiHa and MDAMB453) and sensitive (SaOS2 and WM115) tumor cell lines were examined for the relationship between radiation sensitivity and DNA methylation. Treatment of cells with 5-aza-dC and TSA prior to irradiation enhanced DNA strand breaks, G2/M phase arrest, apoptosis and cell death. Exposure to γ-radiation led to global demethylation in a time-dependent manner in tumor cells in relation to resistance and sensitivity to radiation with concomitant activation of p16(INK4a) and ATM gene promoters. These results provide important information on alterations in DNA methylation as one of the determinants of radiation effects, which may be associated with altered gene expression. Our results may help in delineating the mechanisms of radiation resistance in tumor cells, which can influence diagnosis, prognosis and

  1. The fate of radiation induced giant-nucleated cells of human skin fibroblasts

    Science.gov (United States)

    Almahwasi, A. A.; Jeynes, J. C.; Bradley, D. A.; Regan, P. H.

    2017-11-01

    Radiation-induced giant-nucleated cells (GCs) have been observed to occur within survivors of irradiated cancerous and within healthy cells, both in vivo and in vitro. The expression of such morphological alterations is associated with genomic instability. This study was designed to investigate the fate of GCs induced in a normal human fibroblast cell line (AG1522) after exposure to 0.2, 1 or 2 Gy of X-ray or proton irradiation. The total of 79 individual AG1522 GCs present at 7, 14 or 21 days after each dose point were analysed from fluorescence microscopy images captured over approximately 120 h. The GCs were identified at the beginning of the observation period for each time point post-irradiation and the area of the cell nucleus was measured (μm2) using a cell-recognition MATLAB code. The results demonstrate that the majority of GCs had undergone a prolonged mitotic arrest, which might be an indication of the survival strategy. The live cell microscopy confirms that a giant-nucleated cell formed 14 days after exposure to 0.2 Gy of proton irradiation was divided into two asymmetrical normal-sized cells. These results suggest that a small fraction of GCs can proliferate and form progeny. Some of GCs had disappeared from the microscopy fields. The rate of their loss was decreased as the dose increased but there remains the potential for them to have progeny that could continue to proliferate, ultimately contributing to development of cancer risk. This important method to access delayed effects in normal tissues could act as a potential radioprotective assay for a dose-limiting parameter when applying radiotherapy. These results might have important implications in evaluating risk estimates for patients during radiation therapy treatment.

  2. Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells.

    Science.gov (United States)

    Voos, Patrick; Fuck, Sebastian; Weipert, Fabian; Babel, Laura; Tandl, Dominique; Meckel, Tobias; Hehlgans, Stephanie; Fournier, Claudia; Moroni, Anna; Rödel, Franz; Thiel, Gerhard

    2018-01-01

    Impairment or stimulation of the immune system by ionizing radiation (IR) impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation and alters functional properties of these immune cells, we exposed human immortalized Jurkat cells and peripheral blood lymphocytes (PBL) to X-ray doses between 0.1 and 5 Gy. This resulted in cellular responses, which are typically observed also in naïve T-lymphocytes in response of T-cell receptor immune stimulation or mitogens. These responses include oscillations of cytosolic Ca 2+ , an upregulation of CD25 surface expression, interleukin-2 and interferon-γ synthesis, elevated expression of Ca 2+ sensitive K + channels and an increase in cell diameter. The latter was sensitive to inhibition by the immunosuppressant cyclosporine A, Ca 2+ buffer BAPTA-AM, and the CDK1-inhibitor RO3306, indicating the involvement of Ca 2+ -dependent immune activation and radiation-induced cell cycle arrest. Furthermore, on a functional level, Jurkat and PBL cell adhesion to endothelial cells was increased upon radiation exposure and was highly dependent on an upregulation of integrin beta-1 expression and clustering. In conclusion, we here report that IR impacts on immune activation and functional properties of T-lymphocytes that may have implications in both toxic effects and treatment response to combined radiation and immune therapy in cancer patients.

  3. Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells

    Directory of Open Access Journals (Sweden)

    Patrick Voos

    2018-04-01

    Full Text Available Impairment or stimulation of the immune system by ionizing radiation (IR impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation and alters functional properties of these immune cells, we exposed human immortalized Jurkat cells and peripheral blood lymphocytes (PBL to X-ray doses between 0.1 and 5 Gy. This resulted in cellular responses, which are typically observed also in naïve T-lymphocytes in response of T-cell receptor immune stimulation or mitogens. These responses include oscillations of cytosolic Ca2+, an upregulation of CD25 surface expression, interleukin-2 and interferon-γ synthesis, elevated expression of Ca2+ sensitive K+ channels and an increase in cell diameter. The latter was sensitive to inhibition by the immunosuppressant cyclosporine A, Ca2+ buffer BAPTA-AM, and the CDK1-inhibitor RO3306, indicating the involvement of Ca2+-dependent immune activation and radiation-induced cell cycle arrest. Furthermore, on a functional level, Jurkat and PBL cell adhesion to endothelial cells was increased upon radiation exposure and was highly dependent on an upregulation of integrin beta-1 expression and clustering. In conclusion, we here report that IR impacts on immune activation and functional properties of T-lymphocytes that may have implications in both toxic effects and treatment response to combined radiation and immune therapy in cancer patients.

  4. Proteome analysis of Radiation-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    Song, Jie Young; Lim, Hee Soon; Kim, Hyung Doo; Shim, Ji Young; Han, Young Soo; Son, Hyeog Jin Son; Yun, Yeon Sook

    2005-01-01

    Pulmonary fibrosis is perhaps the most universal late effect of organ damage after both chemical insult and irradiation in the treatment of lung cancer. The use chemotherapy and radiation therapy, alone or combined, can be associated with clinically significant pulmonary toxicity, which leads to pneumonia and pulmonary fibrosis. It is also reported that about 100,000 people in the United States are suffered from pulmonary fibrosis. Therefore, pulmonary fibrosis will be more focused by medicinal researchers. Because current therapies, aimed at inhibiting pulmonary inflammation that often precedes fibrosis, are effective only in a minority of suffered patients, novel therapeutic methods are highly needed. Some researchers have used bleomycininduced pulmonary fibrosis as a basis for looking at the molecular mechanisms of fibrosis, and total gene expression was monitored using genomics method. However, radiation-induced pulmonary fibrosis has not been fully focused and investigated. Here, we have analyzed changes in gene expression in response to γ- irradiation by using proteomic analysis

  5. Acupuncture treatment of patients with radiation-induced xerostomia

    International Nuclear Information System (INIS)

    Blom, M.; Dawidson, I.; Johnson, G.; Angmar-Maansson, B.; Fernberg, J.-O.

    1996-01-01

    Xerostomia is a common and usually irreversible side effect in patients receiving radiation therapy (>50 Gy) for head and neck cancer. Of 38 patients with radiation-induced xerostomia, 20 in the experimental group were treated with classical acupuncture and 18 patients in the control group received superficial acupuncture as placebo. Within both groups the patients showed significantly increased salivary flow rates after the acupuncture treatment. In the experimental group 68% and in the control group 50% of the patients had increased salivary flow rates at the end of the observation period. Among those patients who had had all their salivary glands irradiated, 50% in both groups showed increased salivary flow rates (>20%) by the end of the observation period of 1 year. The study indicates that among the patients who had increased salivary flow rates already after the first 12 acupuncture sessions, the majority had high probability of continual improvement after the completion of acupuncture treatment. (Author)

  6. Acupuncture treatment of patients with radiation-induced xerostomia

    Energy Technology Data Exchange (ETDEWEB)

    Blom, M.; Dawidson, I.; Johnson, G.; Angmar-Maansson, B. [Karolinska Inst., Huddinge (Sweden). Dept. of Cardiology; Fernberg, J.-O. [Karolinska Hospital, Stockholm (Sweden). Dept. of General Oncology

    1996-05-01

    Xerostomia is a common and usually irreversible side effect in patients receiving radiation therapy (>50 Gy) for head and neck cancer. Of 38 patients with radiation-induced xerostomia, 20 in the experimental group were treated with classical acupuncture and 18 patients in the control group received superficial acupuncture as placebo. Within both groups the patients showed significantly increased salivary flow rates after the acupuncture treatment. In the experimental group 68% and in the control group 50% of the patients had increased salivary flow rates at the end of the observation period. Among those patients who had had all their salivary glands irradiated, 50% in both groups showed increased salivary flow rates (>20%) by the end of the observation period of 1 year. The study indicates that among the patients who had increased salivary flow rates already after the first 12 acupuncture sessions, the majority had high probability of continual improvement after the completion of acupuncture treatment. (Author).

  7. Contribution of bystander effects in radiation induced genotoxicity

    International Nuclear Information System (INIS)

    Zhou, H.; Persaud, R.; Gillispie, J.; Randers-Pehrson, G.; Hei, T.K.; Suzuki, Masao

    2005-01-01

    The controversial use of a linear, no threshold extrapolation model for low dose risk assessment is based on the accepted dogma that the deleterious effects of ionizing radiation such as mutagenesis and carcinogenesis are attributable mainly to direct damage to DNA. However, this extrapolation was challenged by the recent reports on the bystander phenomenon. The bystander effect contributes to this debate by implying that the biological effects of low doses, where not all cells are traversed by a charged particle, are amplified by the transfer of factors to un-irradiated neighbors. This interested phenomenon implies that a linear extrapolation of risks from high to low doses may underestimate rather than over estimate low dose risks. Together with some radiation-induced phenomena such as adaptive response and genomic instability, the radiobiological response at low doses is likely to be a complex interplay among many factors. (author)

  8. Radiation-induced degradation of 4-chloroaniline in aqueous solution

    International Nuclear Information System (INIS)

    Sanchez, M.; Wolfger, H.; Getoff, N.

    2002-01-01

    The radiation-induced decomposition of 4-chloroaniline (4-ClA) was studied under steady-state conditions using aqueous solutions saturated with air, pure oxygen, N 2 O, argon and argon in the presence of t-Butanol. Using HPLC-method, the initial G-values of the substrate degradation as well as of a number of radiolytic products were determined. The formation of aminophenols, chlorophenols, aniline and phenol in addition to chloride, ammonia, formaldehyde and mixture of aldehydes as well as carboxylic acids was studied as a function of absorbed dose. Based on the experimental data, probable reaction mechanisms for the degradation of 4-ClA by γ-rays and the formation of the identified products are presented

  9. Radiation-induced decomposition of anion exchange resins

    International Nuclear Information System (INIS)

    Baidak, Aliaksandr; LaVerne, Jay A.

    2010-01-01

    Radiation-induced degradation of the strongly basic anion exchange resin Amberlite TM IRA400 in NO 3 - , Cl - and OH - forms has been studied. The research focused on the formation of molecular hydrogen in the gamma-radiolysis of water slurries of these quaternary ammonium resins with varying water content. Extended studies with various electron scavengers (NO 3 - , N 2 O and O 2 ) prove an important role of e solv - in the formation of H 2 from these resins. An excess production of H 2 in these systems at about 85% water weight fraction was found to be due to trimethylamine, dimethylamine and other compounds that leach from the resin to the aqueous phase. Irradiations with 5 MeV 4 He ions were performed to simulate the effects of α-particles.

  10. Structure and radiation induced swelling of steels and alloys

    International Nuclear Information System (INIS)

    Parshin, A.M.

    1983-01-01

    Regularities of vacancy void formation and radiation induced swelling of austenitic chromium-nickel steels and alloyse ferritic steels as well as titanium α-alloys under radiation by light and heavy ions and neutrons are considered. Possible methods for preparation of alloys with increased resistance to radiation swelling are described. Accounting for investigations into ferritic steels and α-alloys of titanium the basic way of weakening vacancy smelling is development of continuous homogeneous decomposition of solid solution using alloying with vividly expressed incubation period at a certain volumetric dilatation as well as decompositions of the type of ordering, K-state, lamination of solid solutions, etc. Additional alloying of solid solutions is also shown to be necessary for increasing recrystallization temperature of cold-deformed steel

  11. Radiation-induced degradation of chlorophenols in aqueous solution

    International Nuclear Information System (INIS)

    Hu Jun; Wang Jianlong

    2005-01-01

    Radiation processing is a promising technology for applications in environmental protection, which includes wastewater treatment, micro-polluted drinking water treatment and the treatment of industrial wastewater containing various toxic and nonbiodegradable pollutants, municipal sewage and sludge disinfection, and flue gas desulfuration, etc. The paper reviews manly the recent progresses in radiolysis of chlorinated phenols in aqueous solution. Advantages and existing problems of the method in this particular application ar discussed. Mechanisms of radiation-induced degradation of chlorophenols, and the factors affecting the degradation efficiency, are discussed, too. It is concluded that combined approaches, such ozone oxidation and other methods, are of great help to the radiation processing application, in terms of lowering down the dose and increasing the efficient of pollutant removal. (authors)

  12. Radiation-induced spindle cell sarcoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Khan Mubeen

    2009-01-01

    Full Text Available Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.

  13. Induction, development, and inhibition of radiation-induced macrobodies

    International Nuclear Information System (INIS)

    Adam, W.J.; Grunewald, R.

    1975-01-01

    Coleus shoots were exposed to 100,000 R of γ radiation and the fine structure of the apical meristems was examined. Meristems were fixed at various postirradiation times. An ultrastructural body was found associated with irradiated tissue, bound by a single membrane, containing dense osmiophilic bodies, and usually associated with radiation-induced vacuoles. The development of these new bodies, and the effects of both dose rate and light during the postirradiation period on their development were examined. Reduction of the dose rate by a factor of two inhibited the formation of these macrobodies through the 24 hour postirradiation period. Meristems kept in the dark during the 24 hour postirradiation period had macrobodies similar in form to the macrobodies from the meristems of the 16 hour postirradiation period which were exposed to light. Superlethal doses were used to achieve these results. Similarities between our results and those achieved with lower lethal doses are discussed

  14. Controlled release of biofunctional substances by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Yoshida, M.; Kumakura, M.; Kaetsu, I.

    1978-01-01

    The controlled release of potassium chloride from flat circular matrices made by radiation-induced polymerization of a glass-forming monomer at low temperatures has been studied. The water-particle phase content formed in a poly(diethylene glycol dimethacrylate) matrix was controlled by the addition of polyethylene glycol 600. The dispersed water-particle phase content in the matrix was estimated directly and by scanning electron microscopic observations. The release of potassium chloride from the matrix increased linearly with the square root of time. The water content of the matrix had an important effect on the release rate which increases roughly in proportion to water content. This effect can be attributed to the apparent increase of the rate of drug diffusion. (author)

  15. Controlled release of biofunctional substances by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Yoshida, M.; Kumakura, M.; Kaetsu, I.

    1978-01-01

    The release behaviour of a drug from flat circular capsules obtained by radiation-induced polymerization at low temperatures and with different hydrophilic properties has been studied. The effect of various factors on release property was investigated. The release process could be divided into three parts, an initial quick release stage, stationary state release stage and a retarded release stage. Release behaviour in the stationary state was examined using Noyes-Whitney and Higuchi equations. It was shown that the hydrophilic property of polymer matrix expressed by water content was the most important effect on diffusion and release rate. Rigidity of the polymer may also affect diffusivity. The first quick release step could be attributed to rapid dissolution of drug in the matrix surface due to polymer swelling. (author)

  16. Liv. 52 protection against radiation induced lesions in mammalian liver

    International Nuclear Information System (INIS)

    Saini, M.R.; Saini, N.

    1985-01-01

    Effect of Liv. 52 on mammalian liver was studied after whole-body exposure to 5.5 Gy of 60 Co gamma radiation. It was found that the drug protected the organ against radiation-induced changes. The protective effect was manifested in the form of early recovery as indicated by the absence of pathological changes like cytoplasmic degranulation, loss of nulei from many cells and abnormal architecture at 10 days and restoration of normal structure by 4 weeks. Liv. 52 may neutralize the peroxides formed from water molecules after irradiation which are toxic and cause the damage to the organ. Thus it seems that the drug may act as detoxicating agent. (author)

  17. Radiatively induced breaking of conformal symmetry in a superpotential

    International Nuclear Information System (INIS)

    Arbuzov, A.B.; Cirilo-Lombardo, D.J.

    2016-01-01

    Radiatively induced symmetry breaking is considered for a toy model with one scalar and one fermion field unified in a superfield. It is shown that the classical quartic self-interaction of the superfield possesses a quantum infrared singularity. Application of the Coleman–Weinberg mechanism for effective potential leads to the appearance of condensates and masses for both scalar and fermion components. That induces a spontaneous breaking of the initial classical symmetries: the supersymmetry and the conformal one. The energy scales for the scalar and fermion condensates appear to be of the same order, while the renormalization scale is many orders of magnitude higher. A possibility to relate the considered toy model to conformal symmetry breaking in the Standard Model is discussed.

  18. Radiation-induced malignant tumors of skin and their histogenesis

    International Nuclear Information System (INIS)

    Li Guomin; Chen Yunchi; Yang Yejing

    1987-01-01

    Seven cases of radiation-induced malignant tumors and 60 cases of chronic radiation damage of skin are reported. Severe hyperplasia, false epitheliomatoid hyperpiasia and atypical proliferation of epithelia and atypical proliferation of fibrohistocytes were the main changes found in chronic radiation damage of skin. The development of malignant tumors from chronic radiation damage of skin can be divided into 4 periods: necrotic and degenerative change period, benign proliferative period, atypical proliferative period and malignant change period. The incidence of hyperplastic changes of skin is related to the time elapse after irradiation and the integrated dose of radiation. The longer the duration after irradiation and the larger the integrated dose are, the higher will be the incidence of hyperplastic changes

  19. Radiation induced phosphorus segregation in austenitic and ferritic alloys

    International Nuclear Information System (INIS)

    Brimhall, J.L.; Baer, D.R.; Jones, R.H.

    1984-01-01

    The radiation induced surface segregation (RIS) of phosphorus in stainless steel attained a maximum at a dose of 0.8 dpa then decreased continually with dose. This decrease in the surface segregation of phosphorus at high dose levels has been attributed to removal of the phosphorus layer by ion sputtering. Phosphorus is not replenished since essentially all of the phosphorus within the irradiation zone has been segregated to the surface. Sputter removal can explain the previously reported absence of phosphorus segregation in ferritic alloys irradiated at high dosessup(1,2) (>1 dpa) since irradiation of ferritic alloys to low doses has shown measurable RIS. This sputtering phenomenon places an inherent limitation to the heavy ion irradiation technique for the study of surface segregation of impurity elements. The magnitude of the segregation in ferritics is still much less than in stainless steel which can be related to the low damage accumulation in these alloys. (orig.)

  20. Promotion of initiated cells by radiation-induced cell inactivation.

    Science.gov (United States)

    Heidenreich, W F; Paretzke, H G

    2008-11-01

    Cells on the way to carcinogenesis can have a growth advantage relative to normal cells. It has been hypothesized that a radiation-induced growth advantage of these initiated cells might be induced by an increased cell replacement probability of initiated cells after inactivation of neighboring cells by radiation. Here Monte Carlo simulations extend this hypothesis for larger clones: The effective clonal expansion rate decreases with clone size. This effect is stronger for the two-dimensional than for the three-dimensional situation. The clones are irregular, far from a circular shape. An exposure-rate dependence of the effective clonal expansion rate could come in part from a minimal recovery time of the initiated cells for symmetric cell division.

  1. Radiation-induced formation of cavities in amorphous germanium

    International Nuclear Information System (INIS)

    Wang, L.M.; Birtcher, R.C.

    1989-01-01

    Prethinned polycrystalline Ge TEM samples were irradiated with 1.5 MeV Kr + ions at room temperature while structural and morphological changes were observed in situ in the Argonne High Voltage Electron Microscope-Tandem Facility. After a Kr + dose of 1.2x10 14 ions/cm 2 , the irradiated Ge was completely amorphized. A high density of small void-like cavities was observed after a Kr + dose of 7x10 14 ions/cm 2 . With increasing Kr + ion dose, these cavities grew into large holes transforming the irradiated Ge into a sponge-like porous material after 8.5x10 15 ions/cm 2 . The radiation-induced nucleation of void-like cavities in amorphous material is astonishing, and the final structure of the irradiated Ge with enormous surface area may have potential applications

  2. Radiation-induced polymerization for the immobilization of penicillin acylase

    International Nuclear Information System (INIS)

    Boccu, E.; Carenza, M.; Lora, S.; Palma, G.; Veronese, F.M.

    1987-01-01

    The immobilization of Escherichia coli penicillin acylase was investigated by radiation-induced polymerization of 2-hydroxyethyl methacrylate at low temperature. A leak-proof composite that does not swell in water was obtained by adding the cross-linking agent trimethylolpropane trimethacrylate to the monomer-aqueous enzyme mixture. Penicillin acylase, which was immobilized with greater than 70% yield, possessed a higher Km value toward the substrate 6-nitro-3-phenylacetamidobenzoic acid than the free enzyme form (Km = 1.7 X 10(-5) and 1 X 10(-5) M, respectively). The structural stability of immobilized penicillin acylase, as assessed by heat, guanidinium chloride, and pH denaturation profiles, was very similar to that of the free-enzyme form, thus suggesting that penicillin acylase was entrapped in its native state into aqueous free spaces of the polymer matrix

  3. Distraction osteogenesis of radiation-induced orbitozygomatic hypoplasia.

    Science.gov (United States)

    Grover, Ramon; Murray, Dylan; Fialkov, Jeffrey A

    2008-05-01

    In the last decade, the application of distraction osteogenesis to the craniofacial skeleton has grown to include not only deformities of the mandible, but of the midface, palate, dentoalveolar region, and calvarium. A major advantage of distraction osteogenesis lies in the simultaneous soft tissue histogenesis that accompanies the bony distraction process, allowing for potentially lower relapse rates and improved cosmesis. Although this may seem appropriately suited to irradiation-induced deformities of both hard and soft tissues, there is little in the literature as to the efficacy of this technique in patients who have received radiotherapy. To introduce an effective application of this technology, and highlight some advantages and disadvantages of its application in the irradiated craniofacial skeleton, we present a case of distraction osteogenesis of the orbitozygomatic complex in a patient with radiation induced orbitozygomatic hypoplasia.

  4. Radiation-induced bilateral common carotid artery stenosis

    International Nuclear Information System (INIS)

    Kobayashi, Nobuaki; Nakagawa, Yoku; Tashiro, Kunio; Abe, Hiroshi

    1986-01-01

    A case of radiation-induced bilateral common carotid artery stenosis is reported. This 60 years old housewife was hospitalized in 1982 because of sudden onset of mild left hemiparesis. Twenty-five years ago, she underwent radiation therapy of approximately 5,000 rads to the anterior cervical region because of thyroid cancer. Angiograms in 1982 revealed bilateral common carotid artery stenosis, especially in the right common carotid artery, the legion of which were included within the field of radiation performed in 1952. Right thromboendarterectomy was performed in 1983. At operation, slight periarterial fibrosis with calcified arteriosclerotic change was found, and dissection between the thickened intima and the media was not so difficult. Histological change of resected thromboendarterium was similar to the one observed in the pure arteriosclerotic disease. (author)

  5. A review of radiation-induced demagnetization of permanent magnets

    Science.gov (United States)

    Samin, Adib J.

    2018-05-01

    Radiation-induced demagnetization of permanent magnets is important for a number of applications including space missions, particle accelerators and robots designed to carry out rescue missions at nuclear accidents where magnet failure can lead to serious consequences. This topic has been studied by several investigators over the past three decades and in this work, a review of the available literature is conducted and some general conclusions and trends are presented. In short, it can be gleaned that magnetism loss is dependent on the type of radiation, the energy of the incoming particle and the overall dose or fluence. Furthermore, magnetism loss also shows a dependence on the type of the irradiated magnet, the coercivity of the magnet, the demagnetizing field and the temperature of irradiation.

  6. Molecular analysis of radiation-induced mutations in vitro

    International Nuclear Information System (INIS)

    Kronenberg, A.

    1996-01-01

    This review will focus on the nature of specific locus mutations detected in mammalian cells exposed in vitro to different types of ionizing radiations. Ionizing radiation has been shown to produce a wide variety of heritable alterations in DNA. These range from single base pair substitutions to stable loss or translocation of large portions of whole chromosomes. Data will be reviewed for certain test systems that reveal different mutation spectra. Techniques for the analysis of molecular alterations include applications of the polymerase chain reaction, some of which may be coupled with DNA sequence analysis, and a variety of hybridization-based techniques. The complexity of large scale rearrangements is approached with cytogenetic techniques including high resolution banding and various applications of the fluorescence in situ hybridization (FISH) technique. Radiation-induced mutant frequencies and mutation spectra are a function of the linkage constraints on the recovery of viable mutants for a given locus and test system. 44 refs

  7. Kinetics of radiation-induced precipitation at the alloy surface

    Science.gov (United States)

    Lam, N. Q.; Nguyen, T.; Leaf, G. K.; Yip, S.

    1988-05-01

    Radiation-induced precipitation of a new phase at the surface of an alloy during irradiation at elevated temperatures was studied with the aid of a kinetic model of segregation. The preferential coupling of solute atoms with the defect fluxes gives rise to a strong solute enrichment at the surface, which, if surpassing the solute solubility limit, leads to the formation of a precipitate layer. The moving precipitate/matrix interface was accommodated by means of a mathematical scheme that transforms spatial coordinates into a reference frame in which the boundaries are immobile. Sample calculations were performed for precipitation of the γ'-Ni 3Si layer on Ni-Si alloys undergoing electron irradiation. The dependences of the precipitation kinetics on the defect-production rate, irradiation temperature, internal defect sink concentration and alloy composition were investigated systematically.

  8. Radiation induced defects and thermoluminescence mechanism in aluminum oxide

    Energy Technology Data Exchange (ETDEWEB)

    Atobe, K.; Kobayashi, T.; Awata, T. [Naruto Univ. of Education, Tokushima (Japan); Okada, M. [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst; Nakagawa, M. [Kagawa Univ., Faculty of Education, Takamatsu, Kagawa (Japan)

    2001-01-01

    The thermoluminescence of the irradiated aluminum oxides were measured to study the radiation induced defects and their behaviors. Neutron and {gamma}-ray irradiation were performed for a shingle crystal of the high purity aluminum oxide. The thermoluminescence glow curve and its activation energy were measured. The spectroscopy measurement on the thermoluminescence and the absorption are also carried out. The observed 430 and 340 nm peaks are discussed relating to the F{sup +} and F centers, respectively. Activation state of the F center transits to 3P state through 1P state by emitting phonons. Trapped electron on 3P state emits phonon of 2.9 eV (430 nm) during transition to the ground state. The above reaction can be written by the equation. F{sup +} + e {yields} (F){sup *} {yields} F + h{nu}(2.9 eV, 470 nm). (Katsuta, H.)

  9. Probabilistic methodology for estimating radiation-induced cancer risk

    International Nuclear Information System (INIS)

    Dunning, D.E. Jr.; Leggett, R.W.; Williams, L.R.

    1981-01-01

    The RICRAC computer code was developed at Oak Ridge National Laboratory to provide a versatile and convenient methodology for radiation risk assessment. The code allows as input essentially any dose pattern commonly encountered in risk assessments for either acute or chronic exposures, and it includes consideration of the age structure of the exposed population. Results produced by the analysis include the probability of one or more radiation-induced cancer deaths in a specified population, expected numbers of deaths, and expected years of life lost as a result of premature fatalities. These calculatons include consideration of competing risks of death from all other causes. The program also generates a probability frequency distribution of the expected number of cancers in any specified cohort resulting from a given radiation dose. The methods may be applied to any specified population and dose scenario

  10. Radiation induced crystallinity damage in poly(L-lactic acid)

    CERN Document Server

    Kantoglu, O

    2002-01-01

    The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

  11. Factors that modify risks of radiation-induced cancer

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors)

  12. Radiation induced mutant crop varieties: accomplishment and societal deployment

    International Nuclear Information System (INIS)

    D'Souza, S.F.

    2009-01-01

    One of the peaceful applications of atomic energy is in the field of agriculture. It finds application in crop improvement, crop nutrition, crop protection and food preservation. Genetic improvement of crop plants is a continuous endeavor. Success of a crop improvement programme depends on the availability of large genetic variability, which a plant breeder can combine to generate new varieties. In nature, occurrence of natural variability in the form of spontaneous mutations is extremely low (roughly 10 -6 ), which can be enhanced to several fold (approximately 10 -3 ) by using ionizing radiations or chemical mutagens. Radiation induced genetic variability in crop plants is a valuable resource from which plant breeder can select and combine different desired characteristics to produce better crop varieties. Crop improvement programmes at Bhabha Atomic Research Centre (BARC) envisage radiation based induced mutagenesis along with recombination breeding in country's important cereals (rice and wheat), oilseeds (groundnut, mustard, soybean and sunflower), grain legumes (blackgram, mungbean, pigeonpea and cowpea), banana and sugarcane

  13. Binding of radiation-induced phenylalanine radicals to DNA

    International Nuclear Information System (INIS)

    Schans, G.P. van der; Rijn, C.J.S. van; Bleichrodt, J.F.

    1975-11-01

    When an aqueous solution of double-stranded DNA of bacteriophage PM2 containing phenylalanine and saturated with N 2 O is irradiated with γ-rays, radiation-induced phenylalanine radicals are bound covalently. Under the conditions used about 25 phenylalanine molecules may be bound per lethal hit. Also for single-stranded PM2 DNA, most of the phenylalanine radicals bound are non-lethal. Evidence is presented that in double-stranded DNA an appreciable fraction of the single-strand breaks is induced by phenylalanine radicals. Radiation products of phenylalanine and the phenylalanine bound to the DNA decrease the sensitivity of the DNA to the induction of single-strand breaks. There are indications that the high efficiency of protection by radiation products of phenylalanine is due to their positive charge, which will result in a relatively high concentration of these compounds in the vicinity of the negatively charged DNA molecules

  14. Radiation-induced bone tumours in the guinea-pig

    International Nuclear Information System (INIS)

    Knowles, J.F.

    1981-01-01

    A remarkably high proportion of guinea-pigs given localized irradiations of 20 Gy x-rays developed bone tumours, 46% of all irradiated with 20 Gy and 86% of those that survived at least a year. Untreated controls were not included in the present experiment, but the authors refer to an earlier experiment using guinea-pigs from the same colony where no bone tumour occurred in 69 unirradiated animals followed for their natural life span i.e. up to 87 months. It is concluded that the author's strain of guinea-pig (details given in a previous paper, Int. J. Radiol. Biol., 40, 265) is particularly prone to radiation-induced bone tumours. Their possible value for investigating processes associated with radiation induction of bone tumours is further enhanced by their relatively large size and long life span (up to 7 years). (U.K.)

  15. Gamma radiation induced and natural variability for nodulation in legumes

    Energy Technology Data Exchange (ETDEWEB)

    Maherchandani, N; Rana, O P.S. [Haryana Agricultural Univ., Hissar (India). Dept. of Genetics

    1977-09-01

    Gamma radiation induced variability for nodulation was studied in 112 M4 mutant lines of cowpea variety C-15-2. Ten lines superior in nodulation to the original variety have been identified. Natural variability for nodulation and plant growth was investigated in 75 genotypes of chickpea. A number of genotype were found to be superior to cultivated variety C-235 for nodulation characters. Nodule characters were found to be related to dry matter accumulation but not to grain yield. Another experiment on 10 varieties of chick pea conducted under aseptic conditions revealed that host genotypes showed specificity for Rhizobial strains and different Rhizobial strains differed in their effectiveness on different host genotypes. H 551 and H 355 were the most responsive varieties.

  16. Non-radiation induced signals in TL dosimetry

    International Nuclear Information System (INIS)

    German, U.; Weinstein, M.

    2002-01-01

    One source of background signals, which are non-radiation related, is the reader system and it includes dark current, external contaminants and electronic spikes. These factors can induce signals equivalent to several hundredths of mSv. Mostly, the effects are minimised by proper design of the TLD reader, but some effects are dependent on proper operation of the system. The other main group of background signals originate in the TL crystal and is due to tribothermoluminescence, dirt, chemical reactions and stimulation by visible or UV light. These factors can have a significant contribution, equivalent to over several mSv, depending on whether the crystal is bare or protected by PTFE. Working in clean environments, monitoring continuously the glow curve and performing glow curve deconvolution are suggested to minimise non-radiation induced spurious signals. (author)

  17. Radiological-morphological synopsis of radiation-induced lung fibrosis

    International Nuclear Information System (INIS)

    Bublitz, G.

    1977-01-01

    As delayed radiation damage after treatment of bronchial carcinoma and mamma carcinoma, fibroses occur as a reaction of the tissues. They have become a clinical-functional syndrome because of their uniform clinicaL-radiological symptomatology and pathophysiology. Pulmonary fibrosis as delayed radiation damage has a special importance with its two different radiation effects on connective tissue: a) on existing structures, b) delayed alterations of the connective tissue. As seen from experiments on lungs of men and rats, radiation-induced alterations can be measured by testing the different solubilities of the collagen types. In addition to the pathologically disordered collagen production, 9 weeks after the irradiation the radiation fibrosis leads to an isolated increase of insoluble collagen corresponding to the formation of metabolism-resistant fibrils. (MG) [de

  18. Radiation-induced crosslinking of poly(vinylidene fluoride)

    International Nuclear Information System (INIS)

    Makuuchi, Keizo

    1977-07-01

    The factors influencing radiation-induced crosslinking efficiency of poly(vinylidene fluoride) (PVdF) have been studied. Results of the basic research on irradiation conditions (dose rate and atmosphere) and initial physical properties of PVdF (structure of molecular chain and molecular mobility of chain segment) showed that crosslinking efficiency is raised in irradiation at high temperature above 50 0 C under vacuum in the presence of an absorbent for the evolved hydrogen fluoride. The crosslinking reaction is also accelerated with irregular molecular structure such as head-to-head bond in main chain. High crosslinking efficiency is obtained by addition of a polyfunctional monomer having good solubility with PVdF. Mechanical properties of PVdF, the strength at high temperature near the melting point in particular, are improved by crosslinking in the presence of a polyfunctional monomer. (auth.)

  19. Studies on radiation induced changes in bovine hemoglobin type A

    International Nuclear Information System (INIS)

    Wdzieczak, J.; Duda, W.; Leyko, W.

    1978-01-01

    In this paper the structural and functional changes of gamma irradiated bovine hemoglobin are presented. Aqueous solutions/1%/of HbO 2 were irradiated in air with doses ranging from 1 to 4 Mrad. Isoelectric focusing indicated change of the charge of irradiated hemoglobin. The isoelectric point of hemoglobin was displaced towards more acid values with increasing doses, up from 1 Mrad. Fingerprint analysis and peptide column chromatography of irradiated hemoglobin demonstrated disturbances increasing with the dose. These changes were confirmed by amino acid analysis which showed that Cys, Met, Trp, His, Pro and Tyr residues were destroyed or modified following irradiation. At doses exceeding 1 Mrad the irradiated solutions of hemoglobin showed a decrease of heme-heme interaction and an increase of affinity for oxygen. Differences observed in oxygen-dissociation curves seem to be correlated with the radiation induced destruction of amino acid residues which are responsible for the functional properties of hemoglobin. (auth.)

  20. Radiation-induced DNA damage and cellular lethality

    International Nuclear Information System (INIS)

    Sakai, K.; Okada, S.

    1984-01-01

    Radiation-induced DNA scissions and their repair were investigated in mammalian cells using an alkaline separation method. DNA breaks in mouse L5178Y cells and Chinese hamster V79 cells were grouped into three in terms of their repair profile; fast-reparable breaks (FRBs; T1/2 = 5 min), slow-reparable breaks (SRBs; T1/2 = 70 min) and non-reparable breaks (NRBs). The three types of DNA lesions were studied under conditions where cellular radiosensitivity was modified. The authors obtained the following results: 1. Cell cycle fluctuation: L5178Y showed maximum sensitivity at M and G/sub 1/-S boundary, and minimum sensitivity at G/sub 1/ and late S. Cycle dependency was not found for FRBs or SRBs, but NRBs showed bimodal fluctuation with peaks at M and G/sub 1/-S, and with bottoms at G/sub 1/ and late S. 2. Different sensitivity of L5178Y and V79: L5178Y cells were more sensitive to X-rays (D/sub ο/ = 0.9 Gy) than V79 (D/sub ο/ = 1.8 Gy). The amount of FRBs or SRBs was identical in the two cell lines. However, the amount of NRBs in L5178Y was greater than that in V79. 3. Split dose irradiation: The time interval between two doses resulted in a gradual decrease of NRBs. The time course of the decrease was similar to the split dose recovery in terms of cell death. The parallel relationship between NRBs and cell killing implies that NRBs could play an important role in radiation-induced cell death

  1. Association of single nucleotide polymorphisms with radiation-induced esophagitis

    International Nuclear Information System (INIS)

    Zhang Li; Wang Lvhua; Yang Ming; Ji Wei; Zhao Lujun; Yang Weizhi; Zhou Zongmei; Ou Guangfei; Lin Dongxin

    2008-01-01

    Objective: To evaluate the relationship between single nucleotide polymorphism(SNP) of candidate genes and radiation-induced esophagitis (RIE) in patients with lung cancer. Methods: Between Jan. 2004 and Aug. 2006, 170 patients with pathologically diagnosed lung cancer were enrolled in this study. The total target dose was 45-70 Gy (median 60 Gy). One hundred and thirty-two patients were treated with three-dimensional conformal radiotherapy(3DCRT) and 38 with two-dimensional radiotherapy(2DRT). Forty-one patients received radiotherapy alone, 78 received sequential chemoradiotherapy and 51 received concurrent chemoradiotherapy. Thirty-seven SNPs in 20 DNA repair genes were analyzed by using PCR- based restricted fragment length polymorphism (RFLP). These genes were apoptosis and inflammatory cytokine genes including ATM, ERCC1, XRCC3, XRCCI, XPD, XPC, XPG, NBS1, STK15, ZNF350, ADPRT, TP53, FAS, FASL, CYP2D6*4, CASPASE8, COX2,TGF-β, CD14 and ACE. The endpoint was grade ≥2 R I E. Results: Forty of the 170 patients developed grade ≥2 R I E, including 36 in grade 2 and 4 in grade 3. Univariate analysis revealed that radiation technique and concurrent chemoradiotherapy were statistically significant relatives to the incidence of R I E (P=0.032, 0.049), and both of them had the trend associating with the esophagitis (P=0.072, 0.094). An increased incidence of esophagitis was observed associating with the TGF-β 1 -509T and XPD 751Lys/Lys genotypes (χ 2 =5.65, P=0.017; χ 2 =3.84, P=0.048) in multivariate analysis. Conclusions: Genetic polymorphisms in TGF-β 1 gene and XPD gene have a significant association with radiation-induced esophagitis. (authors)

  2. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    Science.gov (United States)

    Ahmad, S. B.; McNeill, F. E.; Byun, S. H.; Prestwich, W. V.; Seymour, C.; Mothersill, C. E.

    2012-10-01

    The aim of this work is quantify the light emitted as a result of charged particle interaction in materials which may be of relevance to radiation induced "bystander effects" studies. We have developed a system which employs single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. The system uses a fast photomultiplier tube with a peak cathode response at 420 nm. It has been tested in a proof-of-principle experiment using polystyrene targets. Light output, as a result of irradiation, was measured. The luminescence yield appears to have a non-linear behavior with the incident ion fluence: it rises exponentially to an asymptotic value. The target was irradiated with beam energies varying from 1 to 2 MeV and showed saturation at or before an incident fluence rate of 3 × 1013 H+/cm2 s. The average saturation value for the photon output was found to be 40 × 106 cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28 × 103, 10 × 106, and 35 × 106 cps for wavelengths of 280 ± 5 nm, 320 ± 5 nm and 340 ± 5 nm respectively. The light output reaches a maximum value because of damage induced in the polymer. Our measurements indicate a "damage cross section" of the order of 10-14 cm2. The average radiant intensity was found to increase at wavelengths of 280 and 320 nm when the proton energy was increased. This was not found to occur at 340 nm. In conclusion, the light emission at specific wavelengths was found to depend upon the incident proton fluence and the proton energy. The wavelengths of the emitted light measured in this study have significance for the understanding of radiation induced bystander effects.

  3. Defense mechanisms against radiation induced teratogenic damage in mice

    International Nuclear Information System (INIS)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T.

    2002-01-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair

  4. Effect of salidroside on radiation-induced bone marrow adipogenesis

    International Nuclear Information System (INIS)

    Zhu Jincan; Chen Xiaoyu; Liu Chengcheng; Zhu Aizhen; Liu Shantao; Liu Gexiu

    2014-01-01

    Objective: To investigate the potential and underlying molecular mechanism of salidroside in ameliorating radiation-induced bone marrow adipogenesis and stimulating hematopoiesis. Methods: The female BALB/c mice aged 6-7 weeks were randomly divided into normal control group, radiation group and salidroside group. The radiation group and salidroside group were irradiated with 6.0 Gy of "6"0Co γ-rays. The salidroside group was intraperitoneally injected with 30 mg·kg"-"1·d"-"1 salidroside at 12 h and then every day until 8th d after radiation. The normal control group and radiation group were treated with equal volume of saline as control of salidroside. At 14 d after radiation, the mice weight, peripheral blood count, femur bone marrow histology, and the proportion of adipocyte area were measured, and the expressions of PPAR-γ and FABP4 were detected by q-PCR. Results: After irradiation, the numbers of white blood cells, hemoglobin and platelet in peripheral blood were reduced obviously, and the percentage of adipocyte area was increased significantly. Compared with mice in the radiation group, salidroside inhibited adipogenesis and reduced the proportion of adipocyte area (t = 13.31, P < 0.05) by reducing the expressions of PPAR-γ and FABP4 (t = 8.64, 13.19, P < 0.05). The number of white blood cells was partly recovered at 7 d after irradiation (t = 5.80, P < 0.05). Both white blood cells and hemoglobinin in peripheral blood of the salidroside group were higher than those in the radiation group at 14 d after irradiation. Conclusions: Salidroside could inhibit radiation-induced bone marrow adipogenesis and regulate bone marrow microenvironment, thereby promotes hematopoietic recovery in mice after radiation injury. (authors)

  5. Radiation-induced apoptosis of lymphocytes in peripheral blood

    International Nuclear Information System (INIS)

    Oh, Yoon Kyeong; Lee, Tae Bum; Nam, Taek Keun; Kee, Keun Hong; Choi, Cheol Hee

    2003-01-01

    This study quantitatively evaluated the apoptosis in human peripheral blood lymphocytes using flow cytometry, and investigated the possibility of using this method, with a small amount of blood, and the time and dose dependence of radiation-induced apoptosis. Peripheral blood lymphocytes were isolated from the heparinized venous blood of 11 healthy volunteers, 8 men and 3 women, with each 10 ml of blood being divided into 15 samples. The blood lymphocytes were irradiated using a linear accelerator at a dose rate of 2.4 Gy/min, to deliver doses of 0.5, 1, 2 and 5 Gy. The control samples, and irradiated cells, were maintained in culture medium for 24, 48 and 72 hours following the irradiation. The number of apoptotic cells after the in vitro X-irradiation was measured by flow cytometry after incubation periods of 24, 48 and 72 hours. We also observed the apoptotic cells using a DNA fragmentation assay and electron microscopy. The rate of spontaneous apoptosis increased in relation to the time interval following irradiation (1.761±0.161, 3.563±0.564, 11.098±2.849, at 24, 48, and 72 hours). The apoptotic cells also increased in the samples irradiated with 0.5, 1, 2 and 5 Gy, in a radiation dose and time interval after irradiation manner, with the apoptosis being too great at 72 hours after irradiation. The dose-response curves were characterized by an initial steep increase in the number of apoptotic cells for irradiation doses below 2 Gy, with a flattening of the curves as the dose approached towards 5 Gy. The flow cytometric assay technique yielded adequate data, and required less than 1 mL of blood. The time and dose dependence of the radiation-induced apoptosis, was also shown. It is suggested that the adequate time interval required for the evaluation of apoptosis would be 24 to 48 hours after blood sampling

  6. Radiation-induced thyroid cancer after radiotherapy for childhood cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiravova, M. [Department of Nuclear Medicine and Endocrinology, Faculty Hospital Motol, Uk, Prague (Czech Republic)

    2012-07-01

    Full text of the publication follows: The thyroid gland in children is among the most sensitive organs to the carcinogenic effects of ionizing radiation, and very young children are at especially high risk. Due to extreme sensitivity of the thyroid gland in children, there is a risk of radiation - induced thyroid cancer even when the thyroid gland is outside the irradiated field. Increased incidence of thyroid cancer has been noted following radiotherapy not only for childhood Hodgkin disease (majority of observed patients), but also for non-Hodgkin lymphoma, neuroblastoma, Wilms tumor, acute lymphocytic leukemia and tumors of the central nervous system also. Radiation-induced tumors begin to appear 5-10 years after irradiation and excess risk persists for decades, perhaps for the remainder of life. The incidence of thyroid cancer is two- to threefold higher among females than males. Most of the thyroid cancers that occur in association with irradiation are of the papillary type, for which the cure rate is high if tumors are detected early. Our Department in co-operation with Department of Children Hematology and Oncology Charles University Second Faculty of Medicine and Faculty Hospital Motol monitors patients after therapy for cancer in childhood for the long term period. The monitoring is focused on detection of thyroid disorders that occur as last consequences of oncology therapy, especially early detection of nodular changes in thyroid gland and thyroid carcinogenesis. The survey presents two patients observed in our department that were diagnosed with the papillary thyroid carcinoma which occurred 15 and more years after radiotherapy for childhood cancer. After total thyroidectomy they underwent therapy with radioiodine. After radiotherapy it is necessary to pursue a long-term following and assure interdisciplinary co-operation which enables early detection of last consequences of radiotherapy, especially the most serious ones as secondary carcinogenesis

  7. Simulating Space Radiation-Induced Breast Tumor Incidence Using Automata.

    Science.gov (United States)

    Heuskin, A C; Osseiran, A I; Tang, J; Costes, S V

    2016-07-01

    Estimating cancer risk from space radiation has been an ongoing challenge for decades primarily because most of the reported epidemiological data on radiation-induced risks are derived from studies of atomic bomb survivors who were exposed to an acute dose of gamma rays instead of chronic high-LET cosmic radiation. In this study, we introduce a formalism using cellular automata to model the long-term effects of ionizing radiation in human breast for different radiation qualities. We first validated and tuned parameters for an automata-based two-stage clonal expansion model simulating the age dependence of spontaneous breast cancer incidence in an unexposed U.S. We then tested the impact of radiation perturbation in the model by modifying parameters to reflect both targeted and nontargeted radiation effects. Targeted effects (TE) reflect the immediate impact of radiation on a cell's DNA with classic end points being gene mutations and cell death. They are well known and are directly derived from experimental data. In contrast, nontargeted effects (NTE) are persistent and affect both damaged and undamaged cells, are nonlinear with dose and are not well characterized in the literature. In this study, we introduced TE in our model and compared predictions against epidemiologic data of the atomic bomb survivor cohort. TE alone are not sufficient for inducing enough cancer. NTE independent of dose and lasting ∼100 days postirradiation need to be added to accurately predict dose dependence of breast cancer induced by gamma rays. Finally, by integrating experimental relative biological effectiveness (RBE) for TE and keeping NTE (i.e., radiation-induced genomic instability) constant with dose and LET, the model predicts that RBE for breast cancer induced by cosmic radiation would be maximum at 220 keV/μm. This approach lays the groundwork for further investigation into the impact of chronic low-dose exposure, inter-individual variation and more complex space radiation

  8. Radiation-induced brachial plexus neuropathy in breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, N.K.; Pfeiffer, P.; Mondrup, K.; Rose, C. (Odense Univ. Hospital (Denmark). Dept. of Neurology Odense Univ. Hospital (Denmark). Dept. of Clinical Neurophysiology Odense Univ. Hospital (Denmark). Dept. of Oncology R)

    1990-01-01

    The incidence and latency period of radiation-induced brachial plexopathy (RBP) were assessed in 79 breast cancer patients by a neurological follow-up examination at least 60 months (range 67-130 months) after the primary treatment. All patients were treated primarily with simple mastectomy, axillary nodal sampling and radiotherapy (RT). Postoperatively, pre- and postmenopausal patients were randomly allocated chemotherapy for antiestrogen treatment. All patients were recurrence-free at time of examination. Clinically, 35% (25-47%) of the patients had RBP; 19% (11-29%) had definite RBP, i.e. were physically disabled, and 16% (9-26%) had probable RBP. Fifty percent (31-69%) had affection of the entire plexus, 18% (7-35%) of the upper trunk only, and 4% (1-18%) of the lower trunk. In 28% (14-48%) of cases assessment of a definite level was not possible. RBP was more common after radiotherapy and chemotherapy (42%) than after radiotherapy alone (26%) but the difference was not statistically significant (p = 0.10). The incidence of definite RBP was significantly higher in the younger age group (p = 0.02). This could be due to more extensive axillary surgery but also to the fact that chemotherapy was given to most premenopausal patients. In most patients with RBP the symptoms began during or immediately after radiotherapy, and were thus without significant latency. Chemotherapy might enhance the radiation-induced effect on nerve tissue, thus diminishing the latency period. Lymphedema was present in 22% (14-32%), especially in the older patients, and not associated with the development of RBP. In conclusion, the damaging effect of RT on peripheral nerve tissue was documented. Since no successful treatment is available, restricted use of RT to the brachial plexus is warranted, especially when administered concomitantly with cytotoxic therapy. (orig.).

  9. Genetic analysis of radiation-induced mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, R.; Wakabayashi, Y.; Niwa, O.

    2003-01-01

    Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

  10. Radiation induces aerobic glycolysis through reactive oxygen species

    International Nuclear Information System (INIS)

    Zhong, Jim; Rajaram, Narasimhan; Brizel, David M.; Frees, Amy E.; Ramanujam, Nirmala; Batinic-Haberle, Ines; Dewhirst, Mark W.

    2013-01-01

    Background and purpose: Although radiation induced reoxygenation has been thought to increase radiosensitivity, we have shown that its associated oxidative stress can have radioprotective effects, including stabilization of the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1 is known to regulate many of the glycolytic enzymes, thereby promoting aerobic glycolysis, which is known to promote treatment resistance. Thus, we hypothesized that reoxygenation after radiation would increase glycolysis. We previously showed that blockade of oxidative stress using a superoxide dismutase (SOD) mimic during reoxygenation can downregulate HIF-1 activity. Here we tested whether concurrent use of this drug with radiotherapy would reduce the switch to a glycolytic phenotype. Materials and methods: 40 mice with skin fold window chambers implanted with 4T1 mammary carcinomas were randomized into (1) no treatment, (2) radiation alone, (3) SOD mimic alone, and (4) SOD mimic with concurrent radiation. All mice were imaged on the ninth day following tumor implantation (30 h following radiation treatment) following injection of a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Hemoglobin saturation was measured by using hyperspectral imaging to quantify oxygenation state. Results: Mice treated with radiation showed significantly higher 2-NBDG fluorescence compared to controls (p = 0.007). Hemoglobin saturation analysis demonstrated reoxygenation following radiation, coinciding with the observed increase in glycolysis. The concurrent use of the SOD mimic with radiation demonstrated a significant reduction in 2-NBDG fluorescence compared to effects seen after radiation alone, while having no effect on reoxygenation. Conclusions: Radiation induces an increase in tumor glucose demand approximately 30 h following therapy during reoxygenation. The use of an SOD mimic can prevent the increase in aerobic glycolysis when used

  11. MKP1 phosphatase mediates G1-specific dephosphorylation of H3Serine10P in response to DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Ajit K.; Khan, Shafqat A.; Sharda, Asmita; Reddy, Divya V; Gupta, Sanjay, E-mail: sgupta@actrec.gov.in

    2015-08-15

    Highlights: • Reversible reduction of H3S10 phosphorylation after DNA damage is G1 phase specific. • Dynamic balance between MAP kinases, MKP1 and MSK1 regulate H3S10P during DDR. • MKP1 associates with chromatin bearing γH2AX in response to DNA damage. • Inhibition of MKP1 activity with specific inhibitor promotes radiation-induced cell death. - Abstract: Histone mark, H3S10 phosphorylation plays a dual role in a cell by maintaining relaxed chromatin for active transcription in interphase and condensed chromatin state in mitosis. The level of H3S10P has also been shown to alter on DNA damage; however, its cell cycle specific behavior and regulation during DNA damage response is largely unexplored. In the present study, we demonstrate G1 cell cycle phase specific reversible loss of H3S10P in response to IR-induced DNA damage is mediated by opposing activities of phosphatase, MKP1 and kinase, MSK1 of the MAP kinase pathway. We also show that the MKP1 recruits to the chromatin in response to DNA damage and correlates with the decrease of H3S10P, whereas MKP1 is released from chromatin during recovery phase of DDR. Furthermore, blocking of H3S10 dephosphorylation by MKP1 inhibition impairs DNA repair process and results in poor survival of WRL68 cells. Collectively, our data proposes a pathway regulating G1 cell cycle phase specific reversible reduction of H3S10P on IR induced DNA damage and also raises the possibility of combinatorial modulation of H3S10P with specific inhibitors to target the cancer cells in G1-phase of cell cycle.

  12. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    Energy Technology Data Exchange (ETDEWEB)

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R., E-mail: akennedy@mail.med.upenn.edu

    2014-03-15

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.

  13. Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

    International Nuclear Information System (INIS)

    Kandasamy, S.B.; Hunt, W.A.

    1990-01-01

    Exposure of rats to 1-15 Gy of gamma radiation induced hyperthermia, whereas exposure to 20-150 Gy produced hypothermia. Since radiation exposure induced the release of prostaglandins (PGs) and histamine, the role of PGs and histamine in radiation-induced temperature changes was examined. Radiation-induced hyper- and hypothermia were antagonized by pretreatment with indomethacin, a cyclooxygenase inhibitor. Intracerebroventricular administration of PGE2 and PGD2 induced hyper- and hypothermia, respectively. Administration of SC-19220, a specific PGE2 antagonist, attenuated PGE2- and radiation-induced hyperthermia, but it did not antagonize PGD2- or radiation-induced hypothermia. Consistent with an apparent role of histamine in hypothermia, administration of disodium cromoglycate (a mast cell stabilizer), mepyramine (H1-receptor antagonist), or cimetidine (H2-receptor antagonist) attenuated PGD2- and radiation-induced hypothermia. These results suggest that radiation-induced hyperthermia is mediated via PGE2 and that radiation-induced hypothermia is mediated by another PG, possibly PGD2, via histamine

  14. The effect of ethanol on the γ radiation induced polymerization of styrene

    International Nuclear Information System (INIS)

    Zhang Xujia; Ha Hongfei; Wu Jilan

    1990-01-01

    The γ radiation induced polymerization of styrene in the presence of ethanol was studied at dose rate of 5 x 10 17 eV/ml min. The result showed that the radiation induced polymerization of styrene was sensitized by ethanol. The experimental results were in agreement with the theoretical calculation of WAS equation. The mechanism of sensitization was proposed as proton transfer reaction

  15. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    Science.gov (United States)

    Kennedy, Ann

    The hypothesis being evaluated in this research program is that control of radiation induced oxidative stress will reduce the risk of radiation induced adverse biological effects occurring as a result of exposure to the types of radiation encountered during space travel. As part of this grant work, we have evaluated the protective effects of several antioxidants and dietary supplements and observed that a mixture of antioxidants (AOX), containing L-selenomethionine, N-acetyl cysteine (NAC), ascorbic acid, vitamin E succinate, and alpha-lipoic acid, is highly effective at reducing space radiation induced oxidative stress in both in vivo and in vitro systems, space radiation induced cytotoxicity and malignant transformation in vitro [1-7]. In studies designed to determine whether the AOX formulation could affect radiation induced mortality [8], it was observed that the AOX dietary supplement increased the 30-day survival of ICR male mice following exposure to a potentially lethal dose (8 Gy) of X-rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 hours following exposure to doses of 1 Gy and 8 Gy. Antioxidant treatment also resulted in increased bone marrow cell counts following irradiation, and prevented peripheral lymphopenia following 1 Gy irradiation. Supplementation with antioxidants in irradiated animals resulted in several gene expression changes: the antioxidant treatment was associated with increased Bcl-2, and decreased Bax, caspase-9 and TGF-β1 mRNA expression in the bone marrow following irradiation. These results suggest that modulation of apoptosis may be mechanistically involved in hematopoietic system radioprotection by antioxidants. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow following sub-lethal or potentially lethal irradiation. Taken together

  16. Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout mice

    International Nuclear Information System (INIS)

    Jin Jie; Wang Yu; Xu Yang; Chen Shilei; Wang Junping; Ran Xinze; Su Yongping; Wang Jin

    2014-01-01

    Steroid receptor coactivator-3 (SRC-3), a multifunctional transcriptional coactivator, plays an important role in regulation of cell apoptosis in chemoresistant cancer cells. However, its role in radiation-induced apoptosis in hematopoietic cells is still unclear. In this study, we used SRC-3 knockout (SRC-3 -/- ) mice to assess the role of SRC-3 in radiation-induced hematopoietic injury in vivo. After a range of doses of irradiation, SRC-3 -/- mice exhibited lower counts of peripheral blood cells and bone marrow (BM) mononuclear cells and excessive BM depression, which resulted in a significantly higher mortality compared with wildtype mice. Moreover, BM mononuclear cells obtained from SRC-3 -/- mice showed a remarkable increase in radiation-induced apoptosis. Collectively, our data demonstrate that SRC-3 plays a role in radiation-induced apoptosis of BM hematopoietic cells. Regulation of SRC-3 might influence the radiosensitivity of hematopoietic cells, which highlights a potential therapeutic target for radiation-induced hematopoietic injury. (author)

  17. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma.

    Science.gov (United States)

    Mohammadianpanah, M; Gramizadeh, B; Omidvari, Sh; Mosalaei, A

    2004-01-01

    Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  18. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma

    Directory of Open Access Journals (Sweden)

    Mohammadianpanah M

    2004-07-01

    Full Text Available Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  19. Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91

    Energy Technology Data Exchange (ETDEWEB)

    Wharry, Janelle P.; Jiao Zhijie; Shankar, Vani [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States); Busby, Jeremy T. [Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37831 (United States); Was, Gary S., E-mail: gsw@umich.edu [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States)

    2011-10-01

    Radiation-induced segregation in ferritic-martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 deg. C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni-Si-Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures.

  20. Appearance of radiation-induced lesions after radiotherapy for Hodgkin's disease of the mediastinum and lungs

    Energy Technology Data Exchange (ETDEWEB)

    Zomer-Drozda, J [Instytut Onkologii, Warsaw (Poland)

    1976-01-01

    The incidence of radiation-induced lesions of lung tissue adjacent to the mediastinum and covered by radiation was established on the basis of a retrospective analysis of radiograms of 245 patients treated at the Institute of Oncology in Warsaw in the years 1951-1968, who received radiotherapy to the mediastinal lymph nodes. The radiation-induced lesions were divided into 4 grades depending on their extent and intensity of pulmonary tissue damage. Criteria for classification of radiation-induced fibrosis into the above mentioned grades were established. The correlation between radiation-induced injury and the doses of X-rays applied to the mediastinal lymph nodes was analysed. The importance of radiation-induced changes in the mediastinum and lungs for the diagnosis of recurrences in the irradiated fields, in the marginal areas and granulomatous infiltrations in pulmonary tissue is discussed.

  1. Design principles of the yeast G1/S switch.

    Directory of Open Access Journals (Sweden)

    Xiaojing Yang

    2013-10-01

    Full Text Available A hallmark of the G1/S transition in budding yeast cell cycle is the proteolytic degradation of the B-type cyclin-Cdk stoichiometric inhibitor Sic1. Deleting SIC1 or altering Sic1 degradation dynamics increases genomic instability. Certain key facts about the parts of the G1/S circuitry are established: phosphorylation of Sic1 on multiple sites is necessary for its destruction, and both the upstream kinase Cln1/2-Cdk1 and the downstream kinase Clb5/6-Cdk1 can phosphorylate Sic1 in vitro with varied specificity, cooperativity, and processivity. However, how the system works as a whole is still controversial due to discrepancies between in vitro, in vivo, and theoretical studies. Here, by monitoring Sic1 destruction in real time in individual cells under various perturbations to the system, we provide a clear picture of how the circuitry functions as a switch in vivo. We show that Cln1/2-Cdk1 sets the proper timing of Sic1 destruction, but does not contribute to its destruction speed; thus, it acts only as a trigger. Sic1's inhibition target Clb5/6-Cdk1 controls the speed of Sic1 destruction through a double-negative feedback loop, ensuring a robust all-or-none transition for Clb5/6-Cdk1 activity. Furthermore, we demonstrate that the degradation of a single-phosphosite mutant of Sic1 is rapid and switch-like, just as the wild-type form. Our mathematical model confirms our understanding of the circuit and demonstrates that the substrate sharing between the two kinases is not a redundancy but a part of the design to overcome the trade-off between the timing and sharpness of Sic1 degradation. Our study provides direct mechanistic insight into the design features underlying the yeast G1/S switch.

  2. The TCP4 transcription factor of Arabidopsis blocks cell division in yeast at G1 → S transition

    International Nuclear Information System (INIS)

    Aggarwal, Pooja; Padmanabhan, Bhavna; Bhat, Abhay; Sarvepalli, Kavitha; Sadhale, Parag P.; Nath, Utpal

    2011-01-01

    Highlights: → TCP4 is a class II TCP transcription factor, that represses cell division in Arabidopsis. → TCP4 expression in yeast retards cell division by blocking G1 → S transition. → Genome-wide expression studies and Western analysis reveals stabilization of cell cycle inhibitor Sic1, as possible mechanism. -- Abstract: The TCP transcription factors control important aspects of plant development. Members of class I TCP proteins promote cell cycle by regulating genes directly involved in cell proliferation. In contrast, members of class II TCP proteins repress cell division. While it has been postulated that class II proteins induce differentiation signal, their exact role on cell cycle has not been studied. Here, we report that TCP4, a class II TCP protein from Arabidopsis that repress cell proliferation in developing leaves, inhibits cell division by blocking G1 → S transition in budding yeast. Cells expressing TCP4 protein with increased transcriptional activity fail to progress beyond G1 phase. By analyzing global transcriptional status of these cells, we show that expression of a number of cell cycle genes is altered. The possible mechanism of G1 → S arrest is discussed.

  3. Influence of radiation induced defect clusters on silicon particle detectors

    Energy Technology Data Exchange (ETDEWEB)

    Junkes, Alexandra

    2011-10-15

    The Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN) addresses some of today's most fundamental questions of particle physics, like the existence of the Higgs boson and supersymmetry. Two large general-purpose experiments (ATLAS, CMS) are installed to detect the products of high energy protonproton and nucleon-nucleon collisions. Silicon detectors are largely employed in the innermost region, the tracking area of the experiments. The proven technology and large scale availability make them the favorite choice. Within the framework of the LHC upgrade to the high-luminosity LHC, the luminosity will be increased to L=10{sup 35} cm{sup -2}s{sup -1}. In particular the pixel sensors in the innermost layers of the silicon trackers will be exposed to an extremely intense radiation field of mainly hadronic particles with fluences of up to {phi}{sub eq}=10{sup 16} cm{sup -2}. The radiation induced bulk damage in silicon sensors will lead to a severe degradation of the performance during their operational time. This work focusses on the improvement of the radiation tolerance of silicon materials (Float Zone, Magnetic Czochralski, epitaxial silicon) based on the evaluation of radiation induced defects in the silicon lattice using the Deep Level Transient Spectroscopy and the Thermally Stimulated Current methods. It reveals the outstanding role of extended defects (clusters) on the degradation of sensor properties after hadron irradiation in contrast to previous works that treated effects as caused by point defects. It has been found that two cluster related defects are responsible for the main generation of leakage current, the E5 defects with a level in the band gap at E{sub C}-0.460 eV and E205a at E{sub C}-0.395 eV where E{sub C} is the energy of the edge of the conduction band. The E5 defect can be assigned to the tri-vacancy (V{sub 3}) defect. Furthermore, isochronal annealing experiments have shown that the V{sub 3} defect

  4. Influence of radiation induced defect clusters on silicon particle detectors

    International Nuclear Information System (INIS)

    Junkes, Alexandra

    2011-10-01

    The Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN) addresses some of today's most fundamental questions of particle physics, like the existence of the Higgs boson and supersymmetry. Two large general-purpose experiments (ATLAS, CMS) are installed to detect the products of high energy protonproton and nucleon-nucleon collisions. Silicon detectors are largely employed in the innermost region, the tracking area of the experiments. The proven technology and large scale availability make them the favorite choice. Within the framework of the LHC upgrade to the high-luminosity LHC, the luminosity will be increased to L=10 35 cm -2 s -1 . In particular the pixel sensors in the innermost layers of the silicon trackers will be exposed to an extremely intense radiation field of mainly hadronic particles with fluences of up to Φ eq =10 16 cm -2 . The radiation induced bulk damage in silicon sensors will lead to a severe degradation of the performance during their operational time. This work focusses on the improvement of the radiation tolerance of silicon materials (Float Zone, Magnetic Czochralski, epitaxial silicon) based on the evaluation of radiation induced defects in the silicon lattice using the Deep Level Transient Spectroscopy and the Thermally Stimulated Current methods. It reveals the outstanding role of extended defects (clusters) on the degradation of sensor properties after hadron irradiation in contrast to previous works that treated effects as caused by point defects. It has been found that two cluster related defects are responsible for the main generation of leakage current, the E5 defects with a level in the band gap at E C -0.460 eV and E205a at E C -0.395 eV where E C is the energy of the edge of the conduction band. The E5 defect can be assigned to the tri-vacancy (V 3 ) defect. Furthermore, isochronal annealing experiments have shown that the V 3 defect exhibits a bistability, as does the leakage current. In oxygen

  5. Radiation-induced alternative transcripts as detected in total and polysome-bound mRNA.

    Science.gov (United States)

    Wahba, Amy; Ryan, Michael C; Shankavaram, Uma T; Camphausen, Kevin; Tofilon, Philip J

    2018-01-02

    Alternative splicing is a critical event in the posttranscriptional regulation of gene expression. To investigate whether this process influences radiation-induced gene expression we defined the effects of ionizing radiation on the generation of alternative transcripts in total cellular mRNA (the transcriptome) and polysome-bound mRNA (the translatome) of the human glioblastoma stem-like cell line NSC11. For these studies, RNA-Seq profiles from control and irradiated cells were compared using the program SpliceSeq to identify transcripts and splice variations induced by radiation. As compared to the transcriptome (total RNA) of untreated cells, the radiation-induced transcriptome contained 92 splice events suggesting that radiation induced alternative splicing. As compared to the translatome (polysome-bound RNA) of untreated cells, the radiation-induced translatome contained 280 splice events of which only 24 were overlapping with the radiation-induced transcriptome. These results suggest that radiation not only modifies alternative splicing of precursor mRNA, but also results in the selective association of existing mRNA isoforms with polysomes. Comparison of radiation-induced alternative transcripts to radiation-induced gene expression in total RNA revealed little overlap (about 3%). In contrast, in the radiation-induced translatome, about 38% of the induced alternative transcripts corresponded to genes whose expression level was affected in the translatome. This study suggests that whereas radiation induces alternate splicing, the alternative transcripts present at the time of irradiation may play a role in the radiation-induced translational control of gene expression and thus cellular radioresponse.

  6. Radiation-induced bystander effects in cultured human stem cells.

    Directory of Open Access Journals (Sweden)

    Mykyta V Sokolov

    2010-12-01

    Full Text Available The radiation-induced "bystander effect" (RIBE was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR. RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed.Human bone-marrow mesenchymal stem cells (hMSC and embryonic stem cells (hESC were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05. A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05.These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.

  7. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, S.B., E-mail: ahmad.rabilal@gmail.com [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); McNeill, F.E., E-mail: fmcneill@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Byun, S.H., E-mail: soohyun@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Prestwich, W.V., E-mail: prestwic@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Seymour, C., E-mail: seymouc@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Mothersill, C.E., E-mail: mothers@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada)

    2012-10-01

    The aim of this work is quantify the light emitted as a result of charged particle interaction in materials which may be of relevance to radiation induced 'bystander effects' studies. We have developed a system which employs single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. The system uses a fast photomultiplier tube with a peak cathode response at 420 nm. It has been tested in a proof-of-principle experiment using polystyrene targets. Light output, as a result of irradiation, was measured. The luminescence yield appears to have a non-linear behavior with the incident ion fluence: it rises exponentially to an asymptotic value. The target was irradiated with beam energies varying from 1 to 2 MeV and showed saturation at or before an incident fluence rate of 3 Multiplication-Sign 10{sup 13} H{sup +}/cm{sup 2} s. The average saturation value for the photon output was found to be 40 Multiplication-Sign 10{sup 6} cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28 Multiplication-Sign 10{sup 3}, 10 Multiplication-Sign 10{sup 6}, and 35 Multiplication-Sign 10{sup 6} cps for wavelengths of 280 {+-} 5 nm, 320 {+-} 5 nm and 340 {+-} 5 nm respectively. The light output reaches a maximum value because of damage induced in the polymer. Our measurements indicate a 'damage cross section' of the order of 10{sup -14} cm{sup 2}. The average radiant intensity was found to increase at wavelengths of 280 and 320 nm when the proton energy was increased. This was not found to occur at 340 nm. In conclusion, the light emission at specific wavelengths was found to depend upon the incident proton fluence and the proton energy. The wavelengths of the emitted light measured in this study have significance for the understanding of radiation induced bystander effects.

  8. Phase III evaluation of sucralfate for radiation-induced esophagitis

    International Nuclear Information System (INIS)

    McGinnis, W.L.; Loprinzi, C.L.; Buskirk, S.J.; Sloan, J.A.; Novotny, P.J.; Drummond, R.G.; Frank, A.R.; Shanahan, T.G.

    1996-01-01

    Purpose/Objective: To evaluate whether an oral sucralfate solution could prevent or alleviate symptoms of radiation-induced esophagitis in patients receiving thoracic radiation therapy. Materials and Methods: Patients considered for this trial must have been adults scheduled to receive thoracic radiation therapy to include the mediastinum to a dose of ≥ 5,000 cGy using 150 to 200 cGy per fraction or ≥ 4,000 cGy using ≥ 300 cGy per fraction. Contraindications to study participation included a known intolerance to sucralfate; previous radiation to the chest; planned use of sucralfate off study; pregnant or nursing women; cancers involving the mucosa of the esophagus; and/or an inability to take oral medications. Patients were stratified by their radiation therapy treatment plan, their age and their sex. Following stratification, they were randomized in a double blind manner to receive a sucralfate solution or an identical-appearing placebo solution. Esophagitis was measured by the treating physician, using the RTOG esophagitis toxicity grading criteria, at weekly intervals during the course of radiation therapy. In addition, patients completed short questionnaires weekly during the course of radiation therapy and for four weeks following completion of their radiation treatment program. Results: One hundred and two patients were randomized onto this study between August of 1993 and July of 1994. One patient was ineligible and four patients were cancelled prior to starting any study medication, leaving 97 total evaluable patients. All of the stratification factors were well balanced but there was a slightly higher incidence of current tobacco use in the placebo group. There was a differential drop out rate between the two arms. During the first two treatment weeks, only two of the placebo patients (4%) compared to 20 of the sucralfate patients (40%) dropped out of the study. After the second week, relatively equal drop out rates were seen with 9 sucralfate

  9. Hyperbaric Oxygen Therapy for Radiation-Induced Cystitis and Proctitis

    International Nuclear Information System (INIS)

    Oliai, Caspian; Fisher, Brandon; Jani, Ashish; Wong, Michael; Poli, Jaganmohan; Brady, Luther W.; Komarnicky, Lydia T.

    2012-01-01

    Purpose: To provide a retrospective analysis of the efficacy of hyperbaric oxygen therapy (HBOT) for treating hemorrhagic cystitis (HC) and proctitis secondary to pelvic- and prostate-only radiotherapy. Methods and Materials: Nineteen patients were treated with HBOT for radiation-induced HC and proctitis. The median age at treatment was 66 years (range, 15–84 years). The range of external-beam radiation delivered was 50.0–75.6 Gy. Bleeding must have been refractory to other therapies. Patients received 100% oxygen at 2.0 atmospheres absolute pressure for 90–120 min per treatment in a monoplace chamber. Symptoms were retrospectively scored according to the Late Effects of Normal Tissues—Subjective, Objective, Management, Analytic (LENT-SOMA) scale to evaluate short-term efficacy. Recurrence of hematuria/hematochezia was used to assess long-term efficacy. Results: Four of the 19 patients were lost to follow-up. Fifteen patients were evaluated and received a mean of 29.8 dives: 11 developed HC and 4 proctitis. All patients experienced a reduction in their LENT-SOMA score. After completion of HBOT, the mean LENT-SOMA score was reduced from 0.78 to 0.20 in patients with HC and from 0.66 to 0.26 in patients with proctitis. Median follow-up was 39 months (range, 7–70 months). No cases of hematuria were refractory to HBOT. Complete resolution of hematuria was seen in 81% (n = 9) and partial response in 18% (n = 2). Recurrence of hematuria occurred in 36% (n = 4) after a median of 10 months. Complete resolution of hematochezia was seen in 50% (n = 2), partial response in 25% (n = 1), and refractory bleeding in 25% (n = 1). Conclusions: Hyperbaric oxygen therapy is appropriate for radiation-induced HC once less time-consuming therapies have failed to resolve the bleeding. In these conditions, HBOT is efficacious in the short and long term, with minimal side effects.

  10. Safety consequences of the release of radiation induced stored energy

    International Nuclear Information System (INIS)

    Prij, J.

    1994-08-01

    Due to the disposal of HLW in a salt formation gamma energy will be deposited in the rock salt. Most of this energy will be converted into heat, whilst a small part will create defects in the salt crystals. Energy is stored in the damaged crystals. Due to uncertainties in the models and differences in the disposal concepts the estimated values for the stored energy range from 10 to 1000 J/g in the most heavily damaged crystals close to the waste containers. The amount of radiation damage decays exponentially with increasing distance from the containers and at distances larger than 0.2 m the stored energy can be neglected. Given the uncertainties in the model predictions and in the possible release mechanism an instantaneous release of stored energy cannot be excluded completely. Therefore the thermo-mechanical consequences of a postulated instantaneous release of an extremely high amount of radiation induced stored energy have been estimated. These estimations are based on the quasi-static solutions for line and point sources. To account for the dynamic effects and the occurrence of fractures an amplification factor has been derived from mining experience with explosives. A validation of this amplification factor has been given using post experimental observations of two nuclear explosions in a salt formation. For some typical disposal concepts in rock salt the extent of the fractured zone has been estimated. It appeared that the radial extent of the fractured zone is limited to 5 m. Given the much larger distance between the individual boreholes and the distance between the boreholes and the boundary of the salt formation (more than 100 m), the probability of a release of radiation induced stored energy creating a pathway for the nuclides from the containers to the groundwater, is extremely low. The radiological consequences of a groundwater intrusion scenario induced by this very unprobable pathway are bounded by the 'standard' groundwater intrusion

  11. Formation of radiation induced precipitates in VVER RPV materials

    International Nuclear Information System (INIS)

    Platonov, P.A.; Chernobaeva, A.A.

    2016-01-01

    This paper presents an analysis of experimental results received in course of research of copper-enriched precipitates (Cu-precipitates) and nickel-manganese-silicon clusters (Ni-Mn-Si clusters), which are formed in steels of VVER-type reactor pressure vessels (RPVs) under neutron irradiation. Based on this analysis, a hypothetical model is suggested for cluster formation in course of evolution of a cascade region. The model presumes cluster formation in two stages. At the first stage, in course of cascade region crystallization, a stable cluster is formed in the center of the cascade region, which consists of vacancies and Cu atoms following the mechanism of the inverse Kirkendall effect. At the second stage, diffusion of Ni, Mn and P atoms with a flow of vacancies from the matrix takes place to form a cluster. The size of a cluster is limited by a balance of vacancies' flows entering and leaving the cluster. The paper also considers a possibility of stabilization of atomic-vacancy cluster due to uneven distribution of Ni, Mn and P atoms, which explains dependence of cluster density on the content of these elements. Kinetics of cluster formation and evolution presumed by suggested model is analyzed. It is demonstrated that a fall in cluster density and an increase in their size under high irradiation doses may be caused by a decrease of matrix supersaturation with vacancies resulting from high density of dislocation loops. - Highlights: • The analysis of the mechanism of formation of radiation-induced clusters in RPV steels has been done. • Radiation-induced clusters are formed after the mechanism based on the inverse Kirkendall effect in two stages. • At post-dynamic stage a flow of vacancies moving to the center of the cascade entrains Cu atoms contained and forms a stable atom-vacancies cluster. • At the 2nd stage Cu, Ni, Mn, Si atoms forming complexes with vacancies diffuse into a cluster driving out Fe and Cr atoms from the cluster. • The cluster

  12. Perinatal radiation-induced renal damage in the beagle

    International Nuclear Information System (INIS)

    Jaenke, R.S.; Angleton, G.M.

    1990-01-01

    The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated

  13. Radiation-induced bystander effects in vivo are sex specific

    International Nuclear Information System (INIS)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-01-01

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes

  14. Gamma radiation induced changes in nuclear waste glass containing Eu

    Science.gov (United States)

    Mohapatra, M.; Kadam, R. M.; Mishra, R. K.; Kaushik, C. P.; Tomar, B. S.; Godbole, S. V.

    2011-10-01

    Gamma radiation induced changes were investigated in sodium-barium borosilicate glasses containing Eu. The glass composition was similar to that of nuclear waste glasses used for vitrifying Trombay research reactor nuclear waste at Bhabha Atomic Research Centre, India. Photoluminescence (PL) and electron paramagnetic resonance (EPR) techniques were used to study the speciation of the rare earth (RE) ion in the matrix before and after gamma irradiation. Judd-Ofelt ( J- O) analyses of the emission spectra were done before and after irradiation. The spin counting technique was employed to quantify the number of defect centres formed in the glass at the highest gamma dose studied. PL data suggested the stabilisation of the trivalent RE ion in the borosilicate glass matrix both before and after irradiation. It was also observed that, the RE ion distributes itself in two different environments in the irradiated glass. From the EPR data it was observed that, boron oxygen hole centre based radicals are the predominant defect centres produced in the glass after irradiation along with small amount of E’ centres. From the spin counting studies the concentration of defect centres in the glass was calculated to be 350 ppm at 900 kGy. This indicated the fact that bulk of the glass remained unaffected after gamma irradiation up to 900 kGy.

  15. Submandibular salivary gland transfer prevents radiation-induced xerostomia

    International Nuclear Information System (INIS)

    Jha, Naresh; Seikaly, Hadi; McGaw, Timothy; Coulter, Linda

    2000-01-01

    Background: Xerostomia is a significant morbidity of radiation therapy in the management of head and neck cancers. We hypothesized that the surgical transfer of one submandibular salivary gland to submental space, outside the proposed radiation field, prior to starting radiation treatment, would prevent xerostomia. Methods: We are conducting a prospective clinical trial where the submandibular gland is transferred as part of the surgical intervention. The patients are followed clinically, with salivary flow studies and University of Washington quality of life questionnaire. Results: We report early results of 16 patients who have undergone this procedure. Seven patients have finished and 2 patients are currently undergoing radiation treatment. In 2 patients, no postoperative radiation treatment was indicated. Two patients are waiting to start radiation treatment and 2 patients refused treatment after surgery. The surgical transfer was abandoned in 1 patient. All of the transferred salivary glands were positioned outside the proposed radiation fields and were functional. The patients did not complain of any xerostomia and developed only minimal oral mucositis. There were no surgical complications. Conclusions: Surgical transfer of a submandibular salivary gland to the submental space (outside the radiation field) preserves its function and prevents the development of radiation-induced xerostomia

  16. Radiation-induced grafting of acrylic acid onto polyethylene filaments

    International Nuclear Information System (INIS)

    Kaji, K.; Sakurada, I.; Okada, T.

    1981-01-01

    Radiation-induced grafting of acrylic acid onto high density polyethylene (PE) filaments was carried out in order to raise softening temperature and impart flame retardance and hydrophilic properties. Mutual γ-irradiation method was employed for the grafting in a mixture of acrylic acid (AA), ethylene dichloride and water containing a small amount of ferrous ammonium sulfate. The rate of grafting was very low at room temperature. On the other hand, large percent grafts were obtained when the grafting was performed at an elevated temperature. Activation energy for the initial rate of grafting was found to be 17 kcal/mol between 20 and 60 0 C and 10 kcal/ mol between 60 and 80 0 C. Original PE filament begins to shrink at 70 0 C, shows maximum shrinkage of 50% at 130 0 C and then breaks off at 136 0 C. When a 34% AA graft is converted to metallic salt the graft filament retains its filament form even above 300 0 C and gives maximum shrinkage of 15%. Burning tests by a wire-netting basket method indicate that graft filaments and their metallic salts do not form melting drops upon burning and are self-extinguishing. Original PE filament shows no moisture absorption; however, that of AA-grafted PE increases with increasing graft percent. (author)

  17. Toxic clinical hypoxic radiation sensitizers plus radiation-induced toxicity

    International Nuclear Information System (INIS)

    Richmond, R.C.

    1984-01-01

    The operational definition espoused twelve years ago that clinical hypoxic radiation sensitizers should be nontoxic interferes with the recognition and research of useful radiation sensitizers. Eight years ago the toxic antitumor drug cis-dichlorodiammineplatinum(II) was reported to be a hypoxic radiation sensitizer and the selective antitumor action of this drug was stressed as potentially creating tumor-targeted radiation sensitization. This rationale of oxidative antitumor drugs as toxic and targeted clinical sensitizers is useful, and has led to the study reported here. The antitumor drug cis-(1,1-cyclobutane-dicarboxylato)diammineplatinum(II), or JM-8, is being tested in clinical trials. Cells of S. typhimurium in PBS in the presence of 0.2mM JM-8 are found to be sensitized to irradiation under hypoxic, but not oxic, conditions. JM-8 is nontoxic to bacteria at this concentration, but upon irradiation the JM-8 solution becomes highly toxic. This radiation induced toxicity of JM-8 preferentially develops from hypoxic solution, and thus contributes to the rationale of hypoxic tumor cell destruction

  18. Long term radiological features of radiation-induced lung damage.

    Science.gov (United States)

    Veiga, Catarina; Landau, David; McClelland, Jamie R; Ledermann, Jonathan A; Hawkes, David; Janes, Sam M; Devaraj, Anand

    2018-02-01

    To describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation. Baseline and 12-month CT scans of 33 patients were reviewed from a phase I/II clinical trial of isotoxic chemoradiation (IDEAL CRT). CT findings were scored in three categories derived from eleven sub-categories: (1) parenchymal change, defined as the presence of consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or reticulation; (2) lung volume reduction, identified through reduction in lung height and/or distortions in fissures, diaphragm, anterior junction line and major airways anatomy, and (3) pleural changes, either thickening and/or effusion. Six patients were excluded from the analysis due to anatomical changes caused by partial lung collapse and abscess. All remaining 27 patients had radiological evidence of lung damage. The three categories, parenchymal change, shrinkage and pleural change were present in 100%, 96% and 82% respectively. All patients had at least two categories of change present and 72% all three. GGOs, reticulation and traction bronchiectasis were present in 44%, 52% and 37% of patients. Parenchymal change, lung shrinkage and pleural change are present in a high proportion of patients and are frequently identified in RILD. GGOs, reticulation and traction bronchiectasis are common at 12 months but not diagnostic. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Spontaneous and radiation induced gene conversion in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Rao, B.S.; Murthy, M.S.S.

    1977-01-01

    Spontaneous and radiation induced gene conversion to arginine independence was studied in a heteroallelic diploid strain of yeast Saccharomyces cerevisiae BZ 34. When stationary phase cells were incubated in phosphate buffer (pH 7 ) at 30 0 C under aerated condition for 48 hours, the conversion frequency increased by a factor of about 1000 times the background. This was found to be so even when the cells were incubated in saline (0.85%) or distilled water. Various conditions influencing this enhancement have been investigated. Conversion frequency enhancement was not significant under anoxic conditions and was absent at low temperatures and in log phase cells. Caffeine could inhibit this enhancement when present in the suspension medium. These results can be explained on the basis of the induction of meiosis in cells held in buffer. Microscopic examination confirmed this view. Under conditions not favourable for the onset of meiosis there is no significant enhancement in conversion frequency. In stationary phase cells exposed to series of gamma doses, the conversion frequency increases with dose. Post irradiation incubation in buffer further increases the conversion frequency. However, the increase expressed as the ratio of the conversion frequency on buffer holding to that on immediate plating decreased with increasing dose. This decrease in enhancement with increasing dose may be due to the dose dependent inhibition of meiosis. (author)

  20. R and D activities on radiation induced mutation breeding

    International Nuclear Information System (INIS)

    Lapade, A.G.; Asencion, A.B.; Santos, I.S.; Grafia, A.O.; Veluz, AM.S.; Barrida, A.C.; Marbella, L.J.

    1996-01-01

    This paper summarizes the accomplishments, prospects and future plans of mutation breeding for crop improvement at the Philippine Nuclear Research Institute (PNRI). Mutation induction has become a proven way creating variation within a crop variety and inducing desired attributes that cannot be found in nature or have been lost during evolution. Several improved varieties with desirable traits were successfully developed through induced mutation breeding at our research institute. In rice, mutation breeding has resulted in the development of new varieties: (1) PARC 2, (2) Milagrosa mutant, (3) Bengawan mutant and (4) Azmil mutant. Mutation breeding in leguminous crops has led to the induction of an improved L 114 soybean mutant that is shorter that the original variety but yield about 40% more. Several PAEC mungbean varieties characterized with long pods that are non-shattering were also induced. In asexually propagated crops, an increase in yield and chlorophyll mutants were obtained in sweet potatos. Likewise, chlorophyll mutant which look-like 'ornamental bromeliads' and a mutant with reduced spines have been developed in pineapple Queen variety. At present, we have started a new project in mutation breeding in ornamentals. Tissue culture is being utilized in our mutation breeding program. In the near future, radiation induced mutagenesis coupled with in vitro culture techniques on protoplast culture and somatic hybridization will be integrated into our mutation breeding program to facilitate the production of new crop varieties. (author)

  1. Hybrid model of the radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Braga, Viviane V.B.; Faria, Fernando Pereira de; Grynberg, Suely Epsztein

    2013-01-01

    The radiation-induced bystander effect (RIBE) refer to biological alterations in non-irradiated cells that occupy the same medium (culture or tissue) of irradiated cells. The biochemical mechanisms of the RIBE are not completely elucidated. However, several experiments indicate its existence. The objective of this work is to quantify the effect via stochastic and deterministic approaches. The hypotheses of the model are: a) one non-irradiated healthy cell interacts with signals that propagate through the medium. These signals are released by irradiated cells. At the time of interaction cell-signal, the cell can become damaged and signaling or damage and not signaling; b) Both types of damage cells repair with certain rate becoming health cells; c) The diffusion of signals obey the discrete diffusion equation with decay in two dimensions. d) The signal concentration released by irradiated cells depends on the dose in the low dose range (< 0.3 Gy) and saturates for higher dose values. As expected, the temporal analysis of the model as a function of the repair rate shows that the survival fraction decreases as the repair rate is reduced. The analysis of the extent of damage triggered by a signal concentration released by a single irradiated cell at time zero show that the damage grows with the maximum simulation time. The results show good agreement with the experimental data. The stochastic and deterministic methods used are in qualitative agreement, as expected. (author)

  2. Solvent influence during radiation induced grafting of styrene in PVDF

    International Nuclear Information System (INIS)

    Ferreira, Henrique P.; Parra, Duclerc F.; Lugao, Ademar B.

    2013-01-01

    Radiation-induced grafting was studied to produce styrene grafted poly(vinylidene fluoride) (PVDF) membranes. PVDF films with 0.125 mm thickness were irradiated at doses between 5 and 20 kGy in the presence of styrene/N,N-dimethylformamide (DMF), styrene/acetone or styrene/toluene solutions (1:1, v/v) at dose rate of 5 kGy h -1 by simultaneous method, using gamma rays from a Co-60, under nitrogen atmosphere and at room temperature. The films were characterized before and after modification by grafting yield (GY %), infrared spectroscopy (FT-IR), scanning electron microscopy (SEM and EDS), differential scanning calorimetry (DSC) and thermogravimetry (TG/DTG). GY results shows that grafting increases with dose and toluene hinders the grafting, leading to a small GY comparing to DMF and acetone. It was possible to confirm the grafting of styrene by FT-IR due to the new characteristics peaks and by the TG and DSC due to changes in thermal behavior of the grafted material. SEM and EDS show surface and cross-section distribution of the grafting, which takes place on the surface and heterogeneously with toluene as solvent and homogeneously and penetrating into the inner layers of the matrix using DMF and acetone as solvent. (author)

  3. Radiation induced defect flux behaviors at zirconium based component

    International Nuclear Information System (INIS)

    Choi, Sang Il; Kim, Ji Hyun; Kwon, Jun Hyun; Lee, Gyeong Geun

    2013-01-01

    In commercial reactor core, structure materials are located in high temperature and high pressure environment. Therefore, main concern of structure materials is corrosion and mechanical properties change than radiation effects on materials. However, radiation effects on materials become more important phenomena because research reactor condition is different from commercial reactor. The temperature is lower than 100 .deg. C and radiation dose is much higher than that of commercial reactor. Among the radiation effect on zirconium based metal, radiation induced growth (RIG), known as volume conservative distortion, is one of the most important phenomena. Recently, theoretical RIG modeling based on radiation damage theory (RDT) and balance equation are developed. However, these growth modeling have limited framework of single crystal and high temperature. To model theoretical RIG in research reactor, qualitative mechanism must be set up. Therefore, this paper intent is establishing defect flux mechanism of zirconium base metal in research reactor for RIG modeling. After than theoretical RIG work will be expanded to research reactor condition

  4. Radiation induced degradation of dyes-An overview

    International Nuclear Information System (INIS)

    Rauf, M.A.; Ashraf, S. Salman

    2009-01-01

    Synthetic dyes are a major part of our life. Products ranging from clothes to leather accessories to furniture all depend on extensive use of organic dyes. An unfortunate side effect of extensive use of these chemicals is that huge amounts of these potentially carcinogenic compounds enter our water supplies. Various advanced oxidation processes (AOPs) including the use of high-energy radiation have been developed to degrade these compounds. In this review, dye decoloration and degradation as a result of its exposure to high energy radiation such as gamma radiation and pulsed electron beam are discussed in detail. The role of various transient species such as ·H, ·OH and e aq - are taken into account as reported by various researchers. Literature citations in this area show that e aq - is very effective in decolorization but is less active in the further degradation of the products formed. The degradation of the dyes is initiated exclusively by ·OH attack on electron-rich sites of the dye molecules. Additionally, various parameters that affect the efficiency of radiation induced degradation of dyes, such as effect of radiation dose, oxygen, pH, hydrogen peroxide, added ions and dye classes are also reviewed and summarized. Lastly, pilot plant application of radiation for wastewater treatment is briefly discussed.

  5. Genomic rearrangement in radiation-induced murine myeloid leukemia

    International Nuclear Information System (INIS)

    Ishihara, Hiroshi

    1994-01-01

    After whole body irradiation of 3Gy X ray to C3H/He male mice, acute myeloid leukemia is induced at an incidence of 20 to 30% within 2 years. We have studied the mechanism of occurrence of this radiation-induced murine myeloid leukemia. Detection and isolation of genomic structural aberration which may be accumulated accompanied with leukemogenesis are helpful in analyzing the complicated molecular process from radiation damage to leukemogenesis. So, our research work was done in three phases. First, structures of previously characterized oncogenes and cytokine-related genes were analyzed, and abnormal structures of fms(protooncogene encoding M-CSF receptor gene)-related and myc-related genes were found in several leukemia cells. Additionally, genomic structural aberration of IL-3 gene was observed in some leukemia cells, so that construction of genomic libraries and cloning of the abnormal IL-3 genomic DNAs were performed to characterize the structure. Secondly, because the breakage of chromosome 2 that is frequently observed in myeloid leukemia locates in proximal position of IL-1 gene cluster in some cases, the copy number of IL-1 gene was determined and the gene was cloned. Lastly, the abnormal genome of leukemia cell was cloned by in-gel competence reassociation method. We discussed these findings and evaluated the analysis of the molecular process of leukemogenesis using these cloned genomic fragments. (author)

  6. Pilocarpine and carbacholine in treatment of radiation-induced xerostomia

    International Nuclear Information System (INIS)

    Joensuu, H.; Bostroem, P.; Makkonen, T.

    1993-01-01

    Twenty-four patients with radiation-related xerostomia were treated with oral pilocarpine solution 6 mg t.i.d., and after a 4-week drug-free period 16 of these patients were treated with carbacholine 2 mg tablets t.i.d. Basal and stimulated whole saliva flow rates were measured before commencing the drug treatment, and after 1 and 12 weeks on treatment. On a subjective linear scale both pilocarpine (p=0.01) and carbacholine (p=0.02) improved mouth moistness. Only 2 of the 8 patients with no basal or stimulated saliva flow reported some subjective benefit from the drug treatment, whereas all 8 patients with less severe xerostomia improved (p=0.007). However, the salivary flow rates measured 12 h after the last drug dose did not improve with either drug. Both drugs were generally well tolerated. It is concluded that both drugs may be useful in the treatment of radiation-induced xerostomia among patients with residual salivary function. (author). 6 refs., tabs

  7. Effect of radiation-induced amorphization on smectite dissolution.

    Science.gov (United States)

    Fourdrin, C; Allard, T; Monnet, I; Menguy, N; Benedetti, M; Calas, G

    2010-04-01

    Effects of radiation-induced amorphization of smectite were investigated using artificial irradiation. Beams of 925 MeV Xenon ions with radiation dose reaching 73 MGy were used to simulate the effects generated by alpha recoil nuclei or fission products in the context of high level nuclear waste repository. Amorphization was controlled by X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. An important coalescence of the smectite sheets was observed which lead to a loss of interparticle porosity. The amorphization is revealed by a loss of long-range structure and accompanied by dehydroxylation. The dissolution rate far-from-equilibrium shows that the amount of silica in solution is two times larger in the amorphous sample than in the reference clay, a value which may be enhanced by orders of magnitude when considering the relative surface area of the samples. Irradiation-induced amorphization thus facilitates dissolution of the clay-derived material. This has to be taken into account for the safety assessment of high level nuclear waste repository, particularly in a scenario of leakage of the waste package which would deliver alpha emitters able to amorphize smectite after a limited period of time.

  8. Hybrid model of the radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Viviane V.B.; Faria, Fernando Pereira de; Grynberg, Suely Epsztein, E-mail: vitoriabraga06@gmail.com, E-mail: fernandopereirabh@gmail.com, E-mail: seg@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    The radiation-induced bystander effect (RIBE) refer to biological alterations in non-irradiated cells that occupy the same medium (culture or tissue) of irradiated cells. The biochemical mechanisms of the RIBE are not completely elucidated. However, several experiments indicate its existence. The objective of this work is to quantify the effect via stochastic and deterministic approaches. The hypotheses of the model are: a) one non-irradiated healthy cell interacts with signals that propagate through the medium. These signals are released by irradiated cells. At the time of interaction cell-signal, the cell can become damaged and signaling or damage and not signaling; b) Both types of damage cells repair with certain rate becoming health cells; c) The diffusion of signals obey the discrete diffusion equation with decay in two dimensions. d) The signal concentration released by irradiated cells depends on the dose in the low dose range (< 0.3 Gy) and saturates for higher dose values. As expected, the temporal analysis of the model as a function of the repair rate shows that the survival fraction decreases as the repair rate is reduced. The analysis of the extent of damage triggered by a signal concentration released by a single irradiated cell at time zero show that the damage grows with the maximum simulation time. The results show good agreement with the experimental data. The stochastic and deterministic methods used are in qualitative agreement, as expected. (author)

  9. Chromatin Structure and Radiation-Induced Intrachromosome Exchange

    Science.gov (United States)

    Mangala; Zhang, Ye; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    We have recently investigated the location of breaks involved in intrachromosomal type exchange events, using the multicolor banding in situ hybridization (mBAND) technique for human chromosome 3. In human epithelial cells exposed to both low- and high-LET radiations in vitro, intrachromosome exchanges were found to occur preferentially between a break in the 3p21 and one in the 3q11. Exchanges were also observed between a break in 3p21 and one in 3q26, but few exchanges were observed between breaks in 3q11 and 3q26, even though the two regions were on the same arm of the chromosome. To explore the relationships between intrachromosome exchanges and chromatin structure, we used probes that hybridize the three regions of 3p21, 3q11 and 3q26, and measured the distance between two of the three regions in interphase cells. We further analyzed fragile sites on the chromosome that have been identified in various types of cancers. Our results demonstrated that the distribution of breaks involved in radiation-induced intrachromosome aberrations depends upon both the location of fragile sites and the folding of chromatins

  10. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    Science.gov (United States)

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  11. Radiation-induced bystander effects in vivo are sex specific

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  12. Radiation-induced optic neuropathy: A magnetic resonance imaging study

    International Nuclear Information System (INIS)

    Guy, J.; Mancuso, A.; Beck, R.; Moster, M.L.; Sedwick, L.A.; Quisling, R.G.; Rhoton, A.L. Jr.; Protzko, E.E.; Schiffman, J.

    1991-01-01

    Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain

  13. Mechanisms of radiation-induced neoplastic cell transformation

    International Nuclear Information System (INIS)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

  14. Contribution to the study of radiation induced bone tissue cancer

    International Nuclear Information System (INIS)

    Bouet, Monique.

    1975-01-01

    In this work four original observations of more or less long-delayed cancers induced by ionizing radiations are compared with 34 other cases in the literature, after which an attempt is made to establish a general and prognostic synthesis of the results; the indications to emerge are as follows: - Ionizing radiation-induced cancers are very rare, especially when compared with the extensive therapeutic use made of X-rays; - The probability of radio-cancer formation, though no figures are given in the many papers consulted, seems nevertheless to be higher in cases of benign lesion irradiation; - Induced cancers have been observed after treatments with all types of radiation, whether or not the lesion is tumoral or cancerous, whatever the patient's age at the time of irradiations; - As a general rule these neoplasms appear after a variable latency period but usually from the 6th post-radiotherapy year onwards, with a greater frequency range between 6 and 12 years; - These induced cancers are generally epitheliomas or sarcomas, the latter being noticeably more predominant than in the case of spontaneous cancers. Leukoses may also be observed [fr

  15. Radiation-induced-radioresistance: mechanisms and modification radioprotection

    International Nuclear Information System (INIS)

    Bala, Madhu

    2005-01-01

    Full text: The term radiation-induced-radioresistance (RIR) has been chosen to explain a particular class of resistance against lethal doses of radiation, which is transient and is induced by pre-exposure to low doses of radiation. This is a genetically governed phenomenon and is different from adaptation which in one of its several senses, refers to evolutionary transformation into new behavioural patterns. RIR is understood to be an evolutionarily conserved fundamental cellular defense mechanism. Small doses of radiation acting as stress stimuli evoke a concerted action of molecular pathways which help the organism to cope-up with the genotoxic effects of lethal doses of radiation given subsequently. Such molecular pathways are a complex interplay of genetic and biochemical entities and are increasingly becoming the focus of research world over. Most of our information on this subject has been gathered from prokaryotes, simpler eukaryotes, human cells and the epidemiological studies. A number of genes such as GADD 45, CDKN1A, PBP74, DIR1, DDR have been reported by to participate in RIR. However, till date, the mechanism of RIR remain poorly understood. In this deliberation some of our findings on mechanisms of RIR will be presented. Further, modification of RIR by a metabolic modifier, presently under clinical investigations for tumor radiotherapy, will also be presented

  16. Radiation-induced cancer of the skin in man

    International Nuclear Information System (INIS)

    Kiyono, Kunihiro; Moriya, Kumiko; Kobayashi, Toshio

    1981-01-01

    Eight cases of radiation induced cancer of the skin observed at the Shinshu University during 30 years from 1951 to 1938 were reported. All of the tumors were squamous cell carcinomas; 7 out of 8 cases occurred in males. Primary conditions for which irradiation was given were 6 cases of benign disorders of various skin disease and 2 cases of spinal tuberculosis. The mean age at which these patients were first subjected to radiation therapy was 31 years. At the time when the diagnosis of skin cancer was established, the mean age was 47 years, with a range from 35 to 58 years. The latent period distributed between 9 and 28 years, with the average of 16.4 years. The estimated radiation doses sufficient to induce cancer of the skin was found to be some thousands R or more, the lowest irradiation dose being about 2,000 R. There was no close correlation between the radiation dose and the latent period, nor between the age of the patient at the time of irradiation and the latent period. The tumors usually occurred in the skin areas where extensive irradiation changes were shown, especially in ulcerative area. (author)

  17. Alteration of radiation-induced hematotoxicity by amifostine

    International Nuclear Information System (INIS)

    Momm, Felix; Bechtold, Christine; Rudat, Volker; Strnad, Vratislav; Tsekos, Alexander; Fischer, Karin; Henke, Michael

    2001-01-01

    Purpose: To investigate whether amifostine can reduce radiation hematotoxicity. Patients and Methods: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5x2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m 2 amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n=501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. Results: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10 3 /mm 3 to 5.8x10 3 /mm 3 (difference: 2.3x10 3 /mm 3 ). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. Conclusion: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study

  18. Radiation induced chemical reaction of carbon monoxide and hydrogen mixture

    International Nuclear Information System (INIS)

    Sugimoto, Shun-ichi; Nishii, Masanobu

    1985-01-01

    Previous studies of radiation induced chemical reactions of CO-H 2 mixture have revealed that the yields of oxygen containing products were larger than those of hydrocarbons. In the present study, methane was added to CO-H 2 mixture in order to increase further the yields of the oxygen containing products. The yields of most products except a few products such as formaldehyde increased with the addition of small amount of methane. Especially, the yields of trioxane and tetraoxane gave the maximum values when CO-H 2 mixture containing 1 mol% methane was irradiated. When large amounts of methane were added to the mixture, the yields of aldehydes and carboxylic acids having more than two carbon atoms increased, whereas those of trioxane and tetraoxane decreased. From the study at reaction temperature over the range of 200 to 473 K, it was found that the yields of aldehydes and carboxylic acids showed maxima at 323 K. The studies on the effects of addition of cationic scavenger (NH 3 ) and radical scavenger (O 2 ) on the products yields were also carried out on the CO-H 2 -CH 4 mixture. (author)

  19. Radiation-induced grafting of TMPM onto polypropylene

    International Nuclear Information System (INIS)

    Wang Huiliang; Li Hong; Chen Wenxiu

    1995-01-01

    The gamma radiation-induced graft copolymerization of 2,2,6,6-tetramethyl-4-piperidinyl-methacrylate (TMPM), a very effective hindered amine light stabilizer (HALS), onto polypropylene was investigated by simultaneous- irradiation technique. The various synthesis conditions on the graft content was studied. It was found that benzene, CCl 4 and petroleum ether are more effective than other solvents, the percent grafting reached 7.1% for benzene. The percent grafting is higher when graft copolymerization is carried out in argon atmosphere than those in air. For all the grafting copolymerization carried out in benzene and CCl 4 , percent grafting increase linearly from 1 to 5 Mrad and beyond 5 Mrad, a tendency to level off appeared. At a constant dose, the percent grafting was found to be higher at high dose rate until 228 rad/s. Percent grafting also increased continuously with increasing monomer concentration up to 2.85 mol/L, but significant increase in grafting was observed only up to 1.14 mol/L

  20. Radiation induced sarcoma after treatment of glioblastoma: case report

    International Nuclear Information System (INIS)

    Rosa, Victor Domingos Lisita; Anjos, Caroline Souza dos; Candido, Priscila Barile Marchi; Dias Junior, Antonio Soares; Santos, Evandro Airton Sordi dos; Godoy, Antonio Carlos Cavalcante; Saggioro, Fabiano P.; Carlotti Junior, Carlos Gilberto; Oliveira, Harley Francisco de; Peria, Fernanda Maris

    2016-01-01

    Introduction: Glioblastoma multiform is the most lethal central nervous system neoplasm, with a median survival of around 13 months and the worst prognosis among all gliomas. The therapeutic approach of glioblastoma consists in neurosurgery with maximum possible resection of tumor volume, followed by radiotherapy and chemotherapy. Radiotherapy reduces the risk of tumor recurrence through direct and indirect damage to tumor deoxyribonucleic acid. The long-term effects of radiation therapy include tissue necrosis, vasculopathy, and radiation-induced neoplasia. The most reported secondary intracranial malignant tumors include meningiomas, gliomas, and sarcomas. The latency period between skull radiotherapy and the appearance of radioinduced lesions varies in the literature from six months to 47 years, with an average of 18.7 years. Case report: The present report describes the appearance of high-grade spindle cell sarcoma after ten months in a patient who received glioblastoma treatment at Hospital das Clínicas of Ribeirão Preto of the University of São Paulo. Conclusion: The rarity of this association is probably due to the poor survival of patients with glioblastoma, thus limiting the time to development of secondary neoplasia

  1. Radiation induced homogeneous precipitation in undersaturated solid-solutions

    International Nuclear Information System (INIS)

    Cauvin, R.; Martin, G.

    1979-01-01

    A TEM study of 1 MeV electron irradiated Al 1.9 at% Zn solid solution shows that Zn precipitates form, under irradiation at temperatures well above the Zn solvus temperature outside irradiation. The corresponding upward shift of this temperature is dose rate dependent. This new example of radiation-induced precipitation exhibits unexpected features, which are not accounted for by the available models: (1) no correlation exists between the location of the precipitates and that of the point defects sinks; (2) the precipitation of incoherent β-phase with atomic volume smaller than that of the matrix, and of coherent G.P. zones both occurs; (3) the size of the coherent β precipitates saturates at large dose. A general mechanism for solute concentration fluctuations under irradiation is proposed which qualitatively accounts for the formation of coherent G.P. zones and for the nucleation of solute clusters with more complex structures. A reanalysis of Russell's model (1977) for the growth of incoherent precipitates shows that it may qualitatively account for the observed behavior of the β phase precipitates. (Auth.)

  2. Sucralfate for the treatment of radiation induced mucositis

    International Nuclear Information System (INIS)

    Belka, C.; Hoffmann, W.; Paulsen, F.; Bamberg, M.

    1997-01-01

    Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation. (orig.) [de

  3. Radiation-induced hypoxia may perpetuate late normal tissue injury

    International Nuclear Information System (INIS)

    Vujaskovic, Zeljko; Anscher, Mitchell S.; Feng, Q.-F.; Rabbani, Zahid N.; Amin, Khalid; Samulski, Thaddeus S.; Dewhirst, Mark W.; Haroon, Zishan A.

    2001-01-01

    Purpose: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. Methods and Materials: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry. Results: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-β, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways. Conclusion: A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines

  4. Modification of radiation-induced DNA lesions by oxygen

    International Nuclear Information System (INIS)

    Meyn, R.E.; Jenkins, W.T.

    1984-01-01

    The efficiency of DNA strand break production by radiation under aerated and hypoxic conditions was determined in CHO cells using the technique of alkaline elution. The resulting oxygen enhancement ratio was surprisingly high, 7.8. When the pH of the elution was increased from 12.1, the normally used pH, to 12.8, a substantial increase in the strand breaks produced in the hypoxic cells was observed, resulting in an OER of 4.8. This difference in susceptibility of DNA strand break detection as a function of pH suggested a difference in the type of lesions produced in DNA when irradiated under aerated and hypoxic conditions. Further experiments to examine the DNA-protein crosslinks produced by radiation suggested that the apparent lower level of strand breaks in hypoxic cells may be due to a higher level of DNA-protein crosslinks produced under hypoxic conditions. Thus, oxygen may not only act by modifying the quantity of radiation-induced DNA lesions but may also cause qualitative changes. If the different types of DNA lesions have different contributions to lethality, the OER for cell survival may represent a complex composite of these changes at the molecular level

  5. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  6. Outcome of Carotid Artery Stenting for Radiation-Induced Stenosis

    International Nuclear Information System (INIS)

    Dorresteijn, Lucille; Vogels, Oscar; Leeuw, Frank-Erik de; Vos, Jan-Albert; Christiaans, Marleen H.; Ackerstaff, Rob; Kappelle, Arnoud C.

    2010-01-01

    Purpose: Patients who have been irradiated at the neck have an increased risk of symptomatic stenosis of the carotid artery during follow-up. Carotid angioplasty and stenting (CAS) can be a preferable alternative treatment to carotid endarterectomy, which is associated with increased operative risks in these patients. Methods and Materials: We performed a prospective cohort study of 24 previously irradiated patients who underwent CAS for symptomatic carotid stenosis. We assessed periprocedural and nonprocedural events including transient ischemic attack (TIA), nondisabling stroke, disabling stoke, and death. Patency rates were evaluated on duplex ultrasound scans. Restenosis was defined as a stenosis of >50% at the stent location. Results: Periprocedural TIA rate was 8%, and periprocedural stroke (nondisabling) occurred in 4% of patients. After a mean follow-up of 3.3 years (range, 0.3-11.0 years), only one ipsilateral incident event (TIA) had occurred (4%). In 12% of patients, a contralateral incident event was present: one TIA (4%) and two strokes (12%, two disabling strokes). Restenosis was apparent in 17%, 33%, and 42% at 3, 12, and 24 months, respectively, although none of the patients with restenosed vessels became symptomatic. The length of the irradiation to CAS interval proved the only significant risk factor for restenosis. Conclusions: The results of CAS for radiation-induced carotid stenosis are favorable in terms of recurrence of cerebrovascular events at the CAS site.

  7. Radiation-induced aneusomic clones in bone marrow of rats

    International Nuclear Information System (INIS)

    Kohno, Sei-Ichi; Ishihara, Takaaki

    1976-01-01

    Wistar rats 3 months old were given a single whole-body X-irradiation with 700 R. They were killed 9.3 months, on average, after irradiation. From the bone marrows of the 23 irradiated rats, 54 clones of cells with radiation-induced chromosome abnormalities ranging from 3.3 to 78.3% in size were obtained. Karyotype analysis at the banding level showed that 43 out of the 54 clones had balanced chromosome constitutions and that the remaining 11 clones were unbalanced. The 43 balanced clones consisted of 33 clones with reciprocal translocations, 6 with inversions and 4 with both translocations and inversions. The 11 unbalanced clones were made up of 7 aneuploid clones and 4 pseudo-diploid clones. Of the 54 clones, 15 were large with frequencies of more than 25%. Contrary to general belief that cells with unbalanced chromosome constitutions have less capacity to proliferate than those with balanced ones, 8 of the 15 large clones, especially all, except 1, of the largest 6 clones were unbalanced, either aneuploid or pseudo-diploid

  8. Radiation-induced intestinal lesions. Prognosis and surgical management

    International Nuclear Information System (INIS)

    Van Haecke, P.; Vitaux, J.; Michot, F.; Hay, J.-M.; Flamant, Y.; Maillard, J.-N.

    1981-01-01

    Thirteen patients with intestinal lesions consecutive to radiotherapy for carcinoma of the uterus were operated upon between 1973 and 1979. The small bowel was involved in 9 patients and the colon and rectum in 4 patients. Urinary tract lesions were associated in 3 patients of each group. Intestinal necrosis, progression of the lesions and extensive pelvic fibrosis were the only criteria of poor prognosis. Twenty-two operations were performed: 4 for urinary tract lesions and 18 for intestinal lesions. Five patients died during the immediate post-operative period and five died within 2 to 30 months after surgery, including 4 whose carcinoma recurred. The operative technique should be selected according to the extent and severity of radiation-induced damage, as determined by pre-operative examination and thorough exploration of the abdominal cavity once opened. Limited lesions of the small bowel can be treated by resection, but intestinal bypass with latero-lateral anastomosis seems to be preferable in cases with extensive lesions. Patients with colorectal lesions should have defunctioning colostomy prior to any other procedure dictated by the state of affairs. Multiple anastomosis, extensive resections and excessive dissections should be avoided [fr

  9. The process and promotion of radiation-induced cell death

    International Nuclear Information System (INIS)

    Sasaki, Hiroshi

    1998-01-01

    Radiation-induced cell death is divided into reproductive and interphase death, whose process can be revealed by time-lapse observations. Pedigree analyses of progenies derived from a surviving progenitor cell have shown that moribund cells appear in clusters among cells which are apparently undamaged (lethal sectoring). Sister cell fusion, which likely results from chromosome bridge, is the most frequently observed cell abnormality leading to reproductive death. While interphase death does not occur unless the dose exceeds 10 Gy for low LET radiation such as X-rays, high-LET radiation is very effective at inducing interphase death (RBE: ≅3 at 230 keV/μm). Expression or fixation of potentially lethal damage (PLD) is closely associated with cell cycle events and enhanced by inducing premature chromosome condensation (PCC) at a nonpermissive temperature in tsBN2 cells with a ts-defect in RCC1 protein (a regulator of chromatin condensation) which monitors the completion of DNA replication. Furthermore, higher-order structural changes in nuclear matrix such as induced by leptomycin B, an inhibitor of CRM1 (chromosome region maintenance) protein, also play an important role in the fixation of PLD. (author)

  10. Radiation-induced bystander effects in vivo are sex specific.

    Science.gov (United States)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naïve cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  11. Radiation induced destruction of thebaine, papaverine and noscapine in methanol

    International Nuclear Information System (INIS)

    Kantoğlu, Ömer; Ergun, Ece

    2016-01-01

    The presence of methanol decreases the efficiency of radiation-induced decomposition of alkaloids in wastewater. Intermediate products were observed before the complete degradation of irradiated alkaloids. In order to identify the structure of the by-products and the formation pathway, thebaine, papaverine and noscapine solutions were prepared in pure methanol and irradiated using a 60 Co gamma cell at absorbed doses of 0, 1, 3, 5, 7, 10, 30, 50 and 80 kGy. The dose-dependent alkaloid degradation and by-product formation were monitored by ESI mass spectrometer. Molecular structures of the by-products and reaction pathways were proposed. Oxygenated and methoxy group containing organic compounds was observed in the mass spectra of irradiated alkaloids. At initial dose values oxygenated by-products were formed due to the presence of dissolved oxygen in solutions. After the consumption of dissolved oxygen with radicals, the main mechanism was addition of solvent radicals to alkaloid structure. However, it was determined that alkaloids and by-products were completely degraded at doses higher than 50 kGy. The G-value and degradation efficiency of alkaloids were also evaluated. - Highlights: • Oxygenated and methoxy group containing by-products were observed in the mass spectra. • The addition of methanol radiolysis products to alkaloid structure was suggested. • Intermediate products were decomposed at doses above 50 kGy. • The destruction efficiency and degradation G-value of alkaloids were calculated.

  12. Radiation-induced apoptosis in F9 teratocarcinoma cells

    International Nuclear Information System (INIS)

    Langley, R.E.; Palayoor, S.T.; Coleman, C.N.; Bump, E.A.

    1994-01-01

    We have found that F9 murine teratocarcinoma cells undergo morphological changes and internucleosomal DNA fragmentation characteristic of apoptosis after exposure to ionizing radiation. We studied the time course, radiation dose-response, and the effects of protein and RNA synthesis inhibitors on this process. The response is dose dependent in the range 2-12 Gy. Internucleosomal DNA fragmentation can be detected as early as 6 h postirradiation and is maximal by 48 h. Cycloheximide, a protein synthesis inhibitor, and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole, an RNA synthesis inhibitor, both induced internucleosomal DNA fragmentation in the unirradiated cells and enhanced radiation-induced DNA fragmentation. F9 cells can be induced to differentiate into cells resembling endoderm with retinoic acid. After irradiation, differentiated F9 cells exhibit less DNA fragmentation than stem cells. This indicates that ionizing radiation can induce apoptosis in non-lymphoid tumours. We suggest that embryonic tumour cells may be particularly susceptible to agents that induce apoptosis. (Author)

  13. Radiation-induced