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Sample records for radiation inducible gene

  1. Radiation-induced gene responses

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Paunesku, T.; Shearin-Jones, P.; Oryhon, J.

    1996-01-01

    In the process of identifying genes that are differentially regulated in cells exposed to ultraviolet radiation (UV), we identified a transcript that was repressed following the exposure of cells to a combination of UV and salicylate, a known inhibitor of NF-kappaB. Sequencing this band determined that it has identify to lactate dehydrogenase, and Northern blots confirmed the initial expression pattern. Analysis of the sequence of the LDH 5' region established the presence of NF-kappaB, Sp1, and two Ap-2 elements; two partial AP- 1; one partial RE, and two halves of E-UV elements were also found. Electromobility shift assays were then performed for the AP-1, NF- kappaB, and E-UV elements. These experiments revealed that binding to NF-kappaB was induced by UV but repressed with salicylic acid; UV did not affect AP-1 binding, but salicylic acid inhibited it alone or following UV exposure; and E-UV binding was repressed by UV, and salicylic acid had little effect. Since the binding of no single element correlated with the expression pattern of LDH, it is likely that multiple elements govern UV/salicylate-mediated expression

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. Mechanisms of radiation-induced gene responses

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Paunesku, T.

    1996-01-01

    In the process of identifying genes differentially expressed in cells exposed ultraviolet radiation, we have identified a transcript having a 26-bp region that is highly conserved in a variety of species including Bacillus circulans, yeast, pumpkin, Drosophila, mouse, and man. When the 5' region (flanking region or UTR) of a gene, the sequence is predominantly in +/+ orientation with respect to the coding DNA strand; while in the coding region and the 3' region (UTR), the sequence is most frequently in the +/-orientation with respect to the coding DNA strand. In two genes, the element is split into two parts; however, in most cases, it is found only once but with a minimum of 11 consecutive nucleotides precisely depicting the original sequence. The element is found in a large number of different genes with diverse functions (from human ras p21 to B. circulans chitonase). Gel shift assays demonstrated the presence of a protein in HeLa cell extracts that binds to the sense and antisense single-stranded consensus oligomers, as well as to the double- stranded oligonucleotide. When double-stranded oligomer was used, the size shift demonstrated as additional protein-oligomer complex larger than the one bound to either sense or antisense single-stranded consensus oligomers alone. It is speculated either that this element binds to protein(s) important in maintaining DNA is a single-stranded orientation for transcription or, alternatively that this element is important in the transcription-coupled DNA repair process

  8. 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...

  9. 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

  10. 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.

  11. Genistein-induced alterations of radiation-responsive gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Grace, M.B. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: grace@afrri.usuhs.mil; Blakely, W.F.; Landauer, M.R. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    In order to clarify the molecular mechanism of radioprotection and understand biological dosimetry in the presence of medical countermeasure-radioprotectants, their effects on ionizing radiation (IR)-responsive molecular biomarkers must be examined. We used genistein in a radiation model system and measured gene expression by multiplex QRT-PCR assay in drug-treated healthy human blood cultures. Genistein has been demonstrated to be a radiosensitizer of malignant cells and a radioprotector against IR-induced lethality in a mouse model. Whole-blood cultures were supplemented with 50, 100, and 200{mu}M concentrations of genistein, 16 h prior to receiving a 2-Gy ({sup 60}Co-{gamma} rays, 10 cGy/min) dose of IR. Total RNA was isolated from whole blood 24 h postirradiation for assessments. Combination treatments of genistein and IR resulted in no significant genistein effects on ddb2 and bax downstream transcripts to p53, or proliferating cell-nuclear antigen, pcna, necessary for DNA synthesis and cell-cycle progression. Use of these radiation-responsive targets would be recommended for dose-assessment applications. We also observed decreased expression of pro-survival transcript, bcl-2. Genistein and IR-increased expression of cdkn1a and gadd45a, showing that genistein also stimulates p53 transcriptional activity. These results confirm published molecular signatures for genistein in numerous in vitro models. Evaluation of gene biomarkers may be further exploited for devising novel radiation countermeasure and/or therapeutic strategies.

  12. Low-Dose Radiation Induces Genes Promoting Cell Survival

    International Nuclear Information System (INIS)

    Liu, Shu-Zheng; Chen, Dong; Mu, Ying

    1999-01-01

    Apoptosis is an important process controlling homeostasis of the body. It is influenced by stimuli constantly arising from the external and internal environment of the organism. It is well known that radiation could induce apoptosis of cells in vitro and in vivo. However, the dose-effect relationship of apoptosis extending to the low-dose range has scarcely been studied. Here, the molecular basis of the phenomenon is explored by examining the changes in expression of some of the proapoptotic and antiapoptotic genes

  13. Radiation and desiccation response motif mediates radiation induced gene expression in D. radiodurans

    International Nuclear Information System (INIS)

    Anaganti, Narasimha; Basu, Bhakti; Apte, Shree Kumar

    2015-01-01

    Deinococcus radiodurans is an extremophile that withstands lethal doses of several DNA damaging agents such as gamma irradiation, UV rays, desiccation and chemical mutagens. The organism responds to DNA damage by inducing expression of several DNA repair genes. At least 25 radiation inducible gene promoters harbour a 17 bp palindromic sequence known as radiation and desiccation response motif (RDRM) implicated in gamma radiation inducible gene expression. However, mechanistic details of gamma radiation-responsive up-regulation in gene expression remain enigmatic. The promoters of highly radiation induced genes ddrB (DR0070), gyrB (DR0906), gyrA (DR1913), a hypothetical gene (DR1143) and recA (DR2338) from D. radiodurans were cloned in a green fluorescence protein (GFP)-based promoter probe shuttle vector pKG and their promoter activity was assessed in both E. coli as well as in D. radiodurans. The gyrA, gyrB and DR1143 gene promoters were active in E. coli although ddrB and recA promoters showed very weak activity. In D. radiodurans, all the five promoters were induced several fold following 6 kGy gamma irradiation. Highest induction was observed for ddrB promoter (25 fold), followed by DR1143 promoter (15 fold). The induction in the activity of gyrB, gyrA and recA promoters was 5, 3 and 2 fold, respectively. To assess the role of RDRM, the 17 bp palindromic sequence was deleted from these promoters. The promoters devoid of RDRM sequence displayed increase in the basal expression activity, but the radiation-responsive induction in promoter activity was completely lost. The substitution of two conserved bases of RDRM sequence yielded decreased radiation induction of PDR0070 promoter. Deletion of 5 bases from 5'-end of PDR0070 RDRM increased basal promoter activity, but radiation induction was completely abolished. Replacement of RDRM with non specific sequence of PDR0070 resulted in loss of basal expression and radiation induction. The results demonstrate that

  14. Radiation-induced gene expression in the nematode caenorhabditis elegans

    International Nuclear Information System (INIS)

    Nelson, G.A.; Jones, T.A.; Chesnut, A.; Smith, A.L.

    2002-01-01

    We used the nematode C. elegans to characterize the genotoxic and cytotoxic effects of ionizing radiation in a simple animal model emphasizing the unique effects of charged particle radiation. Here we demonstrate by reverse transcription polymerase chain reaction (RT-PCR) differential display and whole genome microarray hybridization experiments that gamma rays, accelerated protons and iron ions at the same physical dose lead to unique transcription profiles. 599 of 17871 genes analyzed (3.4%) showed differential expression 3 hrs after exposure to 3 Gy of radiation. 193 were up-regulated, 406 were down-regulated and 90% were affected only by a single species of radiation. A novel statistical clustering technique identified the regulatory relationships between the radiation-modulated genes and showed that genes affected by each radiation species were associated with unique regulatory clusters. This suggests that independent homeostatic mechanisms are activated in response to radiation exposure as a function of track structure or ionization density. (author)

  15. 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

  16. 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)

  17. Infrequent alterations of the P53 gene in rat skin cancers induced by ionising-radiation

    International Nuclear Information System (INIS)

    Jin, Y.; Burns, F.J.; Garte, S.J.; Hosselet, S.; New York Univ., NY

    1996-01-01

    Radiation carcinogenesis almost certainly involves multiple genetic alterations. Identification of such genetic alterations would provide information to help understand better the molecular mechanism or radiation carcinogenesis. The energy released by ionizing radiation has the potential to produce DNA strand breaks, major gene deletions or rearrangements, and other base damages. Alterations of the p53 gene, a common tumour suppressor gene altered in human cancers, were examined in radiation-induced rat skin cancers. Genomic DNA from a total of 33rat skin cancers induced by ionizing radiation was examined by Southern blot hybridization for abnormal restriction fragment patterns in the p53 gene. A abnormal p53 restriction pattern was found in one of 16 cancers induced by electron radiation and in one of nine cancers induced by neon ions. The genomic DNA from representative cancers, including the two with an abnormal restriction pattern was further examined by polymerase chain reaction amplification and direct sequencing in exons 5-8 of the p53 gene. The results showed that one restriction fragment length polymorphism (RFLP)-positive cancer induced by electron radiation had a partial gene deletion which was defined approximately between exons 2-8, while none of the other cancers showed sequence changes. Our results indicate that the alterations in the critical binding region of the p53 gene are infrequent in rat skin cancers induced by either electron or neon ion radiation. (Author)

  18. 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

  19. 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.

  20. Identification of novel senescence-associated genes in ionizing radiation-induced senescent carcinoma cells

    International Nuclear Information System (INIS)

    Lee, Jae Seon; Kim, Bong Cho; Han, Na Kyung; Hong, Mi Na; Park, Su Min; Yoo, Hee Jung; Chu, In Sun; Lee, Sun Hee

    2009-01-01

    Cellular senescence is considered as a defense mechanism to prevent tumorigenesis. Ionizing radiation (IR) induces stress-induced premature senescence as well as apoptosis in various cancer cells. Senescent cells undergo functional and morphological changes including large and flattened cell shape, senescence-associated β-galactosidase (SA-βGal) activity, and altered gene expressions. Even with the recent findings of several gene expression profiles and supporting functional data, it is obscure that mechanism of IR-induced premature senescence in cancer cells. We performed microarray analysis to identify the common regulated genes in ionizing radiation-induced prematurely senescent human carcinoma cell lines

  1. Innate immune genes including a mucin-like gene, mul-1, induced by ionizing radiation in Caenorhabditis elegans.

    Science.gov (United States)

    Kimura, Takafumi; Takanami, Takako; Sakashita, Tetsuya; Wada, Seiichi; Kobayashi, Yasuhiko; Higashitani, Atsushi

    2012-10-01

    The effect of radiation on the intestine has been studied for more than one hundred years. It remains unclear, however, whether this organ uses specific defensive mechanisms against ionizing radiation. The infection with Pseudomonas aeruginosa (PA14) in Caenorhabditis elegans induces up-regulation of innate immune response genes. Here, we found that exposure to ionizing radiation also induces certain innate immune response genes such as F49F1.6 (termed mul-1), clec-4, clec-67, lys-1 and lys-2 in the intestine. Moreover, pre-treatment with ionizing radiation before seeding on PA14 lawn plate significantly increased survival rate in the nematode. We also studied transcription pathway of the mul-1 in response to ionizing radiation. Induction of mul-1 gene was highly dependent on the ELT-2 transcription factor and p38 MAPK. Moreover, the insulin/IGF-1 signal pathway works to enhance induction of this gene. The mul-1 gene showed a different induction pattern from the DNA damage response gene, ced-13, which implies that the expression of this gene might be triggered as an indirect effect of radiation. Silencing of the mul-1 gene led to growth retardation after treatment with ionizing radiation. We describe the cross-tolerance between the response to radiation exposure and the innate immune system.

  2. Antitumor bystander effect induced by radiation-inducible target gene therapy combined with α particle irradiation

    International Nuclear Information System (INIS)

    Liu Hui; Jin Chufeng; Wu Yican; Ge Shenfang; Wu Lijun; FDS Team

    2012-01-01

    In this work, we investigated the bystander effect of the tumor and normal cells surrounding the target region caused by radiation-inducible target gene therapy combined with α-particle irradiation. The receptor tumor cell A549 and normal cell MRC-5 were co-cultured with the donor cells irradiated to 0.5 Gy or the non-irradiated donor cells, and their survival and apoptosis fractions were evaluated. The results showed that the combined treatment of Ad-ET and particle irradiation could induce synergistic antitumor effect on A549 tumor cell, and the survival fraction of receptor cells co-cultured with the irradiated cells decreased by 6%, compared with receptor cells co-cultured with non-irradiated cells, and the apoptosis fraction increased in the same circumstance, but no difference was observed with the normal cells. This study demonstrates that Ad-ET combined with α-particle irradiation can significantly cause the bystander effect on neighboring tumor cells by inhibiting cell growth and inducing apoptosis, without obvious toxicity to normal cells. This suggests that combining radiation-inducible TRAIL gene therapy and irradiation may improve tumor treatment efficacy by specifically targeting tumor cells and even involving the neighboring tumor cells. (authors)

  3. 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

  4. 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

  5. Gene expression profiling distinguishes between spontaneous and radiation-induced rat mammary carcinomas

    International Nuclear Information System (INIS)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Kakinuma, Shizuko; Shimada, Yoshiya; Yamashita, Satoshi; Ushijima, Toshikazu

    2008-01-01

    The ability to distinguish between spontaneous and radiation-induced cancers in humans is expected to improve the resolution of estimated risk from low dose radiation. Mammary carcinomas were obtained from Sprague-Dawley rats that were either untreated (n=45) or acutely γ-irradiated (1 Gy; n=20) at seven weeks of age. Gene expression profiles of three spontaneous and four radiation-induced carcinomas, as well as those of normal mammary glands, were analyzed by microarrays. Differential expression of identified genes of interest was then verified by quantitative polymerase chain reaction (qPCR). Cluster analysis of global gene expression suggested that spontaneous carcinomas were distinguished from a heterogeneous population of radiation-induced carcinomas, though most gene expressions were common. We identified 50 genes that had different expression levels between spontaneous and radiogenic carcinomas. We then selected 18 genes for confirmation of the microarray data by qPCR analysis and obtained the following results: high expression of Plg, Pgr and Wnt4 was characteristic to all spontaneous carcinomas; Tnfsf11, Fgf10, Agtr1a, S100A9 and Pou3f3 showed high expression in a subset of radiation-induced carcinomas; and increased Gp2, Areg and Igf2 expression, as well as decreased expression of Ca3 and noncoding RNA Mg1, were common to all carcinomas. Thus, gene expression analysis distinguished between spontaneous and radiogenic carcinomas, suggesting possible differences in their carcinogenic mechanism. (author)

  6. Tissue specific promoters improve the localization of radiation-inducible gene expression

    International Nuclear Information System (INIS)

    Hallahan, Dennis; Kataoka, Yasushi; Kuchibhotla, Jaya; Virudachalam, Subbu; Weichselbaum, Ralph

    1996-01-01

    Purpose: Site-specific activation of gene expression can be achieved by the use of a promoter that is induced by physical agents such as x-rays. The purpose of the present study was to determine whether site-specific activation of gene therapy can also be achieved within the vascular endothelium by use of radiation-inducible promoters. We studied induction of promoter-reporter gene constructs using previously identified radiation-promoters from c-jun, c-fos, Egr-1, ICAM-1, ELAM-1 after transfection into in the vascular endothelium. Methods: The following radiation-inducible genetic constructs were created: The ELAM-1 promoter fragment was cloned into pOGH to obtain the pE-sel(-587 +35)GH reporter construct. The ICAM-1 promoter fragment (-1162/+1) was cloned upstream of the CAT coding region of the pCAT-plasmid (Promega) after removal of the SV40 promoter by Bgl2/Stu1 digestion to create the pBS-CAT plasmid. The 132 to +170 bp segment of the 5' untranslated region of the c-jun promoter was cloned to the CAT reporter gene to create the -132/+170 cjun-CAT. The Egr-1 promoter fragment (-425/+75) was cloned upstream of the CAT coding region to create the pE425-CAT plasmid. Tandem repeats of the AP-1 binding site were cloned upstream of the CAT coding region (3 xTRE-CAT). Tandem repeats of the Egr binding site (EBS) were cloned upstream of the CAT coding region (EBS-CAT). Human vascular endothelial cells from both large vessel and small vessel origin (HUVEC and HMEC), as well as human tumor cell lines were transfected with plasmids -132/+170 cjun-CAT, pE425-CAT, 3 xTRE-CAT, EBS-CAT, pE-sel-GH and pBS-CAT by use of liposomes. Humor tumor cell lines included SQ20B (squamous), RIT3 (sarcoma), and HL525 (leukemia). Each plasmid was cotransfected with a plasmid containing a CMV promoter linked to the LacZ gene (1 μg). Transfected cells were treated with mock irradiation or x-rays. Cell extracts were assayed for reporter gene expression. Results: Radiation-induced gene

  7. Radiation-induced genomic instability, and the cloning and functional analysis of its related gene

    International Nuclear Information System (INIS)

    Muto, Masahiro; Kanari, Yasuyoshi; Kubo, Eiko; Yamada, Yutaka

    2000-01-01

    Exposure to ionizing radiation produces a number of biological consequences including gene mutations, chromosome aberrations, cellular transformation and cell death. The classical view has been that mutations occur at the sites of DNA damage, that is, damage produced by radiation is converted into a mutation during subsequent DNA replication or as a consequence of enzymatic repair processes. However, many investigators have presented evidence for an alternative mechanism to explain these biological effects. This evidence suggests that radiation may induce a process of genomic instability that is transmissible over many generations of cell replication and that serves to enhance the probability of the occurrence of such genetic effects among the progeny of the irradiated cell after many generations of cell replication. If such a process exists in vivo, it could have significant implications for mechanisms of carcinogenesis. Exposure of B10 mice to fractionated X-irradiation induces a high incidence of thymic lymphomas, whereas the incidence in STS/A mice is very low. Such strain differences are presumably determined genetically, and various genetic factors have been reported to be involved in radiation-induced lymphomagenesis. The mechanism of radiation-induced lymphomagenesis appears to develop through a complex and multistep process. Using this experimental system, we characterized the prelymphoma cells induced by radiation, and identified the genetic changes preceding the development of thymic lymphomas by comparing the oncogenic alterations with the pattern of T cell receptor (TCR) γ rearrangements. In these studies, the latent expression of some chromosomal aberrations and p53 mutations in irradiated progeny has been interpreted to be a manifestation of genomic instability. In the present report we review the results of in vivo studies conducted in our laboratory that support the hypothesis of genomic instability induced by radiation, and we describe the

  8. Molecular cytogenetics of radiation-induced gene mutations in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Aleksandrov, I.D.; Aleksandrova, M.V.; Lapidus, I.L.; Karpovskij, A.L.

    1996-01-01

    The classical paradigm of spatially unrelated lesions for gene mutations and chromosomal exchange breakpoints induced by ionizing radiations in eukaryotic cells was re-examined in the experiments on the mapping of gamma-ray- or neutron-induced breakpoints in and outside of white (w) and vestigial (vg) genes of Drosophila melanogaster using the in situ hybridization of the large fragments of the genes under study with the polythene chromosomes of the relevant mutants. The results for the random sample of 60 inversion and translocation breakpoints analysed to date have shown that (i) 50% of them are mapped as the hot spots within big introns of both the genes, and (ii) 21 of 60 breaks (35%) are located outside of genes. It is important to note that 26% (16/60) of the breakpoints analysed are flanked by the deletions, the sizes of which vary from the quarter to a whole of the gene. It was found that the deletions flank both the inversion and translocation breakpoints and arise more often after action of neutrons than photons. An unexpectedly high frequency of the multiple-damaged w and vg mutants that have the gene/point mutation and additional, but separate, chromosome exchange (the so-called double- or triple-site mutants) has shown that the genetic danger of ionizing radiation is higher than usually accepted on the base of single gene/point mutation assessments. 11 refs., 3 figs

  9. P53 Gene Mutation as Biomarker of Radiation Induced Cell Injury and Genomic Instability

    International Nuclear Information System (INIS)

    Mukh-Syaifudin

    2006-01-01

    Gene expression profiling and its mutation has become one of the most widely used approaches to identify genes and their functions in the context of identify and categorize genes to be used as radiation effect markers including cell and tissue sensitivities. Ionizing radiation produces genetic damage and changes in gene expression that may lead to cancer due to specific protein that controlling cell proliferation altered the function, its expression or both. P53 protein encoded by p53 gene plays an important role in protecting cell by inducing growth arrest and or cell suicide (apoptosis) after deoxyribonucleic acid (DNA) damage induced by mutagen such as ionizing radiation. The mutant and thereby dysfunctional of this gene was found in more than 50% of various human cancers, but it is as yet unclear how p53 mutations lead to neoplastic development. Wild-type p53 has been postulated to play a role in DNA repair, suggesting that expression of mutant forms of p53 might alter cellular resistance to the DNA damage caused by radiation. Moreover, p53 is thought to function as a cell cycle checkpoint after irradiation, also suggesting that mutant p53 might change the cellular proliferative response to radiation. P53 mutations affect the cellular response to DNA damage, either by increasing DNA repair processes or, possibly, by increasing cellular tolerance to DNA damage. The association of p53 mutations with increased radioresistance suggests that alterations in the p53 gene might lead to oncogenic transformation. Current attractive model of carcinogenesis also showed that p53 gene is the major target of radiation. The majority of p53 mutations found so far is single base pair changes ( point mutations), which result in amino acid substitutions or truncated forms of the p53 protein, and are widely distributed throughout the evolutionary conserved regions of the gene. Examination of p53 mutations in human cancer also shows an association between particular carcinogens and

  10. Development of radiation-inducible promoters for use in nitric oxide synthase gene therapy of cancer

    International Nuclear Information System (INIS)

    Hirst, D.G.; Worthington, J.; Adams, C.; Robson, T.; Scott, S.D.

    2003-01-01

    Full text: The free radical nitric oxide (NO) at nM concentrations performs multiple signaling roles that are essential for survival. These processes are regulated via the enzymes nNOS and eNOS, but another isoform, inducible nitric oxide synthase (iNOS) is capable of generating much higher concentrations (mM) over longer periods, resulting in the generation of very toxic species such as peroxynitrite. At high concentrations NO has many of the characteristics of an ideal anticancer molecule: it is cytotoxic (pro-apoptotic via peroxynitrite), it is a potent chemical radiosensitizer, it is anti-angiogenic and anti-metastatic. Thus, we see iNOS gene therapy as a strategy for targeting the generation of high concentrations of NO to tumours for therapeutic benefit. iNOS gene therapy should be used in combination with radiotherapy; so it is logical that the use of a radiation-inducible promoter should be part of the targeting strategy. We have tested several candidate promoters in vitro and in vivo. The WAF1 promoter has many of the properties desirable for therapeutic use including: rapid 3-4 fold induction at X-ray doses of 2 and 4Gy and no significant leakiness. WAF1 also has the advantage of being inducible by hypoxia and by the final product, NO. We have also tested the synthetic CArG promoter and demonstrated that, in addition to a high level of radiation inducibility, it is also inducible by NO. We have also been able to demonstrate potent radiosensitization (SER 2.0-2.5) in tumour cells in vitro and in vivo using iNOS gene transfer with constitutive or radiation-inducible promoters. We have also tested the use of iNOS gene therapy in combination with cisplatin and shown significant enhancement

  11. Gene alterations in radiation-induced F344 rat lung tumors

    International Nuclear Information System (INIS)

    Kelly, G.; Hahn, F.F.

    1994-01-01

    The p53 tumor suppressor gene is frequently altered in all major histopathologic types of human lung tumors. Reported p53 mutations include base substitutions, allelic loss, rearrangements, and deletions. Point mutations resulting in base substitutions are clustered within a highly conserved region of the gene encoding exons 508, and mutations in this region substantially extend the half-life of the p53 protein. In addition to its prominent importance in lung carcinogenesis, the p53 gene plays a critical role in the cellular response to genetic damage caused by radiation. Specifically, the protein product of p53 induces a pause or block at the G 1 to S boundary of the cell cycle following radiation-caused DNA damage. This G 1 block may allow the cell time to repair the damaged DNA prior to replication. Cells lacking a functional p53 protein fail to pause for repair and consequently accumulate mutations in the genome at an accelerated rate. p53 has also been implicated as a controlling factor in apoptosis or in programmed cell death induced by DNA-damaging agents, such as ionizing radiation. The p53 gene is mutated in approximately 50% of squamous cell carcinomas from uranium miners who inhaled high doses of radon daughters. The purpose of the present study was to determine if a similar percentage of squamous cell carcinomas with p53 mutations developed in the lungs of rats exposed to aerosols of 239 PuO 2

  12. Overexpression and amplification of the c-myc gene in mouse tumors induced by chemical and radiations

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Ohtsura; Enoki, Yoshitaka; Yokoro, Kenjiro

    1989-03-01

    We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 /alpha/-tocopherol-induced sacromas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification. (author).

  13. Isolation and identification of gene mediating radiation-induced apoptosis in human leukemia U937 cells

    International Nuclear Information System (INIS)

    Tong Xin; Luo Ying; Dong Yan; Sun Zhixian

    1998-01-01

    Objective: Increasing evidences suggest that Caspase family proteases play an important role in the effector mechanism of apoptotic cell death. Radiation (IR) can induce apoptosis in tumor cells, so it is very important to isolate and identify the member of the Caspase family proteases involved in IR-induced apoptosis, and this would contribute to the understanding of the mechanism responsible for apoptosis execution. Methods: A PCR approach to isolate genes for IR-induced apoptosis was developed. The approach used degenerated oligonucleotide encoding the highly conserved peptides that were present in all known Caspases. Results: Protease inhibitors special for Caspases could block the apoptotic cell death caused by IR, and Caspase-3 was isolated from irradiated human leukemia U937 cells. Conclusion: Caspases involve in IR-induced apoptosis, and Caspase-3 is the pivotal element of IR-induced apoptosis

  14. Effect of genes controlling radiation sensitivity on chemically induced mutations in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Prakash, L.

    1976-01-01

    The effect of 16 different genes (rad) conferring radiation sensitivity on chemically induced reversion in the yeast Saccharomyces cerevisiae was determined. The site of reversion used was a well-defined chain initiation mutant mapping in the structural gene coding for iso-1-cytochrome c. High doses of EMS and HNO 2 resulted in decreased reversion of cyc1-131 in rad6, rad9 and rad15 strains compared to the normal RAD + strains. In addition, rad52 greatly decreased EMS reversion of cyc1-131 but had no effect on HNO 2 -induced reversion; rad18, on the other hand, increased HNO 2 -induced reversion but did not alter EMS-induced reversion. When NQO was used as the mutagen, every rad gene tested, except for rad18, had an effect on reversion; rad6, rad9, rad15, rad17, rad18, rad22, rev1, rev2, and rev3 lowered NQO reversion while rad1, rad2, rad3, rad4, rad10, rad12, and rad16 increased it compared to the RAD + strain. The effect of rad genes on chemical mutagenesis is discussed in terms of their effect on uv mutagenesis. It is concluded that although the nature of the repair pathways may differ for uv- and chemically-induced mutations in yeast, a functional repair system is required for the induction of mutation by the chemical agents NQO, EMS, and HNO 2

  15. Spatially Fractionated Radiation Induces Cytotoxicity and Changes in Gene Expression in Bystander and Radiation Adjacent Murine Carcinoma Cells

    Science.gov (United States)

    Asur, Rajalakshmi S.; Sharma, Sunil; Chang, Ching-Wei; Penagaricano, Jose; Kommuru, Indira M.; Moros, Eduardo G.; Corry, Peter M.; Griffin, Robert J.

    2012-01-01

    Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) regions, in two different murine carcinoma cell lines following exposure to a single irradiation dose of 10 Gy. Murine SCK mammary carcinoma cells and SCCVII squamous carcinoma cells were irradiated using a brass collimator to create a GRID pattern of nine circular fields 12 mm in diameter with a center-to-center distance of 18 mm. Similar to the typical clinical implementation of GRID, this is approximately a 50:50 ratio of direct and bystander exposure. We also performed experiments by irradiating separate cultures and transferring the medium to unirradiated bystander cultures. Clonogenic survival was evaluated in both cell lines to determine the occurrence of radiation-induced bystander effects. For the purpose of our study, we have defined bystander cells as GRID adjacent cells that received approximately 1 Gy scatter dose or unirradiated cells receiving conditioned medium from irradiated cells. We observed significant bystander killing of cells adjacent to the GRID irradiated regions compared to sham treated controls. We also observed bystander killing of SCK and SCCVII cells cultured in conditioned medium obtained from cells irradiated with 10 Gy. Therefore, our results confirm the occurrence of bystander effects following exposure to a high-dose of radiation and suggest that cell-to-cell contact is not required for these effects. In addition, the gene expression profile for DNA damage and cellular stress response signaling in SCCVII cells after GRID exposure was studied

  16. Differential gene expression before and after ionizing radiation of subcutaneous fibroblasts identifies breast cancer patients resistant to radiation-induced fibrosis

    DEFF Research Database (Denmark)

    Alsner, Jan; Rødningen, Olaug K.; Overgaard, Jens

    2007-01-01

    BACKGROUND AND PURPOSE: Differentially gene expression between patients with either very low or very high risk of radiation-induced fibrosis (RIF) in patient-derived fibroblasts after irradiation has previously been reported. In the present study, we are investigating the robustness of radiation...... and changes in radiation-induced gene expression in fibroblasts. MATERIAL AND METHODS: Gene expression was analysed by quantitative real-time PCR before and after a fractionated scheme with 3x3.5Gy/3 days in fibroblasts derived from 26 patients with breast cancer treated with post-mastectomy radiotherapy....... RESULTS: Robust radiation-induced changes in gene expression were observed, with differential gene expression between low and high risk patients being most pronounced for the fold induction level ('after' value divided by 'before' value for each patient). When including patients with intermediate risk...

  17. Radiation-induced pulmonary gene expression changes are attenuated by the CTGF antibody Pamrevlumab.

    Science.gov (United States)

    Sternlicht, Mark D; Wirkner, Ute; Bickelhaupt, Sebastian; Lopez Perez, Ramon; Tietz, Alexandra; Lipson, Kenneth E; Seeley, Todd W; Huber, Peter E

    2018-01-18

    Fibrosis is a delayed side effect of radiation therapy (RT). Connective tissue growth factor (CTGF) promotes the development of fibrosis in multiple settings, including pulmonary radiation injury. To better understand the cellular interactions involved in RT-induced lung injury and the role of CTGF in these responses, microarray expression profiling was performed on lungs of irradiated and non-irradiated mice, including mice treated with the anti-CTGF antibody pamrevlumab (FG-3019). Between group comparisons (Welch's t-tests) and principal components analyses were performed in Genespring. At the mRNA level, the ability of pamrevlumab to prolong survival and ameliorate RT-induced radiologic, histologic and functional lung deficits was correlated with the reversal of a clear enrichment in mast cell, macrophage, dendritic cell and mesenchymal gene signatures. Cytokine, growth factor and matrix remodeling genes that are likely to contribute to RT pneumonitis and fibrosis were elevated by RT and attenuated by pamrevlumab, and likely contribute to the cross-talk between enriched cell-types in injured lung. CTGF inhibition had a normalizing effect on select cell-types, including immune cells not typically regarded as being regulated by CTGF. These results suggest that interactions between RT-recruited cell-types are critical to maintaining the injured state; that CTGF plays a key role in this process; and that pamrevlumab can ameliorate RT-induced lung injury in mice and may provide therapeutic benefit in other immune and fibrotic disorders.

  18. The ionizing radiation inducible gene PARX/ARAP2 participates in Rho and ARF signaling

    International Nuclear Information System (INIS)

    Wong, J.A.; Chen, Z.; Zhao, Y.; Vallis, K.A.; Marignani, P.A.; Randazzo, P.A.

    2003-01-01

    Full text: PARX/ARAP2 is a novel protein that we identified in a gene trap screen for ionizing radiation (IR)-regulated genes. It belongs to a recently described family of proteins that link Rho, ADP-ribosilation factor (ARF) and phosphoinositide 3-kinase (PI3-K) signaling. We have cloned the full length human PARX. Domain analysis of the predicted protein revealed a sterile-alpha motif, five pleckstrin homology domains, a RhoGTPase activating domain (RhoGAP) and an ARF activating domain (ARFGAP). PARX is early inducible by IR in a dose-dependent manner in murine ES cells and in several human B-cell lymphoma lines with up to six-fold induction at the mRNA level at 2 hours (10 Gy). Thus, the kinetics of PARX induction follows the pattern of the rapid response typical of many stress-induced immediate-early genes. PARX expression is also induced in response to other cellular stressors including sorbitol and bleomycin. PARX induction is dependent on PI3-K activity and can be suppressed by the PI3-K inhibitor LY294002. Induction of PARX in response to IR has been observed in cell lines that are p53 mutant indicating up-regulation independent of normal p53 function. The role of p53 in PARX induction is currently being studied using cell lines expressing temperature sensitive p53. Biochemical studies reveal that human PARX has in vivo RhoGAP activity for Rac1 and phosphatidylinositol 3,4,5-trisphosphate dependent ARFGAP activity for ARF1, ARF5 and ARF6. Also, temporal changes in PARX cellular localization following IR are currently being investigated using confocal microscopy. PARX is a gene with a potential role in the cellular response to genotoxic stress, and may illuminate the currently unclear role the small GTPases Rho and ARF play in the radiation response

  19. Transcription of five p53- and Stat-3-Inducible genes after ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Grace, M.B. [Uniformed Services University (USUHS), Armed Forces Radiobiology Research Institute, Building 42, RM 3321, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: grace@afrri.usuhs.mil; Blakely, W.F. [Uniformed Services University (USUHS), Armed Forces Radiobiology Research Institute, Building 42, RM 3321, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    Ionizing radiation (IR) produces temporal- and dose-dependent changes in multiple gene mRNA targets that are potential biomarkers of radiation dose. We confirmed IR-induced changes in expression of gadd45a, ddb-2, and cdkn1a downstream transcripts of p53 by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) assay in total RNA samples from the whole blood of radiotherapy patients undergoing total-body irradiation [Amundson, S.A., Grace, M.B., McLeland, C.B., Epperly, M.W., Yeager, A., Zhan, Q., Greenberger, J.S., Fornace Jr., A.J., 2004. Human in vivo radiation-induced biomarkers: gene expression changes in radiotherapy patients. Cancer Res. 64, 6368-6371.]. We now confirm dose-dependent up-regulation of bax in addition to these p53-dependent transcripts, and bcl-2, a downstream transcript of Stat-3, in ex vivo irradiated blood samples from healthy unrelated volunteers. Together these biomarkers represent pathways involved in growth arrest, DNA damage, and apoptosis. The objectives of this study were to (1) investigate the relationship between baseline mRNA expression levels, and (2) define expression patterns in response to IR in a large cohort (n=20). Whole-blood samples were irradiated ex vivo to measure gene expression in samples from (i) three healthy donors over a broad dose range (0, 0.25, 0.50, 0.75, 1, 2, and 3 Gy), and (ii) 20 healthy donors at two doses, 0.25 and 2.5 Gy. Expression level variance ({sigma}{sub 2}) of baseline values (0 Gy) showed negligible inter-individual variation with all values {<=}1.0. {sigma}{sub 2}values=0.50bax, 0.25 bcl-2, 0.73 gadd45a, 0.66 cdkn1a, and 1.0 ddb-2. Meaningful IR dose-responses were observed for bax, gadd45a, and ddb-2 profiles and the ratio of bax:bcl-2 mRNA expression over a broad dose range. QRT-PCR studies were extended in the lower dose range (0, 0.1, 0.5, 0.75, and 1 Gy). Results showed that bax:bcl-2 ratio initially favors bax expression at doses of <1Gy, with IR-induced dose responses

  20. Modulation of radiation-induced base excision repair pathway gene expression by melatonin

    Directory of Open Access Journals (Sweden)

    Saeed Rezapoor

    2017-01-01

    Full Text Available Objective: Approximately 70% of all cancer patients receive radiotherapy. Although radiotherapy is effective in killing cancer cells, it has adverse effects on normal cells as well. Melatonin (MLT as a potent antioxidant and anti-inflammatory agent has been proposed to stimulate DNA repair capacity. We investigated the capability of MLT in the modification of radiation-induced DNA damage in rat peripheral blood cells. Materials and Methods: In this experimental study, male rats (n = 162 were divided into 27 groups (n = 6 in each group including: irradiation only, vehicle only, vehicle with irradiation, 100 mg/kg MLT alone, 100 mg/kg MLT plus irradiation in 3 different time points, and control. Subsequently, they were irradiated with a single whole-body X-ray radiation dose of 2 and 8 Gy at a dose rate of 200 MU/min. Rats were given an intraperitoneal injection of MLT or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were also taken 8, 24, and 48 h postirradiation, in order to measure the 8-oxoguanine glycosylase1 (Ogg1, Apex1, and Xrcc1 expression using quantitative real-time-polymerase chain reaction. Results: Exposing to the ionizing radiation resulted in downregulation of Ogg1, Apex1, and Xrcc1 gene expression. The most obvious suppression was observed in 8 h after exposure. Pretreatments with MLT were able to upregulate these genes when compared to the irradiation-only and vehicle plus irradiation groups (P < 0.05 in all time points. Conclusion: Our results suggested that MLT in mentioned dose may result in modulation of Ogg1, Apex1, and Xrcc1 gene expression in peripheral blood cells to reduce X-ray irradiation-induced DNA damage. Therefore, administration of MLT may increase the normal tissue tolerance to radiation through enhancing the cell DNA repair capacity. We believed that MLT could play a radiation toxicity reduction role in patients who have undergone radiation treatment as a part of cancer radiotherapy.

  1. Was Muller's 1946 Nobel Prize research for radiation-induced gene mutations peer-reviewed?

    Science.gov (United States)

    Calabrese, Edward J

    2018-06-06

    This historical analysis indicates that it is highly unlikely that the Nobel Prize winning research of Hermann J. Muller was peer-reviewed. The published paper of Muller lacked a research methods section, cited no references, and failed to acknowledge and discuss the work of Gager and Blakeslee (PNAS 13:75-79, 1927) that claimed to have induced gene mutation via ionizing radiation six months prior to Muller's non-data Science paper (Muller, Science 66(1699):84-87, 1927a). Despite being well acclimated into the scientific world of peer-review, Muller choose to avoid the peer-review process on his most significant publication. It appears that Muller's actions were strongly influenced by his desire to claim primacy for the discovery of gene mutation. The actions of Muller have important ethical lessons and implications today, when self-interest trumps one's obligations to society and the scientific culture that supports the quest for new knowledge and discovery.

  2. Gene expression and hormone autonomy in radiation-induced tumors of Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Persinger, S.M.; Town, C.D.

    1989-01-01

    In order to study the molecular genetics of factor controlling plant cell growth, we have isolated a group of radiation-induced tumors from Arabidopsis thaliana. Tumors appeared on plants derived from 60 Co gamma-irradiated seed or seedlings, and are capable of hormone-autonomous growth in culture. We have used vertebrate oncogene probes to explore the hypothesis that the tumors arose by the radiation-induced activation of growth-regulating plant oncogenes. One probe, int-2, was used to isolate cDNA clones representing an mRNA differentially expressed between tumors and hormone-dependent callus tissue. The genomic organization and function of this and other differentially expressed Arabidopsis sequences are being further characterized. A second area of study concerns the hormonal status of individual tumors. Tumor tissue varies in color, texture, and degree of differentiation: while some tumors appear undifferentiated, one consistently produces roots, and others occasionally develop shoots or leaflets. The tumors have characteristic growth rates on hormone-free medium, and growth in response to exogenous hormones differs among the tumors themselves and from wild-type. Characterization of the relationships between hormonal status, morphogenesis, and gene expression should yield valuable insights into the mechanisms regulating plant growth and development

  3. Effects of a chromosome-3 mutator gene on radiation-induced mutability in Drosophila melanogaster females

    Energy Technology Data Exchange (ETDEWEB)

    Sankaranarayanan, K. (Rijksuniversiteit Leiden (Netherlands). Dept. of Radiation Genetics and Chemical Mutagenesis; Cohen (J.A.) Inst. voor Radiopathologie en Stralenbescherming, Leiden (Netherlands))

    1982-01-01

    A series of X-irradiation experiments was carried out using Drosophila melanogaster females homozygous for a third chromosome mutator gene and females which had a similar genetic background except that the mutator-bearing third chromosomes were substituted by normal wild-type chromosomes. In the present work, the sensitivity of the pre-meiotic germ cells of mutator and normal females to the X-ray induction (2000 R) of sex-linked recessive lethals was studied. In addition, experiments were conducted to examine the sensitivity of the immature (stage 7; prophase I of meiosis) oocytes of both kinds of females to the induction of dominant lethals, X-linked recessive lethals and X-chromosome losses. The results show that in pre-meiotic germ cells, the frequencies of radiation-induced recessive lethals are similar in both kinds of females. However, the proportion of these mutations that occur in clusters of size 3 and higher, is higher in mutator than in normal females. In stage-7 oocytes, the frequencies of radiation-induced dominant lethals and sex-linked recessive lethals were similar in both kinds of females. The X-loss frequencies however, were consistently higher in mutator females although statistical significance was obtained only at higher exposures (3000 and 3750 R) and not at lower ones (750-2250 R). Possible reasons for the discrepancy between the present results and those of Gold and Green with respect to pre-meiotic germ cells are discussed.

  4. Construction and identification of double-gene co-expression vector with radiation-inducible human TRAIL and endostatin

    International Nuclear Information System (INIS)

    Li Yanbo; Guo Caixia; Gong Pingsheng; Liu Yang; Liangshuo; Wang Hongfang; Wang Jianfeng; Gong Shouliang

    2010-01-01

    Objective: To construct a recombinant plasmid pshuttle-Egr1-shTRAIL-shES containing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin double genes. Methods: The secretary endostatin gene (shES) fragment was amplified from the pMD19T-endostatin vector by PCR. The shES gene was ligated to pMD19Tand sequenced. Finally, using the gene recombinant technique, the recombinant plasmid pshuttle-Egr1- shTRAIL-shES with radiation-inducible Egr1 promoter, secretary TRAIL and endostatin double-gene was constructed. Results: The sequence of the shES gene was in concordance with that anticipated indicating shES gene was acquired successfully.Moreover, the results acquired by PCR and restrictive digestion identification of the recombinant plasmid pshuttle-Egr1-shTRAIL-shES and all the vectors refered to its construction confirmed that pshuttle-Egr1-shTRAIL-shES was constructed correctly. Conclusion: The radiation-inducible double-gene co-expression vector pshuttle-Egr1-shTRAIL-shES is constructed successfully, which would set the experimental foundation for further study on the anti-tumor effect of TRAIL and endostatin double-gene-radiotherapy and its related mechanisms. (authors)

  5. Differential gene expression before and after ionizing radiation of subcutaneous fibroblasts identifies breast cancer patients resistant to radiation-induced fibrosis

    International Nuclear Information System (INIS)

    Alsner, Jan; Rodningen, Olaug K.; Overgaard, Jens

    2007-01-01

    Background and purpose: Differentially gene expression between patients with either very low or very high risk of radiation-induced fibrosis (RIF) in patient-derived fibroblasts after irradiation has previously been reported. In the present study, we are investigating the robustness of radiation-induced changes in gene expression in fibroblasts, whether differential expression is more pronounced when looking at the fold induction levels, taking into account the differences in background expression levels between patients, and whether there is a linear correlation between individual risk of RIF and changes in radiation-induced gene expression in fibroblasts. Material and methods: Gene expression was analysed by quantitative real-time PCR before and after a fractionated scheme with 3 x 3.5 Gy/3 days in fibroblasts derived from 26 patients with breast cancer treated with post-mastectomy radiotherapy. Results: Robust radiation-induced changes in gene expression were observed, with differential gene expression between low and high risk patients being most pronounced for the fold induction level ('after' value divided by 'before' value for each patient). When including patients with intermediate risk, there was no linear correlation between individual risk of RIF and differential expression of the genes investigated. Rather, differential gene expression could divide patients into two clearly separated groups, a larger, sensitive group and a smaller resistant group. Conclusions: Differential gene expression in irradiated fibroblasts might be an important tool in the identification of differences in the genetic background between patients with variable risk of RIF, and in the identification of new targets for prevention and intervention of the fibrotic process

  6. 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)

  7. cDNA cloning and transcriptional controlling of a novel low dose radiation-induced gene and its function analysis

    International Nuclear Information System (INIS)

    Zhou Pingkun; Sui Jianli

    2002-01-01

    Objective: To clone a novel low dose radiation-induced gene (LRIGx) and study its function as well as its transcriptional changes after irradiation. Methods: Its cDNA was obtained by DDRT-PCR and RACE techniques. Northern blot hybridization was used to investigate the gene transcription. Bioinformatics was employed to analysis structure and function of this gene. Results: LRIGx cDNA was cloned. The sequence of LRIGx was identical to a DNA clone located in human chromosome 20 q 11.2-12 Bioinformatics analysis predicted an encoded protein with a conserved helicase domain. Northern analysis revealed a ∼8.5 kb transcript which was induced after 0.2 Gy as well as 0.02 Gy irradiation, and the transcript level was increased 5 times at 4 h after 0.2 Gy irradiation. The induced level of LRIGx transcript by 2.0 Gy high dose was lower than by 0.2 Gy. Conclusion: A novel low dose radiation-induced gene has been cloned. It encodes a protein with a conserved helicase domain that could involve in DNA metabolism in the cellular process of radiation response

  8. Radiation-Induced Upregulation of Gene Expression From Adenoviral Vectors Mediated by DNA Damage Repair and Regulation

    International Nuclear Information System (INIS)

    Nokisalmi, Petri; Rajecki, Maria; Pesonen, Sari; Escutenaire, Sophie; Soliymani, Rabah; Tenhunen, Mikko; Ahtiainen, Laura; Hemminki, Akseli

    2012-01-01

    Purpose: In the present study, we evaluated the combination of replication-deficient adenoviruses and radiotherapy in vitro. The purpose of the present study was to analyze the mechanism of radiation-mediated upregulation of adenoviral transgene expression. Methods and Materials: Adenoviral transgene expression (luciferase or green fluorescent protein) was studied with and without radiation in three cell lines: breast cancer M4A4-LM3, prostate cancer PC-3MM2, and lung cancer LNM35/enhanced green fluorescent protein. The effect of the radiation dose, modification of the viral capsid, and five different transgene promoters were studied. The cellular responses were studied using mass spectrometry and immunofluorescence analysis. Double strand break repair was modulated by inhibitors of heat shock protein 90, topoisomerase-I, and DNA protein kinase, and transgene expression was measured. Results: We found that a wide range of radiation doses increased adenoviral transgene expression regardless of the cell line, transgene, promoter, or viral capsid modification. Treatment with adenovirus, radiation, and double strand break repair inhibitors resulted in persistence of double strand breaks and subsequent increases in adenovirus transgene expression. Conclusions: Radiation-induced enhancement of adenoviral transgene expression is linked to DNA damage recognition and repair. Radiation induces a global cellular response that results in increased production of RNA and proteins, including adenoviral transgene products. This study provides a mechanistic rationale for combining radiation with adenoviral gene delivery.

  9. 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.

  10. Radiation induced genomic instability

    International Nuclear Information System (INIS)

    Morgan, W.

    2003-01-01

    This presentation will focus on delayed genetic effects occurring in the progeny of cells after exposure to ionizing radiation. We have developed a model system for investigating those genetic effects occurring multiple generations after radiation exposure. The presentation will describe some of the delayed effects observed after radiation exposures including delayed chromosomal rearrangements, and recombination events as determined by a plasmid based assay system. We will present new data on how changes in gene expression as measured by differential display and DNA microarray analysis provides a mechanism by which cells display a memory of irradiation, and introduce candidate genes that may play a role in initiating and perpetuation the unstable phenotype. These results will be discussed in terms of the recently described non-targeted Death Inducing Effect (DIE) where by secreted factors from clones of unstable cells can elicit effects in non irradiated cells and may serve to perpetuate the unstable phenotype in cells that themselves were not irradiated

  11. 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

  12. Entropic effects in formation of chromosome territories: towards understanding of radiation-induced gene translocation frequency

    Science.gov (United States)

    Gudowska-Nowak, Ewa; Ritter, Sylvia; Durante, Marco; Deperas-Standylo, Joanna; Ciesla, Michal

    2012-07-01

    A detailed understanding of structural organization of biological target, such as geometry of an inter-phase chromosome, is an essential prerequisite for gaining deeper insight into relationship between radiation track structure and radiation-induced biological damage [1]. In particular, coupling of biophysical models aimed to describe architecture of chromosomes and their positioning in a cell nucleus [2-4] with models of local distribution of ionizations caused by passing projectiles, are expected to result in more accurate estimates of aberration induction caused by radiation. There is abundant experimental evidence indicating that arrangements of chromosomes in eukaryotic cell nucleus is non-random and has been evolutionary conserved in specific cell types. Moreover, the radial position of a given chromosome territory (CT) within the cell nucleus has been shown to correlate with its size and gene density. Usually it is assumed that chromosomal geometry and positioning result from the action of specific forces acting locally, such as hydrogen bonds, electrostatic, Van der Waals or hydrophobic interactions operating between nucleosomes and within their interiors. However, it is both desirable and instructive to learn to what extend organization of inter-phase chromosomes is affected by nonspecific entropic forces. In this study we report results of a coarse-grained analysis of a chromatin structure modeled by two distinct approaches. In the first method, we adhere to purely statistical analysis of chromatin packing within a chromosome territory. On the basis of the polymer theory, the chromatin fiber of diameter 30nm is approximated by a chain of spheres, each corresponding to about 30 kbp. Random positioning of the center of the domain is repeated for 1000 spherical nuclei. Configuration of the domain is determined by a random packing of a polymer (a string of identical beads) in estimated fraction of space occupied by a chromosome of a given length and mass

  13. Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

    International Nuclear Information System (INIS)

    Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

    2005-01-01

    The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

  14. Genetic and molecular analyses of UV radiation-induced mutations in the fem-3 gene of Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P S; De Wilde, D; Dwarakanath, V N [Texas Christian Univ., Fort Worth, TX (United States). Dept. of Biology

    1995-06-01

    The utility of a new target gene (fem-3) is described for investigating the molecular nature of mutagenesis in the nematode Caenorhabditis elegans. As a principal attribute, this system allows for the selection, maintenance and molecular analysis of any type of mutation that disrupts the gene, including deletions. In this study, 86 mutant strains were isolated, of which 79 proved to have mutations in fem-3. Twenty of these originally tested as homozygous inviable. Homozygous inviability was expected, as Stewart and coworkers had previously observed that, unlike in other organisms, most UV radiation-induced mutations in C. elegans are chromosomal rearrangements of deficiencies (Mutat. Res 249, 37-54, 1991). However, additional data, including Southern blot analyses on 49 of the strains, indicated that most of the UV radiation-induced fem-3 mutations were not deficiencies, as originally inferred from their homozygous inviability. Instead, the lethals were most likely ``coincident mutations`` in linked, essential genes that were concomitantly induced. As such, they were lost owing to genetic recombination during stock maintenance. As in mammalian cells, yeast and bacteria, the frequency of coincident mutations was much higher than would be predicted by chance. (Author).

  15. A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Fornace, Jr, A J

    2007-03-03

    Abstract for final report for project entitled A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo which has been supported by the DOE Low Dose Radiation Research Program for approximately 7 years. This project has encompassed two sequential awards, ER62683 and then ER63308, in the Gene Response Section in the Center for Cancer Research at the National Cancer Institute. The project was temporarily suspended during the relocation of the Principal Investigators laboratory to the Dept. of Genetics and Complex Diseases at Harvard School of Public Health at the end of 2004. Remaining support for the final year was transferred to this new site later in 2005 and was assigned the DOE Award Number ER64065. The major aims of this project have been 1) to characterize changes in gene expression in response to low-dose radiation responses; this includes responses in human cells lines, peripheral blood lymphocytes (PBL), and in vivo after human or murine exposures, as well as the effect of dose-rate on gene responses; 2) to characterize changes in gene expression that may be involved in bystander effects, such as may be mediated by cytokines and other intercellular signaling proteins; and 3) to characterize responses in transgenic mouse models with relevance to genomic stability. A variety of approaches have been used to study transcriptional events including microarray hybridization, quantitative single-probe hybridization which was developed in this laboratory, quantitative RT-PCR, and promoter microarray analysis using genomic regulatory motifs. Considering the frequent responsiveness of genes encoding cytokines and related signaling proteins that can affect cellular metabolism, initial efforts were initiated to study radiation responses at the metabolomic level and to correlate with radiation-responsive gene expression. Productivity includes twenty-four published and in press manuscripts

  16. Cloning of low dose radiation induced gene RIG1 by RACE based on non-cloned cDNA library

    International Nuclear Information System (INIS)

    Luo Ying; Sui Jianli; Tie Yi; Zhang Yuanping; Zhou Pingkun; Sun Zhixian

    2001-01-01

    Objective: To obtain full-length cDNA of radiation induced new gene RIG1 based on its EST fragment. Methods: Based on non-cloned cDNA library, enhanced nested RACE PCR and biotin-avidin labelled probe for magnetic bead purification was used to obtain full-length cDNA of RIG1. Results: About 1 kb of 3' end of RIG1 gene was successfully cloned by this set of methods and cloning of RIG1 5' end is proceeding well. Conclusion: The result is consistent with the design of experiment. This set of protocol is useful for cloning of full-length gene based on EST fragment

  17. UV Radiation and Visible Light Induce hsp70 Gene Expression in the Antarctic Psychrophilic Ciliate Euplotes focardii.

    Science.gov (United States)

    Fulgentini, Lorenzo; Passini, Valerio; Colombetti, Giuliano; Miceli, Cristina; La Terza, Antonietta; Marangoni, Roberto

    2015-08-01

    The psychrophilic ciliate Euplotes focardii inhabits the shallow marine coastal sediments of Antarctica, where, over millions of years of evolution, it has reached a strict molecular adaptation to such a constant-temperature environment (about -2 °C). This long evolution at sub-zero temperatures has made E. focardii unable to respond to heat stress with the activation of its heat shock protein (hsp) 70 genes. These genes can, however, be expressed in response to other stresses, like the oxidative one, thus indicating that the molecular adaptation has exclusively altered the heat stress signaling pathways, while it has preserved hsp70 gene activation in response to other environmental stressors. Since radiative stress has proved to be affine to oxidative stress in several organisms, we investigated the capability of UV radiation to induce hsp70 transcription. E. focardii cell cultures were exposed to several different irradiation regimes, ranging from visible only to a mixture of visible, UV-A and UV-B. The irradiation values of each spectral band have been set to be comparable with those recorded in a typical Antarctic spring. Using Northern blot analysis, we measured the expression level of hsp70 immediately after irradiation (0-h-labeled samples), 1 h, and 2 h from the end of the irradiation. Surprisingly, our results showed that besides UV radiation, the visible light was also able to induce hsp70 expression in E. focardii. Moreover, spectrophotometric measurements have revealed no detectable endogenous pigments in E. focardii, making it difficult to propose a possible explanation for the visible light induction of its hsp70 genes. Further research is needed to conclusively clarify this point.

  18. Activation of transcription factor AP-2 mediates UVA radiation- and singlet oxygen-induced expression of the human intercellular adhesion molecule 1 gene

    International Nuclear Information System (INIS)

    Grether-Beck, S.; Olaizola-Horn, S.; Schmitt, H.; Grewe, M.

    1996-01-01

    UVA radiation is the major component of the UV solar spectrum that reaches the earth, and the therapeutic application of UVA radiation is increasing in medicine. Analysis of the cellular effects of UVA radiation has revealed that exposure of human cells to UVA radiation at physiological doses leads to increased gene expression and that this UVA response is primarily mediated through the generation of singlet oxygen. In this study, the mechanisms by which UVA radiation induces transcriptional activation of the human intercellular adhesion molecule 1 (ICAM-1) were examined. UVA radiation was capable of inducing activation of the human ICAM-1 promoter and increasing OCAM-1 mRNA and protein expression. These UVA radiation effects were inhibited by singlet oxygen quenchers, augmented by enhancement of singlet oxygen life-time, and mimicked in unirradiated cells by a singlet oxygen-generating system. UVA radiation as well as singlet oxygen-induced ICAM-1 promoter activation required activation of the transcription factor AP-2. Accordingly, both stimuli activated AP-2, and deletion of the putative AP-2-binding site abrogated ICAM-1 promoter activation in this system. This study identified the AP-2 site as the UVA radiation- and singlet oxygen-responsive element of the human ICAM-1 gene. The capacity of UVA radiation and/or singlet oxygen to induce human gene expression through activation of AP-2 indicates a previously unrecognized role of this transcription factor in the mammalian stress response. 38 refs., 3 figs., 3 tabs

  19. Functional characterisation of an Arabidopsis gene strongly induced by ionising radiation: the gene coding the poly(ADP-ribose)polymerase-1 (AthPARP-1)

    International Nuclear Information System (INIS)

    Doucet-Chabeaud, G.

    2000-01-01

    Arabidopsis thaliana, the model-system in plant genetics, has been used to study the responses to DNA damage, experimentally introduced by γ-irradiation. We have characterised a radiation-induced gene coding a 111 kDa protein, AthPARP-1, homologous to the human poly(ADP-ribose)polymerase-1 (hPARP-1). As hPARP-1 is composed by three functional domain with characteristic motifs, AthPARP-1 binds to DNA bearing single-strand breaks and shows DNA damage-dependent poly(ADP-ribosyl)ation. The preferential expression of AthPARP-1 in mitotically active tissues is in agreement with a potential role in the maintenance of genome integrity during DNA replication, as proposed for its human counterpart. Transcriptional gene activation by ionising radiation of AthPARP-1 and AthPARP-2 genes is to date plant specific activation. Our expression analyses after exposure to various stress indicate that 1) AthPARP-1 and AthPARP-2 play an important role in the response to DNA lesions, particularly they are activated by genotoxic agents implicating the BER DNA repair pathway 2) AthPARP-2 gene seems to play an additional role in the signal transduction induced by oxidative stress 3) the observed expression profile of AthPARP-1 is in favour of the regulation of AthPARP-1 gene expression at the level of transcription and translation. This mode of regulation of AthPARP-1 protein biosynthesis, clearly distinct from that observed in animals, needs the implication of a so far unidentified transcription factor that is activated by the presence of DNA lesions. The major outcome of this work resides in the isolation and characterisation of such new transcription factor, which will provide new insight on the regulation of plant gene expression by genotoxic stress. (author) [fr

  20. Differences in correlation of mRNA gene expression in mice sensitive and resistant to radiation-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    Johnston, C.J.; Piedboeuf, B.; Finkelstein, J.N.; Baggs, R.; Rubin, P.

    1995-01-01

    Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The purpose of this study was to determine if extracellular matrix protein and transforming growth factor β mRNA expression are altered late in the course of pulmonary fibrosis after irradiation, and then to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Radiation-sensitive (C57BL/6) and radiation-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabeled cDNA probes for collagens I, III and IV, fibronectin, and transforming growth factor β 1 and β 3 . Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceralde-hyde-3-phosphate dehydrogenase. Alterations in mRNA abundance were observed in the sensitive mice at all times, while levels in the resistant mice were unaffected until 26 weeks after irradiation. The relationship between extracellular matrix protein per se and increased mRNA abundance suggests that late matrix protein accumulation may be a function of gene expression. Differences in levels of transforming growth factor βmRNA may lead to strain-dependent variation in fibrotic response and may also contribute to the radiation-induced component of pulmonary fibrosis. 32 refs., 5 figs

  1. Detection of retinoblastoma gene deletions in spontaneous and radiation-induced mouse lung adenocarcinomas by polymerase chain reaction

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-01-01

    A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma gene using histological sections from radiation-induced and spontaneous tumors as the DNA source. Six mouse Rb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mouse Rb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (5.69 Gy 60 Co γ rays or 0.6 Gy JANUS neutrons, which have been found to have approximately equal radiobiological effectiveness) were analyzed for mouse Rb deletions. Tumors in 6 neutron-irradiated mice had no mouse Rb deletions. However, 1 of 6 tumors from γ-irradiated mice (17%) and 6 of 18 spontaneous tumors from unirradiated mice (33%) showed a deletion in one or both mouse Rb alleles. All deletions detected were in the 5' region of the mouse Rb gene. 36 refs., 2 figs., 2 tabs

  2. Cloning of radiation-induced new gene RS1 expressed in mouse intestinal epithelium by enhanced RACE

    International Nuclear Information System (INIS)

    Wang Fengchao; Wang Junping; Su Yongping; Gao Jinsheng; Lou Shufen; Liu Xiaohong; Ren Jiong; Zhang Bo

    2003-01-01

    Objective: To obtain full-length cDNA of radiation-induced new gene RS1 expressed in mouse intestinal epithelium. Methods: The tissue expression profile of RS1 was analyzed by semi-quantitative RT-PCR to find the target tissue which highly expresses RS1. The total RNA extracted from the corresponding tissue was taken as the template for reverse-transcription. Enhanced RACE PCR was used to clone the full-length cDNA of RS1, including enrichment of the target gene through biotin-labeled probe for magnetic bead purification and nested PCR. Results: About a 2 kb long 3' end was successfully cloned and cloning of the 5' end proceeded well. Conclusion: The result is consistent with our experiment design. The set of combined techniques has been identified with the cloning of full-length cDNA from EST sequence especially when the optimal gene-specific primers are not available or the expression level of target gene is low

  3. Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome

    International Nuclear Information System (INIS)

    Leadon, S.A.; Copper, P.K.

    1993-01-01

    Cells from patients with Cockayne syndrome (CS), which are sensitive to killing by UV although overall damage removal appears normal, are specifically defective in repair of UV damage in actively transcribe genes. Because several CS strains display cross-sensitivity to killing by ionizing radiation, the authors examined whether ionizing radiation-induced damage in active genes is preferentially repaired by normal cells and whether the radiosensitivity of CS cells can be explained by a defect in this process. They found that ionizing radiation-induced damage was repaired more rapidly in the transcriptionally active metallothionein IIA (MTIIA) gene than in the inactive MTIIB gene or in the genome overall in normal cells as a result of faster repair on the transcribed strand of MTIIA. Cells of the radiosensitive CS strain CS1AN are completely defective in this strand-selective repair of ionizing radiation-induced damage, although their overall repair rate appears normal. CS3BE cells, which are intermediate in radiosensitivity, do exhibit more rapid repair of the transcribed strand but at a reduced rate compared to normal cells. Xeroderma pigmentosum complementation group A cells, which are hypersensitive to UV light because of a defect in the nucleotide excision repair pathway but do not show increased sensitivity to ionizing radiation, preferentially repair ionizing radiation-induced damage on the transcribed strand of MTIIA. Thus, the ability to rapidly repair ionizing radiation-induced damage in actively transcribing genes correlates with cell survival. The results extend the generality of preferential repair in active genes to include damage other than bulky lesions

  4. Exposure to ionizing radiation induced persistent gene expression changes in mouse mammary gland

    Data.gov (United States)

    National Aeronautics and Space Administration — Six to eight week old female C57BL/6J mice were exposed to 2 Gy of whole body xce xb3 radiation and mammary glands were surgically removed 2-month after radiation....

  5. Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas.

    Science.gov (United States)

    Showler, Kaye; Nishimura, Mayumi; Daino, Kazuhiro; Imaoka, Tatsuhiko; Nishimura, Yukiko; Morioka, Takamitsu; Blyth, Benjamin J; Kokubo, Toshiaki; Takabatake, Masaru; Fukuda, Maki; Moriyama, Hitomi; Kakinuma, Shizuko; Fukushi, Masahiro; Shimada, Yoshiya

    2017-03-01

    The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

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

    Science.gov (United States)

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

    1988-04-01

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

  7. Non-homologous end-joining genes are not inactivated in human radiation-induced sarcomas with genomic instability

    International Nuclear Information System (INIS)

    Lefevre, S.H.; Coquelle, A.; Gonin-Laurent, N.

    2005-01-01

    DNA double-strand break (DSB) repair pathways are implicated in the maintenance of genomic stability. However the alterations of these pathways, as may occur in human tumor cells with strong genomic instability, remain poorly characterized. We analyzed the loss of heterozygosity (LOH) and the presence of mutations for a series of genes implicated in DSB repair by non-homologous end-joining in five radiation-induced sarcomas devoid of both active Tp53 and Rb1. LOH was recurrently observed for 8 of the 9 studied genes (KU70, KU80, XRCC4, LIG4, Artemis, MRE11, RAD50, NBS1) but not for DNA-PKcs. No mutation was found in the remaining allele of the genes with LOH and the mRNA expression did not correlate with the allelic status. Our findings suggest that non-homologous end-joining repair pathway alteration is unlikely to be involved in the high genomic instability observed in these tumors. (author)

  8. Profiling of differentially expressed genes induced by ionizing radiation in thymus cells of C57 mice

    International Nuclear Information System (INIS)

    Li Zhiheng; Li Yu

    2007-01-01

    Objective: Microarrays was used to text changes, of gene expression of thymus cell in C57 mice one moth after exposed to 1 Gy γ-ray irradiation. Methods: The difference of gene express between irradiated and un-irradiated mice being analysis by Agilent mouse oligo microarrays. Results: In the observed 21319 known genes, 107 up-regulated at least 2-fo1d (13 excess 4-fold); whereas 9 genes were down-regulated 2-fold (2 more 4-fo1d). The function of theses genes are known as some basic metabolic process. Conclusions: The gene changed in the experiment involved embryo development, organ formation and maintain, immunity or stress, protein compose, apoptosis, signal transduction. The number of gene is much more than that of down-regulated. It ought to be noticed that the gens which coding horny protein in embryo development, and ought also to be noticed that the gens which involve the function of PI3-K. (authors)

  9. Radiobiology effects of radiation-induced horseradish peroxidase/indole-3-acetic suicide gene expression in lung cancer cells

    International Nuclear Information System (INIS)

    Xiong Jie; Zhou Yunfeng; Wang Weifeng; Sun Wenjie; Liao Zhengkai; Zhou Fuxiang; Xie Conghua

    2010-01-01

    Objective: To detect specific cell killing effect of radiation combined with horseradish peroxidase (HRP)/indole-3-acetic (IAA) suicide gene therapy controlled by a novel radio-inducible and cancer-specific chimeric gene promoter in lung cancer. Methods: We constructed a plasmid expressing HRP enzyme under the control of chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 CArG elements, a plasmid expressing HRP enzyme under the control of hTERT promoter carrying single CArG element, and two control plasmids, which named pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc, respectively. After radiation, the proliferation inhibition and apoptosis induction effect of each type of plasmid in lung cancer cells (A549, SPC-A1) and normal lung cells (hEL) was detected by cell counting and Annexin V-FITC staining. The change of radiosensitivity of lung cancer cells with plasmid system was also detected by clonogenic assays. Results: After a single dose radiation of 6 Gy,the average proliferation inhibition rates of pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc systems were 72.92% ,40.60% , 51.00% and 25.19% (F= 67.31, P< 0.01) in A549 cells, 64.63%, 30.02%, 48.23% and 23.16% (F=64.94, P< 0.01) in SPC-A1 cells, and 20.81%, 18.05%, 44.20% and 18.32% (F=52.19, P<0.01) in normal hEL cells, respectively. The average early apoptosis rates of these four plasmid systems were 36.63%, 22.30%, 24.33% and 12.53% (F =50.99, P <0.01) in A549 cells, 33.73%, 17.37%, 22.43% and 11.20% (F = 20. 76, P < 0.01) in SPC-A1 cells, and 13.53 %, 12.5%, 21.93% and 12.16% (F = 15.08, P < 0.01) in normal hEL cells,respectively. The sensitizing enhancement ratios of the four plasmid systems were 3.45, 2.29, 3.05 and 1.21 in A549 cells, while 2.68, 2.15, 3.05 and 1.21 in SPC-A1 cells, respectively. Conclusions: The new suicide gene system controlled by chimeric promoter may provide a novel therapeutic modality for lung cancer. (authors)

  10. Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in vitro.

    Science.gov (United States)

    Yoshino, Hironori; Iwabuchi, Miyu; Kazama, Yuka; Furukawa, Maho; Kashiwakura, Ikuo

    2018-04-01

    Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis.

  11. Effect of Bcl-2/Bax gene expression on apoptosis of spermatogenic cells of mouse testes induced by low dose radiation

    International Nuclear Information System (INIS)

    Liu Guangwei; Wang Chunyan; Lu Zhe; Liu Shunchun; Gong Shouliang

    2003-01-01

    The different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptosis and Bcl-2 and Bax protein expression were measured with flow cytometry and immunohistochemical method, respectively. The results showed the apoptosis in all kinds of spermatogenic cells induced by low dose radiation (LDR) had a obvious regularity. When the doses were 0.025 and 0.05 Gy, spermatogonia apoptosis was dominant. With the increase of irradiation dose (0.075-0.2 Gy), spermatocytes also showed an apoptotic change, but the apoptotic percentage of spermatogonia was significantly higher than that of spermatocytes. Moreover, the apoptosis of spermatids and spermatozoa scarcely occurred after LDR. Bax protein was primarily expressed in spermatogonia and spermatocytes, and the former was significantly higher than that of the latter after LDR. With the increase of irradiation dose, Bax protein expression showed a upgrading tendency, but that of spermatids and spermatozoa scarcely occurred. Bcl-2 protein was primarily expressed in spermatids and spermatozoa, but the Bcl-2 protein expressions of spermatogonia and spermatocytes scarcely occurred after LDR. These results imply that the interacting regulation of Bcl-2 and Bax gene expression might be involved in selective apoptosis of spermatogenic cells induced by LDR, which provided an experimental evidence for further exploring the apoptotic mechanism of adaptive response of spermatogenic cells by LDR

  12. 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)

  13. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-01-01

    From 1971--1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF 1 mice irradiated with 60 Co γ-rays or JANUS fission-spectrum neutrons. Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice were analyzed for mRb deletions. In all normal mouse tissues studies all six mRb exon fragments were present on Southern blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, 1 of 6 tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  14. 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

  15. A genome-wide search for genes involved in the radiation-induced gastroschisis

    International Nuclear Information System (INIS)

    Hillebrandt, S.; Streffer, C.

    1997-01-01

    Whole genome linkage analysis of gastroschisis (abdominal wall defect) using geno-typing with micro-satellites of affected BC1 mice [(HLGxC57BL/6J)xHLG] was performed. The HLG inbred strain shows an increased risk in gastroschisis after irradiation of embryos in the 1-cell stage. Previous studies demonstrated, that gastroschisis is a poly-genic trait with a recessive mode of inheritance. Since a recessive inheritance of gastroschisis is assumed, the involved genes must be linked to markers showing a high level of homozygosity in the affected animals. For marker loci on the chromosome 13 and 19 a significantly increased number of homozygotes has been found in mice with gastroschisis comparing to mice without this malformation. The linkage analysis performed by us allowed determining intervals likely to contain genes related to gastroschisis on these two chromosomes. The highest lod score value has been found for the marker locus D19MIT27 very close to Pax2 (lod score=1.23; p=0.017). For the marker D13MIT99 a lod score of 0.85 (p=0.047) was calculated. However, markers more close to the homeo-box gene Msx-2 on the chromosome 13 show lower lod score values than D13MIT99, suggesting that this homeo-box gene is probably not involved in gastroschisis. According to the classification of results of the linkage analysis of complex traits described by Lander and Kruglyak (1995), our data provide a suggestive evidence for the involvement of the analyzed intervals on the chromosomes 19 and 13 to gastroschisis. Further studies are necessary to prove this linkage. (authors)

  16. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1993-01-01

    From 1971 to 1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF 1 mice irradiated with 60 Co γ rays or JANUS fission-spectrum neutrons; normal and tumor tissues from mice in these studies were preserved in paraffin blocks. A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma (mRb) gene in the paraffin-embedded tissues. Microtomed sections were used as the DNA source in PCR reaction mixtures. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments (relative to control PCR products) on a Southern blot indicated a deletion of that portion of the mRb gene. The tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice (569 cGy of 60 Co γ rays or 60 cGy of JANUS neutrons, doses that have been found to have approximately equal biological effectiveness in the BCF, mouse) were analyzed for mRb deletions. In all normal mouse tissues studies, all six mRb exon fragments were present on Southem blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, I of 6 tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice had a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  17. Screening of radiation-induced genes in human lymphoblastoid cells irradiated with 20 cGy of γ-ray by gene chip

    International Nuclear Information System (INIS)

    Wang Huiping; Long Xianhui; Xu Qinzhi; Bai Bei; Sui Jianli; Zhou Pingkun

    2006-01-01

    cDNA gene chip was used to detect the transcriptional profile of human lymphoblasts cells irradiated with 20 cGy of 60 Co γ-ray. The microarray contains 14112 cDNA probing corresponding to 14112 human genes. The results showed that the transcription level of 83 genes changed; among which 21 genes were up-regulated. Most of them were associated with signal transduction, cell cycle regulation, cellular immunity, cytoskeleton and movement, etc. It indicated that low-dose irradiation can modulate the expression of a series of functional genes, which is the primary molecular basis of cellular responses to radiation. (authors)

  18. Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

    International Nuclear Information System (INIS)

    Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

    2009-01-01

    Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 ± 9.01 vs. 41.94 ± 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 ± 1303 vs. 1667 ± 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 ± 1084 vs. 1566 ± 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

  19. Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?

    International Nuclear Information System (INIS)

    Hong, J.-H.; Chiang, C.-S.; Tsao, C.-Y.; Lin, P.-Y.; Wu, C.-J.; McBride, William H.

    2001-01-01

    Purpose: To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes. Methods and Materials: At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-α, mIL-1α, mIL-1β, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-γ) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay. Results: Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg) suppresses both basal cytokine mRNA levels and this early response when given immediately after irradiation. However, by 24 h, in mice treated with DEX alone or DEX plus radiation, there was a strong rebound effect that lasted up to 3 days. Modification of the early radiation-induced response by DEX did not change the second wave of cytokine gene expression in the lung that occurs at 1 to 2 weeks, suggesting that early cytokine gene induction might not determine subsequent molecular events. A single dose of DEX attenuated, but did not completely suppress, increases in cytokine mRNA levels induced by lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no significant rebound effect was seen. Five days of dexamethasone treatment in the pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and, again, there was a rebound effect after withdrawal of the drug. Conclusions: Our findings suggest that short-term use of dexamethasone can temporarily suppress radiation-induced pro-inflammatory cytokine gene expression, but there may be a rebound after drug withdrawal and the drug does little to change the essence and course of the pneumonitic process

  20. Quantification of gene expression modulation at the human genome wide induced by low doses of ionizing radiations

    International Nuclear Information System (INIS)

    Nosel, Ingrid

    2013-01-01

    The main goal of this study is to identify the molecular mechanisms involved in the response to low doses of ionizing radiation by using oligonucleotide micro-arrays. The results presented in this study demonstrate the relevance of this tool in the characterization of changes in gene expression at low doses of g radiation. All experimentations conducted were conducted on T CD4+ human lymphocytes. From this model we tried to characterize in 600 minutes after irradiation the molecular players in response to a dose range of 5 and 500 mGy. In this study, we highlight two types of molecular response. First, a dose-dependent response to irradiation involving groups of genes whose proteins are implicated in the response to DNA damage and in the p53 signaling pathway. The expression of the majority of the genes is modulated from 100 mGy. The second type of response is independent of the irradiation dose and the proteins encoded are involved in the mechanism of oxidative phosphorylation. Some of these genes could potentially be regulated by a family of transcription factor with an ETS domain. These ETS factors are known to be potential targets of the MAPKinase pathway. All these genes are modulated from 5 mGy and are therefore potential molecular players involved in the cellular response to ionizing stress with a low intensity. (author)

  1. Ultraviolet B radiation induces impaired lifecycle traits and modulates expression of cytochrome P450 (CYP) genes in the copepod Tigriopus japonicus.

    Science.gov (United States)

    Puthumana, Jayesh; Lee, Min-Chul; Park, Jun Chul; Kim, Hui-Su; Hwang, Dae-Sik; Han, Jeonghoon; Lee, Jae-Seong

    2017-03-01

    To evaluate the effects of ultraviolet B (UV-B) radiation at the developmental, reproductive, and molecular levels in aquatic invertebrates, we measured UV-B-induced acute toxicity, impairments in developmental and reproductive traits, and UV-B interaction with the entire family of cytochrome P450 (CYP) genes in the intertidal benthic copepod Tigriopus japonicus. We found a significant, dose-dependent reduction (Pcopepods through the predicted AhR-mediated up-regulation of CYP genes. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Rapid screening of spontaneous and radiation-induced structural changes at the vestigial gene of Drosophila melanogaster by polymerase chain reaction

    International Nuclear Information System (INIS)

    Aleksandrov, I.D.; Lapidus, I.L.; Aleksandrova, M.V.; Karpovskij, A.L.; Korablinova, S.V.; Levkovich, N.V.

    1998-01-01

    A total of 27 independent isolated spontaneous and gamma-ray-induced heritable mutations at the vestigial gene of Drosophila melanogaster were analysed by a rapid deletion screening method with polymerase chain reaction (PCR) amplification. According to the results obtained 36.4% (4 of 11) of spontaneous mutants and 62.5% (10 of 16) of gamma-ray-induced ones have revealed deficiency of one or more fragments studied. The rest of spontaneous and radiation mutants showed no alterations in the PCR patterns, indicating possible small scale changes (point mutations) inside the gene region studied or, probably, the gross lesions situated elsewhere. The distribution of the mutation damages in the gene region studied are discussed

  3. Mitigating effects of L-selenomethionine on low-dose iron ion radiation-induced changes in gene expression associated with cellular stress.

    Science.gov (United States)

    Nuth, Manunya; Kennedy, Ann R

    2013-07-01

    Ionizing radiation associated with highly energetic and charged heavy (HZE) particles poses a danger to astronauts during space travel. The aim of the present study was to evaluate the patterns of gene expression associated with cellular exposure to low-dose iron ion irradiation, in the presence and absence of L-selenomethionine (SeM). Human thyroid epithelial cells (HTori-3) were exposed to low-dose iron ion (1 GeV/n) irradiation at 10 or 20 cGy with or without SeM pretreatment. The cells were harvested 6 and 16 h post-irradiation and analyzed by the Affymetrix U133Av2 gene chip arrays. Genes exhibiting a 1.5-fold expression cut-off and 5% false discovery rate (FDR) were considered statistically significant and subsequently analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) for pathway analysis. Representative genes were further validated by real-time RT-PCR. Even at low doses of radiation from iron ions, global genome profiling of the irradiated cells revealed the upregulation of genes associated with the activation of stress-related signaling pathways (ubiquitin-mediated proteolysis, p53 signaling, cell cycle and apoptosis), which occurred in a dose-dependent manner. A 24-h pretreatment with SeM was shown to reduce the radiation effects by mitigating stress-related signaling pathways and downregulating certain genes associated with cell adhesion. The mechanism by which SeM prevents radiation-induced transformation in vitro may involve the suppression of the expression of genes associated with stress-related signaling and certain cell adhesion events.

  4. Dose-effect of ionizing radiation-induced PIG3 gene expression alteration in human lymphoblastoid AHH-1 cells and human peripheral blood lymphocytes.

    Science.gov (United States)

    Liu, Qing-Jie; Zhang, De-Qin; Zhang, Qing-Zhao; Feng, Jiang-Bin; Lu, Xue; Wang, Xin-Ru; Li, Kun-Peng; Chen, De-Qing; Mu, Xiao-Feng; Li, Shuang; Gao, Ling

    2015-01-01

    To identify new ionizing radiation (IR)-sensitive genes and observe the dose-effect of gene expression alteration (GEA) induced by IR. Microarray was used to screen the differentially expressed genes in human lymphoblastoid cells (AHH-1) using three doses of (60)Co γ-rays (0.5-8 Gy at 1 Gy/min). Given that p53-inducible gene 3 (PIG3) was consistently upregulated, the GEA of PIG3 in AHH-1 cells and human peripheral blood lymphocytes (HPBL) induced by γ-rays (1 Gy/min) was measured at messenger RNA (mRNA) and protein levels. The GEA of PIG3 in AHH-1 cells exposed to neutron radiation (californium-252, 0.073 Gy/min) was also quantified. PIG3 was one of the seven differentially expressed genes found in the microarray analysis. The PIG3 mRNA and protein levels in AHH-1 cells were significantly increased from 1-10 Gy of γ-rays 8-72 h or 8-168 h after exposure, respectively. The enhancement was also observed in AHH-1 cells from 0.4-1.6 Gy of neutrons 48 h post-irradiation. The PIG3 mRNA levels (mRNA copy numbers) in HPBL were significantly increased from 1-8 Gy of γ-rays within 4-24 h post-irradiation, but the highest increase in signal-to-noise responsiveness is approximately two-fold, which was less than that of AHH-1 (approximately 20-fold). IR can upregulate the PIG3 gene expression in AHH-1 and HPBL in the early phase after exposure; however, the IR induced expression levels of PIG3 are greater in AHH-1 than HPBL.

  5. Ultraviolet B radiation induces impaired lifecycle traits and modulates expression of cytochrome P450 (CYP) genes in the copepod Tigriopus japonicus

    Energy Technology Data Exchange (ETDEWEB)

    Puthumana, Jayesh; Lee, Min-Chul; Park, Jun Chul; Kim, Hui-Su; Hwang, Dae-Sik; Han, Jeonghoon, E-mail: jeonghoon@skku.edu; Lee, Jae-Seong, E-mail: jslee2@skku.edu

    2017-03-15

    Highlights: • Impaired effects of UV-B on the copepod Tigriopus japonicus were examined. • Modulation of entire CYP genes were analyzed in response to UV-B. • CYP inhibitor (PBO) confirmed the role of CYP in UV-B induced mortality. • Low-dose UV-B found induce developmental delays, and higher doses cause reproductive impairments. • Study predicted the mechanistic effects of UV-B in copepods through the AhR-mediated up-regulation of CYP genes. - Abstract: To evaluate the effects of ultraviolet B (UV-B) radiation at the developmental, reproductive, and molecular levels in aquatic invertebrates, we measured UV-B-induced acute toxicity, impairments in developmental and reproductive traits, and UV-B interaction with the entire family of cytochrome P450 (CYP) genes in the intertidal benthic copepod Tigriopus japonicus. We found a significant, dose-dependent reduction (P < 0.05) in the survival of T. japonicus that began as a developmental delay and decreased fecundity. The 48 h LD10 and LD50 were 1.35 and 1.84 kJ/m{sup 2}, and the CYP inhibitor (PBO) elevated mortality, confirming the involvement of CYP genes in UV-B induced toxicity. Low-dose UV-B (1.5 kJ/m{sup 2}) induced developmental delays, and higher doses (6–18 kJ/m{sup 2}) caused reproductive impairments in ovigerous females. The significant up-regulation of CYP genes belonging to clans 2/3/MT/4/20 in T. japonicus exposed to UV-B (12 kJ/m{sup 2}) confirmed molecular interaction between UV-B and CYP genes. Moreover, orphan CYPs, such as CYP20A1, provide good insight on the deorphanization of invertebrate CYPs. Overall, these results demonstrate the involvement of UV-B radiation in the expression of all the CYP genes in T. japonicus and their susceptibility to UV-B radiation. This will provide a better understanding of the mechanistic effects of UV-B in copepods through the predicted AhR-mediated up-regulation of CYP genes.

  6. Ultraviolet B radiation induces impaired lifecycle traits and modulates expression of cytochrome P450 (CYP) genes in the copepod Tigriopus japonicus

    International Nuclear Information System (INIS)

    Puthumana, Jayesh; Lee, Min-Chul; Park, Jun Chul; Kim, Hui-Su; Hwang, Dae-Sik; Han, Jeonghoon; Lee, Jae-Seong

    2017-01-01

    Highlights: • Impaired effects of UV-B on the copepod Tigriopus japonicus were examined. • Modulation of entire CYP genes were analyzed in response to UV-B. • CYP inhibitor (PBO) confirmed the role of CYP in UV-B induced mortality. • Low-dose UV-B found induce developmental delays, and higher doses cause reproductive impairments. • Study predicted the mechanistic effects of UV-B in copepods through the AhR-mediated up-regulation of CYP genes. - Abstract: To evaluate the effects of ultraviolet B (UV-B) radiation at the developmental, reproductive, and molecular levels in aquatic invertebrates, we measured UV-B-induced acute toxicity, impairments in developmental and reproductive traits, and UV-B interaction with the entire family of cytochrome P450 (CYP) genes in the intertidal benthic copepod Tigriopus japonicus. We found a significant, dose-dependent reduction (P < 0.05) in the survival of T. japonicus that began as a developmental delay and decreased fecundity. The 48 h LD10 and LD50 were 1.35 and 1.84 kJ/m"2, and the CYP inhibitor (PBO) elevated mortality, confirming the involvement of CYP genes in UV-B induced toxicity. Low-dose UV-B (1.5 kJ/m"2) induced developmental delays, and higher doses (6–18 kJ/m"2) caused reproductive impairments in ovigerous females. The significant up-regulation of CYP genes belonging to clans 2/3/MT/4/20 in T. japonicus exposed to UV-B (12 kJ/m"2) confirmed molecular interaction between UV-B and CYP genes. Moreover, orphan CYPs, such as CYP20A1, provide good insight on the deorphanization of invertebrate CYPs. Overall, these results demonstrate the involvement of UV-B radiation in the expression of all the CYP genes in T. japonicus and their susceptibility to UV-B radiation. This will provide a better understanding of the mechanistic effects of UV-B in copepods through the predicted AhR-mediated up-regulation of CYP genes.

  7. Radiation-induced progressive decreasing in the expression of reverse transcriptase gene of hEST2 and telomerase activity

    International Nuclear Information System (INIS)

    Zhu Hanneng; Chen Wenying; Xiong Sidong

    2000-01-01

    Telomerase is a ribonucleoprotein complex that adds heximeric repeats called telomeres to the growing ends of chromosomal DNA. Telomerase activity is present in a vast majority of tumors but is repressed in most normal tissues. Human telomerase catalytic subunit gene (hEST2) reverse transcriptase (RT) segment was cloned by PCR according to the sequence published in GeneBank. PCR was used to investigate the expression of the hEST2 RT segment in diverse tumors as well as in various normal tissues. Results indicated that hEST2 RT segment was detectable in tumor cells lines but not in normal cells and tissues. In order to identify the relationship between telomerase and the biological effect of radiation injury, HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60 Co-ray irradiation at RNA level and protein level. Quantitative PCR determined that expression of hEST2 RT segment that encodes seven motifs of the human telomeras decreased with increasing dosage of radiation. In addition, a PCR-based telomeric repeat amplification protocol was used to assay telomerase activity after exposure to radiation. The results strongly support the experiments we had made: Telomerase activity decreases with increasing dosage of radiation. We conclude that detection of the hEST2 RT segment by Northern blotting is a new method for detecting telomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation. (author)

  8. 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.

  9. Effects of expression level of DNA repair-related genes involved in the NHEJ pathway on radiation-induced cognitive impairment

    International Nuclear Information System (INIS)

    Zhang Liyuan; Chen Liesong; Sun Rui; Ji Shengjun; Ding Yanyan; Wu Jia; Tian Ye

    2013-01-01

    Cranial radiation therapy can induce cognitive decline. Impairments of hippocampal neurogenesis are thought to be a paramountly important mechanism underlying radiation-induced cognitive dysfunction. In the mature nervous system, DNA double-strand breaks (DSBs) are mainly repaired by non-homologous end-joining (NHEJ) pathways. It has been demonstrated that NHEJ deficiencies are associated with impaired neurogenesis. In our study, rats were randomly divided into five groups to be irradiated by single doses of 0 (control), 0 (anesthesia control), 2, 10, and 20 Gy, respectively. The cognitive function of the irradiated rats was measured by open field, Morris water maze and passive avoidance tests. Real-time PCR was also used to detect the expression level of DNA DSB repair-related genes involved in the NHEJ pathway, such as XRCC4, XRCC5 and XRCC6, in the hippocampus. The influence of different radiation doses on cognitive function in rats was investigated. From the results of the behavior tests, we found that rats receiving 20 Gy irradiation revealed poorer learning and memory, while no significant loss of learning and memory existed in rats receiving irradiation from 0-10 Gy. The real-time PCR and Western blot results showed no significant difference in the expression level of DNA repair-related genes between the 10 and 20 Gy groups, which may help to explain the behavioral results, id est (i.e.) DNA damage caused by 0-10 Gy exposure was appropriately repaired, however, damage induced by 20 Gy exceeded the body's maximum DSB repair ability. Ionizing radiation-induced cognitive impairments depend on the radiation dose, and more directly on the body's own ability to repair DNA DSBs via the NHEJ pathway. (author)

  10. 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

  11. Study of genes induced by ionizing radiations at Arabidopsis thaliana: identification and molecular characterization of the ATGR1 gene, a new gene encoding a protein involved in plant cell division

    International Nuclear Information System (INIS)

    Deveaux, Yves

    1999-01-01

    DNA damage, that can be experimentally introduced by ionizing radiation (IR), induces complex signal transduction pathways leading to cell recovery or, alternatively to programmed cell death if damages are too severe. To identify the inducible components of the response to genotoxic stress in plants, we have screened by Differential Display for mRNAs that rapidly and strongly accumulate after IR treatment in A. thaliana cells. We have characterized ATGR1, a new single copy Arabidopsis gene encoding a PEST-box protein of unknown function. In unstressed plant organs the ATGR1 mRNA is hardly detectable, whereas the protein is present in extracts prepared from roots, shoot meristems and inflorescences, that all contain large amounts of actively dividing cells. This pattern is confirmed by immuno localisation on tissue sections that shows constitutive ATGR1 protein expression covering the root elongation zone, the shoot meristem, leaf primordial and the ovules of developing flowers. Histochemical analysis of transgenic plants expressing the GUS reporter gene under the control of the ATGR1 promoter, demonstrate that the developmental and tissue-specific profile of ATGR1 protein expression is conferred by the gene promoter. The massive, transient and dose-dependent accumulation of ATGR1 transcripts after IR treatment observed in all plant organs does not lead to significant changes in ATGR1 protein pattern. Stable ATGR1 protein overexpression, as exemplified by transgenic A. thaliana plants that contain a 35S promoter-ATGR1 gene fusion, does not induce notable changes of the overall ATGR1 protein level, but leads to male and female sterility. The cause of sterility is a lack of correct chromosome assembly and distribution at the stage metaphase II of meiosis. Taken together our results show that i) ATGR1 gene expression is associated to cell division during plant development ii) the ATGR1 protein level is regulated at the transcriptional and post-transcriptional level iii

  12. 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)

  13. Radiation induced microbial pesticide

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Young Keun; Kim, Jae Sung; Kim, Jin Kyu; Lee, Sang Jae

    2000-01-01

    To control 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 13 kinds of fungi. Mutants of K1 and YS1 strains were induced by gamma-ray radiation and showed promising antifungal activities. These wild type and mutants showed resistant against more than 27 kinds of commercial pesticides among 30 kinds of commercial pesticides test particularly, YS1-1006 mutant strain showed resistant against hydrogen oxide. And mutants had increased antifungal activity against Botryoshaeria dothidea. These results suggested that radiation could be an useful method for the induction of functional mutants. (author)

  14. Dependence of the expression of the radiation-induced gene conversion to arginine independence in diploid yeast on the amino acid concentration: effect on allelic mapping

    International Nuclear Information System (INIS)

    Murthy, M.S.S.; Rao, B.S.; Deorukhakar, V.V.

    1976-01-01

    The yield of radiation-induced gene conversion to arginine independence in diploid yeast depended on the concentration of the amino acid both in the plating medium and in the intracellular pool. By depletion of the level of arginine in the intracellular pool of amino acid or by provision of arginine at 0.4 mg/l of the plating medium, the yield was varied by a factor as high as 20. This may be important in studies of the genetic mapping of alleles based on the slope of conversion frequency versus dose line

  15. The genetics of radiation-induced osteosarcoma

    International Nuclear Information System (INIS)

    Rosemann, M.; Kuosaite, V.; Nathrath, M.; Atkinson, M.J.

    2002-01-01

    Individual genetic variation can influence susceptibility to the carcinogenic effects of many environmental carcinogens. In radiation-exposed populations those individuals with a greater genetically determined susceptibility would be at greater risk of developing cancer. To include this modification of risk into radiation protection schemes it is necessary to identify the genes responsible for determining individual sensitivity. Alpha-particle-induced osteosarcoma in the mouse has been adopted as a model of human radiation carcinogenesis, and genome-wide screens have been conducted for allelic imbalance and genetic linkage. These studies have revealed a series of genes involved in determining the sensitivity to radiogenic osteosarcoma formation. (author)

  16. Radio-induced genes

    International Nuclear Information System (INIS)

    Rigaud, O.; Kazmaier, M.

    2000-01-01

    The monitoring system of the DNA integrity of an irradiated cell does not satisfy oneself to recruit the enzymes allowing the repair of detected damages. It sends an alarm signal whom transmission leads to the activation of specific genes in charge of stopping the cell cycle, the time to make the repair works, or to lead to the elimination of a too much damaged cell. Among the numerous genes participating to the monitoring of cell response to irradiation, the target genes of the mammalian P53 protein are particularly studied. Caretaker of the genome, this protein play a central part in the cell response to ionizing radiations. this response is less studied among plants. A way to tackle it is to be interested in the radioinduced genes identification in the vegetal cell, while taking advantage of knowledge got in the animal field. The knowledge of the complete genome of the arabette (arabidopsis thaliana), the model plant and the arising of new techniques allow to lead this research at a previously unknown rhythm in vegetal biology. (N.C.)

  17. The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sunaoshi, Masaaki [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Blyth, Benjamin J. [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Morioka, Takamitsu [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kaminishi, Mutsumi [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shang, Yi [Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Shimada, Yoshiya [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Tachibana, Akira [Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); and others

    2015-09-15

    Highlights: • T-cell lymphoma incidence, latency and weight did not change with age at exposure. • Lymphomas had frequent loss of heterozygosity on chromosomes 4, 11 and 19. • These lesions targeted the Cdkn2a, Ikaros and Pten tumor suppressor genes. • Age at exposure may influence which tumor suppressor genes are lost in each tumor. • The mechanisms of tumor suppressor gene loss were different at each locus. - Abstract: Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2

  18. Profiles of Gene Expression Induced by Ionizing Radiation in Different Human Cell Types. Doctoral thesis prepared at SCK-CEN and defended in 2005

    International Nuclear Information System (INIS)

    Mori, M.

    2006-01-01

    Ionizing radiation disrupts chemical bonds in biomolecules, such as proteins and DNA, which result in important cellular damage. Exposure to relatively high doses of ionizing radiation such as those delivered to the tumor in a radiotherapy protocol is generally lethal for the cell. However, non-lethal dose of ionizing radiation can be delivered during radiotherapy to the healthy tissue surrounding the tumor. Although the effects of ionizing radiation at the cellular level are quite well established (cell cycle arrest, senescence, apoptosis, mitotic catastrophe), questions remain concerning the molecular pathways regulating these cellular responses, including those differentiating the responses between tumor and normal cells. In normal cells, the p53 protein plays a central role. However, the efficacy of radiation treatments on tumor cells is often reduced because of the frequent inactivation of the p53 protein in those cells. Our study used the microarray technology to investigate the molecular pathways induced by irradiation in transformed and nontransformed human cells. Profiles of gene expression obtained with cDNA microarrays were regarded as steps to characterize the general response to ionizing radiation and, possibly also, differentiating the response between transformed and nontransformed cells. Possible implications of such research include the development of radiosensitizing (to maximize the effect of radiotherapeutic irradiation) and of radioprotecting strategies. Transcriptional profiles were investigated in transformed (Jurkat, HL60) and non-transformed (freshly isolated lymphocyte subpopulations) cells of hematopoietic origin. Also, because HeLa carcinoma-derived cells expressing human papilloma virus (HPV) 18 derived E2 protein represent a reliable model to study the p53 pathway, which is normally activated in response to radiation, molecular profiles were obtained to characterize this pathway in these cells

  19. 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

  20. Radiation-induced nondisjunction

    International Nuclear Information System (INIS)

    Uchida, I.A.

    1979-01-01

    The methodology and results of epidemiological studies of the effects of preconception diagnostic x-rays of the abdomen on chromosome segregation in humans are described. The vast majority of studies show the same positive, though not significant, trend to increased nondisjunction among the offspring of irradiated women. The results of the various studies, however, cannot be pooled because of differing methodologies used. Abnormal chromosome segregation during mitotic division has been inducted experimentally by the in vitro exposure of human lymphocytes to a low dose of 50 R gamma irradiation. First meiotic nondisjunction has been successfully induced by whole body exposure of female mice to a low dose of radiation. The question of time-related repair of the mechanism involved in chromosome segregation is raised

  1. Soluble TGF-β type II receptor gene therapy reduces TGF-β activity in irradiated lung tissue and protects lungs from radiation-induced injury

    International Nuclear Information System (INIS)

    Vujaskovic, Z.; Rabbani, Z.; Zhang, X.; Samulski, T.V.; Li, C.-Y.; Anscher, M.S.

    2003-01-01

    Full text: The objective was to determine whether administration of recombinant human adenoviral vector carrying soluble TGF-β1 type II receptor (TβR-II) gene reduces availability of active TGFβ1 and protects lung from radiation-induced injury. Female Fisher-344 rats were randomized into four groups to receive: 1) Control 2) Adenoviral green fluorescent protein vector (AdGFP) alone 3) Radiation (RT) + Adenoviral vector with TGF-β1 type II receptor gene (AdexTβR-II-Fc) 4) RT alone. Animals were irradiated to right hemithorax using a single dose of 30 Gy. The packaging and production of a recombinant adenovirus carrying the fused human TβR-II-IgG1 Fc gene was achieved by use of the AdEasy system. The treatment vector AdexTbR-II-Fc (1.5*1010 PFU) and control vector AdGFP (1*109 PFU) were injected i.v. 24 hrs after RT. Respiratory rate was measured as an index of pulmonary function weekly for 5 weeks post RT. Structural damage was scored histologically. Immunohistochemistry was performed to identify activated macrophages. ELISA was used to quantify active TGF-β1 in tissue homogenate. Western blot was used to determine TβR-II expression in plasma and lung tissue. Animals receiving treatment vector AdexTbR-II-Fc have elevated plasma levels of soluble TβR-II at 24 and 48 hours after injection. In the RT+AdexTbR-II-Fc group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment compared to RT alone group. Histology revealed a significant reduction in lung structural damage in animals receiving gene therapy after RT vs RT alone (p=0.0013). There was also a decrease in the number of activated macrophage (p= 0.02) in RT+AdexTbR-II-Fc group vs RT alone. The tissue protein expression of active TGF-β1 was significantly reduced in rats receiving RT+AdexTbR-II-Fc treatment (p<0.05). This study shows the ability of adenovirus mediated soluble TβR-II gene therapy to reduce tissue levels of active TGF-β1 and ameliorate radiation-induced

  2. 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

  3. 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

  4. Reoxygenation of human coronary smooth muscle cells suppresses HIF-1{alpha} gene expression and augments radiation-induced growth delay and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Grumann, T.; Arab, A.; Bode, C.; Hehrlein, C. [Dept. of Cardiology, Univ. Clinic of Freiburg (Germany); Guttenberger, R. [Dept. of Radiotherapy, Univ. Clinic of Freiburg (Germany)

    2006-01-01

    Background and Purpose: Catheter-based coronary brachytherapy with {beta}- and {gamma}-radiation is an evidence-based method to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation, but the outcome may be PTCA are hypoxic. A lack of oxygen decreases the effect of low LET (linear energy transfer) irradiation. The authors assumed that reoxygenation of hypoxic human coronary smooth muscle cells (HCSMCs) improves the results of coronary brachytherapy. The expression of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) gene, and the rates of growth and apoptosis of hypoxic and reoxygenated HCSMCs after {gamma}-iradiation were therefore analyzed. Material and Methods: An in vitro model of megacolonies of HCSMCs was developed. After exposure to chronic hypoxia the HCSMCs were irradiated with graded doses of 2, 4, 8, and 16 Gy using a {sup 60}Co source either under hypoxia (pO{sub 2}<3 mmHg) or after reoxygenation (pO{sub 2}{approx}150 mmHg). RT-PCR (reverse transcription-polymerase chain reaction) analysis was used to quantify HIF-1{alpha} gene expression and the growth of HCSMC megacolonies was measured serially. The oxygen enhancement ratio (OER) was calculate from the specific growth delay. Apoptosis of HCSMCs was quantified by counting cells with specific DNA strand breaks using the TUNEL assy. Results: HIF-1{alpha} gene expression was markedly suppressed in reoxygenated cells versus hypoxic cells 30 min after {gamma}-irradiation at all radiation doses (158{+-}46% vs. 1,675{+-}1,211%; p<0.01). Apoptosis was markedly increased in reoxygenated HCSMCs. The OER was 1.8(95% CI[confidence interval]1.3-2.4). Therefore, reoxygenated HCSMCs require 44% less radiation dose to achieve the equivalent biological radiation effect compared to hypoxic HCSMCs. Conclusion: Reoxygenation of coronary smooth muscle cells should be considered an option to increase efficacy of coronary brachytherapy. This could be used to reduce radiation dose

  5. 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)

  6. Protective Role of Hsp27 Protein Against Gamma Radiation-Induced Apoptosis and Radiosensitization Effects of Hsp27 Gene Silencing in Different Human Tumor Cells

    International Nuclear Information System (INIS)

    Aloy, Marie-Therese; Hadchity, Elie; Bionda, Clara; Diaz-Latoud, Chantal; Claude, Line; Rousson, Robert; Arrigo, Andre-Patrick; Rodriguez-Lafrasse, Claire

    2008-01-01

    Purpose: The ability of heat shock protein 27 (Hsp27) to protect cells from stressful stimuli and its increased levels in tumors resistant to anticancer therapeutics suggest that it may represent a target for sensitization to radiotherapy. In this study, we investigate the protective role of Hsp27 against radiation-induced apoptosis and the effect of its attenuation in highly expressing radioresistant cancer cell lines. Methods and Materials: We examined clonogenic death and the kinetics of apoptotic events in different tumor cell lines overexpressing or underexpressing Hsp27 protein irradiated with photons. The radiosensitive Jurkat cell line, which does not express Hsp27 constitutively or in response to γ-rays, was stably transfected with Hsp27 complementary DNA. Attenuation of Hsp27 expression was accomplished by antisense or RNAi (interfering RNA) strategies in SQ20B head-and-neck squamous carcinoma, PC3 prostate cancer, and U87 glioblastoma radioresistant cells. Results: We measured concentration-dependent protection against the cytotoxic effects of radiation in Jurkat-Hsp27 cells, which led to a 50% decrease in apoptotic cells at 48 hours in the highest expressing cells. Underlying mechanisms leading to radiation resistance involved a significant increase in glutathione levels associated with detoxification of reactive oxygen species, a delay in mitochondrial collapse, and caspase activation. Conversely, attenuation of Hsp27 in SQ20B cells, characterized by their resistance to apoptosis, sensitizes cells to irradiation. This was emphasized by increased apoptosis, decreased glutathione basal level, and clonogenic cell death. Sensitization to irradiation was confirmed in PC3 and U87 radioresistant cells. Conclusion: Hsp27 gene therapy offers a potential adjuvant to radiation-based therapy of resistant tumors

  7. Radiation-modulated gene expression in C. elegans

    International Nuclear Information System (INIS)

    Nelson, G.A.; Bayeta, E.; Perez, C.; Lloyd, E.; Jones, T.; Smith, A.; Tian, J.

    2003-01-01

    Full text: We use the nematode C. elegans to characterize the genotoxic and cytotoxic effects of ionizing radiation with emphasis effects of charged particle radiation and have described the fluence vs. response relationships for mutation, chromosome aberration and certain developmental errors. These endpoints quantify the biological after repair and compensation pathways have completed their work. In order to address the control of these reactions we have turned to gene expression profiling to identify genes that uniquely respond to high LET species or respond differentially as a function of radiation properties. We have employed whole genome microarray methods to map gene expression following exposure to gamma rays, protons and accelerated iron ions. We found that 599 of 17871 genes analyzed showed differential expression 3 hrs after exposure to 3 Gy of at least one radiation types. 193 were up-regulated, 406 were down-regulated, and 90% were affected by only one species of radiation. Genes whose transcription levels responded significantly mapped to definite statistical clusters that were unique for each radiation type. We are now trying to establish the functional relationships of the genes their relevance to mitigation of radiation-induced damage. Three approaches are being used. First, bioinformatics tools are being used to determine the roles of genes in co-regulated gene sets. Second, we are applying the technique of RNA interference to determine whether our radiation-induced genes affect cell survival (measured in terms of embryo survival) and chromosome aberration (intestinal anaphase bridges). Finally we are focussing on the response of the most strongly-regulated gene in our data set. This is the autosomal gene, F36D3.9, whose predicted structure is that of a cysteine protease resembling cathepsin B. An enzymological approach is being used to characterize this gene at the protein level. This work was supported by NASA Cooperative Agreement NCC9-149

  8. 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)

  9. Radiation-induced enteropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sher, M.E.; Bauer, J. (Mount Sinai Hospital, New York, NY (USA))

    1990-02-01

    The incidence of chronic radiation enteritis appears to have risen in recent years due to the increasing utilization of radiotherapy for abdominal and pelvic malignancies. The etiology, pathogenesis, and management of radiation enteritis are discussed. Two case reports exemplify the progressive nature of the disease. Case 1 demonstrates the classical picture of multiple exacerbations and remissions of partial small bowel obstruction and the eventual need for surgical management ten years after radiation therapy. Case 2 presents the more severe sequelae of an acute perforation with a 14-yr latency period. Predisposing factors in the progression of radiation injury include excessive radiation, underlying cardiovascular disease, fixation of the bowel, and an asthenic habitus. In both cases, radiation injury was localized to a discrete segment of bowel; therefore, resection with a primary end-to-end anastomosis was performed. In addition, diseased bowel was eliminated and, therefore, would not cause further complications such as intractable bleeding or fistula formation. The review focuses on current knowledge which may be applied to the treatment and prevention of radiation enteritis.

  10. Carcinogenesis induced by low-dose radiation

    Directory of Open Access Journals (Sweden)

    Piotrowski Igor

    2017-11-01

    Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

  11. Basic reactions induced by radiation

    International Nuclear Information System (INIS)

    Charlesby, A.

    1980-01-01

    This paper summarises some of the basic reactions resulting from exposure to high energy radiation. In the initial stages energy is absorbed, but not necessarily at random, giving radical and ion species which may then react to promote the final chemical change. However, it is possible to intervene at intermediate stages to modify or reduce the radiation effect. Under certain conditions enhanced reactions are also possible. Several expressions are given to calculate radiation yield in terms of energy absorbed. Some analogies between radiation-induced reactions in polymers, and those studied in radiobiology are outlined. (author)

  12. 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

  13. Radiation-induced cataract

    International Nuclear Information System (INIS)

    Martignoni, K.

    1986-01-01

    Dose assessments for cataract threshold doses are available based on epidemiological studies of radiotherapy patients, survivors of the nuclear bombing of Hiroshima and Nagasaki, and of persons with occupational exposure to radiation. According to these, short-term application of low-level LET radiation of a dose ranging between 0.5 and 2.0 Gy may suffice to cause a cataract in the course of a few months or years which results in inpairment of vision (UNSCEAR, 1982). In fractionated irradiation, cataractogenic threshold dose increases to 4 Sv at treatment times between 3 weeks and 3 months, and to more than 5 Sv at more than 3 months (ICRP 41). Densely ionizing radiation must be assumed to have threshold doses between 2 and 20 Sv. An ICRP assessment (ICRP Publ. No. 41, 1984) gives a threshold dose of more than 8 Sv for a vision-impairing cataract if these was protracted irradiation at a low-level dose rate. Concerning radiation protection, a maximum lens dose of 150 mSv per annum was recommended which should not be exceeded. This indicates a maximum of 7.5 Sv of exposure throughout a period of 50 years of working life. (orig./HP) [de

  14. 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.)

  15. Molecular epidemiology of radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Trosko, J.E.

    1996-01-01

    The role of ionizing radiation in carcinogenesis is discussed. Every cell contains proto-oncogenes, which if damaged may lead to cell transformation. Every cell also contains tumor suppressor genes, which guard against transformation. Thus, transformation would seem to require a double injury to the DNA in a cell. Ionizing radiation is known to be a relatively weak mutagen, but a good clastogen (inducer of chromosome breaks, deletions and rearrangements). Ionizing radiation may therefore be a 'promoter' of cancer, i.e. a stimulant of the clonal expansion of transformed cells, if it kills enough cells to induce compensatory hyperplasia - i.e. rapid growth of cells. Ionizing radiation may be a 'progressor', if it deactivates tumor suppressor genes tending to suppress the growth of existing clones of transformed cells resulting from any of numerous causes. It may therefore be an oversimplification to say that radiation causes cancer; rather, it seems to be a weak initiator, an indirect promoter, and a late-stage progressor. 2 figs

  16. Peculiarities of radiation induced craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Sataev, N.M. (Uzbekskij Nauchno-Issledovatel' skij Inst. Onkologii i Radiologii, Tashkent (USSR))

    1982-03-01

    Due to intracranial implantation of a radiosource in rabbit brain craniopharyngioma appeared. Its specific feature is grandular differentiation of embryonal epithelium of residuals of hypophysical (craniopharyngial) passage and the presence of focuses of blood vessel tumor degeneration of hemangioma type in its stroma. It is suggested that radiation craniopharyngioma is developed along the way of epigenetic changes of cellular elements of embryonal epithelium induced by radiation.

  17. Peculiarities of radiation induced craniopharyngioma

    International Nuclear Information System (INIS)

    Sataev, N.M.

    1982-01-01

    Due to intracranial implantation of a radiosource in rabbit brain craniopharyngioma appeared. Its specific feature is grandular differentiation of embryonal epithelium of residuals of hypophysical (craniopharyngial) passage and the presence of focuses of blood vessel tumor degeneration of hemangioma type in its stroma. It is suggested that radiation craniopharyngioma is developed along the way of epigenetic changes of cellular elements of embryonal epithelium induced by radiation

  18. Nature of mutants induced by ionizing radiation in cultured hamster cells. III. Molecular characterization of HPRT-deficient mutants induced by. gamma. -rays or. cap alpha. -particles showing that the majority have deletions of all or part of the hprt gene

    Energy Technology Data Exchange (ETDEWEB)

    Thacker, J

    1986-05-01

    DNA from 58 independent HPRT-deficient mutants of V79 hamster cells induced by ionizing radiation was analysed by Southern blot hybridization to a full-length hamster hprt cDNA. About half of the ..gamma..-ray-induced mutants (20/43) were apparently total gene deletions, because they lacked all functional hprt gene sequences hybridizing to the cDNA probe. Another 10 mutants showed various partial deletions and/or rearrangements of the hprt gene. The remaining 13 mutants showed no detectable change in comparison to the structure of the normal gene, which correlated well with previous characterization of these mutants indicating that most carry point mutations in the hprt gene. Thus, 70% or more of radiation-induced HPRT-deficient mutants arise through large genetic changes, especially deletions of all or part of the hprt gene. 16 references, 4 figures, 1 table.

  19. Induced pluripotency with endogenous and inducible genes

    International Nuclear Information System (INIS)

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-01-01

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

  20. Radiation-induced myelomatosis

    International Nuclear Information System (INIS)

    Cuzick, J.

    1981-01-01

    It is well known that radiation can cause myeloid leukemia. However, no excess of chronic lymphocytic leukemia has been observed. Myelomatosis, like chronic lymphocytic leukemia, is a tumor of B lymphocytes. To determine whether this disease has a radiogenic origin, we surveyed all cohorts of persons exposed to radiation for which data on cancer-related mortaility are available. An excess of myeloma was found in most cohorts. However, a striking deficit was found in two groups irradiated intensely for uterine neoplasms (three cases observed, 10.71 expected; P = 0.012). All other groups combined had a highly significant excess (50 observed, 22.21 expected; P = 2 x 10 -7 ). The largest relative risk appeared among persons receiving internal doses of α-particles (14 observed, 3.24 expected; P = 2 x 10 -5 ), but a significant excess (13 observed, 6.33 expected; P = 0.026) was also found in patients receiving only therapeutic or diagnostic γ-rays or x-rays. Most cases occurred 15 to 25 years after exposure

  1. Radiation induced emulsion polymerization

    International Nuclear Information System (INIS)

    Stannett, V.T.; Stahel, E.P.

    1990-01-01

    High energy radiation is particularly favored for the initiation of emulsion polymerization. The yield of free radicals, for example, from the radiolysis of the aqueous phase, is high; G(radical) values of 5-7. In addition, the rather special kinetics associated with emulsion polymerization lead, in general, to very large kinetic chain lengths, even with 'non-ideal' monomers such as vinyl acetate. Together, high polymerization rates at low doses become possible. There are some important advantages of radiation polymerization compared with chemical initiators, such as potassium persulfate. Perhaps the most important among them is the temperature independence of the initiation step. This makes low temperature polymerization very accessible. With monomers such as vinyl acetate, where chain termination to monomer is predominant, low temperatures lead to often highly desirable higher molecular weights. With styrene, the classical ideally behaved monomer, there are the advantages such as, for example, the feasibility of using cationic monomers. These and some attendant disadvantages are discussed in detail, including pilot plant studies

  2. 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

  3. 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)

  4. 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.)

  5. Association of genetic variants in apoptosis genes FAS and FASL with radiation-induced late toxicity after prostate cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Thurner, E.M.; Krenn-Pilko, S.; Kapp, K.S.; Langsenlehner, T. [Medical University of Graz, Department of Therapeutic Radiology and Oncology, Graz (Austria); Langsenlehner, U. [Division of Internal Medicine, GKK Outpatient Department, Graz (Austria); Renner, W. [Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz (Austria); Gerger, A. [Medical University of Graz, Division of Oncology, Department of Internal Medicine, Graz (Austria)

    2014-03-15

    Fas ligand (FASL) triggers apoptotic cell death by cross-linking with its receptor FAS, and after irradiation, expression of FAS and FASL is increased. In the present study, we investigated the association between common polymorphisms in the genes for FAS and FASL and the risk of late side effects after radiotherapy for prostate cancer. The role of FAS (- 1377G > A, rs2234767 and - 670A > G, rs1800682) and FASL (- 844C > T, rs763110) gene polymorphisms in the development of high-grade late rectal and/or urinary toxicity (defined as late toxicity EORTC/RTOG grade ≥ 2) was analyzed in 607 prostate cancer patients treated with radiotherapy. DNA was isolated and the selected polymorphisms were determined by 5'-nuclease (TaqMan) assays. After a median follow-up time of 82 months, high-grade late rectal and/or urinary toxicity was observed in 175 patients (29.7 %). Univariate analysis revealed a significantly decreased risk of high-grade late toxicity in carriers of the FASL - 844T allele. After adjusting for covariates, patients harboring at least one - 844T allele (CT or TT genotype) remained at decreased risk of high-grade late toxicity compared with patients harboring the CC genotype [hazard ratio (HR) 0.585, 95 %CI 0.39-0.878; p = 0.010]. For patients with the - 844TT genotype, the HR was 0.404 (95 %CI 0.171-0.956; p = 0.039) in multivariate analysis. No significant associations were found for the remaining polymorphisms analyzed. These results provide the first evidence that the presence of the FASL - 844T variant allele may have a protective effect against the development of high-grade late rectal and/or urinary side effects after prostate cancer radiotherapy. (orig.) [German] Fas-Ligand (FASL) triggert durch Bindung an seinen Rezeptor FAS den apoptotischen Zelltod, desweiteren konnte nach Bestrahlung eine Ueberexpression von FAS und FASL beobachtet werden. Ziel der vorliegenden prospektiven Studie war die Untersuchung der Zusammenhaenge von

  6. Fracture induced electromagnetic radiation

    International Nuclear Information System (INIS)

    Frid, V; Rabinovitch, A; Bahat, D

    2003-01-01

    In our laboratory, we combine accurate electromagnetic radiation (EMR) measurements during fracture of rocks (carbonate and igneous) and transparent materials (glass, PMMA and glass ceramics) with careful fractographic methods. A critical analysis of experimental observations, accumulated here during the last decade together with supporting material from the works of other authors are used in this study to demonstrate the failure of all current models to explain the properties of EMR arising from fracture. The basic elements of a new model are proposed. These are (a) the EMR amplitude increases as long as the crack continues to grow, since new atomic bonds are severed and their contribution is added to the EMR. As a result, the atoms on both sides of the bonds are moved to 'non-equilibrium' positions relative to their steady state ones and begin to oscillate collectively in a manner similar to Debye model bulk oscillations - 'surface vibrational optical waves'; (b) when the crack halts, the waves and the EMR pulse amplitude decay by relaxation. These basic elements are already enough to describe the characteristics of the experimentally obtained isolated individual EMR pulses. These characteristics include the shape of the EMR pulse envelope, and the frequency, time duration and rise - fall time of the pulse

  7. Fracture induced electromagnetic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Frid, V [Geological and Environmental Sciences Department, Deichmann Rock Mechanics Laboratory of the Negev, Ben Gurion University of the Negev, Beer Sheva (Israel); Rabinovitch, A [Physics Department, Deichmann Rock Mechanics Laboratory of the Negev, Ben Gurion University of the Negev, Beer Sheva (Israel); Bahat, D [Geological and Environmental Sciences Department, Deichmann Rock Mechanics Laboratory of the Negev, Ben Gurion University of the Negev, Beer Sheva (Israel)

    2003-07-07

    In our laboratory, we combine accurate electromagnetic radiation (EMR) measurements during fracture of rocks (carbonate and igneous) and transparent materials (glass, PMMA and glass ceramics) with careful fractographic methods. A critical analysis of experimental observations, accumulated here during the last decade together with supporting material from the works of other authors are used in this study to demonstrate the failure of all current models to explain the properties of EMR arising from fracture. The basic elements of a new model are proposed. These are (a) the EMR amplitude increases as long as the crack continues to grow, since new atomic bonds are severed and their contribution is added to the EMR. As a result, the atoms on both sides of the bonds are moved to 'non-equilibrium' positions relative to their steady state ones and begin to oscillate collectively in a manner similar to Debye model bulk oscillations - 'surface vibrational optical waves'; (b) when the crack halts, the waves and the EMR pulse amplitude decay by relaxation. These basic elements are already enough to describe the characteristics of the experimentally obtained isolated individual EMR pulses. These characteristics include the shape of the EMR pulse envelope, and the frequency, time duration and rise - fall time of the pulse.

  8. 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.

  9. 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.)

  10. Diseases induced by ionising radiation

    International Nuclear Information System (INIS)

    1984-11-01

    An interim report is presented by the Industrial Injuries Advisory Council in accordance with Section 141 of the Social Security Act 1975 on the question whether the terms of prescription for occupational diseases induced by ionising radiation should be amended to cover a wider range of conditions. A lack of persuasive statistical data has prevented reliable estimates of health risks of radiation workers in the UK to be made. However the report gives details of the progress made so far and the difficulties encountered. (U.K.)

  11. An oncolytic adenovirus regulated by a radiation-inducible promoter selectively mediates hSulf-1 gene expression and mutually reinforces antitumor activity of I131-metuximab in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Yan; Fang, Lin; Zhang, Quan'an; Zheng, Qin; Tong, Jinlong; Fu, Xiaohui; Jiang, Xiaoqing; Su, Changqing; Zheng, Junnian

    2013-06-01

    Gene therapy and antibody approaches are crucial auxiliary strategies for hepatocellular carcinoma (HCC) treatment. Previously, we established a survivin promoter-regulated oncolytic adenovirus that has inhibitory effect on HCC growth. The human sulfatase-1 (hSulf-1) gene can suppress the growth factor signaling pathways, then inhibit the proliferation of cancer cells and enhance cellular sensitivity to radiotherapy and chemotherapy. I(131)-metuximab (I(131)-mab) is a monoclonal anti-HCC antibody that conjugated to I(131) and specifically recognizes the HAb18G/CD147 antigen on HCC cells. To integrate the oncolytic adenovirus-based gene therapy and the I(131)-mab-based radioimmunotherapy, this study combined the CArG element of early growth response-l (Egr-l) gene with the survivin promoter to construct a radiation-inducible enhanced promoter, which was used to recombine a radiation-inducible oncolytic adenovirus as hSulf-1 gene vector. When I(131)-mab was incorporated into the treatment regimen, not only could the antibody produce radioimmunotherapeutic effect, but the I(131) radiation was able to further boost adenoviral proliferation. We demonstrated that the CArG-enhanced survivin promoter markedly improved the proliferative activity of the oncolytic adenovirus in HCC cells, thereby augmenting hSulf-1 expression and inducing cancer cell apoptosis. This novel strategy that involved multiple, synergistic mechanisms, including oncolytic therapy, gene therapy and radioimmunotherapy, was demonstrated to exert an excellent anti-cancer outcome, which will be a promising approach in HCC treatment. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Asim [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Mukhopadhyay, Nitai D. [Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia (United States); Ning, Yi [Department of Family Medicine and Population Health, Virginia Commonwealth University, Richmond, Virginia (United States); Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Mikkelsen, Ross B., E-mail: rmikkels@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States)

    2015-10-01

    Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the

  13. A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

    International Nuclear Information System (INIS)

    Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi; Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S.; Mikkelsen, Ross B.

    2015-01-01

    Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the

  14. Radiation induced estane polymer crosslinking

    International Nuclear Information System (INIS)

    Fletcher, M.; Foster, P.

    1997-01-01

    The exposure of polymeric materials to radiation has been known to induce the effects of crosslinking and degradation. The crosslinking phenomena comes about when two long chain polymers become linked together by a primary bond that extends the chain and increases the viscosity, molecular weight and the elastic modules of the polymer. This process has been observed in relatively short periods of time with fairly high doses of radiation, on the order of several megarads/hour. This paper address low dose exposure over long periods of time to determine what the radiation effects are on the polymeric binder material in PBX 9501. An experimental sample of binder material without explosives will be placed into a thermal and radiation field produced from a W-48 put mod 0. Another sample will be placed in a thermal environment without the radiation. The following is the test plan that was submitted to the Pantex process. The data presented here will be from the first few weeks of exposure and this test will be continued over the next few years. Subsequent data will hopefully be presented in the next compatibility and aging conference

  15. Increased radiation-induced transformation in C3H/10T1/2 cells after transfer of an exogenous c-myc gene

    International Nuclear Information System (INIS)

    Sorrentino, V.; Drozdoff, V.; Zeitz, L.; Fleissner, E.

    1987-01-01

    C3H/10T 1/2 cells were infected with a retroviral vector expressing a mouse c-myc oncogene and a drug-selection marker. The resulting cells, morphologically indistinguishable from C3H/10T l/1, displayed a greatly enhanced sensitivity to neoplastic transformation by ionizing radiation or by a chemical carcinogen. Constitutive expression of myc therefore appears to synergize with an initial carcinogenic event, providing a function analogous to a subsequent event that apparently is required for the neoplastic transformation of these cells. This cell system should prove useful in exploring early stages in radiation-induced transformation

  16. 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)

  17. Influence of radiation-induced apoptosis on development brain in molecular regulation

    International Nuclear Information System (INIS)

    Gu Guixiong

    2000-01-01

    An outline of current status on the influence of radiation on the development brain was given. Some genes as immediate early gene, Bcl-2 family, p53, heat shock protein and AT gene play an important regulation role in ionizing radiation-induced development brain cells apoptosis. And such biological factor as nerve growth factor, interleukin-1, tumor necrosis factor, basic fibroblast growth factor, transforming growth factor and so on have a vital protection function against ionizing radiation-induced cells apoptosis

  18. Enteral peptide formulas inhibit radiation induced enteritis and apoptosis in intestinal epithelial cells and suppress the expression and function of Alzheimer's and cell division control gene products

    International Nuclear Information System (INIS)

    Cope, F.O.; Issinger, O.G.; McArdle, A.H.; Shapiro, J.; Tomei, L.D.

    1991-01-01

    Studies have shown that patients receiving enteral peptide formulas prior to irradiation have a significantly reduced incidence of enteritis and express a profound increase in intestinal cellularity. Two conceptual approaches were taken to describe this response. First was the evaluation in changes in programmed intestinal cell death and secondly the evaluation of a gene product controlling cell division cycling. This study provided a relationship between the ratio of cell death to cell formulations. The results indicate that in the canine and murine models, irradiation induces expression of the Alzheimer's gene in intestinal crypt cells, while the incidence of apoptosis in apical cells is significantly increased. The use of peptide enteral formulations suppresses the expression of the Alzheimer's gene in crypt cells, while apoptosis is eliminated in the apical cells of the intestine. Concomitantly, enteral peptide formulations suppress the function of the CK-II gene product in the basal and baso-lateral cells of the intestine. These data indicate that although the mitotic index is significantly reduced in enterocytes, this phenomenon alone is not sufficient to account for the peptide-induced radio-resistance of the intestine. The data also indicate a significant reduction of normal apoptosis in the upper lateral and apical cells of the intestinal villi. Thus, the ratio of cell death to cell replacement is significantly decreased resulting in an increase in villus height and hypertrophy of the apical villus cells. Thus, peptide solutions should be considered as an adjunct treatment both in radio- and chemotherapy

  19. Mobile-phone radiation-induced perturbation of gene-expression profiling, redox equilibrium and sporadic-apoptosis control in the ovary of Drosophila melanogaster.

    Science.gov (United States)

    Manta, Areti K; Papadopoulou, Deppie; Polyzos, Alexander P; Fragopoulou, Adamantia F; Skouroliakou, Aikaterini S; Thanos, Dimitris; Stravopodis, Dimitrios J; Margaritis, Lukas H

    2017-04-03

    The daily use by people of wireless communication devices has increased exponentially in the last decade, begetting concerns regarding its potential health hazards. Drosophila melanogaster four days-old adult female flies were exposed for 30 min to radiation emitted by a commercial mobile phone at a SAR of 0.15 W/kg and a SAE of 270 J/kg. ROS levels and apoptotic follicles were assayed in parallel with a genome-wide microarrays analysis. ROS cellular contents were found to increase by 1.6-fold (x), immediately after the end of exposure, in follicles of pre-choriogenic stages (germarium - stage 10), while sporadically generated apoptotic follicles (germarium 2b and stages 7-9) presented with an averaged 2x upregulation in their sub-population mass, 4 h after fly's irradiation with mobile device. Microarray analysis revealed 168 genes being differentially expressed, 2 h post-exposure, in response to radiofrequency (RF) electromagnetic field-radiation exposure (≥1.25x, P mobile-phone radiation for 30 min has an immediate impact on ROS production in animal's ovary, which seems to cause a global, systemic and non-targeted transcriptional reprogramming of gene expression, 2 h post-exposure, being finally followed by induction of apoptosis 4 h after the end of exposure. Conclusively, this unique type of pulsed radiation, mainly being derived from daily used mobile phones, seems capable of mobilizing critical cytopathic mechanisms, and altering fundamental genetic programs and networks in D. melanogaster.

  20. Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.

    Directory of Open Access Journals (Sweden)

    Jiamin Zhang

    Full Text Available Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD. ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group, as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.

  1. A fast, simple method for screening radiation susceptibility genes by RNA interference

    International Nuclear Information System (INIS)

    Tsuji, Atsushi B.; Sudo, Hitomi; Sugyo, Aya; Otsuki, Marika; Miyagishi, Makoto; Taira, Kazunari; Imai, Takashi; Harada, Yoshi-nobu

    2005-01-01

    Radiotherapy can cause unacceptable levels of damage to normal tissues in some cancer patients. To understand the molecular mechanisms underlying radiation-induced physiological responses, and to be able to predict the radiation susceptibility of normal tissues in individual patients, it is important to identify a comprehensive set of genes responsible for radiation susceptibility. We have developed a simple and rapid 96-well screening protocol using cell proliferation assays and RNA interference to identify genes associated with radiation susceptibility. We evaluated the performance of alamarBlue-, BrdU-, and sulforhodamine B-based cell proliferation assays using the 96-well format. Each proliferation assay detected the known radiation susceptibility gene, PRKDC. In a trial screen using 28 shRNA vectors, another known gene, CDKN1A, and one new radiation susceptibility gene, ATP5G3, were identified. Our results indicate that this method may be useful for large-scale screens designed to identify novel radiation susceptibility genes

  2. 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

  3. Tunnel effect in excited and ionized states of nucleic acid bases and some aspects of radiation-induced point gene mutations

    International Nuclear Information System (INIS)

    Pleticha-Lansky, R.

    1975-01-01

    Radiation induced perturbations of the genetic code are discussed from the standpoint of the frequency and specificity of mutations. According to Lowdin's theory of tautomeric rearrangement of nucleic acid base pairs through the tunnel effect, it is probable, that the proton potential in hydrogen bridges can be also effected by the incorporation of some radiolytic products of purines and pyrimidines into DNA as mistake bases. In this way it is possible, to eliminate any exo-or endogeneous energetic irradiation of the biological material and so to eliminate various undesirable damages of DNA. Thus higher specificity in the controlling of the genetic code changes would result. (F.G.)

  4. Perspectives in the paradigm of radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Sugakhara, T.; Vatanabe, M.; Niva, O.; Nikajdo, O.

    1995-01-01

    Carcinogenesis is analysed as a multistage process consisting of initiation, promotion and progression. This model includes the mutation of oncogenes and the loss of hetrezygosity by tumor-suppressor genes. The threshold concept of radiation cancerogenesis is proposed, under which ionizing radiation can induce in somatic cell genetic effects a s result of DNA damage and epigenetic changes as well. The epigenetic changes (through DNA or cytoplasma) can be stabilized as mutations observed in many cancer cells and play a dominant role in radiation cancerogenesis induction. The ration of epigenetic and genetic effects largely depends on radiation doses

  5. 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

  6. Approach of combined cancer gene therapy and radiation: response of promoters to ionizing radiation

    International Nuclear Information System (INIS)

    Anstett, A.

    2005-09-01

    Gene therapy is an emerging cancer treatment modality. We are interested in developing a radiation-inducible gene therapy system to sensitize the tumor vasculature to the effects of ionizing radiation (IR) treatment. An expression system based on irradiation-inducible promoters will drive the expression of anti-tumor genes in the tumor vasculature. Solid tumors are dependent on angio genesis, a process in which new blood vessels are formed from the pre-existing vasculature. Vascular endothelial cells are un transformed and genetically stable, thus avoiding the problem of resistance to the treatments. Vascular endothelial cells may therefore represent a suitable target for this therapeutic gene therapy strategy.The identification of IR-inducible promoters native to endothelial cells was performed by gene expression profiling using cDNA micro array technology. We describe the genes modified by clinically relevant doses of IR. The extension to high doses aimed at studying the effects of total radiation delivery to the tumor. The radio-inductiveness of the genes selected for promoter study was confirmed by RT-PCR. Analysis of the activity of promoters in response to IR was also assessed in a reporter plasmid. We found that authentic promoters cloned onto a plasmid are not suitable for cancer gene therapy due to their low induction after IR. In contrast, synthetic promoters containing repeated sequence-specific binding sites for IR-activated transcription factors such as NF-κB are potential candidates for gene therapy. The activity of five tandemly repeated TGGGGACTTTCCGC elements for NF-κB binding in a luciferase reporter was increased in a dose-dependent manner. Interestingly, the response to fractionated low doses was improved in comparison to the total single dose. Thus, we put present evidence that a synthetic promoter for NF-κB specific binding may have application in the radio-therapeutic treatment of cancer. (author)

  7. 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

  8. Effect of gene time on acute radiation mucositis and dermatitis

    International Nuclear Information System (INIS)

    Li Suyan; Gao Li; Yin Weibo; Xu Guozhen; Xiao Guangli

    2002-01-01

    Objective: To evaluate the effect of recombinant human epidermal growth factor (Gene Time) on acute mucositis and dermatitis induced by radiation. Methods: 120 head and neck cancer patients were randomized into 3 groups: 1. Mucositis prophylactic application (MPA) group with control, 2. Mucositis therapeutic application (MTA) group with control and 3. Dermatitis therapeutic application (DTA) group with control. Prophylactic application of drug consisted of spraying the Gene Time preparation on the irradiated skin or mucous membrane as radiotherapy was being carried out. This was compared with control patients who received routine conventional skin care. Therapeutic application was started as grade I radiation mucositis or dermatitis appeared. The evaluation of acute radiation mucositis and dermatitis was done according to the systems proposed by RTOG or EORTC. Results: The results showed that in the MPA group, the rate of radiation mucositis at ≤10 Gy was 20% (4/20) as compared to the 70% (14/20) of the control (P = 0.004). During the course of radiation, the incidences of grade III, IV acute radiation mucositis and dermatitis were always lower than the control. In therapeutic application of Gene Time, the response rate of acute radiation mucositis was also better than the control (90% vs 50%) (P = 0.016) and that of acute dermatitis was similar (95% vs 50%) (P = 0.005). Moreover, the ≤3 d rate of healing of grade III dermatitis in the application group was 3/7 as compared to the 0/14 of the control. Conclusion: Prophylactic application of recombinant human epidermal growth factor is able to postpone the development of radiation mucositis. This preparation is also able to lower the incidence of grade III, IV mucositis and dermatitis both by therapeutic and prophylactic application in addition to the hastened healing of grade III dermatitis

  9. 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.

  10. 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

  11. 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

  12. The effect of ultraviolet-B radiation on gene expression and pigment composition in etiolated and green pea leaf tissue: UV-B-induced changes are gene-specific and dependent upon the developmental stage

    International Nuclear Information System (INIS)

    Jordan, B.R.; James, P.E.; Strid, A.; Anthony, R.G.

    1994-01-01

    The effect of ultraviolet-B radiation (UV-B: 280–320nm) on gene expression and pigment composition has been investigated in pea tissue at different stages of development. Pea (Pisum sativum L., cv. Feltham First) seedlings were grown for 17d and then exposed to supplementary UV-B radiation. Chlorophyll a per unit fresh weight decreased by more than 20% compared with control levels after exposure to UV-B radiation for 7d. In contrast, chlorophyll b content remained the same or increased slightly. Leaf protein biosynthesis, as determined by 35 S-methionine incorporation, was rapidly inhibited by UV-B radiation, although the steady-state levels of proteins were either unchanged or only slightly altered. RNA transcripts for the chlorophyll a/b binding protein (cab) were also rapidly reduced to low or even undetectable levels in the expanded third leaf or younger leaf bud tissue after exposure to UV-B radiation. In contrast, cab RNA transcripts were either low or undetectable in etiolated pea tissue, but increased substantially in light and during exposure to UV-B radiation. The cab RNA transcripts were still present at control levels in pea plants after 7d of greening under supplementary UV-B radiation or UV-B alone. The protein composition changed significantly over the 7d of greening, but no differences could be detected between the light treatments. The increase in chlorophyll content was slightly greater during de-etiolation under supplementary UV-B radiation than under control irradiance. Under UV-B radiation alone, chlorophyll was synthesized at a greatly reduced rate. Changes in protective pigments were also determined. Anthocyanins did not change in either etiolated or green tissue exposed to UV-B radiation. However, other flavonoids increased substantially in either tissue during exposure to light and UV-B radiation. The RNA levels for chalcone synthase were measured in green and etiolated tissue exposed to UV-B radiation. The chs RNA transcripts were

  13. 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

  14. Diseases induced by ionizing radiation

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    The instruction sheet for medical examinations presents information on clinical symptoms and diagnostic procedures relating to the following cases: 1. Acute radiation injury due to whole-body exposure; 2. acute, local radiation injury due to partial body exposure; 3. chronic general affections due to whole-body exposure; 4. chronic, local affections due to partial body exposure; 5. delayed radiation effects. (HP) [de

  15. 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

  16. 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)

  17. 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)

  18. 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

  19. Radiation-induced thyroid disease

    International Nuclear Information System (INIS)

    Maxon, H.R.

    1985-01-01

    Ionizing radiation has been demonstrated to result in a number of changes in the human thyroid gland. At lower radiation dose levels (between 10 and 1500 rads), benign and malignant neoplasms appear to be the dominant effect, whereas at higher dose levels functional changes and thyroiditis become more prevalent. In all instances, the likelihood of the effect is related to the amount and type of radiation exposure, time since exposure, and host factors such as age, sex, and heredity. The author's current approach to the evaluation of patients with past external radiation therapy to the thyroid is discussed. The use of prophylactic thyroxine (T4) therapy is controversial. While T4 therapy may not be useful in preventing carcinogenesis when instituted many years after radiation exposure, theoretically T4 may block TSH secretion and stimulation of damaged cells to undergo malignant transformation when instituted soon after radiation exposure

  20. Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: A role for NF-κB-STAT3-directed gene expression

    International Nuclear Information System (INIS)

    Ivanov, Vladimir N.; Ghandhi, Shanaz A.; Zhou, Hongning; Huang, Sarah X.; Chai, Yunfei; Amundson, Sally A.; Hei, Tom K.

    2011-01-01

    Mitochondrial DNA depleted (ρ 0 ) human skin fibroblasts (HSF) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-κB and STAT3 signaling pathways, and by decreased activity of mitochondrial death pathway, compared to the parental ρ + HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor mediated death pathway remained highly active, and exogenous TRAIL in a combination with cycloheximide (CHX) induced higher levels of apoptosis in ρ 0 cells compared to ρ + HSF. Global gene expression analysis using microarray and qRT-PCR demonstrated that mRNA expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, and IGFL2), cytokines (IL6, ΙL17Β, ΙL18, ΙL19, and ΙL28Β) and cytokine receptors (IL1R1, IL21R, and IL31RA) were substantially decreased after mitochondrial DNA depletion. Some of these genes were targets of NF-κB and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation further induced expression of several NF-κB/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in ρ + HSF, but this response was substantially decreased in ρ 0 HSF. Suppression of the IKK-NF-κB pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated ρ + HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in HSF, especially after alpha-irradiation. Collectively, our results indicated that NF-κB activation was partially lost in ρ 0 HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-κB targets, further suppressing IL6-JAK2-STAT3 that in concert with NF-κB regulated protection against TRAIL-induced apoptosis.

  1. 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

  2. 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)

  3. 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)

  4. Application of radiation-induced apoptosis in radiation oncology and radiation protection

    International Nuclear Information System (INIS)

    Crompton, N.E.A.; Emery, G.C.; Ozsahin, M.; Menz, R.; Knesplova, L.; Larsson, B.

    1997-01-01

    A rapid assay of the ability of lymphocytes to respond to radiation-induced damage is presented. Age and genetic dependence of radiation response have been quantified. The assay is sensitive to low doses of radiation. Its ability to assess the cytotoxic response of blood capillaries to radiation has been evaluated. (author)

  5. 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)

  6. Radiation-induced renovascular hypertension

    International Nuclear Information System (INIS)

    Staab, G.E.; Tegtmeyer, C.J.; Constable, W.C.

    1976-01-01

    Radiation is known to produce changes in the small vessels and interstitium of the kidneys resulting in hypertension. Two cases of renal artery stenosis and resultant hypertension secondary to abdominal irradiation are reported and the literature is reviewed

  7. Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun; Kang, Jeong Wook [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Dong Won [Department of Plastic Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Oh, Sang Ho [Department of Dermatology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Yun-Sil [College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewah Womans University, Seoul 120-750 (Korea, Republic of); Lee, Eun-Jung [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-05-08

    Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.

  8. The progress of tumor gene-radiotherapy induced by Egr-1 promoter

    International Nuclear Information System (INIS)

    Guo Rui; Li Biao

    2010-01-01

    The promoter of early growth response gene-1 (Egr-1) is a cis-acting element of Egr-1, and its activity is regulated by inducers such as ionizing radiation, free radical. In designated gene-radiotherapy system, radiation combined with therapeutic gene (such as tumor necrosis factor-α gene, suicide gene) can spatially and temporally regulate therapeutic gene expression in the irradiated field, produced a marked effect, while little systemic toxicities were observed. The combination of radiotherapy and gene therapy is promising in tumor therapy. (authors)

  9. Regulation of gene expression in mammalian cells following ionizing radiation

    International Nuclear Information System (INIS)

    Boothman, D.A.; Lee, S.W

    1991-01-01

    Mammalian cells use a variety of mechanisms to control the expression of new gene transcrips elicited in response to ionizing radiation. Damage-induced proteins have been found which contain DNA binding sites located within the promoter regions of SV40 and human thymidine kinase genes. DNA binding proteins as well as proteins which bind to specific DNA lesions (e.g., XIP bp 175 binds specifically to X-ray-damaged DNA) may play a role in the initial recognition of DNA damage and may initiate DNA repair processes, along with new transcription. Mammalian gene expression after DNA damage is also regulated via the stabilization of preexisting mRNA transcripts. Stabilized mRNA transcripts are translated into protein products not previously present in the cell due to undefined posttranscriptional modifications. Thus far, the only example of mRNA stabilization following X-irradiation is the immediate induction of tissue-type plasminogen activator. Mammalian cells synthesize new mRNA transcripts indirect response to DNA damage. Using cDNA cloning, Northern RNA blotting and nuclear run-on techniques, the levels of a variety of known and previously unknown genes dramatically increase following X-irradiation. These genes/proteins now include; a) DNA binding transcripts factors, such as the UV-responsive element binding factors, ionizing radiation-induced DNA-binding proteins, and XIP bP 175; b) proto-oncogenes, such as c-fos, c-jun, and c-myc; c) several growth-related genes, (e.g., the gadd genes, protein kinase C, IL-1, and thymidine kinase); and d) a variety of other genes, including proteases, tumor necrosis factor-alpha, and DT diaphorase. Mammalian cells respond to X-irradiation by eliciting a very complex series of events resulting in the appearance of new genes and proteins. These gene products may affect DNA repair, adaptive responses, apoptosis, SOS-type mutagenic response, and/or carcinogenesis. (J.P.N.)

  10. Radiation-induced neurobehavioral dysfunctions

    International Nuclear Information System (INIS)

    Manda, Kailash

    2013-01-01

    There is a lacuna between sparsely reported immediate effects and the well documented delayed effects on cognitive functions seen after ionizing radiation exposure. We reported the radiation-dose dependent incongruity in the early cognitive changes and its correlation with the structural aberration as reported by imaging study. The delayed effect of radiation was investigated to understand the role of hippocampal neurogenesis in the functional recovery of cognition. C57BL/6 mice were exposed to different doses of γ-radiation and 24 hrs after exposure, the stress and anxiety levels were examined in the Open Field Exploratory Paradigms (OFT). 48hrs after irradiation, the hippocampal dependent recognition memory was observed by the Novel Object Recognition Test (NORT) and the cognitive function related to memory processing and recall was tested using the Elevated Plus Maze (EPM). Visualization of damage to the brain was done by diffusion tensor imaging at 48 hours post-irradiation. Results indicate a complex dose independent effect on the cognitive functions immediately after exposure to gamma rays. Radiation exposure caused short term memory dysfunctions at lower doses which were seen to be abrogated at higher doses, but the long term memory processing was disrupted at higher doses. The Hippocampus emerged as one of the sensitive regions to be affected by whole body exposure to gamma rays, which led to profound immediate alterations in cognitive functions. Furthermore, the results indicate a cognitive recovery process, which might be dependent on the extent of damage to the hippocampal region. While evaluating the delayed effect of radiation on the hippocampal neurogenesis, we observed that higher doses groups showed comparatively more adaptive regenerative neurogenic potential which they could not sustain at later stages. Our studies reported an important hitherto uncovered phenomenon of neurobehavioral dysfunctions in relation to radiation dose. Nevertheless, a

  11. 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)

  12. Gene expression profiles following high-dose exposure to gamma radiation in salmonella enterica serovar typhimurium

    International Nuclear Information System (INIS)

    Lim, Sang Yong; Jung, Sun Wook; Joe, Min Ho; Kim, Dong Ho

    2008-01-01

    Microarrays can measure the expression of thousands of genes to identify the changes in expression between different biological states. To survey the change of whole Salmonella genes after a relatively high dose of gamma radiation (1 kGy), transcriptome dynamics were examined in the cells by using DNA microarrays. At least 75 genes were induced and 89 genes were reduced two-fold or more after irradiation. Several genes located in pSLT plasmid, cyo operon, and Gifsy prophage were induced along with many genes encoding uncharacterized proteins.While, the expression of genes involved in the virulence of Salmonella as well as metabolic functions were decreased. Although the radiation response as a whole could not be illustrated by using DNA microarrays, the data suggest that the response to high dose of irradiation might be more complex than the SOS response

  13. Gene expression profiles following high-dose exposure to gamma radiation in salmonella enterica serovar typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Yong; Jung, Sun Wook; Joe, Min Ho; Kim, Dong Ho [Radiation Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2008-08-15

    Microarrays can measure the expression of thousands of genes to identify the changes in expression between different biological states. To survey the change of whole Salmonella genes after a relatively high dose of gamma radiation (1 kGy), transcriptome dynamics were examined in the cells by using DNA microarrays. At least 75 genes were induced and 89 genes were reduced two-fold or more after irradiation. Several genes located in pSLT plasmid, cyo operon, and Gifsy prophage were induced along with many genes encoding uncharacterized proteins.While, the expression of genes involved in the virulence of Salmonella as well as metabolic functions were decreased. Although the radiation response as a whole could not be illustrated by using DNA microarrays, the data suggest that the response to high dose of irradiation might be more complex than the SOS response.

  14. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry S

    2005-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

  15. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry S

    2006-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

  16. Radiation-induced liver damage

    International Nuclear Information System (INIS)

    Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

    1977-01-01

    Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

  17. Radiation-induced transgenerational instability.

    Science.gov (United States)

    Dubrova, Yuri E

    2003-10-13

    To date, the analysis of mutation induction has provided an irrefutable evidence for an elevated germline mutation rate in the parents directly exposed to ionizing radiation and a number of chemical mutagens. However, the results of numerous publications suggest that radiation may also have an indirect effect on genome stability, which is transmitted through the germ line of irradiated parents to their offspring. This review describes the phenomenon of transgenerational instability and focuses on the data showing increased cancer incidence and elevated mutation rates in the germ line and somatic tissues of the offspring of irradiated parents. The possible mechanisms of transgenerational instability are also discussed.

  18. P53 tumor suppressor gene and protein expression is altered in cell lines derived from spontaneous and alpha-radiation-induced canine lung tumors

    International Nuclear Information System (INIS)

    Tierney, L.A.; Johnson, N.F.; Lechner, J.F.

    1994-01-01

    Mutations in the p53 tumor suppressor gene are the most frequently occurring gene alterations in malignant human cancers, including lung cancer. In lung cancer, common point mutations within conserved exons of the p53 gene result in a stabilized form of mutant protein which is detectable in most cases by immunohistochemistry. In addition to point mutations, allelic loss, rearrangements, and deletions of the p53 gene have also been detected in both human and rodent tumors. It has been suggested that for at least some epithelial neoplasms, the loss of expression of wild-type p53 protein may be more important for malignant transformation than the acquisition of activating mutations. Mechanisms responsible for the loss of expression of wild-type protein include gene deletion or rearrangement, nonsense or stop mutations, mutations within introns or upstream regulatory regions of the gene, and accelerated rates of degradation of the protein by DNA viral oncoproteins

  19. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong

    2005-01-01

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  20. 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

  1. 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

  2. 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

  3. 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.)

  4. Basic molecular biology in radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Rytoemaa, T.

    1992-01-01

    The tumour suppressor gene p53 is 'guardian of the genome'. If a DNA molecule (each chromosome has one DNA molecule) is damaged by an external factor, such as ionizing radiation, the protein product of the p53 gene stops the cell's proliferative activity until the damage is repaired. If the repair fails, the p53 gene product normally triggers programmed death of the cell. P53 gene itself is commonly damaged by radiation (or by another DNA-damaging factor). The altered gene product fails to control the integrity of the genome, and it also prevents the guardian action of the protein which is produced by the intact allele (each cell has two p53 genes). Under these circumstances any subsequent damage to DNA, induced e.g. by a chemical, is easily 'fixed'. Potentially critical sites for an additional DNA damage are the proto-oncogens (when damaged these genes are called oncogens), which commonly act as components of the regulatory network in a cell. Permanent malfunction of the signal network may then lead to uncontrolled cell growth, resulting in a malignant clone (=cancer). This simplified molecular model seems to be the common mechanism in many (or most) human cancers. (orig.)

  5. Radiation-induced breast cancer

    International Nuclear Information System (INIS)

    Price, J.L.

    1977-01-01

    Concern is expressed over a recent U.K. newspaper report (The Times, 21 January 1977, 5) on the possible hazards of mammography, as women may over-react to the extent of refusing mammography. The problems of radiation risk estimates, particularly at low dose levels, are very briefly reviewed. Recent improvements in mammography techniques have minimised the radiation hazard. Conflicting reports of the mortality rates following mammography screening programmes are discussed. In England and Wales, breast cancer is the commonest cause of death in women aged 35 to 54, and it would be unfortunate if the possible benefits of screening were denied to this age group before the latest mammographic techniques have been fully evaluated. (U.K.)

  6. Radiation-induced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Price, J L [Hammersmith Hospital, London (UK). Postgraduate Medical School

    1977-03-12

    Concern is expressed over a recent U.K. newspaper report (The Times, 21 January 1977, 5) on the possible hazards of mammography, as women may over-react to the extent of refusing mammography. The problems of radiation risk estimates, particularly at low dose levels, are very briefly reviewed. Recent improvements in mammography techniques have minimised the radiation hazard. Conflicting reports of the mortality rates following mammography screening programmes are discussed. In England and Wales, breast cancer is the commonest cause of death in women aged 35 to 54, and it would be unfortunate if the possible benefits of screening were denied to this age group before the latest mammographic techniques have been fully evaluated.

  7. Radiation-induced cerebrovascular complications

    International Nuclear Information System (INIS)

    Naito, Haruko; Koizumi, Nobuhiko; Nihei, Kenji; Taguchi, Nobuyuki; Tanaka, Haruki.

    1982-01-01

    A 3-year-old boy with non-Hodgkin malignant lymphoma came to complete remission after combined chemotherapy, intrathecal methotrexate, and whole brain irradiation of 2,400 rad. Two years after diagnosis, he developed it hemiparesis. CT scan showed cerebral infarction and hydrocephalus, and angiography revealed obstruction of the left middle cerebral artery. He survived with marked neurological deficits and no relapse of lymphoma. The literature was reviewed concerning complications after radiation to the brain. (Kondo, M.)

  8. 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)

  9. 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

  10. 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)

  11. 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

  12. 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.)

  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. Radiation Induced Precipitation in Iron

    Energy Technology Data Exchange (ETDEWEB)

    Solly, B

    1964-02-15

    Foils of iron have been neutron-irradiated in the Swedish re- search reactor R2 to integrated doses in the range 10{sup 17} - 10{sup 19} nvt (> 1 MeV) and examined by transmission electron microscopy. Features have been observed having diffraction contrast similar to that of the prismatic dislocation loops formed in f.c.c. metals by the collapse of point-defect clusters. The features have been shown to be due to precipitation of impurities at radiation damage centres in the iron matrix.

  15. Radiation Induced Precipitation in Iron

    International Nuclear Information System (INIS)

    Solly, B.

    1964-02-01

    Foils of iron have been neutron-irradiated in the Swedish re- search reactor R2 to integrated doses in the range 10 17 - 10 19 nvt (> 1 MeV) and examined by transmission electron microscopy. Features have been observed having diffraction contrast similar to that of the prismatic dislocation loops formed in f.c.c. metals by the collapse of point-defect clusters. The features have been shown to be due to precipitation of impurities at radiation damage centres in the iron matrix

  16. Ionizing radiation induced genomic instability and its relation to radiation carcinogenesis

    International Nuclear Information System (INIS)

    Wang Zhongwen

    2000-01-01

    There are widespread testimonies that the genomic instability induced by ionizing irradiation exits in mammal and its vitro cells. Genomic instability can enhance the frequency of genetic changes among the progeny of the original irradiated cells. In the radiation-leukemogenesis, there is no significant difference between controls and CBA/H mouses of PPI (preconception patent irradiation), but the offsprings of the PPI recipients show a different character (shorter latent period and higher incidence) after an extra γ-radiation. The radiation-induced genomic instability may get the genome on the verge of mutation and lead to carcinogens following mutation of some critical genes. The genomic instability, as the early event of initiation of carcinomas, may be play a specific or unique role

  17. 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)

  18. 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)

  19. Radiation-induced heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Stroobandt, R; Knieriem, H J; De Wolf, L; Joossens, J V

    1975-01-01

    A 45-year old woman underwent a radical mastectomy in 1965 for carcinoma of the left breast with metastasis in the left axillar lymph nodes. Fifty per cent of the heart received 4,000 rads during postoperative X-ray therapy. Patient developed radiopneumonia and symptoms of acute pericarditis in 1967. Constrictive pericarditis developed gradually from 1972 on. A pericardiectomy was performed in June 1974 and a thickened pericardium could be removed. Light and electron microscopic examination of a surgical biopsy of the left ventricular epi-myocardium revealed epicardial fibrosis, interstitial fibrosis of the myocardium and perivascular fibrosis. The diagnosis of post-radiation pericarditis was made. The myocardial involvement may be responsible for the subsequent clinical course.

  20. 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/

  1. Radiation-induced Genomic Instability and Radiation Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Sowa, Marianne B.; Kim, Grace J.; Morgan, William F.

    2013-01-19

    The obvious relationships between reactive oxygen and nitrogen species, mitochondrial dysfunction, inflammatory type responses and reactive chemokines and cytokines suggests a general stress response induced by ionizing radiation most likely leads to the non-targeted effects described after radiation exposure. We argue that true bystander effects do not occur in the radiation therapy clinic. But there is no question that effects outside the target volume do occur. These “out of field effects” are considered very low dose effects in the context of therapy. So what are the implications of non-targeted effects on radiation sensitivity? The primary goal of therapy is to eradicate the tumor. Given the genetic diversity of the human population, lifestyle and environment factors it is likely some combination of these will influence patient outcome. Non-targeted effects may contribute to a greater or lesser extent. But consider the potential situation involving a partial body exposure due to a radiation accident or radiological terrorism. Non-targeted effects suggest that the tissue at risk for demonstrating possible detrimental effects of radiation exposure might be greater than the volume actually irradiated.

  2. 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.)

  3. 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.

  4. 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.

  5. Bio-molecular alterations induced by a chemical or radiating stress in isolated human cells

    International Nuclear Information System (INIS)

    Gault, N.

    2004-01-01

    After having recalled some aspects of radiobiology (effects of ionizing radiations, molecular targets of radiations, cellular responses with respect to the radiation), the author discusses various aspects of radio-sensitivity: intrinsic radio-sensitivity of tumoral and normal cells, DNA injuries and in vitro radio-sensitivity, genes of susceptibility to ionizing radiations, clustered injuries. Then she reports investigations performed by infrared micro-spectroscopy: characterization of pathological lines, of biological processes, of oxidative injuries induced by xenobiotics, of injuries induced by ionizing radiations

  6. Radiation Induced Polymerization of Pyrrole

    International Nuclear Information System (INIS)

    Sarada Idris; Ratnam, C.T.; Ahmad Ashrif Abu Bakar

    2016-01-01

    We demonstrate the polymerization of pyrrole by gamma irradiation. The pyrrole films were exposed to gamma ray from cobalt 60 source at doses ranging from 0 to 150 kGy. The films were subjected to structural and morphological analyses by using FTIR, SEM and AFM techniques. Similar studies were also made on pristine pyrrole film which serve as control. Results revealed that pyrrole has been successfully polymerized through irradiation induced reactions. The SEM images depicted the formation of cauliflower shape upon gamma irradiation. The structural changes of pyrrole also evidenced by FTIR spectra. Surface topography and roughness of pyrrole before and after gamma irradiation found to show significant differences. (author)

  7. Gene expression in Catla catla (Hamilton) subjected to acute and protracted doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Anbumani, S., E-mail: aquatox1982@gmail.com; Mohankumar, Mary N., E-mail: marynmk@gmail.com

    2016-09-15

    Highlights: • Gamma radiation induced up- and down- regulation of cell cycle genes. • Protracted dose-rate induced gene up-regulation to facilitate cell survival. • bcl-2 gene facilitates repair at protracted dose and cell death at acute exposures. • gadd45α, cdk1 and bcl-2 genes work in concert to promote ‘repair’ and ‘death’ circuitries in fish blood cells. - Abstract: Studies on transcriptional modulation after gamma radiation exposure in fish are limited. Cell cycle perturbations and expression of apoptotic genes were investigated in the fish, Catla catla after acute and protracted exposures to gamma radiation over a 90 day period. Significant changes in gene expression were observed between day 1 and 90 post-exposure. Gamma radiation induced a significant down-regulation of target genes gadd45α, cdk1 and bcl-2 from day 1 to day 3 after protracted exposure, whereas it persists till day 6 upon acute exposure. From day 12 onwards, Gadd45α, cdk1 and bcl-2 genes were up-regulated following protracted exposure, indicating DNA repair, cell-cycle arrest and apoptosis. There exists a linear correlation between these genes (gadd45α – r = 0.85, p = 0.0073; cdk1 – r = 0.86, p = 0.0053; bcl-2 – r = 0.89, p = 0.0026) at protracted exposures. This is the first report on the dual role of bcl-2 gene in fish exposed to acute and protracted radiation and correlation among the aforementioned genes that work in concert to promote ‘repair’ and ‘death’ circuitries in fish blood cells.

  8. Gene expression in Catla catla (Hamilton) subjected to acute and protracted doses of gamma radiation

    International Nuclear Information System (INIS)

    Anbumani, S.; Mohankumar, Mary N.

    2016-01-01

    Highlights: • Gamma radiation induced up- and down- regulation of cell cycle genes. • Protracted dose-rate induced gene up-regulation to facilitate cell survival. • bcl-2 gene facilitates repair at protracted dose and cell death at acute exposures. • gadd45α, cdk1 and bcl-2 genes work in concert to promote ‘repair’ and ‘death’ circuitries in fish blood cells. - Abstract: Studies on transcriptional modulation after gamma radiation exposure in fish are limited. Cell cycle perturbations and expression of apoptotic genes were investigated in the fish, Catla catla after acute and protracted exposures to gamma radiation over a 90 day period. Significant changes in gene expression were observed between day 1 and 90 post-exposure. Gamma radiation induced a significant down-regulation of target genes gadd45α, cdk1 and bcl-2 from day 1 to day 3 after protracted exposure, whereas it persists till day 6 upon acute exposure. From day 12 onwards, Gadd45α, cdk1 and bcl-2 genes were up-regulated following protracted exposure, indicating DNA repair, cell-cycle arrest and apoptosis. There exists a linear correlation between these genes (gadd45α – r = 0.85, p = 0.0073; cdk1 – r = 0.86, p = 0.0053; bcl-2 – r = 0.89, p = 0.0026) at protracted exposures. This is the first report on the dual role of bcl-2 gene in fish exposed to acute and protracted radiation and correlation among the aforementioned genes that work in concert to promote ‘repair’ and ‘death’ circuitries in fish blood cells.

  9. 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

  10. 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

  11. Visual sensations induced by Cherenkov radiation

    International Nuclear Information System (INIS)

    McNulty, P.J.; Pease, V.P.; Bond, V.P.

    1975-01-01

    Pulses of relativistic singly charged particles entering the eyeball induce a variety of visual phenomena by means of Cerenkov radiation generated during their passage through the vitreous. These phenomena are similar in appearance to many of the visual sensations experienced by Apollo astronauts exposed to the cosmic rays in deep space

  12. 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)

  13. Ionizing Radiation Affects Gene Expression in Mouse Skin and Bone

    Science.gov (United States)

    Terada, Masahiro; Tahimic, Candice; Sowa, Marianne B.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Alwood, Joshua; Globus, Ruth K.

    2017-01-01

    Future long-duration space exploration beyond low earth orbit will increase human exposure to space radiation and microgravity conditions as well as associated risks to skeletal health. In animal studies, radiation exposure (greater than 1 Gy) is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Definitive measurements and detection of bone loss typically require large and specialized equipment which can make their application to long duration space missions logistically challenging. Towards the goal of developing non-invasive and less complicated monitoring methods to predict astronauts' health during spaceflight, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (IR). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and IR (0.5 Gy 56Fe 600 MeV/n and 0.5 Gy 1H 150 MeV/n), euthanized at one and 11 days post-irradiation (IR). To determine the extent of bone loss, tibiae were harvested and cancellous microarchitecture in the proximal tibia quantified ex vivo using microcomputed tomography (microCT). Statistical analysis was performed using Student's t-test. At one day post-IR, expression of FGF18 in skin was significantly greater (3.8X) than sham-irradiated controls, but did not differ at 11 days post IR. Expression levels of other genes associated with antioxidant response (Nfe2l2, FoxO3 and Sod1) and the cell cycle (Trp53, Cdkn1a, Gadd45g) did not significantly differ between the control and IR groups

  14. 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

  15. The essential role of the Deinococcus radiodurans ssb gene in cell survival and radiation tolerance.

    Directory of Open Access Journals (Sweden)

    J Scott Lockhart

    Full Text Available Recent evidence has implicated single-stranded DNA-binding protein (SSB expression level as an important factor in microbial radiation resistance. The genome of the extremely radiation resistant bacterium Deinococcus radiodurans contains genes for two SSB homologs: the homodimeric, canonical Ssb, encoded by the gene ssb, and a novel pentameric protein encoded by the gene ddrB. ddrB is highly induced upon exposure to radiation, and deletions result in decreased radiation-resistance, suggesting an integral role of the protein in the extreme resistance exhibited by this organism. Although expression of ssb is also induced after irradiation, Ssb is thought to be involved primarily in replication. In this study, we demonstrate that Ssb in D. radiodurans is essential for cell survival. The lethality of an ssb deletion cannot be complemented by providing ddrB in trans. In addition, the radiation-sensitive phenotype conferred by a ddrB deletion is not alleviated by providing ssb in trans. By altering expression of the ssb gene, we also show that lower levels of transcription are required for optimal growth than are necessary for high radiation resistance. When expression is reduced to that of E. coli, ionizing radiation resistance is similarly reduced. UV resistance is also decreased under low ssb transcript levels where growth is unimpaired. These results indicate that the expression of ssb is a key component of both normal cellular metabolism as well as pathways responsible for the high radiation tolerance of D. radiodurans.

  16. 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

  17. Cataracts induced by microwave and ionizing radiation

    International Nuclear Information System (INIS)

    Lipman, R.M.; Tripathi, B.J.; Tripathi, R.C.

    1988-01-01

    Microwaves most commonly cause anterior and/or posterior subcapsular lenticular opacities in experimental animals and, as shown in epidemiologic studies and case reports, in human subjects. The formation of cataracts seems to be related directly to the power of the microwave and the duration of exposure. The mechanism of cataractogenesis includes deformation of heat-labile enzymes, such as glutathione peroxide, that ordinarily protect lens cell proteins and membrane lipids from oxidative damage. Oxidation of protein sulfhydryl groups and the formation of high-molecular-weight aggregates cause local variations in the orderly structure of the lens cells. An alternative mechanism is thermoelastic expansion through which pressure waves in the aqueous humor cause direct physical damage to the lens cells. Cataracts induced by ionizing radiation (e.g., X-rays and gamma rays) usually are observed in the posterior region of the lens, often in the form of a posterior subcapsular cataract. Increasing the dose of ionizing radiation causes increasing opacification of the lens, which appears after a decreasing latency period. Like cataract formation by microwaves, cataractogenesis induced by ionizing radiation is associated with damage to the lens cell membrane. Another possible mechanism is damage to lens cell DNA, with decreases in the production of protective enzymes and in sulfur-sulfur bond formation, and with altered protein concentrations. Until further definitive conclusions about the mechanisms of microwaves and ionizing radiation induced cataracts are reached, and alternative protective measures are found, one can only recommend mechanical shielding from these radiations to minimize the possibility of development of radiation-induced cataracts. 74 references

  18. 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

  19. 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

  20. 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

  1. 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

  2. Chromosomal instability induced by ionizing radiation

    International Nuclear Information System (INIS)

    Morgan, W.F.; Marder, B.A.; Day, J.P.

    1995-01-01

    There is accumulating evidence indicating genomic instability can manifest multiple generations after cellular exposure to DNA damaging agents. For instance, some cells surviving exposure to ionizing radiations show delayed reproductive cell death, delayed mutation and / or delayed chromosomal instability. Such instability, especially chromosome destabilization has been implicated in mutation, gene amplification, cellular transformation, and cell killing. To investigate chromosomal instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells. The relationship between delayed chromosomal destabilization and other endpoints of genomic instability, namely; delayed mutation and gene amplification will be discussed, as will the potential cytogenetic and molecular mechanisms contributing to delayed chromosomal instability

  3. 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

  4. Dual responsive promoters to target therapeutic gene expression to radiation-resistant hypoxic tumor cells

    International Nuclear Information System (INIS)

    Chadderton, Naomi; Cowen, Rachel L.; Sheppard, Freda C.D.; Robinson, Suzanne; Greco, Olga; Scott, Simon D.; Stratford, Ian J.; Patterson, Adam V.; Williams, Kaye J.

    2005-01-01

    Purpose: Tumor hypoxia is unequivocally linked to poor radiotherapy outcome. This study aimed to identify enhancer sequences that respond maximally to a combination of radiation and hypoxia for use in genetic radiotherapy approaches. Methods and materials: The influence of radiation (5 Gy) and hypoxia (1% O 2 ) on reporter-gene expression driven by hypoxia (HRE) and radiation (Egr-1) responsive elements was evaluated in tumor cells grown as monolayers or multicellular spheroids. Hypoxia-inducible factor-1α (HIF-1α) and HIF-2α protein expression was monitored in parallel. Results: Of the sequences tested, an HRE from the phosphoglycerate kinase-1 gene (PGK-18[5+]) was maximally induced in response to hypoxia plus radiation in all 5 cell lines tested. The additional radiation treatment afforded a significant increase in the induction of PGK-18[5+] compared with hypoxia alone in 3 cell lines. HIF-1α/2α were induced by radiation but combined hypoxia/radiation treatment did not yield a further increase. The dual responsive nature of HREs was maintained when spheroids were irradiated after delivery of HRE constructs in a replication-deficient adenovirus. Conclusions: Hypoxia-responsive enhancer element sequences are dually responsive to combined radiation and hypoxic treatment. Their use in genetic radiotherapy in vivo could maximize expression in the most radio-resistant population at the time of radiation and also exploit microenvironmental changes after radiotherapy to yield additional switch-on

  5. 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)

  6. 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.

  7. Radiation-induced reactions in polydimethyl siloxanes

    International Nuclear Information System (INIS)

    Menhofer, H.

    1988-01-01

    The dissertation reports an investigation into the behaviour of polydimethyl soloxanes (PDMS) subject to the radiation field of a 60 Co-γ radiation source at different irradiation conditions. Several different analytical methods have been applied for the detection of chemical changes in the material and their effects on the polymeric segment mobility. Application of the ESR-spintrap technique identifies the primary radicals x CH 3 , -Si x , and -Si-CH 2 x , induced by the radiolysis of the PDMS. The individual rates of radical formation have been found to be strongly dependent on temperature. (orig./LU) [de

  8. 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

  9. 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

  10. Circadian transitions in radiation dose-dependent augmentation of mRNA levels for DNA damage-induced genes elicited by accurate real-time RT-PCR quantification

    International Nuclear Information System (INIS)

    Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko

    2010-01-01

    Molecular mechanisms of intracellular response after DNA-damage by exposure to ionizing radiation have been studied. In the case of cells isolated from living body of human and experimental animals, alteration of the responsiveness by physiological oscillation such as circadian rhythm must be considered. To examine the circadian variation in the response of p53-responsible genes p21, mdm2, bax, and puma, we established a method to quantitate their mRNA levels with high reproducibility and accuracy based on real-time reverse transcription polymerase chain reaction (RT-PCR) and compared the levels of responsiveness in mouse hemocytes after diurnal irradiation to that after nocturnal irradiation. Augmentations of p21 and mdm2 mRNA levels with growth-arrest and of puma mRNA before apoptosis were confirmed by time-course experiment in RAW264.7, and dose-dependent increases in the peak levels of all the RNA were shown. Similarly, the relative RNA levels of p21, mdm2, bax, and puma per glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also increased dose-dependently in peripheral blood and bone marrow cells isolated from whole-body-irradiated mice. Induction levels of all messages reduced by half after nighttime irradiation as compared with daytime irradiation in blood cells. In marrow cells, nighttime irradiation enhanced the p21 and mdm2 mRNA levels than daytime irradiation. No significant difference in bax or puma mRNA levels was observed between nighttime and daytime irradiation in marrow cells. This suggests that early-stage cellular responsiveness in DNA damage-induced genes is modulated between diurnal and nocturnal irradiation. (author)

  11. 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

  12. Molecular mechanism of apoptosis and characterization of apoptosis induced by radiation

    International Nuclear Information System (INIS)

    Li Yumin; Zhang Yuguang; Li Yukun

    1999-01-01

    The major discoveries of apoptosis research in recent years were reviewed briefly. The mechanisms of caspases/ICE gene family and bcl-2 gene family on apoptosis were analyzed. And the signal transduction pathway of apoptosis found currently has been summarized. The characterizations of apoptosis induced by radiation such as time-effects, dose-effects and the radiosensibility were summed up

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Heat pump processes induced by laser radiation

    Science.gov (United States)

    Garbuny, M.; Henningsen, T.

    1980-01-01

    A carbon dioxide laser system was constructed for the demonstration of heat pump processes induced by laser radiation. The system consisted of a frequency doubling stage, a gas reaction cell with its vacuum and high purity gas supply system, and provisions to measure the temperature changes by pressure, or alternatively, by density changes. The theoretical considerations for the choice of designs and components are dicussed.

  18. Radiation-induced structural changes, (2)

    International Nuclear Information System (INIS)

    Ogasawara, M.; Matsuyama, T.

    1992-11-01

    This seminar is aimed at understanding both the physical and chemical aspects of the structural changes of materials induced by photons or ionizing radiation. The seminar was held on December 19th, 1991 and from February 13 to 14th, 1992 in this institute. The most active areas of the material science, in addition to the previous subjects, such as organic superconductors, silicon-based polymers, and fullerenes were included in this seminar. (J.P.N.)

  19. 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)

  20. 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

  1. Gene conversion and reversion events in Saccharomyces cerevisiae. Model for study of gamma radiation damage

    International Nuclear Information System (INIS)

    Moreno, Damaris; Fuentes, Jorge L.; Prieto Miranda, Enrique F.; Sanchez Lamar, Angel; Baluja, Ligia

    2004-01-01

    Radiosensitivity and kinetics of induction of gene conversion and reversion events in Saccharomyces cerevisiae strain D7 to gamma radiation at dose ranges from 100 to 800 Gy and 50 to 300 Gy respectively were studied. A source of 60Co PX- -30 at a dose rate of 49,43 GY/min was utilized. The cell survival curve showed DL50 of 150 Gy. Cell death kinetics was linear and adjusted over 98 %. The induction of gene conversion events was significant in relation to control from 50 Gy on. However, gene reversion was significant only at 200 Gy. Generally speaking, gene conversion event frequencies were higher than those of reversion, which indicates that gamma radiation preferably induces recombinogenic events. Both the conversion and reversion events showed exponential dependence on gamma radiation dose. The relative benefits of this test for mutagenesis and anti-mutagenesis studies were debated in this paper

  2. 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.)

  3. Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

    Science.gov (United States)

    Lorimore, S A; Wright, E G

    2003-01-01

    To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

  4. 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)

  5. Expression of TIMP1, TIMP2 genes by ionizing radiation

    International Nuclear Information System (INIS)

    Park, Kun Koo; Jin, Jung Sun; Park, Ki Yong; Lee, Yun Hee; Kim, Sang Yoon; Noh, Young Ju; Ahn, Seung Do; Kim, Jong Hoon; Choi, Eun Kyung; Chang, Hye Sook

    2001-01-01

    Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angio genesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity (D o ), radiation cytotoxicity and metastatic potential were measured by clonogenic assay, MTT assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promotor region was cloned and TIMP1 luciferase reporter vector was constructed, The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was performed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promotor. D o of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. MTT assay confirmed cell viability, over 94% at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-l and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 spectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell

  6. Gene Expression Analysis of Four Radiation-resistant Bacteria

    OpenAIRE

    Gao, Na; Ma, Bin-Guang; Zhang, Yu-Sheng; Song, Qin; Chen, Ling-Ling; Zhang, Hong-Yu

    2009-01-01

    To investigate the general radiation-resistant mechanisms of bacteria, bioinformatic method was employed to predict highly expressed genes for four radiation-resistant bacteria, i.e. Deinococcus geothermalis (D. geo), Deinococcus radiodurans (D. rad), Kineococcus radiotolerans (K. rad) and Rubrobacter xylanophilus (R. xyl). It is revealed that most of the three reference gene sets, i.e. ribosomal proteins, transcription factors and major chaperones, are generally highly expressed in the four ...

  7. Identification of molecular mechanisms of radiation-induced vascular damage in normal tissues using microarray analyses

    International Nuclear Information System (INIS)

    Kruse, J.J.C.M.; Te Poele, J.A.M.; Russell, N.S.; Boersma, L.J.; Stewart, F.A.

    2003-01-01

    Radiation-induced telangiectasia, characterized by thin-walled dilated blood vessels, can be a serious late complication in patients that have been previously treated for cancer. It might cause cosmetic problems when occurring in the skin, and excessive bleeding requiring surgery when occurring in rectal mucosa. The mechanisms underlying the development of radiation-induced telangiectasia are unclear. The aim of the present study is to determine whether microarrays are useful for studying mechanisms of radiation-induced telangiectasia. The second aim is to test the hypotheses that telangiectasia is characterized by a final common pathway in different tissues. Microarray experiments were performed using amplified RNA from (sham)irradiated mouse tissues (kidney, rectum) at different intervals (1-30 weeks) after irradiation. After normalization procedures, the differentially expressed genes were identified. Control/repeat experiments were done to confirm that the observations were not artifacts of the array procedure. The mouse kidney experiments showed significant upregulation of 31 and 42 genes and downregulation of 9 and 4 genes at 10 and 20 weeks after irradiation, respectively. Irradiated mouse rectum has 278 upregulated and 537 downregulated genes at 10 weeks and 86 upregulated and 29 downregulated genes at 20 weeks. During the development of telangiectasia, 19 upregulated genes and 5 downregulated genes were common to both tissues. Upregulation of Jagged-1, known to play a role in angiogenesis, is particularly interesting in the context of radiation-induced telangiectasia. Microarrays are affective discovery tools to identify novel genes of interest, which may be involved in radiation-induced normal tissue injury. Using information from control arrays (particularly straight color, color reverse and self-self experiments) allowed for a more accurate and reproducible identification of differentially expressed genes than the selection of an arbitrary 2-fold change

  8. Breast cancer induced by protracted radiation exposures

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1997-01-01

    The experience at Hiroshima/Nagasaki demonstrated that breast cancer can be induced by single doses of ionizing radiation following latencies of 10-40 years. Several epidemiological studies, usually involving ancillary low-LET radiation to the breast, have demonstrated that breast cancer can be induced by protracted exposures, with similar latencies, and with similar dependencies on dose. Radiobiologically these results suggest that the target cells involved were deficient in repair of low-LET damage even when the protraction was over months to years. Since three-quarters of breast tumors originate in the ducts where their proliferation is controlled by menstrual-cycle timed estrogen/progesterone secretions, these cells periodically were in cycle. Thus, the two main elements of a conceptual model for radon-induced lung cancer -- kinetics and deficient repair -- are satisfied. The model indicates that breast cancer could be the cumulative effect of protracted small exposures, the risk from any one of which ordinarily would be quite small. (author)

  9. 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)

  10. 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

  11. 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

  12. Characteristics of radiation-induced neoplastic transformation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B.

    1986-01-01

    Data are presented to support the hypothesis that the initial step in the morphologic transformation of irradiated rodent (BALB/3T3) cells is a frequent cellular event involving a large fraction of the irradiated population. This process appears to involve DNA damage, but not to represent a targeted mutation in specific structural gene(s). Morphologic transformation and immortalization appear to be distinct steps in the overall process of transformation. In contradistinction to rodent cells, immortalization is a very rare event in human diploid cells which is induced at extremely low frequencies. The hypothesis is presented that immortality develops among clones of cells bearing stable chromosomal rearrangements which emerge during the proliferation of a population of radiation damaged cells.

  13. Specific gene mutations induced by heavy ions

    International Nuclear Information System (INIS)

    Freeling, M.; Karoly, C.W.; Cheng, D.S.K.

    1980-01-01

    This report summarizes our heavy-ion research rationale, progress, and plans for the near future. The major project involves selecting a group of maize Adh1 mutants induced by heavy ions and correlating their altered behavior with altered DNA nucleotide sequences and sequence arrangements. This research requires merging the techniques of classical genetics and recombinant DNA technology. Our secondary projects involve (1) the use of the Adh gene in the fruit fly, Drosophila melanogaster, as a second system with which to quantify the sort of specific gene mutants induced by heavy ions as compared to x rays, and (2) the development of a maize Adh1 pollen in situ monitor for environmental mutagens

  14. Molecular targets in radiation-induced blood-brain barrier disruption

    International Nuclear Information System (INIS)

    Nordal, Robert A.; Wong, C. Shun

    2005-01-01

    Disruption of the blood-brain barrier (BBB) is a key feature of radiation injury to the central nervous system. Studies suggest that endothelial cell apoptosis, gene expression changes, and alteration of the microenvironment are important in initiation and progression of injury. Although substantial effort has been directed at understanding the impact of radiation on endothelial cells and oligodendrocytes, growing evidence suggests that other cell types, including astrocytes, are important in responses that include induced gene expression and microenvironmental changes. Endothelial apoptosis is important in early BBB disruption. Hypoxia and oxidative stress in the later period that precedes tissue damage might lead to astrocytic responses that impact cell survival and cell interactions. Cell death, gene expression changes, and a toxic microenvironment can be viewed as interacting elements in a model of radiation-induced disruption of the BBB. These processes implicate particular genes and proteins as targets in potential strategies for neuroprotection

  15. Radiation induced mutations for plant selection

    International Nuclear Information System (INIS)

    Brunner, H.

    1994-01-01

    The successful use of plant breeding for improving crops requires the existence of genetic variation of useful traits. Unfortunately, the desired variation is often lacking. However, radiation can be used to induce mutations and thereby generate genetic variation from which desired mutants may be selected. Mutation induction has become a proven way of creating variation within a crop variety. It offers the possibility of inducing desired attributes that either cannot be expressed in nature or have been lost during evolution. More than 1700 mutant cultivars of crop plants with significantly improved attributes such as increased yield, improved quality, disease and stress resistance, have been released worldwide in the last thirty years. The Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has contributed to these achievements through the promotion of research and development in mutation breeding techniques using nuclear and related biotechnological methods and the provision of in plant breeding is then transferred to Member States of the IAEA and the FAO through training in mutation breeding methods and the provision of technical advice. Moreover, radiation treatment services are provided to foster applications of nuclear techniques in crop improvement programmes of member states and more specifically to render direct support to plant breeders by efficient generation of mutations. Plant materials are standardized prior to radiation exposure to warrant reproducibility of the induced effects within practical limits and a radiosensitivity test is implemented to affirm useful doses for applied objectives of a request. This review deals with irradiation methods applied at the IAEA laboratories for the efficient induction of mutations in seeds, vegetative propagules and tissue and cell cultures and the establishment of genetically variable populations upon which selection of desired traits can be based. 3 tabs., 18 refs. (author)

  16. Tetracycline inducible gene manipulation in serotonergic neurons.

    Directory of Open Access Journals (Sweden)

    Tillmann Weber

    Full Text Available The serotonergic (5-HT neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA mouse line (TPH2-tTA that allows temporal and spatial control of tetracycline (Ptet controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ. In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox. Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20 were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We

  17. Development of Gene Expression Signatures for Practical Radiation Biodosimetry

    International Nuclear Information System (INIS)

    Paul, Sunirmal; Amundson, Sally A.

    2008-01-01

    Purpose: In a large-scale radiologic emergency, estimates of exposure doses and radiation injury would be required for individuals without physical dosimeters. Current methods are inadequate for the task, so we are developing gene expression profiles for radiation biodosimetry. This approach could provide both an estimate of physical radiation dose and an indication of the extent of individual injury or future risk. Methods and Materials: We used whole genome microarray expression profiling as a discovery platform to identify genes with the potential to predict radiation dose across an exposure range relevant for medical decision making in a radiologic emergency. Human peripheral blood from 10 healthy donors was irradiated ex vivo, and global gene expression was measured both 6 and 24 h after exposure. Results: A 74-gene signature was identified that distinguishes between four radiation doses (0.5, 2, 5, and 8 Gy) and controls. More than one third of these genes are regulated by TP53. A nearest centroid classifier using these same 74 genes correctly predicted 98% of samples taken either 6 h or 24 h after treatment as unexposed, exposed to 0.5, 2, or ≥5 Gy. Expression patterns of five genes (CDKN1A, FDXR, SESN1, BBC3, and PHPT1) from this signature were also confirmed by real-time polymerase chain reaction. Conclusion: The ability of a single gene set to predict radiation dose throughout a window of time without need for individual pre-exposure controls represents an important advance in the development of gene expression for biodosimetry

  18. 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.)

  19. 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)

  20. 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).

  1. A mathematical model for leukemogenesis of radiation-induced acute myeloid leukemia in C3H/He mice

    International Nuclear Information System (INIS)

    Kai, M.; Ban, N.

    2002-01-01

    We developed a mathematical model in leukemogenesis of acute myeloid leukemia(AML) in C3H/He mice irradiated. Our previous study indicated that the leukemogenesis of AML was associated with a deletion of chromosome 2 directly induced by acute radiation. We hypothesized that radiation-induced AML needs both inactivation of one allele of a causative gene directly induced by acute radiation and another mutational event at the other allele. We analyzed data using a two-stage stochastic model for carcinogenesis. Model fitting was based on the maximum likelihood method. Our model analysis suggested that a single exposure might induce the long-lasting delayed cell death of radiation-induced initiated cells, and that the incidence of AML may be determined through both radiation-induced initiation and persistent increase of delayed cell death of the initiated cell induced by radiation

  2. Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

    Science.gov (United States)

    Warters, Raymond L.; Packard, Ann T.; Kramer, Gwen F.; Gaffney, David K.; Moos, Philip J.

    2009-01-01

    Although skin is usually exposed during human exposures to ionizing radiation, there have been no thorough examinations of the transcriptional response of skin fibroblasts and keratinocytes to radiation. The transcriptional response of quiescent primary fibroblasts and keratinocytes exposed to from 10 cGy to 5 Gy and collected 4 h after treatment was examined. RNA was isolated and examined by microarray analysis for changes in the levels of gene expression. Exposure to ionizing radiation altered the expression of 279 genes across both cell types. Changes in RNA expression could be arranged into three main categories: (1) changes in keratinocytes but not in fibroblasts, (2) changes in fibroblasts but not in keratinocytes, and (3) changes in both. All of these changes were primarily of p53 target genes. Similar radiation-induced changes were induced in immortalized fibroblasts or keratinocytes. In separate experiments, protein was collected and analyzed by Western blotting for expression of proteins observed in microarray experiments to be overexpressed at the mRNA level. Both Q-PCR and Western blot analysis experiments validated these transcription changes. Our results are consistent with changes in the expression of p53 target genes as indicating the magnitude of cell responses to ionizing radiation. PMID:19580510

  3. 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

  4. 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.

  5. Allogeneic radiation chimeras induced in SPF mice

    International Nuclear Information System (INIS)

    Sado, Toshihiko; Kamisaku, Hitoko

    1977-01-01

    During the past two decades much has been learned concerning the immunobiology of bone marrow chimeras induced in experimental animals as well as in man. However, from the basic as well as clinical points of view, there still remain many unsolved questions yet to be resolved. In this presentation, we discussed some of our recent results on the immunobiology of radiation chimeras induced in specific-pathogen-free (SPF) mice. These included the following: (a) contribution of graft versus host reaction (GVHR) as well non- GVHR mediated immunologic mechanism(s) to the expression of immunologic dysfunctions observed in allogeneic and certain semiallogeneic chimeras, (b) existence of immunoregulatory mechanism as a basis for the apparent lack of immunologic reactivity (tolerance) to the host- as well as to the donor-type alloantigens in situ in successful allogeneic bone marrow chimeras, and (c) the effect of microflora of the environment on the stability of such immunoregulatory mechanisms and its possible mechanism of action. (auth.)

  6. Adaptive response to ionizing radiation in normal human skin fibroblasts. Enhancement of DNA repair rate and modulation of gene expression

    International Nuclear Information System (INIS)

    Toledo, S.M. de; Mitchel, R.E.J.; Azzam, E.; Ottawa Univ., ON; Raaphorst, G.P.

    1994-01-01

    Low doses and dose rates of ionizing radiation enhance the rate of DNA repair in human fibroblasts and protect the cells against radiation-induced micronucleus formation. Chronic exposures reduce the mRNA levels of the genes topoisomerase II and FACC-1 (Fanconi's anemia, group C). (authors). 11 refs., 1 tab., 2 figs

  7. Development of a radiation-responsive gene expression system

    International Nuclear Information System (INIS)

    Ogawa, Ryohei; Morii, Akihiro; Watanabe, Akihiko

    2013-01-01

    We have obtained a promoter enhancing expression of a gene of our interest connected downstream after activation in response to radiation stimulation and it could be used in radiogenetic therapy, a combination between radiotherapy and gene therapy. The promoter has been chosen out of a library of DNA fragments constructed by connecting the TATA box to randomly combined binding sequences of transcription factors that are activated in response to radiation. Although it was shown that the promoter activation was cell type specific, it turned out that radiation responsive promoters could be obtained for a different type of cells by using another set of transcription factor binding sequences, suggesting that the method would be feasible to obtain promoters functioning in any type of cells. Radiation reactivity of obtained promoters could be improved by techniques such as random introduction of point mutations. The improved promoters significantly enhanced expression of the luciferase gene connected downstream in response to radiation even in vivo, in addition, a gene cassette composed of one such promoter and the fcy::fur gene was confirmed useful for suicide gene therapy as shown in vitro simulation experiment, suggesting possible clinical application. (author)

  8. Progress in research on ionizing radiation-induced microRNA

    International Nuclear Information System (INIS)

    Hu Zheng; Tie Yi; Sun Zhixian; Zheng Xiaofei

    2011-01-01

    MicroRNAs (miRNAs) are small single-stranded noncoding RNAs consisting of 21-23 nucleotides that play important gene-regulatory roles in eukaryotes by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. A growing body of evidence indicates that alterations in miRNA expression may occur following exposure to several oxidative stress including ionizing radiation. So miRNAs may serve as potential new targets for co-therapies aiming to improve the effects of radiation disease therapy in cancer patients. The progress in research on ionizing radiation-induced miRNAs is reviewed in this paper. (authors)

  9. Radiation induced micrencephaly in guinea pigs

    International Nuclear Information System (INIS)

    Wagner, L.K.; Johnston, D.A.; Felleman, D.J.

    1991-01-01

    A brain weight deficit of about 70 mg was induced at doses of approximately 75-mGy and a deficit of 60 mg was induced at 100 mGy. This confirms the effects projected and observed by Wanner and Edwards. Although the data do not demonstrate a clear dose-response relationship between the 75-mGy and 100-mGy groups, the data are statistically consistent with a dose-response effect because of the overlapping confidence intervals. The lack of a statistically significant observation is most likely related to the small difference in doses and the limited numbers of animals examined. There are several factors that can influence the brain weight of guinea pig pups, such as caging and housing conditions, the sex of the animal, and litter size. These should be taken into account for accurate analysis. Dam weight did not appear to have a significant effect. The confirmation of a micrencephalic effect induced x rays at doses of 75-mGy during this late embryonic stage of development is consistent with the findings of small head size induced in those exposed prior to the eight week of conception at Hiroshima. This implies a mechanism for micrencephaly different from those previously suggested and lends credence to a causal relation between radiation and small head size in humans at low doses as reported by Miller and Mulvihill. 16 refs., 13 tabs

  10. 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

  11. Photorhabdus luminescens genes induced upon insect infection

    Directory of Open Access Journals (Sweden)

    Jung Kirsten

    2008-05-01

    Full Text Available Abstract Background Photorhabdus luminescens is a Gram-negative luminescent enterobacterium and a symbiote to soil nematodes belonging to the species Heterorhabditis bacteriophora. P.luminescens is simultaneously highly pathogenic to insects. This bacterium exhibits a complex life cycle, including one symbiotic stage characterized by colonization of the upper nematode gut, and a pathogenic stage, characterized by release from the nematode into the hemocoel of insect larvae, resulting in rapid insect death caused by bacterial toxins. P. luminescens appears to sense and adapt to the novel host environment upon changing hosts, which facilitates the production of factors involved in survival within the host, host-killing, and -exploitation. Results A differential fluorescence induction (DFI approach was applied to identify genes that are up-regulated in the bacterium after infection of the insect host Galleria mellonella. For this purpose, a P. luminescens promoter-trap library utilizing the mCherry fluorophore as a reporter was constructed, and approximately 13,000 clones were screened for fluorescence induction in the presence of a G. mellonella larvae homogenate. Since P. luminescens has a variety of regulators that potentially sense chemical molecules, like hormones, the screen for up-regulated genes or operons was performed in vitro, excluding physicochemical signals like oxygen, temperature or osmolarity as variables. Clones (18 were obtained exhibiting at least 2.5-fold induced fluorescence and regarded as specific responders to insect homogenate. In combination with a bioinformatics approach, sequence motifs were identified in these DNA-fragments that are similar to 29 different promoters within the P. luminescens genome. By cloning each of the predicted promoters upstream of the reporter gene, induction was verified for 27 promoters in vitro, and for 24 promoters in viable G. mellonella larvae. Among the validated promoters are some known

  12. 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)

  13. Radiation induced color in topaz crystals

    International Nuclear Information System (INIS)

    Castagnet, A.C.; Rocca, H.C.C.; Rostilato, M.E.C.M.

    1989-08-01

    The presence of defects and impurities in the crystal lattice alters the eletric field distribution within the crystal, allowing the electrons to occupy energy levels in the forbbiden band. Ionizing radiation supply the required energy to permit the electrons originaly bound to lattice atoms, to occupy effectively those intermediate levels, forming color centers. Dependig upon the nature and energy of the radiation, it is possible to produce defects in regions of the crystal, generating color centers. Based on these premises, a technique to induce color in originally colorless topaz, by using the IEA-R1 nuclear reactor, was developed at Engineering and Industrial Application Department (TE). Samples were irradiated inside iron capsules coated with cadmium foils. The iron, and principaly the cadmium, absorb the thermal neutrons that could activate crystal impurities generating long-lived radioisotopes. The epithermal neutrons that overpass the iron and cadmium barriers interact with the crystal atoms, causing lattice defects which give rise to color center, by subsequent ionization processes. The procedure used at TE induces permanent blue color, in natural colorless topaz. (author) [pt

  14. 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.

  15. Differential Effects of Alpha-Particle Radiation and X-Irradiation on Genes Associated with Apoptosis

    International Nuclear Information System (INIS)

    Chauhan, V.; Howland, M.; Chen, J.; Kutzner, B.; Wilkins, R.C.

    2011-01-01

    This study examined differential effects of alpha-(α) particle radiation and X-rays on apoptosis and associated changes in gene expression. Human monocytic cells were exposed to a-particle radiation and X-rays from 0 to 1.5 Gy. Four days postexposure, cell death was measured by flow cytometry and 84 genes related to apoptosis were analyzed using real-time PCR. On average, 33% of the cells were apoptotic at 1.5 Gy of a-particle radiation. Transcript profiling showed statistical expression of 15 genes at all three doses tested. Cells exposed to X-rays were <5% apoptotic at ∼1.5 Gy and induced less than a 2-fold expression in 6 apoptotic genes at the higher doses of radiation. Among these 6 genes, Fas and TNF-α were common to the α-irradiated cells. This data suggests that α-particle radiation initiates cell death by TNF-a and Fas activation and through intermediate signalling mediators that are distinct from X-irradiated cells

  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. Alteration in expression of defence genes in Pisum sativum after exposure to supplementary ultraviolet-B radiation

    International Nuclear Information System (INIS)

    Strid, A.

    1993-01-01

    Alterations in the amounts of mRNA for different types of defence genes after exposure of peas to supplementary ultraviolet-B radiation are demonstrated. The expression of the genes which encode the chalcone synthase of the flavonoid biosynthetic pathway and glutathione reductase was induced, while a decrease was found for the chloroplastic radical-scavenging enzyme, superoxide dismutase. (author)

  18. 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

  19. The relevance of cytokines in the radiation-induced lung reaction. Experimental basis and clinical significance

    International Nuclear Information System (INIS)

    Ruebe, C.E.; Ruebe, C.; Rodemann, H.P.

    2004-01-01

    Methods: published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. Results and conclusion: the major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-β (TGF-β) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-β-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely. (orig.)

  20. UV-induced changes in cell cycle and gene expression within rabbit lens epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Sidjanin, D. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences; Grdina, D. [Argonne National Lab., IL (United States); Woloschak, G.E. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences

    1994-11-01

    Damage to lens epithelial cells is a probable initiation process in cataract formation induced by ultraviolet radiation. These experiments investigated the ability of 254 nm radiation on cell cycle progression and gene expression in rabbit lens epithelial cell line N/N1003A. No changes in expression of c-fos, c-jun, alpha- tubulin, or vimentin was observed following UV exposure. Using flow cytometry, an accumulation of cells in G1/S phase of the cell cycle 1 hr following exposure. The observed changes in gene expression, especially the decreased histone transcripts reported here may play a role in UV induced inhibition of cell cycle progression.

  1. Development of radiation-induced mutation techniques and functional genomics studies

    International Nuclear Information System (INIS)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek

    2012-01-01

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative·structural·functional genomics studies for useful traits

  2. Radiation Gene-expression Signatures in Primary Breast Cancer Cells.

    Science.gov (United States)

    Minafra, Luigi; Bravatà, Valentina; Cammarata, Francesco P; Russo, Giorgio; Gilardi, Maria C; Forte, Giusi I

    2018-05-01

    In breast cancer (BC) care, radiation therapy (RT) is an efficient treatment to control localized tumor. Radiobiological research is needed to understand molecular differences that affect radiosensitivity of different tumor subtypes and the response variability. The aim of this study was to analyze gene expression profiling (GEP) in primary BC cells following irradiation with doses of 9 Gy and 23 Gy delivered by intraoperative electron radiation therapy (IOERT) in order to define gene signatures of response to high doses of ionizing radiation. We performed GEP by cDNA microarrays and evaluated cell survival after IOERT treatment in primary BC cell cultures. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate candidate genes. We showed, for the first time, a 4-gene and a 6-gene signature, as new molecular biomarkers, in two primary BC cell cultures after exposure at 9 Gy and 23 Gy respectively, for which we observed a significantly high survival rate. Gene signatures activated by different doses of ionizing radiation may predict response to RT and contribute to defining a personalized biological-driven treatment plan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. 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 - .

  4. 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.

  5. Influence of mutations in some structural genes of heat-shock proteins on radiation resistance of Escherichia coli

    International Nuclear Information System (INIS)

    Verbenko, V.N.; Kuznetsova, L.V.; Bikineeva, E.G.; Kalinin, V.L.

    1992-01-01

    Lethal effects of γ-irradiation were studied in Escherichia coli strains with normal repair genotype and in radiation-resistant Gam r strains, both carrying additional mutations in the structural genes dnaK, grpE, groES or groEL. The null mutation ΔdnaK52::Cm r enhanced radiation sensitivity of wild-type cells and abolished the effect of heat induced rediation-resistance (ETIRR) and elevated radiation resistance of the Gam r strains

  6. 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

  7. 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.

  8. In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

    Science.gov (United States)

    Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

    2015-01-01

    The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

  9. 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)

  10. Radiation-induced structural changes. 3

    International Nuclear Information System (INIS)

    Kondo, Yasuhiro; Matsuyama, Tomochika; Ogasawara, Masaaki

    1993-05-01

    This meeting is the fourth of series meetings on the structural change in materials induced by ionizing radiation. The present meeting was organized to discuss specifically on the x-ray storage phosphors such as BaFBr:Eu 2+ or RbI x Br 1-x :Tl and to get a clear understanding of the present status of the research on the storage mechanisms, nature of the rare earth impurities, and the optical properties of BaFBr. It was also expected that all the participants became aware of unsolved problems in these storage materials and that some of them would start research work on the storage phosphors. Therefore this report was edited mainly to provide basic knowledge correlated with the storage phosphors and related phenomena rather than to report simply on the experimental results. (J.P.N.)

  11. 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)

  12. 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.

  13. 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

  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. Naturally occurring and radiation-induced tumors in SPF mice, and genetic influence in radiation leukemogenesis

    International Nuclear Information System (INIS)

    Kasuga, T.

    1979-01-01

    The data obtained so far in this study point to a strong genetic influence not only on the types and incidence of naturally occurring and radiation-induced tumors but also on radiation leukemogenesis. (Auth.)

  16. Radiation induced mutations in Phaseolus vulgaris L

    International Nuclear Information System (INIS)

    Al-Rubeai, M.A.F.

    1982-01-01

    A selection of various macro- and micro-mutations was undertaken in the M2 generation of Phaseolus vulgaris cultivars after seed exposure to acute gamma radiation doses of 2.5, 5, 7, 10 and 15 Kr. The chlorophyll mutation was positively correlated with dose. Nevertheless, the highest frequency was at 7 Kr. Several interesting morphological mutants were observed. There were dwarf, stiff stem, shiny small leaf, narrow leaf and green giant mutants. Two selected micromutants were superior in seed yield capacity to their parents. The high yields were related to the high number of pods per plant. In 'The Prince' (seed color: red with beige marbling) several mutants with seeds of black color marbled with beige were selected. These seeds gave M3 segregants exhibiting a range of seed colors including white. Many of these M3 plants were short, early flowering and highly sterile. The work demonstrated that the pigmentation character can readily be changed, and confirmed that the variability induced by radiation can be exploited to obtain desirable mutations. (Author) [pt

  17. 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.

  18. 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)

  19. 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

  20. 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

  1. Radiation application on development of marker genes for genetic manipulation

    International Nuclear Information System (INIS)

    Lee, Young Il

    1997-04-01

    This state of art report was dealt with the recent progress of genetic engineering techniques and prospect of gene manipulation. Especially the selection of new genetic marker genes such as variants to environmental stress, pest or insect resistance, herbicide resistance and nutritional requirement was reviewed by using plant cell and tissue culture combined with radiation mutation induction. Biotechnology has taken us from the era hybrid plants to the era of transgenic plants. Although there are still many problems to solve in transformation method and the regeneration of transformed cell and tissue. Genetic marker genes are very important material to improve the technique of genetic manipulation. Most of the genes have been developed by radiation. (author). 180 refs., 6 tabs

  2. Signal Network Analysis of Plant Genes Responding to Ionizing Radiation

    International Nuclear Information System (INIS)

    Kim, Dong Sub; Kim, Jinbaek; Kim, Sang Hoon

    2012-12-01

    In this project, we irradiated Arabidopsis plants with various doses of gamma-rays at the vegetative and reproductive stages to assess their radiation sensitivity. After the gene expression profiles and an analysis of the antioxidant response, we selected several Arabidopsis genes for uses of 'Radio marker genes (RMG)' and conducted over-expression and knock-down experiments to confirm the radio sensitivity. Based on these results, we applied two patents for the detection of two RMG (At3g28210 and At4g37990) and development of transgenic plants. Also, we developed a Genechip for use of high-throughput screening of Arabidopsis genes responding only to ionizing radiation and identified RMG to detect radiation leaks. Based on these results, we applied two patents associated with the use of Genechip for different types of radiation and different growth stages. Also, we conducted co-expression network study of specific expressed probes against gamma-ray stress and identified expressed patterns of duplicated genes formed by whole/500kb segmental genome duplication

  3. Inducement of radionuclides targeting therapy by gene transfection

    International Nuclear Information System (INIS)

    Luo Quanyong

    2001-01-01

    The author presents an overview of gene transfection methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to intake radiolabeled antibody and peptide targeting and thus increase their therapeutic effect in radiotherapy. The current research include inducement of radioimmunotherapy through CEA gene transfection, inducement of iodine-131 therapy by sodium iodide symporter gene transfection and inducement of MIBG therapy by noradrenaline transporter gene transfection. These studies raise the prospect that gene-therapy techniques could be used to enable the treatment of a wide range of tumors with radiopharmaceuticals of established clinical acceptability

  4. The sensitivity of active and inactive chromatin to ionizing radiation-induced DNA strand breakage

    International Nuclear Information System (INIS)

    Chiu, S.-M.; Oleinick, N.L.

    1982-01-01

    The sensitivity of DNA in actively transcribing and inactive states has been compared with regard to γ-radiation-induced single-strand break (SSB) induction. The results indicate that chromatin organization is important in the determination of the sensitivity of cellular DNA toward γ-radiation: Not only the yield but also the rate of repair of SSB is greater in the actively transcribing genes than in the total nuclear DNA. (author)

  5. Shock wave induced sonoporation and gene transfer

    Science.gov (United States)

    Miller, Douglas L.

    2003-10-01

    During shockwave (SW) treatment, cavitation activity can be applied for cell killing. A bonus is that some surviving cells appear to be briefly permeabilized, or sonoporated, allowing them to take up large molecules including DNA. In vitro research has indicated that as the number of SW increased, survival declined exponentially but the number of sonoporated cells increased to better than 50% of survivors for 1000 SW. In vivo tests have demonstrated SW-induced tumor ablation could indeed be accompanied by the transfection of marker plasmids into mouse B16 melanoma tumors in vivo. With intratumor injection of plasmid DNA and air bubbles, significant results were obtained for only 400 SW. In a trial of cancer therapy, the effects of 500 SW combined with interleukin-12 immuno-gene therapy was observed on the progression of two mouse tumors, B16 melanoma and RENCA renal carcinoma. The combination of SW and IL-12 plasmid injection provided a statistically significant inhibition of tumor growth relative to SW alone for both tumor models, demonstrating feasibility for this treatment method. In the future, the development of intravenous gene delivery and improved transfection, together with image-guided ultrasound treatment, should lead to the clinical application of ultrasound enhanced gene therapy. [Work supported by NIH Grant No. EB002782.

  6. The role of radiation types and dose in induced genomic instability

    International Nuclear Information System (INIS)

    Kadhim Munira, A.

    2007-01-01

    Complete text of publication follows. Genomic Instability (GI) is defined as long-term alterations induced by low-dose exposure to a variety of genotoxic agents in mammalian cells that act to increase the 'apparent' spontaneous mutation frequency.GI is a hallmark of tumorigenic progression and is observed in the progeny of irradiated and bystander cells as the delayed and stochastic appearance of de novo chromosomal aberrations, gene mutations and delayed lethal mutations both in vitro and in vivo. It occurs at a frequency several orders of magnitude greater than would be expected for mutation in a single gene, implying that GI is a multigenic phenomenon. The expression of GI can be influenced by genotype, cell type and radiation quality; however the underlying mechanisms are not fully understood. While several studies have demonstrated GI induction by high and low LET radiation, our work on human and mouse primary cell systems has shown significant differences in the capacity to induce GI and the spectrum of alterations depending on LET. These differences might be attributed to differences in radiation track structure, radiation dose and radiation exposure regime (distribution of hit and un hit cells). In this presentation I shall review the role of radiation quality; describe the possible mechanisms underlining the observed differences between radiation type and present results of experiments demonstrating that the dose of low LET radiation might be the most significant factor in determining the role of radiation type in the induction of GI.

  7. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    OpenAIRE

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components...

  8. 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

  9. 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 ...

  10. 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 ...

  11. 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.

  12. Ionizing and ultraviolet radiation enhances the efficiency of DNA mediated gene transfer in vitro

    International Nuclear Information System (INIS)

    Perez, C.F.

    1984-08-01

    The enhancement effects of ionizing and non-ionizing radiation on the efficiency of DNA mediated gene transfer were studied. Confluent Rat-2 cells were transfected with purified SV40 viral DNA, irradiated with either X-rays or ultraviolet, trypsinized, plated, and assayed for the formation of foci on Rat-2 monolayers. Both ionizing and ultraviolet radiation enhanced the frequency of A-gene transformants/survivor compared to unirradiated transfected cells. These enhancements were non-linear and dose dependent. A recombinant plasmid, pOT-TK5, was constructed that contained the SV40 virus A-gene and the Herpes Simplex virus (HSV) thymidine kinase (TK) gene. Confluent Rat-2 cells transfected with pOT-TK5 DNA and then immediately irradiated with either X-rays or 330 MeV/amu argon particles at the Berkeley Bevalac showed a higher frequency of HAT + colonies/survivor than unirradiated transfected cells. Rat-2 cells transfected with the plasmid, pTK2, containing only the HSV TK-gene were enhanced for TK-transformation by both X-rays and ultraviolet radiation. The results demonstrate that radiation enhancement of the efficiency of DNA mediated gene transfer is not explained by increased nuclear uptake of the transfected DNA. Radiation increases the competence of the transfected cell population for genetic transformation. Three models for this increased competence are presented. The targeted integration model, the inducible recombination model, the partition model, and the utilization of DNA mediated gene transfer for DNA repair studies are discussed. 465 references

  13. Ionizing and ultraviolet radiation enhances the efficiency of DNA mediated gene transfer in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Perez, C.F.

    1984-08-01

    The enhancement effects of ionizing and non-ionizing radiation on the efficiency of DNA mediated gene transfer were studied. Confluent Rat-2 cells were transfected with purified SV40 viral DNA, irradiated with either X-rays or ultraviolet, trypsinized, plated, and assayed for the formation of foci on Rat-2 monolayers. Both ionizing and ultraviolet radiation enhanced the frequency of A-gene transformants/survivor compared to unirradiated transfected cells. These enhancements were non-linear and dose dependent. A recombinant plasmid, pOT-TK5, was constructed that contained the SV40 virus A-gene and the Herpes Simplex virus (HSV) thymidine kinase (TK) gene. Confluent Rat-2 cells transfected with pOT-TK5 DNA and then immediately irradiated with either X-rays or 330 MeV/amu argon particles at the Berkeley Bevalac showed a higher frequency of HAT/sup +/ colonies/survivor than unirradiated transfected cells. Rat-2 cells transfected with the plasmid, pTK2, containing only the HSV TK-gene were enhanced for TK-transformation by both X-rays and ultraviolet radiation. The results demonstrate that radiation enhancement of the efficiency of DNA mediated gene transfer is not explained by increased nuclear uptake of the transfected DNA. Radiation increases the competence of the transfected cell population for genetic transformation. Three models for this increased competence are presented. The targeted integration model, the inducible recombination model, the partition model, and the utilization of DNA mediated gene transfer for DNA repair studies are discussed. 465 references.

  14. 5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-Induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis

    Science.gov (United States)

    2012-07-22

    modulate cell cycle progression and apoptosis. INTRODUCTION Because of the increasing threat posed by nuclear weapons [1], there is a pressing need for both...Detection System ( Bio -Rad Laboratories, Hercules CA) on 96-well microtiter plates with optical caps. Reactions were performed in a total volume of 50 µL... antigen -induced arthritis by dehydroepiandrosterone (DHEA). Inflamm Res 2004;53:189–98. 56. Auci D, Nicoletti F, Mangano K et al. Anti-inflammatory and

  15. 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)

  16. 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)

  17. 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

  18. 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)

  19. 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.

  20. Effect of genes controlling radiation sensitivity on chemical mutagenesis in yeast

    International Nuclear Information System (INIS)

    Prakash, L.

    1975-01-01

    Ultraviolet radiation, x radiation, nitrogen mustard, methyl methanesulfonate, and dimethyl sulfate were found to revert all the tester strains with the same efficiency or without any dependence on simple types of base-pair changes, and it was concluded that these mutagens were nonspecific in the types of base-pair changes produced. The cycl-131 tester was used in studies designed to determine the genetic control of mutation induction using a variety of mutagens. The rad 6 and rad g genes greatly reduce the frequency of chemically induced reversion of cycl-131

  1. Impact of Solar Radiation on Gene Expression in Bacteria

    Directory of Open Access Journals (Sweden)

    Sabine Matallana-Surget

    2013-07-01

    Full Text Available Microorganisms often regulate their gene expression at the level of transcription and/or translation in response to solar radiation. In this review, we present the use of both transcriptomics and proteomics to advance knowledge in the field of bacterial response to damaging radiation. Those studies pertain to diverse application areas such as fundamental microbiology, water treatment, microbial ecology and astrobiology. Even though it has been demonstrated that mRNA abundance is not always consistent with the protein regulation, we present here an exhaustive review on how bacteria regulate their gene expression at both transcription and translation levels to enable biomarkers identification and comparison of gene regulation from one bacterial species to another.

  2. The genetics of radiation-induced and sporadic osteosarcoma: a unifying theory?

    International Nuclear Information System (INIS)

    Rosemann, Michael; Kuosaite, Virginija; Nathrath, Michaela; Atkinson, Michael J.

    2002-01-01

    Cancer is a disease of the genome, with the neoplastic phenotype being passed from one cell generation to the other. Radiation-induced cancer has often been considered to represent a unique entity amongst neoplasia, with the energy deposition being held responsible for both direct (gene mutations) and indirect (bystander effects, induced instability etc) alterations to the cellular genome. However, radiogenic tumours in man and experimental animals appear to be physiologically and genetically indistinguishable from their sporadic counterparts, suggesting that the aetiologies of these two tumour types are in fact closely related. We have conducted a general screen of the genetic alterations in radiation-induced mouse osteosarcoma, a tumour that is histopathologically indistinguishable from human sporadic osteosarcoma. Comparison of the two tumour types indicates the existence of a common set of genetic changes, providing additional evidence to support the concept that the molecular pathology of radiation-induced malignancy is no different to that of sporadic cancers. (author)

  3. Radiation-induced adaptive response and intracellular signal transduction pathways

    International Nuclear Information System (INIS)

    Tachibana, Akira

    2009-01-01

    As an essential biological function, cells can sense the radiation even at low dose and respond to it, and which is one of bases of the radiation-induced adaptive response (AR) where effects caused by high dose radiation are reduced by prior exposure to low dose radiation (LDR). Here described are studies of AR in well established m5S cells on the intracellular signal transduction that involves sensing of LDR and transmitting of its signal within the cell network. The first signal for AR yielded by LDR on the cell membrane is exactly unknown though hydrogen peroxide and phorbol ester (PMA) can reportedly cause AR. As PMA activates protein kinase C (PKC) and its inhibitors suppress AR, participation of PKC in AR has been suggested and supported by studies showing PKCα activation by LDR. In addition, p38 mitogen-activated protein kinase (MAPK) is shown to participate in AR by those facts that the enzyme is activated by LDR, a p38 MAPK inhibitor suppresses AR, and PKC inhibitors suppress the enzyme activation, which also suggesting that the signaling from PKC to p38 MAPK can become operative by LDR. However, the possible reverse signaling is also suggested, and thus the activation of positive feedback mechanism is postulated in PKC/p38 MAPK/phospholipase δ1/ PKC pathway. Cells introduced with siRNA against Prkca gene (coding PKCs) produce reduced amount of the enzyme, particularly, of PKCα. In those cells, AR by 5 Gy X-ray is not observed and thereby PKCα is involved in AR. The signaling in AR is only partly elucidated at present as above, and more detailed studies including identification of more PKC subtypes and signaling to DNA repair system are considered necessary. (K.T.)

  4. 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)

  5. 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)

  6. Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans

    International Nuclear Information System (INIS)

    Fujimori, Akira; Yaoi, Takeshi; Ogi, Hiroshi; Wang Bing; Suetomi, Katsutoshi; Sekine, Emiko; Yu Dong; Kato, Takamitsu; Takahashi, Sentaro; Okayasu, Ryuichi; Itoh, Kyoko; Fushiki, Shinji

    2008-01-01

    Microcephaly is a malformation associated with in utero exposed atomic bomb survivors and can be induced in mice by fetal exposure to ionizing radiation (IR). The pathogenesis of IR-induced microcephaly, however, has not been fully understood. Our analyses of high-coverage expression profiling (HiCEP) demonstrated that the abnormal spindle-like microcephaly associated gene (ASPM) was down-regulated in irradiated human diploid fibroblasts. ASPM was recently reported as the causative gene for MCPH-5, the most common type of congenital microcephaly in humans. Here, we show that the expression of the Aspm gene was significantly reduced by IR in various human and murine cells. Additionally, Aspm was found downregulated in the irradiated fetal mouse brain, particularly in the ventricular zones. A similar suppression was observed in the irradiated neurosphere cultures. This is the first report suggesting that the suppression of Aspm by IR could be the initial molecular target leading to the future microcephaly formation

  7. 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

  8. 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)

  9. 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

  10. Gene expression profiles in cervical cancer with radiation therapy alone and chemo-radiation therapy

    International Nuclear Information System (INIS)

    Lee, Kyu Chan; Kim, Joo Young; Hwang, You Jin; Kim, Meyoung Kon; Choi, Myung Sun; Kim, Chul Young

    2003-01-01

    To analyze the gene expression profiles of uterine cervical cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a cDNA microarray. Sixteen patients, 8 with squamous cell carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated with concurrent chemo-radiation, were included in the study. Before the starting of the treatment, tumor biopsies were carried out, and the second time biopsies were performed after a radiation dose of 16.2-27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were performed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during chemoradiation therapy. The 33P-labeled cDNAs were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the cDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel. The data were normalized by the Z transformation, and the comparisons were performed on the Z-ratio values calculated. The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved in cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, including G protein coupled receptor kinase 6, were decreased with the Z-ratio values of below -2.0. After the radiation therapy, most of the genes, with a previously increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were

  11. Radiation-induced adaptive response in fetal mice: a micro-array study

    International Nuclear Information System (INIS)

    Vares, G.; Bing, Wang; Mitsuru, Nenoi; Tetsuo, Nakajima; Kaoru, Tanaka; Isamu, Hayata

    2006-01-01

    Exposure of sublethal doses of ionizing radiation can induce protective mechanisms against a subsequent higher dose irradiation. This phenomenon called radio-adaptation (or adaptive response - AR), has been described in a wide range of biological models. In a series of studies, we demonstrated the existence of a radiation-induced AR in mice during late organogenesis. For better understanding of molecular mechanisms underlying AR in our model, we performed a global analysis of transcriptome regulations in cells collected from whole mouse fetuses. Using cDNA micro-arrays, we studied gene expression in these cells after in utero priming exposure to irradiation. Several combinations of radiation dose and dose-rate were applied to induce or not an AR in our system. Gene regulation was observed after exposure to priming radiation in each condition. Student's t-test was performed in order to identify genes whose expression modulation was specifically different in AR-inducing an( non-AR-inducing conditions. Genes were ranked according to their ability in discriminating AR-specific modulations. Since AR genes were implicated in variety of functions and cellular processes, we applied a functional classification algorithm, which clustered genes in a limited number of functionally related group: We established that AR genes are significantly enriched for specific keywords. Our results show a significant modulation of genes implicated in signal transduction pathways. No AR-specific alteration of DNA repair could be observed. Nevertheless, it is likely that modulation of DNA repair activity results, at least partly, from post-transcriptional regulation. One major hypothesis is that de-regulations of signal transduction pathways and apoptosis may be responsible for AR phenotype. In previous work, we demonstrated that radiation-induced AR in mice during organogenesis is related to Trp53 gene status and to the occurrence of radiation-induced apoptosis. Other work proposed that p53

  12. DNA repair gene polymorphisms in relation to chromosome aberration frequencies in retired radiation workers

    International Nuclear Information System (INIS)

    Wilding, Craig S.; Relton, Caroline L.; Rees, Gwen S.; Tarone, Robert E.; Whitehouse, Caroline A.; Tawn, E. Janet

    2005-01-01

    Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC] n microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC] n microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873mSv. When the interaction between radiation dose and each DNA repair gene polymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele >=20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations

  13. Stochastic biological response to radiation. Comprehensive analysis of gene expression

    International Nuclear Information System (INIS)

    Inoue, Tohru; Hirabayashi, Yoko

    2012-01-01

    Authors explain that the radiation effect on biological system is stochastic along the law of physics, differing from chemical effect, using instances of Cs-137 gamma-ray (GR) and benzene (BZ) exposures to mice and of resultant comprehensive analyses of gene expression. Single GR irradiation is done with Gamma Cell 40 (CSR) to C57BL/6 or C3H/He mouse at 0, 0.6 and 3 Gy. BE is given orally at 150 mg/kg/day for 5 days x 2 weeks. Bone marrow cells are sampled 1 month after the exposure. Comprehensive gene expression is analyzed by Gene Chip Mouse Genome 430 2.0 Array (Affymetrix) and data are processed by programs like case normalization, statistics, network generation, functional analysis etc. GR irradiation brings about changes of gene expression, which are classifiable in common genes variable commonly on the dose change and stochastic genes variable stochastically within each dose: e.g., with Welch-t-test, significant differences are between 0/3 Gy (dose-specific difference, 455 pbs (probe set), in stochastic 2113 pbs), 0/0.6 Gy (267 in 1284 pbs) and 0.6/3 Gy (532 pbs); and with one-way analysis of variation (ANOVA) and hierarchial/dendrographic analyses, 520 pbs are shown to involve the dose-dependent 226 and dose-specific 294 pbs. It is also shown that at 3 Gy, expression of common genes are rather suppressed, including those related to the proliferation/apoptosis of B/T cells, and of stochastic genes, related to cell division/signaling. Ven diagram of the common genes of above 520 pbs, stochastic 2113 pbs at 3 Gy and 1284 pbs at 0.6 Gy shows the overlapping genes 29, 2 and 4, respectively, indicating only 35 pbs are overlapping in total. Network analysis of changes by GR shows the rather high expression of genes around hub of cAMP response element binding protein (CREB) at 0.6 Gy, and rather variable expression around CREB hub/suppressed expression of kinesin hub at 3 Gy; in the network by BZ exposure, unchanged or low expression around p53 hub and suppression

  14. Investigation of epigenetic gene regulation in Arabidopsis modulated by gamma radiation

    International Nuclear Information System (INIS)

    Woo, Hye Ryun; Kim, Jae Sung; Lee, Myung Jin; Lee, Dong Joon; Kim, Young Min; Jung, Joon Yong; Han, Wan Keun; Kang, Soo Jin

    2011-12-01

    To investigate epigenetic gene regulation in Arabidopsis modulated by gamma radiation, we examined the changes in DNA methylation and histone modification after gamma radiation and investigated the effects of gamma radiation on epigenetic information and gene expression. We have selected 14 genes with changes in DNA methylation by gamma radiation, analyzed the changes of histone modification in the selected genes to reveal the relationship between DNA methylation and histone modification by gamma radiation. We have also analyzed the effects of gamma radiation on gene expression to investigate the relationship between epigenetic information and gene expression by gamma radiation. The results will be useful to reveal the effects of gamma radiation on DNA methylation, histone modification and gene expression. We anticipate that the information generated in this proposal will help to find out the mechanism underlying the changes in epigenetic information by gamma radiation

  15. Bystander Effect Induced by UV Radiation; why should we be interested? 

    Directory of Open Access Journals (Sweden)

    Maria Widel

    2012-11-01

    Full Text Available The bystander effect, whose essence is an interaction of cells directly subjected to radiation with adjacent non-subjected cells, via molecular signals, is an important component of ionizing radiation action. However, knowledge of the bystander effect in the case of ultraviolet (UV radiation is quite limited. Reactive oxygen and nitrogen species generated by UV in exposed cells induce bystander effects in non-exposed cells, such as reduction in clonogenic cell survival and delayed cell death, oxidative DNA damage and gene mutations, induction of micronuclei, lipid peroxidation and apoptosis. Although the bystander effect after UV radiation has been recognized in cell culture systems, its occurrence in vivo has not been studied. However, solar UV radiation, which is the main source of UV in the environment, may induce in human dermal tissue an inflammatory response and immune suppression, events which can be considered as bystander effects of UV radiation. The oxidative damage to DNA, genomic instability and the inflammatory response may lead to carcinogenesis. UV radiation is considered one of the important etiologic factors for skin cancers, basal- and squamous-cell carcinomas and malignant melanoma. Based on the mechanisms of actions it seems that the UV-induced bystander effect can have some impact on skin damage (carcinogenesis?, and probably on cells of other tissues. The paper reviews the existing data about the UV-induced bystander effect and discusses a possible implication of this phenomenon for health risk. 

  16. Candidate gene biodosimeters of mice and human exposure to ionizing radiation by quantitative reverse transcription polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Hamed Rezaeejam

    2015-01-01

    Full Text Available Understanding of cellular responses to ionizing radiation (IR is essential for the development of predictive markers useful for assessing human exposure. Biological markers of exposure to IR in human populations are of great interest for assessing normal tissue injury in radiation oncology and for biodosimetry in nuclear incidents and accidental radiation exposures. Traditional radiation exposure biomarkers based on cytogenetic assays (biodosimetry, are time-consuming and do not provide results fast enough and requires highly trained personnel for scoring. Hence, the development of rapid biodosimetry methods is one of the highest priorities. Exposure of cells to IR activates multiple signal transduction pathways, which result in complex alterations in gene-expression. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR has become the benchmark for the detection and quantification of RNA targets and is being utilized increasingly in monitoring the specific genes with more accurately and sensitively. This review evaluates the RT-qPCR as a biodosimetry method and we investigated the papers from 2000 up to now, which identified the genes-expression related the DNA repair, cell cycle checkpoint, and apoptosis induced by ionization radiation in peripheral blood and determined as biodosimeters. In conclusion, it could be say that RT-qPCR technique for determining the specific genes as biodosimeters could be a fully quantitative reliable and sensitive method. Furthermore, the results of the current review will help the researchers to recognize the most expressed genes induced by ionization radiation.

  17. Radiation induced cancer: risk assessment and prevention

    International Nuclear Information System (INIS)

    Shore, R.E.

    1984-01-01

    A number of factors have to be considered in defining the cancer risk from ionizing radiation. These include the radiation sensitivity of the target tissue(s), the temporal pattern of risk, the shape of the dose-incidence curve, the effects of low dose rates, host susceptibility factors, and synergism with other environmental exposures. For the population as a whole the largest sources of radiation exposure are natural background radiation and medical/dental radiation. Radiation exposures in the medical field make up the largest volume of occupational exposures as well. Although new technologies offer opportunities to lower exposures, worker training, careful exposure monitoring with remedial feedback, and monitoring to prevent unnecessary radiodiagnostic procedures may be even more important means of reducing radiation exposure. Screening of irradiated populations can serve a useful preventive function, but only for those who have received very high doses

  18. Function and regulation of ATF 3 expression induced by ionizing radiation

    International Nuclear Information System (INIS)

    Fan, Feiyue; Wang, Yong; Du, Liqin; Zhan, Qimin

    2008-01-01

    Full text: Ionizing radiation results in a series of damages of mammalian cells as a genotoxic stress. There are some genes expressed after cells damaged, in which ATF 3, a member of ATF/CREB family of transcription factors, is one of them. In this report, we demonstrate that ATF 3 can be induced by ionizing radiation. The induction of ATF 3 protein requires normal status of p53 function in cells. There are some quantitative relationships between ATF 3 induction and dosages of radiation or time post-irradiation. In another word, ATF 3 expression induced by ionizing radiation present dose- and time-dependent. The regulation of ATF 3 expression refers to program of promoter and transcription. Radiation induces ATF 3 expression by activating the promoter and RNA transcription. In method of tetracycline-inducible system (tet-off), we have found that over-expression of ATF 3 protein brings caspase/PARP proteins into cleavage, which induces cell programmed death, and suppresses cell growth. Meanwhile, it was found that ATF 3 expression could slow down progression of cell from G 1 to S phase. It indicates ATF 3 protein might play a negative role in the control of cell cycle progression. It is very excited that expression of ATF 3 protein did not only suppress cell growth, but also demonstrated protecting effect of cell growth suppression resulting from ionizing radiation. It is suggested that ATF 3 protein might take part in the damage repair process of cells. (author)

  19. 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

  20. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    Energy Technology Data Exchange (ETDEWEB)

    Makarova, Kira S.; Omelchenko, Marina V.; Gaidamakova, Elena K.; Matrosova, Vera Y.; Vasilenko, Alexander; Zhai, Min; Lapidus, Alla; Copeland, Alex; Kim, Edwin; Land, Miriam; Mavrommatis, Konstantinos; Pitluck, Samuel; Richardson, Paul M.; Detter, Chris; Brettin, Thomas; Saunders, Elizabeth; Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.; Wolf, Yuri I.; Sorokin, Alexander; Gerasimova, Anna V.; Gelfand, Mikhail S.; Fredrickson, James K.; Koonin, Eugene V.; Daly, Michael J.

    2007-07-24

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at itsoptimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  1. 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.

  2. 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

  3. Identification and Expression Profiling of Radiation-sensitive Genes Using Plant Model System, Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Kim, Dong-Sub; Kang, Si-Yong; Lee, Geung-Joo; Kim, Jin-Baek

    2008-06-01

    The purpose of this study is to characterize genes specifically expressed in response to ionizing energy (gamma-rays) of acute irradiation and elucidate signalling mechanisms via functional analysis of isolated genes in Arabidopsis thaliana. Recent improvements in DNA microarray technologies and bioinformatics have made it possible to look for common features of ionizing radiation-responsive genes and their regulatory regions. It has produced massive quantities of gene expression and other functional genomics data, and its application will increase in plant genomics. In this study, we used oligonucleotide microarrays to detect the Arabidopsis genes expressed differentially by a gamma-irradiation during the vegetative (VT, 21 DAG) and reproductive (RT, 28 DAG) stages. Wild-type (Ler) Arabidopsis was irradiated with gamma-rays with 100 and 800 Gy doses. Among the 21,500 genes represented in the Agilent chip, approximately 13,500 ( ∼ 61.4 %) responsive genes to ν -irradiation were expressed with signal intensity greater than 192 when compared to the combined control (non-irradiated vegetative and reproductive pool). Expression patterns of several radiation inducible genes were confirmed by RT-PCR and Northern blotting. Our microarray results may contribute to an overall understanding of the type and quantities of genes that are expressed by an acute gamma-irradiation. In addition, to investigate the oxidative damage caused by irradiation, RT-PCR analysis for the expression of antioxidant isoenzyme genes, and a Transmission Electron Microscope (TEM) observation for visualizing the H 2 O 2 scavenging activity in leaves were applied

  4. Identification and Expression Profiling of Radiation-sensitive Genes Using Plant Model System, Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong-Sub; Kang, Si-Yong; Lee, Geung-Joo; Kim, Jin-Baek

    2008-06-15

    The purpose of this study is to characterize genes specifically expressed in response to ionizing energy (gamma-rays) of acute irradiation and elucidate signalling mechanisms via functional analysis of isolated genes in Arabidopsis thaliana. Recent improvements in DNA microarray technologies and bioinformatics have made it possible to look for common features of ionizing radiation-responsive genes and their regulatory regions. It has produced massive quantities of gene expression and other functional genomics data, and its application will increase in plant genomics. In this study, we used oligonucleotide microarrays to detect the Arabidopsis genes expressed differentially by a gamma-irradiation during the vegetative (VT, 21 DAG) and reproductive (RT, 28 DAG) stages. Wild-type (Ler) Arabidopsis was irradiated with gamma-rays with 100 and 800 Gy doses. Among the 21,500 genes represented in the Agilent chip, approximately 13,500 ({sup {approx}}61.4 %) responsive genes to {nu} -irradiation were expressed with signal intensity greater than 192 when compared to the combined control (non-irradiated vegetative and reproductive pool). Expression patterns of several radiation inducible genes were confirmed by RT-PCR and Northern blotting. Our microarray results may contribute to an overall understanding of the type and quantities of genes that are expressed by an acute gamma-irradiation. In addition, to investigate the oxidative damage caused by irradiation, RT-PCR analysis for the expression of antioxidant isoenzyme genes, and a Transmission Electron Microscope (TEM) observation for visualizing the H{sub 2}O{sub 2} scavenging activity in leaves were applied.

  5. Bystander effects in UV-induced genomic instability: Antioxidants inhibit delayed mutagenesis induced by ultraviolet A and B radiation

    Directory of Open Access Journals (Sweden)

    Dahle Jostein

    2005-01-01

    Full Text Available Abstract Background Genomic instability is characteristic of many types of human cancer. Recently, we reported that ultraviolet radiation induced elevated mutation rates and chromosomal instability for many cell generations after ultraviolet irradiation. The increased mutation rates of unstable cells may allow them to accumulate aberrations that subsequently lead to cancer. Ultraviolet A radiation, which primarily acts by oxidative stress, and ultraviolet B radiation, which initially acts by absorption in DNA and direct damage to DNA, both produced genomically unstable cell clones. In this study, we have determined the effect of antioxidants on induction of delayed mutations by ultraviolet radiation. Delayed mutations are indicative of genomic instability. Methods Delayed mutations in the hypoxanthine phosphoribosyl transferase (hprt gene were detected by incubating the cells in medium selectively killing hprt mutants for 8 days after irradiation, followed by a 5 day period in normal medium before determining mutation frequencies. Results The UVB-induced delayed hprt mutations were strongly inhibited by the antioxidants catalase, reduced glutathione and superoxide dismutase, while only reduced glutathione had a significant effect on UVA-induced delayed mutations. Treatment with antioxidants had only minor effects on early mutation frequenies, except that reduced glutathione decreased the UVB-induced early mutation frequency by 24 %. Incubation with reduced glutathione was shown to significantly increase the intracellular amount of reduced glutathione. Conclusion The strong effects of these antioxidants indicate that genomic instability, which is induced by the fundamentally different ultraviolet A and ultraviolet B radiation, is mediated by reactive oxygen species, including hydrogen peroxide and downstream products. However, cells take up neither catalase nor SOD, while incubation with glutathione resulted in increased intracellular levels of

  6. Gene activation by induced DNA rearrangements

    International Nuclear Information System (INIS)

    Schnipper, L.E.; Chan, V.; Sedivy, J.; Jat, P.; Sharp, P.A.

    1989-01-01

    A murine cell line (EN/NIH) containing the retroviral vector ZIPNeoSV(x)1 that was modified by deletion of the enhancer elements in the viral long terminal repeats has been used as an assay system to detect induced DNA rearrangements that result in activation of a transcriptionally silent reporter gene encoded by the viral genome. The spontaneous frequency of G418 resistance is less than 10(-7), whereas exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the combination of UV irradiation plus TPA resulted in the emergence of drug resistant cell lines at a frequency of 5 per 10(6) and 67 per 10(6) cells, respectively. In several of the cell lines that were analyzed a low level of amplification of one of the two parental retroviral integrants was observed, whereas in others no alteration in the region of the viral genome was detected. To determine the effect of the SV40 large T antigen on induced DNA rearrangements, EN/NIH cells were transfected with a temperature sensitive (ts) mutant of SV40 T. Transfectants were maintained at the permissive temperature (33 degrees C) for varying periods of time (1-5 days) in order to vary SV40 T antigen exposure, after which they were shifted to 39.5 degrees C for selection in G418. The frequency of emergence of drug resistant cell clones increased with duration of exposure to large T antigen (9-52 per 10(6) cells over 1-5 days, respectively), and all cell lines analyzed demonstrated DNA rearrangements in the region of the neo gene. A novel 18-kilobase pair XbaI fragment was cloned from one cell line which revealed the presence of a 2.0-kilobase pair EcoRI segment containing an inverted duplication which hybridized to neo sequences. It is likely that the observed rearrangement was initiated by the specific binding of large T antigen to the SV40 origin of replication encoded within the viral genome

  7. Role of X-ray-inducible genes and proteins in adaptive survival responses

    International Nuclear Information System (INIS)

    Meyers, M.; Schea, R.A.; Petrowski, A.E.; Seabury, H.; McLaughlin, P.W.; Lee, I.; Lee, S.W.; Boothman, D.A.

    1992-01-01

    Certain X-ray-inducible genes and their corresponding protein products, appearing following low priming doses of ionizing radiation may subsequently give rise to an adaptive survival response, ultimately leading to increased radioresistance. Further, this adaptive radioresistance may be due to increased DNA repair (or misrepair) processes. Ultimately, the function of low-dose-induced cDNA clones within the cell is hoped to elucidate to follow the effects of specific gene turn-off on adaptive responses. Future research must determine the various functions of adaptive response gene products so that the beneficial or deleterious consequences of adaptive responses, which increases resistance to ionizing radiation, can be determined. (author). 19 refs., 1 fig

  8. 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)

  9. 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.

  10. A preliminary study on action mechanisms of surviving expression in cell apoptosis induced by high-LET radiation

    International Nuclear Information System (INIS)

    Jin Xiaodong; Li Qiang; Gong Li; Wu Qingfeng; Li Ping; Dai Zhongying; Liu Xinguo; Tao Jiajun

    2010-01-01

    It has been proven that over-expression of surviving in cancerous cell lines is related to the radioresistance of cells to high-LET radiation in previous work. In this study, action mechanisms of surviving gene in apoptosis induced by high-LET radiation were investigated. We found that inhibiting surviving by siRNA had no notable influence on Bcl-2 and Bax expressions induced by carbon ions. Surviving depressed cell apoptosis through the inhibition of the activities of caspase-3 and -9 possibly in cell apoptosis induced by high-LET radiation. (authors)

  11. Induced Compton scattering effects in radiation transport approximations

    International Nuclear Information System (INIS)

    Gibson, D.R. Jr.

    1982-01-01

    In this thesis the method of characteristics is used to solve radiation transport problems with induced Compton scattering effects included. The methods used to date have only addressed problems in which either induced Compton scattering is ignored, or problems in which linear scattering is ignored. Also, problems which include both induced Compton scattering and spatial effects have not been considered previously. The introduction of induced scattering into the radiation transport equation results in a quadratic nonlinearity. Methods are developed to solve problems in which both linear and nonlinear Compton scattering are important. Solutions to scattering problems are found for a variety of initial photon energy distributions

  12. Induced Compton-scattering effects in radiation-transport approximations

    International Nuclear Information System (INIS)

    Gibson, D.R. Jr.

    1982-02-01

    The method of characteristics is used to solve radiation transport problems with induced Compton scattering effects included. The methods used to date have only addressed problems in which either induced Compton scattering is ignored, or problems in which linear scattering is ignored. Also, problems which include both induced Compton scattering and spatial effects have not been considered previously. The introduction of induced scattering into the radiation transport equation results in a quadratic nonlinearity. Methods are developed to solve problems in which both linear and nonlinear Compton scattering are important. Solutions to scattering problems are found for a variety of initial photon energy distributions

  13. 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

  14. 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.

  15. The mRNA expression of XRCC repair genes in mice after γ-ray radiation

    International Nuclear Information System (INIS)

    Wang Qin; Yue Jingyin; Li Jin; Mu Chuanjie; Fan Feiyue

    2006-01-01

    Objective: To investigate the role of XRCC repair genes in radioresistance of IRM-2 inbred mice. Methods: Northern hybridization was used to measure mRNA expression of XRCC1 and XRCC5 genes in IRM-2 inbred mice. ICR/JCL and 615 after exposure to different doses of γ-ray radiation at different postirradiation time. Results: The levels of XRCC1 and XRCC5 mRNA expression in control IRM-2 mice were higher significantly than those in their control parental mice (P<0.01 and P<0.05). The mRNA expression of XRCC genes in ICR/JCL and 615 mice all increased to some extent after exposure 1, 2 and 4 Gy radiation. But the levels were significantly higher at 2h postirradiation (P<0.05) . The levels of XRCC mRNA expression in IRM-2 mice did not increase significnatly compared with the control mice after exposure 1 and 2 Gy radiation. But the levels of XRCC1 and XRCC5 mRNA expression increased markedly at 4Gy 1h postirradiation (P<0.05 and P<0.01). Conclusion: The basal levels of XRCC1 and XRCC5 mRNA expression in IRM-2 mice were high. The high level of XRCC5 mRNA expression was involved in the repair of DNA double strand breaks induced by higher dose radiation, which perhaps was one of radioresistance causes of IRM-2 mice. (authors)

  16. 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

  17. Low-dose radiation-induced endothelial cell retraction

    International Nuclear Information System (INIS)

    Kantak, S.S.; Onoda, J.M.; Diglio, C.A.; Harper Hospital, Detroit, MI

    1993-01-01

    The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema. (author)

  18. Skin aspergillosis induced in the region of radiation ulcer

    International Nuclear Information System (INIS)

    Niimura, Yumiko; Nakauchi, Yohichi; Ushijima, Tsugako

    1980-01-01

    A case of skin aspergillosis in the region of radiation ulcer which was caused by Aspergillus fumigatus was reported. The patient was a 51 year-old man. This fungal infection was probably induced by a local factor, that is, chronic radiation ulcer. Histological findings suggested that Aspergillus fumigatus which increased saprophytically at the beginning possessed parasitic nature gradually, invaded into connective tissues in the deep layer of true skin, and made radiation ulcer more intractable. (Tsunoda, M.)

  19. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    OpenAIRE

    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.

  20. Identification of human genes involved in cellular responses to ionizing radiation: molecular and cellular studies of gene encoding the p68 helicase in mammalian cells

    International Nuclear Information System (INIS)

    Menaa, F.

    2003-12-01

    Cells submitted to genotoxic factors -like IR- activate several and important mechanisms such as repair, cell cycle arrest or 'apoptosis' to maintain genetic integrity. So, the damaged cells will induce many and different genes. The human transcriptome analysis by 'SSH' method in a human breast carcinoma cell line MCF7 γ-irradiated versus not irradiated, allowed to identify about one hundred genes. Among of these genes, we have focused our study on a radio-induced gene encoding the p68 helicase. In the conditions of irradiation used, our results show that the kinetic and the regulation of this gene expression differs between the nature of radiations used. Indeed, in γ-irradiated mammalian cells, ATM, a protein kinase activated by DSB and IR, is required to induce quickly P68 gene via the important transcription factor p53 stabilized by IR. In the case of UVC-irradiated cells, the P68 gene induction is late and the intracellular signalling pathway that lead to this induction is independent from the p53 protein. Finally, we show that the p68 protein under-expression is responsible for an increased radiosensitivity of MCF7 cells. Consequently, we can postulate that the p68 protein is involved in cellular responses to radiations to reduce the increased radiosensitivity of cells exposed to γ-rays. (author)

  1. 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)

  2. 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)

  3. 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)

  4. HPRT gene locus mutation in peripheral blood lymphocytes induced by internal exposure to radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Jingyong, Zhao; Yongzhong, Xu; Tao, Zhao; Fengmei, Cui; Liuyi, Wang; Qinhua, Lao [Suzhou Univ., Suzhou (China). Radiation Medicine Department

    2001-07-01

    HPRT gene locus mutation in peripheral blood lymphocytes induced by internal exposure to radionuclides was performed and the relationships between mutation frequency and dose were studied. Rats were injected intravenously with radionuclides, the blood was sampled at different time after injection; HPRT gene locus mutation frequency (GMF) were examined by methods of multi-nucleus cell and Brdurd assay, working out the Dose-response function. GMF rose with the increase of dose and dose-rates and were clearly interrelated. The HPRT gene locus mutation is very sensitive to radiation and may be used as a biological dosimeter.

  5. Modulating factors in the expression of radiation-induced oncogenic transformation

    International Nuclear Information System (INIS)

    Hall, E.J.; Hei, T.K.

    1990-01-01

    Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing α-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene

  6. Smad, but not MAPK, pathway mediates the expression of type I collagen in radiation induced fibrosis

    International Nuclear Information System (INIS)

    Yano, Hiroyuki; Hamanaka, Ryoji; Nakamura, Miki; Sumiyoshi, Hideaki; Matsuo, Noritaka; Yoshioka, Hidekatsu

    2012-01-01

    Highlights: ► We examine how radiation affects the expression level and signal pathway of collagen. ► TGF-β1 mRNA is elevated earlier than those of collagen genes after irradiation. ► Smad pathway mediates the expression of collagen in radiation induced fibrosis. ► MAPK pathways are not affected in the expression of collagen after irradiation. -- Abstract: Radiation induced fibrosis occurs following a therapeutic or accidental radiation exposure in normal tissues. Tissue fibrosis is the excessive accumulation of collagen and other extracellular matrix components. This study investigated how ionizing radiation affects the expression level and signal pathway of type I collagen. Real time RT-RCR showed that both α1and α2 chain of type I collagen mRNA were elevated from 48 h after irradiation with 10 Gy in NIH3T3 cells. The relative luciferase activities of both genes and type I collagen marker were elevated at 72 h. TGF-β1 mRNA was elevated earlier than those of type I collagen genes. A Western blot analysis showed the elevation of Smad phosphorylation at 72 h. Conversely, treatment with TGF-β receptor inhibitor inhibited the mRNA and relative luciferase activity of type I collagen. The phosphorylation of Smad was repressed with the inhibitor, and the luciferase activity was cancelled using a mutant construct of Smad binding site of α2(I) collagen gene. However, the MAPK pathways, p38, ERK1/2 and JNK, were not affected with specific inhibitors or siRNA. The data showed that the Smad pathway mediated the expression of type I collagen in radiation induced fibrosis.

  7. Smad, but not MAPK, pathway mediates the expression of type I collagen in radiation induced fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Hiroyuki [Department of Matrix Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Division of Radioisotope Research, Department of Research Support, Research Promotion Project, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Hamanaka, Ryoji; Nakamura, Miki [Cell Biology, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Sumiyoshi, Hideaki; Matsuo, Noritaka [Department of Matrix Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Yoshioka, Hidekatsu, E-mail: hidey@oita-u.ac.jp [Department of Matrix Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer We examine how radiation affects the expression level and signal pathway of collagen. Black-Right-Pointing-Pointer TGF-{beta}1 mRNA is elevated earlier than those of collagen genes after irradiation. Black-Right-Pointing-Pointer Smad pathway mediates the expression of collagen in radiation induced fibrosis. Black-Right-Pointing-Pointer MAPK pathways are not affected in the expression of collagen after irradiation. -- Abstract: Radiation induced fibrosis occurs following a therapeutic or accidental radiation exposure in normal tissues. Tissue fibrosis is the excessive accumulation of collagen and other extracellular matrix components. This study investigated how ionizing radiation affects the expression level and signal pathway of type I collagen. Real time RT-RCR showed that both {alpha}1and {alpha}2 chain of type I collagen mRNA were elevated from 48 h after irradiation with 10 Gy in NIH3T3 cells. The relative luciferase activities of both genes and type I collagen marker were elevated at 72 h. TGF-{beta}1 mRNA was elevated earlier than those of type I collagen genes. A Western blot analysis showed the elevation of Smad phosphorylation at 72 h. Conversely, treatment with TGF-{beta} receptor inhibitor inhibited the mRNA and relative luciferase activity of type I collagen. The phosphorylation of Smad was repressed with the inhibitor, and the luciferase activity was cancelled using a mutant construct of Smad binding site of {alpha}2(I) collagen gene. However, the MAPK pathways, p38, ERK1/2 and JNK, were not affected with specific inhibitors or siRNA. The data showed that the Smad pathway mediated the expression of type I collagen in radiation induced fibrosis.

  8. Cytogenetic responses to ionizing radiation exposure of human fibroblasts with knocked-down expressions of various DNA damage signaling genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry; Wu, Honglu

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with up-regulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. Here, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yields of MN and/or CA formation were significantly increased by suppressed expression of some of the selected genes in DSB and other DNA repair pathways. Knocked-down expression of other genes showed significant impact on cell cycle progression, possibly because of severe impairment of DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

  9. Development of radiation-induced mutation techniques and functional genomics studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek [KAERI, Daejeon (Korea, Republic of); and others

    2012-01-15

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative{center_dot}structural{center_dot}functional genomics studies for useful traits.

  10. Radiation-induced mutation breeding of papaya

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Y. K. [Horticulture Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Kuala Lumpur (Malaysia)

    2009-05-15

    Irradiation-induced mutation breeding of papaya commenced at the Malaysian Agricultural Research and Development Institute (MARDI) in August, 2000. This research was initiated under a Coordinated Research Project (CRP - D23023) with assistance from the International Atomic Energy Agency (IAEA). In the preliminary dosimetry study, seeds from two local papaya varieties, Sekaki and Eksotika were irradiated, either as dry seeds or as pre-soaked seeds (soaked overnight in water and surface-dried) with radiation doses ranging from 0 to 300 Gy. 100 Gy dose was lethal for all wet presoaked seeds while dry seed did not show loss of viability, even at 300 Gy. From the growth data it was estimated that dose of 525 Gy reduced shoot elongation by 50%, and this dose was recommended for mass irradiation of dry seeds. For wet, pre-soaked seeds results indicated that 42.5 Gy was the optimal dose for mass irradiation. At this dose, both seeds germination and seedlings growth were reduced by 50%. In a massive irradiation experiment 2,000 Eksotika seeds were irradiated at 42.5 Gy (pre-soaked) and another 2,000 at 525 Gy (dry). In the M2 population, numerous physiological defects were observed, including stem splitting, leaf variegation and puckering, and crinkled dwarfs. In the M3 population, a wide variability was recorded for a number of traits. M3 seedlings derived from presoaked seeds irradiated a low 42.5 Gy dose presented a high number of plants that were shorter and more vigorous in leaf development compared to those irradiated at 525 Gy and to non-irradiated control seedlings. The distribution patterns of M3 progenies for nine quantitative field characters showed great variation, often exceeding the limits of the control population. There appears to be good prospects in improving Eksotika papaya especially in the development of dwarf trees with lower fruit bearing stature, higher total soluble solids in fruits and larger fruit size. Several M2 and M3 putative mutants also

  11. 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

  12. Radiation-induced coronary artery disease

    International Nuclear Information System (INIS)

    Dunsmore, L.D.; LoPonte, M.A.; Dunsmore, R.A.

    1986-01-01

    This report describes three patients who developed myocardial infarction at an untimely age, 4 to 12 years after radiation therapy for Hodgkin's disease. These cases lend credence to the cause and effect relation of such therapy to coronary artery disease

  13. Ferulic acid ameliorates radiation induced duodenal inflammation

    International Nuclear Information System (INIS)

    Das, Ujjal; Manna, Krishnendu; Sengupta, Aaveri; Biswas, Sushobhan; Chakrabarty, Arpita; Dey, Sanjit

    2016-01-01

    Ionizing radiation creates oxidative stress followed by inflammation through reactive oxygen species (ROS) and altering the status of redox sensitive enzymes. In the current study we aimed to evaluate the effect of ferulic acid (FA) on increasing doses of ionizing radiation mediated oxidative stress and inflammation using in vivo murine duodenum. To delineate the hypothesis we exposed mice with 2.5, 5 and 10 Gy gamma radiation doses in presence and absence of the (FA). FA was administered orally at a fixed dose of 50mg/ kg bw for 5 days before radiation exposure. Different techniques such as biochemical assays, immune blot, and microscopic analysis for histopathology, flow cytometry and scanning electron microscopy were employed to achieve the goal

  14. Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Furlong, Hayley; Mothersill, Carmel; Lyng, Fiona M.; Howe, Orla

    2013-01-01

    Highlights: ► Molecular mechanisms involved in the production of a radiation induced bystander effect are not well known. ► We investigate gene expression changes in apoptotic genes in both direct and bystander responses. ► We demonstrate initiation of the apoptotic cascade in a bystander response. ► Lower doses reveal a specific but differential response related to apoptosis compared to higher doses. - Abstract: It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05 Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5 Gy dose point and genes were not always expressed within 1 h but were sometimes expressed 24 h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05 Gy and 0.5 Gy at both time points therefore not

  15. Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Furlong, Hayley, E-mail: hayley.furlong@dit.ie [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Mothersill, Carmel [Medical Physics and Applied Radiation Sciences, Nuclear Research Building, 1280 Hamilton, Ontario L8S 4K1 (Canada); Lyng, Fiona M. [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Howe, Orla [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland)

    2013-01-15

    Highlights: ► Molecular mechanisms involved in the production of a radiation induced bystander effect are not well known. ► We investigate gene expression changes in apoptotic genes in both direct and bystander responses. ► We demonstrate initiation of the apoptotic cascade in a bystander response. ► Lower doses reveal a specific but differential response related to apoptosis compared to higher doses. - Abstract: It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05 Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5 Gy dose point and genes were not always expressed within 1 h but were sometimes expressed 24 h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05 Gy and 0.5 Gy at both time points therefore not

  16. Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

    International Nuclear Information System (INIS)

    Abderrahmani, Rym; Francois, Agnes; Buard, Valerie; Benderitter, Marc; Sabourin, Jean-Christophe; Crandall, David L.; Milliat, Fabien

    2009-01-01

    Purpose: To investigate effects of plasminogen activator inhibitor 1 (PAI-1) genetic deficiency and pharmacological PAI-1 inhibition with PAI-039 in a mouse model of radiation-induced enteropathy. Methods and Materials: Wild-type (Wt) and PAI-1 -/- knockout mice received a single dose of 19 Gy to an exteriorized localized intestinal segment. Sham and irradiated Wt mice were treated orally with 1 mg/g of PAI-039. Histological modifications were quantified using a radiation injury score. Moreover, intestinal gene expression was monitored by real-time PCR. Results: At 3 days after irradiation, PAI-039 abolished the radiation-induced increase in the plasma active form of PAI-1 and limited the radiation-induced gene expression of transforming growth factor β1 (TGF-β1), CTGF, PAI-1, and COL1A2. Moreover, PAI-039 conferred temporary protection against early lethality. PAI-039 treatment limited the radiation-induced increase of CTGF and PAI-1 at 2 weeks after irradiation but had no effect at 6 weeks. Radiation injuries were less severe in PAI-1 -/- mice than in Wt mice, and despite the beneficial effect, 3 days after irradiation, PAI-039 had no effects on microscopic radiation injuries compared to untreated Wt mice. Conclusions: A genetic deficiency of PAI-1 is associated with amelioration of late radiation enteropathy. Pharmacological inhibition of PAI-1 by PAI-039 positively impacts the early, acute phase increase in plasma PAI-1 and the associated radiation-induced gene expression of inflammatory/extracellular matrix proteins. Since PAI-039 has been shown to inhibit the active form of PAI-1, as opposed to the complete loss of PAI-1 in the knockout animals, these data suggest that a PAI-1 inhibitor could be beneficial in treating radiation-induced tissue injury in acute settings where PAI-1 is elevated.

  17. Long-term effects of ionizing radiation on gene expression in a zebrafish model.

    Directory of Open Access Journals (Sweden)

    Lahcen Jaafar

    Full Text Available Understanding how initial radiation injury translates into long-term effects is an important problem in radiation biology. Here, we define a set of changes in the transcription profile that are associated with the long-term response to radiation exposure. The study was performed in vivo using zebrafish, an established radiobiological model organism. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose or 1.0 Gy (moderate dose of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. As a basis for comparison, 16-week old adults were exposed at the same doses and analyzed after 4 hours. Statistical analysis was performed in a way to minimize the effects of multiple comparisons. The responses to these two treatment regimes differed greatly: 360 probe sets were associated primarily with the long-term response, whereas a different 2062 probe sets were associated primarily with the response when adults of the same age were irradiated 4 hours before exposure. Surprisingly, a ten-fold difference in radiation dose (0.1 versus 1.0 Gy had little effect. Analysis at the gene and pathway level indicated that the long-term response includes the induction of cytokine and inflammatory regulators and transcription and growth factors. The acute response includes the induction of p53 target genes and modulation of the hypoxia-induced transcription factor-C/EBP axis. Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue.

  18. γ-radiation induced tetracycline removal in an aqueous solution

    International Nuclear Information System (INIS)

    Zhou Fei; Guo Zhaobing; Zhang Chaozhi; Lin Mingyue; Wu Menglong; Zhao Yongfu

    2012-01-01

    Degradation effect of tetracycline (TC) by γ-radiation was investigated in an aqueous solution. The effects of initial concentrations of TC, pH values, combining with H 2 O 2 or CH 3 OH on degradation of TC were studied. Results showed that TC can be effectively degradated by γ-irradiation in an aqueous solution. Degradation of TC could be remarkably improved both in acid solution and alkaline solution, especially when pH value was 9.0. In addition, H 2 O 2 could gently promote degradation of TC induced by γ-radiation. While, CH 3 OH markedly restrained degradation of TC induced by γ-radiation. The degradation mechanism of TC was supposed by results of quantum chemical calculations and LC-MS. Results proved that degradation of TC induced by γ-radiation was mainly ascribed to · OH oxidation. (authors)

  19. 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

  20. 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.)

  1. Free radicals in wood induced by γ-radiation

    International Nuclear Information System (INIS)

    Xu Honglin; Zhang Wenhui

    1994-01-01

    The free radicals in wood induced by γ-radiation were studied by electron spin resonance. The fine structure of the ESR signal from sawdust samples irradiated could be resolved into various radicals. These free radicals have a very long lifetime. The major spectrum for the free radicals will exponentially increased along with the radiation dose according to Y 1-Exp(-α a D). The intensity of radiation radicals is dependent on tree species. The stronger the intensity of mechanic free radicals is, the stronger the intensity of radiation free radicals

  2. Non-targeted bystander effects induced by ionizing radiation

    International Nuclear Information System (INIS)

    Morgan, William F.; Sowa, Marianne B.

    2007-01-01

    Radiation-induced bystander effects refer to those responses occurring in cells that were not subject to energy deposition events following ionizing radiation. These bystander cells may have been neighbors of irradiated cells, or physically separated but subject to soluble secreted signals from irradiated cells. Bystander effects have been observed in vitro and in vivo and for various radiation qualities. In tribute to an old friend and colleague, Anthony V. Carrano, who would have said 'well what are the critical questions that should be addressed, and so what?', we review the evidence for non-targeted radiation-induced bystander effects with emphasis on prevailing questions in this rapidly developing research field, and the potential significance of bystander effects in evaluating the detrimental health effects of radiation exposure

  3. 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

  4. Radiations - induced disorders in ovarian function

    International Nuclear Information System (INIS)

    Saleh, S.; Roushdy, H.M.; Abdel-Aziz, M.T.; Eldenshary, A.E.; Abdel-Khalek, A.; Ramadan, L.A.

    1988-01-01

    The effect of whole body gamma radiation exposure (7.5 and 6.5 Gy) on the secretory activity and the structure of the ovaries was investigated. The parameters studied were serum levels of oestrogen, progesterone, Lh and FSH, beside histopathological studies of the ovaries of femaler rats. These were measured on the next day after radiation exposure and then after one two oestrus cycles. Whole body gamma - irradiation of females rats at two levels of exposure progressively decreased the level of oestrogen and progesterone while increased the level of LH and FSH as compared with the control. moreover, the changes in the ovaries were demonstrated in the histopathological investigation. Keywords: Radiation exposure - ovarian function - hormone radioimmunoassay - oestrogen - progesterone - LH - FSH

  5. Radiation-induced emesis in monkeys

    International Nuclear Information System (INIS)

    Mattsson, J.L.; Yochmowitz, M.G.

    1980-01-01

    To determine the emesis ED 50 for 60 Co radiation, 15 male rhesus monkeys were exposed to whole-body radiation doses ranging from 350 to 550 rad midline tissue dose. An up-and-down sequence of exposures was used. Step size between doses was 50 rad, and dose rate was 20 rad/min. There had been no access to food for 1 to 2 h. The ED 50 +- SE was found to be 446 +- 27 rad. To determine the effect of motion on emesis ED 50 , six more monkeys were exposed to 60 Co radiation as above, except that the chair in which they were seated was oscillated forward and backward 5 to 15 0 (pitch axis) at a variable rate not exceeding 0.3 Hz. Radioemesis ED 50 +- SE with motion was 258 +- 19 rad, a value significantly lower (P < 0.01) than for stationary monkeys

  6. Radiation-induced changes in carboxymethylated chitosan

    International Nuclear Information System (INIS)

    Huang Ling; Peng Jing; Zhai Maolin; Li Jiuqiang; Wei Genshuan

    2007-01-01

    This study focuses on the radiation effect of γ-ray on carboxymethylated chitosan (CM-chitosan) in solid state. The changes in molecular weight of CM-chitosan with absorbed dose were monitored by viscosity method. Experimental results indicated that random chain scissions took place under irradiation. Radiation chemical yield (G d ) of CM-chitosan in solid state with N 2 -saturated was 0.49, which showed CM-chitosan has high radiation stability. Biomaterials composed of CM-chitosan can be thought to sterilize with low absorbed dose. FTIR and UV spectra showed that main chain structures of CM-chitosan were retained, carbonyl/carboxyl groups were formed and partial amino groups were eliminated in high absorbed dose. XRD patterns identified that the degradation of CM-chitosan occurred mostly in amorphous region

  7. Radiation induced cancer risk, detriment and radiation protection

    International Nuclear Information System (INIS)

    Sinclair, W.K.

    1992-01-01

    Recommendations on radiation protection limits for workers and for the public depend mainly on the total health detriment estimated to be the result of low dose ionizing radiation exposure. This detriment includes the probability of a fatal cancer, an allowance for the morbidity due to non-fatal cancer and the probability of severe hereditary effects in succeeding generations. In a population of all ages, special effects on the fetus particularly the risk of mental retardation at defined gestational ages, should also be included. Among these components of detriment after low doses, the risk of fatal cancer is the largest and most important. The estimates of fatal cancer risk used by ICRP in the 1990 recommendations were derived almost exclusively from the study of the Japanese survivors of the atomic bombs of 1945. How good are these estimates? Uncertainties associated with them, apart from those due to limitations in epidemiological observation and dosimetry, are principally those due to projection forward in time and extrapolation from high dose and dose rate to low dose and dose rate, each of which could after the estimate by a factor of 2 or so. Recent estimates of risk of cancer derived directly from low dose studies are specific only within very broad ranges of risk. Nevertheless, such studies are important as confirmation or otherwise of the estimates derived from the atomic bomb survivors. Recent U.S. British and Russian studies are examined in this light. (author)

  8. Overexpression of matrix metalloproteinase-12 (MMP-12) correlates with radiation-induced lung fibrosis

    International Nuclear Information System (INIS)

    Jung, Myung Gu; Jeong, Ye Ji; Lee, Haejune; Lee, Sujae

    2014-01-01

    MMPs are classified into five subgroups: collagenases (MMP-1, MMP-8, MMP-13), gelatinases (MMP-2, MMP-9), stromelysins (MMP-3, MMP-10, MMP-11), as well as metalloelastase (MMP-12), the membrane-type MMPs (MMP14, MMP15), and other MMPS (e. g., MMP-19, and MMP20). MMP-12 (matrix metalloproteinase12), also known as macrophage metalloelastase, was first identified as an elastolytic metalloproteinase secreted by inflammatory macrophages 30 years ago. MMP-12 degrades extracellular matrix (ECM) components to facilitate tissue remodeling. It can degrade elastin and other substrates, such as type IV collagen, fibronectin, laminin, gelatin, vitronectin, entactin, heparin, and chondroitin sulfates. In the lung, MMP-12 is identified in alveolar macrophages of cigarette smokers as an elastolytic MMP. Inactivation of the MMP-12 gene in knockout mice demonstrates a critical role of MMP-12 in smoking-induced chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the effects of MMP-12 by radiation in lung, so we evaluate that MMP-12 expression pattern in normal lung tissue and cancer cell following radiation. Radiation induced lung injury most commonly occurs as a result of radiation therapy administered to treat cancer. The present study demonstrates that MMP-12 was highly increased in the lung damaged by radiation Thus, MMP-12 might be of potential relevance as a clinically diagnostic tool and sensitive biomarker for radiation induced lung injury and fibrosis

  9. Overexpression of matrix metalloproteinase-12 (MMP-12) correlates with radiation-induced lung fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Gu; Jeong, Ye Ji; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Sujae [Hanyang Univ., Seoul (Korea, Republic of)

    2014-05-15

    MMPs are classified into five subgroups: collagenases (MMP-1, MMP-8, MMP-13), gelatinases (MMP-2, MMP-9), stromelysins (MMP-3, MMP-10, MMP-11), as well as metalloelastase (MMP-12), the membrane-type MMPs (MMP14, MMP15), and other MMPS (e. g., MMP-19, and MMP20). MMP-12 (matrix metalloproteinase12), also known as macrophage metalloelastase, was first identified as an elastolytic metalloproteinase secreted by inflammatory macrophages 30 years ago. MMP-12 degrades extracellular matrix (ECM) components to facilitate tissue remodeling. It can degrade elastin and other substrates, such as type IV collagen, fibronectin, laminin, gelatin, vitronectin, entactin, heparin, and chondroitin sulfates. In the lung, MMP-12 is identified in alveolar macrophages of cigarette smokers as an elastolytic MMP. Inactivation of the MMP-12 gene in knockout mice demonstrates a critical role of MMP-12 in smoking-induced chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the effects of MMP-12 by radiation in lung, so we evaluate that MMP-12 expression pattern in normal lung tissue and cancer cell following radiation. Radiation induced lung injury most commonly occurs as a result of radiation therapy administered to treat cancer. The present study demonstrates that MMP-12 was highly increased in the lung damaged by radiation Thus, MMP-12 might be of potential relevance as a clinically diagnostic tool and sensitive biomarker for radiation induced lung injury and fibrosis.

  10. Assessment of Radiation Induced Therapeutic Effect and Cytotoxicity in Cancer Patients Based on Transcriptomic Profiling

    Directory of Open Access Journals (Sweden)

    Sajjad Karim

    2016-02-01

    Full Text Available Toxicity induced by radiation therapy is a curse for cancer patients undergoing treatment. It is imperative to understand and define an ideal condition where the positive effects notably outweigh the negative. We used a microarray meta-analysis approach to measure global gene-expression before and after radiation exposure. Bioinformatic tools were used for pathways, network, gene ontology and toxicity related studies. We found 429 differentially expressed genes at fold change >2 and p-value <0.05. The most significantly upregulated genes were synuclein alpha (SNCA, carbonic anhydrase I (CA1, X-linked Kx blood group (XK, glycophorin A and B (GYPA and GYPB, and hemogen (HEMGN, while downregulated ones were membrane-spanning 4-domains, subfamily A member 1 (MS4A1, immunoglobulin heavy constant mu (IGHM, chemokine (C-C motif receptor 7 (CCR7, BTB and CNC homology 1 transcription factor 2 (BACH2, and B-cell CLL/lymphoma 11B (BCL11B. Pathway analysis revealed calcium-induced T lymphocyte apoptosis and the role of nuclear factor of activated T-cells (NFAT in regulation of the immune response as the most inhibited pathways, while apoptosis signaling was significantly activated. Most of the normal biofunctions were significantly decreased while cell death and survival process were activated. Gene ontology enrichment analysis revealed the immune system process as the most overrepresented group under the biological process category. Toxicity function analysis identified liver, kidney and heart to be the most affected organs during and after radiation therapy. The identified biomarkers and alterations in molecular pathways induced by radiation therapy should be further investigated to reduce the cytotoxicity and development of fatigue.

  11. The use of recombinant DNA techniques to study radiation-induced damage, repair and genetic change in mammalian cells

    International Nuclear Information System (INIS)

    Thacker, J.

    1986-01-01

    A brief introduction is given to appropriate elements of recombinant DNA techniques and applications to problems in radiobiology are reviewed with illustrative detail. Examples are included of studies with both 254 nm ultraviolet light and ionizing radiation and the review progresses from the molecular analysis of DNA damage in vitro through to the nature of consequent cellular responses. The review is dealt with under the following headings: Molecular distribution of DNA damage, The use of DNA-mediated gene transfer to assess damage and repair, The DNA double strand break: use of restriction endonucleases to model radiation damage, Identification and cloning of DNA repair genes, Analysis of radiation-induced genetic change. (UK)

  12. Premature Senescence Induced by Ionizing Radiation Requires AKT Activity and Reactive Oxygen Species in Glioma

    International Nuclear Information System (INIS)

    Lee, Je Jung; Kim, Bong Cho; Yoo, Hee Jung; Lee, Jae Seon

    2010-01-01

    Loss of PTEN, a tumor suppressor gene has frequently observed in human gliomas, which conferred AKT activation and resistance to ionizing radiation (IR) and anti-cancer drugs. Recent reports have shown that AKT activation induces premature senescence through increase of oxygen consumption and inhibition of expression of ROS scavenging enzymes. In this study, we compared cellular response to IR in the PTEN-deficient U87, U251, U373 or PTEN-proficient LN18, LN428 glioma cells

  13. Gene expression analysis after low dose ionising radiation exposure of the developing organism

    International Nuclear Information System (INIS)

    Abderrafi Benotmane, M.

    2007-01-01

    Measuring gene expression using microarrays is relevant to many areas of biology and medicine, such as follow up of developmental stages and diseases onset, and treatment study. Since there can be tens of thousands of distinct probes on an array, each micro array experiment can accomplish the equivalent number of genetic tests in parallel. Arrays have therefore dramatically accelerated many types of investigations. For example, microarrays can be used to identify stress response genes by comparing gene expression in challenged versus normal cells. In the Molecular and Cellular Biology lab (MCB), the micro array experiments are performed within the Genomic Platform, fully equipped to analyse either the behaviour of bacteria during long space flight, the effect of low dose ionising radiation on the developing organism in mice, or the human individual radiation sensitivity. For the low dose effect, two main stages of development are of interest; 1) the gastrula stage at which ionizing radiation can induce several malformations. 2) the organogenesis. During brain development, epidemiological studies of the atomic bomb survivors of Hiroshima/Nagasaki showed increased risk of mental retardation in children of women exposed between weeks 8-15 of pregnancy or at a lower extend between weeks 15 to 25

  14. Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

    International Nuclear Information System (INIS)

    Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

    2017-01-01

    Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

  15. Overexpression of p53, MDM2 proteins in some atr radiation-induced skin ulcers

    International Nuclear Information System (INIS)

    Gu Qingyang; Gao Yabing; Wang Dewen; Cui Yufang; Zhao Po; Yang Zhixiang; Zhou Jie

    2000-01-01

    An animal model of radiation-induced skin ulcer was set up with 140 rats, which were locally irradiated with 35-55 Gy γ-rays. The pathological changes were observed for 1 year. Immunohistochemical studies were performed in 72 rat radiation skin ulcer specimens using anti-p53 and anti-MDM2 proteins polyclonal antibodies. The results showed that the positive rate for overexpression of p53 protein was 9.7%, and for that of MDM2 was 19.4%. The overexpression of p53 was mainly seen in the nuclei of activated squamous epithelial cells, and in fibroblasts, endotheliocytes in deeper part of the skin ulcers. The overexpression of MDM2 had the same localizations. It is suggested that the changes of p53 and MDM2, genes and proteins, may be related to the cancer transformation and poor healing of radiation-induced skin ulcers

  16. Significance of radiation-induced bystander effects in radiation therapy

    International Nuclear Information System (INIS)

    Suzuki, Masao

    2014-01-01

    Since 1994, a Phase I/II clinical study and radiotherapy have carried out using carbon-ion beams produced with the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences. Now we constructed the new treatment facility for the advanced carbon-ion therapy at HIMAC applying a 3D fast spot scanning system with pencil beams. In the field of fundamental biological studies for high-LET heavy ions, there are some reports regarding bystander effects after exposure to alpha particles derived from 238 Pu or He-ion microbeams. However, only limited sets of studies have examined bystander effects after exposure to different ion species heavier than helium, such as carbon ions. We have been investigating bystander cellular responses in both normal human and human tumor cells irradiated with the HIMAC carbon ions. Bystander cell-killing effect was observed in the cells harboring wild-type P53 gene, but not in the P53-mutated cells. Moreover, observed bystander effect was suppressed by treating with a specific inhibitor of gap-junction mediated cell-cell communication. There is clear evidence that the carbon-ion irradiation enables the enhanced cell killing in cells with wild-type P53 gene via gap-junction mediated bystander effect. (author)

  17. 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

  18. Radiation-induced life shortening. Annex K

    International Nuclear Information System (INIS)

    1982-01-01

    The purpose of this Annex is to review the cumulative evidence in the field of non-neoplastic long-term effects of whole-body irradiation. In particular, the existence and extent of life-span shortening in irradiated animals and man, and the relationships of life shortening to the physical and biological variables which may influence this effect of radiation are examined.

  19. Radiation-induced cerebellar chondrosarcoma. Case report

    International Nuclear Information System (INIS)

    Bernstein, M.; Perrin, R.G.; Platts, M.E.; Simpson, W.J.

    1984-01-01

    The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation

  20. Prevention Of Radiation Induced Hematological Alterations By ...

    African Journals Online (AJOL)

    The modulatory influence of Rosmarinus officinalis (rosemary) leaves extract was investigated in Swiss albino mice at a dose of 3 Gy gamma radiation. For this purpose, adult Swiss albino mice were irradiated with 3 Gy gamma rays in the presence (experimental) or absence (control) of rosemary (1000 mg/kg body wt.).

  1. Crack velocity measurement by induced electromagnetic radiation

    International Nuclear Information System (INIS)

    Frid, V.; Rabinovitch, A.; Bahat, D.

    2006-01-01

    Our model of electromagnetic radiation (EMR) emanated from fracture implies that EMR amplitude is proportional to crack velocity. Soda lime glass samples were tested under uniaxial tension. Comparison of crack velocity observed by Wallner line analysis and the peak amplitude of EMR signals registered during the test, showed very good correlation, validating this proportionality

  2. Radiation recall dermatitis induced by trastuzumab

    Directory of Open Access Journals (Sweden)

    Emre Kaynak

    2014-12-01

    Full Text Available Radiation recall phenomenon is an acute, egzematous reaction that develops throughout a previously irradiated area, precipitated by the administration of docetaxel, doxorubicin, gemcitabine and paclitaxel. We report a 52-year-old woman with breast cancer who received locoregional radiotherapy followed by trastuzumab monotherapy. Three day after the first cycle of trastuzumab monotherapy, dermatitis developed in the previously irradiated skin.

  3. Crack velocity measurement by induced electromagnetic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Frid, V. [Deichmann Rock Mechanics Laboratory of the Negev, Geological and Environmental Sciences Department, Ben Gurion University of the Negev, Beer Sheva (Israel)]. E-mail: vfrid@bgu.ac.il; Rabinovitch, A. [Deichmann Rock Mechanics Laboratory of the Negev, Physics Department, Ben Gurion University of the Negev, Beer Sheva (Israel); Bahat, D. [Deichmann Rock Mechanics Laboratory of the Negev, Geological and Environmental Sciences Department, Ben Gurion University of the Negev, Beer Sheva (Israel)

    2006-07-31

    Our model of electromagnetic radiation (EMR) emanated from fracture implies that EMR amplitude is proportional to crack velocity. Soda lime glass samples were tested under uniaxial tension. Comparison of crack velocity observed by Wallner line analysis and the peak amplitude of EMR signals registered during the test, showed very good correlation, validating this proportionality.

  4. Vacuum alignment and radiatively induced Fermi scale

    Directory of Open Access Journals (Sweden)

    Alanne Tommi

    2017-01-01

    Full Text Available We extend the discussion about vacuum misalignment by quantum corrections in models with composite pseudo-Goldstone Higgs boson to renormalisable models with elementary scalars. As a concrete example, we propose a framework, where the hierarchy between the unification and the Fermi scale emerges radiatively. This scenario provides an interesting link between the unification and Fermi scale physics.

  5. Hyperprolactinemia from radiation-induced hypothalamic hypopituitarism

    International Nuclear Information System (INIS)

    Corkill, G.; Hanson, F.W.; Gold, E.M.; White, V.A.

    1980-01-01

    In 1975 Samaan et al., described the effects of radiation damage of the hypothalamus in 15 patients with head and neck cancer. Shalet et al., in 1977 described endocrine morbidity in adults who as children had been irradiated for brain tumors. This report describes instances of hyperprolactinemia and associated hypothalamic, pituitary, and thyroid dysfunction following irradiation of a young adult female for brain neoplasia

  6. [Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

    Science.gov (United States)

    Sevost'ianova, N N; Trofimov, A V; Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

    2010-01-01

    The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

  7. 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

  8. Induced resistance and gene expression in wheat against leaf rust ...

    African Journals Online (AJOL)

    uvp

    2013-05-15

    May 15, 2013 ... 2Department of Soil, Crop and Climate Sciences, University of the Free State, P.O Box ... Key words: Wheat leaf rust, induced resistance, priming, gene ..... transformation: susceptibility of transgenic Nicotiana sylvestris plants.

  9. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    Science.gov (United States)

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  10. 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

  11. Consequences of PAI-1 specific deletion in endothelium on radiation-induced intestinal damage

    International Nuclear Information System (INIS)

    Rannou, Emilie

    2015-01-01

    Radiation-induced injury to healthy tissues is a real public health problem, since they are one of the most limiting factors that restrict efficiency of radiation therapy. This problematic is also part of the French Cancer Plan 2014-2017, and involves clinical research. Concepts surrounding the development of radiation-induced damage have gradually evolved into a contemporary and integrated view of the pathogenesis, involving all compartments of target tissue. Among them, endothelium seems to be central in the sequence of interrelated events that lead to the development of radiation-induced damage, although there are rare concrete elements that support this concept. By using new transgenic mouse models, this PhD project provides a direct demonstration of an endothelium-dependent continuum in evolution of radiation-induced intestinal damage. Indeed, changes in the endothelial phenotype through targeted deletion of the gene SERPINE1, chosen because of its key role in the development of radiation enteritis, influences various parameters of the development of the disease. Thus, lack of PAI-1 secretion by endothelial cells significantly improves survival of the animals, and limits severity of early and late tissue damage after a localized small bowel irradiation. Furthermore, these mice partially KO for PAI-1 showed a decrease in the number of apoptotic intestinal stem cells in the hours following irradiation, a decrease in the macrophages infiltrate density one week after irradiation, and a change in the polarization of macrophages throughout the pathophysiological process. In an effort to protect healthy tissues from radiation therapy side effects, without hindering the cancer treatment, PAI-1 seems to be an obvious therapeutic target. Conceptually, this work represents the direct demonstration of the link between endothelium phenotype and radiation enteritis pathogenesis. (author)

  12. Induction of cytochrome P450 1 genes and stress response genes in developing zebrafish exposed to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Behrendt, Lars [Biology Department, Redfield 352 MS-32, Woods Hole Oceanographic Institution, 45 Water Street, Woods Hole, MA 02543 (United States); Joensson, Maria E. [Biology Department, Redfield 352 MS-32, Woods Hole Oceanographic Institution, 45 Water Street, Woods Hole, MA 02543 (United States); Department of Environmental Toxicology, Uppsala University (Sweden); Goldstone, Jared V. [Biology Department, Redfield 352 MS-32, Woods Hole Oceanographic Institution, 45 Water Street, Woods Hole, MA 02543 (United States); Stegeman, John J., E-mail: jstegeman@whoi.edu [Biology Department, Redfield 352 MS-32, Woods Hole Oceanographic Institution, 45 Water Street, Woods Hole, MA 02543 (United States)

    2010-06-01

    Ultraviolet (UV) radiation damages cell molecules, and has been suggested to up-regulate mammalian cytochrome P4501 (CYP1) genes through an aryl hydrocarbon receptor (AHR) mediated mechanism. In this study, embryos and larvae of zebrafish (Danio rerio) were exposed to UV to determine the effects on expression of CYP1 and stress response genes in vivo in these fish. Zebrafish embryos were exposed for varying times to UV on two consecutive days, with exposure beginning at 24 and 48 h post-fertilization (hpf). Embryos exposed for 2, 4 or 6 h twice over 2 days to UVB (0.62 W/m{sup 2}; 8.9-26.7 kJ/m{sup 2}) plus UVA (2.05 W/m{sup 2}; 29.5-144.6 kJ/m{sup 2}) had moderately (2.4 {+-} 0.8-fold) but significantly up-regulated levels of CYP1A. UVA alone had no effect on CYP1A expression. Proliferating cellular nuclear antigen (PCNA) and Cu-Zn superoxide dismutase (SOD1) transcript levels were induced (2.1 {+-} 0.2 and 2.3 {+-} 0.5-fold, respectively) in embryos exposed to two 6-h pulses of 0.62 W/m{sup 2} UVB (26.8 kJ/m{sup 2}). CYP1A was induced also in embryos exposed to higher intensity UVB (0.93 W/m{sup 2}) for two 3-h or two 4-h pulses (20.1 or 26.8 kJ/m{sup 2}). CYP1B1, SOD1 and PCNA expression was induced by the two 3-h pulses of the higher intensity UVB, but not after two 4-h pulses of the higher intensity UVB, possibly due to impaired condition of surviving embryos, reflected in a mortality of 34% at that UVB dose. A single 8-h long exposure of zebrafish larvae (8 dpf) to UVB at 0.93 W/m{sup 2} (26.8 kJ/m{sup 2}) significantly induced CYP1A and CYP1B1 expression, but other CYP1 genes (CYP1C1, CYP1C2 and CYP1D1) showed no significant increase. The results show that UVB can induce expression of CYP1 genes as well stress response genes in developing zebrafish, and that UVB intensity and duration influence the responses.

  13. A novel radiation responsive cis-acting element regulates gene induction and mediates tissue injury

    International Nuclear Information System (INIS)

    Hallahan, Dennis E.; Virudachalam, Subbulakshmi; Kuchibahtla, Jaya

    1997-01-01

    Purpose: The intracellular adhesion molecule (ICAM-1) binds and activates inflammatory cells and thereby contributes to the pathogenesis of tissue injury. To characterize a model for radiation-induction of tissue injury, we studied radiation-mediated lung injury in mice deficient in the ICAM-1 gene. To study the mechanisms of x-ray mediated ICAM induction, we studied transcriptional activation of the ICAM promoter and nuclear protein binding to the 5' untranslated region of the ICAM gene. Methods: Immunohistochemistry and immunofluorescence were used to study the histologic pattern of ICAM expression in irradiated tissue. The ICAM-1 knockout mice were bred with wild type mice to create heterozygous mice with attenuated ICAM expression. ICAM -/-, ICAM+/- and ICAM +/+ mice were treated with thoracic irradiation and lung sections were stained for leukocyte common antigen (CD45) to study inflammation. To study the mechanism of x-ray induction of ICAM, we linked the 5' untranslated region of the ICAM gene to the luciferase reporter gene and delated DNA segments from the promoter to determine which elements are required for induction. We performed electrophoretic mobility shift analysis of nuclear proteins from irradiated endothelial cells to study transcription factor activation. Results: Immunohistochemistry showed dose and time dependent increases in ICAM protein expression in irradiated lungs which was prolonged as compared to endothelial cells in vitro. The histologic pattern of ICAM expression was in the capillary endothelium and was distinct from the pattern of expression of other radiation-inducible adhesion molecules. ICAM knockout mice had no ICAM expression and no inflammatory cell accumulation in the irradiated lung. ICAM+/+ mice developed leukocyte adhesion to irradiated endothelium within hours of irradiation and radiation pneumonitis 5 to 6 weeks later. The DNA sequence between -981 and -769 (relative to start codon) contains two 16-base pair repeats, each

  14. 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

  15. 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

  16. Molecular Characterization of a stress-induced NAC Gene ...

    Indian Academy of Sciences (India)

    lenovo

    1Cotton Research Center, Shandong Academy of Agricultural Sciences, Jinan 250100, China. 2College of Life ... Running title: GhSNAC3 gene in Cotton ... Quantitative RT-PCR analysis indicated that GhSNAC3 was induced by high salinity, drought ..... simple and general method for transferring genes into plants. Science ...

  17. Induced mutations of rust resistance genes in wheat

    International Nuclear Information System (INIS)

    McIntosh, R.A.

    1983-01-01

    Induced mutations are being used as a tool to study genes for resistance in wheat. It was found that Pm1 can be separated from Lr20 and Sr15, but these two react like a single pleiotropic gene. Mutants were further examined in crosses and backmutations have been attempted. (author)

  18. Identification of salt-stress induced differentially expressed genes in ...

    African Journals Online (AJOL)

    Identification of salt-stress induced differentially expressed genes in barley leaves using the annealingcontrol- primer-based GeneFishing technique. S Lee, K Lee, K Kim, GJ Choi, SH Yoon, HC Ji, S Seo, YC Lim, N Ahsan ...

  19. Control of phenylalanine ammonia-lyase gene promoters from pea by UV radiation

    International Nuclear Information System (INIS)

    Pluskota, W.E.; Michalczyk, D.J.; Gorecki, R.J.

    2005-01-01

    The gene fusion system was used to study UV light-control of PS PAL1 and PS PAL2 genes encoding phenylalanine ammonia-lyase of pea. The induction of pea PAL promoters was analysed in transgenic tobacco plants. Binary plasmids (derivatives of pBI101.2 vector) containing 5' regulatory fragments of PS PAL1 and PS PAL2 linked to reporter genes (GUS, LUC) were constructed. The analyses were performed with the use of single constructs (containing one variant of PS PAL promoter and one reporter gene) and dual constructs (containing both PS PAL1 and PS PAL2 promoters connected with different reporter genes). The use of dual constructs enabled the evaluation of both PS PAL promoters activity in the same plant. The analyses of in vitro grown plants have shown that both PAL promoters are strongly induced in leaves subjected to UV radiation. In some cases, the UV-stimulated expression exceeded the exposed areas. This phenomenon was observed more often in the leaves of plants containing the PS PAL1::GUS than PS PAL2::GUS construct. Removal of boxes 2, 4, 5 from PS PAL1 promoter and deletion of its 5' end region (-339 to -1394) decreases the level of gene expression but does not eliminate its responsiveness to UV

  20. Radiation-induced transformations of cellulose ethers

    International Nuclear Information System (INIS)

    Nud'ga, L.A.; Petropavlovskii, G.S.; Plisko, E.A.; Isakova, O.V.; Ershov, B.G.

    1988-01-01

    The purpose of this investigation was to study the transformation which take place under the action of γ-radiation in a number of cellulose ethers containing both saturated (carboxymethyl, hydroxyethyl) and unsaturated (allyl, methacryloyl) groups. Irradiation was carried out on a 60 Co unit in air at 77 and 300 K; the dose rate was 37 and 50 kGy/h respectively. The EPR spectra of γ-irradiated hydroxyethyl- and allylhydroxyethylcelluloses are identical. Under the action of γ-radiation extensive changes took place in cellulose ethers which are exhibited in degradation or the formation of three-dimensional structures and are accompanied by a change in the functional composition. The efficiency in the formation of radicals and their localization are determined by the nature and number of substituents in the cellulose ethers

  1. Simulation of radiation-induced defects

    CERN Document Server

    Peltola, Timo

    2015-09-14

    Mainly due to their outstanding performance the position sensitive silicon detectors are widely used in the tracking systems of High Energy Physics experiments such as the ALICE, ATLAS, CMS and LHCb at LHC, the world's largest particle physics accelerator at CERN, Geneva. The foreseen upgrade of the LHC to its high luminosity (HL) phase (HL-LHC scheduled for 2023), will enable the use of maximal physics potential of the facility. After 10 years of operation the expected fluence will expose the tracking systems at HL-LHC to a radiation environment that is beyond the capacity of the present system design. Thus, for the required upgrade of the all-silicon central trackers extensive measurements and simulation studies for silicon sensors of different designs and materials with sufficient radiation tolerance have been initiated within the RD50 Collaboration. Supplementing measurements, simulations are in vital role for e.g. device structure optimization or predicting the electric fields and trapping in the silicon...

  2. Radiation induced growth of micro crystallites

    International Nuclear Information System (INIS)

    Meisel, D.

    1991-01-01

    Generation of colloidal particles during the radiolysis of aqueous solutions was already observed in the early days of radiation chemistry. Systematic studies using radiation chemistry techniques as synthetic tools in the preparation of colloidal particles, primarily metallic particles, were begun approximately a decade ago in conjunction since they were found to catalyze multi-electron redox processes. A large number of metallic colloidal particles were then synthesized, including silver, gold, platinum, iridium, nickel, cadmium, and others. More recently, attention has turned to semiconductor colloidal particles. The stimulus to these studies is the observation of quantum size effects in small semiconductor particles that exhibit hybrid properties between those of the molecular species and the solid state bulk material. In the following we discuss our own observations on the evolution of semiconductor particles whose growth has been initiated by pulse radiolysis. 13 refs., 2 figs

  3. Laser radiation effect on radiation-induced defects in heavy ion tracks in dielectrics

    International Nuclear Information System (INIS)

    Egorov, A.N.; Zhiryakov, B.M.; Kushin, V.V.; Lyapidevskij, V.K.; Khokhlov, N.B.

    1988-01-01

    Possibility of laser radiation resonance effect on radiation-induced defects in heavy ion tracks in dielectric materials is investigated. Absorption spectra in infrared, visible and ultraviolet ranges for cellulose nitrate samples irradiated by 6 MeV/nucleon 58 Ni ions and reactor gamma radiation are measured. Absorption spectra for irradiated and reference samples are presented. Two absorption bands λ 1 =0.33 μm (E 1 =3.9 eV) and λ 2 =0.72 μm (E 2 =1.7 eV) are detected. Etching rate decrease in a track under laser radiation effect is noticed. 3 refs.; 1 fig

  4. 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

  5. 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.

  6. 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

  7. Connexin43 gene and its irradiation-induced expression

    International Nuclear Information System (INIS)

    Long Xianhui; Zhou Pingkun

    2005-01-01

    Gap junctions, composed of connexin protein subunits, provide the important channel for the intercellular communication. Connexin43, the most popular component of the connexin protein family, is widely expressed in multiple tissues and cell lines and plays an important role in cell proliferation, differention and tissue homeostasis. Recently it was reported that the expression of connexin43 gene is remarkedly up-regulated by low dose ionizing radiation, the available data suggest connexin43 gene to be a poten-tial sensitive bio-marker in radiation damage. (authors)

  8. Umbelliferone suppresses radiation induced DNA damage and apoptosis in hematopoietic cells of mice

    International Nuclear Information System (INIS)

    Jayakumar, S.; Bhilwade, H.N.; Chaubey, R.C.

    2012-01-01

    in DNA damage in the peripheral leukocytes. This was also reflected in the frequency of micronucleated erythrocytes present in bone marrow. Gene expression studies on splenic lymphocytes showed that the umbelliferone pre treatment reduces the level of induction of radiation induced BAX level, and increased the expression of bc12 levels. Our study clearly demonstrated the radioprotective potential of UMB in vitro and in vivo. (author)

  9. 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

  10. Effects of Ionizing Radiation on Murine Gene Expression in Skin and Bone

    Science.gov (United States)

    Terada, Masahiro; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Alwood, Joshua; Tahimic, Candice; Sowa, Marianne B.; Globus, Ruth K.

    2017-01-01

    Long duration spaceflight causes a negative calcium balance and reduces bone density in astronauts. The potential for exposure to space radiation to contribute to lasting decrements in bone mass is not yet understood. Sustained changes to bone mass have a relatively long latency for development, however skin is a radiation sensitive organ and changes in skin gene expression may serve as an early radiation biomarker of exposures and may correlate with adverse effects on skeletal tissue. Previous studies have shown that FGF18 gene expression levels of hair follicles collected from astronauts on the ISS rose over time. In the hair follicle, FGF18 signaling mediates radioresistance in the telogen by arresting the cell cycle, and FGF18 has the potential to function as a radioprotector. In bone, FGF18 appears to regulate cell proliferation and differentiation positively during osteogenesis and negatively during chondrogenesis. Cellular defense responses to radiation are shared by a variety of organs, hence in this study, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We have examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (TBI). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and TBI (0.5 Gy Fe-56 600 MeV/n and 0.5 Gy H-1 150 MeV/n). Animals were euthanized one and 11 days post-IR. Statistical analysis was performed via a Student's ttest. In skin samples one day after IR, skin expression of FGF18 was significantly greater (3.8X) than sham-irradiated controls (3.8X), but did not differ 11 days post TBI. Expression levels of other radiation related genes (Nfe2l2, Trp53, Cdkn1a, FoxO3

  11. 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

  12. Hypermethylation of gene promoters in peripheral blood leukocytes in humans long term after radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmina, Nina S., E-mail: nin-kuzmin@youndex.ru; Lapteva, Nellya Sh.; Rubanovich, Alexander V.

    2016-04-15

    Some human genes known to undergo age-related promoter hypermethylation. These epigenetic modifications are similar to those occurring in the course of certain diseases, e.g. some types of cancer, which in turn may also associate with age. Given external genotoxic factors may additionally contribute to hypermethylation, this study was designed to analyzes, using methylation-sensitive polymerase chain reaction (PCR), the CpG island hypermethylation in RASSF1A, CDKN2A (including p16/INK4A and p14/ARF) and GSTP1 promoters in peripheral blood leukocytes of individuals exposed to ionizing radiation long time ago. One hundred and twenty-four irradiated subjects (24–77 years old at sampling: 83 Chernobyl Nuclear Power Plant clean-up workers, 21 nuclear workers, 20 residents of territories with radioactive contamination) and 208 unirradiated volunteers (19–77 years old at sampling) were enrolled. In addition, 74 non-exposed offspring (2–51 years old at sampling) born to irradiated parents were examined. The frequency of individuals displaying promoter methylation of at least one gene in exposed group was significantly higher as compared to the control group (OR=5.44, 95% CI=2.62–11.76, p=3.9×10{sup −7}). No significant difference was found between the frequency of subjects with the revealed promoter methylation in the group of offspring born to irradiated parents and in the control group. The increase in the number of methylated loci of RASSF1A and p14/ARF was associated with age (β=0.242; p=1.7×10{sup −5}). In contrast, hypermethylation of p16/INK4A and GSTP1 genes correlated with the fact of radiation exposure only (β=0.290; p=1.7×10{sup −7}). The latter finding demonstrates that methylation changes in blood leukocytes of healthy subjects exposed to radiation resemble those reported in human malignancies. Additional studies are required to identify the dose-response of epigenetic markers specifically associating with radiation-induced premature aging

  13. Hypermethylation of gene promoters in peripheral blood leukocytes in humans long term after radiation exposure

    International Nuclear Information System (INIS)

    Kuzmina, Nina S.; Lapteva, Nellya Sh.; Rubanovich, Alexander V.

    2016-01-01

    Some human genes known to undergo age-related promoter hypermethylation. These epigenetic modifications are similar to those occurring in the course of certain diseases, e.g. some types of cancer, which in turn may also associate with age. Given external genotoxic factors may additionally contribute to hypermethylation, this study was designed to analyzes, using methylation-sensitive polymerase chain reaction (PCR), the CpG island hypermethylation in RASSF1A, CDKN2A (including p16/INK4A and p14/ARF) and GSTP1 promoters in peripheral blood leukocytes of individuals exposed to ionizing radiation long time ago. One hundred and twenty-four irradiated subjects (24–77 years old at sampling: 83 Chernobyl Nuclear Power Plant clean-up workers, 21 nuclear workers, 20 residents of territories with radioactive contamination) and 208 unirradiated volunteers (19–77 years old at sampling) were enrolled. In addition, 74 non-exposed offspring (2–51 years old at sampling) born to irradiated parents were examined. The frequency of individuals displaying promoter methylation of at least one gene in exposed group was significantly higher as compared to the control group (OR=5.44, 95% CI=2.62–11.76, p=3.9×10 −7 ). No significant difference was found between the frequency of subjects with the revealed promoter methylation in the group of offspring born to irradiated parents and in the control group. The increase in the number of methylated loci of RASSF1A and p14/ARF was associated with age (β=0.242; p=1.7×10 −5 ). In contrast, hypermethylation of p16/INK4A and GSTP1 genes correlated with the fact of radiation exposure only (β=0.290; p=1.7×10 −7 ). The latter finding demonstrates that methylation changes in blood leukocytes of healthy subjects exposed to radiation resemble those reported in human malignancies. Additional studies are required to identify the dose-response of epigenetic markers specifically associating with radiation-induced premature aging and/or with

  14. Investigating Gene Function in Cereal Rust Fungi by Plant-Mediated Virus-Induced Gene Silencing.

    Science.gov (United States)

    Panwar, Vinay; Bakkeren, Guus

    2017-01-01

    Cereal rust fungi are destructive pathogens, threatening grain production worldwide. Targeted breeding for resistance utilizing host resistance genes has been effective. However, breakdown of resistance occurs frequently and continued efforts are needed to understand how these fungi overcome resistance and to expand the range of available resistance genes. Whole genome sequencing, transcriptomic and proteomic studies followed by genome-wide computational and comparative analyses have identified large repertoire of genes in rust fungi among which are candidates predicted to code for pathogenicity and virulence factors. Some of these genes represent defence triggering avirulence effectors. However, functions of most genes still needs to be assessed to understand the biology of these obligate biotrophic pathogens. Since genetic manipulations such as gene deletion and genetic transformation are not yet feasible in rust fungi, performing functional gene studies is challenging. Recently, Host-induced gene silencing (HIGS) has emerged as a useful tool to characterize gene function in rust fungi while infecting and growing in host plants. We utilized Barley stripe mosaic virus-mediated virus induced gene silencing (BSMV-VIGS) to induce HIGS of candidate rust fungal genes in the wheat host to determine their role in plant-fungal interactions. Here, we describe the methods for using BSMV-VIGS in wheat for functional genomics study in cereal rust fungi.

  15. Radiation induced desynaptic mutants in barley

    International Nuclear Information System (INIS)

    Srivastava, H.M.

    1974-01-01

    Spontaneous occurrence of asynapsis and desynapsis has been frequently reported in a number of crop plants (Beadle 1930, 1933; Beasley and Brown 1942; Li et al. 1945; Magoon et al. 1961; Miller 1963) and other angiospermic texa (Calarier 1955; Chennaveraiah and Krisnappa 1968; Ehrenberg 1949; Johnson 1941, 1944; Roy and Jha 1958). However, there are only a few reports of induced asynapsis or desynapsis (Gottschalk and Baquar 1971; Martini and Bozzini 1966). The present paper deals with the morphology and meiotic behavior of gamma-ray induced barley mutants showing high degree of desynapsis resulting in partial to complete sterility. (author)

  16. Expression of MDM2 in an acute lymphocytic leukemia mice model induced by γ-radiation

    International Nuclear Information System (INIS)

    Huang Yuecheng; Cai Jianming; Han Ling; Gao Fu; Cui Jianguo; Gao Jianguo

    2004-01-01

    Objective: To investigate the role of the MDM 2 in the process of carcinogenesis induced by γ-rays and its molecular mechanisms. Methods: Animal model of radiation-induced leukemia was established by γ-irradiation. According to the histological and morphological results, mice tissues were divided into three groups: cancerization group, incancerization group and control group. Expression of MDM 2 protein and mRNA in thymus/bone marrow was detected with Western blot and in situ hybridization (ISH), respectively. The authors also examined the protein phosphorylation level of MDM 2 protein by immunoprecipitation (IP). PCR-SSCP was performed to detect gene mutation. Results: A mice leukemia model was successfully established as verified by pathological findings and confirmed by transplantation test in nude mice. The protein expression in thymus/bone marrow in irradiation groups was significantly higher than that in controls (P 2 was found to be hyper-phosphorylated in the cancerization group as compared with other groups. No gene mutation was detected by SSCP/silver-staining assay in the tumor samples. Conclusion: MDM 2 may be involved in the development and progression of leukemia induced by γ-irradiation. The over-expression but not gene mutation may be responsible for malignant transformation induced by radiation. Phosphorylation is at least partly attributed to activation of MDM 2

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Differential expression of ozone-induced gene during exposures to ...

    African Journals Online (AJOL)

    Differential expression of ozone-induced gene during exposures to salt stress in Polygonum sibiricum Laxm leaves, stem and underground stem. ... PcOZI-1 mRNA in untreated plants was detected at low levels in underground stem, leaves and at higher levels in stem. PcOZI-1 mRNA accumulation was transiently induced ...

  2. 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

  3. 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

  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. 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)

  6. 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

  7. 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)

  8. 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).

  9. Social impacts induced by radiation risk in Fukushima prefecture

    International Nuclear Information System (INIS)

    Murayama, Takehiko

    2011-01-01

    An accident of Fukushima Daiichi nuclear power plant induced by an earthquake of M9.0 and subsequent tsunami gave various kinds of impacts around the plant. After reviewing arguments of local governments for low dose radiation risk, this paper analyzed social impacts by the risk in terms of a gap of emergency response between national and local governments, corruption of communities in various levels induced by plural statements for risk levels in low level radiation, and economic impacts for agricultural crops made in Fukushima prefecture. Afterwards, clues for improving the situation were discussed, which include understanding of characteristics of public perception, attitudes of experts and interactive risk communication. (author)

  10. 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

  11. The radiation induced degradation of polymers

    International Nuclear Information System (INIS)

    Wilski, H.

    1987-01-01

    A compilation was made of all data about the radiation stability of thermoplastic polymeric materials, published in the literature up to the end of 1985. From those experiments in which the irradiation was carried out in air half value doses (elongation) (= hvd) as a measure of radiation stability were extracted and compared on the basis of the chemical structure of the polymers, the chemical composition of the materials under test and the dose rate, respectively. The first result is that our knowledge of the radiation stability of polymers, if irradiated in air, is still very incomplete. On the other hand enough data were found for some polymers, to see that there is a region at low dose rates where the half value dose Dsub(e) increases with the dose rate (dD/dt) according to the equation Dsub(e)=Dsub(el).(dD/dt)sup(n). This seems to be the normal behavior. Values for the hvd at 1 Gy/h (in air) were found to lie between 1 and 500 kGy (with PTFE and PS at the respective ends of the scale), whereas n varied only between 0.1 and 0.4. The range of validity of the equation and the magnitude of the coefficients strongly depend on the chemical nature of the polymer and also on the kind and amount of the additives used. At dose rates in the neighborhood of 10 5 Gy/h the influence of the dose rate (and the atmosphere) disappears. (author)

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Radiation-induced anorexia in Syrian hamsters

    International Nuclear Information System (INIS)

    Kindt, A.; Sattler, E.L.; Schraub, A.

    1980-01-01

    The recovery of Syrian hamsters after split dose application (interval 11 days) was studied on the basis of the weight response and of food uptake. Two periods of weight loss and anorexia can be distinguished, an early one immediately after irradiation and a secondary one 6-10 days later. The secondary response is a function of the radiation dose and allows to distinguish survivors from non-survivors, since it is much more pronounced and longerlasting in the latter than in the former. The first response appears not to be influenced by a previous conditioning irradiation. (orig.) [de

  17. Radiation-induced corrosion of stellite-6

    International Nuclear Information System (INIS)

    Behazin, M.; Wren, J.C.

    2012-09-01

    Stellite-6 is a Co-based (58%) alloy that is used for components that require high wear-resistance, such as valve facings and ball bearings in nuclear reactors. In the reactor core, stable 59 Co can be neutron activated by absorption of a neutron to become the radioactive isotope, 60 Co. The 60 Co that is created constitutes a safety hazard for plant workers who have to perform maintenance on the reactor. One of the operational and safety issues in a nuclear reactor is the potential corrosion of Co-based alloys and the introduction of dissolved Co ions into the reactor core. While the corrosion of Stellite-6 has been studied its corrosion behaviour with ionizing radiation present has not been well established. Corrosion kinetics depend on both the aqueous redox conditions and the physical and chemical nature of the alloy surface. The high radiation fields present in a reactor core will cause water to decompose to a range of redox-active species (both highly oxidizing (e.g., ·OH, H 2 O 2 ) and highly reducing (e.g., ·eaq - , ·O 2 - )). These species can significantly influence corrosion kinetics. The effect of γ-radiation on the corrosion of Stellite-6 at pH 10.6 was investigated at temperatures ≤ 150 deg. C. Since the corrosion rate depends strongly on the type of oxide that is present on the material surface, the focus of this corrosion study was to establish the mechanism by which radiolysis affects the nature of the oxide that is present on Stellite-6. The results show that γ-radiation (at a dose rate of 5.5 kGy.h -1 ) increases the corrosion potential on Stellite-6 from -0.7 VSCE to 0.12 VSCE . The corrosion potential without irradiation present is in a potential range where oxidation is limited to the formation of a Co (OH) 2 and CoCr 2 O 4 outer oxide layer on a pre-existing Cr 2 O 3 film. The corrosion potential with irradiation is in a potential range where further oxidation of Co (OH) 2 to CoOOH also occurs. However, since CoOOH is less soluble than

  18. Radiation-induced anorexia in Syrian hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Kindt, A.; Sattler, E.L.; Schraub, A.

    1980-10-01

    The recovery of Syrian hamsters after split dose application (interval 11 days) was studied on the basis of the weight response and of food uptake. Two periods of weight loss and anorexia can be distinguished, an early one immediately after irradiation and a secondary one 6-10 days later. The secondary response is a function of the radiation dose and allows to distinguish survivors from non-survivors, since it is much more pronounced and longerlasting in the latter than in the former. The first response appears not to be influenced by a previous conditioning irradiation.

  19. Radiation induced oxidation for water remediation

    International Nuclear Information System (INIS)

    Gehringer, P.

    1997-01-01

    The action of ionizing radiation on halogenated hydrocarbons, in the presence and absence of ozone, was studied in water and wastewater. The combined ozone/electron-beam irradiation process was found especially suited for remediation of low-level contaminated groundwater. This combined treatment was often more effective than irradiation alone for wastewater decontamination. It reduced the COD without a simultaneous increase of BOD. Introduction of gaseous ozone directly into the irradiation chamber improved the water-flow turbulence, allowing treatment in layers thicker than the penetration range of the electrons, with increased decontamination efficiency. (author)

  20. 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

  1. Radiation-induced secretory protein, clusterin. Its inductive mechanism and biological significance

    International Nuclear Information System (INIS)

    Suzuki, Masatoshi; Boothman, D.A.

    2007-01-01

    This paper describes biochemistry of secretory clusterin (C), its radiation-inductive mechanism and biological significance. C is a glycoprotein found to be secreted from cells given various stresses like radiation and ultraviolet (UV)-ray, and participates to red cell clustering. Human C gene locates on the chromosome 8p21-p12, C has MW of 60 kDa, its precursor undergoes the degrading processing to α- and β-chains to form their heterodimer before glycosylation, and the C is finally secreted. So many other names have been given to C due to its numerous functions which have been discovered in other fields, such as apolipoprotein J. C is abundant in plasma, milk, urine, cerebrospinal fluid, semen, etc. Within 24 hr after X-ray irradiation, extracellular insulin-like growth factor-1 (IGF-1) level is elevated, and through its binding to the receptor, Src/MAPK signaling participates to C expression. Nuclear C, also induced by radiation, is a splicing variant of C and not secreted from cells. C is induced by radiation with as low dose as 2 cGy, which is different from induction of nuclear C. Secreted C is incorporated in cells by endocytosis and promotes the intracellular survival reaction through IGF-1 receptor/MAPK/Egr-1 pathway, whereas nuclear C induces cell apoptosis via unknown mechanism. Further studies are required for elucidation of the roles of secretory and nuclear C in cellular radiation responses. (R.T.)

  2. Screening of hypoxia-inducible genes in sporadic ALS.

    LENUS (Irish Health Repository)

    Cronin, Simon

    2008-10-01

    Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations in these genes may reduce the levels or functioning of their products. VEGF and ANG belong to a larger group of angiogenic genes that are up-regulated under hypoxic conditions. We hypothesized that common genetic variation across other members of this group may also predispose to sporadic ALS. To screen other hypoxia-inducible angiogenic genes for association with SALS, we selected 112 tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes. Screening for association was performed in 270 Irish individuals with typical SALS and 272 ethnically matched unrelated controls. SNPs showing association in the Irish phase were genotyped in a replication sample of 281 Swedish sporadic ALS patients and 286 Swedish controls. Seven markers showed association in the Irish. The one modest replication signal observed in the Swedish replication sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs. the Irish cohort. We failed to detect association of common variation across 24 candidate hypoxia-inducible angiogenic genes with SALS.

  3. Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

    Directory of Open Access Journals (Sweden)

    Marta Miró-Murillo

    Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

  4. Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones

    Directory of Open Access Journals (Sweden)

    Matthew D Fountain

    2016-11-01

    Full Text Available Introduction: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated. Methods: C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by H&E, Masson’s Trichrome and Ki-67 staining at 1, 4, 10, 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45 respectively. Results: Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as one week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy.Conclusions: Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.

  5. 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)

  6. 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)

  7. Radiation-induced apoptosis in F9 teratocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Langley, R E; Palayoor, S T; Coleman, C N; Bump, E A [Joint Center for Radiation Therapy and Dana Farber Cancer Inst., Boston (United States)

    1994-05-01

    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-[beta]-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).

  8. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  9. Radiation induced bystander effects: mechanisms and implication for low dose radiation risk assessment

    International Nuclear Information System (INIS)

    Hei, T.L.; Randers-Pehrson, G.; Zhou, H.

    2003-01-01

    Using a precision microbeam to target an exact fraction of cells in a population and irradiated their nuclei with exactly one alpha particle each, we found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non-hit cells contributing significantly to the response. In fact, irradiation of 10% of a mammalian cell population with a single alpha particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. Although the bystander observations have been well established, the underlying mechanism(s) remain largely unknown. There are indications that multiple pathways are involved in the bystander phenomenon and different cell types respond differently to the bystander signaling. In confluent monolayers, there is evident that gap junctional communication is crucial in mediating the bystander effect whereas reactive oxygen and reactive nitrogen species have been implicated as the mediating molecules in sub-confluent cultures. Although p53 is not necessary for the expression of bystander effect, there is evident that repair deficient cells may express a higher bystander response. Using cDNA microarrays, a number of cellular signaling genes have been shown to be differentially expressed among bystander cells. The functional roles of these genes in the bystander effect will be discussed. The bystander observations imply that the relevant target for various radiobiological endpoints is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimate for low dose radiation exposure. (Work supported by NIH grants CA 49062 and CA-RR11623)

  10. Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

    Energy Technology Data Exchange (ETDEWEB)

    Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C., E-mail: prabhat-goswami@uiowa.edu

    2013-11-01

    Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays, were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.

  11. The BK(Ca) channels deficiency as a possible reason for radiation-induced vascular hypercontractility.

    Science.gov (United States)

    Kyrychenko, Sergii; Tishkin, Sergey; Dosenko, Victor; Ivanova, Irina; Novokhatska, Tatiana; Soloviev, Anatoly

    2012-01-01

    It is likely that large-conductance Ca²⁺-activated K⁺ (BK(Ca)) channels channelopathy tightly involved in vascular malfunctions and arterial hypertension development. In the present study, we compared the results of siRNAs-induced α-BK(Ca) gene silencing and vascular abnormalities produced by whole-body ionized irradiation in rats. The experimental design comprised RT-PCR and patch clamp technique, thoracic aorta smooth muscle (SM) contractile recordings and arterial blood pressure (BP) measurements on the 30th day after whole body irradiation (6Gy) and following siRNAs KCNMA1 gene silencing in vivo. The expression profile of BK(Ca) mRNA transcripts in SM was significantly decreased in siRNAs-treated rats in a manner similar to irradiated SM. In contrast, the mRNA levels of K(v) and K(ATP) were significantly increased while L-type calcium channels mRNA transcripts demonstrated tendency to increment. The SMCs obtained from irradiated animals and after KCNMA1 gene silencing showed a significant decrease in total K⁺ current density amplitude. Paxilline (500 nM)-sensitive components of outward current were significantly decreased in both irradiated and gene silencing SMCs. KCNMA1 gene silencing increased SM sensitivity to norepinephrine while Ach-induced relaxation had decreased. The silencing of KCNMA1 had no significant effect on BP while radiation produced sustained arterial hypertension. Therefore, radiation alters the form and function of the BK(Ca) channel and this type of channelopathy may contribute to related vascular abnormalities. Nevertheless, it is unlikely that BK(Ca) can operate as a crucial factor for radiation-induced arterial hypertension. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Radiation-induced endometriosis in Macaca mulatta

    International Nuclear Information System (INIS)

    Fanton, J.W.; Golden, J.G.

    1991-01-01

    Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, and minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively

  13. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ''wasted'' mice

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Libertin, C.R.; Weaver, P.; Churchill, M.; Chang-Liu, C.M.

    1993-01-01

    Mice recessive for the autosomal gene ''wasted'' (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/· mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/· mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/· and not from wst/wst or parental control BCF 1 mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage

  14. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ``wasted`` mice

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ., Maywood, IL (United States); Libertin, C.R.; Weaver, P. [Loyola Univ., Maywood, IL (United States); Churchill, M.; Chang-Liu, C.M. [Argonne National Lab., IL (United States)

    1993-09-01

    Mice recessive for the autosomal gene ``wasted`` (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/{center_dot} mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{center_dot} mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/{center_dot} and not from wst/wst or parental control BCF{sub 1} mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

  15. MiR-21 is involved in radiation-induced bystander effects

    Science.gov (United States)

    Xu, Shuai; Ding, Nan; Pei, Hailong; Hu, Wentao; Wei, Wenjun; Zhang, Xurui; Zhou, Guangming; Wang, Jufang

    2014-01-01

    Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication. PMID:25483031

  16. Radiation induced degradation of DNA in photodynamic therapy of cancer

    International Nuclear Information System (INIS)

    Ion, Rodica; Scarlat, F.; Niculescu, V.I.R.; Scarlat, Fl.; Gunaydin, Keriman

    2001-01-01

    DNA is a critical cellular target for oxidative processes induced by physical and chemical stresses. It is known that the direct effect of ionizing radiation on DNA results mainly in base ionization and may lead to mutation, carcinogenesis and cell death. The degradation of DNA induced by laser and ionizing radiation (electron and photon beam) is analyzed in this paper. The ionizing radiation degradation of DNA is a radical process. A series of lesions among the major base degradation product has been measured in isolated DNA exposed to gamma radiation in aerated aqueous solution. Degradation can be accounted for by the formation of hydroxyl radicals upon radiolysis of water (indirect effect). The production of DNA damage by ionizing radiation involves two mechanisms, direct and indirect effects. Direct effect leads to ionization and excitation of DNA molecules, while indirect effect is due to the interaction of reactive species, in particular of OH radicals produced by water radiolysis, with targets in DNA. The relative contribution of the two mechanisms in damaging DNA depends on the type of radiation. Single strand breaks and base damage seem to be mainly produced by the attack of hydroxyl radicals on DNA, whereas double strand breaks result predominantly of direct energy deposition. The four bases are degraded in high yield. Direct effect has been mimicked by photo-induced electron abstraction from the bases producing their radical cation. The base damage may also occur from the formation of radical cation of purine and pyrimidine components. When DNA is irradiated in solution, single strand breaks are mainly due to the abstraction of an H atom from the 4 ' position of 2 ' -deoxyribose by the attack of OH radicals produced by water radiolysis. Quantification of the modified bases showed the guanine is the preferential target. Ionizing radiation induces several types of DNA modifications, including chain breaks, DNA-protein cross-links, oxidized DNA bases

  17. 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 in