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Sample records for radiation induces p53-independent

  1. Isofraxidin, a potent reactive oxygen species (ROS) scavenger, protects human leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in p53-independent manner.

    PubMed

    Li, Peng; Zhao, Qing-Li; Wu, Li-Hua; Jawaid, Paras; Jiao, Yu-Fei; Kadowaki, Makoto; Kondo, Takashi

    2014-06-01

    Ionizing radiation (IR) leads to oxidizing events such as excessive reactive oxygen species (ROS) in the exposed cells, resulting in further oxidative damage to lipids, proteins and DNA. To screen the potential radio-protective drug, the intracellular ROS was measured in irradiated U937 cells pretreated with 80 candidate traditional herbal medicine, respectively. Isofraxidin (IF) was one possible radio-protector in these 80 drugs. This study investigated the radio-protective role of IF, a Coumarin compound, in human leukemia cell lines, for the first time. Results indicate that IF protects against IR-induced apoptosis in U937 cells in the time- and concentration- dependent manner. IF decreases IR-induced intracellular ROS generation, especially hydroxyl radicals formation, inhibits IR-induced mitochondrial membrane potential loss and reduces IR-induced high intracellular Ca(2+) levels regardless of ER stress. IF down-regulates the expression of caspase-3, phospho-JNK, phospho-p38 and activates Bax in mitochondria. IF inhibits cytochrome c release from mitochondria to cytosol. IF also moderates IR-induced Fas externalization and caspase-8 activation. IF also exhibits significant protection against IR-induced cell death in other leukemia cell lines such as Molt-4 cells and HL60 cells regardless of p53. Taken together, the data demonstrate that IF protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner. PMID:24692054

  2. Neem oil limonoids induces p53-independent apoptosis and autophagy.

    PubMed

    Srivastava, Pragya; Yadav, Neelu; Lella, Ravi; Schneider, Andrea; Jones, Anthony; Marlowe, Timothy; Lovett, Gabrielle; O'Loughlin, Kieran; Minderman, Hans; Gogada, Raghu; Chandra, Dhyan

    2012-11-01

    Azadirachta indica, commonly known as neem, has a wide range of medicinal properties. Neem extracts and its purified products have been examined for induction of apoptosis in multiple cancer cell types; however, its underlying mechanisms remain undefined. We show that neem oil (i.e., neem), which contains majority of neem limonoids including azadirachtin, induced apoptotic and autophagic cell death. Gene silencing demonstrated that caspase cascade was initiated by the activation of caspase-9, whereas caspase-8 was also activated late during neem-induced apoptosis. Pretreatment of cancer cells with pan caspase inhibitor, z-VAD inhibited activities of both initiator caspases (e.g., caspase-8 and -9) and executioner caspase-3. Neem induced the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, suggesting the involvement of both caspase-dependent and AIF-mediated apoptosis. p21 deficiency caused an increase in caspase activities at lower doses of neem, whereas p53 deficiency did not modulate neem-induced caspase activation. Additionally, neem treatment resulted in the accumulation of LC3-II in cancer cells, suggesting the involvement of autophagy in neem-induced cancer cell death. Low doses of autophagy inhibitors (i.e., 3-methyladenine and LY294002) did not prevent accumulation of neem-induced LC3-II in cancer cells. Silencing of ATG5 or Beclin-1 further enhanced neem-induced cell death. Phosphoinositide 3-kinase (PI3K) or autophagy inhibitors increased neem-induced caspase-3 activation and inhibition of caspases enhanced neem-induced autophagy. Together, for the first time, we demonstrate that neem induces caspase-dependent and AIF-mediated apoptosis, and autophagy in cancer cells. PMID:22915764

  3. Depression of p53-independent Akt survival signals after high-LET radiation in mutated p53 cells

    NASA Astrophysics Data System (ADS)

    Ohnishi, Takeo; Takahashi, Akihisa; Nakagawa, Yosuke

    Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses the activities of serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signals were analyzed with Western blotting analysis 1 h, 2 h, 3 h and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis.Akt-related protein levels were decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G _{2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and depresses cell growth by suppressing Akt-related signals, even in the mp53 cells.

  4. Adenovirus type 5 early region 4 is responsible for E1A-induced p53-independent apoptosis.

    PubMed Central

    Marcellus, R C; Teodoro, J G; Wu, T; Brough, D E; Ketner, G; Shore, G C; Branton, P E

    1996-01-01

    In the absence of E1B, the 289- and 243-residue E1A products of human adenovirus type 5 induce p53-dependent apoptosis. However, our group has shown recently that the 289-residue E1A protein is also able to induce apoptosis by a p53-independent mechanism (J. G. Teodoro, G. C. Shore, and P. E. Branton, Oncogene 11:467-474, 1995). Preliminary results suggested that p53-independent cell death required expression of one or more additional adenovirus early gene products. Here we show that both the E1B 19-kDa protein and cellular Bcl-2 inhibit or significantly delay p53-independent apoptosis. Neither early region E2 or E3 appeared to be necessary for such cell death. Analysis of a series of E1A mutants indicated that mutations in the transactivation domain and other regions of E1A correlated with E1A-mediated transactivation of E4 gene expression. Furthermore, p53-deficient human SAOS-2 cells infected with a mutant which expresses E1B but none of the E4 gene products remained viable for considerably longer times than those infected with wild-type adenovirus type 5. In addition, an adenovirus vector lacking both E1 and E4 was unable to induce DNA degradation and cell killing in E1A-expressing cell lines. These data showed that an E4 product is essential for E1A-induced p53-independent apoptosis. PMID:8709247

  5. p53 independent G0/G1 arrest and apoptosis induced by a novel retinoid in human breast cancer cells.

    PubMed

    Shao, Z M; Dawson, M I; Li, X S; Rishi, A K; Sheikh, M S; Han, Q X; Ordonez, J V; Shroot, B; Fontana, J A

    1995-08-01

    The biological activity of a novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) was investigated in human breast carcinoma (HBC) cells. Although capable of selective binding to the RAR gamma nuclear receptor, AHPN inhibited the growth of a number of HBC cell lines via RAR- or RXR-independent pathways. AHPN also inhibited the growth of the human leukemia cell line HL-60R which does not possess functional RARs. RA significantly inhibited AP-1 mediated gene activation in MCF-7 cells while AHPN displayed no such anti-AP-1 activity. Retinoids normally are cytostatic in their inhibition of breast carcinoma growth and permit cell proliferation upon their removal, wher as AHPN induced G0/G1 arrest within 6h followed by apoptosis. In MCF-7 cells that harbor wild type p53, AHPN-induced G0/G1 arrest and apoptosis was accompanied by p53-independent regulation of WAF1/CIP1 as well as bax mRNA levels while bcl-2 mRNA levels were decreased. In MDA-MB-231 cells which possess a mutant p53, AHPN-mediated G0/G1 arrest and apoptosis was also associated with a concomitant up regulation of WAF1/CIP1 mRNA while these cells did not express bax or bcl-2 messages. Thus AHPN represents a novel retinoid that induces G0/G1 arrest and apoptosis via a unique pathway which appears to involve activation of known downstream effectors of p53 in a p53-independent manner. PMID:7630633

  6. Methylsulfonylmethane Induces p53 Independent Apoptosis in HCT-116 Colon Cancer Cells

    PubMed Central

    Karabay, Arzu Zeynep; Koc, Asli; Ozkan, Tulin; Hekmatshoar, Yalda; Sunguroglu, Asuman; Aktan, Fugen; Buyukbingol, Zeliha

    2016-01-01

    Methylsulfonylmethane (MSM) is an organic sulfur-containing compound which has been used as a dietary supplement for osteoarthritis. MSM has been shown to reduce oxidative stress and inflammation, as well as exhibit apoptotic or anti-apoptotic effects depending on the cell type or activating stimuli. However, there are still a lot of unknowns about the mechanisms of actions of MSM. In this study, MSM was tested on colon cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis revealed that MSM inhibited cell viability and increased apoptotic markers in both HCT-116 p53 +/+ and HCT-116 p53 −/− colon cancer cells. Increased poly (ADP-ribose) polymerase (PARP) fragmentation and caspase-3 activity by MSM also supported these findings. MSM also modulated the expression of various apoptosis-related genes and proteins. Moreover, MSM was found to increase c-Jun N-terminal kinases (JNK) phosphorylation in both cell lines, dose-dependently. In conclusion, our results show for the first time that MSM induces apoptosis in HCT-116 colon cancer cells regardless of their p53 status. Since p53 is defective in >50% of tumors, the ability of MSM to induce apoptosis independently of p53 may offer an advantage in anti-tumor therapy. Moreover, the remarkable effect of MSM on Bim, an apoptotic protein, also suggests its potential use as a novel chemotherapeutic agent for Bim-targeted anti-cancer therapies. PMID:27428957

  7. Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

    SciTech Connect

    Nakagawa, Yosuke; Takahashi, Akihisa; Kajihara, Atsuhisa; Yamakawa, Nobuhiro; Imai, Yuichiro; Ota, Ichiro; Okamoto, Noritomo; Mori, Eiichiro; Noda, Taichi; Furusawa, Yoshiya; Kirita, Tadaaki; Ohnishi, Takeo

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer High-LET radiation induces efficiently apoptosis regardless of p53 gene status. Black-Right-Pointing-Pointer We examined whether high-LET radiation depresses the Akt-survival signals. Black-Right-Pointing-Pointer High-LET radiation depresses of survival signals even in the mp53 cancer cells. Black-Right-Pointing-Pointer High-LET radiation activates Caspase-9 through depression of survival signals. Black-Right-Pointing-Pointer High-LET radiation suppresses cell growth through depression of survival signals. -- Abstract: Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G{sub 2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp

  8. Inhibition of AKT/FoxO3a signaling induced PUMA expression in response to p53-independent cytotoxic effects of H1: A derivative of tetrandrine.

    PubMed

    Zhang, Yin-Xu; Liu, Xiao-Mei; Wang, Jing; Li, Jun; Liu, Ying; Zhang, Hua; Yu, Xue-Wen; Wei, Ning

    2015-01-01

    PUMA (p53 unregulated modulator of apoptosis), a BH3-only Bcl-2 family member, can be induced by p53-dependent and p53-independent manners. It plays an important role as regulator of cellular apoptosis. Herein, we evaluate the effects of H1 (a derivative of tetrandrine) on induction of PUMA and underlie its potential mechanism in p53-independent cytotoxic response. Anti-proliferative activity and evidently cytotoxic activity of H1 were observed in wild-type and p53 null cells. Further studies demonstrated that H1 resulted in an increase of cleaved PARP, decease of survivin and elevation of p-H2AX. What is more, H1 significantly induced PUMA expression in a concentration- and time-dependent manner and caused an increase of Bax/Bcl-2 ratio in p53 null cells. Of note, knockdown of PUMA attenuated cytotoxic activity of H1. Further studies demonstrated that inhibition of AKT/FoxO3a signaling contributed to H1-mediated PUMA induction. Targeted suppression of AKT/FoxO3a signaling by siRNA could overcome H1-mediated PUMA induction. In addition, H1 significantly suppressed NF-κB activity and caused an increase of early apoptotic and late apoptotic cells, and elevated caspase-3 activity. Taken together, we found that inhibition of AKT/FoxO3a signaling may contribute to H1-mediated PUMA induction, suggesting that inhibition of AKT/FoxO3a signaling result in PUMA expression in response to p53-independent cytotoxic effects of H1. PMID:25893985

  9. Ursolic Acid, a Pentacyclin Triterpene, Potentiates TRAIL-induced Apoptosis through p53-independent Up-regulation of Death Receptors

    PubMed Central

    Prasad, Sahdeo; Yadav, Vivek R.; Kannappan, Ramaswamy; Aggarwal, Bharat B.

    2011-01-01

    Discovery of the molecular targets of traditional medicine and its chemical footprints can validate the use of such medicine. In the present report, we investigated the effect of ursolic acid (UA), a pentacyclic triterpenoid found in rosemary and holy basil, on apoptosis induced by TRAIL. We found that UA potentiated TRAIL-induced apoptosis in cancer cells. In addition, UA also sensitized TRAIL-resistant cancer cells to the cytokine. When we investigated the mechanism, we found that UA down-regulated cell survival proteins and induced the cell surface expression of both TRAIL receptors, death receptors 4 and 5 (DR4 and -5). Induction of receptors by UA occurred independently of cell type. Gene silencing of either receptor by small interfering RNA reduced the apoptosis induced by UA and the effect of TRAIL. In addition, UA also decreased the expression of decoy receptor 2 (DcR2) but not DcR1. Induction of DRs was independent of p53 because UA induced DR4 and DR5 in HCT116 p53−/− cells. Induction of DRs, however, was dependent on JNK because UA induced JNK, and its pharmacologic inhibition abolished the induction of the receptors. The down-regulation of survival proteins and up-regulation of the DRs required reactive oxygen species (ROS) because UA induced ROS, and its quenching abolished the effect of the terpene. Also, potentiation of TRAIL-induced apoptosis by UA was significantly reduced by both ROS quenchers and JNK inhibitor. In addition, UA was also found to induce the expression of DRs, down-regulate cell survival proteins, and activate JNK in orthotopically implanted human colorectal cancer in a nude mouse model. Overall, our results showed that UA potentiates TRAIL-induced apoptosis through activation of ROS and JNK-mediated up-regulation of DRs and down-regulation of DcR2 and cell survival proteins. PMID:21156789

  10. 2-Phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells.

    PubMed

    Steele, Andrew J; Prentice, Archibald G; Hoffbrand, A Victor; Yogashangary, Birunthini C; Hart, Stephen M; Lowdell, Mark W; Samuel, Edward R; North, Janet M; Nacheva, Elisabeth P; Chanalaris, Anastasios; Kottaridis, Panagiotis; Cwynarski, Kate; Wickremasinghe, R Gitendra

    2009-08-01

    We studied the actions of 2-phenylacetylenesulfonamide (PAS) on B-chronic lymphocytic leukemia (CLL) cells. PAS (5-20 microM) initiated apoptosis within 24 hours, with maximal death at 48 hours asassessed by morphology, cleavage of poly(ADP-ribose) polymerase (PARP), caspase 3 activation, and annexin V staining. PAS treatment induced Bax proapoptotic conformational change, Bax movement from the cytosol to the mitochondria, and cytochrome c release, indicating that PAS induced apoptosis via the mitochondrial pathway. PAS induced approximately 3-fold up-regulation of proapoptotic Noxa protein and mRNA levels. In addition, Noxa was found unexpectedly to be bound to Bcl-2 in PAS-treated cells. PAS treatment of CLL cells failed to up-regulate p53, suggesting that PAS induced apoptosis independently of p53. Furthermore, PAS induced apoptosis in CLL isolates with p53 gene deletion in more than 97% of cells. Normal B lymphocytes were as sensitive to PAS-induced Noxa up-regulation and apoptosis as were CLL cells. However, both T lymphocytes and bone marrow hematopoietic progenitor cells were relatively resistant to PAS. Our data suggest that PAS may represent a novel class of drug that induces apoptosis in CLL cells independently of p53 status by a mechanism involving Noxa up-regulation. PMID:19515722

  11. NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner

    PubMed Central

    Hebar, Alexandra; Rütgen, Barbara C.; Selzer, Edgar

    2012-01-01

    The new molecular entity quinoxalinhydrazide derivative NVX-412 was identified as a promising drug candidate for the treatment of various cancer types due to its strong cytotoxic activity and relative specificity. Here, we provide first data about the mechanisms of action of NVX-412. We show that NVX-412 exerts its anti-neoplastic activity in a p53-independent manner and induces S-phase arrest and DNA damage as assessed by γH2AX staining. We suggest a bi-modal (dose-dependent) mode of action of NVX-412, being primarily cytostatic at lower and predominantly cytotoxic at higher concentrations. Based on the broad and consistent anti-neoplastic activity observed, NVX-412 holds promise as an effective drug candidate for the treatment of various cancer types, especially for hematological malignancies with highly unmet medical need. PMID:23028738

  12. A Dual-Targeting, p53-Independent, Apoptosis-Inducing Platinum(II) Anticancer Complex, [Pt(BDIQQ)]Cl

    PubMed Central

    Suntharalingam, Kogularamanan; Wilson, Justin J.; Lin, Wei; Lippard, Stephen J.

    2014-01-01

    The therapeutic index and cellular mechanism of action of [Pt(BDIQQ)]Cl, a monocationic, square-planar platinum(II) complex, are reported. [Pt(BDIQQ)]Cl was used to treat several cell lines, including wild type and cisplatin-resistant ovarian carcinoma cells (A2780 and A2780CP70) and non-proliferating lung carcinoma cells (A549). [Pt(BDIQQ)]Cl selectively kills cancer over healthy cells and exhibits no cross-resistance with cisplatin. The mechanism of cell killing was established through detailed cell-based assays. [Pt(BDIQQ)]Cl exhibits dual-threat capabilities, targeting nuclear DNA and mitochondria simultaneously. [Pt(BDIQQ)]Cl induces DNA damage, leading to p53 enrichment, mitochondrial membrane potential depolarisation, and caspase-mediated apoptosis. [Pt(BDIQQ)]Cl also accumulates in the mitochondria, resulting in direct mitochondrial damage. Flow cytometric studies demonstrated that [Pt(BDIQQ)]Cl has no significant effect on cell cycle progression. Remarkably, p53-status is a not a determinant of [Pt(BDIQQ)]Cl activity. In p53-null cells, [Pt(BDIQQ)]Cl induces cell death through mitochondrial dysfunction. Cancers with p53-null status could therefore be targeted using [Pt(BDIQQ)]Cl. PMID:24514456

  13. Depletion of the cisplatin targeted HMGB-box factor UBF selectively induces p53-independent apoptotic death in transformed cells

    PubMed Central

    Hamdane, Nourdine; Herdman, Chelsea; Mars, Jean-Clement; Stefanovsky, Victor; Tremblay, Michel G.; Moss, Tom

    2015-01-01

    Cisplatin-DNA adducts act as strong decoys for the Upstream Binding Factor UBF (UBTF) and have been shown to inhibit transcription of the ribosomal RNA genes by RNA polymerase I. However, it is unclear if this plays a significant role in the chemotherapeutic activity of cis- or carboplatin. We find that cisplatin in fact induces a very rapid displacement of UBF from the ribosomal RNA genes and strong inhibition of ribosomal RNA synthesis, consistent with this being an important factor in its cytotoxicity. Using conditional gene deletion, we recently showed that UBF is an essential factor for transcription of the ribosomal RNA genes and for ribosome biogenesis. We now show that loss of UBF arrests cell proliferation and induces fully penetrant, rapid and synchronous apoptosis, as well as nuclear disruption and cell death, specifically in cells subjected to oncogenic stress. Apoptosis is not affected by homozygous deletion of the p53 gene and occurs equally in cells transformed by SV40 T antigens, by Myc or by a combination of Ras & Myc oncogenes. The data strongly argue that inhibition of UBF function is a major factor in the cytotoxicity of cisplatin. Hence, drug targeting of UBF may be a preferable approach to the use of the highly toxic platins in cancer therapy. PMID:26317157

  14. Depletion of the cisplatin targeted HMGB-box factor UBF selectively induces p53-independent apoptotic death in transformed cells.

    PubMed

    Hamdane, Nourdine; Herdman, Chelsea; Mars, Jean-Clement; Stefanovsky, Victor; Tremblay, Michel G; Moss, Tom

    2015-09-29

    Cisplatin-DNA adducts act as strong decoys for the Upstream Binding Factor UBF (UBTF) and have been shown to inhibit transcription of the ribosomal RNA genes by RNA polymerase I. However, it is unclear if this plays a significant role in the chemotherapeutic activity of cis- or carboplatin. We find that cisplatin in fact induces a very rapid displacement of UBF from the ribosomal RNA genes and strong inhibition of ribosomal RNA synthesis, consistent with this being an important factor in its cytotoxicity. Using conditional gene deletion, we recently showed that UBF is an essential factor for transcription of the ribosomal RNA genes and for ribosome biogenesis. We now show that loss of UBF arrests cell proliferation and induces fully penetrant, rapid and synchronous apoptosis, as well as nuclear disruption and cell death, specifically in cells subjected to oncogenic stress. Apoptosis is not affected by homozygous deletion of the p53 gene and occurs equally in cells transformed by SV40 T antigens, by Myc or by a combination of Ras & Myc oncogenes. The data strongly argue that inhibition of UBF function is a major factor in the cytotoxicity of cisplatin. Hence, drug targeting of UBF may be a preferable approach to the use of the highly toxic platins in cancer therapy. PMID:26317157

  15. Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway.

    PubMed

    Pavlou, Demetria; Kirmizis, Antonis

    2016-03-01

    Protein N-terminal acetylation is an abundant post-translational modification in eukaryotes implicated in various fundamental cellular and biochemical processes. This modification is catalysed by evolutionarily conserved N-terminal acetyltransferases (NATs) whose deregulation has been linked to cancer development and thus, are emerging as useful diagnostic and therapeutic targets. Naa40 is a highly selective NAT that acetylates the amino-termini of histones H4 and H2A and acts as a sensor of cell growth in yeast. In the present study, we examine the role of Naa40 in cancer cell survival. We demonstrate that depletion of Naa40 in HCT116 and HT-29 colorectal cancer cells decreases cell survival by enhancing apoptosis, whereas Naa40 reduction in non-cancerous mouse embryonic fibroblasts has no effect on cell viability. Specifically, Naa40 knockdown in colon cancer cells activates the mitochondrial caspase-9-mediated apoptotic cascade. Consistent with this, we show that caspase-9 activation is required for the induced apoptosis because treatment of cells with an irreversible caspase-9 inhibitor impedes apoptosis when Naa40 is depleted. Furthermore, the effect of Naa40-depletion on cell-death is mediated through a p53-independent mechanism since p53-null HCT116 cells still undergo apoptosis upon reduction of the acetyltransferase. Altogether, these findings reveal an anti-apoptotic role for Naa40 and exhibit its potential as a therapeutic target in colorectal cancers. PMID:26666750

  16. The DR6 protein from human herpesvirus-6B induces p53-independent cell cycle arrest in G{sub 2}/M

    SciTech Connect

    Schleimann, Mariane H.; Hoberg, Søren; Solhøj Hansen, Aida; Bundgaard, Bettina; Witt, Christoffer T.; Kofod-Olsen, Emil; Höllsberg, Per

    2014-03-15

    HHV-6B infection inhibits cell proliferation in G{sub 2}/M, but no protein has so far been recognized to exert this function. Here we identify the protein product of direct repeat 6, DR6, as an inhibitor of G{sub 2}/M cell-cycle progression. Transfection of DR6 reduced the total number of cells compared with mock-transfected cells. Lentiviral transduction of DR6 inhibited host cell DNA synthesis in a p53-independent manner, and this inhibition was DR6 dose-dependent. A deletion of 66 amino acids from the N-terminal part of DR6 prevented efficient nuclear translocation and the ability to inhibit DNA synthesis. DR6-induced accumulation of cells in G{sub 2}/M was accompanied by an enhanced expression of cyclin B1 that accumulated predominantly in the cytoplasm. Pull-down of cyclin B1 brought down pCdk1 with the inactivating phosphorylation at Tyr15. Together, DR6 delays cell cycle with an accumulation of cells in G{sub 2}/M and thus might be involved in HHV-6B-induced cell-cycle arrest. - Highlights: • HHV-6B-encoded DR6 protein inhibits cell proliferation. • DR6 inhibits host cell DNA synthesis independent of p53. • DR6 delays the cell cycle in G{sub 2}/M. • An N-terminal sequence is necessary for DR6 function. • DR6 induces cytoplasmic accumulation of cyclin B1.

  17. Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis of H1299 cells via ROS-dependent and p53-independent NF-κB activation

    SciTech Connect

    Yun, Hong Shik; Baek, Jeong-Hwa; Yim, Ji-Hye; Lee, Su-Jae; Lee, Chang-Woo; Song, Jie-Young; Um, Hong-Duck; Park, Jong Kuk; Park, In-Chul; Hwang, Sang-Gu

    2014-07-11

    Highlights: • HRP-3 is a radiation- and anticancer drug-responsive protein in H1299 cells. • Depletion of HRP-3 induces apoptosis of radio- and chemoresistant H1299 cells. • Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. • ROS generation enhances NF-κB activity, which acts as an upstream signal in the c-Myc/Noxa apoptotic pathway. - Abstract: We previously identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistant biomarker in p53 wild-type A549 cells and found that p53-dependent induction of the PUMA pathway was a critical event in regulating the radioresistant phenotype. Here, we found that HRP-3 knockdown regulates the radioresistance of p53-null H1299 cells through a distinctly different molecular mechanism. HRP-3 depletion was sufficient to cause apoptosis of H1299 cells by generating substantial levels of reactive oxygen species (ROS) through inhibition of the Nrf2/HO-1 antioxidant pathway. Subsequent, ROS-dependent and p53-independent NF-κB activation stimulated expression of c-Myc and Noxa proteins, thereby inducing the apoptotic machinery. Our results thus extend the range of targets for the development of new drugs to treat both p53 wild-type or p53-null radioresistant lung cancer cells.

  18. Phorbol esters induce death in MCF-7 breast cancer cells with altered expression of protein kinase C isoforms. Role for p53-independent induction of gadd-45 in initiating death.

    PubMed Central

    de Vente, J E; Kukoly, C A; Bryant, W O; Posekany, K J; Chen, J; Fletcher, D J; Parker, P J; Pettit, G J; Lozano, G; Cook, P P

    1995-01-01

    Protein kinase C (PKC) modulates growth, differentiation and apoptosis in a cell-specific fashion. Overexpression of PKC-alpha in MCF-7 breast cancer cells (MCF-7-PKC-alpha cell) leads to expression of a more transformed phenotype. The response of MCF-7 and MCF-7-PKC-alpha cells to phorbol esters (TPA) was examined. TPA-treated MCF-7 cells demonstrated a modest cytostatic response associated with a G1 arrest that was accompanied by Cip1 expression and retinoblastoma hypophosphorylation. While p53 was detected in MCF-7 cells, evidence for TPA-induced stimulation of p53 transcriptional activity was not evident. In contrast, TPA treatment induced death of MCF-7-PKC-alpha cells. Bryostatin 1, another PKC activator, exerted modest cytostatic effects on MCF-7 cells while producing a cytotoxic response at low doses in MCF-7-PKC-alpha cells that waned at higher concentrations. TPA-treated MCF-7-PKC-alpha cells accumulated in G2/M, did not express p53, displayed decreased Cip1 expression, and demonstrated a reduction in retinoblastoma hypophosphorylation. TPA-treated MCF-7-PKC-alpha cells expressed gadd-45 which occurred before the onset of apoptosis. Thus, alterations in the PKC pathway can modulate the decision of a breast cancer cell to undergo death or differentiation. In addition, these data show that PKC activation can induce expression of gadd45 in a p53-independent fashion. Images PMID:7560079

  19. The p90 ribosomal S6 kinase (RSK) inhibitor BI-D1870 prevents gamma irradiation-induced apoptosis and mediates senescence via RSK- and p53-independent accumulation of p21WAF1/CIP1

    PubMed Central

    Neise, D; Sohn, D; Stefanski, A; Goto, H; Inagaki, M; Wesselborg, S; Budach, W; Stühler, K; Jänicke, R U

    2013-01-01

    The p90 ribosomal S6 kinase (RSK) family is a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. As they are almost exclusively activated downstream of extracellular signal-regulated kinases 1 and 2 (ERK1/2), therapeutic intervention by RSK inhibition is less likely to produce such severe side effects as those observed following inhibition of the upstream master regulators Raf, MEK and ERK1/2. Here, we report that BI-D1870, a potent small molecule inhibitor of RSKs, induces apoptosis, although preferentially, in a p21-deficient background. On the other hand, BI-D1870 also induces a strong transcription- and p53-independent accumulation of p21 protein and protects cells from gamma irradiation (γIR)-induced apoptosis, driving them into senescence even in the absence of γIR. Although we identified p21 in in vitro kinase assays as a novel RSK substrate that specifically becomes phosphorylated by RSK1-3 at Ser116 and Ser146, RNA-interference, overexpression and co-immunoprecipitation studies as well as the use of SL0101, another specific RSK inhibitor, revealed that BI-D1870 mediates p21 accumulation via a yet unknown pathway that, besides its off-site targets polo-like kinase-1 and AuroraB, also does also not involve RSKs. Thus, this novel off-target effect of BI-D1870 should be taken into serious consideration in future studies investigating the role of RSKs in cellular signaling and tumorigenesis. PMID:24136223

  20. v-Src Generates a p53-Independent Apoptotic Signal

    PubMed Central

    Webb, Brian L.; Jimenez, Elsa; Martin, G. Steven

    2000-01-01

    Evasion of apoptosis appears to be a necessary event in tumor progression. Some oncogenes, such as c-myc and E1A, induce apoptosis in the absence of survival factors. However, others, such as bcl-2 and v-src, activate antiapoptotic pathways. For v-Src, these antiapoptotic pathways are dependent on the function of Ras, phosphatidylinositol (PI) 3-kinase, and Stat3. Here we asked whether v-Src can activate a proapoptotic signal when survival signaling is inhibited. We show that when the functions of Ras and PI 3-kinase are inhibited, v-src-transformed Rat-2 fibroblasts undergo apoptosis, evidenced by loss of adherence, nuclear fragmentation, and chromosomal DNA degradation. The apoptotic response is dependent on activation of caspase 3. Under similar conditions nontransformed Rat-2 cells undergo considerably lower levels of apoptosis. Apoptosis induced by v-Src is accompanied by a loss of mitochondrial membrane potential and release of cytochrome c and is blocked by overexpression of bcl-2, indicating that it is mediated by the mitochondrial pathway. However apoptosis induced by v-Src is not accompanied by an increase in the level of p53 and is not dependent on p53 function. Thus v-Src generates a p53-independent proapoptotic signal. PMID:11094078

  1. Structural Determinants of p53-Independence in Anticancer Ruthenium-Arene Schiff-Base Complexes.

    PubMed

    Chow, Mun Juinn; Babak, Maria V; Wong, Daniel Yuan Qiang; Pastorin, Giorgia; Gaiddon, Christian; Ang, Wee Han

    2016-07-01

    p53 is a key tumor suppressor gene involved in key cellular processes and implicated in cancer therapy. However, it is inactivated in more than 50% of all cancers due to mutation or overexpression of its negative regulators. This leads to drug resistance and poor chemotherapeutic outcome as most clinical drugs act via a p53-dependent mechanism of action. An attractive strategy to circumvent this resistance would be to identify new anticancer drugs that act via p53-independent mode of action. In the present study, we identified 9 Ru (II)-Arene Schiff-base (RAS) complexes able to induce p53-independent cytotoxicity and discuss structural features that are required for their p53-independent activity. Increasing hydrophobicity led to an increase in cellular accumulation in cells with a corresponding increase in efficacy. We further showed that all nine complexes demonstrated p53-independent activity. This was despite significant differences in their physicochemical properties, suggesting that the iminoquinoline ligand, a common structural feature for all the complexes, is required for the p53-independent activity. PMID:27174050

  2. Decarbamoyl mitomycin C (DMC) activates p53-independent ataxia telangiectasia and rad3 related protein (ATR) chromatin eviction

    PubMed Central

    Xiao, Gu; Kue, Pao; Bhosle, Rahul; Bargonetti, Jill

    2015-01-01

    Interstrand crosslinks induce DNA replication fork stalling that in turn activates the ATR-dependent checkpoint and DNA repair on nuclear chromatin. Mitomycin C (MC) and Decarbamoyl Mitomycin C (DMC) induce different types of DNA crosslinks with DMC being a more cytotoxic agent. We previously reported that the novel DMC induced β–interstrand DNA crosslinks induce a p53-independent form of cell death. The p53-independent DMC cytotoxicity associates with the activation, and subsequent depletion, of Chk1. In this study we further dissect the novel DMC signal transduction pathway and asked how it influences chromatin-associated proteins. We found that treatment with DMC, but not MC, stimulated the disassociation of ATR from chromatin and re-localization of ATR to the cytoplasm. The chromatin eviction of ATR was coupled with the formation of nuclear Rad51 foci and the phosphorylation of Chk1. Furthermore, DMC but not MC, activated expression of gadd45α mRNA. Importantly, knocking down p53 via shRNA did not inhibit the DMC-induced disassociation of ATR from chromatin or reduce the activation of transcription of gadd45α. Our results suggest that DMC induces a p53-independent disassociation of ATR from chromatin that facilitates Chk1 checkpoint activation and Rad51 chromatin recruitment. Our findings provide evidence that ATR chromatin eviction in breast cancer cells is an area of study that should be focused on for inducing p53-independent cell death. PMID:25565400

  3. JKA97, a Novel Benzylidene Analog of Harmine, Exerts Anti-Cancer Effects by Inducing G1 Arrest, Apoptosis, and p53-Independent Up-Regulation of p21

    PubMed Central

    Qin, Jiang-Jiang; Wang, Ming-Hai; Sharma, Horrick; Buolamwini, John K.; Wang, Hui; Zhang, Ruiwen

    2012-01-01

    JKA97, a benzylidene analog of harmine, has been found to be a promising drug candidate for human cancer therapy, although the underlying molecular mechanisms have not been fully demonstrated. In this study, we evaluated the effects of JKA97 on human breast cancer cells in vitro and in vivo. JKA97 inhibited the growth and proliferation of MCF7 (p53 wild-type), MCF7 (p53 knockdown), and MDA-MB-468 (p53 mutant) cells in a dose-dependent manner. Treatment with JKA97 arrested breast cancer cells in G1 phase and induced apoptosis. JKA97 also significantly suppressed the growth of MCF7 and MDA-MB-468 xenograft tumors. It regulated the expression levels of G1 phase regulators, such as p21, p27, cyclinE, and cylinD1. JKA97 activated p21 transcription, independent of p53, but had little effect on p21 protein stability/degradation. In summary, our results suggest that JKA97 inhibits human breast cancer cell growth through activating p21, independent of p53, which provides a basis for developing this compound as a novel drug for human breast cancer therapy. PMID:22558087

  4. p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation

    PubMed Central

    2013-01-01

    Background To determine whether ceramide is responsible for the induction of p53-independent early or late apoptosis in response to high- and low-Linear-Energy-Transfer (LET) irradiation. Methods Four cell lines displaying different radiosensitivities and p53-protein status were irradiated with photons or 33.4 or 184 keV/μm carbon ions. The kinetics of ceramide production was quantified by fluorescent microscopy or High-Performance-Liquid-Chromatogaphy and the sequence of events leading to apoptosis by flow cytometry. Results Regardless of the p53-status, both low and high-LET irradiation induced an early ceramide production in radiosensitive cells and late in the radioresistant. This production strongly correlated with the level of early apoptosis in radiosensitive cells and delayed apoptosis in the radioresistant ones, regardless of radiation quality, tumor type, radiosensitivity, or p53-status. Inhibition of caspase activity or ceramide production showed that, for both types of radiation, ceramide is essential for the initiation of early apoptosis in radiosensitive cells and late apoptosis following mitotic catastrophe in radioresistant cells. Conclusions Ceramide is a determining factor in the onset of early and late apoptosis after low and high-LET irradiation and is the mediator of the p53-independent-apoptotic pathway. We propose that ceramide is the molecular bridge between mitotic catastrophe and the commitment phase of delayed apoptosis in response to irradiation. PMID:23530619

  5. Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing.

    PubMed

    Galanos, Panagiotis; Vougas, Konstantinos; Walter, David; Polyzos, Alexander; Maya-Mendoza, Apolinar; Haagensen, Emma J; Kokkalis, Antonis; Roumelioti, Fani-Marlen; Gagos, Sarantis; Tzetis, Maria; Canovas, Begoña; Igea, Ana; Ahuja, Akshay K; Zellweger, Ralph; Havaki, Sofia; Kanavakis, Emanuel; Kletsas, Dimitris; Roninson, Igor B; Garbis, Spiros D; Lopes, Massimo; Nebreda, Angel; Thanos, Dimitris; Blow, J Julian; Townsend, Paul; Sørensen, Claus Storgaard; Bartek, Jiri; Gorgoulis, Vassilis G

    2016-07-01

    The cyclin-dependent kinase inhibitor p21(WAF1/CIP1) (p21) is a cell-cycle checkpoint effector and inducer of senescence, regulated by p53. Yet, evidence suggests that p21 could also be oncogenic, through a mechanism that has so far remained obscure. We report that a subset of atypical cancerous cells strongly expressing p21 showed proliferation features. This occurred predominantly in p53-mutant human cancers, suggesting p53-independent upregulation of p21 selectively in more aggressive tumour cells. Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. Mechanistically, sustained p21 accumulation inhibited mainly the CRL4-CDT2 ubiquitin ligase, leading to deregulated origin licensing and replication stress. Collectively, our data reveal the tumour-promoting ability of p21 through deregulation of DNA replication licensing machinery-an unorthodox role to be considered in cancer treatment, since p21 responds to various stimuli including some chemotherapy drugs. PMID:27323328

  6. Data for a proteomic analysis of p53-independent induction of apoptosis by bortezomib.

    PubMed

    Yerlikaya, Azmi; Okur, Emrah; Tarık Baykal, Ahmet; Acılan, Ceyda; Boyacı, İhsan; Ulukaya, Engin

    2014-12-01

    This data article contains data related to the research article entitled, "A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line" by Yerlikaya et al. [1]. The research article presented 2-DE and nLC-MS/MS based proteomic analysis of proteasome inhibitor bortezomib-induced changes in the expression of cellular proteins. The report showed that GRP78 and TCEB2 were over-expressed in response to treatment with bortezomib for 24 h. In addition, the report demonstrated that Hsp70, the 26S proteasome non-ATPase regulatory subunit 14 and sequestosome 1 were increased at least 2 fold in p53-deficient 4T1 cells. The data here show for the first time the increased expressions of Card10, Dffb, Traf3 and Trp53bp2 in response to inhibition of the 26S proteasome. The information presented here also shows that both Traf1 and Xiap (a member of IAPs) are also downregulated simultaneously upon proteasomal inhibition. The increases in the level of Card10 and Trp53bp2 proteins were verified by Western blot analysis in response to varying concentrations of bortezomib for 24 h. PMID:26217687

  7. ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies

    PubMed Central

    Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O.; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E.; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C.; Orlowski, Robert; Sarbassov, Dos D.; Lorenzi, Philip L.; Huang, Xuelin; Neelapu, Sattva S.; McDonnell, Timothy; Miranda, Roberto N.; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R. Eric.; Andreeff, Michael

    2016-01-01

    The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. PMID:26884599

  8. ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.

    PubMed

    Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C; Orlowski, Robert; Sarbassov, Dos D; Lorenzi, Philip L; Huang, Xuelin; Neelapu, Sattva S; McDonnell, Timothy; Miranda, Roberto N; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R Eric; Andreeff, Michael

    2016-02-16

    The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. PMID:26884599

  9. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides.

    PubMed

    Liu, Jung-Sen; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Inbaraj, Baskaran Stephen; Lu, Jyh-Feng; Chen, Bing-Huei

    2015-07-01

    The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50 ) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). PMID:25781909

  10. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides

    PubMed Central

    Liu, Jung-Sen; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Inbaraj, Baskaran Stephen; Lu, Jyh-Feng; Chen, Bing-Huei

    2015-01-01

    The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). PMID:25781909

  11. The Wnt Target Protein Peter Pan Defines a Novel p53-independent Nucleolar Stress-Response Pathway.

    PubMed

    Pfister, Astrid S; Keil, Marina; Kühl, Michael

    2015-04-24

    Proper ribosome formation is a prerequisite for cell growth and proliferation. Failure of this process results in nucleolar stress and p53-mediated apoptosis. The Wnt target Peter Pan (PPAN) is required for 45 S rRNA maturation. So far, the role of PPAN in nucleolar stress response has remained elusive. We demonstrate that PPAN localizes to mitochondria in addition to its nucleolar localization and inhibits the mitochondrial apoptosis pathway in a p53-independent manner. Loss of PPAN induces BAX stabilization, depolarization of mitochondria, and release of cytochrome c, demonstrating its important role as an anti-apoptotic factor. Staurosporine-induced nucleolar stress and apoptosis disrupt nucleolar PPAN localization and induce its accumulation in the cytoplasm. This is accompanied by phosphorylation and subsequent cleavage of PPAN by caspases. Moreover, we show that PPAN is a novel interaction partner of the anti-apoptotic protein nucleophosmin (NPM). PPAN depletion induces NPM and upstream-binding factor (UBF) degradation, which is independent of caspases. In summary, we provide evidence for a novel nucleolar stress-response pathway involving PPAN, NPM, and BAX to guarantee cell survival in a p53-independent manner. PMID:25759387

  12. Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action

    PubMed Central

    Mrozek-Wilczkiewicz, Anna; Rams-Baron, Marzena; Kryštof, Vladimír; Musiol, Robert

    2015-01-01

    A group of styrylquinolines were synthesized and tested for their anti-proliferative activity. Anti-proliferative activity was evaluated against the human colon carcinoma cell lines that had a normal expression of the p53 protein (HCT116 p53+/+) and mutants with a disabled TP53 gene (HCT116 p53-/-) and against the GM 07492 normal human fibroblast cell line. A SAR study revealed the importance of Cl and OH as substituents in the styryl moiety. Several of the compounds that were tested were found to have a marked anti-proliferative activity that was similar to or better than doxorubicin and were more active against the p53 null than the wild type cells. The cellular localization tests and caspase activity assays suggest a mechanism of action through the mitochondrial pathway of apoptosis in a p53-independent manner. The activity of the styrylquinoline compounds may be associated with their DNA intercalating ability. PMID:26599982

  13. Discovery and optimization of new benzofuran derivatives against p53-independent malignant cancer cells through inhibition of HIF-1 pathway.

    PubMed

    Yang, Ying-Rui; Wei, Jin-Lian; Mo, Xiao-Fei; Yuan, Zhen-Wei; Wang, Jia-Lin; Zhang, Chao; Xie, Yi-Yue; You, Qi-Dong; Sun, Hao-Peng

    2016-06-01

    p53-independent malignant cancer is still severe health problem of human beings. HIF-1 pathway is believed to play an important role in the survival and developing progress of such cancers. In the present study, with the aim to inhibit the proliferation of p53-independent malignant cells, we disclose the optimization of 6a, the starting compound which is discovered in the screening of in-house compound collection. The structure-activity relationship (SAR) is summarized. The most potent derivative 8d, inhibits the proliferation of both p53-null and p53-mutated cells through inhibition of HIF-1 pathway. Our findings here provide a new chemotype in designing potent anticancer agent especially against those p53-independent malignant tumors. PMID:27101893

  14. Residues in the alternative reading frame tumor suppressor that influence its stability and p53-independent activities

    SciTech Connect

    Tommaso, Anne di; Hagen, Jussara; Tompkins, Van; Muniz, Viviane; Dudakovic, Amel; Kitzis, Alain; Ladeveze, Veronique; Quelle, Dawn E.

    2009-04-15

    The Alternative Reading Frame (ARF) protein suppresses tumorigenesis through p53-dependent and p53-independent pathways. Most of ARF's anti-proliferative activity is conferred by sequences in its first exon. Previous work showed specific amino acid changes occurred in that region during primate evolution, so we programmed those changes into human p14ARF to assay their functional impact. Two human p14ARF residues (Ala{sup 14} and Thr{sup 31}) were found to destabilize the protein while two others (Val{sup 24} and Ala{sup 41}) promoted more efficient p53 stabilization and activation. Despite those effects, all modified p14ARF forms displayed robust p53-dependent anti-proliferative activity demonstrating there are no significant biological differences in p53-mediated growth suppression associated with simian versus human p14ARF residues. In contrast, p53-independent p14ARF function was considerably altered by several residue changes. Val{sup 24} was required for p53-independent growth suppression whereas multiple residues (Val{sup 24}, Thr{sup 31}, Ala{sup 41} and His{sup 60}) enabled p14ARF to block or reverse the inherent chromosomal instability of p53-null MEFs. Together, these data pinpoint specific residues outside of established p14ARF functional domains that influence its expression and signaling activities. Most intriguingly, this work reveals a novel and direct role for p14ARF in the p53-independent maintenance of genomic stability.

  15. Induction of p53-Independent Apoptosis by the Adenovirus E4orf4 Protein Requires Binding to the Bα Subunit of Protein Phosphatase 2A

    PubMed Central

    Marcellus, Richard C.; Chan, Helen; Paquette, Denis; Thirlwell, Sarah; Boivin, Dominique; Branton, Philip E.

    2000-01-01

    Previous studies have indicated that the E4orf4 protein of human adenovirus type 2 (Ad2) induces p53-independent apoptosis. We believe that this process may play a role in cell death and viral spread at the final stages of productive infection. E4orf4 may also be of therapeutic value in treating some diseases, including cancer, through its ability to induce apoptosis when expressed individually. The only previously identified biochemical function of E4orf4 is its ability to associate with the Bα subunit of protein phosphatase 2A (PP2A). We have used a genetic approach to determine the role of such interactions in E4orf4-induced cell death. E4orf4 deletion mutants were of only limited value, as all were highly defective. We found that E4orf4 proteins from most if not all adenovirus serotypes induced cell death, and thus point mutations were introduced that converted the majority of highly conserved residues to alanines. Such mutants were used to correlate Bα-subunit binding, association with PP2A activity, and cell killing following the transfection of appropriate cDNAs into p53-null H1299 or C33A cells. The results indicated that binding of the Bα subunit is essential for induction of cell death, as every mutant that failed to bind efficiently was totally defective for cell killing. This class of mutations (class I) largely involved residues between amino acids 51 and 89. Almost all E4orf4 mutant proteins that associated with PP2A killed cancer cells at high levels; however, several mutants that associated with significant levels of PP2A were defective for killing (class II). Thus, binding of E4orf4 to PP2A is essential for induction of p53-independent apoptosis, but E4orf4 may possess one or more additional functions required for cell killing. PMID:10933694

  16. p53-independent functions of the p19ARF tumor suppressor

    PubMed Central

    Weber, Jason D.; Jeffers, John R.; Rehg, Jerold E.; Randle, David H.; Lozano, Guillermina; Roussel, Martine F.; Sherr, Charles J.; Zambetti, Gerard P.

    2000-01-01

    The p19ARF tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that p19ARF can act independently of the Mdm2-p53 axis in tumor surveillance. Reintroduction of ARF into TKO mouse embryo fibroblasts (MEFs), but not into those lacking both p53 and ARF, arrested the cell division cycle in the G1 phase. Inhibition of the retinoblastoma protein had no effect on the ability of ARF to arrest TKO MEFs. Thus, in the absence of Mdm2, p19ARF interacts with other targets to inhibit cell proliferation. PMID:10995391

  17. RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis

    PubMed Central

    Saporita, Anthony J.; Chang, Hsiang-Chun; Winkeler, Crystal L.; Apicelli, Anthony J.; Kladney, Raleigh D.; Wang, Jianbo; Townsend, R. Reid; Michel, Loren S.; Weber, Jason D.

    2011-01-01

    The p19ARF tumor suppressor limits ribosome biogenesis and responds to hyperproliferative signals to activate the p53 checkpoint response. While its activation of p53 has been well characterized, ARF’s role in restraining nucleolar ribosome production is poorly understood. Here we report the use of a mass spectroscopic analysis to identify protein changes within the nucleoli of Arf-deficient mouse cells. Through this approach, we discovered that ARF limited the nucleolar localization of the RNA helicase DDX5 which promotes the synthesis and maturation of rRNA, ultimately increasing ribosome output and proliferation. ARF inhibited the interaction between DDX5 and nucleophosmin (NPM), preventing association of DDX5 with the rDNA promoter and nuclear pre-ribosomes. In addition, Arf-deficient cells transformed by oncogenic RasV12 were addicted to DDX5, since reduction of DDX5 was sufficient to impair RasV12-driven colony formation in soft agar and tumor growth in mice. Taken together, our findings indicate that DDX5 is a key p53-independent target of the ARF tumor suppressor and is a novel non-oncogene participant in ribosome biogenesis. PMID:21937682

  18. Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways.

    PubMed

    Chiang, Kun-Chun; Tsui, Ke-Hung; Chung, Li-Chuan; Yeh, Chun-Nan; Feng, Tsui-Hsia; Chen, Wen-Tsung; Chang, Phei-Lang; Chiang, Hou-Yu; Juang, Horng-Heng

    2014-01-01

    Cisplatin is a widely used anti-cancer drug. The B-cell translocation gene 2 (BTG2) is involved in the cell cycle transition regulation. We evaluated the cisplatin effects on prostate cancer cell proliferation and the expressions of BTG2, p53, androgen receptor (AR) and prostate specific antigen (PSA) in prostate carcinoma, p53 wild-type LNCaP or p53-null PC-3, cells. Cisplatin treatments attenuated cell prostate cancer cell growth through inducing Go/G1 cell cycle arrest in lower concentration and apoptosis at higher dosage. Cisplatin treatments enhanced p53 and BTG2 expression, repressed AR and PSA expression, and blocked the activation of androgen on the PSA secretion in LNCaP cells. BTG2 knockdown in LNCaP cells attenuated cisplatin-mediated growth inhibition. Cisplatin enhanced BTG2 gene expression dependent on the DNA fragment located within -173 to -82 upstream of BTG2 translation initiation site in prostate cancer cells. Mutation of the p53 response element from GGGCAGAGCCC to GGGCACC or mutation of the NFκB response element from GGAAAGTCC to GGAAAGGAA by site-directed mutagenesis abolished the stimulation of cisplatin on the BTG2 promoter activity in LNCaP or PC-3 cells, respectively. Our results indicated that cisplatin attenuates prostate cancer cell proliferation partly mediated by upregulation of BTG2 through the p53-dependent pathway or p53-independent NFκB pathway. PMID:24981574

  19. Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways

    PubMed Central

    Chiang, Kun-Chun; Tsui, Ke-Hung; Chung, Li-Chuan; Yeh, Chun-Nan; Feng, Tsui-Hsia; Chen, Wen-Tsung; Chang, Phei-Lang; Chiang, Hou-Yu; Juang, Horng-Heng

    2014-01-01

    Cisplatin is a widely used anti-cancer drug. The B-cell translocation gene 2 (BTG2) is involved in the cell cycle transition regulation. We evaluated the cisplatin effects on prostate cancer cell proliferation and the expressions of BTG2, p53, androgen receptor (AR) and prostate specific antigen (PSA) in prostate carcinoma, p53 wild-type LNCaP or p53-null PC-3, cells. Cisplatin treatments attenuated cell prostate cancer cell growth through inducing Go/G1 cell cycle arrest in lower concentration and apoptosis at higher dosage. Cisplatin treatments enhanced p53 and BTG2 expression, repressed AR and PSA expression, and blocked the activation of androgen on the PSA secretion in LNCaP cells. BTG2 knockdown in LNCaP cells attenuated cisplatin-mediated growth inhibition. Cisplatin enhanced BTG2 gene expression dependent on the DNA fragment located within -173 to -82 upstream of BTG2 translation initiation site in prostate cancer cells. Mutation of the p53 response element from GGGCAGAGCCC to GGGCACC or mutation of the NFκB response element from GGAAAGTCC to GGAAAGGAA by site-directed mutagenesis abolished the stimulation of cisplatin on the BTG2 promoter activity in LNCaP or PC-3 cells, respectively. Our results indicated that cisplatin attenuates prostate cancer cell proliferation partly mediated by upregulation of BTG2 through the p53-dependent pathway or p53-independent NFκB pathway. PMID:24981574

  20. Overexpression of TDP-43 causes partially p53-dependent G2/M arrest and p53-independent cell death in HeLa cells.

    PubMed

    Lee, Kikyo; Suzuki, Hiroaki; Aiso, Sadakazu; Matsuoka, Masaaki

    2012-01-11

    It has been hypothesized that the dysregulation of transactive response DNA-binding protein-43 (TDP-43) in neurons is closely linked to the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions. However, it remains undefined whether the dysregulation of TDP-43 in non-neuronal cells, such as glial cells, contributes to the pathogenesis of these neurodegenerative diseases. Primarily using HeLa cells, we show that a low-grade overexpression of TDP-43, 2- to 5-fold greater than endogenous expression, which is thought to mimic the gain of function of TDP-43, induced cell cycle arrest at the G2/M phase and cell death in cultured non-neuronal cells. Since the activation of p53 may induce G2/M arrest and/or cell death in many abnormal situations, we examined the mechanism underlying G2/M arrest from the standpoint of p53 regulation. It was determined that the TDP-43-induced G2/M arrest was attenuated, while TDP-43-induced death was not attenuated, in cells in which the p53 function was compromised. These data collectively indicate that TDP-43 causes G2/M arrest in a partially p53-dependent manner and it causes cell death in a p53-independent manner in cycling cells. Because it is likely that the impaired proliferation in glial cells causes a decrease in the neuron-supporting ability, these findings further suggests that the gain of function of TDP-43 may cause neurotoxicity by inducing cell cycle arrest and death in glial cells. PMID:22133803

  1. Genome-scale functional analysis of the human genes modulating p53 activity by regulating MDM2 expression in a p53-independent manner.

    PubMed

    Kim, Dong Min; Choi, Seung-Hyun; Yeom, Young Il; Min, Sang-Hyun; Kim, Il-Chul

    2016-09-16

    MDM2, a critical negative regulator of p53, is often overexpressed in leukemia, but few p53 mutations are found, suggesting that p53-independent MDM2 expression occurs due to alterations in MDM2 upstream regulators. In this study, a high MDM2 transcription level was observed (41.17%) regardless of p53 expression in patient with acute myeloid leukemia (AML). Therefore, we performed genome-scale functional screening of the human genes modulating MDM2 expression in a p53-independent manner. We searched co-expression profiles of genes showing a positive or negative pattern with MDM2 expression in a DNA microarray database, selected1089 links, and composed a screening library of 368 genes. Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2. These results indicate that p53-independent upregulation of MDM2 by increasing selected clones may lead to oncogenesis in AML and that MDM2-modulating genes are novel potential targets for AML treatment. PMID:27524244

  2. Endogenous Human MDM2-C Is Highly Expressed in Human Cancers and Functions as a p53-Independent Growth Activator

    PubMed Central

    Okoro, Danielle R.; Arva, Nicoleta; Gao, Chong; Polotskaia, Alla; Puente, Cindy; Rosso, Melissa; Bargonetti, Jill

    2013-01-01

    Human cancers over-expressing mdm2, through a T to G variation at a single nucleotide polymorphism at position 309 (mdm2 SNP309), have functionally inactivated p53 that is not effectively degraded. They also have high expression of the alternatively spliced transcript, mdm2-C. Alternatively spliced mdm2 transcripts are expressed in many forms of human cancer and when they are exogenously expressed they transform human cells. However no study to date has detected endogenous MDM2 protein isoforms. Studies with exogenous expression of splice variants have been carried out with mdm2-A and mdm2-B, but the mdm2-C isoform has remained virtually unexplored. We addressed the cellular influence of exogenously expressed MDM2-C, and asked if endogenous MDM2-C protein was present in human cancers. To detect endogenous MDM2-C protein, we created a human MDM2-C antibody to the splice junction epitope of exons four and ten (MDM2 C410) and validated the antibody with in vitro translated full length MDM2 compared to MDM2-C. Interestingly, we discovered that MDM2-C co-migrates with MDM2-FL at approximately 98 kDa. Using the validated C410 antibody, we detected high expression of endogenous MDM2-C in human cancer cell lines and human cancer tissues. In the estrogen receptor positive (ER+) mdm2 G/G SNP309 breast cancer cell line, T47D, we observed an increase in endogenous MDM2-C protein with estrogen treatment. MDM2-C localized to the nucleus and the cytoplasm. We examined the biological activity of MDM2-C by exogenously expressing the protein and observed that MDM2-C did not efficiently target p53 for degradation or reduce p53 transcriptional activity. Exogenous expression of MDM2-C in p53-null human cancer cells increased colony formation, indicating p53-independent tumorigenic properties. Our data indicate a role for MDM2-C that does not require the inhibition of p53 for increasing cancer cell proliferation and survival. PMID:24147044

  3. Emulsified isoflurane treatment inhibits the cell cycle and respiration of human bronchial epithelial 16HBE cells in a p53-independent manner.

    PubMed

    Yang, Hui; Deng, Jia; Jiang, Yingying; Chen, Jiao; Zeng, Xianzheng; He, Zhiyang; Jiang, Xiaojuan; Li, Zhuoning; Jiang, Chunling

    2016-07-01

    Emulsified isoflurane (EIso), as a result of its rapid anesthetic induction, recovery and convenience, is widely used as a novel intravenous general anesthetic. Treatment with EIso can reduce injuries caused by ischemia/reperfusion (I/R) to organs, including the heart, lung and liver, without knowing understanding the molecular mechanism. The present study hypothesized that treatment with EIso can affect the physiological processes of human lung bronchial epithelial cells (16HBE) prior to I/R. To test this hypothesis, the present study first constructed stable p53 knockdown and synthesis of cytochrome c oxidase (SCO)2 knockdown 16HBE cells. The above cells were subsequently treated with EIso at a concentration of 0.1 and 0.2% for 24 h. The relevant concentration of fat emulsion was used as a negative control. The expression levels of p53, p21, SCO1, SCO2 and Tp53‑induced glycolysis and apoptosis regulator (TIGAR) were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. Subsequently, the cell proliferation, respiration and glycolysis were investigated. The results revealed that EIso treatment significantly decreased the transcription of TIGAR, SCO1 and SCO2, and increased the transcription of p21, which are all p53 target genes, in a p53-independent manner. The cell cycle was inhibited by arresting cells at the G0/G1 phase. Respiration was reduced, which caused a decrease in oxygen consumption and the accumulation of lactate and reactive oxygen species. Taken together, EIso treatment inhibited the proliferation and respiration, and promoted glycolysis in 16HBE cells. This regulatory pathway may represent a protective mechanism of EIso treatment by inhibiting cell growth and decreasing the oxygen consumption from I/R. PMID:27176636

  4. The anti-leukemic activity of sodium dichloroacetate in p53mutated/null cells is mediated by a p53-independent ILF3/p21 pathway

    PubMed Central

    Agnoletto, Chiara; Brunelli, Laura; Melloni, Elisabetta; Pastorelli, Roberta; Casciano, Fabio; Rimondi, Erika; Rigolin, Gian Matteo; Cuneo, Antonio; Secchiero, Paola; Zauli, Giorgio

    2015-01-01

    B-chronic lymphocytic leukemia (B-CLL) patients harboring p53 mutations are invariably refractory to therapies based on purine analogues and have limited treatment options and poor survival. Having recently demonstrated that the mitochondria-targeting small molecule sodium dichloroacetate (DCA) exhibits anti-leukemic activity in p53wild-type B-CLL cells, the aim of this study was to evaluate the effect of DCA in p53mutated B-CLL cells and in p53mutated/null leukemic cell lines. DCA exhibited comparable cytotoxicity in p53wild-type and p53mutated B-CLL patient cell cultures, as well as in p53mutated B leukemic cell lines (MAVER, MEC-1, MEC-2). At the molecular level, DCA promoted the transcriptional induction of p21 in all leukemic cell types investigated, including p53null HL-60. By using a proteomic approach, we demonstrated that DCA up-regulated the ILF3 transcription factor, which is a known regulator of p21 expression. The role of the ILF3/p21 axis in mediating the DCA anti-leukemic activity was underscored by knocking-down experiments. Indeed, transfection with ILF3 and p21 siRNAs significantly decreased both the DCA-induced p21 expression and the DCA-mediated cytotoxicity. Taken together, our results emphasize that DCA is a small molecule that merits further evaluation as a therapeutic agent also for p53mutated leukemic cells, by acting through the induction of a p53-independent pathway. PMID:25544776

  5. Bi-transgenic Mice Reveal that K-rasVal12 Augments a p53-independent Apoptosis When Small Intestinal Villus Enterocytes Reenter the Cell Cycle

    PubMed Central

    Coopersmith, Craig M.; Chandrasekaran, Chitra; McNevin, M. Shane; Gordon, Jeffrey I.

    1997-01-01

    Studies in cell culture systems have indicated that oncogenic forms of Ras can affect apoptosis. Activating mutations of Ras occur in ∼30% of all human tumors and 50% of colorectal carcinomas. Since these mutations appear at early or intermediate stages in multistep journeys to neoplasia, an effect on apoptosis may help determine whether initiated cells progress towards a more neoplastic state. We have tested the effects of K-rasVal12 on apoptosis in transgenic mice. A lineage-specific promoter was used to direct expression of human K-rasVal12, with or without wild-type (wt) or mutant SV-40 T antigens (TAg), in postmitotic villus enterocytes, the principal cell type of the small intestinal epithelium. Enterocytes can be induced to reenter the cell cycle by TAgWt. Reentry is dependent upon the ability of TAg to bind pRB and is associated with a p53-independent apoptosis. Analyses of K-rasVal12 × TAgWt bi-transgenic animals indicated that K-rasVal12 can enhance this apoptosis threefold but only in cycling cells; increased apoptosis does not occur when K-rasVal12 is expressed alone or with a TAg containing Glu107,108→ Lys107,108 substitutions that block its ability to bind pRB. Analysis of bi-transgenic K-rasVal12 × TAgWt mice homozygous for wild-type or null p53 alleles established that the enhancement of apoptosis occurs through a p53-independent mechanism, is not attributable to augmented proliferation or to an increase in abortive cell cycle reentry (compared to TAgWt mice), and is not associated with detectable changes in the crypt–villus patterns of expression of apoptotic regulators (Bcl-2, Bcl-xL, Bak, and Bax) or mediators of epithelial cell–matrix interactions and survival (e.g., α5β1 integrin and its ligand, fibronectin). Coexpression of K-rasVal12 and TAgWt produces dysplasia. The K-rasVal12-augmented apoptosis is unrelated to this dysplasia; enhanced apoptosis is also observed in cycling nondysplastic enterocytes that produce K-rasVal12 and a

  6. The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways

    PubMed Central

    Wong, Fang Cheng; Woo, Chern Chiuh; Hsu, Annie; Tan, Benny Kwong Huat

    2013-01-01

    Breast cancer is currently the leading cause of cancer-related deaths among women globally. Notably, medicinal plant extracts may be a potential source for treatments of breast cancer. Vernonia amygdalina (VA) is a woody shrub reported to have not only diverse therapeutic effects but also anti-cancer properties. However, current research about the mechanisms of the anti-cancer potential of VA has been limited. This study aimed to investigate the mechanisms of action of VA that underlie its anti-cancer effects in human breast cancer cell lines (MCF-7 and MDA-MB-231 cells). Results from MTT assay revealed that VA inhibits the proliferation of MCF-7 and MDA-MB-231, in a time- and dose-dependent manner. The underlying mechanism of this growth inhibition involved the stimulation of cell-type specific G1/S phase cell cycle arrest in only MCF-7 cells, and not in MDA-MB-231 cells. While the growth arrest was associated with increased levels of p53 and p21, and a concomitant decrease in the levels of cyclin D1 and cyclin E, it was shown that VA causes cell cycle arrest through a p53-independent pathway as tested by the wild type p53 inhibitor, pifithrin-α. Furthermore, this study revealed that VA induces apoptosis in the two cell lines, as indicated by the increase in Annexin V-positive cells and sub-G1 population, and that this VA-induced apoptosis occurred through both extrinsic and intrinsic apoptotic pathways. The apoptosis in MCF-7 cells was also likely to be caspase-dependent and not p53 transcriptional-dependent. Given that approximately 70% of diagnosed breast cancers express ER-α, a crucial finding was that VA inhibits the expression of ER-α and its downstream player, Akt, highlighting the potential clinical significance of VA. Moreover, VA exhibits synergism when combined with doxorubicin, suggesting that it can complement current chemotherapy. Overall, this study demonstrates the potential applications of VA as an anti-cancer drug for breast cancer treatment

  7. Potential therapeutic role of Tridham in human hepatocellular carcinoma cell line through induction of p53 independent apoptosis

    PubMed Central

    2013-01-01

    . Conclusion These results suggest that TD induces apoptosis of Huh7 cells through activation of Bax and triggered caspase cascade, independent of p53 function. This study throws light on the mechanistic action of TD in triggering apoptosis in Huh 7 cells. PMID:24256980

  8. p53-independent activation of the hdm2-P2 promoter through multiple transcription factor response elements results in elevated hdm2 expression in estrogen receptor alpha-positive breast cancer cells.

    PubMed

    Phelps, Monika; Darley, Matthew; Primrose, John N; Blaydes, Jeremy P

    2003-05-15

    The negative-regulatory feedback loop between p53 and hdm2 forms part of a finely balanced regulatory network of proteins that controls cell cycle progression and commitment to apoptosis. Expression of hdm2, and its mouse orthologue mdm2, is known to be induced by p53, but recent evidence has demonstrated mdm2 expression can also be regulated via p53-independent pathways. However the p53 independent mechanisms that control transcription of the human hdm2 gene have not been studied. Differential levels of hdm2 mRNA and protein expression have been reported in several types of human malignancy, including breast cancers in which hdm2 expression correlates with positive estrogen receptor alpha (ERalpha) status. Experimental models have demonstrated that hdm2 overexpression can promote breast cancer development. Here, we show that the elevated level of hdm2 protein in ERalpha(+ve) breast cancer cell lines such as MCF-7 and T47D is because of transcription from the p53-inducible P2 promoter of hdm2. The P2 promoter is inactive in ERalpha(-ve) cell lines such as SKBr3. Hdm2-P2 promoter activity in T47D cells is independent of p53, as well as of known regulators of the mouse mdm2-P2 promoter, including ERalpha and ras-raf-mitogen-activated protein/extracellular signal-regulated kinase (MEK) mitogen-activated protein kinase (MAPK) signaling. We show that hdm2-P2 activity in T47D cells is dependent on the integrity of both an evolutionarily conserved composite binding site for AP1 and ETS family transcription factors (AP1-ETS) and a nonconserved upstream (nnGGGGC)(5) repeat sequence. Lack of hdm2-P2 activity in ERalpha(-ve) cells is shown to be a consequence of reduced transcriptional activation through the AP1-ETS element. Overexpression of ETS2 in SKBr3 cells reconstitutes AP1-ETS element-dependent hdm2-P2 promoter activity, resulting in increased levels of hdm2 protein in the cells. Our findings support the hypothesis that the elevated levels of hdm2 expression reported

  9. Estrogen receptor alpha (ERα/ESR1) mediates the p53-independent overexpression of MDM4/MDMX and MDM2 in human breast cancer

    PubMed Central

    Swetzig, Wendy M.; Wang, Jianmin; Das, Gokul M.

    2016-01-01

    MDM2 and MDM4 are heterodimeric, non-redundant oncoproteins that potently inhibit the p53 tumor suppressor protein. MDM2 and MDM4 also enhance the tumorigenicity of breast cancer cells in in vitro and in vivo models and are overexpressed in primary human breast cancers. Prior studies have characterized Estrogen Receptor Alpha (ERα/ESR1) as a regulator of MDM2 expression and an MDM2- and p53-interacting protein. However, similar crosstalk between ERα and MDM4 has not been investigated. Moreover, signaling pathways that mediate the overexpression of MDM4 in human breast cancer remain to be elucidated. Using the Cancer Genome Atlas (TCGA) breast invasive carcinoma patient cohort, we have analyzed correlations between ERα status and MDM4 and MDM2 expression in primary, treatment-naïve, invasive breast carcinoma samples. We report that the expression of MDM4 and MDM2 is elevated in primary human breast cancers of luminal A/B subtypes and associates with ERα-positive disease, independently of p53 mutation status. Furthermore, in cell culture models, ERα positively regulates MDM4 and MDM2 expression via p53-independent mechanisms, and these effects can be blocked by the clinically-relevant endocrine therapies fulvestrant and tamoxifen. Additionally, ERα also positively regulates p53 expression. Lastly, we report that endogenous MDM4 negatively regulates ERα expression and forms a protein complex with ERα in breast cancer cell lines and primary human breast tumor tissue. This suggests direct signaling crosstalk and negative feedback loops between ERα and MDM4 expression in breast cancer cells. Collectively, these novel findings implicate ERα as a central component of the p53-MDM2-MDM4 signaling axis in human breast cancer. PMID:26909605

  10. Induction of p53-independent apoptosis by a novel synthetic hexahydrocannabinol analog is mediated via Sp1-dependent NSAID-activated gene-1 in colon cancer cells.

    PubMed

    Thapa, Dinesh; Babu, Dinesh; Park, Min-A; Kwak, Mi-Kyoung; Lee, Yong-Rok; Kim, Jeong Min; Kwon, Taeg Kyu; Kim, Jung-Ae

    2010-07-01

    Nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) has received greater attention as a novel molecular target for anti-cancer therapeutics in recent years. We identified a novel synthetic hexahydrocannabinol analog, LYR-8 [(1-((9S)-1-hydroxy-6,6,9-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-2-yl)ethanone)], as a potent NAG-1 and apoptosis inducer in a panel of human cancer cells. LYR-8 did not possess any affinity for cannabinoid receptor CB(1) or CB(2), which eliminates the concern about potential psychoactive side effects. LYR-8 dramatically induced NAG-1 expression and apoptosis in HCT116 (wild-type p53) and HT29 (mutant p53) colon cancer cells. The NAG-1 expression by LYR-8 was not blocked by pifithrin-alpha, a specific p53 inhibitor, which was different from doxorubicin that induced p53-dependent NAG-1 transcriptional activity. The induction of NAG-1 promoter activity by LYR-8 was strongly correlated with increased Sp1 activation as noted in various luc-promoter activities. Furthermore, pretreatment with the specific Sp1 inhibitor mithramycin A completely reversed the LYR-8-induced NAG-1 expression in both HCT116 and HT29 cells. Knockdown of NAG-1 using siRNA significantly reversed LYR-8-induced cell death in both wild-type and mutant p53-expressing colon cancer cells. Furthermore, sensitization with NAG-1 inducer sulindac sulfide synergized LYR-8-induced cell death in both colon cancer cells. These results suggest that induction of NAG-1 via Sp1 activation is a promising therapeutic approach in cancer treatment, and that a novel compound like LYR-8 could be a potent chemotherapeutic agent for colon cancers including p53-mutated cancer. PMID:20230799

  11. Epigallocatechin-3-gallate prevents autoimmune-associated down- regulation of p21 in salivary gland cells through a p53-independent pathway.

    PubMed

    Dickinson, Douglas; Yu, Hongfang; Ohno, Seiji; Thomas, Cristina; Derossi, Scott; Ma, Yat-Ho; Yates, Nicole; Hahn, Emily; Bisch, Frederick; Yamamoto, Tetsuya; Hsu, Stephen

    2014-02-01

    The submandibular salivary glands of non-obese diabetic (NOD) mice, a model for Sjogren's syndrome and type-1 diabetes, show an elevated level of proliferating cell nuclear antigen (PCNA), a protein involved in cell proliferation and repair of DNA damage. We reported previously that epigallocatechin-3-gallate (EGCG), the most abundant green tea catechin, normalizes the PCNA level. PCNA's activity can be regulated by the cyclin-dependent kinase inhibitor p21, which is also important for epithelial cell differentiation. In turn, expression of p21 and PCNA are partially regulated by Rb phosphorylation levels. EGCG was found to modulate p21 expression in epithelial cells, suggesting that EGCG-induced p21 could be associated with down-regulation of PCNA in vivo. The current study examined the protein levels of p21 and p53 (which can up-regulate p21) in NOD mice fed with either water or EGCG, and the effect of EGCG on p21 and p53 in cell line models with either normal or defective Rb. In NOD mice, the p21 level was low, and EGCG normalized it. In contrast to HSG cells with functional Rb, negligible expression of p21 in NS-SVAC cells that lack Rb was not altered by EGCG treatment. Inhibition of p53 by siRNA demonstrated that p21 and p53 were induced independently in HSG cells by a physiological concentration range of EGCG, suggesting p53 could be an important but not conditional factor associated with p21 expression. In conclusion, PCNA and p21 levels are altered inversely in the NOD model for SS and in HSG cells, and warrant further study as candidate new markers for salivary dysfunction associated with xerostomia. Induction of p21 by EGCG could provide clinically useful normalization of salivary glands by promoting differentiation and reducing PCNA levels. PMID:24329914

  12. Modulation of Radiation-Induced Apoptosis by Thiolamines

    NASA Technical Reports Server (NTRS)

    Warters, R. L.; Roberts, J. C.; Wilmore, B. H.; Kelley, L. L.

    1997-01-01

    Exposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) induced apoptosis in the mouse TB8-3 hybridoma after 60-minute (LD(sub50) = 4.5mM) or during a 20-hour (LD(sub50) = 0.15 mM) exposure. In contrast, a 20-hour exposure to 17 mM L-cysteine or 10 mM cysteamine was required to induce 50 percent apoptosis within 20 hours. Apoptosis was not induced by either a 60-minute or 20-hour exposure to 10 mM of the thiazolidime prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). Thiolamine-induced apoptosis appeared to be a p53-independent process since it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4mM for 15 minutes) or cysteine (10mM for 60 minutes) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM for 3 hours) did not. Treatment with either WR-1065, cysteine, RibCys or RibCyst for 60 minutes beginning 60 minutes after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with either cysteine, cysteamine or RibCys for 20 hours beginning 60 minutes after irradiation enhanced radiation-induced apoptosis. Similar experiments could not be conducted with WR-1065 because of its extreme toxicity. Our results indicate that thiolamine enhancement of radiation-induced apoptosis is not involved in their previously reported capacity to reduce radiation-induced mutations.

  13. A Zebrafish Model of 5q-Syndrome Using CRISPR/Cas9 Targeting RPS14 Reveals a p53-Independent and p53-Dependent Mechanism of Erythroid Failure.

    PubMed

    Ear, Jason; Hsueh, Jessica; Nguyen, Melinda; Zhang, QingHua; Sung, Victoria; Chopra, Rajesh; Sakamoto, Kathleen M; Lin, Shuo

    2016-05-20

    5q-syndrome is a distinct form of myelodysplastic syndrome (MDS) where a deletion on chromosome 5 is the underlying cause. MDS is characterized by bone marrow failures, including macrocytic anemia. Genetic mapping and studies using various models support the notion that ribosomal protein S14 (RPS14) is the candidate gene for the erythroid failure. Targeted disruption of RPS14 causes an increase in p53 activity and p53-mediated apoptosis, similar to what is observed with other ribosomal proteins. However, due to the higher risk for cancer development in patients with ribosome deficiency, targeting the p53 pathway is not a viable treatment option. To better understand the pathology of RPS14 deficiency in 5q-deletion, we generated a zebrafish model harboring a mutation in the RPS14 gene. This model mirrors the anemic phenotype seen in 5q-syndrome. Moreover, the anemia is due to a late-stage erythropoietic defect, where the erythropoietic defect is initially p53-independent and then becomes p53-dependent. Finally, we demonstrate the versatility of this model to test various pharmacological agents, such as RAP-011, L-leucine, and dexamethasone in order to identify molecules that can reverse the anemic phenotype. PMID:27216296

  14. p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function.

    PubMed

    Xu-Monette, Zijun Y; Zhang, Shanxiang; Li, Xin; Manyam, Ganiraju C; Wang, Xiao-Xiao; Xia, Yi; Visco, Carlo; Tzankov, Alexandar; Zhang, Li; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William W L; van Krieken, J Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhao, Xiaoying; Møller, Michael B; Parsons, Ben M; Winter, Jane N; Piris, Miguel A; Medeiros, L Jeffrey; Young, Ken H

    2016-02-01

    The role of p53 family member p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6 translocation. p63 was an independent favorable prognostic factor in DLBCL, which was most significant in patients with International Prognostic Index (IPI) >2, and in activated-B-cell-like DLBCL patients with wide- type TP53. The prognostic impact in germinal-center-B-cell-like DLBCL was not apparent, which was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize each other. In summary, p63 has p53-like and p53-independent functions and favorable prognostic impact, however this protective effect can be abolished by TP53 mutations. PMID:26878872

  15. p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function

    PubMed Central

    Manyam, Ganiraju C.; Wang, Xiao-xiao; Xia, Yi; Visco, Carlo; Tzankov, Alexandar; Zhang, Li; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Zhao, Xiaoying; Møller, Michael B.; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Medeiros, L. Jeffrey; Young, Ken H.

    2016-01-01

    The role of p53 family member, p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6 translocation. p63 was an independent favorable prognostic factor in DLBCL, which was most significant in patients with International Prognostic Index (IPI) >2, and in activated-B-cell–like DLBCL patients with wide-type TP53. The prognostic impact in germinal-center-B-cell–like DLBCL was not apparent, which was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize each other. In summary, p63 has p53-like and p53-independent functions and favorable prognostic impact, however this protective effect can be abolished by TP53 mutations. PMID:26878872

  16. Gamma radiation alters cell cycle and induces apoptosis in p53 mutant E6.1 Jurkat cells.

    PubMed

    Ahmadianpour, Mohammad Reza; Abdolmaleki, Parviz; Mowla, Seyed Javad; Hosseinkhani, Saman

    2013-01-01

    This study aimed at investigating the effect of gamma radiation with 1.5, 3.0 and 7.5 Gy doses on apoptosis induction, cell cycle alteration and increment of amount of p-ATM (phosphorylated ATM) and p-E2F1 (phosphorylated E2F1) proteins in Jurkat T-lymphoblastoid E6.1 cells. Exposure of human p53 mutant Jurkat cells to gamma radiation resulted in apoptosis, which was detected by luminometric and flow cytometric analysis. Also, phosphorylated ATM (ataxia telangiectasia mutated) and E2F1 (elongation factor) proteins were detected by western blot analysis. Based on luminescence detection data the lethal dose of 7.5 Gy induced cell death 12 h after exposure (p<0.05) while sub-lethal doses of 1.5 and 3.0 Gy induced apoptosis 18 h after exposure (p<0.05). Flow cytometric analysis revealed a G2 arrest 24h after exposure to 3.0 and 7.5 Gy. This arrest was accompanied by cell death with an increasing rate of occurrence up to 72 h after exposure. Western blot analysis showed that 1 h after cell irradiation by 1.5, 3.0 and 7.5 Gy, the amount of p-ATM increased to its maximum rate and remained constant up to 6 h, and then it decreased. Moreover, the amount of phosphorylated E2F1 (Ser-31) increased 2 h after exposure to the same doses and remained constant up to 12 h after irradiation. Survival and cell division of treated Jurkat cells showed a decrease compared to the control group. We believe that ionizing radiation-induced DNA damage activates a p53-independent apoptosis pathway via back-up systems in which the phosphorylation of ATM and E2F1 proteins was involved. Thus, gamma radiation can induce apoptosis and cell cycle alteration in Jurkat cells via a P53-independent pathway. PMID:23079488

  17. Radiation-induced gliomas

    PubMed Central

    Prasad, Gautam; Haas-Kogan, Daphne A.

    2013-01-01

    Radiation-induced gliomas represent a relatively rare but well-characterized entity in the neuro-oncologic literature. Extensive retrospective cohort data in pediatric populations after therapeutic intracranial radiation show a clearly increased risk in glioma incidence that is both patient age- and radiation dose/volume-dependent. Data in adults are more limited but show heightened risk in certain groups exposed to radiation. In both populations, there is no evidence linking increased risk associated with routine exposure to diagnostic radiation. At the molecular level, recent studies have found distinct genetic differences between radiation-induced gliomas and their spontaneously-occurring counterparts. Clinically, there is understandable reluctance on the part of clinicians to re-treat patients due to concern for cumulative neurotoxicity. However, available data suggest that aggressive intervention can lead to improved outcomes in patients with radiation-induced gliomas. PMID:19831840

  18. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    DOE PAGESBeta

    Lemon, Jennifer A.; Taylor, Kristina; Verdecchia, Kyle; Phan, Nghi; Boreham, Douglas R.

    2014-01-01

    Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levelsmore » of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation.« less

  19. Radiation-induced osteochondromas

    SciTech Connect

    Libshitz, H.I.; Cohen, M.A.

    1982-03-01

    Radiation-induced osteochondromas, either single or multiple, occur more commonly than is generally recognized. The incidence following irradiation for childhood malignancy is approximately 12%. Any open epiphysis is vulnerable. Age at irradiation, time of appearance following therapy, dose and type of radiation, and clinical course in 14 cases are dicussed. Due to growth of the lesion and/or pain, 3 tumors were excised. None revealed malignant degeneration.

  20. Radiation-Induced Bioradicals

    NASA Astrophysics Data System (ADS)

    Lahorte, Philippe; Mondelaers, Wim

    This chapter represents the second part of a review in which the production and application of radiation-induced radicals in biological matter are discussed. In part one the general aspects of the four stages (physical, physicochemical, chemical and biological) of interaction of radiation with matter in general and biological matter in particular, were discussed. Here an overview is presented of modem technologies and theoretical methods available for studying these radiation effects. The relevance is highlighted of electron paramagnetic resonance spectroscopy and quantum chemical calculations with respect to obtaining structural information on bioradicals, and a survey is given of the research studies in this field. We also discuss some basic aspects of modem accelerator technologies which can be used for creating radicals and we conclude with an overview of applications of radiation processing in biology and related fields such as biomedical and environmental engineering, food technology, medicine and pharmacy.

  1. Radiation-induced schwannomas

    SciTech Connect

    Rubinstein, A.B.; Reichenthal, E.; Borohov, H.

    1989-06-01

    The histopathology and clinical course of three patients with schwannomas of the brain and high cervical cord after therapeutic irradiation for intracranial malignancy and for ringworm of the scalp are described. Earlier reports in the literature indicated that radiation of the scalp may induce tumors in the head and neck. It is therefore suggested that therapeutic irradiation in these instances was a causative factor in the genesis of these tumors.

  2. Radiation Induced Genomic Instability

    SciTech Connect

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  3. [Radiation-induced neuropathy].

    PubMed

    Kolak, Agnieszka; Starosławska, Elzbieta; Kieszko, Dariusz; Cisek, Paweł; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Dobrzyńska-Rutkowska, Aneta; Łopacka-Szatan, Karolina; Burdan, Franciszek

    2013-12-01

    Radiation-induced neuropathy is commonly observed among oncological patients. Radiation can affect the nervous tissue directly or indirectly by inducing vasculopathy or dysfunction of internal organs. Symptoms may be mild and reversible (e.g., pain, nausea, vomiting, fever, drowsiness, fatigue, paresthesia) or life-threatening (cerebral oedema, increased intracranial pressure, seizures). Such complications are clinically divided into peripheral (plexopathies, neuropathies of spinal and cranial nerves) and central neuropathy (myelopathy, encephalopathy, cognitive impairment). The degree of neuronal damages primarily depends on the total and fractional radiation dose and applied therapeutic methods. The conformal and megavoltage radiotherapy seems to be the safeties ones. Diagnostic protocol includes physical examination, imaging (in particular magnetic resonance), electromyography, nerve conduction study and sometimes histological examination. Prevention and early detection of neurological complications are necessary in order to prevent a permanent dysfunction of the nervous system. Presently their treatment is mostly symptomatic, but in same cases a surgical intervention is required. An experimental and clinical data indicates some effectiveness of different neuroprotective agents (e.g. anticoagulants, vitamin E, hyperbaric oxygen, pentoxifylline, bevacizumab, methylphenidate, donepezil), which should be administered before and/or during radiotherapy. PMID:24490474

  4. [Radiation-induced cancers].

    PubMed

    Dutrillaux, B

    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 dose 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 of tumour-suppressor genes. These 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. PMID:9868399

  5. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    SciTech Connect

    Lemon, Jennifer A.; Taylor, Kristina; Verdecchia, Kyle; Phan, Nghi; Boreham, Douglas R.

    2014-01-01

    Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation.

  6. Differential effects of p53 on bystander phenotypes induced by gamma ray and high LET heavy ion radiation

    NASA Astrophysics Data System (ADS)

    He, Mingyuan; Dong, Chen; Konishi, Teruaki; Tu, Wenzhi; Liu, Weili; Shiomi, Naoko; Kobayashi, Alisa; Uchihori, Yukio; Furusawa, Yoshiya; Hei, Tom K.; Dang, Bingrong; Shao, Chunlin

    2014-04-01

    High LET particle irradiation has several potential advantages over γ-rays such as p53-independent response. The purpose of this work is to disclose the effect of p53 on the bystander effect induced by different LET irradiations and underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR (mutated p53) were exposed to either low or high LET irradiation, then their mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN) induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also measured. It was found that the mitochondrial dysfunction, p66Shc activation, and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after γ-ray irradiation, but all of them were increased in both cell lines after carbon and iron irradiation. Consistently, the bystander effect of MN formation in HL-7702 cells was only triggered by γ-irradiated TK6 cells but not by γ-irradiated HMy2.CIR cells. But this bystander effect was induced by both lymphocyte cell lines after heavy ion irradiation. PFT-μ, an inhibitor of p53, only partly inhibited ROS generation and bystander effect induced by 30 keV/μm carbon-irradiated TK6 cells but failed to suppress the bystander effect induced by the TK6 cells irradiated with either 70 keV/μm carbon or 180 keV/μm iron. The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the bystander effect on HL-7702 cells. These results clearly demonstrate that the bystander effect is p53-dependent for low LET irradiation, but it is p53-independent for high LET irradiation which may be because of p53-independent ROS generation due to mitochondrial dysfunction.

  7. Errors inducing radiation overdoses.

    PubMed

    Grammaticos, Philip C

    2013-01-01

    There is no doubt that equipments exposing radiation and used for therapeutic purposes should be often checked for possibly administering radiation overdoses to the patients. Technologists, radiation safety officers, radiologists, medical physicists, healthcare providers and administration should take proper care on this issue. "We must be beneficial and not harmful to the patients", according to the Hippocratic doctrine. Cases of radiation overdose are often reported. A series of cases of radiation overdoses have recently been reported. Doctors who were responsible, received heavy punishments. It is much better to prevent than to treat an error or a disease. A Personal Smart Card or Score Card has been suggested for every patient undergoing therapeutic and/or diagnostic procedures by the use of radiation. Taxonomy may also help. PMID:24251304

  8. Radiation-induced disease.

    PubMed

    Bobrow, M

    1993-01-01

    The term radiation covers a wide spectrum of forms of energy, most of which have at one stage or another been suspected of causing human ill health. In general, study of the effects of radiation on health involves a mix of scientific disciplines, from population epidemiology to physics, which are seldom if ever found in a single scientist. As a result, interdisciplinary communication is of the utmost importance, and is a potent source of misunderstanding and misinformation. The forms of radiation which have been most specifically associated with health effects include ionizing and ultraviolet radiation. Claimed effects of electromagnetic and microwave radiation (excluding thermal effects) are too indefinite for detailed consideration. Ionizing radiation is a well-documented mutagen, which clearly causes cancers in humans, and human exposure has been increased by atomic weapons testing and medical and industrial uses of radioactivity. There is also a growing awareness of the possible role of some types of natural radiation, such as radon, in causing disease. Ultraviolet radiation is also associated with cancers, and is suspected of involvement in the increasing incidence of skin cancers in European populations. Factors thought to underlie recent changes in exposure to these mutagens are discussed. PMID:8222990

  9. Radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Kronenberg, A.

    1994-01-01

    Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.

  10. Radiation-induced cardiovascular effects

    NASA Astrophysics Data System (ADS)

    Tapio, Soile

    Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.

  11. Radiation induced estane polymer crosslinking

    SciTech Connect

    Fletcher, M.; Foster, P.

    1997-12-01

    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.

  12. Induced Smith-Purcell radiation

    NASA Astrophysics Data System (ADS)

    Klochkov, D. N.; Artemyev, A. I.; Oganesyan, K. B.; Rostovtsev, Y. V.; Hu, C.-K.

    2010-11-01

    Excitation of induced coherent Smith-Purcell (SP) radiation by relativistic magnetized electron beam in the absence of the resonator is considered within the framework of the dispersion equation. We have found that the dispersion equation for the SP instability is a quadratic equation for frequency. The first-step approximation for solution of the dispersion equation, giving the SP-spectrum of frequency, corresponds to the mirror boundary case, when the electron beam propagates above a plane metal surface (mirror). It was found that the conditions for both the Thompson and the Raman regimes of excitation do not depend on beam current and depend on the height of the beam above the grating surface. The growth rate of the instability in both cases is proportional to the square root of the electron beam current. No feedback is needed to provide the coherent emission.

  13. Sparsely ionizing diagnostic and natural background radiations are likely preventing cancer and other genomic-instability-associated diseases.

    PubMed

    Scott, Bobby R; Di Palma, Jennifer

    2007-01-01

    Routine diagnostic X-rays (e.g., chest X-rays, mammograms, computed tomography scans) and routine diagnostic nuclear medicine procedures using sparsely ionizing radiation forms (e.g., beta and gamma radiations) stimulate the removal of precancerous neo-plastically transformed and other genomically unstable cells from the body (medical radiation hormesis). The indicated radiation hormesis arises because radiation doses above an individual-specific stochastic threshold activate a system of cooperative protective processes that include high-fidelity DNA repair/apoptosis (presumed p53 related), an auxiliary apoptosis process (PAM process) that is presumed p53-independent, and stimulated immunity. These forms of induced protection are called adapted protection because they are associated with the radiation adaptive response. Diagnostic X-ray sources, other sources of sparsely ionizing radiation used in nuclear medicine diagnostic procedures, as well as radioisotope-labeled immunoglobulins could be used in conjunction with apoptosis-sensitizing agents (e.g., the natural phenolic compound resveratrol) in curing existing cancer via low-dose fractionated or low-dose, low-dose-rate therapy (therapeutic radiation hormesis). Evidence is provided to support the existence of both therapeutic (curing existing cancer) and medical (cancer prevention) radiation hormesis. Evidence is also provided demonstrating that exposure to environmental sparsely ionizing radiations, such as gamma rays, protect from cancer occurrence and the occurrence of other diseases via inducing adapted protection (environmental radiation hormesis). PMID:18648608

  14. Medium-induced multi-photon radiation

    NASA Astrophysics Data System (ADS)

    Ma, Hao; Salgado, Carlos A.; Tywoniuk, Konrad

    2011-01-01

    We study the spectrum of multi-photon radiation off a fast quark in medium in the BDMPS/ASW approach. We reproduce the medium-induced one-photon radiation spectrum in dipole approximation, and go on to calculate the two-photon radiation in the Molière limit. We find that in this limit the LPM effect holds for medium-induced two-photon ladder emission.

  15. Radiation-induced gene responses

    SciTech Connect

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

    1996-12-31

    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.

  16. Radiation-induced genomic instability: radiation quality and dose response

    NASA Technical Reports Server (NTRS)

    Smith, Leslie E.; Nagar, Shruti; Kim, Grace J.; Morgan, William F.

    2003-01-01

    Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

  17. Radiation-induced thyroid disease

    SciTech Connect

    Maxon, H.R.

    1985-09-01

    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.

  18. Radiation-induced sarcoma of the thyroid

    SciTech Connect

    Griem, K.L.; Robb, P.K.; Caldarelli, D.D.; Templeton, A.C. )

    1989-08-01

    A 23-year-old white man presented with a thyroid mass 12 years after receiving high-dose radiotherapy for a T2 and N1 lymphoepithelioma of the nasopharynx. Following subtotal thyroidectomy, a histopathologic examination revealed liposarcoma of the thyroid gland. The relationship between sarcomas and irradiation is described and Cahan and colleagues' criteria for radiation-induced sarcomas are reviewed. To our knowledge, we are presenting the first such case of a radiation-induced sarcoma of the thyroid gland.

  19. Radiation-induced neoplasms of the brain

    SciTech Connect

    Kumar, P.P.; Good, R.R.; Skultety, F.M.; Leibrock, L.G.; Severson, G.S.

    1987-04-01

    The histopathology of two patients with radiation-induced neoplasms of the brain following therapeutic irradiation for intracranial malignancies is described. The second neoplasms were an atypical meningioma and a polymorphous cell sarcoma, respectively. They occurred 12 and 23 years after irradiation (4000 rad), within the original field of irradiation. In both cases, the radiation-induced tumors were histologically distinct from the initial medulloblastomas. Both patients were retreated with local irradiation using permanent implantation of radioactive iodine-125 seeds.

  20. Radiation-induced lung injury

    SciTech Connect

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  1. Ultraviolet radiation induced discharge laser

    DOEpatents

    Gilson, Verle A.; Schriever, Richard L.; Shearer, James W.

    1978-01-01

    An ultraviolet radiation source associated with a suitable cathode-anode electrode structure, disposed in a gas-filled cavity of a high pressure pulsed laser, such as a transverse electric atmosphere (TEA) laser, to achieve free electron production in the gas by photoelectric interaction between ultraviolet radiation and the cathode prior to the gas-exciting cathode-to-anode electrical discharge, thereby providing volume ionization of the gas. The ultraviolet radiation is produced by a light source or by a spark discharge.

  2. Radiation-induced intracranial malignant gliomas

    SciTech Connect

    Shapiro, S.; Mealey, J. Jr.; Sartorius, C.

    1989-07-01

    The authors present seven cases of malignant gliomas that occurred after radiation therapy administered for diseases different from the subsequent glial tumor. Included among these seven are three patients who were treated with interstitial brachytherapy. Previously reported cases of radiation-induced glioma are reviewed and analyzed for common characteristics. Children receiving central nervous system irradiation appear particularly susceptible to induction of malignant gliomas by radiation. Interstitial brachytherapy may be used successfully instead of external beam radiotherapy in previously irradiated, tumor-free brain, and thus may reduce the risk of radiation necrosis. 31 references.

  3. [Quantification of radiation-induced genetic risk].

    PubMed

    Ehling, U H

    1987-05-01

    Associated with technical advances of our civilization is a radiation- and chemically-induced increase in the germ cell mutation rate in man. This would result in an increase in the frequency of genetic diseases and would be detrimental to future generations. It is the duty of our generation to keep this risk as low as possible. The estimation of the radiation-induced genetic risk of human populations is based on the extrapolation of results from animal experiments. Radiation-induced mutations are stochastic events. The probability of the event depends on the dose; the degree of the damage does not. The different methods to estimate the radiation-induced genetic risk will be discussed. The accuracy of the predicted results will be evaluated by a comparison with the observed incidence of dominant mutations in offspring born to radiation exposed survivors of the Hiroshima and Nagasaki atomic bombings. These methods will be used to predict the genetic damage from the fallout of the reactor accident at Chernobyl. For the exposure dose we used the upper limits of the mean effective life time equivalent dose from the fallout values in the Munich region. According to the direct method for the risk estimation we will expect for each 100 to 500 spontaneous dominant mutations one radiation-induced mutation in the first generation. With the indirect method we estimate a ratio of 100 dominant spontaneous mutations to one radiation-induced dominant mutation. The possibilities and the limitations of the different methods to estimate the genetic risk will be discussed. The discrepancy between the high safety standards for radiation protection and the low level of knowledge for the toxicological evaluation of chemical mutagens will be emphasized. PMID:3589954

  4. Radiation-induced squamous sialometaplasia

    SciTech Connect

    Leshin, B.; White, W.L.; Koufman, J.A. )

    1990-07-01

    We describe a patient with recurrent acantholytic squamous cell carcinoma following radiation therapy. Mohs micrographic sections revealed extensive squamous sialometaplasia showing striking histologic similarity to the patient's squamous cell carcinoma. Criteria necessary to differentiate squamous sialometaplasia from neoplasm are presented. This differentiation is important to ensure adequate tumor resection without unnecessary sacrifice of tumor-free tissue.

  5. Radiation-induced instability and its relation to radiation carcinogenesis

    NASA Technical Reports Server (NTRS)

    Ullrich, R. L.; Ponnaiya, B.

    1998-01-01

    PURPOSE: A model that identifies radiation-induced genetic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer was previously proposed. In this paper ongoing experiments are discussed which are designed to test this model and its predictions in mouse mammary epithelial cells. RESULTS: Several lines of evidence are presented that appear to support this model: first, the development of delayed mutations in p53 following irradiation in altered growth variants; secondly, the high frequencies for the induction of both instability and transformation following irradiation in mammary epithelial cells; and finally, the demonstration that susceptibility to the induction of cytogenetic instability is a heritable trait that correlates with susceptibility to transformation and radiation-induced mammary cancer. Mice resistant to transformation and mammary cancer development are also resistant to the development of instability after irradiation. In contrast, mice sensitive to transformation and cancer are also sensitive to the development of cytogenetic instability. CONCLUSIONS: Data from this laboratory and from the studies cited above suggest a specific, and perhaps unique, role for radiation-induced instability as a critical early event associated with initiation of the carcinogenic process.

  6. Induced radioactivity from industrial radiation processing

    NASA Astrophysics Data System (ADS)

    Lone, M. A.

    1990-12-01

    Analytic expressions are developed for quantitative analysis of radioactivity induced by radiation processing of products with electrons or photons. These expressions provide reasonable estimates of induced activity much faster than Monte Carlo simulations. Analysis of radioactivity from processing of meat with 10 MeV electrons shows an induced activity of less than 10 mBq/(kgkGy) just after irradiation. This is 4 orders of magnitude less than the natural background activity of about 100 Bq/kg found in meat. Five days after processing the induced activity will reduce by a factor of 300.

  7. Imaging Radiation-Induced Normal Tissue Injury

    PubMed Central

    Robbins, Mike E.; Brunso-Bechtold, Judy K.; Peiffer, Ann M.; Tsien, Christina I.; Bailey, Janet E.; Marks, Lawrence B.

    2013-01-01

    Technological developments in radiation therapy and other cancer therapies have led to a progressive increase in five-year survival rates over the last few decades. Although acute effects have been largely minimized by both technical advances and medical interventions, late effects remain a concern. Indeed, the need to identify those individuals who will develop radiation-induced late effects, and to develop interventions to prevent or ameliorate these late effects is a critical area of radiobiology research. In the last two decades, preclinical studies have clearly established that late radiation injury can be prevented/ameliorated by pharmacological therapies aimed at modulating the cascade of events leading to the clinical expression of radiation-induced late effects. These insights have been accompanied by significant technological advances in imaging that are moving radiation oncology and normal tissue radiobiology from disciplines driven by anatomy and macrostructure to ones in which important quantitative functional, microstructural, and metabolic data can be noninvasively and serially determined. In the current article, we review use of positron emission tomography (PET), single photon emission tomography (SPECT), magnetic resonance (MR) imaging and MR spectroscopy to generate pathophysiological and functional data in the central nervous system, lung, and heart that offer the promise of, (1) identifying individuals who are at risk of developing radiation-induced late effects, and (2) monitoring the efficacy of interventions to prevent/ameliorate them. PMID:22348250

  8. Radiation induced conductivity in space dielectric materials

    SciTech Connect

    Hanna, R.; Paulmier, T. Belhaj, M.; Dirassen, B.; Molinie, P.; Payan, D.; Balcon, N.

    2014-01-21

    The radiation-induced conductivity of some polymers was described mainly in literature by a competition between ionization, trapping/detrapping, and recombination processes or by radiation assisted ageing mechanisms. Our aim is to revise the effect of the aforementioned mechanisms on the complex evolution of Teflon{sup ®} FEP under space representative ionizing radiation. Through the definition of a new experimental protocol, revealing the effect of radiation dose and relaxation time, we have been able to demonstrate that the trapping/recombination model devised in this study agrees correctly with the observed experimental phenomenology at qualitative level and allows describing very well the evolution of radiation induced conductivity with irradiation time (or received radiation dose). According to this model, the complex behavior observed on Teflon{sup ®} FEP may be basically ascribed to the competition between electron/hole pairs generation and recombination: electrons are deeply trapped and act as recombination centers for free holes. Relaxation effects have been characterized through successive irradiations steps and have been again well described with the defined model at qualitative level: recombination centers created by the irradiation induce long term alteration on the electric properties, especially the effective bulk conductivity. One-month relaxation does not allow a complete recovery of the material initial charging behavior.

  9. Radiation induced conductivity in space dielectric materials

    NASA Astrophysics Data System (ADS)

    Hanna, R.; Paulmier, T.; Molinie, P.; Belhaj, M.; Dirassen, B.; Payan, D.; Balcon, N.

    2014-01-01

    The radiation-induced conductivity of some polymers was described mainly in literature by a competition between ionization, trapping/detrapping, and recombination processes or by radiation assisted ageing mechanisms. Our aim is to revise the effect of the aforementioned mechanisms on the complex evolution of Teflon® FEP under space representative ionizing radiation. Through the definition of a new experimental protocol, revealing the effect of radiation dose and relaxation time, we have been able to demonstrate that the trapping/recombination model devised in this study agrees correctly with the observed experimental phenomenology at qualitative level and allows describing very well the evolution of radiation induced conductivity with irradiation time (or received radiation dose). According to this model, the complex behavior observed on Teflon® FEP may be basically ascribed to the competition between electron/hole pairs generation and recombination: electrons are deeply trapped and act as recombination centers for free holes. Relaxation effects have been characterized through successive irradiations steps and have been again well described with the defined model at qualitative level: recombination centers created by the irradiation induce long term alteration on the electric properties, especially the effective bulk conductivity. One-month relaxation does not allow a complete recovery of the material initial charging behavior.

  10. Management of radiation-induced urethral strictures

    PubMed Central

    Hofer, Matthias D.

    2015-01-01

    Radiation as a treatment option for prostate cancer has been chosen by many patients. One of the side effects encountered are radiation-induced urethral strictures which occur in up to 11% of patients. Radiation damage has often left the irradiated field fibrotic and with poor vascularization which make these strictures a challenging entity to treat. The mainstay of urologic management remains an urethroplasty procedure for which several approaches exist with variable optimal indication. Excision and primary anastomoses are ideal for shorter bulbar strictures that comprise the majority of radiation-induced urethral strictures. One advantage of this technique is that it does not require tissue transfers and success rates of 70-95% have consistently been reported. Substitution urethroplasty using remote graft tissue such as buccal mucosa are indicated if the length of the stricture precludes a tension-free primary anastomosis. Despite the challenge of graft survival in radiation-damaged and poorly vascularized recipient tissue, up to 83% of patients have been treated successfully although the numbers described in the literature are small. The most extensive repairs involve the use of tissue flaps, for example gracilis muscle, which may be required if the involved periurethral tissue is unable to provide sufficient vascular support for a post-operative urethral healing process. In summary, radiation-induced urethral strictures are a challenging entity. Most strictures are amenable to excision and primary anastomosis (EPA) with encouraging success rates but substitution urethroplasty may be indicated when extensive repair is needed. PMID:26816812

  11. Radiation-induced intestinal pseudoobstruction

    SciTech Connect

    Perino, L.E.; Schuffler, M.D.; Mehta, S.J.; Everson, G.T.

    1986-10-01

    A case of intestinal pseudoobstruction occurring 30 yr after radiation therapy is described. Mechanical causes of obstruction were excluded by laparotomy. Histology of full-thickness sections of the small bowel revealed vascular ectasia and sclerosis, serosal fibrosis, neuronal proliferation within the submucosa, and degeneration of the muscle fibers of the circular layer of the muscularis propria. On the basis of the clinical and histologic findings we conclude that, in this patient, intestinal pseudoobstruction was due to muscular and neuronal injury from abdominal irradiation.

  12. Radiation-induced hydrogen transfer in metals

    NASA Astrophysics Data System (ADS)

    Tyurin, Yu I.; Vlasov, V. A.; Dolgov, A. S.

    2015-11-01

    The paper presents processes of hydrogen (deuterium) diffusion and release from hydrogen-saturated condensed matters in atomic, molecular and ionized states under the influence of the electron beam and X-ray radiation in the pre-threshold region. The dependence is described between the hydrogen isotope release intensity and the current density and the electron beam energy affecting sample, hydrogen concentration in the material volume and time of radiation exposure to the sample. The energy distribution of the emitted positive ions of hydrogen isotopes is investigated herein. Mechanisms of radiation-induced hydrogen transfer in condensed matters are suggested.

  13. A report on radiation-induced gliomas

    SciTech Connect

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

    1991-01-15

    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.

  14. Mutant lamin A links prophase to a p53 independent senescence program

    PubMed Central

    Moiseeva, Olga; Lessard, Frédéric; Acevedo-Aquino, Mariana; Vernier, Mathieu; Tsantrizos, Youla S; Ferbeyre, Gerardo

    2015-01-01

    Expression of oncogenes or short telomeres can trigger an anticancer response known as cellular senescence activating the p53 and RB tumor suppressor pathways. This mechanism is switched off in most tumor cells by mutations in p53 and RB signaling pathways. Surprisingly, p53 disabled tumor cells could be forced into senescence by expression of a mutant allele of the nuclear envelope protein lamin A. The pro-senescence lamin A mutant contains a deletion in the sequence required for processing by the protease ZMPSTE24 leading to accumulation of farnesylated lamin A in the nuclear envelope. In addition, the serine at position 22, a target for CDK1-dependent phosphorylation, was mutated to alanine, preventing CDK1-catalyzed nuclear envelope disassembly. The accumulation of this mutant lamin A compromised prophase to prometaphase transition leading to invaginations of the nuclear lamina, nuclear fragmentation and impaired chromosome condensation. Cells exited this impaired mitosis without cytokinesis and re-replicated their DNA ultimately arresting in interphase as polyploid cells with features of cellular senescence including increased expression of inflammatory gene products and a significant reduction of tumorigenicity in vivo. PMID:26029982

  15. Deletions linked to TP53 loss drive cancer through p53-independent mechanisms.

    PubMed

    Liu, Yu; Chen, Chong; Xu, Zhengmin; Scuoppo, Claudio; Rillahan, Cory D; Gao, Jianjiong; Spitzer, Barbara; Bosbach, Benedikt; Kastenhuber, Edward R; Baslan, Timour; Ackermann, Sarah; Cheng, Lihua; Wang, Qingguo; Niu, Ting; Schultz, Nikolaus; Levine, Ross L; Mills, Alea A; Lowe, Scott W

    2016-03-24

    Mutations disabling the TP53 tumour suppressor gene represent the most frequent events in human cancer and typically occur through a two-hit mechanism involving a missense mutation in one allele and a 'loss of heterozygosity' deletion encompassing the other. While TP53 missense mutations can also contribute gain-of-function activities that impact tumour progression, it remains unclear whether the deletion event, which frequently includes many genes, impacts tumorigenesis beyond TP53 loss alone. Here we show that somatic heterozygous deletion of mouse chromosome 11B3, a 4-megabase region syntenic to human 17p13.1, produces a greater effect on lymphoma and leukaemia development than Trp53 deletion. Mechanistically, the effect of 11B3 loss on tumorigenesis involves co-deleted genes such as Eif5a and Alox15b (also known as Alox8), the suppression of which cooperates with Trp53 loss to produce more aggressive disease. Our results imply that the selective advantage produced by human chromosome 17p deletion reflects the combined impact of TP53 loss and the reduced dosage of linked tumour suppressor genes. PMID:26982726

  16. Radiation-induced Genomic Instability and Radiation Sensitivity

    SciTech Connect

    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.

  17. Radiation-induced meningiomas in pediatric patients

    SciTech Connect

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

    1988-04-01

    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.

  18. Radiation-induced mutations and plant breeding

    SciTech Connect

    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.

  19. Cataracts induced by microwave and ionizing radiation

    SciTech Connect

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

    1988-11-01

    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.

  20. Bile acids in radiation-induced diarrhea

    SciTech Connect

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

    1987-10-01

    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.

  1. Radiation-induced brain injury: A review

    PubMed Central

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

    2012-01-01

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

  2. Delayed Radiation-Induced Vasculitic Leukoencephalopathy

    SciTech Connect

    Rauch, Philipp J.; Park, Henry S.; Knisely, Jonathan P.S.; Chiang, Veronica L.; Vortmeyer, Alexander O.

    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.

  3. Ionizing Radiation-induced Diseases in Korea

    PubMed Central

    Jeong, Meeseon; Moon, Kieun; Jo, Min-Heui; Kang, Seong-Kyu

    2010-01-01

    Radiation risk has become well known through epidemiological studies of clinically or occupationally exposed populations, animal experiments, and in vitro studies; however, the study of radiation related or induced disease has been limited in Korea. This study is to find the level of occupational radiation exposure for various kinds of accidents, compensated occupational diseases, related studies, and estimations on future occupational disease risks. Research data of related institutions were additionally investigated. About 67% of 62,553 radiation workers had no exposure or less than 1.2 mSv per year. The 5 reported cases on radiation accident patients in Korea occurred during nondestructive testing. According to the recent rapid increase in the number of workers exposed to radiation, a higher social recognition of cancer, and an increasing cancer mortality rate, it is expected that occupational disease compensation will rapidly increase as well. Therefore, it is important to develop scientific and objective decision methods, such as probability of causation and screening dose in the establishment of an exposure and health surveillance system. PMID:21258594

  4. Radiation-induced autophagy: mechanisms and consequences.

    PubMed

    Chaurasia, Madhuri; Bhatt, Anant Narayan; Das, Asmita; Dwarakanath, Bilikere S; Sharma, Kulbhushan

    2016-01-01

    Autophagy is an evolutionary conserved, indispensable, lysosome-mediated degradation process, which helps in maintaining homeostasis during various cellular traumas. During stress, a context-dependent role of autophagy has been observed which drives the cell towards survival or death depending upon the type, time, and extent of the damage. The process of autophagy is stimulated during various cellular insults, e.g. oxidative stress, endoplasmic reticulum stress, imbalances in calcium homeostasis, and altered mitochondrial potential. Ionizing radiation causes ROS-dependent as well as ROS-independent damage in cells that involve macromolecular (mainly DNA) damage, as well as ER stress induction, both capable of inducing autophagy. This review summarizes the current understanding on the roles of oxidative stress, ER stress, DNA damage, altered mitochondrial potential, and calcium imbalance in radiation-induced autophagy as well as the merits and limitations of targeting autophagy as an approach for radioprotection and radiosensitization. PMID:26764568

  5. Radiation-induced mutation at minisatellite loci

    SciTech Connect

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

    1997-10-01

    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 {gamma}-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 {sup 137}Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed.

  6. Heat pump processes induced by laser radiation

    NASA Technical Reports Server (NTRS)

    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.

  7. Study of chemical and radiation induced carcinogenesis

    SciTech Connect

    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  8. Mouse models for radiation-induced cancers.

    PubMed

    Rivina, Leena; Davoren, Michael J; Schiestl, Robert H

    2016-09-01

    Potential ionising radiation exposure scenarios are varied, but all bring risks beyond the simple issues of short-term survival. Whether accidentally exposed to a single, whole-body dose in an act of terrorism or purposefully exposed to fractionated doses as part of a therapeutic regimen, radiation exposure carries the consequence of elevated cancer risk. The long-term impact of both intentional and unintentional exposure could potentially be mitigated by treatments specifically developed to limit the mutations and precancerous replication that ensue in the wake of irradiation The development of such agents would undoubtedly require a substantial degree of in vitro testing, but in order to accurately recapitulate the complex process of radiation-induced carcinogenesis, well-understood animal models are necessary. Inbred strains of the laboratory mouse, Mus musculus, present the most logical choice due to the high number of molecular and physiological similarities they share with humans. Their small size, high rate of breeding and fully sequenced genome further increase its value for use in cancer research. This chapter will review relevant m. musculus inbred and F1 hybrid animals of radiation-induced myeloid leukemia, thymic lymphoma, breast and lung cancers. Method of cancer induction and associated molecular pathologies will also be described for each model. PMID:27209205

  9. Radiation abolishes inducer binding to lactose repressor.

    PubMed

    Gillard, Nathalie; Spotheim-Maurizot, Mélanie; Charlier, Michel

    2005-04-01

    The lactose operon functions under the control of the repressor-operator system. Binding of the repressor to the operator prevents the expression of the structural genes. This interaction can be destroyed by the binding of an inducer to the repressor. If ionizing radiations damage the partners, a dramatic dysfunction of the regulation system may be expected. We showed previously that gamma irradiation hinders repressor-operator binding through protein damage. Here we show that irradiation of the repressor abolishes the binding of the gratuitous inducer isopropyl-1-beta-D-thiogalactoside (IPTG) to the repressor. The observed lack of release of the repressor from the complex results from the loss of the ability of the inducer to bind to the repressor due to the destruction of the IPTG binding site. Fluorescence measurements show that both tryptophan residues located in or near the IPTG binding site are damaged. Since tryptophan damage is strongly correlated with the loss of IPTG binding ability, we conclude that it plays a critical role in the effect. A model was built that takes into account the kinetic analysis of damage production and the observed protection of its binding site by IPTG. This model satisfactorily accounts for the experimental results and allows us to understand the radiation-induced effects. PMID:15799700

  10. Genistein mitigates radiation-induced testicular injury.

    PubMed

    Kim, Joong-Sun; Heo, Kyu; Yi, Joo-Mi; Gong, Eun Ji; Yang, Kwangmo; Moon, Changjong; Kim, Sung-Ho

    2012-08-01

    The present study investigated the radioprotective effect of a multifunctional soy isoflavone, genistein, with the testicular system. Genistein was administered (200 mg/kg body weight) to male C3H/HeN mice by subcutaneous injection 24 h prior to pelvic irradiation (5 Gy). Histopathological parameters were evaluated 12 h and 21 days post-irradiation. Genistein protected the germ cells from radiation-induced apoptosis (p < 0.05 vs vehicle-treated irradiated mice at 12 h post-irradiation). Genistein significantly attenuated radiation-induced reduction in testis weight, seminiferous tubular diameter, seminiferous epithelial depth and sperm head count in the testes (p < 0.05 vs vehicle-treated irradiated mice at 21 days post-irradiation). Repopulation and stem cell survival indices of the seminiferous tubules were increased in the genistein-treated group compared with the vehicle-treated irradiation group at 21 days post-irradiation (p < 0.01). The irradiation-mediated decrease in the sperm count and sperm mobility in the epididymis was counteracted by genistein (p < 0.01), but no effect on the frequency of abnormal sperm was evident. Reactive oxygen species (ROS) were evaluated using DCFDA method and exposure to irradiation elevated ROS levels in the testis and genistein treatment resulted in a significant attenuation of radiation-induced ROS production. The results indicate that genistein protects from testicular dysfunction induced by gamma-irradiation by an antiapoptotic effect and recovery of spermatogenesis. PMID:22162311

  11. Cathodoluminescence of radiation-induced zircon

    NASA Astrophysics Data System (ADS)

    Tsuchiya, Y.; Nishido, H.; Kayama, M.; Noumi, Y.

    2013-12-01

    Zircon occurs as a common accessory mineral in igneous, metamorphic and sedimentary rocks, and maintains much information on thermal history, metamorphic process and natural radiation dose accumulated in the mineral. U-Pb zircon dating (e.g., SHRIMP) is an important tool to interpret a history of the minerals at a micrometer-scale, where cathodoluminescence (CL) image has been used for identification of internal zones and domains having different chemical compositions and/or structures with a high spatial resolution. The CL of zircon is derived from various types of emission centers, which are derived from impurities such as rare earth elements (REE) and structural defects. In fact, the CL features of zircon are closely related to metamorphic process and radiation from contained radionuclides as well as geochemical condition of its formation. Most zircon has yellow emission, which seems to be assigned to UO2 centers or radiation-induced defect during metamictization of the lattice by alpha particles from the decay of U and Th. In this study, the radiation effects on zircon CL have been studied for He+ ion-implanted samples annealed at various temperatures to clarify radiation-induced defect centers involved with the yellow CL emission in zircon. Single crystals of zircon from Malawi (MZ), Takidani granodiorite (TZ) and Kurobegawa granite (KZ) were selected for He+ ion implantation experiments. The polished plates of the samples were implanted by He+ ion 4.0 MeV corresponding to energy of alpha particle from 238 U and 232Th. CL spectra in the range from 300 to 800 nm with 1 nm step were measured by a scanning electron microscopy-cathodoluminescence (SEM-CL). CL spectra of untreated and annealed zircon show emission bands at ~370 nm assigned to intrinsic defect centers and at ~480, ~580 and ~760 nm to trivalent Dy impurity centers (Cesbron et al., 1995; Gaft et al, 2005). CL emissions in the yellow-region were observed in untreated zircon. The TZ and KZ indicate

  12. Estrogen Protects against Radiation-Induced Cataractogenesis

    PubMed Central

    Dynlacht, Joseph R.; Valluri, Shailaja; Lopez, Jennifer; Greer, Falon; DesRosiers, Colleen; Caperell-Grant, Andrea; Mendonca, Marc S.; Bigsby, Robert M.

    2008-01-01

    Cataractogenesis is a complication of radiotherapy when the eye is included in the treatment field. Low doses of densely ionizing space radiation may also result in an increased risk of cataracts in astronauts. We previously reported that estrogen (17-β-estradiol), when administered to ovariectomized rats commencing 1 week before γ irradiation of the eye and continuously thereafter, results in a significant increase in the rate and incidence of cataract formation and a decreased latent period compared to an ovariectomized control group. We therefore concluded that estrogen accelerates progression of radiation-induced opacification. We now show that estrogen, if administered continuously, but commencing after irradiation, protects against radiation cataractogenesis. Both the rate of progression and incidence of cataracts were greatly reduced in ovariectomized rats that received estrogen treatment after irradiation compared to ovariectomized rats. As in our previous study, estradiol administered 1 week prior to irradiation at the time of ovariectomy and throughout the period of observation produced an enhanced rate of cataract progression. Estrogen administered for only 1 week prior to irradiation had no effect on the rate of progression but resulted in a slight reduction in the incidence. We conclude that estrogen may enhance or protect against radiation cataractogenesis, depending on when it is administered relative to the time of irradiation, and may differentially modulate the initiation and progression phases of cataractogenesis. These data have important implications for astronauts and radiotherapy patients. PMID:19138041

  13. Radiation induced carcinoma of the larynx

    SciTech Connect

    Amendola, B.E.; Amendola, M.A.; McClatchey, K.D.

    1985-07-01

    A squamous cell carcinoma presented in a 20 year old female nonsmoker three years after receiving a high dosage of radiation therapy to the base of the skull, face and entire neuroaxis and intense combination chemotherapy for a parameningeal rhabdomyosarcoma of the paranasal sinuses is reported. The larynx received a dose of about 3,500 rads over an eight week period. This dosage in conjunction with the associated intense chemotherapy regimen given to the patient may explain the appearance of a radiation induced tumor in an unusually short latent period. This certainly represents a risk in young patients in whom an aggressive combined approach is taken and the physician should be aware of.

  14. Radiation-induced osteosarcoma of the sphenoid bone

    SciTech Connect

    Tanaka, S.; Nishio, S.; Morioka, T.; Fukui, M.; Kitamura, K.; Hikita, K. )

    1989-10-01

    The case of a patient who developed osteosarcoma in the sphenoid bone 15 years after radiation therapy for a craniopharyngioma is reported. Radiation-induced osteosarcoma of the sphenoid bone has not been reported previously. Reported cases of radiation-induced osteosarcomas are reviewed.

  15. Radiation induced micrencephaly in guinea pigs

    SciTech Connect

    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.

  16. Radiation-induced uterine changes: MR imaging

    SciTech Connect

    Arrive, L.; Chang, Y.C.; Hricak, H.; Brescia, R.J.; Auffermann, W.; Quivey, J.M.

    1989-01-01

    To assess the capability of magnetic resonance (MR) imaging to demonstrate postirradiation changes in the uterus, MR studies of 23 patients who had undergone radiation therapy were retrospectively examined and compared with those of 30 patients who had not undergone radiation therapy. MR findings were correlated with posthysterectomy histologic findings. In premenopausal women, radiation therapy induced (a) a decrease in uterine size demonstrable as early as 3 months after therapy ended; (b) a decrease in signal intensity of the myometrium on T2-predominant MR images, reflecting a significant decrease in T2 relaxation time, demonstrable as early as 1 month after therapy; (c) a decrease in thickness and signal intensity of the endometrium demonstrable on T2-predominant images 6 months after therapy; and (d) loss of uterine zonal anatomy as early as 3 months after therapy. In postmenopausal women, irradiation did not significantly alter the MR imaging appearance of the uterus. These postirradiation MR changes in both the premenopausal and postmenopausal uteri appeared similar to the changes ordinarily seen on MR images of the nonirradiated postmenopausal uterus.

  17. Theory Of Radiation-Induced Attenuation In Optical Fibers

    NASA Technical Reports Server (NTRS)

    Liu, Tsuen-Hsi; Johnston, Alan R.

    1996-01-01

    Improved theory of radiation-induced attenuation of light in optical fibers accounts for effects of dose rates. Based on kinetic aspects of fundamental physics of color centers induced in optical fibers by radiation. Induced attenuation is proportional to density of color centers, and part of this density decays by thermal-annealing/recombination process after irradiation.

  18. Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa.

    PubMed

    Naik, Edwina; Michalak, Ewa M; Villunger, Andreas; Adams, Jerry M; Strasser, Andreas

    2007-02-12

    To identify the mechanisms of ultraviolet radiation (UVR)-induced cell death, for which the tumor suppressor p53 is essential, we have analyzed mouse embryonic fibroblasts (MEFs) and keratinocytes in mouse skin that have specific apoptotic pathways blocked genetically. Blocking the death receptor pathway provided no protection to MEFs, whereas UVR-induced apoptosis was potently inhibited by Bcl-2 overexpression, implicating the mitochondrial pathway. Indeed, Bcl-2 overexpression boosted cell survival more than p53 loss, revealing a p53-independent pathway controlled by the Bcl-2 family. Analysis of primary MEFs lacking individual members of its BH3-only subfamily identified major initiating roles for the p53 targets Noxa and Puma. In the transformed derivatives, where Puma, unexpectedly, was not induced by UVR, Noxa had the dominant role and Bim a minor role. Furthermore, loss of Noxa suppressed the formation of apoptotic keratinocytes in the skin of UV-irradiated mice. Collectively, these results demonstrate that UVR activates the Bcl-2-regulated apoptotic pathway predominantly through activation of Noxa and, depending on cellular context, Puma. PMID:17283183

  19. Analog of microwave-induced resistance oscillations induced in GaAs heterostructures by terahertz radiation

    NASA Astrophysics Data System (ADS)

    Herrmann, T.; Dmitriev, I. A.; Kozlov, D. A.; Schneider, M.; Jentzsch, B.; Kvon, Z. D.; Olbrich, P.; Bel'kov, V. V.; Bayer, A.; Schuh, D.; Bougeard, D.; Kuczmik, T.; Oltscher, M.; Weiss, D.; Ganichev, S. D.

    2016-08-01

    We report on the study of terahertz radiation-induced MIRO-like oscillations of magnetoresistivity in GaAs heterostructures. Our experiments provide an answer on two most intriguing questions—effect of radiation helicity and the role of the edges—yielding crucial information for an understanding of the MIRO (microwave-induced resistance oscillations) origin. Moreover, we demonstrate that the range of materials exhibiting radiation-induced magneto-oscillations can be largely extended by using high-frequency radiation.

  20. Obstructive jaundice due to radiation-induced hepatic duct stricture

    SciTech Connect

    Chandrasekhara, K.L.; Iyer, S.K.

    1984-10-01

    A case of obstructive jaundice due to radiation-induced hepatic duct stricture is reported. The patient received postoperative radiation for left adrenal carcinoma, seven years prior to this admission. The sequelae of hepatobiliary radiation and their management are discussed briefly.

  1. Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro.

    PubMed

    Dyshlovoy, Sergey A; Tabakmakher, Kseniya M; Hauschild, Jessica; Shchekaleva, Regina K; Otte, Katharina; Guzii, Alla G; Makarieva, Tatyana N; Kudryashova, Ekaterina K; Fedorov, Sergey N; Shubina, Larisa K; Bokemeyer, Carsten; Honecker, Friedemann; Stonik, Valentin A; von Amsberg, Gunhild

    2016-01-01

    Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1-6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1-4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P⁺ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading. PMID:27428983

  2. Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

    PubMed Central

    Dyshlovoy, Sergey A.; Tabakmakher, Kseniya M.; Hauschild, Jessica; Shchekaleva, Regina K.; Otte, Katharina; Guzii, Alla G.; Makarieva, Tatyana N.; Kudryashova, Ekaterina K.; Fedorov, Sergey N.; Shubina, Larisa K.; Bokemeyer, Carsten; Honecker, Friedemann; Stonik, Valentin A.; von Amsberg, Gunhild

    2016-01-01

    Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1–6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1–4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P+ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading. PMID:27428983

  3. Treatment of radiation-induced cystitis with hyperbaric oxygen

    SciTech Connect

    Weiss, J.P.; Boland, F.P.; Mori, H.; Gallagher, M.; Brereton, H.; Preate, D.L.; Neville, E.C.

    1985-08-01

    The effects of hyperbaric oxygen on radiation cystitis have been documented in 3 patients with radiation-induced hemorrhagic cystitis refractory to conventional therapy. Cessation of gross hematuria and reversal of cystoscopic bladder changes were seen in response to a series of hyperbaric oxygen treatments of 2 atmosphere absolute pressure for 2 hours. To our knowledge this is the first report of cystoscopically documented healing of radiation-induced bladder injury.

  4. Radiation-induced nausea and vomiting

    PubMed Central

    Habibi, Mohsen; Namimoghadam, Amir; Korouni, Roghaye; Fashiri, Paria; Borzoueisileh, Sajad; Elahimanesh, Farideh; Amiri, Fatemeh; Moradi, Ghobad

    2016-01-01

    Abstract Despite the improvements in cancer screening and treatment, it still remains as one of the leading causes of mortality worldwide. Nausea and vomiting as the side effects of different cancer treatment modalities, such as radiotherapy, are multifactorial and could affect the treatment continuation and patient quality of life. Therefore, the aim of this study was to assess the possible linkage between ABO blood groups and radiation-induced nausea and vomiting (RINV), also its incidence and affecting factors. One hundred twenty-eight patients referring to Tohid hospital of Sanandaj, Iran, were selected and the patients and treatment-related factors were determined in a cross-sectional study. Patients’ nausea and vomiting were recorded from the onset of treatment until 1 week after treatment accomplishment. Also, previous possible nausea and vomiting were recorded. The frequencies of nausea and vomiting and their peak time were examined during the treatment period. The association between ABO blood group and the incidence of radiotherapy-induced nausea and vomiting (RINV) were significant and it seems that A blood group patients are the most vulnerable individuals to these symptoms. The association between Rhesus antigen and the time of maximum severity of RINV may indicate that Rhesus antigen affects the time of maximum severity of RINV. The incidence of RINV was not affected by karnofsky performance status, but it was related to the severity of RINV. Furthermore, among the factors affecting the incidence of nausea and vomiting, nausea and vomiting during patient's previous chemotherapy, radiotherapy region, and background gastrointestinal disease were shown to be three important factors. In addition to familiar RINV-affecting factors, ABO blood group may play an important role and these results address the needs for further studies with larger sample size. PMID:27495037

  5. Radiation-induced degradation of DNA bases

    NASA Astrophysics Data System (ADS)

    Douki, T.; Delatour, T.; Martini, R.; Cadet, J.

    1999-01-01

    Radio-induced degradation of DNA involves radical processes. A series of lesions among the major bases degradation products 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 four bases are degraded in high yield. Direct effect has been mimicked by photo-induced electron abstraction from the bases producing their radical cation. Quantification of the modified bases showed that guanine is the preferential target. This can be explained by its lower oxidation potential and charge transfer phenomena. La décomposition radio-induite de l'ADN fait intervenir des processus radicalaires. Une série de lésions choisies parmi les produits majeurs de dégradation des bases a été mesurée dans de l'ADN isolé exposé au rayonnement en solution aqueuse aérée. Les modifications sont alors dues aux radicaux hydroxyles produits par la radiolyse de l'eau (effet indirect) et les quatre bases sont efficacement dégradées. L'arrachement d'électrons aux bases par photosensibilisation pour produire leur radical cation, a été utilisé comme modèle de l'effet direct. La quantification des bases modifiées montre que la guanine est préférentiellement dégradée. Cette observation peut s'expliquer par le plus faible potentiel d'oxydation de cette base ainsi que par les phénomènes de transfert de charge vers les guanines.

  6. Pravastatin limits radiation-induced vascular dysfunction in the skin.

    PubMed

    Holler, Valerie; Buard, Valerie; Gaugler, Marie-Helene; Guipaud, Olivier; Baudelin, Cedric; Sache, Amandine; Perez, Maria del R; Squiban, Claire; Tamarat, Radia; Milliat, Fabien; Benderitter, Marc

    2009-05-01

    About half of people with cancer are treated with radiation therapy; however, normal tissue toxicity still remains a dose-limiting factor for this treatment. The skin response to ionizing radiation may involve multiple inflammatory outbreaks. The endothelium is known to play a critical role in radiation-induced vascular injury. Furthermore, endothelial dysfunction reflects a decreased availability of nitric oxide. Statins have been reported to preserve endothelial function through their antioxidant and anti-inflammatory activities. In this study, wild type and endothelial nitric oxide synthase (eNOS)(-/-) mice were subjected to dorsal skin irradiation and treated with pravastatin for 28 days. We demonstrated that pravastatin has a therapeutic effect on skin lesions and abolishes radiation-induced vascular functional activation by decreasing interactions between leukocytes and endothelium. Pravastatin limits the radiation-induced increase of blood CCL2 and CXCL1 production expression of inflammatory adhesion molecules such as E-selectin and intercellular adhesion molecule-1, and inflammatory cell migration in tissues. Pravastatin limits the in vivo and in vitro radiation-induced downregulation of eNOS. Moreover, pravastatin has no effect in eNOS(-/-) mice, demonstrating that eNOS plays a key role in the beneficial effect of pravastatin in radiation-induced skin lesions. In conclusion, pravastatin may be a good therapeutic approach to prevent or reduce radiation-induced skin damage. PMID:19212344

  7. Radiation-induced undifferentiated pleomorphic sarcoma after radiation therapy for a desmoid tumour.

    PubMed

    Di Marco, J; Kaci, R; Orcel, P; Nizard, R; Laredo, J-D

    2016-02-01

    Radiation-induced sarcoma is a long-term complication of radiation therapy. The most common secondary neoplasia is the undifferentiated pleomorphic sarcoma, which is usually described in the deep soft tissue of the trunk or extremities. Radiation-induced sarcomas have a poor prognosis. An early diagnosis and management are needed to improve the survival rate of such patients. We presently report a case of a radiation-induced undifferentiated pleomorphic sarcoma of the left gluteus maximus muscle, which developed 25 years after an initial diagnosis of aggressive fibromatosis and 21 years after a tumour recurrence. This case study illustrates the risk of developing a sarcoma in a radiation field and the need for long-term follow-up after radiation therapy. Unnecessary radiation therapy, in particular in the case of benign conditions in young patients, should be avoided. PMID:26725422

  8. Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases.

    PubMed

    Wang, Yingying; Boerma, Marjan; Zhou, Daohong

    2016-08-01

    Exposure to ionizing radiation induces not only apoptosis but also senescence. While the role of endothelial cell apoptosis in mediating radiation-induced acute tissue injury has been extensively studied, little is known about the role of endothelial cell senescence in the pathogenesis of radiation-induced late effects. Senescent endothelial cells exhibit decreased production of nitric oxide and expression of thrombomodulin, increased expression of adhesion molecules, elevated production of reactive oxygen species and inflammatory cytokines and an inability to proliferate and form capillary-like structures in vitro. These findings suggest that endothelial cell senescence can lead to endothelial dysfunction by dysregulation of vasodilation and hemostasis, induction of oxidative stress and inflammation and inhibition of angiogenesis, which can potentially contribute to radiation-induced late effects such as cardiovascular diseases (CVDs). In this article, we discuss the mechanisms by which radiation induces endothelial cell senescence, the roles of endothelial cell senescence in radiation-induced CVDs and potential strategies to prevent, mitigate and treat radiation-induced CVDs by targeting senescent endothelial cells. PMID:27387862

  9. Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases

    PubMed Central

    Wang, Yingying; Boerma, Marjan; Zhou, Daohong

    2016-01-01

    Exposure to ionizing radiation induces not only apoptosis but also senescence. While the role of endothelial cell apoptosis in mediating radiation-induced acute tissue injury has been extensively studied, little is known about the role of endothelial cell senescence in the pathogenesis of radiation-induced late effects. Senescent endothelial cells exhibit decreased production of nitric oxide and expression of thrombomodulin, increased expression of adhesion molecules, elevated production of reactive oxygen species and inflammatory cytokines and an inability to proliferate and form capillary-like structures in vitro. These findings suggest that endothelial cell senescence can lead to endothelial dysfunction by dysregulation of vasodilation and hemostasis, induction of oxidative stress and inflammation and inhibition of angiogenesis, which can potentially contribute to radiation-induced late effects such as cardiovascular diseases (CVDs). In this article, we discuss the mechanisms by which radiation induces endothelial cell senescence, the roles of endothelial cell senescence in radiation-induced CVDs and potential strategies to prevent, mitigate and treat radiation-induced CVDs by targeting senescent endothelial cells. PMID:27387862

  10. Radiation exposure induces inflammasome pathway activation in immune cells.

    PubMed

    Stoecklein, Veit M; Osuka, Akinori; Ishikawa, Shizu; Lederer, Madeline R; Wanke-Jellinek, Lorenz; Lederer, James A

    2015-02-01

    Radiation exposure induces cell and tissue damage, causing local and systemic inflammatory responses. Because the inflammasome pathway is triggered by cell death and danger-associated molecular patterns, we hypothesized that the inflammasome may signal acute and chronic immune responses to radiation. Using a mouse radiation model, we show that radiation induces a dose-dependent increase in inflammasome activation in macrophages, dendritic cells, NK cells, T cells, and B cells as judged by cleaved caspase-1 detection in cells. Time course analysis showed the appearance of cleaved caspase-1 in cells by day 1 and sustained expression until day 7 after radiation. Also, cells showing inflammasome activation coexpressed the cell surface apoptosis marker annexin V. The role of caspase-1 as a trigger for hematopoietic cell losses after radiation was studied in caspase-1(-/-) mice. We found less radiation-induced cell apoptosis and immune cell loss in caspase-1(-/-) mice than in control mice. Next, we tested whether uric acid might mediate inflammasome activation in cells by treating mice with allopurinol and discovered that allopurinol treatment completely blocked caspase-1 activation in cells. Finally, we demonstrate that radiation-induced caspase-1 activation occurs by a Nod-like receptor family protein 3-independent mechanism because radiation-exposed Nlrp3(-/-) mice showed caspase-1 activation profiles that were indistinguishable from those of wild-type mice. In summary, our data demonstrate that inflammasome activation occurs in many immune cell types following radiation exposure and that allopurinol prevented radiation-induced inflammasome activation. These results suggest that targeting the inflammasome may help control radiation-induced inflammation. PMID:25539818

  11. Clinical and dosimetric factors of radiation-induced esophageal injury: Radiation-induced esophageal toxicity

    PubMed Central

    Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

    2005-01-01

    AIM: To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). METHODS: We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT. PMID:15849822

  12. Radiation-induced impairment of neuronal excitability

    SciTech Connect

    Pellmar, T.C.; Tolliver, J.M.; Neel, K.L.

    1988-01-01

    Radiation causes a decrease in the synaptically evoked activity of CA1 hippocampal pyramidal cells. This effect is dose and dose-rate dependent. Hydrogen peroxide, which produces hydroxyl free radicals when combined with FE + 2, produces similar damage. In contrast, the radioprotectant, dithiothreitol, increases the excitability of hippocampal neurons. These studies indicate that radiation can directly affect the function of central neurons.

  13. Radiation-induced charge trapping in bipolar base oxides

    SciTech Connect

    Fleetwood, D.M.; Riewe, L.C.; Witczak, Schrimpf, R.D.

    1996-03-01

    Capacitance-voltage and thermally stimulated current methods are used to investigate radiation induced charge trapping in bipolar base oxides. Results are compared with models of oxide and interface trap charge buildup at low electric fields.

  14. Heavy-ion radiation induced bystander effect in mice

    NASA Astrophysics Data System (ADS)

    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. Coherent microwave radiation from a laser induced plasma

    SciTech Connect

    Shneider, M. N.; Miles, R. B.

    2012-12-24

    We propose a method for generation of coherent monochromatic microwave/terahertz radiation from a laser-induced plasma. It is shown that small-scale plasma, located in the interaction region of two co-propagating plane-polarized laser beams, can be a source of the dipole radiation at a frequency equal to the difference between the frequencies of the lasers. This radiation is coherent and appears as a result of the so-called optical mixing in plasma.

  16. Radiation-induced myeloid leukemia in murine models

    PubMed Central

    2014-01-01

    The use of radiation therapy is a cornerstone of modern cancer treatment. The number of patients that undergo radiation as a part of their therapy regimen is only increasing every year, but this does not come without cost. As this number increases, so too does the incidence of secondary, radiation-induced neoplasias, creating a need for therapeutic agents targeted specifically towards incidence reduction and treatment of these cancers. Development and efficacy testing of these agents requires not only extensive in vitro testing but also a set of reliable animal models to accurately recreate the complex situations of radiation-induced carcinogenesis. As radiation-induced leukemic progression often involves genomic changes such as rearrangements, deletions, and changes in methylation, the laboratory mouse Mus musculus, with its fully sequenced genome, is a powerful tool in cancer research. This fact, combined with the molecular and physiological similarities it shares with man and its small size and high rate of breeding in captivity, makes it the most relevant model to use in radiation-induced leukemia research. In this work, we review relevant M. musculus inbred and F1 hybrid animal models, as well as methods of induction of radiation-induced myeloid leukemia. Associated molecular pathologies are also included. PMID:25062865

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

    SciTech Connect

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

    1997-03-01

    For REC:myc(ch1), Rat1 and Rat1:myc{sub 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 {sup 4}He ions of well defined energies and which compared the dependence of apoptosis and clonogenic survival on {sup 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{sub 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{sub 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{sub 2} phases reduced the relative radioresistance observed for clonogenic survival during late S and G{sub 2} phases. 30 refs., 8 figs.

  18. Hedgehog signaling and radiation induced liver injury: a delicate balance

    PubMed Central

    Kabarriti, Rafi

    2016-01-01

    Radiation-induced liver disease (RILD) is a major limitation of radiation therapy (RT) for the treatment of liver cancer. Emerging data indicate that hedgehog (Hh) signaling plays a central role in liver fibrosis and regeneration after liver injury. Here, we review the potential role of Hh signaling in RILD and propose the temporary use of Hh inhibition during liver RT to radiosensitize HCC tumor cells and inhibit their progression, while blocking the initiation of the radiation-induced fibrotic response in the surrounding normal liver. PMID:26202634

  19. Hyperbaric oxygen: Primary treatment of radiation-induced hemorrhagic cystitis

    SciTech Connect

    Weiss, J.P.; Neville, E.C.

    1989-07-01

    Of 8 patients with symptoms of advanced cystitis due to pelvic radiation treated with hyperbaric oxygen 7 are persistently improved during followup. All 6 patients treated for gross hematuria requiring hospitalization have been free of symptoms for an average of 24 months (range 6 to 43 months). One patient treated for stress incontinence currently is dry despite little change in bladder capacity, implying salutary effect from hyperbaric oxygen on the sphincter mechanism. One patient with radiation-induced prostatitis failed to respond. This experience suggests that hyperbaric oxygen should be considered the primary treatment for patients with symptomatic radiation-induced hemorrhagic cystitis.

  20. Hedgehog signaling and radiation induced liver injury: a delicate balance.

    PubMed

    Kabarriti, Rafi; Guha, Chandan

    2014-07-01

    Radiation-induced liver disease (RILD) is a major limitation of radiation therapy (RT) for the treatment of liver cancer. Emerging data indicate that hedgehog (Hh) signaling plays a central role in liver fibrosis and regeneration after liver injury. Here, we review the potential role of Hh signaling in RILD and propose the temporary use of Hh inhibition during liver RT to radiosensitize HCC tumor cells and inhibit their progression, while blocking the initiation of the radiation-induced fibrotic response in the surrounding normal liver. PMID:26202634

  1. p53 is involved in clearance of ionizing radiation-induced RAD51 foci in a human colon cancer cell line

    SciTech Connect

    Orre, Lukas M. . E-mail: Lukas.Orre@ki.se; Stenerloew, Bo; Dhar, Sumeer; Larsson, Rolf; Lewensohn, Rolf; Lehtioe, Janne

    2006-04-21

    We have investigated p53-related differences in cellular response to DNA damaging agents, focusing on p53s effects on RAD51 protein level and sub-cellular localization post exposure to ionizing radiation. In a human colon cancer cell line, HCT116 and its isogenic p53-/- subcell line we show here p53-independent RAD51 foci formation but interestingly the resolution of RAD51 foci showed clear p53 dependence. In p53 wt cells, but not in p53-/- cells, RAD51 protein level decreased 48 h post irradiation and fluorescence immunostaining showed resolution of RAD51 foci and relocalization of RAD51 to nucleoli at time points corresponding to the decrease in RAD51 protein level. Both cell lines rejoined DNA double strand breaks efficiently with similar kinetics and p53 status did not influence sensitivity to DNA damaging agents. We suggest that p53 has a role in RAD51 clearance post DSB repair and that nucleoli might be sites of RAD51 protein degradation.

  2. Radiation-induced malignant and atypical peripheral nerve sheath tumors

    SciTech Connect

    Foley, K.M.; Woodruff, J.M.; Ellis, F.T.; Posner, J.B.

    1980-04-01

    The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. In all instances the radio-theray was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. The malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation.

  3. Radiation-Induced Problems in Colorectal Surgery.

    PubMed

    Ashburn, Jean H; Kalady, Matthew F

    2016-06-01

    Radiotherapy not only plays a pivotal role in the cancer care pathways of many patients with pelvic malignancies, but can also lead to significant injury of normal tissue in the radiation field (pelvic radiation disease) that is sometimes as challenging to treat as the neoplasms themselves. Acute symptoms are usually self-limited and respond to medical therapy. Chronic symptoms often require operative intervention that is made hazardous by hostile surgical planes and unforgiving tissues. Management of these challenging patients is best guided by the utmost caution and humility. PMID:27247532

  4. Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury

    PubMed Central

    Cotrim, Ana P.; Hyodo, Fuminori; Baum, Bruce J.; Krishna, Murali C.; Mitchell, James B.

    2010-01-01

    Radiation is used in the treatment of a broad range of malignancies. Exposure of normal tissue to radiation may result in both acute and chronic toxicities that can result in an inability to deliver the intended therapy, a range of symptoms, and a decrease in quality of life. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Herein, we review agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury. Few agents are approved for clinical use, but many new compounds show promising results in preclinical testing. PMID:20413641

  5. Radiation-induced cerebellar chondrosarcoma. Case report

    SciTech Connect

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

    1984-07-01

    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.

  6. Hyperprolactinemia from radiation-induced hypothalamic hypopituitarism

    SciTech Connect

    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.

  7. Radiatively induced Fermi scale and unification

    NASA Astrophysics Data System (ADS)

    Alanne, Tommi; Meroni, Aurora; Sannino, Francesco; Tuominen, Kimmo

    2016-05-01

    We consider extensions of the Standard Model in which the hierarchy between the unification and the Fermi scale emerges radiatively. Within the Pati-Salam framework, we show that it is possible to construct a viable model where the Higgs is an elementary pseudo-Goldstone boson, and the correct hierarchy is generated.

  8. RADIATION INDUCED VULCANIZATION OF RUBBER LATEX

    DOEpatents

    Mesrobian, R.B.; Ballantine, D.S.; Metz, D.J.

    1964-04-28

    A method of vulcanizing rubber latex by exposing a mixture containing rubber latex and from about 15 to about 21.3 wt% of 2,5-dichlorostyrene to about 1.1 megarads of gamma radiation while maintaining the temperature of the mixture at a temperature ranging between from about 56 to about 59 deg C is described. (AEC)

  9. p53-independent ibrutinib responses in an Eμ-TCL1 mouse model demonstrates efficacy in high-risk CLL.

    PubMed

    Lee, H J; Gallardo, M; Ma, H; Zhang, X; Larsson, C A; Mejia, A; Hornbaker, M J; Qi, Y; Su, X; Pageon, L R; Quintas-Cardama, A; Post, S M

    2016-01-01

    Deletion of the short-arm of chromosome 17 (17p-) is one of the most critical genetic alterations used in chronic lymphocytic leukemia (CLL) risk stratification. The tumor suppressor TP53 maps to this region, and its loss or mutation accelerates CLL progression, hampers response to chemotherapy and shortens survival. Although florescent in situ hybridization analyses for 17p deletions are routinely performed during clinical diagnoses, p53 mutational status is often unexamined. Given the limited clinical data that exists for frontline treatment of patients with CLL harboring TP53 mutations, there is a need to understand the biology of CLL with TP53 mutations and identify treatment strategies for this subset of patients. Herein, we used a CLL mouse model (Eμ-TCL1) harboring one of the most common TP53 hot-spot mutations observed in CLL (p53(R172H), corresponding to p53(R175H) in humans) to evaluate its impact on disease progression, survival, response to therapy and loss of the remaining wild-type Trp53 allele following ibrutinib treatment. We show that ibrutinib was effective in increasing survival, activating cellular programs outside the p53 pathway and did not place selective pressure on the remaining wild-type Trp53 allele. These data provide evidence that ibrutinib acts as an effective treatment for aggressive forms of CLL with TP53 mutations. PMID:27284738

  10. Radiation-induced biomarkers for the detection and assessment of absorbed radiation doses

    PubMed Central

    Rana, Sudha; Kumar, Raj; Sultana, Sarwat; Sharma, Rakesh Kumar

    2010-01-01

    Radiation incident involving living organisms is an uncommon but a very serious situation. The first step in medical management including triage is high-throughput assessment of the radiation dose received. Radiation exposure levels can be assessed from viability of cells, cellular organelles such as chromosome and different intermediate metabolites. Oxidative damages by ionizing radiation result in carcinogenesis, lowering of the immune response and, ultimately, damage to the hematopoietic system, gastrointestinal system and central nervous system. Biodosimetry is based on the measurement of the radiation-induced changes, which can correlate them with the absorbed dose. Radiation biomarkers such as chromosome aberration are most widely used. Serum enzymes such as serum amylase and diamine oxidase are the most promising biodosimeters. The level of gene expression and protein are also good biomarkers of radiation. PMID:21829314

  11. Radiation induced growth of micro crystallites

    SciTech Connect

    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.

  12. Radiation recall dermatitis induced by trastuzumab.

    PubMed

    Moon, Dochang; Koo, Ja Seung; Suh, Chang-Ok; Yoon, Chang Yun; Bae, Jaehyun; Lee, Soohyeon

    2016-01-01

    We report a case of radiation recall dermatitis caused by trastuzumab. A 55-year-old woman with metastatic breast cancer received palliative first-line trastuzumab/paclitaxel and a salvage partial mastectomy with lymph node dissection was subsequently performed. In spite of the palliative setting, the pathology report indicated that no residual carcinoma was present, and then she underwent locoregional radiotherapy to ensure a definitive response. After radiotherapy, she has maintained trastuzumab monotherapy. Nine days after the fifth cycle of trastuzumab monotherapy, dermatitis in previously irradiated skin developed, with fever. Radiation recall dermatitis triggered by trastuzumab is extremely rare. A high fever developed abruptly with a skin rash. This may be the first case of this sort to be reported. PMID:23543400

  13. Mitigation of radiation induced surface contamination

    DOEpatents

    Klebanoff, Leonard E.; Stulen, Richard H.

    2003-01-01

    A process for mitigating or eliminating contamination and/or degradation of surfaces having common, adventitious atmospheric contaminants adsorbed thereon and exposed to radiation. A gas or a mixture of gases is introduced into the environment of a surface(s) to be protected. The choice of the gaseous species to be introduced (typically a hydrocarbon gas, water vapor, or oxygen or mixtures thereof) is dependent upon the contaminant as well as the ability of the gaseous species to bind to the surface to be protected. When the surface and associated bound species are exposed to radiation reactive species are formed that react with surface contaminants such as carbon or oxide films to form volatile products (e.g., CO, CO.sub.2) which desorb from the surface.

  14. DECOHERENCE EFFECTS OF MOTION-INDUCED RADIATION

    SciTech Connect

    P. NETO; D. DALVIT

    2000-12-01

    The radiation pressure coupling with vacuum fluctuations gives rise to energy damping and decoherence of an oscillating particle. Both effects result from the emission of pairs of photons, a quantum effect related to the fluctuations of the Casimir force. We discuss different alternative methods for the computation of the decoherence time scale. We take the example of a spherical perfectly-reflecting particle, and consider the zero and high temperature limits. We also present short general reviews on decoherence and dynamical Casimir effect.

  15. Simple method to demonstrate radiation-inducible radiation resistance in microbial cells

    SciTech Connect

    Tan, S.T.; Maxcy, R.B.

    1986-01-01

    A simple method for detection of radiation-inducible radiation resistance was developed by irradiating aliquots (0.01 ml) of cell suspension on agar plates. Part of each experimental plate was subjected to an induction treatment, and subsequent radiation resistance was compared with that of untreated cells on the same plate. The UV radiation resistance of a Micrococcus sp. was increased approximately 1.6 times by an induction treatment. This simple procedure of irradiating cells in a fixed position on agar avoided washing, centrifugation, and cell enumeration required in traditional methods.

  16. Process and Radiation Induced Defects in Electronic Materials and Devices

    NASA Technical Reports Server (NTRS)

    Washington, Kenneth; Fogarty, T. N.

    1997-01-01

    Process and radiation induced defects are characterized by a variety of electrical techniques, including capacitance-voltage measurements and charge pumping. Separation of defect type into stacking faults, displacement damage, oxide traps, interface states, etc. and their related causes are discussed. The defects are then related to effects on device parameters. Silicon MOS technology is emphasized. Several reviews of radiation effects and silicon processing exist.

  17. Radiation-induced products of peptides and their enzymatic digestibility

    SciTech Connect

    Gajewski, E.

    1983-01-01

    Chemical characterization of radiation-induced products of peptides and proteins is essential for understanding the effect of ionizing radiation on peptides and proteins. Furthermore, peptides containing radiation-altered amino acid residues might not be completely digestible by proteolytic enzymes. In this work, small homopeptides of Ala, Phe and Met were chosen as model peptides. Lysozyme was used to investigate the effect of ionizing radiation on a small protein. All peptides and lysozyme were irradiated in diluted, oxygen free, N/sub 2/O-saturated aqueous solutions, using a /sup 60/Co-..gamma..-source. HPLC, capillary GC and GC-MS were applied to isolate and characterize the radiation-induced products. The enzymatic digestibility of the products was investigated using aminopeptidase M, leucine aminopeptidase, carboxypeptidase A and carboxypeptidase Y. It was found that irradiation of peptides examined in this work leads to racemization and alteration of amino acid residues and crosslinks between the peptide chains. In addition, it was established that exopeptidases act differently on radiation-induced dimers of peptides composed of aliphatic, aromatic and sulfur-containing amino acids.

  18. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    NASA Technical Reports Server (NTRS)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  19. Panretinal photocoagulation for radiation-induced ocular ischemia

    SciTech Connect

    Augsburger, J.J.; Roth, S.E.; Magargal, L.E.; Shields, J.A.

    1987-08-01

    We present preliminary findings on the effectiveness of panretinal photocoagulation in preventing neovascular glaucoma in eyes with radiation-induced ocular ischemia. Our study group consisted of 20 patients who developed radiation-induced ocular ischemia following cobalt-60 plaque radiotherapy for a choroidal or ciliary body melanoma. Eleven of the 20 patients were treated by panretinal photocoagulation shortly after the diagnosis of ocular ischemia, but nine patients were left untreated. In this non-randomized study, the rate of development of neovascular glaucoma was significantly lower (p = 0.024) for the 11 photocoagulated patients than for the nine who were left untreated.

  20. Intraoperative radiation therapy-induced sarcomas in dogs.

    PubMed

    Hoekstra, H J; Sindelar, W F; Kinsella, T J; Mehta, D M

    1989-12-01

    In a canine model the tolerance of normal and surgically manipulated tissue to intraoperative radiotherapy (IORT) was investigated to provide guidelines for the clinical use of IORT in human cancer patients. A dose of 20 Gy IORT, with or without external beam radiotherapy, was generally well tolerated without significant increased treatment morbidity. Higher doses of IORT (over 30 Gy) have produced radiation-induced sarcomas in some animals followed over a long period. Therefore IORT should be used only in human cancer patients in well controlled studies, in which complications are well documented, and the possibility of radiation-induced malignancies in long-term survival should be considered. PMID:2594971

  1. The Mechanisms of Radiation-Induced Bystander Effect

    PubMed Central

    Najafi, M; Fardid, R; Hadadi, Gh; Fardid, M

    2014-01-01

    The radiation-induced bystander effect is the phenomenon which non-irradiated cells exhibit effects along with their different levels as a result of signals received from nearby irradiated cells. Responses of non-irradiated cells may include changes in process of translation, gene expression, cell proliferation, apoptosis and cells death. These changes are confirmed by results of some In-Vivo studies. Most well-known important factors affecting radiation-induced bystander effect include free radicals, immune system factors, expression changes of some genes involved in inflammation pathway and epigenetic factors. PMID:25599062

  2. Mechanisms of radiation-induced neoplastic cell transformation

    SciTech Connect

    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.

  3. Radiation-induced endometriosis in Macaca mulatta

    SciTech Connect

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

    1991-05-01

    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.

  4. Atorvastatin Ameliorates Radiation-Induced Cardiac Fibrosis in Rats.

    PubMed

    Zhang, KunYi; He, XuYu; Zhou, Yingling; Gao, Lijuan; Qi, Zhengyu; Chen, Jiyan; Gao, Xiuren

    2015-12-01

    Radiation-induced heart injury is one of the major side effects of radiotherapy for thoracic malignancies. Previous studies have shown that radiotherapy induced myocardial fibrosis and intensified myocardial remodeling. In this study, we investigated whether atorvastatin could inhibit radiation-induced heart fibrosis in Sprague-Dawley rats, which were randomly divided into six groups: control; radiation only; and four treatment groups receiving atorvastatin plus radiation (E1, E2, E3 and E4). All rats, except the control group, received local heart irradiation in 7 daily fractions of 3 Gy for a total of 21 Gy. Rats in groups E1 (10 mg/kg/day) and E2 (20 mg/kg/day) received atorvastatin and radiation treatment until week 12 after exposure. Rats in groups E3 (10 mg/kg/day) and E4 (20 mg/kg/day) received atorvastatin treatment from 3 months before irradiation to week 12 after irradiation. The expressions of TGF-β1, Smad2, Smad3, fibronectin, ROCK I and p-Akt in heart tissues were evaluated using real-time PCR or Western blot analyses. Atorvastatin significantly reduced the expression of TGF-β1, Smad3/P-Smad3, ROCK I and p-Akt in rats of the E1-E4 groups and in a dose-dependent manner. Fibronectin exhibited a similar pattern of expression changes. In addition, echocardiography showed that atorvastatin treatment can inhibit the increase of left ventricular end-diastolic dimension, left ventricular end-systolic diameter and left ventricular posterior wall thickness, and prevent the decrease of ejection fraction and fraction shortening in E1-E4 groups compared with the radiation only group. This study demonstrated that radiation exposure increased the expression of fibronectin in cardiac fibroblasts and induced cardiac fibrosis through activation of the TGF-β1/Smad3, RhoA/ROCK, and PI3K/AKT signaling pathways. Statins ameliorated radiation-induced cardiac fibrosis in Sprague-Dawley rats. Our results suggest that atorvastatin is effective for the treatment of radiation-induced

  5. Radiation induced inter-device leakage degradation

    NASA Astrophysics Data System (ADS)

    Hu, Zhi-Yuan; Liu, Zhang-Li; Shao, Hua; Zhang, Zheng-Xuan; Ning, Bing-Xu; Chen, Ming; Bi, Da-Wei; Zou, Shi-Chang

    2011-08-01

    The evolution of inter-device leakage current with total ionizing dose in transistors in 180 nm generation technologies is studied with an N-type poly-gate field device (PFD) that uses the shallow trench isolation as an effective gate oxide. The overall radiation response of these structures is determined by the trapped charge in the oxide. The impacts of different bias conditions during irradiation on the inter-device leakage current are studied for the first time in this work, which demonstrates that the worst condition is the same as traditional NMOS transistors. Moreover, the two-dimensional technology computer-aided design simulation is used to understand the bias dependence.

  6. Radiation-induced basal cell carcinoma

    PubMed Central

    Zargari, Omid

    2015-01-01

    Background: The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. A variety of cancers including basal cell carcinoma (BCC) are seen years after this treatment. Objective: We sought to determine the clinical characteristics of BCCs among irradiated patients. Methods: The clinical records of all patients with BCC in a clinic in north of Iran were reviewed. Results: Of the 58 cases of BCC, 29 had positive history for radiotherapy in their childhood. Multiple BCCs were seen in 79.3% and 10.3% of patients with history and without history of radiotherapy, respectively. Conclusions: X-ray radiation is still a major etiologic factor in developing BCC in northern Iran. Patients with positive history for radiotherapy have higher rate of recurrence. PMID:26114066

  7. The axiverse induced dark radiation problem

    NASA Astrophysics Data System (ADS)

    Acharya, Bobby; Pongkitivanichkul, Chakrit

    2016-04-01

    The string/ M theory Axiverse — a plethora of very light Axion Like Particles (ALPs) with a vast range of masses — is arguably a generic prediction of string/ M theory. String/ M theory also tends to predict that the early Universe is dominated by moduli fields. When the heavy moduli decay, before nucleosynthesis, they produce dark radiation in the form of relativistic ALPs. Generically one estimates that the number of relativistic species grows with the number of axions in the Axiverse, in contradiction to the observations that N eff ≤ 4. We explain this problem in detail and suggest some possible solutions to it. The simplest solution requires that the lightest modulus decays only into its own axion superpartner plus Standard Model particles and this severely constrains the moduli Kahler potential and mass matrix.

  8. Interleukin-32 Positively Regulates Radiation-Induced Vascular Inflammation

    SciTech Connect

    Kobayashi, Hanako; Yazlovitskaya, Eugenia M.; Lin, P. Charles

    2009-08-01

    Purpose: To study the role of interleukin-32 (IL-32), a novel protein only detected in human tissues, in ionizing radiation (IR)-induced vascular inflammation. Methods and Materials: Irradiated (0-6 Gy) human umbilical vein endothelial cells treated with or without various agents-a cytosolic phospholipase A2 (cPLA2) inhibitor, a cyclooxygenase-2 (Cox-2) inhibitor, or lysophosphatidylcholines (LPCs)-were used to assess IL-32 expression by Northern blot analysis and quantitative reverse transcriptase-polymerase chain reaction. Expression of cell adhesion molecules and leukocyte adhesion to endothelial cells using human acute monocytic leukemia cell line (THP-1) cells was also analyzed. Results: Ionizing radiation dramatically increased IL-32 expression in vascular endothelial cells through multiple pathways. Ionizing radiation induced IL-32 expression through nuclear factor {kappa}B activation, through induction of cPLA2 and LPC, as well as induction of Cox-2 and subsequent conversion of arachidonic acid to prostacyclin. Conversely, blocking nuclear factor {kappa}B, cPLA2, and Cox-2 activity impaired IR-induced IL-32 expression. Importantly, IL-32 significantly enhanced IR-induced expression of vascular cell adhesion molecules and leukocyte adhesion on endothelial cells. Conclusion: This study identifies IL-32 as a positive regulator in IR-induced vascular inflammation, and neutralization of IL-32 may be beneficial in protecting from IR-induced inflammation.

  9. Gamma Radiation Induced Calibration Shift for Four Cryogenic Thermometer Types

    NASA Astrophysics Data System (ADS)

    Courts, S. Scott; Yeager, C. J.

    2004-06-01

    Cryogenic temperature sensors utilized in space environments are exposed to ionizing radiation with the total dose dependent upon the length of the mission. Based upon their minimal size and robust packaging, four models of cryogenic Resistance Thermometer Devices (RTDs) manufactured by Lake Shore Cryotronics, Inc. were tested to determine their reliability for space applications with regard to radiation. Samples of Cernox™ RTDs (CX-1050-SD), ruthenium oxide RTDs (models RX-102A-AA and RX-103A-AA), and silicon diode thermometers (model DT-670-SD) were irradiated at room temperature by a cesium-137 gamma source to total doses ranging from 5 Gy to 10 kGy. This paper presents the resulting temperature shifts induced by the gamma radiation as a function of total dose over the 1.4 K to 325 K temperature range. These data show that 1) Cernox™ RTDs exhibit high radiation hardness to 10 kGy from 1.4 K to 325 K, 2) ruthenium oxide RTDs show moderate radiation hardness to 10 kGy below 10 K, and 3) silicon diodes temperature sensors exhibit some radiation tolerance to low levels of radiation (especially below 70 K), but quickly shift calibration at radiation levels above 300 Gy, especially above 100 K.

  10. Clarithromycin Attenuates Radiation-Induced Lung Injury in Mice

    PubMed Central

    Lee, Seung Jun; Yi, Chin-ok; Heo, Rok Won; Song, Dae Hyun; Cho, Yu Ji; Jeong, Yi Yeong; Kang, Ki Mun; Roh, Gu Seob; Lee, Jong Deog

    2015-01-01

    Radiation-induced lung injury (RILI) is a common and unavoidable complication of thoracic radiotherapy. The current study was conducted to evaluate the ability of clarithromycin (CLA) to prevent radiation-induced pneumonitis, oxidative stress, and lung fibrosis in an animal model. C57BL/6J mice were assigned to control, irradiation only, irradiation plus CLA, and CLA only groups. Test mice received single thoracic exposures to radiation and/or oral CLA (100 mg/kg/day). Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group. On a microscopic level, CLA inhibited macrophage influx, alveolar fibrosis, parenchymal collapse, consolidation, and epithelial cell changes. The concentration of collagen in lung tissue was lower in irradiation plus CLA mice. Radiation-induced expression of tumor necrosis factor (TNF)-α, TNF receptor 1, acetylated nuclear factor kappa B, cyclooxygenase 2, vascular cell adhesion molecule 1, and matrix metallopeptidase 9 were also attenuated by CLA. Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA. These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis. PMID:26114656

  11. Clarithromycin Attenuates Radiation-Induced Lung Injury in Mice.

    PubMed

    Lee, Seung Jun; Yi, Chin-ok; Heo, Rok Won; Song, Dae Hyun; Cho, Yu Ji; Jeong, Yi Yeong; Kang, Ki Mun; Roh, Gu Seob; Lee, Jong Deog

    2015-01-01

    Radiation-induced lung injury (RILI) is a common and unavoidable complication of thoracic radiotherapy. The current study was conducted to evaluate the ability of clarithromycin (CLA) to prevent radiation-induced pneumonitis, oxidative stress, and lung fibrosis in an animal model. C57BL/6J mice were assigned to control, irradiation only, irradiation plus CLA, and CLA only groups. Test mice received single thoracic exposures to radiation and/or oral CLA (100 mg/kg/day). Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group. On a microscopic level, CLA inhibited macrophage influx, alveolar fibrosis, parenchymal collapse, consolidation, and epithelial cell changes. The concentration of collagen in lung tissue was lower in irradiation plus CLA mice. Radiation-induced expression of tumor necrosis factor (TNF)-α, TNF receptor 1, acetylated nuclear factor kappa B, cyclooxygenase 2, vascular cell adhesion molecule 1, and matrix metallopeptidase 9 were also attenuated by CLA. Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA. These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis. PMID:26114656

  12. Radiation-induced genomic instability and its implications for radiation carcinogenesis

    NASA Technical Reports Server (NTRS)

    Huang, Lei; Snyder, Andrew R.; Morgan, William F.

    2003-01-01

    Radiation-induced genomic instability is characterized by an increased rate of genetic alterations including cytogenetic rearrangements, mutations, gene amplifications, transformation and cell death in the progeny of irradiated cells multiple generations after the initial insult. Chromosomal rearrangements are the best-characterized end point of radiation-induced genomic instability, and many of the rearrangements described are similar to those found in human cancers. Chromosome breakage syndromes are defined by chromosome instability, and individuals with these diseases are cancer prone. Consequently, chromosomal instability as a phenotype may underlie some fraction of those changes leading to cancer. Here we attempt to relate current knowledge regarding radiation-induced chromosome instability with the emerging molecular information on the chromosome breakage syndromes. The goal is to understand how genetic and epigenetic factors might influence the onset of chromosome instability and the role of chromosomal instability in carcinogenesis.

  13. Kinetics of radiation-induced segregation in ternary alloys. [LMFBR

    SciTech Connect

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

    1982-01-01

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

  14. Data acquisition system used in radiation induced electrical degradation experiments

    SciTech Connect

    White, D.P.

    1995-04-01

    Radiation induced electrical degradation (RIED) of ceramic materials has recently been reported and is the topic of much research at the present time. The object of this report is to describe the data acquisition system for an experiment designed to study RIED at the High Flux Beam Reactor (HFBR) at Brookhaven National Laboratory.

  15. SPHINX Measurements of Radiation Induced Conductivity of Foam

    SciTech Connect

    Ballard, W.P.; Beutler, D.E.; Burt, M.; Dudley, K.J.; Stringer, T.A.

    1998-12-14

    Experiments on the SPHINX accelerator studying radiation-induced conductivity (RIC) in foam indicate that a field-exclusion boundary layer model better describes foam than a Maxwell-Garnett model that treats the conducting gas bubbles in the foam as modifying the dielectric constant. In both cases, wall attachment effects could be important but were neglected.

  16. Laser therapy for severe radiation-induced rectal bleeding

    SciTech Connect

    Ahlquist, D.A.; Gostout, C.J.; Viggiano, T.R.; Pemberton, J.H.

    1986-12-01

    Four patients with chronic hematochezia and transfusion-dependent anemia from postradiation rectal vascular lesions were successfully managed by endoscopic laser coagulation. In all four patients, symptomatic, hematologic, and endoscopic improvement was evident. Laser therapy for severe radiation-induced rectal bleeding seems to be safe and efficacious and should be considered before surgical intervention.

  17. Poor outcome in radiation-induced constrictive pericarditis

    SciTech Connect

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

    1993-01-15

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

  18. SENSITIVITY TO RADIATION-INDUCED CANCER IN HEMOCHROMATOSIS

    EPA Science Inventory

    Determination of dose-response relationships for radiation-induced cancer in segments of the population with high susceptibility is critical for understanding the risks of low dose and low dose rates to humans. Clean-up levels for radionuclides will depend upon the fraction of t...

  19. Radiation-induced segregation in alloy X-750

    SciTech Connect

    Kenik, E.A.

    1996-12-31

    Microstructural and microchemical evolution of an Alloy X-750 heat under neutron irradiation was studied in order to understand the origin of irradiation-assisted stress corrosion cracking. Both clustering of point defects and radiation-induced segregation at interfaces were observed. Although no significant changes in the precipitate structure were observed, boundaries exhibited additional depletion of Cr and Fe and enrichment of Ni.

  20. Countermeasures against space radiation induced oxidative stress in mice.

    PubMed

    Kennedy, A R; Guan, J; Ware, J H

    2007-06-01

    Of particular concern for the health of astronauts during space travel is radiation from protons and high atomic number (Z), high energy particles (HZE particles). Space radiation is known to induce oxidative stress in astronauts after extended space flight. In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by proton and HZE particle radiation in the plasma of CBA mice and the protective effect of dietary supplement agents. The results indicate that exposure to proton and HZE particle radiation significantly decreased the plasma level of total antioxidants in the irradiated CBA mice. Dietary supplementation with L: -selenomethionine (SeM) or a combination of selected antioxidant agents (which included SeM) could partially or completely prevent the decrease in the total antioxidant status in the plasma of animals exposed to proton or HZE particle radiation. These findings suggest that exposure to space radiation may compromise the capacity of the host antioxidant defense system; this adverse biological effect can be prevented at least partially by dietary supplementation with agents expected to have effects on antioxidant activities. PMID:17387501

  1. Radiation-induced dural fibrosarcoma with unusually short latent period

    SciTech Connect

    Ghatak, N.R.; Aydin, F.; Leshner, R.T. Tulane Univ., New Orleans, LA )

    1993-05-01

    Although rare, the occurrence of radiation-induced intracranial neoplasms of various types is well known. Among these tumors, fibrosarcomas, especially in the region of seila turcica, seem to be the most common type. These tumors characteristically occur after a long latent period, usually several years, following radiation therapy. The authors now report a case of apparently radiation-induced fibrosarcoma with some unusual features in a 10-year-old boy who was treated with radiation for medulloblastoma. He received a total dose of 53.2 Gy radiation delivered at 1.8 per fraction with 6 MV acceleration using the standard craniospinal technique. An MRI at 15 months after the completion of radiotherapy showed a mass over the cerebral convexity, which increased two-fold in size within a period of 4 months. A well circumscribed tumor was removed from the fronto-parietal convexity. The tumor measured 5x4.5x1.5 cm and was attached to the dura with invasion of the overlying bone. Histologically, it displayed the characteristic features of a low-grade fibrosarcoma. The patient remains free of tumor 18 months after the surgery. This case emphasizes the potential risk for the development of a second neoplasm following therapeutic radiation and also documents, to the authors' knowledge, the shortest latent period reported so far between administration of radiotherapy and development of an intracranial tumor.

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

    PubMed Central

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  3. Countermeasures for space radiation induced adverse biologic effects

    NASA Astrophysics Data System (ADS)

    Kennedy, A. R.; Wan, X. S.

    2011-11-01

    Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

  4. Radiation-induced decomposition of explosives under extreme conditions

    SciTech Connect

    Giefers, Hubertus; Pravica, Michael; Yang, Wenge; Liermann, Peter

    2008-11-03

    We present high-pressure and high temperature studies of the synchrotron radiation-induced decomposition of powder secondary high explosives pentaerythritol tetranitrate (PETN) and 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) using white beam synchrotron radiation at the 16 BM-B and 16 BM-D sectors of the HP-CAT beamline at the Advanced Photon Source. The radiation-induced decomposition rate TATB showed dramatic slowing with pressure up to 26.6 GPa (the highest pressure studied), implying a positive activation volume of the activated complex. The decomposition rate of PETN varied little with pressure up to 15.7 GPa (the highest pressure studied). Diffraction line intensities were measured as a function of time using energy-dispersive methods. By measuring the decomposition rate as a function of pressure and temperature, kinetic and other constants associated with the decomposition reactions were extracted.

  5. Radiation-induced mutagenicity and lethality in Salmonella typhimurium

    SciTech Connect

    Isildar, M.; Bakale, G.

    1983-01-01

    The mutagenic and lethal effects of ionizing radiation on histidine-deficient auxotrophs of Salmonella typhimurium were studied to improve the understanding of radiation damage to DNA. The auxotrophs were divided into two groups - one which is sensitive to base-pair substitutions and another sensitive to frameshifts. These groups were composed of parent-daughter pairs in which the chemical mutagenicity enhancing plasmid, pKM101, is absent in the parent strain and present in the daughter. Co-60 ..gamma..-radiation and 250 kV x-rays were used to irradiate the bacteria. Irradiation of the frameshift - sensitive strains which carry the pKm101 plasmid doubled the absolute number of induced revertants whereas irradiation of the base-pair substitution sensitive strain which also carries the pKm101 plasmid produced nearly no change in the number of induced revertants. A nearly negligible effect on the mutation rate was observed for all parent strains. (ACR)

  6. Mechanisms of radiation-induced gene responses

    SciTech Connect

    Woloschak, G.E.; Paunesku, T.

    1996-10-01

    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.

  7. The influence of infrared radiation on short-term ultraviolet-radiation-induced injuries

    SciTech Connect

    Kaidbey, K.H.; Witkowski, T.A.; Kligman, A.M.

    1982-05-01

    Because heat has been reported to influence adversely short- and long-term ultraviolet (UV)-radiation-induced skin damage in animals, we investigated the short-term effects of infrared radiation on sunburn and on phototoxic reactions to topical methoxsalen and anthracene in human volunteers. Prior heating of the skin caused suppression of the phototoxic response to methoxsalen as evidenced by an increase in the threshold erythema dose. Heat administered either before or after exposure to UV radiation had no detectable influence on sunburn erythema or on phototoxic reactions provoked by anthracene.

  8. Torin2 Suppresses Ionizing Radiation-Induced DNA Damage Repair.

    PubMed

    Udayakumar, Durga; Pandita, Raj K; Horikoshi, Nobuo; Liu, Yan; Liu, Qingsong; Wong, Kwok-Kin; Hunt, Clayton R; Gray, Nathanael S; Minna, John D; Pandita, Tej K; Westover, Kenneth D

    2016-05-01

    Several classes of inhibitors of the mammalian target of rapamycin (mTOR) have been developed based on its central role in sensing growth factor and nutrient levels to regulate cellular metabolism. However, its ATP-binding site closely resembles other phosphatidylinositol 3-kinase-related kinase (PIKK) family members, resulting in reactivity with these targets that may also be therapeutically useful. The ATP-competitive mTOR inhibitor, Torin2, shows biochemical activity against the DNA repair-associated proteins ATM, ATR and DNA-PK, which raises the possibility that Torin2 and related compounds might radiosensitize cancerous tumors. In this study Torin2 was also found to enhance ionizing radiation-induced cell killing in conditions where ATM was dispensable, confirming the requirement for multiple PIKK targets. Moreover, Torin2 did not influence the initial appearance of γ-H2AX foci after irradiation but significantly delayed the disappearance of radiation-induced γ-H2AX foci, indicating a DNA repair defect. Torin2 increased the number of radiation-induced S-phase specific chromosome aberrations and reduced the frequency of radiation-induced CtIP and Rad51 foci formation, suggesting that Torin2 works by blocking homologous recombination (HR)-mediated DNA repair resulting in an S-phase specific DNA repair defect. Accordingly, Torin2 reduced HR-mediated repair of I-Sce1-induced DNA damage and contributed to replication fork stalling. We conclude that radiosensitization of tumor cells by Torin2 is associated with disrupting ATR- and ATM-dependent DNA damage responses. Our findings support the concept of developing combination cancer therapies that incorporate ionizing radiation therapy and Torin2 or compounds with similar properties. PMID:27135971

  9. Factors that modify risks of radiation-induced cancer

    SciTech Connect

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors).

  10. Radiation-induced DNA damage and chromatin structure

    NASA Technical Reports Server (NTRS)

    Rydberg, B.; Chatterjee, A. (Principal Investigator)

    2001-01-01

    DNA lesions induced by ionizing radiation in cells are clustered and not randomly distributed. For low linear energy transfer (LET) radiation this clustering occurs mainly on the small scales of DNA molecules and nucleosomes. For example, experimental evidence suggests that both strands of DNA on the nucleosomal surface can be damaged in single events and that this damage occurs with a 10-bp modulation because of protection by histones. For high LET radiation, clustering also occurs on a larger scale and depends on chromatin organization. A particularly significant clustering occurs when an ionizing particle traverses the 30 nm chromatin fiber with generation of heavily damaged DNA regions with an average size of about 2 kbp. On an even larger scale, high LET radiation can produce several DNA double-strand breaks in closer proximity than expected from randomness. It is suggested that this increases the probability of misrejoining of DNA ends and generation of lethal chromosome aberrations.

  11. Pulsed radiation-induced attenuation in certain optical fibers

    SciTech Connect

    Weiss, J.D. )

    1992-05-01

    Using the X-ray pulse from the HERMES II simulation machine at Sandia National Laboratories, the pulsed radiation-induced attenuation was measured in two optical fibers considered to be 'nonrad-hard': the 50-micron-core, graded-index fiber from Corning and the plastic (PMMA) fiber from the Mitsubishi Rayon Company. These fibers were exposed to radiation up to doses of 19.5 and 28 krad(Si), respectively. In addition, fits of their post-radiation recovery were made to the geminate recombination model, from which the recombination-rate and generation constants, characteristic of this theory, were determined. These parameters should be useful in determining the response of the fibers to radiation conditions other than those encountered here. 18 refs.

  12. Ionizing radiation-induced mutagenesis: radiation studies in Neurospora predictive for results in mammalian cells

    NASA Technical Reports Server (NTRS)

    Evans, H. H.; DeMarini, D. M.

    1999-01-01

    Ionizing radiation was the first mutagen discovered and was used to develop the first mutagenicity assay. In the ensuing 70+ years, ionizing radiation became a fundamental tool in understanding mutagenesis and is still a subject of intensive research. Frederick de Serres et al. developed and used the Neurospora crassa ad-3 system initially to explore the mutagenic effects of ionizing radiation. Using this system, de Serres et al. demonstrated the dependence of the frequency and spectra of mutations induced by ionizing radiation on the dose, dose rate, radiation quality, repair capabilities of the cells, and the target gene employed. This work in Neurospora predicted the subsequent observations of the mutagenic effects of ionizing radiation in mammalian cells. Modeled originally on the mouse specific-locus system developed by William L. Russell, the N. crassa ad-3 system developed by de Serres has itself served as a model for interpreting the results in subsequent systems in mammalian cells. This review describes the primary findings on the nature of ionizing radiation-induced mutagenesis in the N. crassa ad-3 system and the parallel observations made years later in mammalian cells.

  13. Radiation-Induced Notch Signaling in Breast Cancer Stem Cells

    SciTech Connect

    Lagadec, Chann; Vlashi, Erina; Alhiyari, Yazeed; Phillips, Tiffany M.; Bochkur Dratver, Milana; Pajonk, Frank

    2013-11-01

    Purpose: To explore patterns of Notch receptor and ligand expression in response to radiation that could be crucial in defining optimal dosing schemes for γ-secretase inhibitors if combined with radiation. Methods and Materials: Using MCF-7 and T47D breast cancer cell lines, we used real-time reverse transcription–polymerase chain reaction to study the Notch pathway in response to radiation. Results: We show that Notch receptor and ligand expression during the first 48 hours after irradiation followed a complex radiation dose–dependent pattern and was most pronounced in mammospheres, enriched for breast cancer stem cells. Additionally, radiation activated the Notch pathway. Treatment with a γ-secretase inhibitor prevented radiation-induced Notch family gene expression and led to a significant reduction in the size of the breast cancer stem cell pool. Conclusions: Our results indicate that, if combined with radiation, γ-secretase inhibitors may prevent up-regulation of Notch receptor and ligand family members and thus reduce the number of surviving breast cancer stem cells.

  14. Aging masks detection of radiation-induced brain injury

    PubMed Central

    Shi, Lei; Olson, John; D’Agostino, Ralph; Linville, Constance; Nicolle, Michelle M.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2011-01-01

    Fractionated partial or whole-brain irradiation (fWBI) is a widely used, effective treatment for primary and metastatic brain tumors, but it also produces radiation-induced brain injury, including cognitive impairment. Radiation-induced neural changes are particularly problematic for elderly brain tumor survivors who also experience age-dependent cognitive impairment. Accordingly, we investigated, i] radiation-induced cognitive impairment, and ii] potential biomarkers of radiation-induced brain injury in a rat model of aging. Fischer 344 × Brown Norway rats received fractionated whole-brain irradiation (fWBI rats, 40 Gy, 8 fractions over 4 wk) or sham-irradiation (Sham-IR rats) at 12 months of age; all analyses were performed at 26–30 months of age. Spatial learning and memory were measured using the Morris water maze (MWM), hippocampal metabolites were measured using proton magnetic resonance spectroscopy (1H MRS), and hippocampal glutamate receptor subunits were evaluated using Western blots. Young rats (7–10 month-old) were included to control for age effects. The results revealed that both Sham-IR and fWBI rats exhibited age-dependent impairments in MWM performance; fWBI induced additional impairments in the reversal MWM. 1H MRS revealed age-dependent decreases in neuronal markers, increases in glial markers, but no detectable fWBI-dependent changes. Western blot analysis revealed age-dependent, but not fWBI-dependent, glutamate subunit declines. Although previous studies demonstrated fWBI-induced changes in cognition, glutamate subunits, and brain metabolites in younger rats, age-dependent changes in these parameters appear to mask their detection in old rats, a phenomenon also likely to occur in elderly fWBI patients >70 years of age. PMID:21338580

  15. Chromosome aberrations induced by high-LET radiations

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

  16. Radiation-induced optic neuropathy: A magnetic resonance imaging study

    SciTech Connect

    Guy, J.; Mancuso, A.; Beck, R.; Moster, M.L.; Sedwick, L.A.; Quisling, R.G.; Rhoton, A.L. Jr.; Protzko, E.E.; Schiffman, J. )

    1991-03-01

    Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain.

  17. Radiation induced corrosion of copper for spent nuclear fuel storage

    NASA Astrophysics Data System (ADS)

    Björkbacka, Åsa; Hosseinpour, Saman; Johnson, Magnus; Leygraf, Christofer; Jonsson, Mats

    2013-11-01

    The long term safety of repositories for radioactive waste is one of the main concerns for countries utilizing nuclear power. The integrity of engineered and natural barriers in such repositories must be carefully evaluated in order to minimize the release of radionuclides to the biosphere. One of the most developed concepts of long term storage of spent nuclear fuel is the Swedish KBS-3 method. According to this method, the spent fuel will be sealed inside copper canisters surrounded by bentonite clay and placed 500 m down in stable bedrock. Despite the importance of the process of radiation induced corrosion of copper, relatively few studies have been reported. In this work the effect of the total gamma dose on radiation induced corrosion of copper in anoxic pure water has been studied experimentally. Copper samples submerged in water were exposed to a series of total doses using three different dose rates. Unirradiated samples were used as reference samples throughout. The copper surfaces were examined qualitatively using IRAS and XPS and quantitatively using cathodic reduction. The concentration of copper in solution after irradiation was measured using ICP-AES. The influence of aqueous radiation chemistry on the corrosion process was evaluated based on numerical simulations. The experiments show that the dissolution as well as the oxide layer thickness increase upon radiation. Interestingly, the evaluation using numerical simulations indicates that aqueous radiation chemistry is not the only process driving the corrosion of copper in these systems.

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

    SciTech Connect

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

    1991-03-01

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

  19. Nature of radiation-induced defects in quartz

    NASA Astrophysics Data System (ADS)

    Wang, Bu; Yu, Yingtian; Pignatelli, Isabella; Sant, Gaurav; Bauchy, Mathieu

    2015-07-01

    Although quartz (α-form) is a mineral used in numerous applications wherein radiation exposure is an issue, the nature of the atomistic defects formed during radiation-induced damage has not been fully clarified. Especially, the extent of oxygen vacancy formation is still debated, which is an issue of primary importance as optical techniques based on charged oxygen vacancies have been utilized to assess the level of radiation damage in quartz. In this paper, molecular dynamics simulations are applied to study the effects of ballistic impacts on the atomic network of quartz. We show that the defects that are formed mainly consist of over-coordinated Si and O, as well as Si-O connectivity defects, e.g., small Si-O rings and edge-sharing Si tetrahedra. Oxygen vacancies, on the contrary, are found in relatively low abundance, suggesting that characterizations based on E' centers do not adequately capture radiation-induced structural damage in quartz. Finally, we evaluate the dependence on the incident energy, of the amount of each type of the point defects formed, and quantify unambiguously the threshold displacement energies for both O and Si atoms. These results provide a comprehensive basis to assess the nature and extent of radiation damage in quartz.

  20. Nature of radiation-induced defects in quartz

    SciTech Connect

    Wang, Bu; Yu, Yingtian; Bauchy, Mathieu; Pignatelli, Isabella; Sant, Gaurav

    2015-07-14

    Although quartz (α-form) is a mineral used in numerous applications wherein radiation exposure is an issue, the nature of the atomistic defects formed during radiation-induced damage has not been fully clarified. Especially, the extent of oxygen vacancy formation is still debated, which is an issue of primary importance as optical techniques based on charged oxygen vacancies have been utilized to assess the level of radiation damage in quartz. In this paper, molecular dynamics simulations are applied to study the effects of ballistic impacts on the atomic network of quartz. We show that the defects that are formed mainly consist of over-coordinated Si and O, as well as Si–O connectivity defects, e.g., small Si–O rings and edge-sharing Si tetrahedra. Oxygen vacancies, on the contrary, are found in relatively low abundance, suggesting that characterizations based on E′ centers do not adequately capture radiation-induced structural damage in quartz. Finally, we evaluate the dependence on the incident energy, of the amount of each type of the point defects formed, and quantify unambiguously the threshold displacement energies for both O and Si atoms. These results provide a comprehensive basis to assess the nature and extent of radiation damage in quartz.

  1. Intercellular Adhesion Molecule 1 Knockout Abrogates Radiation Induced Pulmonary Inflammation

    NASA Astrophysics Data System (ADS)

    Hallahan, Dennis E.; Virudachalam, Subbulakshmi

    1997-06-01

    Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is induced by exposure to ionizing radiation. The lung was used as a model to study the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like response. ICAM-1 expression increased in the pulmonary microvascular endothelium and not in the endothelium of larger pulmonary vessels following treatment of mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression, we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody labeling of pulmonary microvascular endothelial cells from human cadaver donors (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify the fluorescence intensity of ICAM in the irradiated lung. These studies showed a dose- and time-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium. Peak expression occurred at 24 h, while threshold dose was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was administered by tail vein injection to mice following thoracic irradiation. Inflammatory cells were quantified by immunofluorescence for leukocyte common antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed attenuation of inflammatory cell infiltration into the lung in response to ionizing radiation exposure. To verify the requirement of ICAM-1 in the inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM-1 was not expressed in the lungs of ICAM-1-deficient mice following treatment with thoracic irradiation. ICAM-1 knockout mice had no increase in the inflammatory cell infiltration into the lung in response to thoracic irradiation. These studies demonstrate a radiation dose-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium, and show that ICAM-1 is required for inflammatory cell infiltration

  2. Intercellular adhesion molecule 1 knockout abrogates radiation induced pulmonary inflammation.

    PubMed

    Hallahan, D E; Virudachalam, S

    1997-06-10

    Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is induced by exposure to ionizing radiation. The lung was used as a model to study the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like response. ICAM-1 expression increased in the pulmonary microvascular endothelium and not in the endothelium of larger pulmonary vessels following treatment of mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression, we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody labeling of pulmonary microvascular endothelial cells from human cadaver donors (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify the fluorescence intensity of ICAM in the irradiated lung. These studies showed a dose- and time-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium. Peak expression occurred at 24 h, while threshold dose was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was administered by tail vein injection to mice following thoracic irradiation. Inflammatory cells were quantified by immunofluorescence for leukocyte common antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed attenuation of inflammatory cell infiltration into the lung in response to ionizing radiation exposure. To verify the requirement of ICAM-1 in the inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM-1 was not expressed in the lungs of ICAM-1-deficient mice following treatment with thoracic irradiation. ICAM-1 knockout mice had no increase in the inflammatory cell infiltration into the lung in response to thoracic irradiation. These studies demonstrate a radiation dose-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium, and show that ICAM-1 is required for inflammatory cell infiltration

  3. Induced movements of giant vesicles by millimeter wave radiation.

    PubMed

    Albini, Martina; Dinarelli, Simone; Pennella, Francesco; Romeo, Stefania; Zampetti, Emiliano; Girasole, Marco; Morbiducci, Umberto; Massa, Rita; Ramundo-Orlando, Alfonsina

    2014-07-01

    Our previous study of interaction between low intensity radiation at 53.37GHz and cell-size system - such as giant vesicles - indicated that a vectorial movement of vesicles was induced. This effect among others, i.e. elongation, induced diffusion of fluorescent dye di-8-ANEPPS, and increased attractions between vesicles was attributed to the action of the field on charged and dipolar residues located at the membrane-water interface. In an attempt to improve the understanding on how millimeter wave radiation (MMW) can induce this movement we report here a real time evaluation of changes induced on the movement of giant vesicles. Direct optical observations of vesicles subjected to irradiation enabled the monitoring in real time of the response of vesicles. Changes of the direction of vesicle movement are demonstrated, which occur only during irradiation with a "switch on" of the effect. This MMW-induced effect was observed at a larger extent on giant vesicles prepared with negatively charged phospholipids. The monitoring of induced-by-irradiation temperature variation and numerical dosimetry indicate that the observed effects in vesicle movement cannot be attributed to local heating. PMID:24704354

  4. Challenges and Opportunities in Radiation-induced Hemorrhagic Cystitis

    PubMed Central

    Zwaans, Bernadette M.M.; Nicolai, Heinz G.; Chancellor, Michael B.; Lamb, Laura E.

    2016-01-01

    As diagnosis and treatment of cancer is improving, medical and social issues related to cancer survivorship are becoming more prevalent. Hemorrhagic cystitis (HC), a rare but serious disease that may affect patients after pelvic radiation or systemic chemotherapy, has significant unmet medical needs. Although no definitive treatment is currently available, various interventions are employed for HC. Effects of nonsurgical treatments for HC are of modest success and studies aiming to control radiation-induced bladder symptoms are lacking. In this review, we present current and advanced therapeutic strategies for HC to help cancer survivors deal with long-term urologic health issues. PMID:27601964

  5. Proton induced radiation damage in fast crystal scintillators

    NASA Astrophysics Data System (ADS)

    Yang, Fan; Zhang, Liyuan; Zhu, Ren-Yuan; Kapustinsky, Jon; Nelson, Ron; Wang, Zhehui

    2016-07-01

    This paper reports proton induced radiation damage in fast crystal scintillators. A 20 cm long LYSO crystal, a 15 cm long CeF3 crystal and four liquid scintillator based sealed quartz capillaries were irradiated by 800 MeV protons at Los Alamos up to 3.3 ×1014 p /cm2. Four 1.5 mm thick LYSO plates were irradiated by 24 GeV protons at CERN up to 6.9 ×1015 p /cm2. The results show an excellent radiation hardness of LYSO crystals against charged hadrons.

  6. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    SciTech Connect

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R.

    2014-03-15

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.

  7. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    PubMed Central

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R.

    2014-01-01

    Purpose/Objectives(s) The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events (SPEs), as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials Ferrets were exposed to 0 – 2 Gray (Gy) of whole body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results The lethal dose of radiation to 50% of the population, known as the LD50, of ferrets was established at ~ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 post-irradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early times post-irradiation when coagulopathies were present and progressively becoming more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions The data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is solely due to the cell killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation induced death at relatively low doses in large mammals. PMID:24495588

  8. The radiation-induced changes in rectal mucosa: Hyperfractionated vs. hypofractionated preoperative radiation for rectal cancer

    SciTech Connect

    Starzewski, Jacek J.; Pajak, Jacek T.; Pawelczyk, Iwona; Lange, Dariusz; Golka, Dariusz . E-mail: dargolka@wp.pl; Brzeziska, Monika; Lorenc, Zbigniew

    2006-03-01

    Purpose: The purpose of the study was the qualitative and quantitative evaluation of acute radiation-induced rectal changes in patients who underwent preoperative radiotherapy according to two different irradiation protocols. Patients and Methods: Sixty-eight patients with rectal adenocarcinoma underwent preoperative radiotherapy; 44 and 24 patients underwent hyperfractionated and hypofractionated protocol, respectively. Fifteen patients treated with surgery alone served as a control group. Five basic histopathologic features (meganucleosis, inflammatory infiltrations, eosinophils, mucus secretion, and erosions) and two additional features (mitotic figures and architectural glandular abnormalities) of radiation-induced changes were qualified and quantified. Results: Acute radiation-induced reactions were found in 66 patients. The most common were eosinophilic and plasma-cell inflammatory infiltrations (65 patients), erosions, and decreased mucus secretion (54 patients). Meganucleosis and mitotic figures were more common in patients who underwent hyperfractionated radiotherapy. The least common were the glandular architectural distortions, especially in patients treated with hypofractionated radiotherapy. Statistically significant differences in morphologic parameters studied between groups treated with different irradiation protocols were found. Conclusion: The system of assessment is a valuable tool in the evaluation of radiation-induced changes in the rectal mucosa. A greater intensity of regenerative changes was found in patients treated with hyperfractionated radiotherapy.

  9. Cosmic-ray induced radiation in low-orbit space objects

    SciTech Connect

    Sandmeier, H.A.

    1980-09-01

    The induced radiation whole body dose received by astronauts in earth orbit is calculated. The induced radiation results from the interaction of primary cosmic rays with the mass of the satellite or space station. (ACR)

  10. Oxidative Stress Mediates Radiation Lung Injury by Inducing Apoptosis

    SciTech Connect

    Zhang Yu; Zhang Xiuwu; Rabbani, Zahid N.; Jackson, Isabel L.; Vujaskovic, Zeljko

    2012-06-01

    Purpose: Apoptosis in irradiated normal lung tissue has been observed several weeks after radiation. However, the signaling pathway propagating cell death after radiation remains unknown. Methods and Materials: C57BL/6J mice were irradiated with 15 Gy to the whole thorax. Pro-apoptotic signaling was evaluated 6 weeks after radiation with or without administration of AEOL10150, a potent catalytic scavenger of reactive oxygen and nitrogen species. Results: Apoptosis was observed primarily in type I and type II pneumocytes and endothelium. Apoptosis correlated with increased PTEN expression, inhibition of downstream PI3K/AKT signaling, and increased p53 and Bax protein levels. Transforming growth factor-{beta}1, Nox4, and oxidative stress were also increased 6 weeks after radiation. Therapeutic administration of AEOL10150 suppressed pro-apoptotic signaling and dramatically reduced the number of apoptotic cells. Conclusion: Increased PTEN signaling after radiation results in apoptosis of lung parenchymal cells. We hypothesize that upregulation of PTEN is influenced by Nox4-derived oxidative stress. To our knowledge, this is the first study to highlight the role of PTEN in radiation-induced pulmonary toxicity.

  11. Opportunities for nutritional amelioration of radiation-induced cellular damage.

    PubMed

    Turner, Nancy D; Braby, Leslie A; Ford, John; Lupton, Joanne R

    2002-10-01

    The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations. PMID:12361786

  12. Opportunities for nutritional amelioration of radiation-induced cellular damage

    NASA Technical Reports Server (NTRS)

    Turner, Nancy D.; Braby, Leslie A.; Ford, John; Lupton, Joanne R.

    2002-01-01

    The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations.

  13. Using Imaging Methods to Interrogate Radiation-Induced Cell Signaling

    SciTech Connect

    Shankaran, Harish; Weber, Thomas J.; Freiin von Neubeck, Claere H.; Sowa, Marianne B.

    2012-04-01

    There is increasing emphasis on the use of systems biology approaches to define radiation induced responses in cells and tissues. Such approaches frequently rely on global screening using various high throughput 'omics' platforms. Although these methods are ideal for obtaining an unbiased overview of cellular responses, they often cannot reflect the inherent heterogeneity of the system or provide detailed spatial information. Additionally, performing such studies with multiple sampling time points can be prohibitively expensive. Imaging provides a complementary method with high spatial and temporal resolution capable of following the dynamics of signaling processes. In this review, we utilize specific examples to illustrate how imaging approaches have furthered our understanding of radiation induced cellular signaling. Particular emphasis is placed on protein co-localization, and oscillatory and transient signaling dynamics.

  14. Radiation-induced hemorrhagic duodenitis associated with sorafenib treatment.

    PubMed

    Yanai, Shunichi; Nakamura, Shotaro; Ooho, Aritsune; Nakamura, Shigeo; Esaki, Motohiro; Azuma, Koichi; Kitazono, Takanari; Matsumoto, Takayuki

    2015-06-01

    Sorafenib, an oral inhibitor of multiple tyrosine kinase receptors, has been widely used as a standard medical treatment for advanced hepatocellular carcinoma (HCC). Here, we report a 66-year-old male patient who developed gastrointestinal bleeding due to radiation-induced hemorrhagic duodenitis associated with sorafenib treatment. We started oral administration of sorafenib because of the recurrence of HCC with lung metastases. The patient had been treated by radiotherapy for para-aortic lymph node metastases from HCC 4 months before the bleeding. Esophagogastroduodenoscopy (EGD) revealed edematous reddish mucosa with friability and telangiectasia in the second portion of the duodenum. Computed tomography and capsule endoscopy revealed that the hemorrhagic lesions were located in the distal duodenum. After discontinuation of sorafenib, the bleeding disappeared and a follow-up EGD confirmed improvement of duodenitis. Based on these findings, the diagnosis of radiation-induced hemorrhagic duodenitis associated with sorafenib was made. PMID:25832768

  15. [Radiation-induced and therapy-related AML/MDS].

    PubMed

    Inaba, Toshiya

    2009-10-01

    Radiation induced acute myeloid leukemia (AML) was recognized a century ago, soon after mankind found radiation. Atomic bomb survivors developed de novo AML with relatively short latency with very high frequency. By contrast, excess occurrence of myelodysplastic syndrome (MDS) as well as solid tumors was found decades late. This difference may be due to etiology that many de novo AML patients harbor chimeric leukemogenic genes caused by chromosomal translocations, while MDS patients rarely carry chimeras. In addition, epigenetic change would play important roles. Therapy related leukemia is mainly caused by topoisomerase II inhibitors that cause de novo AML with an 11q23 translocation or by alkyrating agents that induce MDS/AML with an AML1 point mutation and monosomy 7. PMID:19860183

  16. Probabilistic methodology for estimating radiation-induced cancer risk

    SciTech Connect

    Dunning, D.E. Jr.; Leggett, R.W.; Williams, L.R.

    1981-01-01

    The RICRAC computer code was developed at Oak Ridge National Laboratory to provide a versatile and convenient methodology for radiation risk assessment. The code allows as input essentially any dose pattern commonly encountered in risk assessments for either acute or chronic exposures, and it includes consideration of the age structure of the exposed population. Results produced by the analysis include the probability of one or more radiation-induced cancer deaths in a specified population, expected numbers of deaths, and expected years of life lost as a result of premature fatalities. These calculatons include consideration of competing risks of death from all other causes. The program also generates a probability frequency distribution of the expected number of cancers in any specified cohort resulting from a given radiation dose. The methods may be applied to any specified population and dose scenario.

  17. Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis

    PubMed Central

    Shim, Grace; Ricoul, Michelle; Hempel, William M.; Azzam, Edouard I.; Sabatier, Laure

    2014-01-01

    It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiation-induced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low- and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis. PMID:24486376

  18. Radiation-induced decomposition of PETN and TATB under pressure

    SciTech Connect

    Giefers, Hubertus; Pravica, Michael; Liermann, Hanns-Peter; Yang, Wenge

    2008-10-02

    We have investigated decomposition of PETN and TATB induced by white synchrotron X-ray radiation in a diamond anvil cell at ambient temperature and two pressures, nearly ambient and about 6 GPa. The decomposition rate of TATB decreases significantly when it is pressurized to 5.9 GPa. The measurements were highly reproducible and allowed us to obtain decomposition rates and the order parameters of the reactions.

  19. Interlaboratory comparison of radiation-induced attenuation in optical fibers

    SciTech Connect

    Friebele, E.J.; Lyons, P.B.; Blackburn, J.C.; Henschel, H.; Johan, A.; Krinsky, J.A.; Robinson, A.; Schneider, W.; Smith, D.; Taylor, E.W.; Los Alamos National Lab., NM; Harry Diamond Labs., Adelphi, MD; Fraunhofer-Institut fuer Naturwissenschaftlich-Technische Trendanalysen , Euskirchen; Direction des Recherches, Etudes et Techni

    1989-08-01

    A comparison of the losses induced in step index multimode, graded index multimode and single mode fibers by pulsed radiation exposure has been made among 12 laboratories over a period of 5 years. The recoveries of the incremental attenuations from 10{sup -9} to 10{sup 1} s are reported. Although a standard set of measurement parameters was attempted, differences between the laboratories are evident; possible origins for these are discussed. 18 refs., 18 figs., 7 tabs.

  20. Sulfonic acid catalysts prepared by radiation-induced graft polymerization

    SciTech Connect

    Mizota, Tomotoshi; Tsuneda, Satoshi; Saito, Kyoichi, Saito

    1994-09-01

    In this study, the authors prepared two variations of graft-type acid catalysts with different adjacent groups by radiation-induced graft polymerization (RIGP), and compared the hydrolytic activity of the resultant acid catalysts for methyl acetate with that of commercially available SO{sub 3}H-type ion-exchange beads with different degrees of cross-linking. 8 refs., 3 figs.

  1. Radiation-Induced Alterations in Mitochondria of the Rat Heart

    PubMed Central

    Sridharan, Vijayalakshmi; Aykin-Burns, Nukhet; Tripathi, Preeti; Krager, Kimberly J.; Sharma, Sunil K.; Moros, Eduardo G.; Corry, Peter M.; Nowak, Grazyna; Hauer-Jensen, Martin; Boerma, Marjan

    2014-01-01

    Radiation therapy for the treatment of thoracic cancers may be associated with radiation-induced heart disease (RIHD), especially in long-term cancer survivors. Mechanisms by which radiation causes heart disease are largely unknown. To identify potential long-term contributions of mitochondria in the development of radiation-induced heart disease, we examined the time course of effects of irradiation on cardiac mitochondria. In this study, Sprague-Dawley male rats received image-guided local X irradiation of the heart with a single dose ranging from 3–21 Gy. Two weeks after irradiation, left ventricular mitochondria were isolated to assess the dose-dependency of the mitochondrial permeability transition pore (mPTP) opening in a mitochondrial swelling assay. At time points from 6 h to 9 months after a cardiac dose of 21 Gy, the following analyses were performed: left ventricular Bax and Bcl-2 protein levels; apoptosis; mitochondrial inner membrane potential and mPTP opening; mitochondrial mass and expression of mitophagy mediators Parkin and PTEN induced putative kinase-1 (PINK-1); mitochondrial respiration and protein levels of succinate dehydrogenase A (SDHA); and the 70 kDa subunit of complex II. Local heart irradiation caused a prolonged increase in Bax/Bcl-2 ratio and induced apoptosis between 6 h and 2 weeks. The mitochondrial membrane potential was reduced until 2 weeks, and the calcium-induced mPTP opening was increased from 6 h up to 9 months. An increased mitochondrial mass together with unaltered levels of Parkin suggested that mitophagy did not occur. Lastly, we detected a significant decrease in succinate-driven state 2 respiration in isolated mitochondria from 2 weeks up to 9 months after irradiation, coinciding with reduced mitochondrial levels of succinate dehydrogenase A. Our results suggest that local heart irradiation induces long-term changes in cardiac mitochondrial membrane functions, levels of SDH and state 2 respiration. At any time after

  2. UV radiation induces CXCL5 expression in human skin.

    PubMed

    Reichert, Olga; Kolbe, Ludger; Terstegen, Lara; Staeb, Franz; Wenck, Horst; Schmelz, Martin; Genth, Harald; Kaever, Volkhard; Roggenkamp, Dennis; Neufang, Gitta

    2015-04-01

    CXCL5 has recently been identified as a mediator of UVB-induced pain in rodents. To compare and to extend previous knowledge of cutaneous CXCL5 regulation, we performed a comprehensive study on the effects of UV radiation on CXCL5 regulation in human skin. Our results show a dose-dependent increase in CXCL5 protein in human skin after UV radiation. CXCL5 can be released by different cell types in the skin. We presumed that, in addition to immune cells, non-immune skin cells also contribute to UV-induced increase in CXCL5 protein. Analysis of monocultured dermal fibroblasts and keratinocytes revealed that only fibroblasts but not keratinocytes displayed up regulated CXCL5 levels after UV stimulation. Whereas UV treatment of human skin equivalents, induced epidermal CXCL5 mRNA and protein expression. Up regulation of epidermal CXCL5 was independent of keratinocyte differentiation and keratinocyte-keratinocyte interactions in epidermal layers. Our findings provide first evidence on the release of CXCL5 in UV-radiated human skin and the essential role of fibroblast-keratinocyte interaction in the regulation of epidermal CXCL5. PMID:25690483

  3. [The issue of low doses in radiation therapy and impact on radiation-induced secondary malignancies].

    PubMed

    Chargari, Cyrus; Cosset, Jean-Marc

    2013-12-01

    Several studies have well documented that the risk of secondary neoplasms is increasing among patients having received radiation therapy as part of their primary anticancer treatment. Most frequently, radiation-induced neoplasms occur in volume exposed to high doses. However, the impact of "low" doses (<5 Gy) in radiation-induced carcinogenesis should be clinically considered because modern techniques of intensity-modulated radiation therapy (IMRT) or stereotactic irradiation significantly increase tissue volumes receiving low doses. The risk inherent to these technologies remains uncertain and estimates closely depend on the chosen risk model. According to the (debated) linear no-threshold model, the risk of secondary neoplasms could be twice higher with IMRT, as compared to conformal radiation therapy. It seems that only proton therapy could decrease both high and low doses delivered to non-target volumes. Except for pediatric tumors, for which the unequivocal risk of second malignancies (much higher than in adults) should be taken into account, epidemiological data suggest that the risk of secondary cancer related to low doses could be very low, even negligible in some cases. However, clinical follow-up remains insufficient and a marginal increase in secondary tumors could counterbalance the benefit of a highly sophisticated irradiation technique. It therefore remains necessary to integrate the potential risk of new irradiation modalities in a risk-adapted strategy taking into account therapeutic objectives but also associated risk factors, such as age (essentially), chemotherapy, or life style. PMID:24257106

  4. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    NASA Astrophysics Data System (ADS)

    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

  5. Ionizing Radiation-Induced Cataract in Interventional Cardiology Staff

    PubMed Central

    Bitarafan Rajabi, Ahmad; Noohi, Feridoun; Hashemi, Hassan; Haghjoo, Majid; Miraftab, Mohammad; Yaghoobi, Nahid; Rastgou, Fereydon; Malek, Hadi; Faghihi, Hoshang; Firouzabadi, Hassan; Asgari, Soheila; Rezvan, Farhad; Khosravi, Hamidreza; Soroush, Sara; Khabazkhoob, Mehdi

    2015-01-01

    Background: The use of ionizing radiation has led to advances in medical diagnosis and treatment. Objectives: The purpose of this study was to determine the risk of radiation cataractogenesis in the interventionists and staff performing various procedures in different interventional laboratories. Patients and Methods: This cohort study included 81 interventional cardiology staff. According to the working site, they were classified into 5 groups. The control group comprised 14 professional nurses who did not work in the interventional sites. Participants were assigned for lens assessment by two independent trained ophthalmologists blinded to the study. Results: The electrophysiology laboratory staff received higher doses of ionizing radiation (17.2 ± 11.9 mSv; P < 0.001). There was a significant positive correlation between the years of working experience and effective dose in the lens (P < 0.001). In general, our findings showed that the incidence of lens opacity was 79% (95% CI, 69.9-88.1) in participants with exposure (the case group) and our findings showed that the incidence of lenses opacity was 7.1% (95% CI:2.3-22.6) with the relative risk (RR) of 11.06 (P < 0.001). Conclusions: We believe that the risk of radiation-induced cataract in cardiology interventionists and staff depends on their work site. As the radiation dose increases, the prevalence of posterior eye changes increases. PMID:25789258

  6. Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

    NASA Technical Reports Server (NTRS)

    Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

    2006-01-01

    Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low

  7. Radiation induced genome instability: multiscale modelling and data analysis

    NASA Astrophysics Data System (ADS)

    Andreev, Sergey; Eidelman, Yuri

    2012-07-01

    Genome instability (GI) is thought to be an important step in cancer induction and progression. Radiation induced GI is usually defined as genome alterations in the progeny of irradiated cells. The aim of this report is to demonstrate an opportunity for integrative analysis of radiation induced GI on the basis of multiscale modelling. Integrative, systems level modelling is necessary to assess different pathways resulting in GI in which a variety of genetic and epigenetic processes are involved. The multilevel modelling includes the Monte Carlo based simulation of several key processes involved in GI: DNA double strand breaks (DSBs) generation in cells initially irradiated as well as in descendants of irradiated cells, damage transmission through mitosis. Taking the cell-cycle-dependent generation of DNA/chromosome breakage into account ensures an advantage in estimating the contribution of different DNA damage response pathways to GI, as to nonhomologous vs homologous recombination repair mechanisms, the role of DSBs at telomeres or interstitial chromosomal sites, etc. The preliminary estimates show that both telomeric and non-telomeric DSB interactions are involved in delayed effects of radiation although differentially for different cell types. The computational experiments provide the data on the wide spectrum of GI endpoints (dicentrics, micronuclei, nonclonal translocations, chromatid exchanges, chromosome fragments) similar to those obtained experimentally for various cell lines under various experimental conditions. The modelling based analysis of experimental data demonstrates that radiation induced GI may be viewed as processes of delayed DSB induction/interaction/transmission being a key for quantification of GI. On the other hand, this conclusion is not sufficient to understand GI as a whole because factors of DNA non-damaging origin can also induce GI. Additionally, new data on induced pluripotent stem cells reveal that GI is acquired in normal mature

  8. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

    SciTech Connect

    Cotrim, Ana P.; Yoshikawa, Masanobu; Sunshine, Abraham N.; Zheng Changyu; Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B.; Baum, Bruce J.

    2012-07-15

    Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation {+-} cisplatin. Methods and Materials: Female C3H mice, {approx}8 weeks old, were irradiated with five fractionated doses {+-} cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 Multiplication-Sign 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

  9. Dequalinium blocks macrophage-induced metastasis following local radiation

    PubMed Central

    Kaidar-Person, Orit; Rachman-Tzemah, Chen; Alishekevitz, Dror; Kotsofruk, Ruslana; Miller, Valeria; Nevelsky, Alexander; Daniel, Shahar; Raviv, Ziv; Rotenberg, Susan A.; Shaked, Yuval

    2015-01-01

    A major therapeutic obstacle in clinical oncology is intrinsic or acquired resistance to therapy, leading to subsequent relapse. We have previously shown that systemic administration of different cytotoxic drugs can induce a host response that contributes to tumor angiogenesis, regrowth and metastasis. Here we characterize the host response to a single dose of local radiation, and its contribution to tumor progression and metastasis. We show that plasma from locally irradiated mice increases the migratory and invasive properties of colon carcinoma cells. Furthermore, locally irradiated mice intravenously injected with CT26 colon carcinoma cells succumb to pulmonary metastasis earlier than their respective controls. Consequently, orthotopically implanted SW480 human colon carcinoma cells in mice that underwent radiation, exhibited increased metastasis to the lungs and liver compared to their control tumors. The irradiated tumors exhibited an increase in the colonization of macrophages compared to their respective controls; and macrophage depletion in irradiated tumor-bearing mice reduces the number of metastatic lesions. Finally, the anti-tumor agent, dequalinium-14, in addition to its anti-tumor effect, reduces macrophage motility, inhibits macrophage infiltration of irradiated tumors and reduces the extent of metastasis in locally irradiated mice. Overall, this study demonstrates the adverse effects of local radiation on the host that result in macrophage-induced metastasis. PMID:26348470

  10. Lack of photoprotection against UVB-induced erythema by immediate pigmentation induced by 382 nm radiation

    SciTech Connect

    Black, G.; Matzinger, E.; Gange, R.W.

    1985-11-01

    Immediate pigment darkening (IPD) was induced on the backs of 11 human volunteers of skin types III and IV by exposing the skin to UVA radiation (382 nm). The minimum erythema dose (MED) of UVB radiation was also determined by exposing sites to graduated doses of 304 nm radiation. The order of exposure of distinct anatomic areas was as follow: UVB followed by IPD induction; IPD induction followed by UVB; IPD induction followed 3 h later by UVB; and UVB only. Erythema responses induced by UVB were graded by inspection 24 h later and the MEDs in the 4 areas were compared. The induction of IPD before UVB exposure caused no significant change in the MED compared to sites receiving UVB only, or receiving UVA radiation after UVB, confirming that the IPD reaction does not protect against UVB-induced erythema. There was also no evidence of photorecovery, i.e., an increase in the MED of UVB resulting from exposure to longer wavelength, UV or visible radiation following UVB exposure.

  11. Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non-Small Cell Lung Cancer.

    PubMed

    Feng, Jianguo; Zhang, Shirong; Wu, Kan; Wang, Bing; Wong, Jeffrey Y C; Jiang, Hong; Xu, Rujun; Ying, Lisha; Huang, Haixiu; Zheng, Xiaoliang; Chen, Xufeng; Ma, Shenglin

    2016-05-01

    Lung cancer is a leading cause of cancer-related mortality worldwide, and concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of the chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs, and determined the combination effects of SAHA and cisplatin on human non-small cell lung cancer (NSCLC) cells in response to treatment of ionizing radiation (IR), and on tumor growth of lung cancer H460 xenografts receiving radiotherapy. We also investigated the potential differentiation effect of SAHA and its consequences on cancer cell invasion. Our results showed that SAHA and cisplatin compromise distinct DNA damage repair pathways, and treatment with SAHA enhanced synergistic radiosensitization effects of cisplatin in established NSCLC cell lines in a p53-independent manner, and decreased the DNA damage repair capability in cisplatin-treated primary NSCLC tumor tissues in response to IR. SAHA combined with cisplatin also significantly increased inhibitory effect of radiotherapy on tumor growth in the mouse xenograft model. In addition, SAHA can induce differentiation in stem cell-like cancer cell population, reduce tumorigenicity, and decrease invasiveness of human lung cancer cells. In conclusion, our data suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of a chemoradiotherapy regimen for NSCLC. Mol Cancer Ther; 15(5); 842-53. ©2016 AACR. PMID:26839308

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

    NASA Astrophysics Data System (ADS)

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

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

  13. Gamma radiation induces hydrogen absorption by copper in water

    NASA Astrophysics Data System (ADS)

    Lousada, Cláudio M.; Soroka, Inna L.; Yagodzinskyy, Yuriy; Tarakina, Nadezda V.; Todoshchenko, Olga; Hänninen, Hannu; Korzhavyi, Pavel A.; Jonsson, Mats

    2016-04-01

    One of the most intricate issues of nuclear power is the long-term safety of repositories for radioactive waste. These repositories can have an impact on future generations for a period of time orders of magnitude longer than any known civilization. Several countries have considered copper as an outer corrosion barrier for canisters containing spent nuclear fuel. Among the many processes that must be considered in the safety assessments, radiation induced processes constitute a key-component. Here we show that copper metal immersed in water uptakes considerable amounts of hydrogen when exposed to γ-radiation. Additionally we show that the amount of hydrogen absorbed by copper depends on the total dose of radiation. At a dose of 69 kGy the uptake of hydrogen by metallic copper is 7 orders of magnitude higher than when the absorption is driven by H2(g) at a pressure of 1 atm in a non-irradiated dry system. Moreover, irradiation of copper in water causes corrosion of the metal and the formation of a variety of surface cavities, nanoparticle deposits, and islands of needle-shaped crystals. Hence, radiation enhanced uptake of hydrogen by spent nuclear fuel encapsulating materials should be taken into account in the safety assessments of nuclear waste repositories.

  14. Gamma radiation induces hydrogen absorption by copper in water.

    PubMed

    Lousada, Cláudio M; Soroka, Inna L; Yagodzinskyy, Yuriy; Tarakina, Nadezda V; Todoshchenko, Olga; Hänninen, Hannu; Korzhavyi, Pavel A; Jonsson, Mats

    2016-01-01

    One of the most intricate issues of nuclear power is the long-term safety of repositories for radioactive waste. These repositories can have an impact on future generations for a period of time orders of magnitude longer than any known civilization. Several countries have considered copper as an outer corrosion barrier for canisters containing spent nuclear fuel. Among the many processes that must be considered in the safety assessments, radiation induced processes constitute a key-component. Here we show that copper metal immersed in water uptakes considerable amounts of hydrogen when exposed to γ-radiation. Additionally we show that the amount of hydrogen absorbed by copper depends on the total dose of radiation. At a dose of 69 kGy the uptake of hydrogen by metallic copper is 7 orders of magnitude higher than when the absorption is driven by H2(g) at a pressure of 1 atm in a non-irradiated dry system. Moreover, irradiation of copper in water causes corrosion of the metal and the formation of a variety of surface cavities, nanoparticle deposits, and islands of needle-shaped crystals. Hence, radiation enhanced uptake of hydrogen by spent nuclear fuel encapsulating materials should be taken into account in the safety assessments of nuclear waste repositories. PMID:27086752

  15. Gamma radiation induces hydrogen absorption by copper in water

    PubMed Central

    Lousada, Cláudio M.; Soroka, Inna L.; Yagodzinskyy, Yuriy; Tarakina, Nadezda V.; Todoshchenko, Olga; Hänninen, Hannu; Korzhavyi, Pavel A.; Jonsson, Mats

    2016-01-01

    One of the most intricate issues of nuclear power is the long-term safety of repositories for radioactive waste. These repositories can have an impact on future generations for a period of time orders of magnitude longer than any known civilization. Several countries have considered copper as an outer corrosion barrier for canisters containing spent nuclear fuel. Among the many processes that must be considered in the safety assessments, radiation induced processes constitute a key-component. Here we show that copper metal immersed in water uptakes considerable amounts of hydrogen when exposed to γ-radiation. Additionally we show that the amount of hydrogen absorbed by copper depends on the total dose of radiation. At a dose of 69 kGy the uptake of hydrogen by metallic copper is 7 orders of magnitude higher than when the absorption is driven by H2(g) at a pressure of 1 atm in a non-irradiated dry system. Moreover, irradiation of copper in water causes corrosion of the metal and the formation of a variety of surface cavities, nanoparticle deposits, and islands of needle-shaped crystals. Hence, radiation enhanced uptake of hydrogen by spent nuclear fuel encapsulating materials should be taken into account in the safety assessments of nuclear waste repositories. PMID:27086752

  16. DNA damage in cells exhibiting radiation-induced genomic instability

    DOE PAGESBeta

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

  17. DNA damage in cells exhibiting radiation-induced genomic instability

    SciTech Connect

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesis that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.

  18. Cerenkov emission induced by external beam radiation stimulates molecular fluorescence

    SciTech Connect

    Axelsson, Johan; Davis, Scott C.; Gladstone, David J.; Pogue, Brian W.

    2011-07-15

    Purpose: Cerenkov emission is induced when a charged particle moves faster than the speed of light in a given medium. Both x-ray photons and electrons produce optical Cerenkov photons in everyday radiation therapy of tissue; yet, this phenomenon has never been fully documented. This study quantifies the emissions and also demonstrates that the Cerenkov emission can excite a fluorophore, protoporphyrin IX (PpIX), embedded in biological phantoms. Methods: In this study, Cerenkov emission induced by radiation from a clinical linear accelerator is investigated. Biological mimicking phantoms were irradiated with x-ray photons, with energies of 6 or 18 MV, or electrons at energies 6, 9, 12, 15, or 18 MeV. The Cerenkov emission and the induced molecular fluorescence were detected by a camera or a spectrometer equipped with a fiber optic cable. Results: It is shown that both x-ray photons and electrons, at MeV energies, produce optical Cerenkov photons in tissue mimicking media. Furthermore, we demonstrate that the Cerenkov emission can excite a fluorophore, protoporphyrin IX (PpIX), embedded in biological phantoms. Conclusions: The results here indicate that molecular fluorescence monitoring during external beam radiotherapy is possible.

  19. Ionizing radiation induces human intercellular adhesion molecule-1 in vitro.

    PubMed

    Behrends, U; Peter, R U; Hintermeier-Knabe, R; Eissner, G; Holler, E; Bornkamm, G W; Caughman, S W; Degitz, K

    1994-11-01

    Intercellular adhesion molecule-1 (ICAM-1) plays a central role in various inflammatory reactions and its expression is readily induced by inflammatory stimuli such as cytokines or ultraviolet irradiation. We have investigated the effect of ionizing radiation (IR) on human ICAM-1 expression in human cell lines and skin cultures. ICAM-1 mRNA levels in HL60, HaCaT, and HeLa cells were elevated at 3-6 h after irradiation and increased with doses from 10-40 Gy. The rapid induction of ICAM-1 occurred at the level of transcription, was independent of de novo protein synthesis, and did not involve autocrine stimuli including tumor necrosis factor-alpha and interleukin-1. IR also induced ICAM-1 cell surface expression within 24 h. Immunohistologic analysis of cultured human split skin revealed ICAM-1 upregulation on epidermal keratinocytes and dermal microvascular endothelial cells 24 h after exposure to 6 Gy. In conclusion, we propose ICAM-1 as an important radiation-induced enhancer of immunologic cell adhesion, which contributes to inflammatory reactions after local and total body irradiation. PMID:7963663

  20. DNA damage induced by the direct effect of radiation

    NASA Astrophysics Data System (ADS)

    Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R.

    2008-10-01

    We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB.

  1. Treatment of radiation- and chemotherapy-induced stomatitis

    SciTech Connect

    Carnel, S.B.; Blakeslee, D.B.; Oswald, S.G.; Barnes, M. )

    1990-04-01

    Severe stomatitis is a common problem encountered during either radiation therapy or chemotherapy. Most therapeutic regimens are empirical, with no scientific basis. The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiation- or chemotherapy-induced stomatitis. Eighteen patients were entered into a prospective double-blinded study to test several topical solutions: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride 1.0% (Dyclone); (3) kaolin-pectin solution, diphenhydramine plus saline (KBS); and (4) a placebo solution. Degree of pain relief, duration of relief, side effects, and palatability were evaluated. The results showed that Dyclone provided the most pain relief. Dyclone and viscous lidocaine with 1% cocaine provided the longest pain relief, which averaged 50 minutes This study provides objective data and defines useful guidelines for treatment of stomatitis.

  2. Radiation-induced transmission loss of integrated optic waveguide devices

    NASA Astrophysics Data System (ADS)

    Henschel, Henning; Koehn, Otmar; Schmidt, Hans U.

    1993-04-01

    The radiation sensitivity of different integrated optic (IO) devices was compared under standardized test conditions. We investigated four relatively simple device types made by four different manufacturers. The waveguide materials were proton exchanged LiTaO3, LiNbO3:Ti, Tl-diffused glass, and Ag-diffused glass, respectively. In order to standardize the irradiation parameters we followed the 'Procedure for Measuring Radiation-Induced Attenuation in Optical Fibers and Optical Cables' proposed by the NATO NETG as close as possible. In detail we made pulsed irradiations with dose values of about 500 rad*, 104 rad, and 105 rad, as well as continuous irradiations at a 60Co source with a dose rate of 1300 rad*/min up to a total dose of 104 rad. Device temperatures were about 22 degree(s)C, -50 degree(s)C, and +80 degree(s)C.

  3. Tissue deformation induced by radiation force from Gaussian transducers.

    PubMed

    Myers, Matthew R

    2006-05-01

    Imaging techniques based upon the tissue mechanical response to an acoustic radiation force are being actively researched. In this paper a model for predicting steady-state tissue displacement induced by a radiation force arising from the absorption of Gaussian ultrasound beams is presented. A simple analytic expression is derived that agrees closely with the numerical quadrature of the displacement convolution integrals. The analytic result reveals the dependence of the steady-state axial displacement upon the operational parameters, e.g., an inverse proportional relationship to the tissue shear modulus. The derivation requires that the transducer radius be small compared to the focal length, but accurate results were obtained for transducer radii comparable to the focal length. Favorable comparisons with displacement predictions for non-Gaussian transducers indicate that the theory is also useful for a broader range of transducer intensity profiles. PMID:16708969

  4. Radiation-induced renal disease. A clinicopathologic study.

    PubMed

    Keane, W F; Crosson, J T; Staley, N A; Anderson, W R; Shapiro, F L

    1976-01-01

    Radiation injury to the renal parenchyma is an unusual cause of renal insufficiency. Light, immunofluorescence and electron microscopic studies were performed on the renal tissue from two patients in whom renal insufficiency developed within a year after they received abdominal irradiation. The glomerular lesion in both patients was similar. Mild endothelial cell swelling and basement membrane splitting were noted consistently on light microscopy. The electron microscopic examination revealed marked subendothelial expansion with electron-lucent material associated with deposition of basement membrane-like material adjacent to the endothelial cells. In some capillary loops, the endothelial cell lining appeared to be completely lost. The pathogenesis of radiation-induced renal injury is still uncertain. It is speculated that local activation of the coagulation system with consequent thrombosis of the renal microvasculature may be extremely important. PMID:1251842

  5. Radiation-induced cerebral meningioma: a recognizable entity

    SciTech Connect

    Rubinstein, A.B.; Shalit, M.N.; Cohen, M.L.; Zandbank, U.; Reichenthal, E.

    1984-11-01

    The authors retrospectively analyzed the clinical and histopathological findings in 201 patients with intracranial meningiomas operated on in the period 1978 to 1982. Forty-three of the patients (21.4%) had at some previous time received radiation treatment to their scalp, the majority for tinea capitis. The findings in these 43 irradiated patients were compared with those in the 158 non-irradiated patients. Several distinctive clinical and histological features were identified in the irradiated group, which suggest that radiation-induced meningiomas can be defined as a separate nosological subgroup. The use of irradiation in large numbers of children with tinea capitis in the era prior to the availability of griseofulvin may be responsible for a significantly increased incidence of intracranial meningiomas.

  6. Magnon emission and radiation induced by spin-polarized current

    NASA Astrophysics Data System (ADS)

    Zholud, Andrei; Freeman, Ryan; Cao, Rongxing; Urazhdin, Sergei

    The spin-torque effect due to spin injection into ferromagnets can affect their effective dynamical damping, and modify the magnon populations. The latter leads to the onset of nonlinear damping that can prevent spontaneous current-induced magnetization oscillations. It has been argued that these nonlinear processes can be eliminate by the radiation of magnons excited by local spin injection in extended magnetic films. To test these effects, studied of the effects of spin injection on the magnon populations in nanoscale spin valves and magnetic point contacts. Measurements of the giant magnetoresistance show a significant resistance component that is antisymmetric in current, and linearly dependent on temperature T. This component is significantly larger for the nanopatterned ferromagnets than for point contacts. We interpret our observations in terms of stimulated generation of magnons by the spin current, and their radiation in point contacts. Supported by NSF ECCS-1305586, ECCS-1509794.

  7. Role of Oxidative Damage in Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

  8. Radiation-Induced Phase Transformations in Ilmenite-Group Minerals

    SciTech Connect

    Mitchell, J. N.

    1997-12-31

    Transmission electron microscopy (TEM) is a powerful tool for characterizing and understanding radiation-induced structural changes in materials. We have irradiated single crystals of ilmenite (FeTiO{sub 3}) and geikielite (MgTiO{sub 3}) using ions and electrons to better understand the response of complex oxides to radiation. Ion irradiation experiments of bulk single crystals at 100 K show that ilmenite amorphized at doses of less than 1x10(exp15) Ar(2+)/sq cm and at a damage level in the peak damage region of 1 displacement per atom (dpa). Transmission electron microscopy and electron diffraction of a cross-sectioned portion of this crystal confirmed the formation of a 150 am thick amorphous layer. Geikielite proved to be more radiation resistant, requiring a flux of 2x10(exp 15) Xe(2+)/sq cm to induce amorphization at 100 K. This material did not amorphize at 470 K, despite a dose of 2.5 x10(exp 16) Xe(2+)/sq cm and a damage level as high as 25 dpa. Low temperature irradiations of electron- transparent crystals with 1 MeV Kr(+) also show that ilmenite amorphized after a damage level of 2.25 dpa at 175 K.Similar experiments on geikielite show that the microstructure is partially amorphous and partially crystalline after 10 dpa at 150 K. Concurrent ion and electron irradiation of both materials with 1 MeV Kr(+) and 0.9 MeV electrons produced dislocation loops in both materials, but no amorphous regions were formed. Differences in the radiation response of these isostructural oxides suggests that in systems with Mg-Fe solid solution, the Mg-rich compositions may be more resistant to structural changes.

  9. [Radiation-induced cancers: state of the art in 1997].

    PubMed

    Cosset, J M

    1997-01-01

    Scientists now have available a large amount of data dealing with radiation-induced neoplasms. These data went back to anecdotal observations which were made in the very first years of utilization of X-rays and radioactive elements. In fact, it is essentially the strict follow-up of the Japanese populations irradiated by the Hiroshima and Nagasaki bombing which allowed a more precise evaluation of the carcinogenicity of ionizing radiations. Further refinements came from therapeutical irradiations: it is now possible to study large cohorts of patients given well-known doses in well-defined volumes and followed for more than 20 years. Last but not least, a significant increase in the incidence and mortality of thyroid cancer has been detected in children contaminated by iodine radioisotopes after the Tchernobyl accident. Recently, some data suggested the emergence of "clusters" of leukemias close to some nuclear facilities, but this question remains highly polemical, both in France and in the UK. Other questions are still waiting for a precise answer; of course, the extrapolation of our available data to very low doses delivered at very low dose rates, but also the carcinogenic risk at high doses. For these "high" doses (about 30 to 70 Gy), a competition between mutagenesis and cell killing was expected, so that these dose levels were expected to be less carcinogenic than lower (a few sieverts) doses. Actually, recent data suggest that the carcinogenic risk goes on increasing up to relatively important doses. In addition, carcinogenic factors, such as tabacco, anticancer chemotherapy and individual susceptibility, are found more and more to be closely intricated with ionizing radiation in the genesis of a given cancer. Even if a number of questions are still pending, the already available data allow specialists, both in medicine and radioprotection, to edict strict rules which can be reasonably expected to have significantly reduced the risk of radiation-induced

  10. Erythrocyte stiffness during morphological remodeling induced by carbon ion radiation.

    PubMed

    Zhang, Baoping; Liu, Bin; Zhang, Hong; Wang, Jizeng

    2014-01-01

    The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new

  11. Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

    PubMed Central

    Zhang, Baoping; Liu, Bin; Zhang, Hong; Wang, Jizeng

    2014-01-01

    The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new

  12. Infrared A radiation promotes survival of human melanocytes carrying ultraviolet radiation-induced DNA damage.

    PubMed

    Kimeswenger, Susanne; Schwarz, Agatha; Födinger, Dagmar; Müller, Susanne; Pehamberger, Hubert; Schwarz, Thomas; Jantschitsch, Christian

    2016-06-01

    The link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR-induced non-epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR-induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR-induced DNA damage. IR partly reversed the pro-apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR-induced DNA damage and thereby might contribute to melanomagenesis. PMID:26844814

  13. Measurements of prompt radiation induced conductivity in Teflon (PTFE).

    SciTech Connect

    Hartman, E. Frederick; Zarick, Thomas Andrew; Sheridan, Timothy J.; Preston, E.

    2013-05-01

    We performed measurements of the prompt radiation induced conductivity (RIC) in thin samples of Teflon (PTFE) at the Little Mountain Medusa LINAC facility in Ogden, UT. Three mil (76.2 microns) samples were irradiated with a 0.5 %CE%BCs pulse of 20 MeV electrons, yielding dose rates of 1E9 to 1E11 rad/s. We applied variable potentials up to 2 kV across the samples and measured the prompt conduction current. Details of the experimental apparatus and analysis are reported in this report on prompt RIC in Teflon.

  14. Radiation-induced physical changes in UHMWPE implant components.

    PubMed

    Naidu, S H; Bixler, B L; Moulton, M J

    1997-02-01

    Post-irradiation aging of ultra-high molecular weight polyethylene (UHMWPE) is not well understood. Retrieval studies and in vitro aged specimens have shown oxidative changes along with increases in crystallinity. Critical analysis and review of the polymer science and polymer physics literature shows that while oxidation may be important during the first year post-irradiation, subsequent aging occurs because of initial gamma radiation-induced chain scission leading to eventual isothermal crystallization of polymer chains in the amorphous regions of the UHMWPE bulk. Mechanical properties of aged UHMWPE are not as yet clear and, until such data become available, gamma irradiation sterilization must be used with caution. PMID:9048391

  15. Transient radiation-induced absorption in laser materials

    NASA Astrophysics Data System (ADS)

    Brannon, Paul J.

    1994-06-01

    Transient radiation-induced absorption losses in laser materials have been measured using a pulsed nuclear reactor. Reactor pulse widths of 70 to 90 microsecond(s) and absorbed doses of 1 to 7.5 krad have been used. Transmission recovery times and peak absorption coefficients are given. Materials tested include LiNbO3, GSGG, silica substrates, and filter glasses used in the laser cavity. The filter glasses are tested at discrete wavelengths in the range 440 - 750 nm. Lithium niobate, MgO-doped LiNbO3, GSGG, and the silica substrates are tested at 1061 nm.

  16. Facial reconstruction for radiation-induced skin cancer

    SciTech Connect

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

    1990-04-01

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

  17. Measurements of prompt radiation induced conductivity of Kapton.

    SciTech Connect

    Preston, Eric F.; Zarick, Thomas Andrew; Sheridan, Timothy J.; Hartman, E. Frederick; Stringer, Thomas Arthur

    2010-10-01

    We performed measurements of the prompt radiation induced conductivity in thin samples of Kapton (polyimide) at the Little Mountain Medusa LINAC facility in Ogden, UT. Three mil samples were irradiated with a 0.5 {mu}s pulse of 20 MeV electrons, yielding dose rates of 1E9 to 1E10 rad/s. We applied variable potentials up to 2 kV across the samples and measured the prompt conduction current. Analysis rendered prompt conductivity coefficients between 6E-17 and 2E-16 mhos/m per rad/s, depending on the dose rate and the pulse width.

  18. Radiation-Induced Premelting of Ice at Silica Interfaces

    SciTech Connect

    Schoeder, S.; Reichert, H.; Schroeder, H.; Mezger, M.; Okasinski, J. S.; Dosch, H.; Honkimaeki, V.; Bilgram, J.

    2009-08-28

    The existence of surface and interfacial melting of ice below 0 deg. C has been confirmed by many different experimental techniques. Here we present a high-energy x-ray reflectivity study of the interfacial melting of ice as a function of both temperature and x-ray irradiation dose. We found a clear increase of the thickness of the quasiliquid layer with the irradiation dose. By a systematic x-ray study, we have been able to unambiguously disentangle thermal and radiation-induced premelting phenomena. We also confirm the previously announced very high water density (1.25 g/cm{sup 3}) within the emerging quasiliquid layer.

  19. Radiation-induced pemphigus vulgaris of the breast.

    PubMed

    Vigna-Taglianti, R; Russi, E G; Denaro, N; Numico, G; Brizio, R

    2011-07-01

    Pemphigus vulgaris is a rare autoimmune mucocutaneous bullous disease. Patients with a history of pemphigus vulgaris - who need radiotherapy - may show a long lasting bullous cutaneous manifestation, typical of pemphigus, within radiation fields. The literature describes fewer than 20 radio-induced cases. While systematic corticosteroid therapy has proven to be useful, topical treatment used in association with corticosteroid therapy is rarely described. To our knowledge the use of modern dressing products has never been described. We report our experience in a case in which modern dressing products were usefully associated to systemic therapy. PMID:21511511

  20. Chaos of radiative heat-loss-induced flame front instability.

    PubMed

    Kinugawa, Hikaru; Ueda, Kazuhiro; Gotoda, Hiroshi

    2016-03-01

    We are intensively studying the chaos via the period-doubling bifurcation cascade in radiative heat-loss-induced flame front instability by analytical methods based on dynamical systems theory and complex networks. Significant changes in flame front dynamics in the chaotic region, which cannot be seen in the bifurcation diagrams, were successfully extracted from recurrence quantification analysis and nonlinear forecasting and from the network entropy. The temporal dynamics of the fuel concentration in the well-developed chaotic region is much more complicated than that of the flame front temperature. It exhibits self-affinity as a result of the scale-free structure in the constructed visibility graph. PMID:27036182

  1. Radiation-induced collisional pumping of molecules containing few atoms

    SciTech Connect

    Vasil'ev, G.K.; Chernyshev, Y.A.; Makarov, E.F.; Yakushev, V.G.

    1986-01-01

    The authors analyze the radiation-induced collisional pumping of few-atom molecules by laser emission taking into account both collisional and noncollisional processes of vibrational energy transfer in a molecule. For typical values of the parameters the vibrational energy of the molecules was found to depend on the laser emission intensity; regions of weak absorption, optimum absorption, and saturation appear as the pumping rate rises. Qualitative general conclusions are reached concerning the optimum conditions for the realization, in a medium absorbing laser emission, of either nonequilibrium dissociation or a chemical reaction involving vibrationally excited molecules.

  2. Radiation-induced myocardial perfusion abnormalities in breast cancer patients following external beam radiation therapy

    PubMed Central

    Eftekhari, Mohammad; Anbiaei, Robabeh; Zamani, Hanie; Fallahi, Babak; Beiki, Davood; Ameri, Ahmad; Emami-Ardekani, Alireza; Fard-Esfahani, Armaghan; Gholamrezanezhad, Ali; Seid Ratki, Kazem Razavi; Roknabadi, Alireza Momen

    2015-01-01

    Objective(s): Radiation therapy for breast cancer can induce myocardial capillary injury and increase cardiovascular morbidity and mortality. A prospective cohort was conducted to study the prevalence of myocardial perfusion abnormalities following radiation therapy of left-sided breast cancer patients as compared to those with right–sided cancer. Methods: To minimize potential confounding factors, only those patients with low 10-year risk of coronary artery disease (based on Framingham risk scoring) were included. All patients were initially treated by modified radical mastectomy and then were managed by postoperative 3D Conformal Radiation Therapy (CRT) to the surgical bed with an additional 1-cm margin, delivered by 46-50 Gy (in 2 Gy daily fractions) over a 5-week course. The same dose-adjusted chemotherapy regimen (including anthracyclines, cyclophosphamide and taxol) was given to all patients. Six months after radiation therapy, all patients underwent cardiac SPECT for the evaluation of myocardial perfusion. Results: A total of 71 patients with a mean age of 45.3±7.2 years [35 patients with leftsided breast cancer (exposed) and 36 patients with right-sided cancer (controls)] were enrolled. Dose-volume histogram (DVH) [showing the percentage of the heart exposed to >50% of radiation] was significantly higher in patients with left-sided breast cancer. Visual interpretation detected perfusion abnormalities in 42.9% of cases and 16.7% of controls (P=0.02, Odds ratio=1.46). In semiquantitative segmental analysis, only apical (28.6% versus 8.3%, P=0.03) and anterolateral (17.1% versus 2.8%, P=0.049) walls showed significantly reduced myocardial perfusion in the exposed group. Summed Stress Score (SSS) of>3 was observed in twelve cases (34.3%), while in five of the controls (13.9%),(Odds ratio=1.3). There was no significant difference between the groups regarding left ventricular ejection fraction. Conclusion: The risk of radiation induced myocardial perfusion

  3. Environmental applications of radiation-induced defects in clay minerals

    NASA Astrophysics Data System (ADS)

    Allard, T.

    2011-12-01

    Radiation effects on clay minerals have been studied over the last 35 years, providing a wealth of information on environmental and geological processes. They have been applied to the reconstruction of past radioelement migrations in the geosphere, the dating of clay minerals from soils or the evolution of the physico-chemical properties under irradiation. All known radiation-induced point defects in clay minerals are detected using Electron Paramagnetic Resonance Spectroscopy. They mostly consist in electron holes located on oxygen atoms of the structure, and can be differentiated through their nature and their thermal stability. For instance, several are associated to a π orbital on a Si-O bond. One defect, namely the A-center, is stable over geological periods at ambiant temperature. These point defects are produced mainly by ionizing radiations. By contrast to point defects, it was shown that electron or heavy ion irradiation easily produces amorphization in smectites. Two main applications of radiation-induced defects in clay minerals are derived : (i) the use of defects as tracers of past radioactivity. In geosystems where the age of the clay can be constrained, migrations of radioelements can be reconstructed in natural analogues of the far field of high level nuclear waste repositories. When the dose rate may be assumed constant over time, the paleodose is used to date clay populations, an approach applied to laterites of the Amazon basin. (ii) The influence of radiation on clay mineral properties that remains poorly documented, although it is an important issue in various domains such as the safety assessment of the high level nuclear waste repositories. In case of a leakage of transuranic elements from the radioactive wasteform, alpha recoil nuclei would amorphize smectite after a period much lower than the disposal lifetime. By contrast, amorphisation from ionizing radiation is unlikely over 1 million years. Furthermore, it was shown that amorphization

  4. Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage.

    PubMed

    Hong, Chang-Won; Kim, Young-Mee; Pyo, Hongryull; Lee, Joon-Ho; Kim, Suwan; Lee, Sunyoung; Noh, Jae Myoung

    2013-11-01

    The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-N(ω)-nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N(6)-(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage. PMID:23704776

  5. Galactic cosmic ray-induced radiation dose on terrestrial exoplanets.

    PubMed

    Atri, Dimitra; Hariharan, B; Grießmeier, Jean-Mathias

    2013-10-01

    This past decade has seen tremendous advancements in the study of extrasolar planets. Observations are now made with increasing sophistication from both ground- and space-based instruments, and exoplanets are characterized with increasing precision. There is a class of particularly interesting exoplanets that reside in the habitable zone, which is defined as the area around a star where the planet is capable of supporting liquid water on its surface. Planetary systems around M dwarfs are considered to be prime candidates to search for life beyond the Solar System. Such planets are likely to be tidally locked and have close-in habitable zones. Theoretical calculations also suggest that close-in exoplanets are more likely to have weaker planetary magnetic fields, especially in the case of super-Earths. Such exoplanets are subjected to a high flux of galactic cosmic rays (GCRs) due to their weak magnetic moments. GCRs are energetic particles of astrophysical origin that strike the planetary atmosphere and produce secondary particles, including muons, which are highly penetrating. Some of these particles reach the planetary surface and contribute to the radiation dose. Along with the magnetic field, another factor governing the radiation dose is the depth of the planetary atmosphere. The higher the depth of the planetary atmosphere, the lower the flux of secondary particles will be on the surface. If the secondary particles are energetic enough, and their flux is sufficiently high, the radiation from muons can also impact the subsurface regions, such as in the case of Mars. If the radiation dose is too high, the chances of sustaining a long-term biosphere on the planet are very low. We have examined the dependence of the GCR-induced radiation dose on the strength of the planetary magnetic field and its atmospheric depth, and found that the latter is the decisive factor for the protection of a planetary biosphere. PMID:24143867

  6. Radiatively induced breaking of conformal symmetry in a superpotential

    NASA Astrophysics Data System (ADS)

    Arbuzov, A. B.; Cirilo-Lombardo, D. J.

    2016-07-01

    Radiatively induced symmetry breaking is considered for a toy model with one scalar and one fermion field unified in a superfield. It is shown that the classical quartic self-interaction of the superfield possesses a quantum infrared singularity. Application of the Coleman-Weinberg mechanism for effective potential leads to the appearance of condensates and masses for both scalar and fermion components. That induces a spontaneous breaking of the initial classical symmetries: the supersymmetry and the conformal one. The energy scales for the scalar and fermion condensates appear to be of the same order, while the renormalization scale is many orders of magnitude higher. A possibility to relate the considered toy model to conformal symmetry breaking in the Standard Model is discussed.

  7. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

    PubMed

    Ou, Sai-Hong Ignatius; Weitz, Michael; Jalas, John R; Kelly, Daniel F; Wong, Vanessa; Azada, Michele C; Quines, Oliver; Klempner, Samuel J

    2016-06-01

    Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment. PMID:27133743

  8. Experimental analysis of radiation- and streaming-induced microparticle acoustophoresis

    NASA Astrophysics Data System (ADS)

    Rossi, Massimiliano; Marin, Alvaro; Kähler, Christian J.; Augustsson, Per; Laurell, Thomas; Muller, Peter B.; Barnkob, Rune; Bruus, Henrik

    2012-11-01

    We present an experimental analysis of the acoustophoretic motion of microparticles suspended in a liquid-filled acoustofluidic microchannel. This analysis intends to provide an experimental validation and support to very recent numerical and analytical models of radiation- and streaming-induced microparticle acoustophoresis (see Muller et al., Lab Chip 12, in press, 2012). For the experiments, we used a suspension of water and spherical polystyrene particles in a straight microchannel with rectangular cross section, actuated in its 1.94-MHz resonance by means of a piezoelectric transducer. The particles were labeled with a fluorescent dye and their motion was observed using an epifluorescent microscope. For the analysis, the Astigmatism Particle Tracking Velocimetry (APTV) technique was used to measure the three-dimensional trajectories and velocities of the particles with high precision and resolution (Cierpka et al., Meas Sci Technol 22, 2011). The experiments were performed for different particle sizes, ranging from 0.5- μm particles, dominated by the Stokes drag force induced by the acoustic streaming of the flow, to 5- μm particles, dominated by the acoustic radiation force. The results agree well with the analytical and numerical predictions.

  9. Space-radiation-induced Photon Luminescence of the Moon

    NASA Technical Reports Server (NTRS)

    Wilson, Thomas; Lee, Kerry

    2008-01-01

    We report on the results of a study of the photon luminescence of the Moon induced by Galactic Cosmic Rays (GCRs) and space radiation from the Sun, using the Monte Carlo program FLUKA. The model of the lunar surface is taken to be the chemical composition of soils found at various landing sites during the Apollo and Luna programs, averaged over all such sites to define a generic regolith for the present analysis. This then becomes the target that is bombarded by Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs) above 1 keV in FLUKA to determine the photon fluence albedo produced by the Moon's surface when there is no sunlight and Earthshine. This is to be distinguished from the gamma-ray spectrum produced by the radioactive decay of radiogenic constituents lying in the surface and interior of the Moon. From the photon fluence we derive the spectrum which can be utilized to examine existing lunar spectral data and to design orbiting instrumentation for measuring various components of the space-radiation-induced photon luminescence present on the Moon.

  10. The thermal stability of radiation-induced defects in illite

    NASA Astrophysics Data System (ADS)

    Riegler, T.; Allard, T.; Beaufort, D.; Cantin, J.-L.; von Bardeleben, H. J.

    2016-01-01

    High-purity illite specimens from the Mesoproterozoic unconformity-related uranium deposits of Kiggavik, Thelon basin, Nunavut (Canada), and Shea Creek (Athabasca basin, Saskatchewan, Canada) have been studied using electron paramagnetic resonance spectroscopy to determine the thermal stability of the main radiation-induced defects and question the potential of using illite as a natural dosimeter. The observed spectra are complex as they can show in the same region several contributions: (1) an unstable native defect, (2) the main stable defect named Ai by reference to a previous study (Morichon et al. in Phys Chem Minerals 35:339-346, 2008), (3) a signal at g = 2.063 assigned to a new defect, not yet fully characterized, named Ai2 center and (4) impurities such as vanadyl complex or divalent manganese. Isochronal heating shows that the new signal corresponds to a stable species. Isothermal heating experiments at 400 and 450 °C provide values of half-life extrapolated at room temperature and activation energy of 1.9-29,109 years and 1.3-1.4 eV, respectively, corresponding to the Ai center. These parameters allow the use of stable radiation-induced defects as a record of radioactivity down to the Paleoproterozoic period.

  11. Simvastatin attenuates radiation-induced salivary gland dysfunction in mice

    PubMed Central

    Xu, Liping; Yang, Xi; Chen, Jiayan; Ge, Xiaolin; Qin, Qin; Zhu, Hongcheng; Zhang, Chi; Sun, Xinchen

    2016-01-01

    Objective Statins are widely used lipid-lowering drugs, which have pleiotropic effects, such as anti-inflammation, and vascular protection. In our study, we investigated the radioprotective potential of simvastatin (SIM) in a murine model of radiation-induced salivary gland dysfunction. Design Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent + sham irradiation (IR) (Group I), SIM + sham IR (Group II), IR + solvent (Group III), and IR + SIM (Group IV). SIM (10 mg/kg body weight, three times per week) was administered intraperitoneally 1 week prior to IR through to the end of the experiment. Saliva and submandibular gland tissues were obtained for biochemical, morphological (hematoxylin and eosin staining and Masson’s trichrome), and Western blot analysis at 8 hours, 24 hours, and 4 weeks after head and neck IR. Results IR caused a significant reduction of salivary secretion and amylase activity but elevation of malondialdehyde. SIM remitted the reduction of saliva secretion and restored salivary amylase activity. The protective benefits of SIM may be attributed to scavenging malondialdehyde, remitting collagen deposition, and reducing and delaying the elevation of transforming growth factor β1 expression induced by radiation. Conclusion SIM may be clinically useful to alleviate side effects of radiotherapy on salivary gland. PMID:27471375

  12. Proton-induced radiation damage in germanium detectors

    NASA Technical Reports Server (NTRS)

    Brueckner, J.; Koerfer, M.; Waenke, H.; Schroeder, A. N. F.; Filges, D.; Dragovitsch, P.; Englert, P. A. J.; Starr, R.; Trombka, J. I.

    1991-01-01

    High-purity germanium (HPGe) detectors will be used in future space missions for gamma-ray measurements and will be subject to interactions with energetic particles. To simulate this process, several large-volume n-type HPGe detectors were incrementally exposed to a particle fluence of up to 10 to the 8th protons/sq cm (proton energy: 1.5 GeV) at different operating temperatures (90 to 120 K) to induce radiation damage. Basic scientific and engineering data on detector performance were collected. During the incremental irradiation, the peak shape produced by the detectors showed a significant change from a Gaussian shape to a broad complex structure. After the irradiation, all detectors were thoroughly characterized by measuring many parameters. To remove the accumulated radiation damage, the detectors were stepwise-annealed at temperatures below 110 C, while kept in their specially designed cryostats. This study shows that n-type HPGe detectors can be used in charged-particle environments as high-energy resolution devices until a certain level of radiation damage is accumulated and that the damage can be removed at moderate annealing temperatures and the detector returned to operating condition.

  13. Robust Feedback Control of Flow Induced Structural Radiation of Sound

    NASA Technical Reports Server (NTRS)

    Heatwole, Craig M.; Bernhard, Robert J.; Franchek, Matthew A.

    1997-01-01

    A significant component of the interior noise of aircraft and automobiles is a result of turbulent boundary layer excitation of the vehicular structure. In this work, active robust feedback control of the noise due to this non-predictable excitation is investigated. Both an analytical model and experimental investigations are used to determine the characteristics of the flow induced structural sound radiation problem. The problem is shown to be broadband in nature with large system uncertainties associated with the various operating conditions. Furthermore the delay associated with sound propagation is shown to restrict the use of microphone feedback. The state of the art control methodologies, IL synthesis and adaptive feedback control, are evaluated and shown to have limited success for solving this problem. A robust frequency domain controller design methodology is developed for the problem of sound radiated from turbulent flow driven plates. The control design methodology uses frequency domain sequential loop shaping techniques. System uncertainty, sound pressure level reduction performance, and actuator constraints are included in the design process. Using this design method, phase lag was added using non-minimum phase zeros such that the beneficial plant dynamics could be used. This general control approach has application to lightly damped vibration and sound radiation problems where there are high bandwidth control objectives requiring a low controller DC gain and controller order.

  14. Proton-induced radiation damage in germanium detectors

    SciTech Connect

    Bruckner, J.; Korfer, M.; Wanke, H. , Mainz ); Schroeder, A.N.F. ); Figes, D.; Dragovitsch, P. ); Englert, P.A.J. ); Starr, R.; Trombka, J.I. . Goddard Space Flight Center); Taylor, I. ); Drake, D.M.; Shunk, E.R. )

    1991-04-01

    High-purity germanium (HPGe) detectors will be used in future space missions for gamma-ray measurements and will be subject to interactions with energetic particles. To simulate this process several large-volume n-type HPGe detectors were incrementally exposed to a particle fluence of up to 10{sub 8} protons cm{sup {minus}2} (proton energy: 1.5 GeV) at different operating temperatures (90 to 120 K) to induce radiation damage. Basic scientific as well as engineering data on detector performance were collected. During the incremental irradiation, the peak shape produced by the detectors showed a significant change from a Gaussian shape to a broad complex structure. After the irradiation all detectors were thoroughly characterized by measuring many parameters. To remove the accumulated radiation damage the detectors were stepwise annealed at temperatures T {le} 110{degrees}C while staying specially designed cryostats. This paper shows that n-type HPGe detectors can be used in charged particles environments as high-energy resolution devices until a certain level of radiation damage is accumulated and that the damage can be removed at moderate annealing temperatures and the detector returned to operating condition.

  15. Molecular Mechanisms and Treatment of Radiation-Induced Lung Fibrosis

    PubMed Central

    Ding, Nian-Hua; Li, Jian Jian; Sun, Lun-Quan

    2013-01-01

    Radiation-induced lung fibrosis (RILF) is a severe side effect of radiotherapy in lung cancer patients that presents as a progressive pulmonary injury combined with chronic inflammation and exaggerated organ repair. RILF is a major barrier to improving the cure rate and well-being of lung cancer patients because it limits the radiation dose that is required to effectively kill tumor cells and diminishes normal lung function. Although the exact mechanism is unclear, accumulating evidence suggests that various cells, cytokines and regulatory molecules are involved in the tissue reorganization and immune response modulation that occur in RILF. In this review, we will summarize the general symptoms, diagnostics, and current understanding of the cells and molecular factors that are linked to the signaling networks implicated in RILF. Potential approaches for the treatment of RILF will also be discussed. Elucidating the key molecular mediators that initiate and control the extent of RILF in response to therapeutic radiation may reveal additional targets for RILF treatment to significantly improve the efficacy of radiotherapy for lung cancer patients.

  16. Molecular Mechanisms and Treatment of Radiation-Induced Lung Fibrosis

    PubMed Central

    Ding, Nian-Hua; Li, Jian Jian; Sun, Lun-Quan

    2014-01-01

    Radiation-induced lung fibrosis (RILF) is a severe side effect of radiotherapy in lung cancer patients that presents as a progressive pulmonary injury combined with chronic inflammation and exaggerated organ repair. RILF is a major barrier to improving the cure rate and well-being of lung cancer patients because it limits the radiation dose that is required to effectively kill tumor cells and diminishes normal lung function. Although the exact mechanism is unclear, accumulating evidence suggests that various cells, cytokines and regulatory molecules are involved in the tissue reorganization and immune response modulation that occur in RILF. In this review, we will summarize the general symptoms, diagnostics, and current understanding of the cells and molecular factors that are linked to the signaling networks implicated in RILF. Potential approaches for the treatment of RILF will also be discussed. Elucidating the key molecular mediators that initiate and control the extent of RILF in response to therapeutic radiation may reveal additional targets for RILF treatment to significantly improve the efficacy of radiotherapy for lung cancer patients. PMID:23909719

  17. Radiation induced thyroid neoplasms 1920 to 1987: A vanishing problem

    SciTech Connect

    Mehta, M.P.; Goetowski, P.G.; Kinsella, T.J.

    1989-06-01

    Radiation for benign diseases has been implicated as an etiologic factor in thyroid cancer. From 1930-60, over 2 million children may have been exposed to therapeutic radiation and it is estimated that up to 7% may develop thyroid cancer after a 5-40 year latency. Thyroid stimulating hormone, secondary to radioinduced hypothyroidism, has been implicated as causative in animals. Such data has led to expensive screening programs in high risk patients. Because of a decline in irradiation for benign diseases in children over the last 2 decades, we questioned whether the incidence of radiation induced thyroid neoplasms (RITN) was also decreasing. Twenty-six of 227 patients (11%) with thyroid malignancies seen at our institution from 1974-87 had a history of previous head and neck irradiation. These included 13 papillary, 3 follicular, and 7 mixed carcinomas as well as 2 lymphomas and 1 synovial cell sarcoma. None of these 26 patients had abnormal thyroid function tests at presentation. Mean latency from irradiation to the diagnosis of thyroid cancer was 25.4 years (6-55 year range). Compared to the reported increasing incidence of RITN from 1940-70, there appears to be a significant decrease since 1970. Based on our analysis, the use of expensive screening programs in high risk populations may no longer be warranted. Additionally, the routine use of thyroid replacement in previously irradiated chemically hypothyroid patients is not recommended.30 references.

  18. Radiation-induced defects in clay minerals: A review

    NASA Astrophysics Data System (ADS)

    Allard, Th.; Balan, E.; Calas, G.; Fourdrin, C.; Morichon, E.; Sorieul, S.

    2012-04-01

    Extensive information has been collected on radiation effects on clay minerals over the last 35 years, providing a wealth of information on environmental and geological processes. The fields of applications include the reconstruction of past radioelement migrations, the dating of clay minerals or the evolution of the physico-chemical properties under irradiation. The investigation of several clay minerals, namely kaolinite, dickite, montmorillonite, illite and sudoite, by Electron Paramagnetic Resonance Spectroscopy has shown the presence of defects produced by natural or artificial radiations. These defects consist mostly of electron holes located on oxygen atoms of the structure. The various radiation-induced defects are differentiated through their nature and their thermal stability. Most of them are associated with a π orbital on a Si-O bond. The most abundant defect in clay minerals is oriented perpendicular to the silicate layer. Thermal annealing indicates this defect in kaolinite (A-center) to be stable over geological periods at ambient temperature. Besides, electron or heavy ion irradiation easily leads to an amorphization in smectites, depending on the type of interlayer cation. The amorphization dose exhibits a bell-shaped variation as a function of temperature, with a decreasing part that indicates the influence of thermal dehydroxylation. Two main applications of the knowledge of radiation-induced defects in clay minerals are derived: (i) The use of defects as tracers of past radioactivity. In geological systems where the age of the clay can be constrained, ancient migrations of radioelements can be reconstructed in natural analogues of high level nuclear waste repositories. When the dose rate may be assumed constant over time, the paleodose is used to date clay populations, an approach applied to fault gouges or laterites of the Amazon basin. (ii) The influence of irradiation over physico-chemical properties of clay minerals. An environmental

  19. Radiation-Induced Lymphocyte Apoptosis to Predict Radiation Therapy Late Toxicity in Prostate Cancer Patients

    SciTech Connect

    Schnarr, Kara; Boreham, Douglas; Sathya, Jinka; Julian, Jim; Dayes, Ian S.

    2009-08-01

    Purpose: To examine a potential correlation between the in vitro apoptotic response of lymphocytes to radiation and the risk of developing late gastrointestinal (GI)/genitourinary (GU) toxicity from radiotherapy for prostate cancer. Methods and Materials: Prostate cancer patients formerly enrolled in a randomized study were tested for radiosensitivity by using a radiation-induced lymphocyte apoptosis assay. Apoptosis was measured using flow cytometry-based Annexin-FITC/7AAD and DiOC{sub 6}/7AAD assays in subpopulations of lymphocytes (total lymphocytes, CD4+, CD8+ and CD4-/CD8-) after exposure to an in vitro dose of 0, 2, 4, or 8 Gy. Results: Patients with late toxicity after radiotherapy showed lower lymphocyte apoptotic responses to 8 Gy than patients who had not developed late toxicity (p = 0.01). All patients with late toxicity had apoptosis levels that were at or below the group mean. The negative predictive value in both apoptosis assays ranged from 95% to 100%, with sensitivity values of 83% to 100%. Apoptosis at lower dose points and in lymphocyte subpopulations had a weaker correlation with the occurrence of late toxicity. Conclusions: Lymphocyte apoptosis after 8 Gy of radiation has the potential to predict which patients will be spared late toxicity after radiation therapy. Further research should be performed to identify the specific subset of lymphocytes that correlates with late toxicity, followed by a corresponding prospective study.

  20. Image-based modeling of radiation-induced foci

    NASA Astrophysics Data System (ADS)

    Costes, Sylvain; Cucinotta, Francis A.; Ponomarev, Artem; Barcellos-Hoff, Mary Helen; Chen, James; Chou, William; Gascard, Philippe

    Several proteins involved in the response to DNA double strand breaks (DSB) form microscopically visible nuclear domains, or foci, after exposure to ionizing radiation. Radiation-induced foci (RIF) are believed to be located where DNA damage occurs. To test this assumption, we used Monte Carlo simulations to predict the spatial distribution of DSB in human nuclei exposed to high or low-LET radiation. We then compared these predictions to the distribution patterns of three DNA damage sensing proteins, i.e. 53BP1, phosphorylated ATM and γH2AX in human mammary epithelial. The probability to induce DSB can be derived from DNA fragment data measured experimentally by pulsed-field gel electrophoresis. We first used this probability in Monte Carlo simulations to predict DSB locations in synthetic nuclei geometrically described by a complete set of human chromosomes, taking into account microscope optics from real experiments. Simulations showed a very good agreement for high-LET, predicting 0.7 foci/µm along the path of a 1 GeV/amu Fe particle against measurement of 0.69 to 0.82 foci/µm for various RIF 5 min following exposure (LET 150 keV/µm). On the other hand, discrepancies were shown in foci frequency for low-LET, with measurements 20One drawback using a theoretical model for the nucleus is that it assumes a simplistic and static pattern for DNA densities. However DNA damage pattern is highly correlated to DNA density pattern (i.e. the more DNA, the more likely to have a break). Therefore, we generalized our Monte Carlo approach to real microscope images, assuming pixel intensity of DAPI in the nucleus was directly proportional to the amount of DNA in that pixel. With such approach we could predict DNA damage pattern in real images on a per nucleus basis. Since energy is randomly deposited along high-LET particle paths, RIF along these paths should also be randomly distributed. As expected, simulations produced DNA-weighted random (Poisson) distributions. In

  1. Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation

    PubMed Central

    Ye, Tianyu; Liu, Han-Chun; Wang, Zhuo; Wegscheider, W.; Mani, Ramesh G.

    2015-01-01

    A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. For circularly polarized radiation, the oscillatory magnetoresistive response is hardly sensitive to θ. PMID:26450679

  2. Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation.

    PubMed

    Ye, Tianyu; Liu, Han-Chun; Wang, Zhuo; Wegscheider, W; Mani, Ramesh G

    2015-01-01

    A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. For circularly polarized radiation, the oscillatory magnetoresistive response is hardly sensitive to θ. PMID:26450679

  3. Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation

    SciTech Connect

    Ye, Tianyu; Liu, Han -Chun; Wang, Zhuo; Wegscheider, W.; Mani, Ramesh G.

    2015-10-09

    A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. As a result, for circularly polarized radiation, the oscillatory magnetoresistive response is hardly sensitive to θ.

  4. Fetal radiation exposure induces testicular cancer in genetically susceptible mice.

    PubMed

    Shetty, Gunapala; Comish, Paul B; Weng, Connie C Y; Matin, Angabin; Meistrich, Marvin L

    2012-01-01

    The prevalence of testicular germ cell tumors (TGCT), a common solid tissue malignancy in young men, has been annually increasing at an alarming rate of 3%. Since the majority of testicular cancers are derived from germ cells at the stage of transformation of primordial germ cell (PGC) into gonocytes, the increase has been attributed to maternal/fetal exposures to environmental factors. We examined the effects of an estrogen (diethylstilbestrol, DES), an antiandrogen (flutamide), or radiation on the incidence of testicular germ cell tumors in genetically predisposed 129.MOLF-L1 (L1) congenic mice by exposing them to these agents on days 10.5 and 11.5 of pregnancy. Neither flutamide nor DES produced noticeable increases in testis cancer incidence at 4 weeks of age. In contrast, two doses of 0.8-Gy radiation increased the incidence of TGCT from 45% to 100% in the offspring. The percentage of mice with bilateral tumors, weights of testes with TGCT, and the percentage of tumors that were clearly teratomas were higher in the irradiated mice than in controls, indicating that irradiation induced more aggressive tumors and/or more foci of initiation sites in each testis. This radiation dose did not disrupt spermatogenesis, which was qualitatively normal in tumor-free testes although they were reduced in size. This is the first proof of induction of testicular cancer by an environmental agent and suggests that the male fetus of women exposed to radiation at about 5-6 weeks of pregnancy might have an increased risk of developing testicular cancer. Furthermore, it provides a novel tool for studying the molecular and cellular events of testicular cancer pathogenesis. PMID:22348147

  5. Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice

    PubMed Central

    Shetty, Gunapala; Comish, Paul B.; Weng, Connie C. Y.; Matin, Angabin; Meistrich, Marvin L.

    2012-01-01

    The prevalence of testicular germ cell tumors (TGCT), a common solid tissue malignancy in young men, has been annually increasing at an alarming rate of 3%. Since the majority of testicular cancers are derived from germ cells at the stage of transformation of primordial germ cell (PGC) into gonocytes, the increase has been attributed to maternal/fetal exposures to environmental factors. We examined the effects of an estrogen (diethylstilbestrol, DES), an antiandrogen (flutamide), or radiation on the incidence of testicular germ cell tumors in genetically predisposed 129.MOLF-L1 (L1) congenic mice by exposing them to these agents on days 10.5 and 11.5 of pregnancy. Neither flutamide nor DES produced noticeable increases in testis cancer incidence at 4 weeks of age. In contrast, two doses of 0.8-Gy radiation increased the incidence of TGCT from 45% to 100% in the offspring. The percentage of mice with bilateral tumors, weights of testes with TGCT, and the percentage of tumors that were clearly teratomas were higher in the irradiated mice than in controls, indicating that irradiation induced more aggressive tumors and/or more foci of initiation sites in each testis. This radiation dose did not disrupt spermatogenesis, which was qualitatively normal in tumor-free testes although they were reduced in size. This is the first proof of induction of testicular cancer by an environmental agent and suggests that the male fetus of women exposed to radiation at about 5–6 weeks of pregnancy might have an increased risk of developing testicular cancer. Furthermore, it provides a novel tool for studying the molecular and cellular events of testicular cancer pathogenesis. PMID:22348147

  6. Dosimetric Analysis of Radiation-induced Gastric Bleeding

    SciTech Connect

    Feng, Mary; Normolle, Daniel; Pan, Charlie C.; Dawson, Laura A.; Amarnath, Sudha; Ensminger, William D.; Lawrence, Theodore S.; Ten Haken, Randall K.

    2012-09-01

    Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of {>=}grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD{sub 50} (normal) = 56 Gy and TD{sub 50} (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD{sub 50} value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

  7. Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy.

    PubMed

    Mah, K; Van Dyk, J; Keane, T; Poon, P Y

    1987-02-01

    Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage. PMID:3818385

  8. Chemoprevention of ultraviolet radiation-induced skin cancer.

    PubMed

    Ley, R D; Reeve, V E

    1997-06-01

    The use of chemical and physical sunscreening agents has increased dramatically during the last two to three decades as an effective means of preventing sunbum. The use of high sunprotection factor sunscreens has also been widely promoted for the prevention of skin cancer, including melanoma. Whereas sunscreens are undoubtedly effective in preventing sunbum, their efficacy in preventing skin cancer, especially melanoma, is currently under considerable debate. Sunscreens have been shown to prevent the induction of DNA damage that presumably results from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has been identified as an initiator of skin cancer formation. However, both laboratory and epidemiological studies indicate that sunscreens may not block the initiation or promotion of melanoma formation. These studies suggest that the action spectrum for erythema induction is different than the action spectrum for the induction of melanoma. Indeed, recent reports on the wavelength dependency for the induction of melanoma in a fish model indicate that the efficacy of ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude higher than would be predicted from the induction of erythema in man or nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin cancer have also been reported. Low levels and degree of unsaturation of dietary fats protect against UVR-induced skin cancer in mice humens. Compounds with antioxidant activity, including green tea extracts (polyphenols), have been reported to inhibit UVR-induced skin carcinogenesis. PMID:9255591

  9. Role of Ultraviolet Radiation in Papillomavirus-Induced Disease.

    PubMed

    Uberoi, Aayushi; Yoshida, Satoshi; Frazer, Ian H; Pitot, Henry C; Lambert, Paul F

    2016-05-01

    Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1) that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR), specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans. PMID:27244228

  10. Role of Ultraviolet Radiation in Papillomavirus-Induced Disease

    PubMed Central

    Uberoi, Aayushi; Yoshida, Satoshi; Frazer, Ian H.; Pitot, Henry C.; Lambert, Paul F.

    2016-01-01

    Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1) that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR), specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans. PMID:27244228

  11. Chemoprevention of ultraviolet radiation-induced skin cancer.

    PubMed Central

    Ley, R D; Reeve, V E

    1997-01-01

    The use of chemical and physical sunscreening agents has increased dramatically during the last two to three decades as an effective means of preventing sunbum. The use of high sunprotection factor sunscreens has also been widely promoted for the prevention of skin cancer, including melanoma. Whereas sunscreens are undoubtedly effective in preventing sunbum, their efficacy in preventing skin cancer, especially melanoma, is currently under considerable debate. Sunscreens have been shown to prevent the induction of DNA damage that presumably results from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has been identified as an initiator of skin cancer formation. However, both laboratory and epidemiological studies indicate that sunscreens may not block the initiation or promotion of melanoma formation. These studies suggest that the action spectrum for erythema induction is different than the action spectrum for the induction of melanoma. Indeed, recent reports on the wavelength dependency for the induction of melanoma in a fish model indicate that the efficacy of ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude higher than would be predicted from the induction of erythema in man or nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin cancer have also been reported. Low levels and degree of unsaturation of dietary fats protect against UVR-induced skin cancer in mice humens. Compounds with antioxidant activity, including green tea extracts (polyphenols), have been reported to inhibit UVR-induced skin carcinogenesis. PMID:9255591

  12. Single-Dose Radiation-Induced Oral Mucositis Mouse Model

    PubMed Central

    Maria, Osama Muhammad; Syme, Alasdair; Eliopoulos, Nicoletta; Muanza, Thierry

    2016-01-01

    The generation of a self-resolved radiation-induced oral mucositis (RIOM) mouse model using the highest possibly tolerable single ionizing radiation (RT) dose was needed in order to study RIOM management solutions. We used 10-week-old male BALB/c mice with average weight of 23 g for model production. Mice were treated with an orthovoltage X-ray irradiator to induce the RIOM ulceration at the intermolar eminence of the animal tongue. General anesthesia was injected intraperitoneally for proper animal immobilization during the procedure. Ten days after irradiation, a single RT dose of 10, 15, 18, 20, and 25 Gy generated a RIOM ulcer at the intermolar eminence (posterior upper tongue surface) with mean ulcer floor (posterior epithelium) heights of 190, 150, 25, 10, and 10 μm, respectively, compared to 200 μm in non-irradiated animals. The mean RIOM ulcer size % of the total epithelialized upper surface of the animal tongue was RT dose dependent. At day 10, the ulcer size % was 2, 5, 27, and 31% for 15, 18, 20, and 25 Gy RT, respectively. The mean relative surface area of the total epithelialized upper surface of the tongue was RT dose dependent, since it was significantly decreased to 97, 95, 88, and 38% with 15, 18, 20, and 25 Gy doses, respectively, at day 10 after RT. Subcutaneous injection of 1 mL of 0.9% saline/6 h for 24 h yielded a 100% survival only with 18 Gy self-resolved RIOM, which had 5.6 ± 0.3 days ulcer duration. In conclusion, we have generated a 100% survival self-resolved single-dose RIOM male mouse model with long enough duration for application in RIOM management research. Oral mucositis ulceration was radiation dose dependent. Sufficient hydration of animals after radiation exposure significantly improved their survival. PMID:27446800

  13. Motion-induced radiation from electrons moving in Maxwell's fish-eye.

    PubMed

    Liu, Yangjie; Ang, L K

    2013-01-01

    In Čerenkov radiation and transition radiation, evanescent wave from motion of charged particles transfers into radiation coherently. However, such dissipative motion-induced radiations require particles to move faster than light in medium or to encounter velocity transition to pump energy. Inspired by a method to detect cloak by observing radiation of a fast-moving electron bunch going through it by Zhang et al., we study the generation of electron-induced radiation from electrons' interaction with Maxwell's fish-eye sphere. Our calculation shows that the radiation is due to a combination of Čerenkov radiation and transition radiation, which may pave the way to investigate new schemes of transferring evanescent wave to radiation. PMID:24166002

  14. Motion-induced radiation from electrons moving in Maxwell's fish-eye

    PubMed Central

    Liu, Yangjie; Ang, L. K.

    2013-01-01

    In Čerenkov radiation and transition radiation, evanescent wave from motion of charged particles transfers into radiation coherently. However, such dissipative motion-induced radiations require particles to move faster than light in medium or to encounter velocity transition to pump energy. Inspired by a method to detect cloak by observing radiation of a fast-moving electron bunch going through it by Zhang et al., we study the generation of electron-induced radiation from electrons' interaction with Maxwell's fish-eye sphere. Our calculation shows that the radiation is due to a combination of Čerenkov radiation and transition radiation, which may pave the way to investigate new schemes of transferring evanescent wave to radiation. PMID:24166002

  15. Measurements of prompt radiation induced conductivity of alumina and sapphire.

    SciTech Connect

    Hartman, E. Frederick; Zarick, Thomas Andrew; Sheridan, Timothy J.; Preston, Eric F.

    2011-04-01

    We performed measurements of the prompt radiation induced conductivity in thin samples of Alumina and Sapphire at the Little Mountain Medusa LINAC facility in Ogden, UT. Five mil thick samples were irradiated with pulses of 20 MeV electrons, yielding dose rates of 1E7 to 1E9 rad/s. We applied variable potentials up to 1 kV across the samples and measured the prompt conduction current. Analysis rendered prompt conductivity coefficients between 1E10 and 1E9 mho/m/(rad/s), depending on the dose rate and the pulse width for Alumina and 1E7 to 6E7 mho/m/(rad/s) for Sapphire.

  16. Radiation induces turbulence in particle-laden fluids

    SciTech Connect

    Zamansky, Rémi; Coletti, Filippo; Massot, Marc; Mani, Ali

    2014-07-15

    When a transparent fluid laden with solid particles is subject to radiative heating, non-uniformities in particle distribution result in local fluid temperature fluctuations. Under the influence of gravity, buoyancy induces vortical fluid motion which can lead to strong preferential concentration, enhancing the local heating and more non-uniformities in particle distribution. By employing direct numerical simulations this study shows that the described feedback loop can create and sustain turbulence. The velocity and length scale of the resulting turbulence is not known a priori, and is set by balance between viscous forces and buoyancy effects. When the particle response time is comparable to a viscous time scale, introduced in our analysis, the system exhibits intense fluctuations of turbulent kinetic energy and strong preferential concentration of particles.

  17. Radiation pressure induced difference-sideband generation beyond linearized description

    NASA Astrophysics Data System (ADS)

    Xiong, Hao; Fan, Yu-Wan; Yang, Xiaoxue; Wu, Ying

    2016-08-01

    We investigate radiation-pressure induced generation of the frequency components at the difference-sideband in an optomechanical system, which beyond the conventional linearized description of optomechanical interactions between cavity fields and the mechanical oscillation. We analytically calculate amplitudes of these signals, and identify a simple square-root law for both the upper and lower difference-sideband generation which can describe the dependence of the intensities of these signals on the pump power. Further calculation shows that difference-sideband generation can be greatly enhanced via achieving the matching conditions. The effect of difference-sideband generation, which may have potential application for manipulation of light, is especially suited for on-chip optomechanical devices, where nonlinear optomechanical interaction in the weak coupling regime is within current experimental reach.

  18. Radiation-induced effects and the immune system in cancer

    PubMed Central

    Kaur, Punit; Asea, Alexzander

    2012-01-01

    Chemotherapy and radiation therapy (RT) are standard therapeutic modalities for patients with cancers, and could induce various tumor cell death modalities, releasing tumor-derived antigens as well as danger signals that could either be captured for triggering anti-tumor immune response. Historic studies examining tissue and cellular responses to RT have predominantly focused on damage caused to proliferating malignant cells leading to their death. However, there is increasing evidence that RT also leads to significant alterations in the tumor microenvironment, particularly with respect to effects on immune cells and infiltrating tumors. This review will focus on immunologic consequences of RT and discuss the therapeutic reprogramming of immune responses in tumors and how it regulates efficacy and durability to RT. PMID:23251903

  19. Calculation of radiation-induced creep and stress relaxation

    NASA Astrophysics Data System (ADS)

    Nagakawa, Johsei

    1995-08-01

    Numerical calculation based on a computer simulation of point defect kinetics under stress was performed to predict radiation-induced deformation in an Inconel X-750 bolt in a LWR core and for a 316 stainless steel blanket in experimental fusion reactors with the water-coolant scenario. Although the displacement rate is rather low, modest irradiation creep with nearly linear stress dependence was predicted below 200 MPa at 300°C in the LWR core. This low stress dependence causes significant stress relaxation, which coincides with the experimental data to 2 dpa. An almost equal amount of enhanced irradiation creep strain was predicted at 60°C in both solution annealed and cold worker 316 stainless steel in the water-cooled blanket. The stress relaxation is practically not expected without irradiation in both the cases, but the calculation predicts that it is definitely expected under irradiation.

  20. Radiation-induced polymerization for the immobilization of penicillin acylase

    SciTech Connect

    Boccu, E.; Carenza, M.; Lora, S.; Palma, G.; Veronese, F.M.

    1987-06-01

    The immobilization of Escherichia coli penicillin acylase was investigated by radiation-induced polymerization of 2-hydroxyethyl methacrylate at low temperature. A leak-proof composite that does not swell in water was obtained by adding the cross-linking agent trimethylolpropane trimethacrylate to the monomer-aqueous enzyme mixture. Penicillin acylase, which was immobilized with greater than 70% yield, possessed a higher Km value toward the substrate 6-nitro-3-phenylacetamidobenzoic acid than the free enzyme form (Km = 1.7 X 10(-5) and 1 X 10(-5) M, respectively). The structural stability of immobilized penicillin acylase, as assessed by heat, guanidinium chloride, and pH denaturation profiles, was very similar to that of the free-enzyme form, thus suggesting that penicillin acylase was entrapped in its native state into aqueous free spaces of the polymer matrix.

  1. Characterization of gamma radiation inducible thioredoxin h from Spirogyra varians.

    PubMed

    Yoon, Minchul; Yang, Ho-Yeon; Lee, Seung-Sik; Kim, Dong-Ho; Kim, Gwang-Hoon; Choi, Jong-il

    2013-08-15

    In this study, thioredoxin h (Trxh) was isolated and characterized from the fresh water green alga Spirogyra varians, which was one amongst the pool of proteins induced upon gamma radiation treatment. cDNA clones encoding S. varians thioredoxin h were isolated from a pre-constructed S. varians cDNA library. Trxh had a molecular mass of 13.5kDa and contained the canonical WCGPC active site. Recombinant Trxh showed the disulfide reduction activity, and exhibited insulin reduction activity. Also, Trxh had higher 5,5'-dithiobis(2-nitrobenzoic acid) reduction activity with Arabidopsis thioredoxin reductase (TR) than with Escherichia coli TR. Specific expression of the Trxh gene was further analyzed at mRNA and protein levels and was found to increase by gamma irradiation upto the absorbed dose of 3kGy, suggesting that Trxh may have potential functions in protection of biomolecules from gamma irradiation. PMID:23830452

  2. Radiation-induced degradation of 4-chloroaniline in aqueous solution

    NASA Astrophysics Data System (ADS)

    Sánchez, M.; Wolfger, H.; Getoff, N.

    2002-12-01

    The radiation-induced decomposition of 4-chloroaniline (4-ClA) was studied under steady-state conditions using aqueous solutions saturated with air, pure oxygen, N 2O, argon and argon in the presence of t-Butanol. Using HPLC-method, the initial G-values of the substrate degradation as well as of a number of radiolytic products were determined. The formation of aminophenols, chlorophenols, aniline and phenol in addition to chloride, ammonia, formaldehyde and mixture of aldehydes as well as carboxylic acids was studied as a function of absorbed dose. Based on the experimental data, probable reaction mechanisms for the degradation of 4-ClA by γ-rays and the formation of the identified products are presented.

  3. Research on radiation-induced color change of white topaz

    NASA Astrophysics Data System (ADS)

    Ying, Wang; yong-bao, Gu

    2002-03-01

    In the present study, a method of producing sky blue topaz is studied. A 3-5 MeV scanning electron beam linear accelerator (which is currently used for processing semiconductor devices) was employed to change the color of white topaz under room-temperature conditions, together with a cooling device. A radiation-induced ion color center is formed in white topaz by an electron beam. To finish the irradiation, the total dose needs to be more than 5×10 7-1×10 8 Gy, the temperature of heat-treatment was between 180°C and 280°C in air conditions, after a while, a sky blue topaz was obtained. There was a bright color and no radioactivity was formed in the sky blue topaz by this production method.

  4. Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

    PubMed Central

    Shao, Lijian; Luo, Yi

    2014-01-01

    Abstract Significance: Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Recent Advances: Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Critical Issues: Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. Future Directions: In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression. Antioxid. Redox Signal. 20, 1447–1462. PMID:24124731

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

    PubMed Central

    Lang, J.E.; Zhu, W.; Nokes, B.T.; Sheth, G.R.; Novak, P.; Fuchs, L.; Watts, G.S.; Futscher, B.W.; Mineyev, N.; Ring, A.; LeBeau, L.; Nagle, R.; Cranmer, L.D.

    2014-01-01

    Background Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. Methods We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. Results Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. Conclusion Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS. Synopsis We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a radiation-induced sarcoma (RIS). Our novel RIS cell line constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. PMID:25644184

  6. Radiation-induced leukemia: Comparative studies in mouse and man

    SciTech Connect

    Haas, M.

    1991-01-01

    We now have a clear understanding of the mechanism by which radiation-induced (T-cell) leukemia occurs. In irradiated mice (radiation-induced thymic leukemia) and in man (acute lymphoblastic T-cell leukemia, T-ALL) the mechanism of leukemogenesis is surprisingly similar. Expressed in the most elementary terms, T-cell leukemia occurs when T-cell differentiation is inhibited by a mutation, and pre-T cells attempt but fail to differentiate in the thymus. Instead of leaving the thymus for the periphery as functional T-cells they continue to proliferate in the thymus. The proliferating pre- (pro-) T-cells constitute the (early) acute T-cell leukemia (A-TCL). This model for the mechanism of T-cell leukemogenesis accounts for all the properties of both murine and human A-TCL. Important support for the model has recently come from work by Ilan Kirsch and others, who have shown that mutations/deletions in the genes SCL (TAL), SIL, and LCK constitute primary events in the development of T-ALL, by inhibiting differentiation of thymic pre- (pro-) T-cells. This mechanism of T-cell leukemogenesis brings several specific questions into focus: How do early A-TCL cells progress to become potently tumorigenic and poorly treatable Is it feasible to genetically suppress early and/or progressed A-TCL cells What is the mechanism by which the differentiation-inhibited (leukemic) pre-T cells proliferate During the first grant year we have worked on aspects of all three questions.

  7. Bystander effects in radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Morgan, William F.; Hartmann, Andreas; Limoli, Charles L.; Nagar, Shruti; Ponnaiya, Brian

    2002-01-01

    Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.

  8. Radiation-induced tumors in transplanted ovaries. [Mice

    SciTech Connect

    Covelli, V.; Di Majo, V.; Bassani, B.; Metalli, P.; Silini, G.

    1982-04-01

    A comparison was made of tumor induction in the ovaries of whole-body-irradiation mice (250-kV X rays, doses of 0.25-4.00 Gy) or in ovaries irradiated in vivo and then transplanted intramuscularly into castrated syngeneic hosts. The form of the dose-induction relationships was similar in the two cases, showing a steeply rising branch at doses up to 0.75 Gy followed by a maximum and an elevated plateau up to 4.00 Gy. A higher incidence of tumors in transplanted organs was apparent for doses up to the maximum, which was attributed to castration-induced hormonal imbalance. Specific death rate analysis of mice dying with ovarian tumors showed that in this system radiation acts essentially by decreasing tumor latency. Ovarian tumors were classified in various histological types and their development in time was followed by serial sacrifice. Separate analysis of death rate of animals carrying different tumor classes allowed further resolution of the various components of the tumor induction phenomenon. It was thus possible to show that the overall death rate analysis masks a true effect of induction of granulosa cell tumors in whole-body-irradiation animals. The transplantation technique offers little advantage for the study of radiation induction of ovarian tumor.

  9. Heterogeneous shock-induced thermal radiation in minerals

    NASA Technical Reports Server (NTRS)

    Kondo, K.-I.; Ahrens, T. J.

    1983-01-01

    A 500-channel optical imaging intensifying and spectral digital recording system is used for recording the shock-induced radiation emitted from 406 to 821 nm from transparent minerals during the time interval that a shock wave propagates through the sample. The initial results obtained for single crystals of gypsum, calcite and halite in the 30 to 40 GPa (300 to 400 kbar) pressure range reveal grey-body emission spectra corresponding to temperatures in the 3000 to 4000 K range and emissivities ranging from 0.003 to 0.02. With gypsum and calcite, distinctive line spectra are superimposed on the thermal radiation. The observed color temperatures are greater than the Hugoniot temperature by a factor of 2 to 10; this is calculable on the basis of continuum thermodynamics and equation of state models for the shock states achieved in the three minerals. These observed high temperatures are thought to be real. It is concluded that a large number of closed spaced high temperature shear-band regions are being detected immediately behind the shock front.

  10. Radiation induced effects on mechanical properties of nanoporous gold foams

    SciTech Connect

    Caro, M. E-mail: efu@pku.edu.cn; Fu, E. G. E-mail: efu@pku.edu.cn; Wang, Y. Q.; Martinez, E.; Caro, A.; Mook, W. M.; Sheehan, C.; Baldwin, J. K.

    2014-06-09

    It has recently been shown that due to a high surface-to-volume ratio, nanoporous materials display radiation tolerance. The abundance of surfaces, which are perfect sinks for defects, and the relation between ligament size, defect diffusion, and time combine to define a window of radiation resistance [Fu et al., Appl. Phys. Lett. 101, 191607 (2012)]. Outside this window, the dominant defect created by irradiation in Au nanofoams are stacking fault tetrahedra (SFT). Molecular dynamics computer simulations of nanopillars, taken as the elemental constituent of foams, predict that SFTs act as dislocation sources inducing softening, in contrast to the usual behavior in bulk materials, where defects are obstacles to dislocation motion, producing hardening. In this work we test that prediction and answer the question whether irradiation actually hardens or softens a nanofam. Ne ion irradiations of gold nanofoams were performed at room temperature for a total dose up to 4 dpa, and their mechanical behavior was measured by nanoindentation. We find that hardness increases after irradiation, a result that we analyze in terms of the role of SFTs on the deformation mode of foams.

  11. Radiation induced effects on mechanical properties of nanoporous gold foams

    NASA Astrophysics Data System (ADS)

    Caro, M.; Mook, W. M.; Fu, E. G.; Wang, Y. Q.; Sheehan, C.; Martinez, E.; Baldwin, J. K.; Caro, A.

    2014-06-01

    It has recently been shown that due to a high surface-to-volume ratio, nanoporous materials display radiation tolerance. The abundance of surfaces, which are perfect sinks for defects, and the relation between ligament size, defect diffusion, and time combine to define a window of radiation resistance [Fu et al., Appl. Phys. Lett. 101, 191607 (2012)]. Outside this window, the dominant defect created by irradiation in Au nanofoams are stacking fault tetrahedra (SFT). Molecular dynamics computer simulations of nanopillars, taken as the elemental constituent of foams, predict that SFTs act as dislocation sources inducing softening, in contrast to the usual behavior in bulk materials, where defects are obstacles to dislocation motion, producing hardening. In this work we test that prediction and answer the question whether irradiation actually hardens or softens a nanofam. Ne ion irradiations of gold nanofoams were performed at room temperature for a total dose up to 4 dpa, and their mechanical behavior was measured by nanoindentation. We find that hardness increases after irradiation, a result that we analyze in terms of the role of SFTs on the deformation mode of foams.

  12. Radiation-induced tumor neoantigens: imaging and therapeutic implications

    PubMed Central

    Corso, Christopher D; Ali, Arif N; Diaz, Roberto

    2011-01-01

    Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular changes. One way that IR can affect tumor cells is through the development of neoantigens which are new molecules that tumor cells express at the cell membrane following some insult or change to the cell. There have been numerous reports in the literature of changes in both tumor and tumor vasculature cell surface molecule expression following treatment with IR. The usefulness of neoantigens for imaging and therapeutic applications lies in the fact that they are differentially expressed on the surface of irradiated tumor cells to a greater extent than on normal tissues. This differential expression provides a mechanism by which tumor cells can be “marked” by radiation for further targeting. Drug delivery vehicles or imaging agents conjugated to ligands that recognize and interact with the neoantigens can help to improve tumor-specific targeting and reduce systemic toxicity with cancer drugs. This article provides a review of the molecules that have been reported to be expressed on the surface of tumor cells in response to IR either in vivo or in vitro. Additionally, we provide a discussion of some of the methods used in the identification of these antigens and applications for their use in drug delivery and imaging. PMID:21969260

  13. Radiation-induced sarcomas of the head and neck

    PubMed Central

    Thiagarajan, Anuradha; Iyer, N Gopalakrishna

    2014-01-01

    With improved outcomes associated with radiotherapy, radiation-induced sarcomas (RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stage-matched sarcomas that arise independent of irradiation and surgical resection with clear margins seems to offer the best chance for cure. PMID:25493233

  14. Are Epigenetic Mechanisms Involved in Radiation-Induced Bystander Effects?

    PubMed Central

    Mothersill, Carmel; Seymour, Colin

    2012-01-01

    The “non-targeted effects” of ionizing radiation including bystander effects and genomic instability are unique in that no classic mutagenic event occurs in the cell showing the effect. In the case of bystander effects, cells which were not in the field affected by the radiation show high levels of mutations, chromosome aberrations, and membrane signaling changes leading to what is termed “horizontal transmission” of mutations and information which may be damaging while in the case of genomic instability, generations of cells derived from an irradiated progenitor appear normal but then lethal and non-lethal mutations appear in distant progeny. This is known as “vertical transmission.” In both situations high yields of non-clonal mutations leading to distant occurrence of mutation events both in space and time. This precludes a mutator phenotype or other conventional explanation and appears to indicate a generalized form of stress-induced mutagenesis which is well documented in bacteria. This review will discuss the phenomenology of what we term “non-targeted effects,” and will consider to what extent they challenge conventional ideas in genetics and epigenetics. PMID:22629281

  15. Radiation-induced radioresistance of mammals and risk assessment

    NASA Astrophysics Data System (ADS)

    Smirnova, O.; Yonezawa, M.

    It is shown experimentally that a preliminary low dose exposure can induce radioresistance in mice in two (early and late) periods after preirradiation. The manifestation of such effects is reduced mortality of pre-exposed specimens after challenge acute irradiation, the reason of the animal death being the hematopoietic subsyndrome of the acute radiation syndrome. Therefore, proceeding from the radiobiological concept of the critical system, the theoretical investigation of the influence of preirradiation on mammalian radiosensitivity is conducted by making use of mathematical models of the vital body system, hematopoiesis. Modeling results make it possible to elucidate the mechanisms of the radioprotection effect of low level priming irradiation on mammals. Specifically, the state of acquired radioresistance in mice is caused by reduced radiosensitivity of lymphopoietic and thrombocytopoietic systems in the early period and by reduced radiosensitivity of granulocytopoietic system in the late period after preirradiation. It is important to emphasize that the evaluations of the duration of the early and late periods of postirradiation radioresistance in mice, carried out on the basis of the modeling and experimental investigations, practically coincide. All this demonstrates the effectiveness of joint modeling and experimental methods in studies and predictions of modification effects of preirradiation on mammalian radiosensitivity. The results obtained show the importance of accounting such effects in radiation risk assessments for cosmonauts and astronauts on long-term missions.

  16. Radiation-induced sarcomas of the chest wall

    SciTech Connect

    Souba, W.W.; McKenna, R.J. Jr.; Meis, J.; Benjamin, R.; Raymond, A.K.; Mountain, C.F.

    1986-02-01

    Sixteen patients are presented who had sarcomas of the chest wall at a site where a prior malignancy had been irradiated. The first malignancies included breast cancer (ten cases), Hodgkin's disease (four cases), and others (two cases). Radiation doses varied from 4200 to 5500 R (mean, 4900 R). The latency period ranged from 5 to 28 years (mean, 13 years). The histologic types of the radiation-induced sarcomas were as follows: malignant fibrous histiocytoma, nine cases; osteosarcoma, six cases; and malignant mesenchymoma, one case. The only long-term survivor is alive and well 12 years after resection of a clavicular chondroblastic osteosarcoma. Three cases were recently diagnosed. Despite aggressive multimodality treatment, the remaining 13 patients have all died from their sarcomas (mean survival, 13.5 months). All patients have apparently been cured of their first malignancies. Chemotherapy was ineffective. No treatment, including forequarter amputation, appeared to palliate the patients with supraclavicular soft tissue sarcomas. Major chest wall resection offered good palliation for seven of eight patients with sarcomas arising in the sternum or lateral chest wall. Close follow-up is needed to detect signs of these sarcomas in the ever-increasing number of patients receiving therapeutic irradiation.

  17. Chromatin Structure and Radiation-Induced Intrachromosome Exchange

    NASA Technical Reports Server (NTRS)

    Mangala; Zhang, Ye; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    We have recently investigated the location of breaks involved in intrachromosomal type exchange events, using the multicolor banding in situ hybridization (mBAND) technique for human chromosome 3. In human epithelial cells exposed to both low- and high-LET radiations in vitro, intrachromosome exchanges were found to occur preferentially between a break in the 3p21 and one in the 3q11. Exchanges were also observed between a break in 3p21 and one in 3q26, but few exchanges were observed between breaks in 3q11 and 3q26, even though the two regions were on the same arm of the chromosome. To explore the relationships between intrachromosome exchanges and chromatin structure, we used probes that hybridize the three regions of 3p21, 3q11 and 3q26, and measured the distance between two of the three regions in interphase cells. We further analyzed fragile sites on the chromosome that have been identified in various types of cancers. Our results demonstrated that the distribution of breaks involved in radiation-induced intrachromosome aberrations depends upon both the location of fragile sites and the folding of chromatins

  18. Radiation-induced chromosomal instability in human mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Grossi, G. F.; Yang, T. C.

    1996-01-01

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  19. Radiation-induced chromosomal instability in human mammary epithelial cells

    NASA Astrophysics Data System (ADS)

    Durante, M.; Grossi, G. F.; Yang, T. C.

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

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

    SciTech Connect

    Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won; Oh, Sang Ho; Lee, Yun-Sil; Lee, Eun-Jung; Cho, Jaeho

    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.

  1. RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

    SciTech Connect

    Rousseau, Matthieu; Gaugler, Marie-Helene; Rodallec, Audrey; Bonnaud, Stephanie; Paris, Francois; Corre, Isabelle

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer We explore the role of RhoA in endothelial cell response to ionizing radiation. Black-Right-Pointing-Pointer RhoA is rapidly activated by single high-dose of radiation. Black-Right-Pointing-Pointer Radiation leads to RhoA/ROCK-dependent actin cytoskeleton remodeling. Black-Right-Pointing-Pointer Radiation-induced apoptosis does not require the RhoA/ROCK pathway. Black-Right-Pointing-Pointer Radiation-induced alteration of endothelial adhesion and migration requires RhoA/ROCK. -- Abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial

  2. Hyperbaric Oxygen Therapy for Radiation-Induced Cystitis and Proctitis

    SciTech Connect

    Oliai, Caspian; Fisher, Brandon; Jani, Ashish; Wong, Michael; Poli, Jaganmohan; Brady, Luther W.; Komarnicky, Lydia T.

    2012-11-01

    Purpose: To provide a retrospective analysis of the efficacy of hyperbaric oxygen therapy (HBOT) for treating hemorrhagic cystitis (HC) and proctitis secondary to pelvic- and prostate-only radiotherapy. Methods and Materials: Nineteen patients were treated with HBOT for radiation-induced HC and proctitis. The median age at treatment was 66 years (range, 15-84 years). The range of external-beam radiation delivered was 50.0-75.6 Gy. Bleeding must have been refractory to other therapies. Patients received 100% oxygen at 2.0 atmospheres absolute pressure for 90-120 min per treatment in a monoplace chamber. Symptoms were retrospectively scored according to the Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) scale to evaluate short-term efficacy. Recurrence of hematuria/hematochezia was used to assess long-term efficacy. Results: Four of the 19 patients were lost to follow-up. Fifteen patients were evaluated and received a mean of 29.8 dives: 11 developed HC and 4 proctitis. All patients experienced a reduction in their LENT-SOMA score. After completion of HBOT, the mean LENT-SOMA score was reduced from 0.78 to 0.20 in patients with HC and from 0.66 to 0.26 in patients with proctitis. Median follow-up was 39 months (range, 7-70 months). No cases of hematuria were refractory to HBOT. Complete resolution of hematuria was seen in 81% (n = 9) and partial response in 18% (n = 2). Recurrence of hematuria occurred in 36% (n = 4) after a median of 10 months. Complete resolution of hematochezia was seen in 50% (n = 2), partial response in 25% (n = 1), and refractory bleeding in 25% (n = 1). Conclusions: Hyperbaric oxygen therapy is appropriate for radiation-induced HC once less time-consuming therapies have failed to resolve the bleeding. In these conditions, HBOT is efficacious in the short and long term, with minimal side effects.

  3. Radiation-induced osteosarcomas in the pediatric population

    SciTech Connect

    Koshy, Matthew; Paulino, Arnold C. . E-mail: apaulino@tmh.tmc.edu; Mai, Wei Y.; Teh, Bin S.

    2005-11-15

    Purpose: Radiation-induced osteosarcomas (R-OS) have historically been high-grade, locally invasive tumors with a poor prognosis. The purpose of this study was to perform a comprehensive literature review and analysis of reported cases dealing with R-OS in the pediatric population to identify the characteristics, prognostic factors, optimal treatment modalities, and overall survival of these patients. Methods and Materials: A MEDLINE/PubMed search of articles written in the English language dealing with OSs occurring after radiotherapy (RT) in the pediatric population yielded 30 studies from 1981 to 2004. Eligibility criteria included patients <21 years of age at the diagnosis of the primary cancer, cases satisfying the modified Cahan criteria, and information on treatment outcome. Factors analyzed included the type of primary cancer treated with RT, the radiation dose and beam energy, the latency period between RT and the development of R-OS, and the treatment, follow-up, and final outcome of R-OS. Results: The series included 109 patients with a median age at the diagnosis of primary cancer of 6 years (range, 0.08-21 years). The most common tumors treated with RT were Ewing's sarcoma (23.9%), rhabdomyosarcoma (17.4%), retinoblastoma (12.8%), Hodgkin's disease (9.2%), brain tumor (8.3%), and Wilms' tumor (6.4%). The median radiation dose was 47 Gy (range, 15-145 Gy). The median latency period from RT to the development of R-OS was 100 months (range, 36-636 months). The median follow-up after diagnosis of R-OS was 18 months (1-172 months). The 3- and 5-year cause-specific survival rate was 43.6% and 42.2%, respectively, and the 3- and 5-year overall survival rate was 41.7% and 40.2%, respectively. Variables, including age at RT, primary site, type of tumor treated with RT, total radiation dose, and latency period did not have a significant effect on survival. The 5-year cause-specific and overall survival rate for patients who received treatment for R-OS involving

  4. Mechanisms of Caffeine-Induced Inhibition of UVB Carcinogenesis.

    PubMed

    Conney, Allan H; Lu, Yao-Ping; Lou, You-Rong; Kawasumi, Masaoki; Nghiem, Paul

    2013-01-01

    Sunlight-induced non-melanoma skin cancer is the most prevalent cancer in the United States with more than two million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on non-melanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect. Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345) and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine) inhibits UVB-induced carcinogenesis support the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine's inhibitory effect on UVB-induced carcinogenesis. PMID:23785666

  5. Radiation-induced Vulvar Angiokeratoma Along with Other Late Radiation Toxicities after Carcinoma Cervix: A Rare Case Report

    PubMed Central

    Bhandari, Virendra; Naik, Ayush; Gupta, K L; Kausar, Mehlam

    2016-01-01

    Angiokeratoma including vulvar angiokeratoma is a very rare complication of radiation. Exact incidence is still unknown, we report a case that developed radiation-induced angiokeratoma of skin in the vulvar region along with other late radiation sequelae in the form of bone fracture, new bone formation, bone marrow widening, muscle hypertrophy, and subcutaneous fibrosis, 18 years after radiotherapy to the pelvic region for the treatment of carcinoma cervix. All these late radiation sequel are rare to be seen in a single patient, and none of the case reports could be found in the world literature. PMID:27057045

  6. Industrialization of radiation-induced emulsion polymerization ----technological process and its advantages

    NASA Astrophysics Data System (ADS)

    Zhicheng, Zhang; Manwei, Zhang

    1993-07-01

    A technological process for industrialization of radiation induced emulsion polymerization was introduced briefly. A batch process rather than continuous one was adopted in the industrial-scale production. The advantages of radiation induced emulsion polymerization were described in comparison with chemical initiated process.

  7. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  8. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  9. Effects of subdiaphragmatic vagotomy on the acquisition of a radiation-induced conditioned taste aversion

    SciTech Connect

    Hunt, W.A.; Rabin, B.M.; Lee, J.

    1987-01-01

    The effect of subdiaphragmatic vagotomy on the acquisition of a radiation-induced taste aversion was examined to assess the importance of the vagus nerve in transmitting information on the peripheral toxicity of radiation to the brain. Vagotomy had no effect on taste aversion learning, consistent with reports using other toxins. The data support the involvement of a blood-borne factor in the acquisition of taste aversion induced by ionizing radiation.

  10. Argon plasma coagulation therapy for a hemorrhagic radiation-induced gastritis in patient with pancreatic cancer.

    PubMed

    Shukuwa, Kazutaka; Kume, Keiichiro; Yamasaki, Masahiro; Yoshikawa, Ichiro; Otsuki, Makoto

    2007-01-01

    Radiation-induced gastritis is a serious complication of radiation therapy for pancreatic cancer which is difficult to manage. A 79-year-old man had been diagnosed as having inoperable pancreatic cancer (stage IVa). We encountered this patient with hemorrhagic gastritis induced by external radiotherapy for pancreatic cancer that was well-treated using argon plasma coagulation (APC). After endoscopic treatment using APC, anemia associated with hemorrhagic radiation gastritis improved and required no further blood transfusion. PMID:17603236

  11. Dosimetric Analysis of Radiation-Induced Gastric Bleeding

    PubMed Central

    Feng, Mary; Normolle, Daniel; Pan, Charlie C.; Dawson, Laura A.; Amarnath, Sudha; Ensminger, William D.; Lawrence, Theodore S.; Ten Haken, Randall K.

    2012-01-01

    Purpose Radiation-induced gastric bleeding has been poorly understood. In this study, we describe dosimetric predictors for gastric bleeding after fractionated radiotherapy and compare several predictive models. Materials & Methods The records of 139 sequential patients treated with 3-dimensional conformal radiotherapy (3D-CRT) for intrahepatic malignancies between January 1999 and April 2002 were reviewed. Median follow-up was 7.4 months. Logistic regression and Lyman normal tissue complication probability (NTCP) models for the occurrence of ≥ grade 3 gastric bleed were fit to the data. The principle of maximum likelihood was used to estimate parameters for all models. Results Sixteen of 116 evaluable patients (14%) developed gastric bleeds, at a median time of 4.0 months (mean 6.5 months, range 2.1–28.3 months) following completion of RT. The median and mean of the maximum doses to the stomach were 61 and 63 Gy (range 46 Gy–86 Gy), respectively, after bio-correction to equivalent 2 Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis was most predictive of gastric bleed (AUROC=0.92). Best fit Lyman NTCP model parameters were n =0.10, and m =0.21, with TD50(normal) =56 Gy and TD50(cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD50 value for the cirrhosis patients points out their greater sensitivity. Conclusion This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding, and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation. PMID:22541965

  12. Radiation-Induced Topological Disorder in Irradiated Network Structures

    SciTech Connect

    Hobbs, Linn W.

    2002-12-21

    This report summarizes results of a research program investigating the fundamental principles underlying the phenomenon of topological disordering in a radiation environment. This phenomenon is known popularly as amorphization, but is more formally described as a process of radiation-induced structural arrangement that leads in crystals to loss of long-range translational and orientational correlations and in glasses to analogous alteration of connectivity topologies. The program focus has been on a set compound ceramic solids with directed bonding exhibiting structures that can be described as networks. Such solids include SiO2, Si3N4, SiC, which are of interest to applications in fusion energy production, nuclear waste storage, and device manufacture involving ion implantation or use in radiation fields. The principal investigative tools comprise a combination of experimental diffraction-based techniques, topological modeling, and molecular-dynamics simulations that have proven a rich source of information in the preceding support period. The results from the present support period fall into three task areas. The first comprises enumeration of the rigidity constraints applying to (1) more complex ceramic structures (such as rutile, corundum, spinel and olivine structures) that exhibit multiply polytopic coordination units or multiple modes of connecting such units, (2) elemental solids (such as graphite, silicon and diamond) for which a correct choice of polytope is necessary to achieve correct representation of the constraints, and (3) compounds (such as spinel and silicon carbide) that exhibit chemical disorder on one or several sublattices. With correct identification of the topological constraints, a unique correlation is shown to exist between constraint and amorphizability which demonstrates that amorphization occurs at a critical constraint loss. The second task involves the application of molecular dynamics (MD) methods to topologically-generated models

  13. Role of PECAM-1 in radiation-induced liver inflammation.

    PubMed

    Malik, Ihtzaz Ahmed; Stange, Ina; Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens Friedrich; Ellenrieder, Volker; Wolff, Hendrik Andreas

    2015-10-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-dependent decrease in hepatic PECAM-1, corresponding to an increase in intercellular cell adhesion molecule-1 (ICAM-1) (6 hrs) was detected in WT-mice after irradiation. Immunohistologically, an increased number of neutrophil granulocytes (NG) (but not of mononuclear phagocytes) was observed in the liver of WT and PECAM-1-KO mice at 6 hrs after irradiation. The number of recruited NG was higher and prolonged until 24 hrs in KO compared to WT-mice. Correspondingly, a significant induction of hepatic tumour necrosis factor (TNF)-α and CXC-chemokines (KC/CXCL1 interleukin-8/CXCL8) was detected together with an elevation of serum liver transaminases (6-24 hrs) in WT and KO-mice. Likewise, phosphorylation of signal transducer and activator of transcription-3 (STAT-3) was observed in both animal groups after irradiation. The level of all investigated proteins as well as of the liver transaminases was significantly higher in KO than WT-mice. In the cell-line U937, irradiation led to a reduction in PECAM-1 in parallel to an increased ICAM-1 expression. TNF-α-blockage by anti-TNF-α prevented this change in both proteins in cell culture. Radiation-induced stress conditions induce a transient accumulation of granulocytes within the liver by down-regulation/absence of PECAM-1. It suggests that reduction/lack in PECAM-1 may lead to greater and prolonged inflammation which can be prevented by anti-TNFα. PMID:26177067

  14. Role of PECAM-1 in radiation-induced liver inflammation

    PubMed Central

    Malik, Ihtzaz Ahmed; Stange, Ina; Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens Friedrich; Ellenrieder, Volker; Wolff, Hendrik Andreas

    2015-01-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-dependent decrease in hepatic PECAM-1, corresponding to an increase in intercellular cell adhesion molecule-1 (ICAM-1) (6 hrs) was detected in WT-mice after irradiation. Immunohistologically, an increased number of neutrophil granulocytes (NG) (but not of mononuclear phagocytes) was observed in the liver of WT and PECAM-1-KO mice at 6 hrs after irradiation. The number of recruited NG was higher and prolonged until 24 hrs in KO compared to WT-mice. Correspondingly, a significant induction of hepatic tumour necrosis factor (TNF)-α and CXC-chemokines (KC/CXCL1 interleukin-8/CXCL8) was detected together with an elevation of serum liver transaminases (6–24 hrs) in WT and KO-mice. Likewise, phosphorylation of signal transducer and activator of transcription-3 (STAT-3) was observed in both animal groups after irradiation. The level of all investigated proteins as well as of the liver transaminases was significantly higher in KO than WT-mice. In the cell-line U937, irradiation led to a reduction in PECAM-1 in parallel to an increased ICAM-1 expression. TNF-α-blockage by anti-TNF-α prevented this change in both proteins in cell culture. Radiation-induced stress conditions induce a transient accumulation of granulocytes within the liver by down-regulation/absence of PECAM-1. It suggests that reduction/lack in PECAM-1 may lead to greater and prolonged inflammation which can be prevented by anti-TNFα. PMID:26177067

  15. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

    PubMed Central

    Huang, Yao-Huei; Yang, Pei-Ming; Chuah, Qiu-Yu; Lee, Yi-Jang; Hsieh, Yi-Fen; Peng, Chih-Wen; Chiu, Shu-Jun

    2014-01-01

    Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects. PMID:24813621

  16. PUMA promotes Bax translocation in FOXO3a-dependent pathway during STS-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Zhang, Yingjie; Chen, Qun

    2009-08-01

    PUMA (p53 up-regulated modulator of apoptosis, also called Bbc3) was first identified as a BH3-only Bcl-2 family protein that is transcriptionally up-regulated by p53 and activated upon p53-dependent apoptotic stimuli, such as treatment with DNA-damaging drugs or UV irradiation. Recently studies have been shown that Puma is also up-regulated in response to certain p53-independent apoptotic stimuli, such as growth factor deprivation or treatment with glucocorticoids or STS (staurosporine). However, the molecular mechanisms of PUMA up-regulation and how PUMA functions in response to p53-independent apoptotic stimuli remain poorly understood. In this study, based on real-time single cell analysis, flow cytometry and western blotting technique, we investigated the function of PUMA in living human lung adenocarcinoma cells (ASTC-a-1) after STS treatment. Our results show that FOXO3a was activated by STS stimulation and then translocated from cytosol to nucleus. The expression of PUMA was up-regulated via a FOXO3a-dependent manner after STS treatment, while p53 had little function in this process. Moreover, cell apoptosis and Bax translocation induced by STS were not blocked by Pifithrin-α (p53 inhibitor), which suggested that p53 was not involved in this signaling pathway. Taken together, these results indicate that PUMA promoted Bax translocation in a FOXO3a-dependment pathway during STS-induced apoptosis, while p53 was dispensable in this process.

  17. Effect of Epicatechin against Radiation-Induced Oral Mucositis: In Vitro and In Vivo Study

    PubMed Central

    Kang, Sung Un; Kim, Jang Hee; Oh, Young-Taek; Park, Keun Hyung; Kim, Chul-Ho

    2013-01-01

    Purpose Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC), a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. Experimental Design The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. Results EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. Conclusions This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis. PMID:23874895

  18. Ultrasonic Measurement of Microdisplacement Induced by Acoustic Radiation Force

    NASA Astrophysics Data System (ADS)

    Nagaoka, Ryo; Izumi, Takuya; Komatsu, Yosuke; Kobayashi, Kazuto; Saijo, Yoshifumi

    2013-07-01

    Quantitative evaluation of human skin aging is achieved by measuring the viscoelasticity of the skin. In the present study, microdisplacement induced by acoustic radiation force (ARF) is quantitatively measured by high-frequency ultrasonography (HFUS) and the result is confirmed by laser-Doppler velocimetry (LDV). Poly(vinyl alcohol) (PVA) with 1% cellulose particles was used as the biological phantom. A concave piezoelectric zirconate titanate (PZT) transducer with a diameter and focal length of 3 cm was used as an applicator to generate ARF. Microdisplacement at each depth of PVA was measured by the phased tracking method at 100 MHz of ultrasound with a repetition rate of 2000 Hz. When 80 tone-burst pulses were applied, the displacement measured by HFUS was 9 µm and the same result was obtained by LDV. As the displacement at each depth of PVA is measurable using ARF and the HFUS system, the system could be applied to measuring the viscoelasticity of the layered structure of the human skin.

  19. Ionizing radiation induces heritable disruption of epithelial cell interactions

    NASA Technical Reports Server (NTRS)

    Park, Catherine C.; Henshall-Powell, Rhonda L.; Erickson, Anna C.; Talhouk, Rabih; Parvin, Bahram; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Chatterjee, A. (Principal Investigator)

    2003-01-01

    Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, beta-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell-cell communication, aberrant cell-extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization.

  20. Radiation induced destruction of thebaine, papaverine and noscapine in methanol

    NASA Astrophysics Data System (ADS)

    Kantoğlu, Ömer; Ergun, Ece

    2016-07-01

    The presence of methanol decreases the efficiency of radiation-induced decomposition of alkaloids in wastewater. Intermediate products were observed before the complete degradation of irradiated alkaloids. In order to identify the structure of the by-products and the formation pathway, thebaine, papaverine and noscapine solutions were prepared in pure methanol and irradiated using a 60Co gamma cell at absorbed doses of 0, 1, 3, 5, 7, 10, 30, 50 and 80 kGy. The dose-dependent alkaloid degradation and by-product formation were monitored by ESI mass spectrometer. Molecular structures of the by-products and reaction pathways were proposed. Oxygenated and methoxy group containing organic compounds was observed in the mass spectra of irradiated alkaloids. At initial dose values oxygenated by-products were formed due to the presence of dissolved oxygen in solutions. After the consumption of dissolved oxygen with radicals, the main mechanism was addition of solvent radicals to alkaloid structure. However, it was determined that alkaloids and by-products were completely degraded at doses higher than 50 kGy. The G-value and degradation efficiency of alkaloids were also evaluated.

  1. Outcome of Carotid Artery Stenting for Radiation-Induced Stenosis

    SciTech Connect

    Dorresteijn, Lucille; Vogels, Oscar; Leeuw, Frank-Erik de; Vos, Jan-Albert; Christiaans, Marleen H.; Ackerstaff, Rob; Kappelle, Arnoud C.

    2010-08-01

    Purpose: Patients who have been irradiated at the neck have an increased risk of symptomatic stenosis of the carotid artery during follow-up. Carotid angioplasty and stenting (CAS) can be a preferable alternative treatment to carotid endarterectomy, which is associated with increased operative risks in these patients. Methods and Materials: We performed a prospective cohort study of 24 previously irradiated patients who underwent CAS for symptomatic carotid stenosis. We assessed periprocedural and nonprocedural events including transient ischemic attack (TIA), nondisabling stroke, disabling stoke, and death. Patency rates were evaluated on duplex ultrasound scans. Restenosis was defined as a stenosis of >50% at the stent location. Results: Periprocedural TIA rate was 8%, and periprocedural stroke (nondisabling) occurred in 4% of patients. After a mean follow-up of 3.3 years (range, 0.3-11.0 years), only one ipsilateral incident event (TIA) had occurred (4%). In 12% of patients, a contralateral incident event was present: one TIA (4%) and two strokes (12%, two disabling strokes). Restenosis was apparent in 17%, 33%, and 42% at 3, 12, and 24 months, respectively, although none of the patients with restenosed vessels became symptomatic. The length of the irradiation to CAS interval proved the only significant risk factor for restenosis. Conclusions: The results of CAS for radiation-induced carotid stenosis are favorable in terms of recurrence of cerebrovascular events at the CAS site.

  2. Structural investigation of radiation-induced aggregates of ribonuclease.

    PubMed

    Hajós, G; Delincée, H

    1983-10-01

    Following irradiation of bovine pancreatic ribonuclease in aqueous solution with 60Co gamma-rays protein aggregates are formed. The nature of the bonds linking these radiation-induced aggregates together has been investigated by chromatographic and electrophoretic methods. Thin-layer gel filtration and polyacrylamide gel electrophoresis, both in the presence of sodium dodecyl sulphate, demonstrated the existence of covalent crosslinks between the aggregates. However, non-covalent crosslinking also plays a role in the radiolysis of ribonuclease. Thin-layer gel filtration with and without 6 M urea and 2 per cent beta-mercaptoethanol added to the gel, revealed that only part of the covalent bonds between the aggregates consisted of disulphide linkages. By separation of the reduced aggregates by thin-layer gel filtration and electrophoresis, both with SDS, this finding was substantiated. Densitometric measurements indicated for example that the percentage of covalently linked dimers held together by disulphide bridges amounted to about 40-45 per cent, whereas the remaining 55-60 per cent of the dimers must be linked by other covalent bonds. The existence of covalent crosslinks other than disulphide bonds was also confirmed by isoelectric focusing. By this method definite differences were established between the proteolytic hydrolysates of the reduced aggregates and the reduced monomer of gamma-irradiated ribonuclease. PMID:6605318

  3. Induced swelling in radiation damaged ZrSiO 4

    NASA Astrophysics Data System (ADS)

    Exarhos, G. J.

    1984-02-01

    A hydrothermal gelation method was used to prepare phase pure polycrystalline ZrSiO 4 which was sintered to 95% theoretical density. Actinide doped samples containing 10 wt% 238Pu were prepared by an analogous procedure and incurred bulk radiation damage through internal alpha-decay processes. Undoped samples were subjected to external irradiation from 5.5 MeV alpha sources, and from a 60Co gamma source. Actinide doped ZrSiO 4 exhibits dose dependent swelling caused by displacement processes leading to ingrowth of amorphous regions. Bulk density and XRD measurements, as a function of dose, showed first order exponential ingrowth behavior similar to that observed in other actinide doped materials. Results are compared with reported data for naturally damaged crystals subjected to significantly lower alpha decay rates. No significant dose rate dependence on damage ingrowth has been observed. Kinetic models for the observed dose dependent swelling are proposed and rate constants for damage ingrowth in synthetic and natural crystals are compared. To study localized damage induced by both external alpha and gamma irradiation, vibrational Raman measurements were obtained for several accumulated doses. Results indicate that the initial stage of damage ingrowth is confined to the silicate sublattice. Vibrational results will be discussed in terms of microstructural changes which result from irradiation.

  4. Processability improvement of polyolefins through radiation-induced branching

    NASA Astrophysics Data System (ADS)

    Cheng, Song; Phillips, Ed; Parks, Lewis

    2010-03-01

    Radiation-induced long-chain branching for the purpose of improving melt strength and hence the processability of polypropylene (PP) and polyethylene (PE) is reviewed. Long-chain branching without significant gel content can be created by low dose irradiation of PP or PE under different atmospheres, with or without multifunctional branching promoters. The creation of long-chain branching generally leads to improvement of melt strength, which in turn may be translated into processability improvement for specific applications in which melt strength plays an important role. In this paper, the changes of the melt flow rate and the melt strength of the irradiated polymer and the relationship between long-chain branching and melt strength are reviewed. The effects of the atmosphere and the branching promoter on long-chain branching vs. degradation are discussed. The benefits of improved melt strength on the processability, e.g., sag resistance and strain hardening, are illustrated. The implications on practical polymer processing applications such as foams and films are also discussed.

  5. Ionizing radiation induces heritable disruption of epithelial cell interactions

    PubMed Central

    Park, Catherine C.; Henshall-Powell, Rhonda L.; Erickson, Anna C.; Talhouk, Rabih; Parvin, Bahram; Bissell, Mina J.; Barcellos-Hoff, Mary Helen

    2003-01-01

    Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, β-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell–cell communication, aberrant cell–extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization. PMID:12960393

  6. Investigations of radiation-induced and carrier-enhanced conductivity

    NASA Technical Reports Server (NTRS)

    Meulenberg, A., Jr.; Parker, L. W.; Yadlowski, E. J.; Hazelton, R. C.

    1985-01-01

    A steady-state carrier computer code, PECK (Parker Enhanced Carrier Kinetics), that predicts the radiation-induced conductivity (RIC) produced in a dielectric by an electron beam was developed. The model, which assumes instantly-trapped holes, was then applied to experimental measurements on thin Kapton samples penetrated by an electron beam. Measurements at high bias were matched in the model by an appropriate choice for the trap-modulated electron mobility. A fractional split between front and rear currents measured at zone bias is explained on the basis of beam-scattering. The effects of carrier-enhanced conductivity (CEC) on data obtained for thick, free-surface Kapton samples is described by using an analytical model that incorporates field injection of carriers from the RIC region. The computer code, LWPCHARGE, modified for carrier transport, is also used to predict partial penetration effects associated with CEC in the unirradiated region. Experimental currents and surface voltages, when incorporated in the appropriate models, provide a value for the trap modulated mobility that is in essential agreement with the RIC results.

  7. Revisit on dynamic radiation forces induced by pulsed Gaussian beams.

    PubMed

    Wang, Li-Gang; Chai, Hai-Shui

    2011-07-18

    Motivated by the recent optical trapping experiments using ultra-short pulsed lasers [Opt. Express 18, 7554 (2010); Appl. Opt. 48, G33 (2009)], in this paper we have re-investigated the trapping effects of the pulsed radiation force (PRF), which is induced by a pulsed Gaussian beam acting on a Rayleigh dielectric sphere. Based on our previous model [Opt. Express 15, 10615 (2007)], we have considered the effects arisen from both the transverse and axial PRFs, which lead to the different behaviors of both velocities and displacements of a Rayleigh particle within a pulse duration. Our analysis shows that, for the small-sized Rayleigh particles, when the pulse has the large pulse duration, it might provide the three-dimensional optical trapping; and when the pulse has the short pulse duration, it only provides the two-dimensional optical trapping with the axial movement along the pulse propagation. When the particle is in the vacuum or in the situation with the very weak Brownian motion, the particle can always be trapped stably due to the particle's cumulative momentum transferred from the pulse, and only in this case the trapping effect is independent of pulse duration. Finally, we have predicted that for the large-sized Rayleigh particles, the pulse beam can only provide the two-dimensional optical trap (optical guiding). Our results provide the important information about the trapping mechanism of pulsed tweezers. PMID:21934801

  8. An ESR study of radiation induced radicals in glucose polymers

    NASA Astrophysics Data System (ADS)

    Kameya, Hiromi; Ukai, Mitsuko; Shimoyama, Yuhei

    2013-03-01

    Using electron spin resonance (ESR) spectroscopy with both experimental and theoretical approaches, we revealed the γ-radiation induced radicals in two glucose polymers, cellulose and starch. Before irradiation, ESR signals are silent in both the glucose polymers. After irradiation, a singlet signal at g=2.0 appeared in both the glucose polymers. The twin peaks were invisible in the starch sample. We identified the twin peaks to be a part of triplet signal and analyzed the molecular structure of the cellulose radical. Through theoretical simulations, we revealed, for the first time, that the triplet signal was due to hyperfine interactions of unpaired electron with two protons in the cellulose radical. The third peak within the triplet is overlapped by the free radical at g=2.0. We further found that the cellulose radical does not remain at the rigid limit or the static state, but undergoes axial rotations around C-C and C-H bonds. We concluded that the triplet ESR signal reflects the cellulose radical.

  9. [Radiation-induced damage of mitochondrial genome and its role in long-term effects of irradiation].

    PubMed

    Berogovskaia, N N; Savich, A V

    1994-01-01

    The role of mt-genome mutations in radiation-induced carcinogenesis has been hypothesized. The data on radiation chemistry of nucleic acids has been used to evaluate mutagenic effect of carcinogenic doses of ionizing radiation. The assumptions about the ways of biological augmentation of primary radiation-induced lesions in mt-genome has been given. PMID:8069366

  10. Radiation-induced gene expression in the nematode Caenorhabditis elegans

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.; Jones, Tamako A.; Chesnut, Aaron; Smith, Anna 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 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.

  11. Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

    PubMed Central

    Lall, R; Ganapathy, S; Yang, M; Xiao, S; Xu, T; Su, H; Shadfan, M; Asara, J M; Ha, C S; Ben-Sahra, I; Manning, B D; Little, J B; Yuan, Z-M

    2014-01-01

    Because of insufficient understanding of the molecular effects of low levels of radiation exposure, there is a great uncertainty regarding its health risks. We report here that treatment of normal human cells with low-dose radiation induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting in increased radiation resistance. This metabolic change is highlighted by upregulation of genes encoding glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway, concomitant with downregulation of mitochondrial genes, with corresponding changes in metabolic flux through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1α, which is induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed systemically in mice. This highly sensitive metabolic response to low-dose radiation has important implications in understanding and assessing the health risks of radiation exposure. PMID:24583639

  12. Enhanced homologous recombination is induced by alpha-particle radiation in somatic cells of Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Bian, Po; Liu, Ping; Wu, Yuejin

    Almost 9 percent of cosmic rays which strike the earth's atmosphere are alpha particles. As one of the ionizing radiations (IR), its biological effects have been widely studied. However, the plant genomic instability induced by alpha-particle radiation was not largely known. In this research, the Arabidopsis thaliana transgenic for GUS recombination substrate was used to evaluate the genomic instability induced by alpha-particle radiation (3.3MeV). The pronounced effects of systemic exposure to alpha-particle radiation on the somatic homologous recombination frequency (HRF) were found at different doses. The 10Gy dose of radiation induced the maximal HRF which was 1.9-fold higher than the control. The local radiation of alpha-particle (10Gy) on root also resulted in a 2.5-fold increase of somatic HRF in non-radiated aerial plant, indicating that the signal(s) of genomic instability was transferred to non-radiated parts and initiated their genomic instability. Concurrent treatment of seedlings of Arabidopsis thaliana with alpha-particle and DMSO(ROS scavenger) both in systemic and local radiation signifi- cantly suppressed the somatic HR, indicating that the free radicals produced by alpha-particle radiation took part in the production of signal of genomic instability rather than the signal transfer. Key words: alpha-particle radiation, somatic homologous recombination, genomic instability

  13. Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

    PubMed

    King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

    2016-06-01

    Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration. PMID:27098922

  14. Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation

    DOE PAGESBeta

    Ye, Tianyu; Liu, Han -Chun; Wang, Zhuo; Wegscheider, W.; Mani, Ramesh G.

    2015-10-09

    A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. As a result, for circularly polarized radiation, the oscillatory magnetoresistive response ismore » hardly sensitive to θ.« less

  15. Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

    PubMed Central

    2010-01-01

    Background DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed. Methods Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation. Conclusions An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity. PMID:20868468

  16. Transient radiation-induced absorption in the materials for a GSGG laser

    NASA Astrophysics Data System (ADS)

    Brannon, P. J.

    1993-11-01

    Materials used in the optical elements of a 1,061 m GSGG (gadolinium scandium gallium garnet) laser have been tested for transient radiation-induced absorption. The transient radiation-induced absorption in KK1, Schott S7005 and S7010, and M382 glasses have been determined for discrete wavelengths in the range 440-750 nm. Also, the transient radiation-induced absorption in 'pure' and MgO doped LiNbO3 has been measured at 1,061 nm. Mathematical expressions composed of exponentials are fitted to the data.

  17. Synchrotron-Radiation Induced X-Ray Emission (SRIXE)

    SciTech Connect

    Jones, Keith W.

    1999-09-01

    and increase in scientific use can be maintained for the synchrotron x-ray source. A short summary of the present state of the synchrotron radiation-induced x-ray emission (SRIXE) method is presented here. Basically, SRIXE experiments can include any that depend on the detection. of characteristic x-rays produced by the incident x-ray beam born the synchrotron source as they interact with a sample. Thus, experiments done to measure elemental composition, chemical state, crystal, structure, and other sample parameters can be considered in a discussion of SRIXE. It is also clear that the experimentalist may well wish to use a variety of complementary techniques for study of a given sample. For this reason, discussion of computed microtomography (CMT) and x-ray diffraction is included here. It is hoped that this present discussion will serve as a succinct introduction to the basic ideas of SRIXE for those not working in the field and possibly help to stimulate new types of work by those starting in the field as well as by experienced practitioners of the art. The topics covered include short descriptions of (1) the properties of synchrotron radiation, (2) a description of facilities used for its production, (3) collimated microprobe, (4) focused microprobes, (5) continuum and monoenergetic excitation, (6) detection limits, (7) quantitation, (8) applications of SRIXE, (9) computed microtomography (CMT), and (10)chemical speciation using x-ray absorption near-edge structure (XANES) and extended x-ray absorption fine structure (EXAFS). An effort has been made to cite a wide variety of work from different laboratories to show the vital nature of the field.

  18. Ultraviolet radiation directly induces pigment production by cultured human melanocytes

    SciTech Connect

    Friedmann, P.S.; Gilchrest, B.A.

    1987-10-01

    In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of /sup 14/C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus, it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.

  19. Radiation-induced lung damage: dose-time-fractionation considerations.

    PubMed

    Van Dyk, J; Mah, K; Keane, T J

    1989-01-01

    The comparison of different dose-time-fractionation schedules requires the use of an isoeffect formula. In recent years, the NSD isoeffect formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The proposed procedures allow for the simultaneous derivation of an alpha/beta ratio and a gamma/beta time factor. From animal data in the literature, the derived alpha/beta and gamma/beta ratios for acute lung damage are 5.0 +/- 1.0 Gy and 2.7 +/- 1.4 Gy2/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy2/day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding alpha/beta and gamma/beta ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant alpha/beta and gamma/beta ratios were 0.9 +/- 2.6 Gy and 2.6 +/- 2.5 Gy2/day. The combination of the retrospective and prospective data yielded alpha/beta and gamma/beta ratios of 3.3 +/- 1.5 Gy and 2.4 +/- 1.5 Gy2/day, respectively. One potential advantage of this isoeffect formalism is that it might possibly be applied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffect doses than previously predicted by the estimated single dose (ED) formula. Although we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data. PMID:2928557

  20. Molecular responses of radiation-induced liver damage in rats

    PubMed Central

    CHENG, WEI; XIAO, LEI; AINIWAER, AIMUDULA; WANG, YUNLIAN; WU, GE; MAO, RUI; YANG, YING; BAO, YONGXING

    2015-01-01

    The aim of the present study was to investigate the molecular responses involved in radiation-induced liver damage (RILD). Sprague-Dawley rats (6-weeks-old) were irradiated once at a dose of 20 Gy to the right upper quadrant of the abdomen. The rats were then sacrificed 3 days and 1, 2, 4, 8 and 12 weeks after irradiation and rats, which were not exposed to irradiation were used as controls. Weight measurements and blood was obtained from the rats and liver tissues were collected for histological and apoptotic analysis. Immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were performed to measure the expression levels of mRNAs and proteins, respectively. The serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were increased significantly in the RILD rats. Histological investigation revealed the proliferation of collagen and the formation of fibrotic tissue 12 weeks after irradiation. Apoptotic cells were observed predominantly 2 and 4 weeks after irradiation. The immunohistochemistry, RT-qPCR and western blot analysis all revealed the same pattern of changes in the expression levels of the molecules assessed. The expression levels of transforming growth factor-β1 (TGF-β1), nuclear factor (NF)-κB65, mothers against decapentaplegic homolog 3 (Smad3) and Smad7 and connective tissue growth factor were increased during the recovery period following irradiation up to 12 weeks. The expression levels of tumor necrosis factor-α, Smad7 and Smad4 were only increased during the early phase (first 4 weeks) of recovery following irradiation. In the RILD rat model, the molecular responses indicated that the TGF-β1/Smads and NF-κB65 signaling pathways are involved in the mechanism of RILD recovery. PMID:25483171

  1. Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study

    SciTech Connect

    Seidensticker, Max; Burak, Miroslaw; Kalinski, Thomas; Garlipp, Benjamin; Koelble, Konrad; Wust, Peter; Antweiler, Kai; Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Ricke, Jens

    2015-02-15

    PurposeRadiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA).MethodsPatients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluable liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined.ResultsFourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition.ConclusionsAbsence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.

  2. Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome

    PubMed Central

    Kindekov, Ivan; Mileva, Milka; Krastev, Dimo; Vassilieva, Vladimira; Raynova, Yuliana; Doumanova, Lyuba; Aljakov, Mitko; Idakieva, Krassimira

    2014-01-01

    The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 – dose that kills 100% of the mice at 30 days) from 137Cs with a dose of 2.05 Gy/min. Radiation injuries were manifested by inducing а hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery. PMID:26019540

  3. Deep Friction Massage in Treatment of Radiation-induced Fibrosis: Rehabilitative Care for Breast Cancer Survivors

    PubMed Central

    Warpenburg, Mary J.

    2014-01-01

    Treatment for invasive breast cancer usually involves some combination of surgery, radiation therapy, chemotherapy, hormone therapy, and/or targeted therapy. For approximately 50% of patients, radiation therapy is a component of the therapies used. As a result, radiation-induced fibrosis is becoming a common and crippling side effect, leading to muscle imbalance with a lessened range of motion as well as pain and dysfunction of the vascular and lymphatic systems. No good estimates are available for how many patients experience complications from radiation. Radiation-induced fibrosis can affect the underlying fascia, muscles, organs, and bones within the primary target field and the larger secondary field that is caused by the scatter effect of radioactive elements. For breast cancer patients, the total radiation field may include the neck, shoulder, axillary, and thoracic muscles and the ribs for both the ipsilateral (cancer-affected) and contralateral sides. This case study indicates that therapy using deep friction massage can affect radiation-induced fibrosis beneficially, particularly in the thoracic muscles and the intercostals (ie, the muscles between the ribs). When delivered in intensive sessions using deep friction techniques, massage has the potential to break down fibrotic tissues, releasing the inflammation and free radicals that are caused by radiation therapy. In the course of the massage, painful and debilitating spasms resulting from fibrosis can be relieved and the progressive nature of the radiation-induced fibrosis interrupted. PMID:26770116

  4. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    SciTech Connect

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro; and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  5. The Therapeutic Effect of Adipose-Derived Mesenchymal Stem Cells for Radiation-Induced Bladder Injury

    PubMed Central

    Qiu, Xuefeng; Zhang, Shiwei; Zhao, Xiaozhi; Fu, Kai; Guo, Hongqian

    2016-01-01

    This study was designed to investigate the protective effect of adipose derived mesenchymal stem cells (AdMSCs) against radiation-induced bladder injury (RIBI). Female rats were divided into 4 groups: (a) controls, consisting of nontreated rats; (b) radiation-treated rats; (c) radiation-treated rats receiving AdMSCs; and (d) radiation-treated rats receiving AdMSCs conditioned medium. AdMSCs or AdMSCs conditioned medium was injected into the muscular layer of bladder 24 h after radiation. Twelve weeks after radiation, urinary bladder tissue was collected for histological assessment and enzyme-linked immunosorbent assay (ELISA) after metabolic cage investigation. At the 1 w, 4 w, and 8 w time points following cells injection, 3 randomly selected rats in RC group and AdMSCs group were sacrificed to track injected AdMSCs. Metabolic cage investigation revealed that AdMSCs showed protective effect for radiation-induced bladder dysfunction. The histological and ELISA results indicated that the fibrosis and inflammation within the bladder were ameliorated by AdMSCs. AdMSCs conditioned medium showed similar effects in preventing radiation-induced bladder dysfunction. In addition, histological data indicated a time-dependent decrease in the number of AdMSCs in the bladder following injection. AdMSCs prevented radiation induced bladder dysfunction and histological changes. Paracrine effect might be involved in the protective effects of AdMSCs for RIBI. PMID:27051426

  6. RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma.

    PubMed

    Das, Arabinda; McDonald, Daniel G; Dixon-Mah, Yaenette N; Jacqmin, Dustin J; Samant, Vikram N; Vandergrift, William A; Lindhorst, Scott M; Cachia, David; Varma, Abhay K; Vanek, Kenneth N; Banik, Naren L; Jenrette, Joseph M; Raizer, Jeffery J; Giglio, Pierre; Patel, Sunil J

    2016-06-01

    Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and the ways RN mechanisms differ from regulated cell death (apoptosis) are not well understood. Here, we compare the molecular mechanism of cell death (apoptosis or necrosis) of C6 glioma cells in both in vitro and in vivo (C6 othotopically allograft) models in response to low and high doses of X-ray radiation. Lower radiation doses were used to induce apoptosis, while high-dose levels were chosen to induce radiation necrosis. Our results demonstrate that active caspase-8 in this complex I induces apoptosis in response to low-dose radiation and inhibits necrosis by cleaving RIP1 and RI. When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed. These complexes induce necrosis through the caspase-3-independent pathway mediated by calpain, cathepsin B/D, and apoptosis-inducing factor (AIF). AIF has a dual role in apoptosis and necrosis. At high doses, AIF promotes chromatinolysis and necrosis by interacting with histone H2AX. In addition, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. Analysis of inflammatory markers in matched plasma and cerebrospinal fluid (CSF) isolated from in vivo specimens demonstrated the upregulation of chemokines and cytokines during the necrosis phase. Using RIP1/RIP3 kinase specific inhibitors (Nec-1, GSK'872), we also establish that the RIP1-RIP3 complex regulates programmed necrosis after either high-dose radiation or TNF-α-induced necrosis requires RIP1 and RIP3 kinases. Overall, our data shed new light on the relationship between RIP1/RIP3-mediated programmed necrosis and AIF-mediated caspase-independent programmed necrosis in glioblastoma. PMID:26684801

  7. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    SciTech Connect

    Meng, Zhen; Gan, Ye-Hua

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  8. Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

    PubMed Central

    Acharya, Sanket S.; Fendler, Wojciech; Watson, Jacqueline; Hamilton, Abigail; Pan, Yunfeng; Gaudiano, Emily; Moskwa, Patryk; Bhanja, Payel; Saha, Subhrajit; Guha, Chandan; Parmar, Kalindi; Chowdhury, Dipanjan

    2015-01-01

    Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation. PMID:25972001

  9. Exposure to Heavy Ion Radiation Induces Persistent Oxidative Stress in Mouse Intestine

    PubMed Central

    Datta, Kamal; Suman, Shubhankar; Kallakury, Bhaskar V. S.; Fornace, Albert J.

    2012-01-01

    Ionizing radiation-induced oxidative stress is attributed to generation of reactive oxygen species (ROS) due to radiolysis of water molecules and is short lived. Persistent oxidative stress has also been observed after radiation exposure and is implicated in the late effects of radiation. The goal of this study was to determine if long-term oxidative stress in freshly isolated mouse intestinal epithelial cells (IEC) is dependent on radiation quality at a dose relevant to fractionated radiotherapy. Mice (C57BL/6J; 6 to 8 weeks; female) were irradiated with 2 Gy of γ-rays, a low-linear energy transfer (LET) radiation, and intestinal tissues and IEC were collected 1 year after radiation exposure. Intracellular ROS, mitochondrial function, and antioxidant activity in IEC were studied by flow cytometry and biochemical assays. Oxidative DNA damage, cell death, and mitogenic activity in IEC were assessed by immunohistochemistry. Effects of γ radiation were compared to 56Fe radiation (iso-toxic dose: 1.6 Gy; energy: 1000 MeV/nucleon; LET: 148 keV/µm), we used as representative of high-LET radiation, since it's one of the important sources of high Z and high energy (HZE) radiation in cosmic rays. Radiation quality affected the level of persistent oxidative stress with higher elevation of intracellular ROS and mitochondrial superoxide in high-LET 56Fe radiation compared to unirradiated controls and γ radiation. NADPH oxidase activity, mitochondrial membrane damage, and loss of mitochondrial membrane potential were greater in 56Fe-irradiated mice. Compared to γ radiation oxidative DNA damage was higher, cell death ratio was unchanged, and mitotic activity was increased after 56Fe radiation. Taken together our results indicate that long-term functional dysregulation of mitochondria and increased NADPH oxidase activity are major contributing factors towards heavy ion radiation-induced persistent oxidative stress in IEC with potential for neoplastic transformation. PMID

  10. Obtaining Solutions to Radiation-And Plasma Induced FAilure Modes From Physics

    NASA Technical Reports Server (NTRS)

    Frederickson, A.

    1998-01-01

    A number of performance-limiting spacecraft problems will be qualitatively discussed: Spacecraft Charging, Deep Dielectric Charging, Solar Cell Arcing, Antenna Sparking, High Voltage Power Shorts, Radiation-induced Defects in Semiconductors, and Degradation of Electronic Devices.

  11. The protective effects of trace elements against side effects induced by ionizing radiation

    PubMed Central

    2015-01-01

    Trace elements play crucial role in the maintenance of genome stability in the cells. Many endogenous defense enzymes are containing trace elements such as superoxide dismutase and metalloproteins. These enzymes are contributing in the detoxification of reactive oxidative species (ROS) induced by ionizing radiation in the cells. Zinc, copper, manganese, and selenium are main trace elements that have protective roles against radiation-induced DNA damages. Trace elements in the free salt forms have protective effect against cell toxicity induced by oxidative stress, metal-complex are more active in the attenuation of ROS particularly through superoxide dismutase mimetic activity. Manganese-complexes in protection of normal cell against radiation without any protective effect on cancer cells are more interesting compounds in this topic. The aim of this paper to review the role of trace elements in protection cells against genotoxicity and side effects induced by ionizing radiation. PMID:26157675

  12. [Malignant transformation of human fibroblasts by neutrons and by gamma radiation: Relationship to mutations induced

    SciTech Connect

    1993-12-31

    A brief overview if provided of selected reports presented at the International Symposium on Molecular Mechanisms of Radiation- and Chemical Carcinogen-Induced Cell Transformation held at Mackinac Island, Michigan on September 19-23, 1993.

  13. Gamma radiation induced effects in floppy and rigid Ge-containing chalcogenide thin films

    SciTech Connect

    Ailavajhala, Mahesh S.; Mitkova, Maria; Gonzalez-Velo, Yago; Barnaby, Hugh; Kozicki, Michael N.; Holbert, Keith; Poweleit, Christian; Butt, Darryl P.

    2014-01-28

    We explore the radiation induced effects in thin films from the Ge-Se to Ge-Te systems accompanied with silver radiation induced diffusion within these films, emphasizing two distinctive compositional representatives from both systems containing a high concentration of chalcogen or high concentration of Ge. The studies are conducted on blanket chalcogenide films or on device structures containing also a silver source. Data about the electrical conductivity as a function of the radiation dose were collected and discussed based on material characterization analysis. Raman Spectroscopy, X-ray Diffraction Spectroscopy, and Energy Dispersive X-ray Spectroscopy provided us with data about the structure, structural changes occurring as a result of radiation, molecular formations after Ag diffusion into the chalcogenide films, Ag lateral diffusion as a function of radiation and the level of oxidation of the studied films. Analysis of the electrical testing suggests application possibilities of the studied devices for radiation sensing for various conditions.

  14. The potential influence of radiation-induced microenvironments in neoplastic progression

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

  15. Radiation-induced mechanical property changes in filled rubber

    SciTech Connect

    Maiti, A.; Weisgraber, T. H.; Gee, R. H.; Small, W.; Alviso, C. T.; Chinn, S. C.; Maxwell, R. S.

    2011-06-15

    In a recent paper we exposed a filled elastomer to controlled radiation dosages and explored changes in its cross-link density and molecular weight distribution between network junctions [A. Maiti et al., Phys. Rev. E 83, 031802 (2011)]. Here we report mechanical response measurements when the material is exposed to radiation while being under finite nonzero strain. We observe interesting hysteretic behavior and material softening representative of the Mullins effect, and materials hardening due to radiation. The net magnitude of the elastic modulus depends upon the radiation dosage, strain level, and strain-cycling history of the material. Using the framework of Tobolsky's two-stage independent network theory we develop a model that can quantitatively interpret the observed elastic modulus and its radiation and strain dependence.

  16. Curvature-induced radiation of surface plasmon polaritons propagating around bends

    SciTech Connect

    Hasegawa, Keisuke; Noeckel, Jens U.; Deutsch, Miriam

    2007-06-15

    We present a theoretical study of the curvature-induced radiation of surface plasmon polaritons propagating around bends at metal-dielectric interfaces. We explain qualitatively how the curvature leads to distortion of the phase front, causing the fields to radiate energy away from the metal-dielectric interface. We then quantify, both analytically and numerically, radiation losses and energy transmission efficiencies of surface plasmon polaritons propagating around bends with varying radii as well as sign of curvature.

  17. Changes induced in spice paprika powder by treatment with ionizing radiation and saturated steam

    NASA Astrophysics Data System (ADS)

    Kispéter, J.; Bajúsz-Kabók, K.; Fekete, M.; Szabó, G.; Fodor, E.; Páli, T.

    2003-12-01

    The changes in spice paprika powder induced by ionizing radiation, saturated steam (SS) and their combination were studied as a function of the absorbed radiation dose and the storage time. The SS treatment lead to a decrease in color content (lightening) after 12 weeks of storage, together with the persistence of free radicals and viscosity changes for a longer period. The results suggest that ionizing radiation is a more advantageous method as concerns preservation of the quality of spice paprika.

  18. P2Y6 Receptor-Mediated Microglial Phagocytosis in Radiation-Induced Brain Injury.

    PubMed

    Xu, Yongteng; Hu, Weihan; Liu, Yimin; Xu, Pengfei; Li, Zichen; Wu, Rong; Shi, Xiaolei; Tang, Yamei

    2016-08-01

    Microglia are the resident immune cells and the professional phagocytic cells of the CNS, showing a multitude of cellular responses after activation. However, how microglial phagocytosis changes and whether it is involved in radiation-induced brain injury remain unknown. In the current study, we found that microglia were activated and microglial phagocytosis was increased by radiation exposure both in cultured microglia in vitro and in mice in vivo. Radiation increased the protein expression of the purinergic receptor P2Y6 receptor (P2Y6R) located on microglia. The selective P2Y6 receptor antagonist MRS2578 suppressed microglial phagocytosis after radiation exposure. Inhibition of microglial phagocytosis increased inhibitory factor Nogo-A and exacerbated radiation-induced neuronal apoptosis and demyelination. We also found that the levels of protein expression for phosphorylated Ras-related C3 botulinum toxin substrate 1 (Rac1) and myosin light chain kinase (MLCK) were elevated, indicating that radiation exposure activated Rac1 and MLCK. The Rac1 inhibitor NSC23766 suppressed expression of MLCK, indicating that the Rac1-MLCK pathway was involved in microglial phagocytosis. Taken together, these findings suggest that the P2Y6 receptor plays a critical role in mediating microglial phagocytosis in radiation-induced brain injury, which might be a potential strategy for therapeutic intervention to alleviate radiation-induced brain injury. PMID:26099306

  19. Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies.

    PubMed

    Fleenor, Courtney J; Higa, Kelly; Weil, Michael M; DeGregori, James

    2015-10-01

    Human exposure to ionizing radiation is highly associated with adverse health effects, including reduced hematopoietic cell function and increased risk of carcinogenesis. The hematopoietic deficits manifest across blood cell types and persist for years after radiation exposure, suggesting a long-lived and multi-potent cellular reservoir for radiation-induced effects. As such, research has focused on identifying both the immediate and latent hematopoietic stem cell responses to radiation exposure. Radiation-associated effects on hematopoietic function and malignancy development have generally been attributed to the direct induction of mutations resulting from radiation-induced DNA damage. Other studies have illuminated the role of cellular programs that both limit and enhance radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct but collaborative cellular responses to genotoxic insults are highlighted, with an emphasis on how these programmed responses impact hematopoietic cellular fitness and competition. These radiation-induced cellular programs include apoptosis, senescence and impaired self-renewal within the hematopoietic stem cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular responses act in concert to restore tissue function and prevent selection for adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we propose that these programs can contribute to long-lasting tissue impairment and increased carcinogenesis. PMID:26414506

  20. Radiation Induced Non-targeted Response: Mechanism and Potential Clinical Implications

    PubMed Central

    Hei, Tom K.; Zhou, Hongning; Chai, Yunfei; Ponnaiya, Brian; Ivanov, Vladimir N.

    2012-01-01

    Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced non-targeted/bystander effects represent a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety of biological systems, including 3D human tissue samples and whole organisms, the mechanism is not known. There is recent evidence that the NF-κB-dependent gene expression of interleukin 8, interleukin 6, cyclooxygenase-2, tumor necrosis factor and interleukin 33 in directly irradiated cells produced the cytokines and prostaglandin E2 with autocrine/paracrine functions, which further activated signaling pathways and induced NF-κB-dependent gene expression in bystander cells. The observations that heritable DNA alterations can be propagated to cells many generations after radiation exposure and that bystander cells exhibit genomic instability in ways similar to directly hit cells indicate that the low dose radiation response is a complex interplay of various modulating factors. The potential implication of the non-targeted response in radiation induced secondary cancer is discussed. A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy. PMID:21143185

  1. Radiation-induced meningioma after treatment for pituitary adenoma: Case report and literature review

    SciTech Connect

    Partington, M.D.; Davis, D.H. )

    1990-02-01

    Radiation-induced meningiomas are becoming increasingly well-recognized. We report a case of a 35-year-old man who developed a suprasellar meningioma 9 years after receiving a radiation dose of 4480 cGy for a pituitary adenoma. The literature is also reviewed. 10 references.

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

    NASA Technical Reports Server (NTRS)

    Hada, Megumi; Cucinotta, Francis; Wu, Honglu

    2009-01-01

    The advantage of the multicolor banding in situ hybridization (mBAND) technique is its ability to identify both inter- (translocation to unpainted chromosomes) and intra- (inversions and deletions within a single painted chromosome) chromosome aberrations simultaneously. To study the detailed rearrangement of low- and high-LET radiation induced chromosome aberrations in human epithelial cells (CH184B5F5/M10) in vitro, we performed a series of experiments with Cs-137 gamma rays of both low and high dose rates, neutrons of low dose rate and 600 MeV/u Fe ions of high dose rate, with chromosome 3 painted with multi-binding colors. We also compared the chromosome aberrations in both 2- and 3-dimensional cell cultures. Results of these experiments revealed the highest chromosome aberration frequencies after low dose rate neutron exposures. However, detailed analysis of the radiation induced inversions revealed that all three radiation types induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intra-chromosomal aberrations but few inversions were accompanied by inter-chromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosomal exchanges. The location of the breaks involved in chromosome exchanges was analyzed along the painted chromosome. The breakpoint distribution was found to be randomly localized on chromosome 3 after neutron or Fe ion exposure, whereas non-random distribution with clustering breakpoints was observed after -ray exposure. Our comparison of chromosome aberration yields between 2- and 3-dimensional cell cultures indicated a significant difference for gamma exposures, but not for Fe ion exposures. These experimental results indicated that the track structure of the radiation and the cellular/chromosome structure can both affect radiation-induced chromosome

  3. Radiation induced chemical activity at iron and copper oxide surfaces

    NASA Astrophysics Data System (ADS)

    Reiff, Sarah C.

    The radiolysis of three iron oxides, two copper oxides, and aluminum oxide with varying amounts of water were performed using gamma-rays and 5 MeV 4He ions. The adsorbed water on the surfaces was characterized using temperature programmed desorption and diffuse reflectance infrared spectroscopy, which indicated that all of the oxides had chemisorbed water on the surface. Physisorbed water was observed on the Fe2O 3 and Al2O3 surfaces as well. Molecular hydrogen was produced from adsorbed water only on Fe2O3 and Al 2O3, while the other compounds did not show any hydrogen production due to the low amounts of water on the surfaces. Slurries of varying amounts of water were also examined for hydrogen production, and they showed yields that were greater than the yield for bulk water. However, the yields of hydrogen from the copper compounds were much lower than those of the iron suggesting that the copper oxides are relatively inert to radiation induced damage to nearby water. X-ray diffraction measurements did not show any indication of changes to the bulk crystal structure due to radiolysis for any of the oxides. The surfaces of the oxides were analyzed using Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). For the iron samples, FeO and Fe3O4, Raman spectroscopy revealed areas of Fe2O3 had formed following irradiation with He ions. XPS indicated the formation of a new oxygen species on the iron oxide surfaces. Raman spectroscopy of the copper oxides did not reveal any changes in the surface composition, however, XPS measurements showed a decrease in the amount of OH groups on the surface of Cu2O, while for the CuO samples the amount of OH groups were found to increase following radiolysis. Pristine Al2O3 showed the presence of a surface oxyhydroxide layer which was observed to decrease following radiolysis, consistent with the formation of molecular hydrogen.

  4. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  5. Irradiated esophageal cells are protected from radiation-induced recombination by MnSOD gene therapy.

    PubMed

    Niu, Yunyun; Wang, Hong; Wiktor-Brown, Dominika; Rugo, Rebecca; Shen, Hongmei; Huq, M Saiful; Engelward, Bevin; Epperly, Michael; Greenberger, Joel S

    2010-04-01

    Radiation-induced DNA damage is a precursor to mutagenesis and cytotoxicity. During radiotherapy, exposure of healthy tissues can lead to severe side effects. We explored the potential of mitochondrial SOD (MnSOD) gene therapy to protect esophageal, pancreatic and bone marrow cells from radiation-induced genomic instability. Specifically, we measured the frequency of homologous recombination (HR) at an integrated transgene in the Fluorescent Yellow Direct Repeat (FYDR) mice, in which an HR event can give rise to a fluorescent signal. Mitochondrial SOD plasmid/liposome complex (MnSOD-PL) was administered to esophageal cells 24 h prior to 29 Gy upper-body irradiation. Single cell suspensions from FYDR, positive control FYDR-REC, and negative control C57BL/6NHsd (wild-type) mouse esophagus, pancreas and bone marrow were evaluated by flow cytometry. Radiation induced a statistically significant increase in HR 7 days after irradiation compared to unirradiated FYDR mice. MnSOD-PL significantly reduced the induction of HR by radiation at day 7 and also reduced the level of HR in the pancreas. Irradiation of the femur and tibial marrow with 8 Gy also induced a significant increase in HR at 7 days. Radioprotection by intraesophageal administration of MnSOD-PL was correlated with a reduced level of radiation-induced HR in esophageal cells. These results demonstrate the efficacy of MnSOD-PL for suppressing radiation-induced HR in vivo. PMID:20334517

  6. Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

    Abstract: Radiation-induced bystander effect was 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 and proteomics plays 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 Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

  7. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    PubMed Central

    Jenrow, Kenneth A.; Brown, Stephen L.

    2014-01-01

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs. PMID:25324981

  8. Advanced Interventional Therapy for Radiation-Induced Cardiovascular Disease

    PubMed Central

    2016-01-01

    This report describes the case of a 61-year-old woman who presented with dyspnea, aortic stenosis, and coronary artery disease—typical side effects of radiation therapy for Hodgkin lymphoma. A poor candidate for surgery, she underwent successful high-risk percutaneous coronary intervention and subsequent transcatheter aortic valve replacement. This report highlights some of the cardiovascular-specific sequelae of radiation therapy for cancer treatment; in addition, possible directions for future investigations are discussed. PMID:27547140

  9. Dynamics of radiation induced isomerization for HCN-CNH

    SciTech Connect

    Na, Kyungsun; Jung, Christof; Reichl, L. E.

    2006-07-21

    We have analyzed the dynamics underlying the use of sequential radiation pulses to control the isomerization between the HCN and the CNH molecules. The appearance of avoided crossings among Floquet eigenphases as the molecule interacts with the radiation pulses is the key to understanding the isomerization dynamics, both in the adiabatic and nonadiabatic regimes. We find that small detunings of the incident pulses can have a significant effect on the outcome of the isomerization process for the model we consider.

  10. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    SciTech Connect

    Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali; Hemati, Simin

    2015-07-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.

  11. Phytochemicals for prevention of solar ultraviolet radiation-induced damages.

    PubMed

    Adhami, Vaqar M; Syed, Deeba N; Khan, Naghma; Afaq, Farrukh

    2008-01-01

    While solar light is indispensable for sustenance of life, excessive exposure can cause several skin-related disorders. The UV part of solar radiation, in particular, is linked to disorders ranging from mild inflammatory effects of the skin to as serious as causing several different types of cancers. Changes in lifestyle together with depletion in the atmospheric ozone layer during the last few decades have led to an increase in the incidence of skin cancer. Skin cancers consisting of basal and squamous cell carcinomas are especially linked to the UVB part of solar radiation. Reducing excessive exposure to solar radiation is desirable; however, as this approach is unavoidable, it is suggested that other novel strategies be developed to reduce the effects of solar radiation to skin. One approach to reduce the harmful effects of solar radiation is through the use of phytochemicals, an approach that is popularly known as "Photochemoprotection." In recent years many phytochemicals with potential antioxidant properties have been identified and found to be photoprotective in nature. We describe here some of the most popular phytochemicals being studied that have the potential to reduce the harmful effects associated with solar UV radiation. PMID:18266816

  12. [A case of prednisolone therapy for radiation-induced hemorrhagic cystitis].

    PubMed

    Yanagi, Masato; Nishimura, Taiji; Kurita, Susumu; Lee, Chorsu; Kondo, Yukihiro; Yamazaki, Keiichi

    2011-05-01

    Hemorrhagic cystitis resulting from radiation to pelvic visceral malignant lesions often might be incurable and there have been no established definitive treatment. We experienced a case with severe radiation-induced hemorrhagic cystitis refractory to conventional therapy. The treatment with oral administration of prednisolone was performed and obtained a successful result. Gross hematuria disappeared in 2 weeks in this case. This experience suggested that oral administration of prednisolone could be considered the treatment for patients with radiation-induced hemorrhagic cystitis when usual treatments including transurethral electro-coagulation are unsuccessful. PMID:21846069

  13. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature

    PubMed Central

    Salvo, N.; Barnes, E.; van Draanen, J.; Stacey, E.; Mitera, G.; Breen, D.; Giotis, A.; Czarnota, G.; Pang, J.; De Angelis, C.

    2010-01-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance—and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials. For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase ii and phase iii trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho–McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6). In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus

  14. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature.

    PubMed

    Salvo, N; Barnes, E; van Draanen, J; Stacey, E; Mitera, G; Breen, D; Giotis, A; Czarnota, G; Pang, J; De Angelis, C

    2010-08-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance-and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials.For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase II and phase III trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho-McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6).In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus on

  15. Numerical Investigation of Radiative Heat Transfer in Laser Induced Air Plasmas

    NASA Technical Reports Server (NTRS)

    Liu, J.; Chen, Y. S.; Wang, T. S.; Turner, James E. (Technical Monitor)

    2001-01-01

    Radiative heat transfer is one of the most important phenomena in the laser induced plasmas. This study is intended to develop accurate and efficient methods for predicting laser radiation absorption and plasma radiative heat transfer, and investigate the plasma radiation effects in laser propelled vehicles. To model laser radiation absorption, a ray tracing method along with the Beer's law is adopted. To solve the radiative transfer equation in the air plasmas, the discrete transfer method (DTM) is selected and explained. The air plasma radiative properties are predicted by the LORAN code. To validate the present nonequilibrium radiation model, several benchmark problems are examined and the present results are found to match the available solutions. To investigate the effects of plasma radiation in laser propelled vehicles, the present radiation code is coupled into a plasma aerodynamics code and a selected problem is considered. Comparisons of results at different cases show that plasma radiation plays a role of cooling plasma and it lowers the plasma temperature by about 10%. This change in temperature also results in a reduction of the coupling coefficient by about 10-20%. The present study indicates that plasma radiation modeling is very important for accurate modeling of aerodynamics in a laser propelled vehicle.

  16. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    SciTech Connect

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Lee, Seung-Sook; Park, Sunhoo

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  17. Radiation-Induced Breast Cancer Incidence and Mortality from Digital Mammography Screening: A Modeling Study

    PubMed Central

    Miglioretti, Diana L.; Lange, Jane; van den Broek, Jeroen J.; Lee, Christoph I.; van Ravesteyn, Nicolien T.; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J.; Melnikow, Joy; de Koning, Harry J.; Hubbard, Rebecca A.

    2016-01-01

    Background Estimates of radiation-induced breast cancer risk from mammography screening have not previously considered dose exposure variation or diagnostic work-up after abnormal screening. Objective To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening, considering exposure from screening and diagnostic mammography and dose variation across women. Design Two simulation-modeling approaches using common data on screening mammography from the Breast Cancer Surveillance Consortium and radiation dose from mammography from the Digital Mammographic Imaging Screening Trial. Setting U.S. population. Patients Women aged 40–74 years. Interventions Annual or biennial digital mammography screening from age 40, 45, or 50 until 74. Measurements Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality per 100,000 women screened (harms). Results On average, annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancers (95% confidence interval [CI]=88–178) leading to 16 deaths (95% CI=11–23) relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 radiation-induced breast cancers leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete breast examination (8% of population) were projected to have higher radiation-induced breast cancer incidence and mortality (266 cancers, 35 deaths per 100,000 women), compared to women with small or average breasts (113 cancers, 15 deaths per 100,000 women). Biennial screening starting at age 50 reduced risk of radiation-induced cancers 5-fold. Limitations We were unable to estimate years of life lost from radiation-induced breast cancer. Conclusions Radiation-induced breast cancer incidence and mortality from digital mammography screening are impacted by dose

  18. Bystander effect induced by UV radiation; why should we be interested?

    PubMed

    Widel, Maria

    2012-01-01

    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.  PMID:23175338

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

    PubMed Central

    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

  20. Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice.

    PubMed

    Li, Ming; Du, Aonan; Xu, Jing; Ma, Yanchao; Cao, Han; Yang, Chao; Yang, Xiao-Dong; Xing, Chun-Gen; Chen, Ming; Zhu, Wei; Zhang, Shuyu; Cao, Jianping

    2016-01-01

    The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation, and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein, and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis, and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury, and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure. PMID:27436572

  1. Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice

    PubMed Central

    Li, Ming; Du, Aonan; Xu, Jing; Ma, Yanchao; Cao, Han; Yang, Chao; Yang, Xiao-Dong; Xing, Chun-Gen; Chen, Ming; Zhu, Wei; Zhang, Shuyu; Cao, Jianping

    2016-01-01

    The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation, and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein, and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis, and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury, and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure. PMID:27436572

  2. Management of late radiation-induced rectal injury after treatment of carcinoma of the uterus

    SciTech Connect

    Allen-Mersh, T.G.; Wilson, E.J.; Hope-Stone, H.F.; Mann, C.V.

    1987-06-01

    Sixty-one of 1418 (4.3 per cent) patients treated with radiation for carcinoma of the uterus from 1963 to 1983 had significant radiation-induced complications of the intestine develop which required a surgical opinion considering further management. Ninety-three per cent of these complications involved the rectum. Florid proctitis resolved within two years of onset in 33 per cent of the patients who were managed conservatively while 22 per cent of the patients died of disseminated disease within the same time period. Surgical treatment was eventually necessary in 39 per cent of the patients who were initially treated conservatively for radiation induced proctitis. Rectal excision with coloanal sleeve anastomosis produced a satisfactory result in eight of 11 patients with severe radiation injury involving the rectum. The incidence of radiation-induced and malignant rectovaginal fistula were similar (1 per cent), but disease-induced symptoms tended to occur earlier after primary treatment (a median of eight months) compared with radiation-induced symptoms (a median of 16 months).

  3. Genetic background influences loss of heterozygosity patterns in radiation-induced mouse thymic lymphoma

    PubMed Central

    Hang, Michael; Huang, Yurong; Snijders, Antoine M.; Mao, Jian-Hua

    2015-01-01

    Previous studies have revealed that p53 heterozygous (p53+/−) mice are extremely susceptible to radiation-induced tumorigenesis. To investigate whether genetic background influences radiation induced tumor susceptibility, we crossed p53+/− 129/Sv mice with genetically diverse strains to generate p53+/− F1 hybrids. The results showed that genetic background had a profound impact on tumor latency after exposure to gamma radiation, while the tumor spectrum did not change. We further characterized the thymic lymphomas that arose in the p53+/− mice by genome-wide loss of heterozygosity (LOH) analyses and found that genetic background strongly influenced the frequency of LOH and the loss of which parental allele on different chromosomes. Further research is needed to identify which genetic variations control the LOH patterns in radiation-induced thymic lymphomas and to evaluate its relevance to human cancers. PMID:25932465

  4. Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.

    PubMed

    Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B; Wang, Ya

    2016-06-01

    Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk. PMID:27345200

  5. Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

    NASA Astrophysics Data System (ADS)

    Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

    2016-06-01

    Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

  6. Effect of blue light radiation on curcumin-induced cell death of breast cancer cells

    NASA Astrophysics Data System (ADS)

    Zeng, X. B.; Leung, A. W. N.; Xia, X. S.; Yu, H. P.; Bai, D. Q.; Xiang, J. Y.; Jiang, Y.; Xu, C. S.

    2010-06-01

    In the present study, we have successfully set up a novel blue light source with the power density of 9 mW/cm2 and the wavelength of 435.8 nm and then the novel light source was used to investigate the effect of light radiation on curcumin-induced cell death. The cytotoxicity was investigated 24 h after the treatment of curcumin and blue light radiation together using MTT reduction assay. Nuclear chromatin was observed using a fluorescent microscopy with Hoechst33258 staining. The results showed blue light radiation could significantly enhance the cytotoxicity of curcumin on the MCF-7 cells and apoptosis induction. These findings demonstrated that blue light radiation could enhance curcumin-induced cell death of breast cancer cells, suggesting light radiation may be an efficient enhancer of curcumin in the management of breast cancer.

  7. Anti-apoptotic peptides protect against radiation-induced cell death

    SciTech Connect

    McConnell, Kevin W.; Muenzer, Jared T.; Chang, Kathy C.; Davis, Chris G.; McDunn, Jonathan E.; Coopersmith, Craig M.; Hilliard, Carolyn A.; Hotchkiss, Richard S.; Grigsby, Perry W.; Hunt, Clayton R. . E-mail: chunt@radonc.wustl.edu

    2007-04-06

    The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues.

  8. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    NASA Technical Reports Server (NTRS)

    Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

    2002-01-01

    Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

  9. Gamma-radiation induced changes in the physical and chemical properties of lignocellulose.

    PubMed

    Khan, Ferdous; Ahmad, S R; Kronfli, E

    2006-08-01

    gamma-radiation induced effects on the physical and chemical properties of natural lignocellulose (jute) polymer were investigated. Samples were irradiated to required total doses at a particular dose rate. The changes in the parameters such as the tensile strength, elongation at break, and work done at rupture for the lignocellulose samples on irradiation with the gamma-rays from a cobalt-60 source were measured. The mechanical properties were found to have nonlinear relations with the radiation doses. The chemical stability of irradiated fibers was found to degrade progressively with the increase of radiation dose. Additionally, other chemical changes of the samples due to exposure to high-energy radiation were also investigated using fluorescence and infrared spectroscopic analysis. Differential scanning calorimetry and thermogravimetric studies showed a significant reduction in thermal stability. The wide-angle X-ray diffraction study showed that structural changes of cellulose appeared due to the radiation-induced chemical reaction of lignocellulose. PMID:16903675

  10. Surface photoconductivity of organosilicate glass dielectrics induced by vacuum-ultraviolet radiation

    SciTech Connect

    Zheng, H.; Nichols, M. T.; Pei, D.; Shohet, J. L.; Nishi, Y.

    2013-08-14

    The temporary increase in the electrical surface conductivity of low-k organosilicate glass (SiCOH) during exposure to vacuum-ultraviolet radiation (VUV) is investigated. To measure the photoconductivity, patterned “comb structures” are deposited on dielectric films and exposed to synchrotron radiation in the range of 8–25 eV, which is in the energy range of most plasma vacuum-ultraviolet radiation. The change in photo surface conductivity induced by VUV radiation may be beneficial in limiting charging damage of dielectrics by depleting the plasma-deposited charge.

  11. Resonance laser-induced ionisation of sodium vapour taking radiative transfer into account

    SciTech Connect

    Kosarev, N I; Shaparev, N Ya

    2006-04-30

    The problem of ionisation of atomic sodium in the field of resonance laser radiation is numerically solved taking radiative transfer into account. Seed electrons are produced due to the mechanism of associative ionisation, then they gain energy in superelastic processes (collisions of the second kind) and initiate the avalanche ionisation of the medium by electron impact. We studied the effect of secondary radiation on the laser pulse propagation upon competition between the ionising and quenching electron collisions with excited atoms, on the kinetics of ionisation-induced vapour bleaching, and the plasma channel expansion in the form of a halo. (interaction of laser radiation with matter)

  12. Formation of globular clusters induced by external ultraviolet radiation II: Three-dimensional radiation hydrodynamics simulations

    NASA Astrophysics Data System (ADS)

    Abe, Makito; Umemura, Masayuki; Hasegawa, Kenji

    2016-08-01

    We explore the possibility of the formation of globular clusters under ultraviolet (UV) background radiation. One-dimensional spherical symmetric radiation hydrodynamics (RHD) simulations by Hasegawa et al. have demonstrated that the collapse of low-mass (106-7 M⊙) gas clouds exposed to intense UV radiation can lead to the formation of compact star clusters like globular clusters (GCs) if gas clouds contract with supersonic infall velocities. However, three-dimensional effects, such as the anisotropy of background radiation and the inhomogeneity in gas clouds, have not been studied so far. In this paper, we perform three-dimensional RHD simulations in a semi-cosmological context, and reconsider the formation of compact star clusters in strong UV radiation fields. As a result, we find that although anisotropic radiation fields bring an elongated shadow of neutral gas, almost spherical compact star clusters can be procreated from a "supersonic infall" cloud, since photo-dissociating radiation suppresses the formation of hydrogen molecules in the shadowed regions and the regions are compressed by UV heated ambient gas. The properties of resultant star clusters match those of GCs. On the other hand, in weak UV radiation fields, dark matter-dominated star clusters with low stellar density form due to the self-shielding effect as well as the positive feedback by ionizing photons. Thus, we conclude that the "supersonic infall" under a strong UV background is a potential mechanism to form GCs.

  13. Detecting Radiation-Induced Injury Using Rapid 3D Variogram Analysis of CT Images of Rat Lungs

    SciTech Connect

    Jacob, Rick E.; Murphy, Mark K.; Creim, Jeffrey A.; Carson, James P.

    2013-10-01

    A new heterogeneity analysis approach to discern radiation-induced lung damage was tested on CT images of irradiated rats. The method, combining octree decomposition with variogram analysis, demonstrated a significant correlation with radiation exposure levels, whereas conventional measurements and pulmonary function tests did not. The results suggest the new approach may be highly sensitive for assessing even subtle radiation-induced changes

  14. Endocrine effects of Fukushima: Radiation-induced endocrinopathy

    PubMed Central

    Niazi, Asfandyar Khan; Niazi, Shaharyar Khan

    2011-01-01

    The unfortunate accidents of Chernobyl and Fukushima have led to an enormous amount of radioactive material being released into the atmosphere. Radiation exposure to the human body may be as a result of accidents, such as those in Chernobyl and Fukushima, or due to occupational hazards, such as in the employees of nuclear plants, or due to therapeutic or diagnostic procedures. These different sources of radiations may affect the human body as a whole or may cause localized damage to a certain area of the body, depending upon the extent and dosage of the irradiation. More or less every organ is affected by radiation exposure. Some require a higher dose to be affected while others may be affected at a lower dose. All the endocrine glands are susceptible to damage by radiation exposure; however, pituitary, thyroid and gonads are most likely to be affected. In addition to the endocrine effects, the rates of birth defects and carcinomas may also be increased in the population exposed to excessive radiation. PMID:21731864

  15. Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

    PubMed Central

    Acharya, Munjal M.; Baulch, Janet E.; Lusardi, Theresa A.; Allen, Barrett. D.; Chmielewski, Nicole N.; Baddour, Al Anoud D.; Limoli, Charles L.; Boison, Detlev

    2016-01-01

    Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered

  16. Growth hormone used to control intractable bleeding caused by radiation-induced gastritis

    PubMed Central

    Zhang, Liang; Xia, Wen-Jie; Zhang, Zheng-Sen; Lu, Xin-Liang

    2015-01-01

    Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis. PMID:26309374

  17. Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation.

    PubMed

    Guha, C; Sharma, A; Gupta, S; Alfieri, A; Gorla, G R; Gagandeep, S; Sokhi, R; Roy-Chowdhury, N; Tanaka, K E; Vikram, B; Roy-Chowdhury, J

    1999-12-01

    Hepatic tumors often recur in the liver after surgical resection. Postoperative radiotherapy (RT) could improve survival, but curative RT may induce delayed life-threatening radiation-induced liver damage. Because RT inhibits liver regeneration, we hypothesized that unirradiated, transplanted hepatocytes would proliferate preferentially in a partially resected and irradiated liver, providing metabolic support. We subjected F344 rats to hepatic RT and partial hepatectomy with/without a single intrasplenic, syngeneic hepatocyte transplantation. Hepatocyte transplantation ameliorated radiation-induced liver damage and improved survival of rats receiving RT after partial hepatectomy. We further demonstrated that transplanted hepatocytes extensively repopulate and function in a heavily irradiated rat liver. PMID:10606225

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

    PubMed

    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

  19. Protection of DNA From Ionizing Radiation-Induced Lesions by Asiaticoside.

    PubMed

    Joy, Jisha; Alarifi, Saud; Alsuhaibani, Entissar; Nair, Cherupally K Krishnan

    2015-01-01

    This study aims to investigate whether asiaticoside, a triterpene glycoside, can afford protection to DNA from alterations induced by gamma radiation under in vitro, ex vivo, and in vivo conditions. In vitro studies were done on plasmid pBR322 DNA, ex vivo studies were done on cellular DNA of human peripheral blood leukocytes, and in vivo investigations were conducted on cellular DNA of spleen and bone marrow cells of mice exposed to whole-body gamma radiation. The supercoiled form of the plasmid pBR322 DNA upon exposure to the radiation was converted into relaxed open circular form due to induction of strand breaks. Presence of asiaticoside along with the DNA during irradiation prevented the relaxation of the supercoiled form to the open circular form. When human peripheral blood leukocytes were exposed to gamma radiation, the cellular DNA suffered strand breaks as evidenced by the increased comet parameters in an alkaline comet assay. Asiaticoside, when present along with blood during irradiation ex vivo, prevented the strand breaks and the comet parameters were closer to that of the controls. Whole-body exposure of mice to gamma radiation resulted in a significant increase in comet parameters of DNA of bone marrow and spleen cells of mice as a result of radiation-induced strand breaks in DNA. Administration of asiaticoside prior to whole-body radiation exposure of the mice prevented this increase in radiation-induced increase in comet parameters, which could be the result of protection to DNA under in vivo conditions of radiation exposure. Thus, it can be concluded from the results that asiaticoside can offer protection to DNA from radiation-induced alterations under in vitro, ex vivo, and in vivo conditions. PMID:26756427

  20. Potentiation of radiation-induced regrowth delay in murine tumors by fludarabine.

    PubMed

    Grégoire, V; Hunter, N; Milas, L; Brock, W A; Plunkett, W; Hittelman, W N

    1994-01-15

    Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-monophosphate), an adenine nucleoside analogue, has previously been shown to inhibit the repair of radiation-induced chromosome damage. Thus fludarabine may have therapeutic utility in combination with photon irradiation. The purpose of this study was to determine whether fludarabine could enhance radiation-induced murine tumor regrowth delay and to determine the most effective dose and schedule of the combination. A significant (P < 0.05) absolute regrowth delay enhancement was observed in three murine tumor models (SA-NH, a sarcoma; and MCA-K and MCA-4, mammary carcinomas) when fludarabine (800 mg/kg) was given 1 h prior to 25 Gy gamma-irradiation. While fludarabine enhanced radiation-induced tumor regrowth delay when given between -36 h and +6 h of radiation (SA-NH tumor), the greatest enhancement was observed when fludarabine was given at -24 h prior to irradiation (radiation dose modification factor of 1.82 at -24 h compared to 1.57 at -3 h prior to radiation). The degree of fludarabine enhancement (at -3 or -24 h) was dose dependent at doses above 200 mg/kg. When fludarabine and radiation were administered on a fractionated schedule (fludarabine given 3 h prior to radiation each day for 4 days), the dose modification factor increased to 2.14 (1.63 if the effect of fludarabine alone is subtracted). These results suggest that fludarabine enhances radiation-induced tumor regrowth delay in a more than additive fashion after both single and fractionated treatments, and the degree of enhancement is dependent on the sequence and timing of administration, the fludarabine dose, and the tumor type. Thus, fludarabine may have clinical potential as a radiation enhancer in the treatment of solid tumors. PMID:8275483

  1. Naturally induced secondary radiation in interplanetary space: Preliminary analyses for gamma radiation and radioisotope production from thermal neutron activation

    NASA Astrophysics Data System (ADS)

    Plaza-Rosado, Heriberto

    1991-09-01

    Thermal neutron activation analyses were carried out for various space systems components to determine gamma radiation dose rates and food radiation contamination levels. The space systems components selected were those for which previous radiation studies existed. These include manned space vehicle radiation shielding, liquid hydrogen propellant tanks for a Mars mission, and a food supply used as space vehicle radiation shielding. The computational method used is based on the fast neutron distribution generated by the BRYNTRN and HZETRN transport codes for Galactic Cosmic Rays (GCR) at solar minimum conditions and intense solar flares in space systems components. The gamma dose rates for soft tissue are calculated for water and aluminum space vehicle slab shields considering volumetric source self-attenuation and exponential buildup factors. In the case of the lunar habitat with regolith shielding, a completely exposed spherical habitat was assumed for mathematical convenience and conservative calculations. Activation analysis of the food supply used as radiation shielding is presented for four selected nutrients: potassium, calcium, sodium, and phosphorus. Radioactive isotopes that could represent a health hazard if ingested are identified and their concentrations are identified. For nutrients soluble in water, it was found that all induced radioactivity was below the accepted maximum permissible concentrations.

  2. Naturally induced secondary radiation in interplanetary space: Preliminary analyses for gamma radiation and radioisotope production from thermal neutron activation

    NASA Technical Reports Server (NTRS)

    Plaza-Rosado, Heriberto

    1991-01-01

    Thermal neutron activation analyses were carried out for various space systems components to determine gamma radiation dose rates and food radiation contamination levels. The space systems components selected were those for which previous radiation studies existed. These include manned space vehicle radiation shielding, liquid hydrogen propellant tanks for a Mars mission, and a food supply used as space vehicle radiation shielding. The computational method used is based on the fast neutron distribution generated by the BRYNTRN and HZETRN transport codes for Galactic Cosmic Rays (GCR) at solar minimum conditions and intense solar flares in space systems components. The gamma dose rates for soft tissue are calculated for water and aluminum space vehicle slab shields considering volumetric source self-attenuation and exponential buildup factors. In the case of the lunar habitat with regolith shielding, a completely exposed spherical habitat was assumed for mathematical convenience and conservative calculations. Activation analysis of the food supply used as radiation shielding is presented for four selected nutrients: potassium, calcium, sodium, and phosphorus. Radioactive isotopes that could represent a health hazard if ingested are identified and their concentrations are identified. For nutrients soluble in water, it was found that all induced radioactivity was below the accepted maximum permissible concentrations.

  3. Studies of oxidative degradation of polymers induced by ionizing radiation

    SciTech Connect

    Clough, R.L.; Gillen, K.T.

    1989-01-01

    Radiation effects on polymers in the presence of air are characterized by complicated phenomena such as dose-rate effects and post-irradiation degradation. These time-dependent effects can be understood in these terms: (1) features of the free radical chain-reaction chemistry underlying the oxidation, and (2) oxygen diffusion effects. A profiling technique has been developed to study heterogeneous degradation resulting from oxygen diffusion, and kinetic schemes have been developed to allow long-term aging predictions from short-term high dose-rate experiments. Low molecular weight additives which act either as free-radical scavengers or else as energy-scavengers are effective as stabilizers in radiation-oxidation environments. Non-radical oxidation mechanisms, involving species such as ozone, can also be important in the radiation-oxidation of polymers. 18 refs., 15 figs.

  4. NRF2 mitigates radiation-induced hematopoietic death

    PubMed Central

    Chute, John P.

    2014-01-01

    Fractionated, high-dose total body irradiation (TBI) is used therapeutically to myeloablate and immune suppress patients undergoing hematopoietic stem cell (HSC) transplantation. Acute exposure to ionizing radiation can have fatal effects on the hematopoietic and immune systems. Currently, therapies aimed at ameliorating ionizing radiation–associated toxicities are limited. In the February 2014 issue of the JCI, Kim and colleagues demonstrated that induction of nuclear factor erythroid 2–related factor 2 (NRF2) enhances HSC regeneration and increases survival following ionizing radiation exposure in mice. The results of this study suggest that NRF2 is a novel potential target for the development of therapeutics aimed at mitigating the toxicities of ionizing radiation exposure. PMID:24569364

  5. SOD2-mediated Adaptive Responses Induced by Low Dose Ionizing Radiation via TNF Signaling and Amifostine

    PubMed Central

    Murley, J.S.; Baker, K.L.; Miller, R.C.; Darga, T.E.; Weichselbaum, R.R.; Grdina, D.J.

    2011-01-01

    Manganese superoxide dismutase (SOD2)-mediated adaptive processes that protect against radiation-induced micronuclei formation can be induced in cells following a 2 Gy exposure by previously exposing them to either low dose ionizing radiation (10 cGy) or WR1065 (40 µM), the active thiol form of amifostine. While both adaptive processes culminate with elevated levels of SOD2 enzymatic activities, the underlying pathways differ in complexity, with the tumor necrosis factor α (TNFα) signaling pathway implicated in the low dose radiation-induced response, but not in the thiol-induced pathway. The goal of this study was the characterization of the effects of TNFα receptors1 and 2 (TNFR1, 2) on the adaptive responses induced by low dose irradiation or thiol exposures using micronuclei formation as an endpoint. BFS-1 wild type (WT) cells with functional TNFR1 and 2 were exposed 24 h prior to a 2 Gy dose of ionizing radiation to either 10 cGy or a 40 µM dose of WR1065. BFS2C-SH02 cells defective in TNFR1 and BFS2C-SH22 cells defective in both TNFR1 and 2, generated from BFS2C-SH02 cells by transfection with a murine TNFR2 targeting vector and confirmed to be TNFR2 defective by quantitative PCR, were also exposed under similar conditions for comparison. A 10 cGy dose of radiation induced a significant elevation of SOD2 activity in BFS-1 (P < 0.001) and BFS2C-SH02 (P = 0.005) but not BFS2C-SH22 cells (P = 0.433) as compared to their respective untreated controls. In contrast, WR1065 significantly induced elevations in SOD2 activity in all three cell lines (P = 0.001; P = 0.007; P = 0.020; respectively). A significant reduction in the frequency of radiation-induced micronuclei was observed in each cell line when exposure to a 2 Gy challenge dose of radiation occurred during the period of maximal elevation in SOD2 activity. However, this adaptive effect was completely inhibited if the cells were transfected 24 h prior to low dose radiation or thiol exposure with SOD2 si

  6. [Hyperbaric oxygen therapy and radiation-induced hemorrhagic cystitis].

    PubMed

    Pires, Christophe; Irani, Jacques; Ouaki, Frédéric; Murat, François-Joseph; Doré, Bertrand

    2002-12-01

    Radiotherapy alone or in combination with other modalities is used in the treatment of a large number of pelvic tumours of urological or gynaecological origin. Despite constant progress in this field, medium-term and long-term complications remain frequent and often require difficult long-term management. Radiation cystitis is one of the most frequent complications and directly concerns urologists. Among the various treatment options for haemorrhagic cystitis, hyperbaric oxygen therapy appears to give good short-term and medium-term results. It is currently reserved for cases refractory to the standard treatments for radiation cystitis. PMID:12545623

  7. Radiation Induced Stress Relaxation in Silicone and Polyurethane Elastomers

    SciTech Connect

    Spellman, G; Gourdin, W; Jensen, W; Pearson, M; Fine, I

    2007-08-22

    Many different materials are used in the National Ignition Facility, NIF, located at Lawrence Livermore National Laboratory, LLNL. Some of these are exposed to significant doses of ionizing radiation. Two elastomers are of special interest because they are used in sealing applications with long expected lifetimes. These are LPU4, a polyurethane formulated at LLNL, and Dow Corning DC93-500, a silicone RTV elastomer. In 2004 a program to determine the impact of ionizing radiation on the stress relaxation and compression set characteristics of these two elastomers was undertaken. Since the materials are used in continuous compression and must reliably seal, the primary test utilized was a stress relaxation test. This test provides insight into the ability of a seal to remain functional in a static seal. The test determines how much residual force remains after a certain period of time under compression. The temperature and absorbed radiation dose can dramatically impact this property. In this study the only independent environmental variable studied is the effect of radiation at ambient temperatures. Two levels of radiation exposure were studied, 1 MRad, and 10 MRad. One of the independent test parameters is the compression deflection during storage and in this test the value used was 25%. The need for a compression retention mechanism ruled out radiation exposure in the compressed direction since the high atomic number materials for that device would block the radiation. Therefore, an annular ring was chosen for the specimen shape. The procedures are, as closely as possible, based on ASTM D 6147-97. Since the data is readily obtained at the end of the stress relaxation test, the samples were also evaluated for compression set. Compression set is the essentially permanent deformation incurred in a seal after the seal is compressed for some period of time and then unloaded. Though this is indicative of potential sealing reliability, it is not as direct an indicator of

  8. Effect of mobile phone radiation on pentylenetetrazole-induced seizure threshold in mice

    PubMed Central

    Kouchaki, Ebrahim; Motaghedifard, Morteza; Banafshe, Hamid Reza

    2016-01-01

    Objective(s): Scientific interest in potential mobile phone impact on human brain and performance has significantly increased in recent years. The present study was designed to evaluate the effects of mobile phone radiation on seizure threshold in mice. Materials and methods: BALB/c male mice were randomly divided into three groups: control, acute, and chronic mobile phone radiation for 30, 60, and 90 min with frequency 900 to 950 MHz and pulse of 217 Hz. The chronic group received 30 days of radiation, while the acute group received only once. The intravenous infusion of pentylenetetrazole (5 mg/ml) was used to induce seizure signs. Results: Although acute mobile radiation did not change seizure threshold, chronic radiation decreased the clonic and tonic seizure thresholds significantly. Conclusion: Our data suggests that the continued and prolonged contact with the mobile phone radiation might increase the risk of seizure attacks and should be limited.

  9. Induced emission of extraordinary mode radiation in tokamaks

    NASA Technical Reports Server (NTRS)

    Freund, H. P.; Lee, L. C.

    1979-01-01

    The implications of the formation of a positive slope in the runaway electron tail in tokamak plasmas are investigated in regard to the radiation in the vicinity of the electron plasma frequency. In particular, it is shown that the amplification of extraordinary mode waves may result.

  10. Assessing application vulnerability to radiation-induced SEUs in memory

    NASA Technical Reports Server (NTRS)

    Springer, P. L.

    2001-01-01

    One of the goals of the Remote Exploration and Experimentation (REE) project at JPL is to determine how vulnerable applications are to single event upsets (SEUs) when run in low radiation space environments using commercial-off-the-shelf (COTS) components.

  11. Theory of 2 omegape radiation induced by the bow shock

    NASA Astrophysics Data System (ADS)

    Yoon, Peter H.; Wu, C. S.; Vinas, A. F.-; Reiner, M. J.; Fainberg, J.; Stone, R. G.

    1994-12-01

    A new radiation emission mechanism is proposed to explain electomagnetic radiation observed at twice the electron plasma frequency, 2 omegape, in the upstream region of the Earth's bow shock. This radiation had its origin at the electron foreshock boundary where energetic electron beams and intense narrow-band Langmiur waves are observed. The proposed emission mechanism results from the interaction of the electron beam and Langmuir waves that are backscattered off thermal ions. This interaction is described by a nonlinear dispersion equation which incorporates an effect owing to electron trajectory modulation by the backscattered Langmuir waves. Subsequent analysis of the dispersion equation reveals two important consequences. First, a long-wavelength electrostatic quasi-mode with frequency at 2 omegape is excited, and second, the quasi-mode and the electomagnetic mode are nonlinearly coupled. The implication is that, when the excited 2 omegape quasi-mode propagates in an inhomgeneous medium with slightly decreasing density, the quasi-mode can be converted directly into an electromagnetic mode. Hense the electomagnetic radiation at twice the plasma frequency is generated. Numerical solutions of the dispersion equation with the choice of parameters that describe physical characteristics of the electron foreshock are presented, which illustrates the viability of the new mechanism.

  12. Formation of globular clusters induced by external ultraviolet radiation

    NASA Astrophysics Data System (ADS)

    Hasegawa, Kenji; Umemura, Masayuki; Kitayama, Tetsu

    2009-08-01

    We present a novel scenario for globular cluster (GC) formation, where the ultraviolet (UV) background radiation effectively works so as to produce compact star clusters. Recent observations on the age distributions of GCs indicate that many GCs formed even after the cosmic reionization epoch. This implies that a significant fraction of GCs formed in UV background radiation fields. Also, the star formation in an early-generation of subgalactic objects may be affected by strong UV radiation from pre-formed massive stars, e.g. Population III stars. Here, we explore the formation of GCs in UV radiation fields. For this purpose, we calculate baryon and dark matter (DM) dynamics in spherical symmetry, incorporating the self-shielding effects by solving the radiative transfer of UV radiation. In addition, we prescribe the star formation in cooled gas components and pursue the dynamics of formed stars. As a result, we find that the evolution of subgalactic objects in UV background radiation is separated into three types: (i) prompt star formation, where less massive clouds (~105-8Msolar) are promptly self-shielded and undergo star formation, (ii) delayed star formation, where photoionized massive clouds (>~108Msolar) collapse despite high thermal pressure and are eventually self-shielded to form stars in a delayed fashion, and (iii) supersonic infall, where photoionized less massive clouds (~105-8Msolar) contract with supersonic infall velocity and are self-shielded when a compact core forms. In particular, the type (iii) is a novel type found in the present simulations, and eventually produces a very compact star cluster. The resultant mass-to-light ratios, half-mass radii and velocity dispersions for the three types are compared to the observations of GCs, dwarf spheroidals (dSphs) and ultracompact dwarfs (UCDs). It turns out that the properties of star clusters resulting from supersonic infall match well with those of observed GCs, whereas the other two types are

  13. Mitochondria regulate DNA damage and genomic instability induced by high LET radiation

    NASA Astrophysics Data System (ADS)

    Zhang, Bo; Davidson, Mercy M.; Hei, Tom K.

    2014-04-01

    High linear energy transfer (LET) radiation including α particles and heavy ions is the major type of radiation found in space and is considered a potential health risk for astronauts. Even though the chance that these high LET particles traversing through the cytoplasm of cells is higher than that through the nuclei, the contribution of targeted cytoplasmic irradiation to the induction of genomic instability and other chromosomal damages induced by high LET radiation is not known. In the present study, we investigated whether mitochondria are the potential cytoplasmic target of high LET radiation in mediating cellular damage using a mitochondrial DNA (mtDNA) depleted (ρ0) human small airway epithelial (SAE) cell model and a precision charged particle microbeam with a beam width of merely one micron. Targeted cytoplasmic irradiation by high LET α particles induced DNA oxidative damage and double strand breaks in wild type ρ+ SAE cells. Furthermore, there was a significant increase in autophagy and micronuclei, which is an indication of genomic instability, together with the activation of nuclear factor kappa-B (NF-κB) and mitochondrial inducible nitric oxide synthase (iNOS) signaling pathways in ρ+ SAE cells. In contrast, ρ0 SAE cells exhibited a significantly lower response to these same endpoints examined after cytoplasmic irradiation with high LET α particles. The results indicate that mitochondria are essential in mediating cytoplasmic radiation induced genotoxic damage in mammalian cells. Furthermore, the findings may shed some light in the design of countermeasures for space radiation.

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

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  15. Mitochondria regulate DNA damage and genomic instability induced by high LET radiation

    PubMed Central

    Zhang, Bo; Davidson, Mercy M.; Hei, Tom K.

    2014-01-01

    High linear energy transfer (LET) radiation including α particles and heavy ions is the major type of radiation find in space and is considered a potential health risk for astronauts. Even though the chance that these high LET particles traversing through the cytoplasm of cells is higher than that through the nuclei, the contribution of targeted cytoplasmic irradiation, to the induction of genomic instability and other chromosomal damages induced by high LET radiation is not known. In the present study, we investigated whether mitochondria are the potential cytoplasmic target of high LET radiation in mediating cellular damage using a mitochondrial DNA (mtDNA) depleted (ρ0) human small airway epithelial (SAE) cell model and a precision charged particle microbeam with a beam width of merely one micron. Targeted cytoplasmic irradiation by high LET α particles induced DNA oxidative damage and double strand breaks in wild type ρ+ SAE cells. Furthermore, there was a significant increase in autophagy, micronuclei, which is an indication of genomic instability, together with the activation of nuclear factor kappa-B (NF-κB) and mitochondrial inducible nitric oxide synthase (iNOS) signaling pathways in ρ+ SAE cells. In contrast, ρ0 SAE cells exhibited a significantly lower response to these same endpoints examined after cytoplasmic irradiation with high LET α particles. The results indicate that mitochondria are essential in mediating cytoplasmic radiation induced genotoxic damage in mammalian cells. Furthermore, the findings may shed some light in the design of countermeasures for space radiation. PMID:25072018

  16. Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway.

    PubMed

    Lu, Chi; Xie, Conghua

    2016-06-01

    Radiotherapy is an important treatment modality for esophageal cancer; however, the clinical efficacy of radiotherapy is limited by tumor radioresistance. In the present study, we explored the hypothesis that radiation induces tumor cell autophagy as a cytoprotective adaptive response, which depends on liver kinase B1 (LKB1) also known as serine/threonine kinase 11 (STK11). Radiation-induced Eca-109 cell autophagy was found to be dependent on signaling through the LKB1 pathway, and autophagy inhibitors that disrupted radiation-induced Eca-109 cell autophagy increased cell cycle arrest and cell death in vitro. Inhibition of autophagy also reduced the clonogenic survival of the Eca-109 cells. When treated with radiation alone, human esophageal carcinoma xenografts showed increased LC3B and p-LKB1 expression, which was decreased by the autophagy inhibitor chloroquine. In vivo inhibition of autophagy disrupted tumor growth and increased tumor apoptosis when combined with 6 Gy of ionizing radiation. In summary, our findings elucidate a novel mechanism of resistance to radiotherapy in which radiation-induced autophagy, via the LKB1 pathway, promotes tumor cell survival. This indicates that inhibition of autophagy can serve as an adjuvant treatment to improve the curative effect of radiotherapy. PMID:27109915

  17. A Prospective Cohort Study on Radiation-induced Hypothyroidism: Development of an NTCP Model

    SciTech Connect

    Boomsma, Marjolein J.; Bijl, Hendrik P.; Christianen, Miranda E.M.C.; Beetz, Ivo; Chouvalova, Olga; Steenbakkers, Roel J.H.M.; Laan, Bernard F.A.M. van der; Oosting, Sjoukje F.; Schilstra, Cornelis; Langendijk, Johannes A.

    2012-11-01

    Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. Methods and Materials: The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Results: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm{sup 3}). Model performance was good with an area under the curve (AUC) of 0.85. Conclusions: This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.

  18. Radiation induced oral mucositis: a review of current literature on prevention and management.

    PubMed

    Mallick, Supriya; Benson, Rony; Rath, G K

    2016-09-01

    Oral mucositis (OM) is a major limiting acute side effect of radiotherapy for head and neck cancer. The spectrum of problems associated with mucositis includes oral pain, odynophagia, reduced oral intake, and secondary infections. Incidence of mucositis is increased with addition of concurrent chemotherapy as well as altered fractionation schedules. This leads to treatment interruption and suboptimal disease control. Hence, prevention as well as timely management of OM is necessary for optimum tumor control. We reviewed the English literature with key words "Radiation induced mucositis, Mucositis, Oral Mucositis" to find relevant articles describing incidence, pathophysiology, prophylaxis, and treatment of oral mucositis. Prevention and treatment of OM is an active area of research. Maintenance of oral hygiene is an important part in prevention of OM. A battery of agents including normal saline and alkali (soda bicarbonate) mouth washes, low level laser therapy, and benzydamine (non-steroidal analgesic and anti-inflammatory) have effectiveness in the prevention and treatment of radiation induced oral mucositis. Chlorhexidine mouth gargles are recommended for prevention of chemotherapy induced oral mucositis but is not recommended for radiotherapy associated mucositis. Treatment of co-existing infection is also important and both topical (povidone iodine) and systemic anti fungals should be used judiciously. Radiation induced oral mucositis is a common problem limiting the efficacy of radiation by increasing treatment breaks. Adequate prophylaxis and treatment may limit the severity of radiation mucositis and improve compliance to radiation which may translate in better disease control and survival. PMID:26116012

  19. Comparison of radiation-induced transmission degradation of borosilicate crown optical glass from four different manufacturers

    NASA Astrophysics Data System (ADS)

    Gusarov, Andrei; Doyle, Dominic; Glebov, Leonid; Berghmans, Francis

    2005-09-01

    Space-born optical systems must be tolerant to radiation to guarantee that the required system performance is maintained during prolonged mission times. The radiation-induced absorption in optical glasses is often related with the presence of impurities, which are, intentionally or not, introduced during the manufacturing process. Glass manufacturers use proprietary fabrication processes and one can expect that the radiation sensitivity of nominally identical optical glasses from different manufacturers is different. We studied the gamma-radiation induced absorption of several crown glasses with nd ≈ 1.516 and vd ≈ 64, i.e. NBK7 (Schott), S-BSL7 (Ohara), BSC 517642 (Pilkington) and K8 (Russia). NBK7 recently replaced the well-known BK7. We therefore also compared the radiation response of NBK7 and BK7 glass. Our results show that whereas the glasses are optically similar before irradiation, they show a different induced absorption after irradiation and also different post-radiation recovery kinetics. Taking these differences into account can help to improve the radiation tolerance of optical systems for space applications.

  20. Solar ultraviolet radiation induced variations in the stratosphere and mesosphere

    NASA Technical Reports Server (NTRS)

    Hood, L. L.

    1987-01-01

    The detectability and interpretation of short-term solar UV induced responses of middle atmospheric ozone, temperature, and dynamics are reviewed. The detectability of solar UV induced perturbations in the middle atmosphere is studied in terms of seasonal and endogenic dynamical variations. The interpretation of low-latitude ozone and possible temperature responses on the solar rotation time scale is examined. The use of these data to constrain or test photochemical model predictions is discussed.

  1. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD® in mice

    PubMed Central

    Ghosh, Sanchita P.; Kulkarni, Shilpa; Perkins, Michael W.; Hieber, Kevin; Pessu, Roli L.; Gambles, Kristen; Maniar, Manoj; Kao, Tzu-Cheg; Seed, Thomas M.; Kumar, K. Sree

    2012-01-01

    The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD®, also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex-RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicle-treated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury. PMID:22843617

  2. Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Torous, D.; Lutze-Mann, L.; Winegar, R.

    2000-01-01

    Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

  3. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway.

    PubMed

    Liu, Yunen; Tan, Dehong; Tong, Changci; Zhang, Yubiao; Xu, Ying; Liu, Xinwei; Gao, Yan; Hou, Mingxiao

    2015-12-01

    The purpose of this study was to explore the effect of blueberry anthocyanins (BA) on radiation-induced lung injury and investigate the mechanism of action. Seven days after BA(20 and 80 mg/kg/d)administration, 6 weeks old male Sprague-Dawley rats rats were irradiated by LEKTA precise linear accelerator at a single dose of 20 Gy only once. and the rats were continuously treated with BA for 4 weeks. Moreover, human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with either control-siRNA or siRNA targeting protein kinase R (PKR). Cells were then irradiated and treated with 75 μg/mL BA for 72 h. The results showed that BA significantly ameliorated radiation-induced lung inflammation, lung collagen deposition, apoptosis and PKR expression and activation. In vitro, BA significantly protected cells from radiation-induced cell death through modulating expression of Bcl-2, Bax and Caspase-3. Suppression of PKR by siRNA resulted in ablation of BA protection on radiation-induced cell death and modulation of anti-apoptotic and pro-apoptotic proteins, as well as Caspase-3 expression. These findings suggest that BA is effective in ameliorating radiation-induced lung injury, likely through the PKR signaling pathway. PMID:26551926

  4. Effect of radiation-induced damage on deuterium retention in tungsten, tungsten coatings and Eurofer

    NASA Astrophysics Data System (ADS)

    Ogorodnikova, O. V.; Sugiyama, K.

    2013-11-01

    An influence of radiation-induced damage on hydrogen isotope retention and transport in a bulk tungsten (W), dense nano-structured W coatings and Eurofer was investigated under well-defined laboratory conditions. Radiation-induced defects in W materials and Eurofer were created by irradiation with 20 MeV W ions. Following the damage production, samples were exposed to low-energy deuterium plasma. The deuterium (D) retention in each sample was subsequently measured by nuclear reaction analysis (NRA) for the depth profiling up to 6 μm. It was shown that the D retention at radiation-induced damage is almost equivalent for different W grades after irradiation at high enough fluence. The kinetic of D migration and trapping in damaged area as well as recovery of radiation-induced damage were investigated by loading at different temperatures. It was shown that deuterium retention in tungsten in fusion environment will be dominated by radiation-induced effect in a wide range of investigated temperatures, namely, from room temperature to 1100 K. Whereas displacement damage produced in Eurofer has less pronounced effect on the deuterium accumulation.

  5. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization.

    PubMed

    Meng, Zhen; Gan, Ye-Hua

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. PMID:25770423

  6. Non-Targeted Effects Induced by Ionizing Radiation: Mechanisms and Potential Impact on Radiation Induced Health Effects

    SciTech Connect

    Morgan, William F.; Sowa, Marianne B.

    2015-01-01

    Not-targeted effects represent a paradigm shift from the "DNA centric" view that ionizing radiation only elicits biological effects and subsequent health consequences as a result of an energy deposition event in the cell nucleus. While this is likely true at higher radiation doses (> 1Gy), at low doses (< 100mGy) non-targeted effects associated with radiation exposure might play a significant role. Here definitions of non-targeted effects are presented, the potential mechanisms for the communication of signals and signaling networks from irradiated cells/tissues are proposed, and the various effects of this intra- and intercellular signaling are described. We conclude with speculation on how these observations might lead to and impact long-term human health outcomes.

  7. Pressure-Induced Structural Transformation in Radiation-Amorphized Zircon

    SciTech Connect

    Trachenko, Kostya; Dove, Martin T.; Salje, E. K. H.; Brazhkin, V. V.; Tsiok, O. B.

    2007-03-30

    We study the response of a radiation-amorphized material to high pressure. We have used zircon ZrSiO{sub 4} amorphized by natural radiation over geologic times, and have measured its volume under high pressure, using the precise strain-gauge technique. On pressure increase, we observe apparent softening of the material, starting from 4 GPa. Using molecular dynamics simulation, we associate this softening with the amorphous-amorphous transformation accompanied by the increase of local coordination numbers. We observe permanent densification of the quenched sample and a nontrivial 'pressure window' at high temperature. These features point to a new class of amorphous materials that show a response to pressure which is distinctly different from that of crystals.

  8. A stochastic model of radiation-induced bone marrow damage

    SciTech Connect

    Cotlet, G.; Blue, T.E.

    2000-03-01

    A stochastic model, based on consensus principles from radiation biology, is used to estimate bone-marrow stem cell pool survival (CFU-S and stroma cells) after irradiation. The dose response model consists of three coupled first order linear differential equations which quantitatively describe time dependent cellular damage, repair, and killing of red bone marrow cells. This system of differential equations is solved analytically through the use of a matrix approach for continuous and fractionated irradiations. The analytic solutions are confirmed through the dynamical solution of the model equations using SIMULINK. Rate coefficients describing the cellular processes of radiation damage and repair, extrapolated to humans from animal data sets and adjusted for neutron-gamma mixed fields, are employed in a SIMULINK analysis of criticality accidents. The results show that, for the time structures which may occur in criticality accidents, cell survival is established mainly by the average dose and dose rate.

  9. Radiation-induced extrinsic photoconductivity in Li-doped Si.

    NASA Technical Reports Server (NTRS)

    Fenimore, E.; Mortka, T.; Corelli, J. C.

    1972-01-01

    Investigation of the effects of lithium on radiation-produced complexes having long-time stability by examining the localized energy levels in the forbidden gap which give rise to extrinsic photoconductivity. The levels are found to disappear and in some cases shift with annealing in the 100-450 C temperature range. Due to the complexity of the system and the present lack of adequate theory, no complete analysis of the data obtained could be made.

  10. Radiation combined with thermal injury induces immature myeloid cells.

    PubMed

    Mendoza, April Elizabeth; Neely, Crystal Judith; Charles, Anthony G; Kartchner, Laurel Briane; Brickey, Willie June; Khoury, Amal Lina; Sempowski, Gregory D; Ting, Jenny P Y; Cairns, Bruce A; Maile, Robert

    2012-11-01

    The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sublethal ionization radiation exposure combined with a full-thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a full-thickness contact burn of 20% total body surface area or sham procedure followed by a single whole-body dose of 5-Gy radiation. Serum, spleen, and peripheral lymph nodes were harvested at 3 and 14 days after injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated proinflammatory and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but were significantly elevated after burn alone and RCI at 14 days after injury. In contrast to the T-cell-suppressive nature of myeloid-derived suppressor cells found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in interferon γ and a decrease in interleukin 10. This is consistent with previous work in burn injury indicating that a myeloid-derived suppressor cell-like population increases innate immunity. Radiation combined injury results in the increase in distinct populations of Gr-1CD11b cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host. PMID:23042190

  11. Hubble induced mass in radiation-dominated universe

    NASA Astrophysics Data System (ADS)

    Kawasaki, Masahiro; Takesako, Tomohiro

    2012-05-01

    We reconsider the effective mass of a scalar field which interact with visible sector via Planck-suppressed coupling in supergravity framework. We focus on the radiation-dominated (RD) era after inflation. In this era, the effective mass is given by thermal average of interaction terms. To make our analysis clear, we rely on Kadanoff-Baym equations to evaluate the thermal average. We find that, in RD era, a scalar field acquires the effective mass of the order of H.

  12. Lee-Wick radiation induced bouncing universe models

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Kaushik; Cai, Yi-Fu; Das, Suratna

    2013-04-01

    The present article discusses the effect of a Lee-Wick partner infested radiation phase of the early universe. As Lee-Wick partners can contribute negative energy density it is always possible that at some early phase of the universe when the Lee-Wick partners were thermalized the total energy density of the universe became very small making the effective Hubble radius very big. This possibility gives rise to the probability of a bouncing universe. As will be shown in the article a simple Lee-Wick radiation is not enough to produce a bounce. There can be two possibilities which can produce a bounce in the Lee-Wick radiation phase. One requires a cold dark matter candidate to trigger the bounce and the other possibility requires the bouncing temperature to be fine-tuned such as all the Lee-Wick partners of the standard fields are not thermalized at the bounce temperature. Both the possibilities give rise to a blue-tilted power spectrum of metric perturbations. Moreover the bouncing universe model can predict the lower limit of the masses of the Lee-Wick partners of chiral fermions and massless gauge bosons. The mass limit intrinsically depends upon the bounce temperature.

  13. Phenytoin Induced Erythema Multiforme after Cranial Radiation Therapy.

    PubMed

    Kazanci, Atilla; Tekkök, İsmail Hakkı

    2015-08-01

    The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM. PMID:26361537

  14. Phenytoin Induced Erythema Multiforme after Cranial Radiation Therapy

    PubMed Central

    Tekkök, İsmail Hakkı

    2015-01-01

    The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM. PMID:26361537

  15. Cognitive deficits induced by 56Fe radiation exposure.

    PubMed

    Shukitt-Hale, B; Casadesus, G; Cantuti-Castelvetri, I; Rabin, B M; Joseph, J A

    2003-01-01

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. PMID:12577981

  16. Cognitive deficits induced by 56Fe radiation exposure

    NASA Astrophysics Data System (ADS)

    Shukitt-Hale, B.; Casadesus, G.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  17. Cognitive deficits induced by 56Fe radiation exposure

    NASA Technical Reports Server (NTRS)

    Shukitt-Hale, B.; Casadesus, G.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

    2003-01-01

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Published by Elsevier Science Ltd on behalf of COSPAR.

  18. Cellular neoplastic transformation induced by 916 MHz microwave radiation.

    PubMed

    Yang, Lei; Hao, Dongmei; Wang, Minglian; Zeng, Yi; Wu, Shuicai; Zeng, Yanjun

    2012-08-01

    There has been growing concern about the possibility of adverse health effects resulting from exposure to microwave radiations, such as those emitted by mobile phones. The purpose of this study was to investigate the cellular neoplastic transformation effects of electromagnetic fields. 916 MHz continuous microwave was employed in our study to simulate the electromagnetic radiation of mobile phone. NIH/3T3 cells were adopted in our experiment due to their sensitivity to carcinogen or cancer promoter in environment. They were divided randomly into one control group and three microwave groups. The three microwave groups were exposed to 916 MHz EMF for 2 h per day with power density of 10, 50, and 90 w/m(2), respectively, in which 10 w/m(2) was close to intensity near the antenna of mobile phone. The morphology and proliferation of NIH/3T3 cells were examined and furthermore soft agar culture and animal carcinogenesis assay were carried out to determine the neoplastic promotion. Our experiments showed NIH/3T3 cells changed in morphology and proliferation after 5-8 weeks exposure and formed clone in soft agar culture after another 3-4 weeks depending on the exposure intensity. In the animal carcinogenesis study, lumps developed on the back of SCID mice after being inoculated into exposed NIH/3T3 cells for more than 4 weeks. The results indicate that microwave radiation can promote neoplastic transformation of NIH/3T3cells. PMID:22395787

  19. Simulation of ion beam induced current in radiation detectors and microelectronic devices.

    SciTech Connect

    Vizkelethy, Gyorgy

    2009-10-01

    Ionizing radiation is known to cause Single Event Effects (SEE) in a variety of electronic devices. The mechanism that leads to these SEEs is current induced by the radiation in these devices. While this phenomenon is detrimental in ICs, this is the basic mechanism behind the operation of semiconductor radiation detectors. To be able to predict SEEs in ICs and detector responses we need to be able to simulate the radiation induced current as the function of time. There are analytical models, which work for very simple detector configurations, but fail for anything more complex. On the other end, TCAD programs can simulate this process in microelectronic devices, but these TCAD codes costs hundreds of thousands of dollars and they require huge computing resources. In addition, in certain cases they fail to predict the correct behavior. A simulation model based on the Gunn theorem was developed and used with the COMSOL Multiphysics framework.

  20. Radiation-induced 1/f noise degradation of bipolar linear voltage regulator

    NASA Astrophysics Data System (ADS)

    Qifeng, Zhao; Yiqi, Zhuang; Junlin, Bao; Wei, Hu

    2016-03-01

    Radiation-induced 1/f noise degradation in the LM117 bipolar linear voltage regulator is studied. Based on the radiation-induced degradation mechanism of the output voltage, it is suggested that the band-gap reference subcircuit is the critical component which leads to the 1/f noise degradation of the LM117. The radiation makes the base surface current of the bipolar junction transistors of the band-gap reference subcircuit increase, which leads to an increase in the output 1/f noise of the LM117. Compared to the output voltage, the 1/f noise parameter is more sensitive, it may be used to evaluate the radiation resistance capability of LM117. Project supported by the National Natural Science Foundation of China (Nos. 61076101, 61204092).

  1. Radiation-induced magnetotransport in high-mobility two-dimensional systems: Role of electron heating

    NASA Astrophysics Data System (ADS)

    Lei, X. L.; Liu, S. Y.

    2005-08-01

    Effects of microwave radiation on magnetoresistance are analyzed in a balance-equation scheme that covers regimes of inter- and intra-Landau level processes and takes into account photon-asissted electron transitions as well as radiation-induced change of the electron distribution for high-mobility two-dimensional systems. Short-range scatterings due to background impurities and defects are shown to be the dominant direct contributors to photoresistant oscillations. The electron temperature characterizing the system heating due to irradiation is derived by balancing the energy absorption from the radiation field and the energy dissipation to the lattice through realistic electron-phonon couplings, exhibiting resonant oscillation. Microwave modulations of the Shubnikov-de Haas oscillation amplitude are produced together with microwave-induced resistance oscillations, in agreement with experimental findings. In addition, the suppression of the magnetoresistance caused by low-frequency radiation in the higher magnetic field side is also demonstrated.

  2. Simulation of ion beam induced current in radiation detectors and microelectronic devices.

    SciTech Connect

    Vizkelethy, Gyorgy

    2010-07-01

    Ionizing radiation is known to cause Single Event Effects (SEE) in a variety of electronic devices. The mechanism that leads to these SEEs is current induced by the radiation in these devices. While this phenomenon is detrimental in ICs, this is the basic mechanism behind the operation of semiconductor radiation detectors. To be able to predict SEEs in ICs and detector responses we need to be able to simulate the radiation induced current as the function of time. There are analytical models, which work for very simple detector configurations, but fail for anything more complex. On the other end, TCAD programs can simulate this process in microelectronic devices, but these TCAD codes costs hundreds of thousands of dollars and they require huge computing resources. In addition, in certain cases they fail to predict the correct behavior. A simulation model based on the Gunn theorem was developed and used with the COMSOL Multiphysics framework.

  3. [Radiation-Induced Radiculopathy with Paresis of the Neck and Autochthonous Back Muscles with Additional Myopathy].

    PubMed

    Ellrichmann, G; Lukas, C; Adamietz, I A; Grunwald, C; Schneider-Gold, C; Gold, R

    2016-06-01

    Radiation-induced tissue damage is caused by ionizing radiation mainly affecting the skin, vascular, neuronal or muscle tissue. Early damages occur within weeks and months while late damages may occur months or even decades after radiation.Radiation-induced paresis of the spine or the trunk muscles with camptocormia or dropped-head syndrome are rare but have already been described as long-term sequelae after treatment of Hodgkin's lymphoma. The differential diagnosis includes limb-girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy (FSHD) or lysosomal storage diseases (e. g. Acid Maltase Deficiency). We present the case of a patient with long lasting diagnostics over many months due to different inconclusive results. PMID:27391986

  4. Radiation effects on regeneration and T-cell-inducing function of the thymus

    SciTech Connect

    Hirokawa, K.; Sado, T.

    1984-04-01

    Radiation effects on regeneration and T-cell-inducing function of the thymus were studied in three sets of experiments. When TXB mice were grafted with 1-week-old thymus which had been previously irradiated at various doses, an exponential decrease was observed in the morphological regeneration of the thymus grafts and in their T-cell-inducing function at doses of 600 R and over, showing about 10% that of the control at 1500 R. When in situ thymus of adult mice was locally irradiated, the radiation effect on T-cell-inducing function was less pronounced as compared with the first experiment; i.e., about 40% of the control at 1797 R. When in situ thymus of 1-day-old newborn mice was locally irradiated, regeneration potential of 1-day-old newborn thymus was highly resistant to radiation exposure and no effect on immunological functions was observed even by local irradiation of 2000 R.

  5. Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities

    SciTech Connect

    Roberts, J.L.; Sharrow, S.O.; Singer, A. )

    1990-03-01

    The present study demonstrates that immune tolerance can be achieved in the thymus both by clonal deletion and by clonal inactivation, but that the two tolerant states are induced by cellular elements with different radiation sensitivities. TCR engagement of self antigens on bone marrow-derived, radiation-sensitive (presumably dendritic) cells induces clonal deletion of developing thymocytes, whereas TCR engagement of self antigens on radiation-resistant cellular elements, such as thymic epithelium, induces clonal anergy. The nondeleted, anergic thymocytes can express IL-2-Rs but are unable to proliferate in response to either specific antigen or anti-TCR antibodies, and do develop into phenotypically mature cells that emigrate out of the thymus and into the periphery.

  6. Energy Distribution of Electrons in Radiation Induced-Helium Plasmas. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Lo, R. H.

    1972-01-01

    Energy distribution of high energy electrons as they slow down and thermalize in a gaseous medium is studied. The energy distribution in the entire energy range from source energies down is studied analytically. A helium medium in which primary electrons are created by the passage of heavy-charged particles from nuclear reactions is emphasized. A radiation-induced plasma is of interest in a variety of applications, such as radiation pumped lasers and gaseous core nuclear reactors.

  7. NOS Inhibition Modulates Immune Polarization and Improves Radiation-Induced Tumor Growth Delay.

    PubMed

    Ridnour, Lisa A; Cheng, Robert Y S; Weiss, Jonathan M; Kaur, Sukhbir; Soto-Pantoja, David R; Basudhar, Debashree; Heinecke, Julie L; Stewart, C Andrew; DeGraff, William; Sowers, Anastasia L; Thetford, Angela; Kesarwala, Aparna H; Roberts, David D; Young, Howard A; Mitchell, James B; Trinchieri, Giorgio; Wiltrout, Robert H; Wink, David A

    2015-07-15

    Nitric oxide synthases (NOS) are important mediators of progrowth signaling in tumor cells, as they regulate angiogenesis, immune response, and immune-mediated wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of wound response. We hypothesized that radiation therapeutic efficacy could be improved by targeting NOS following tumor irradiation. Herein, we show enhanced radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post-IR with the constitutive NOS inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME). These results suggest a requirement of T cells for improved radiation tumor response. In support of this observation, tumor irradiation induced a rapid increase in the immunosuppressive Th2 cytokine IL10, which was abated by post-IR administration of L-NAME. In vivo suppression of IL10 using an antisense IL10 morpholino also extended the tumor growth delay induced by radiation in a manner similar to L-NAME. Further examination of this mechanism in cultured Jurkat T cells revealed L-NAME suppression of IR-induced IL10 expression, which reaccumulated in the presence of exogenous NO donor. In addition to L-NAME, the guanylyl cyclase inhibitors ODQ and thrombospondin-1 also abated IR-induced IL10 expression in Jurkat T cells and ANA-1 macrophages, which further suggests that the immunosuppressive effects involve eNOS. Moreover, cytotoxic Th1 cytokines, including IL2, IL12p40, and IFNγ, as well as activated CD8(+) T cells were elevated in tumors receiving post-IR L-NAME. Together, these results suggest that post-IR NOS inhibition improves radiation tumor response via Th1 immune polarization within the tumor microenvironment. PMID:25990221

  8. Feasibility of OCT to detect radiation-induced esophageal damage in small animal models (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jelvehgaran, Pouya; Alderliesten, Tanja; Salguero, Javier; Borst, Gerben; Song, Ji-Ying; van Leeuwen, Ton G.; de Boer, Johannes F.; de Bruin, Daniel M.; van Herk, Marcel B.

    2016-03-01

    Lung cancer survival is poor and radiotherapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to reduced food intake or even fistula formation. Only few direct techniques exist to measure radiation-induced esophageal damage, for which knowledge is needed to improve the balance between risk of tumor recurrence and complications. Optical coherence tomography (OCT) is a minimally-invasive imaging technique that obtains cross-sectional, high-resolution (1-10µm) images and is capable of scanning the esophageal wall up to 2-3mm depth. In this study we investigated the feasibility of OCT to detect esophageal radiation damage in mice. In total 30 mice were included in 4 study groups (1 main and 3 control groups). Mice underwent cone-beam CT imaging for initial setup assessment and dose planning followed by single-fraction dose delivery of 4, 10, 16, and 20Gy on 5mm spots, spaced 10mm apart. Mice were repeatedly imaged using OCT: pre-irradiation and up to 3 months post-irradiation. The control groups received either OCT only, irradiation only, or were sham-operated. We used histopathology as gold standard for radiation-induced damage diagnosis. The study showed edema in both the main and OCT-only groups. Furthermore, radiation-induced damage was primarily found in the highest dose region (distal esophagus). Based on the histopathology reports we were able to identify the radiation-induced damage in the OCT images as a change in tissue scattering related to the type of induced damage. This finding indicates the feasibility and thereby the potentially promising role of OCT in radiation-induced esophageal damage assessment.

  9. Radiation induced polarization in CdTe detectors

    NASA Astrophysics Data System (ADS)

    Vartsky, D.; Goldberg, M.; Eisen, Y.; Shamai, Y.; Dukhan, R.; Siffert, P.; Koebel, J. M.; Regal, R.; Gerber, J.

    1988-01-01

    Polarization induced by irradiation with intense gamma ray sources has been studied in chlorine-compensated CdTe detectors. The influence of several parameters, such as applied field strength, temperature and incident photon flux, on the polarization effect have been investigated. A relationship was found between the degree of polarization, detector efficiency and detector leakage current.

  10. Radiation-induced chromosomal inversions in mice. Technical progress report

    SciTech Connect

    Roderick, T.H.

    1986-01-01

    Chromosomal inversions are being produced for the purpose of establishing efficient systems for assessing induced and spontaneous heritable mutations. The inversions and other chromosomal aberrations produced are used to ask basic questions about meiosis and reproductive performance. Chromosomal structure is being studied by identifying the cytological location of genes and break points related to the inversions. 2 tabs.

  11. Characterization of a novel epigenetic effect of ionizing radiation: the death-inducing effect

    NASA Technical Reports Server (NTRS)

    Nagar, Shruti; Smith, Leslie E.; Morgan, William F.

    2003-01-01

    The detrimental effects associated with exposure to ionizing radiation have long been thought to result from the direct targeting of the nucleus leading to DNA damage; however, the emergence of concepts such as radiation-induced genomic instability and bystander effects have challenged this dogma. After cellular exposure to ionizing radiation, we have isolated a number of clones of Chinese hamster-human hybrid GM10115 cells that demonstrate genomic instability as measured by chromosomal destabilization. These clones show dynamic and persistent generation of chromosomal rearrangements multiple generations after the original insult. We hypothesize that these unstable clones maintain this delayed instability phenotype by secreting factors into the culture medium. To test this hypothesis we transferred filtered medium from unstable cells to unirradiated GM10115 cells. No GM10115 cells were able to survive this medium. This phenomenon by which GM10115 cells die when cultured in medium from chromosomally unstable GM10115 clones is the death-inducing effect. Medium transfer experiments indicate that a factor or factors is/are secreted by unstable cells within 8 h of growth in fresh medium and result in cell killing within 24 h. These factors are stable at ambient temperature but do not survive heating or freezing, and are biologically active when diluted with fresh medium. We present the initial description and characterization of the death-inducing effect. This novel epigenetic effect of radiation has implications for radiation risk assessment and for health risks associated with radiation exposure.

  12. PHD Inhibition Mitigates and Protects Against Radiation-Induced Gastrointestinal Toxicity via HIF2

    PubMed Central

    Taniguchi, Cullen M.; Miao, Yu Rebecca; Diep, Anh N.; Wu, Colleen; Rankin, Erinn B.; Atwood, Todd F.; Xing, Lei; Giaccia, Amato J.

    2014-01-01

    Radiation-induced gastrointestinal (GI) toxicity can be a major source of morbidity and mortality after radiation exposure. There is an unmet need for effective preventative or mitigative treatments against the potentially fatal diarrhea and water loss induced by radiation damage to the GI tract. We report that prolyl hydroxylase inhibition by genetic knockout or pharmacologic inhibition of all PHD isoforms by the small molecule dimethyloxyallylglycine (DMOG) increases HIF expression, improves epithelial integrity, reduces apoptosis, and increases intestinal angiogenesis, all of which are essential for radioprotection. HIF2, but not HIF1, is both necessary and sufficient to prevent radiation-induced GI toxicity and death. Increased VEGF expression contributes to the protective effects of HIF2, since inhibition of VEGF function reversed the radioprotection and radiomitigation afforded by DMOG. Additionally, mortality is reduced from abdominal or total body irradiation even when DMOG is given 24 hours after exposure. Thus, prolyl hydroxylase inhibition represents a new treatment strategy to protect against and mitigate GI toxicity from both therapeutic radiation and potentially lethal radiation exposures. PMID:24828078

  13. Three-dimensional Culture Conditions Lead to Decreased Radiation Induced Crytoxicity in Human Mammary Epithelial Cells

    SciTech Connect

    Sowa, Marianne B.; Chrisler, William B.; Zens, Kyra D.; Ashjian, Emily J.; Opresko, Lee K.

    2010-05-01

    For both targeted and non-targeted exposures, the cellular responses to ionizing radiation have predominantly been measured in two dimensional monolayer cultures. Although convenient for biochemical analysis, the true interactions in vivo depend upon complex interactions between cells themselves and the surrounding extra cellular matrix. This study directly compares the influence of culture conditions on radiation induced cytotoxicity following exposure to low-LET ionizing radiation. Using a three dimensional (3D) human mammary epithelial tissue model, we have found a protective effect of 3D cell culture on cell survival after irradiation. The initial state of the cells (i.e., 2D vs. 3D culture) at the time of irradiation does not alter survival, nor does the presence of extracellular matrix during and after exposure to dose, but long term culture in 3D which offers significant reduction in cytotoxicity at a given dose (e.g. ~4 fold increased survival at 5 Gy). The cell cycle delay induced following exposure to 2 and 5 Gy was almost identical between 2D and 3D culture conditions and cannot account for the observed differences in radiation responses. However the amount of apoptosis following radiation exposure is significantly decreased in 3D culture relative to the 2D monolayer after the same dose. A likely mechanism of the cytoprotective effect afforded by 3D culture conditions is the down regulation of radiation induced apoptosis in 3D structures

  14. The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

    2016-07-01

    Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the genomic methylation changes of heavy-ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

  15. 3D ultrasound Nakagami imaging for radiation-induced vaginal fibrosis

    NASA Astrophysics Data System (ADS)

    Yang, Xiaofeng; Rossi, Peter; Shelton, Joseph; Bruner, Debrorah; Tridandapani, Srini; Liu, Tian

    2014-03-01

    Radiation-induced vaginal fibrosis is a debilitating side-effect affecting up to 80% of women receiving radiotherapy for their gynecological (GYN) malignancies. Despite the significant incidence and severity, little research has been conducted to identify the pathophysiologic changes of vaginal toxicity. In a previous study, we have demonstrated that ultrasound Nakagami shape and PDF parameters can be used to quantify radiation-induced vaginal toxicity. These Nakagami parameters are derived from the statistics of ultrasound backscattered signals to capture the physical properties (e.g., arrangement and distribution) of the biological tissues. In this paper, we propose to expand this Nakagami imaging concept from 2D to 3D to fully characterize radiation-induced changes to the vaginal wall within the radiation treatment field. A pilot study with 5 post-radiotherapy GYN patients was conducted using a clinical ultrasound scanner (6 MHz) with a mechanical stepper. A serial of 2D ultrasound images, with radio-frequency (RF) signals, were acquired at 1 mm step size. The 2D Nakagami shape and PDF parameters were calculated from the RF signal envelope with a sliding window, and then 3D Nakagami parameter images were generated from the parallel 2D images. This imaging method may be useful as we try to monitor radiation-induced vaginal injury, and address vaginal toxicities and sexual dysfunction in women after radiotherapy for GYN malignancies.

  16. Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

    NASA Technical Reports Server (NTRS)

    Weil, M. M.; Kittrell, F. S.; Yu, Y.; McCarthy, M.; Zabriskie, R. C.; Ullrich, R. L.

    2001-01-01

    Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

  17. Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation.

    PubMed

    Denisova, N A; Shukitt-Hale, B; Rabin, B M; Joseph, J A

    2002-12-01

    Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior. PMID:12452775

  18. Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation

    NASA Technical Reports Server (NTRS)

    Denisova, N. A.; Shukitt-Hale, B.; Rabin, B. M.; Joseph, J. A.

    2002-01-01

    Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

  19. Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

    PubMed Central

    Balentova, Sona; Adamkov, Marian

    2015-01-01

    Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

  20. Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review.

    PubMed

    Balentova, Sona; Adamkov, Marian

    2015-01-01

    Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

  1. Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells

    PubMed Central

    Hahn, Hyung Jin; Youn, Hae Jeong; Cha, Hwa Jun; Kim, Karam; An, Sungkwan

    2016-01-01

    Background We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. Objective We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. Methods To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. Results Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. Conclusion These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation. PMID:27489424

  2. Radiation Combined with Thermal Injury Induces Immature Myeloid Cells

    PubMed Central

    Mendoza, April Elizabeth; Neely, Crystal Judith; Charles, Anthony G.; Kartchner, Laurel Briane; Brickey, Willie June; Khoury, Amal Lina; Sempowski, Gregory D.; Ting, Jenny P.Y.; Cairns, Bruce A.; Maile, Robert

    2012-01-01

    The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sub-lethal ionization radiation exposure combined with a full thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a 20% total body surface area (TBSA) full-thickness contact burn or sham procedure followed by a single whole body dose of 5-Gy radiation. Serum, spleen and peripheral lymph nodes were harvested at 3 and 14 days post-injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated pro- and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but was significantly elevated after burn alone and RCI at 14 days post-injury. In contrast to the T-cell suppressive nature of myeloid-derived suppressor cells (MDSC) found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in IFN-γ and a decrease in IL-10. This is consistent with previous work in burn injury indicating that a MDSC-like population increases innate immunity. RCI results in the increase of distinct populations of Gr-1+ CD11b+cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host. PMID:23042190

  3. Unlocking the Combination: Potentiation of Radiation-Induced Antitumor Responses with Immunotherapy

    PubMed Central

    Wattenberg, Max M.; Fahim, Ahmed; Ahmed, Mansoor M.; Hodge, James W.

    2014-01-01

    There is increasing evidence of the potential for radiation therapy to generate antitumor immune responses. The mechanisms of this immune-activating potential include actions on tumor cells such as immunogenic cell death and phenotypic change. Radiation modulates tumor cell surface expression of cell death receptors, tumor-associated antigens and adhesion molecules. This process of immunomodulation sensitizes tumor cells to immune-mediated killing. Radiation also affects immune compartments, including antigen-presenting cells, cytotoxic T lymphocytes and humoral immunity, leading to specific antitumor immune responses. Recognizing the importance of immunity as a potentiator of response to radiation leads to rational augmentation of antitumor immunity by combining radiation and immunotherapy. Targeted immunotherapy manipulates the immune system in a way that best synergizes with radiation. This article discusses the ability of radiation monotherapy to induce antitumor immunity, with a focus on the effect of radiation on antigen-presenting cells and cytotoxic T lymphocytes. We define two important responses generated by tumor cells, immunogenic cell death and immunomodulation, both of which are radiation dose-dependent. In conclusion, we describe the translation of several combination therapies from the preclinical to the clinical setting and identify opportunities for further exploration. PMID:24960415

  4. Upconverted photoluminescence induced by radiative coupling between excitons

    NASA Astrophysics Data System (ADS)

    Matsuda, Takuya; Yokoshi, Nobuhiko; Ishihara, Hajime

    2016-04-01

    We propose an unconventional scheme of photoluminescence in a semiconductor thin film, where the nonlocal correlation between an excitonic wave and light wave prominently enhances the interaction between different excitonic states via radiation beyond the long-wavelength approximation (the so-called excitonic superradiance regime). On the basis of the developed method extending input-output theory, we elucidate atypical photoluminescence effects due to the strong wave-wave correlation. In particular, the upconverted photoluminescence based on the coherent quantum superposition of excitons is found to be highly efficient, i.e., it can be realized by weak pumping without auxiliary systems such as cavities or photonic antennas.

  5. UV radiation-induced skin tumors in Monodelphis domestica.

    PubMed

    Ley, R D; Applegate, L A; Stuart, T D; Fry, R J

    1987-06-01

    Chronic exposure of the skin of the South American opossum (Monodelphis domestica) to ultraviolet radiation (UVR) from an FS-40 sunlamp (280-400 nm) 3 times per week for a total of 200 exposures resulted in the appearance of actinic keratoses, fibrosarcomas, squamous cell carcinomas and keratoacanthomas. At the higher doses of UVR used in this study, moderate to severe hyperplasia was also observed. The susceptibility of this animal to the induction of skin tumors by UVR in conjunction with the capacity to enzymatically photoreactive pyrimidine dimers in cutaneous DNA identifies this animal as a useful model in determining the role of pyrimidine dimers in skin tumor induction by UVR. PMID:3684736

  6. Space radiation-induced effects in polymer photodetectors

    NASA Astrophysics Data System (ADS)

    Taylor, Edward W.; Le, Dang T.; Durstock, Michael F.; Taylor, Barney E.; Claus, Richard O.; Zeng, Tingying; Morath, Christian P.; Cardimona, David A.

    2002-09-01

    Self-assembled polymer photo-detectors (PPDs) composed of ruthenium complex N3 and PPDs based on thin films of poly(p-phenylene vinlyene) with sulfonated polystyrene are examined for their ability to function in a simulated space radiation environment. Examination of the PPD pre- and post- response data following gamma-ray irradiation ranging in total dose from 10 krad(Si) to 100 krad(Si) are examined. The output photovoltage was observed to decrease for all irradiated devices. The brief study was performed at room temperature and a discussion of the preliminary data and results are presented.

  7. Positronics of radiation-induced effects in chalcogenide glassy semiconductors

    SciTech Connect

    Shpotyuk, O.; Kozyukhin, S. A.; Shpotyuk, M.; Ingram, A.; Szatanik, R.

    2015-03-15

    Using As{sub 2}S{sub 3} and AsS{sub 2} glasses as an example, the principal possibility of using positron annihilation spectroscopy methods for studying the evolution of the free volume of hollow nanoobjects in chalcogenide glassy semiconductors exposed to radiation is shown. The results obtained by measurements of the positron annihilation lifetime and Doppler broadening of the annihilation line in reverse chronological order are in full agreement with the optical spectroscopy data in the region of the fundamental absorption edge, being adequately described within coordination defect-formation and physical-aging models.

  8. Recovery of Transplanted Eyebrow From Radiation-Induced Anagen Effluvium.

    PubMed

    Irune, Ekpemi; Bast, Florian; Williams, Gregory; Kirkpatrick, Niall

    2015-01-01

    Ablative surgery for skin cancer of the face can often leave patients with significant deformities. These disfigurements can include loss of hair in conspicuous areas such as the eyebrows, leaving the patients with unsightly facial asymmetry. Eyebrow transplantation serves to address this issue; however, it has often been discouraged in patients who are destined to receive radiotherapy to the cutaneous area in question. This is due to the anagen effluvium effect of radiation therapy on hair follicles. We present a case in which the transplanted eyebrow hair follicles survived the deleterious effects of radiotherapy, leaving the patient with a symmetrical and aesthetically satisfactory eyebrow appearance. PMID:25775615

  9. Ultraviolet Radiation-induced Alteration of Martian Surface Materials

    NASA Technical Reports Server (NTRS)

    Yen, A. S.

    1999-01-01

    The nature and origin of martian surface materials cannot be fully characterized without addressing the unusual reactivity of the soil and the effects of exposure to the unique martian environment. Our laboratory experiments show that ultraviolet radiation at the martian surface can result in the oxidation of metal atoms and the creation of reactive oxygen species on grain surfaces. This process is important in understanding the nature and evolution of martian soils. It can explain the reactivity discovered by the Viking Landers and possibly the origin of the ferric component of the soil.

  10. Multiscale physics of ion-induced radiation damage

    NASA Astrophysics Data System (ADS)

    Surdutovich, Eugene; Solov'yov, Andrey V.

    2013-06-01

    A multiscale approach to the physics of ion-beam cancer therapy, an approach suggested in order to understand the interplay of a large number of phenomena involved in radiation damage scenario occurring on a range of temporal, spatial, and energy scales, is being reviewed. The scenario is described along with a variety of effects that take place on different temporal, spatial, and energy scales and play major roles in the scenario of interaction of ions with tissue. The understanding of these effects leads to a quantitative assessment of relative biological effectiveness that relates the physical quantities, such as dose, to the biological values, such as the probability of cell survival.

  11. Gamma radiation-induced blue shift of resonance peaks of Bragg gratings in pure silica fibres

    NASA Astrophysics Data System (ADS)

    Faustov, A. V.; Gusarov, A. I.; Mégret, P.; Wuilpart, M.; Kinet, D.; Zhukov, A. V.; Novikov, S. G.; Svetukhin, V. V.; Fotiadi, A. A.

    2016-02-01

    We report the first observation of a significant gamma radiation-induced blue shift of the reflection/transmission peak of fibre Bragg gratings inscribed into pure-silica core fibres via multiphoton absorption of femtosecond pulses. At a total dose of ~100 kGy, the shift is ~20 pm. The observed effect is attributable to the ionising radiation-induced decrease in the density of the silica glass when the rate of colour centre formation is slow. We present results of experimental measurements that provide the key parameters of the dynamics of the gratings for remote dosimetry and temperature sensing.

  12. Transient radiation-induced absorption in materials for the DOI laser

    NASA Astrophysics Data System (ADS)

    Brannon, P. J.

    1994-11-01

    This is the final report on a series of experiments concerned with transient radiation-induced absorption in materials for a Cr,Nd:GSGG laser. Both the Sandia National Laboratories SPR III pulsed reactor and the Hermes III pulsed X-ray machine are used as radiation sources. The time dependence and the magnitude of the induced absorption in filter glasses and in doped and undoped LiNbO3 Q-switch materials have been measured. Gain has been observed in Cr,Nd:GSGG, the laser medium, when it is irradiated by X-rays.

  13. Transient radiation-induced absorption in materials for the DOI laser

    SciTech Connect

    Brannon, P.J.

    1995-01-01

    This is the final report on a series of experiments concerned with transient radiation-induced absorption in materials for a Cr,Nd:GSGG laser. Both the Sandia National Laboratories SPR III pulsed reactor and the Hermes III pulsed X-ray machine are used as radiation sources. The time dependence and the magnitude of the induced absorption in filter glasses and in doped and undoped LiNbO{sub 3} Q-switch materials have been measured. Gain has been observed in Cr,Nd:GSGG, the laser medium, when it is irradiated by X-rays.

  14. Antimicrobial fabric adsorbed iodine produced by radiation-induced graft polymerization

    NASA Astrophysics Data System (ADS)

    Aoki, Shoji; Fujiwara, Kunio; Sugo, Takanobu; Suzuki, Koichi

    2013-03-01

    Antimicrobial fabric was synthesized by radiation-induced graft polymerization of N-vinyl pyrrolidone onto polyolefine nonwoven fabric and subsequent adsorption of iodine. In response of the huge request for the antimicrobial material applied to face masks for swine flu in 2009, operation procedure of continuous radiation-induced graft polymerization apparatus was improved. The improved grafting production per week increased 3.8 times compared to the production by former operation procedure. Shipped antimicrobial fabric had reached 130,000 m2 from June until December, 2009.

  15. Radiation-induced transmission loss in low water peak single mode fibers

    NASA Astrophysics Data System (ADS)

    Wang, Tingyun; Xiao, Zhongyin; Luo, Wenyun; Wen, Jianxiang; Yin, Jianchong; Wu, Wenkai; Gong, Renxiang

    2013-12-01

    Radiation-induced transmission loss in Low Water Peak Single Mode (LWPSM) fiber has been investigated. Formation and conversion processes of defect centers also have been proposed using electron spin resonance in the fiber irradiated with gamma rays. When the irradiation dose is low, Germanium electron center (GEC) and self-trapped hole center (STH) occur. With the increase of dose, E' centers (Si and Ge) and nonbridge oxygen hole centers (NBOHCs) generate. With the help of thermal-bleaching or photo-bleaching, the radiation-induced loss of pre-irradiation optical fiber can be reduced effectively. The obtain results also have been analyzed in detail.

  16. Detection of radiation-induced hydrocarbons in baked sponged cake prepared with irradiated liquid egg

    NASA Astrophysics Data System (ADS)

    Schulzki, G.; Spiegelberg, A.; Bögl, K. W.; Schreiber, G. A.

    1995-02-01

    For identification of irradiated food, radiation-induced volatile hydrocarbons (HC) are determined by gas chromatography in the non-polar fraction of fat. However, in complex food matrices the detection is often disturbed by fat-associated compounds. On-line coupling of high performance liquid chromatography (LC) and gas chromatography (GC) is very efficient to remove such compounds from the HC fraction. The high sensitivity of this fast and efficient technique is demonstrated by the example of detection of radiation-induced HC in fat isolated from baked sponge cake which had been prepared with irradiated liquid egg.

  17. Simultaneous measurement of multiple radiation-induced protein expression profiles using the Luminex(TM) system

    NASA Technical Reports Server (NTRS)

    Desai, N.; Wu, H.; George, K.; Gonda, S. R.; Cucinotta, F. A.; Cucniotta, F. A. (Principal Investigator)

    2004-01-01

    Space flight results in the exposure of astronauts to a mixed field of radiation composed of energetic particles of varying energies, and biological indicators of space radiation exposure provides a better understanding of the associated long-term health risks. Current methods of biodosimetry have employed the use of cytogenetic analysis for biodosimetry, and more recently the advent of technological progression has led to advanced research in the use of genomic and proteomic expression profiling to simultaneously assess biomarkers of radiation exposure. We describe here the technical advantages of the Luminex(TM) 100 system relative to traditional methods and its potential as a tool to simultaneously profile multiple proteins induced by ionizing radiation. The development of such a bioassay would provide more relevant post-translational dynamics of stress response and will impart important implications in the advancement of space and other radiation contact monitoring. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  18. Transition radiation at radio frequencies from ultrahigh-energy neutrino-induced showers

    NASA Astrophysics Data System (ADS)

    Motloch, Pavel; Alvarez-Muñiz, Jaime; Privitera, Paolo; Zas, Enrique

    2016-02-01

    Coherent radiation at radio frequencies from high-energy showers fully contained in a dense radio-transparent medium—like ice, salt, soil, or regolith—has been extensively investigated as a promising technique to search for ultrahigh-energy neutrinos. Additional emission in the form of transition radiation may occur when a neutrino-induced shower produced close to the Earth's surface emerges from the ground into atmospheric air. We present the first detailed evaluation of transition radiation from high-energy showers crossing the boundary between two different media. We found that transition radiation is sizable over a wide solid angle and coherent up to ˜1 GHz . These properties encourage further work to evaluate the potential of a large-aperture ultrahigh-energy neutrino experiment based on the detection of transition radiation.

  19. Dipole-fiber systems: radiation field patterns, effective magnetic dipoles, and induced cavity modes

    NASA Astrophysics Data System (ADS)

    Atakaramians, Shaghik; Miroshnichenko, Andrey E.; Shadrivov, Ilya V.; Monro, Tanya M.; Kivshar, Yuri S.; Afshar, Shahraam V.

    2015-12-01

    We study the radiation patterns produced by a dipole placed at the surface of a nanofiber and oriented perpendicular to it, either along the radial (r-oriented) or azimuthal (Φ-oriented) directions. We find that the dipole induces an effective circular cavity-like leaky mode in the nanofiber. The first radiation peak of the Φ-oriented dipole contributes only to TE radiation modes, while the radiation of the r-oriented dipole is composed of both TE and TM radiation modes, with relative contribution depending on the refractive index of the nanofiber. We reveal that the field pattern of the first resonance of a Φ-oriented dipole is associated with a magnetic dipole mode and strong magnetic response of an optical nanofiber.

  20. Study of terahertz-radiation-induced DNA damage in human blood leukocytes

    SciTech Connect

    Angeluts, A A; Esaulkov, M N; Kosareva, O G; Solyankin, P M; Shkurinov, A P; Gapeyev, A B; Pashovkin, T N; Matyunin, S N; Nazarov, M M; Cherkasova, O P

    2014-03-28

    We have carried out the studies aimed at assessing the effect of terahertz radiation on DNA molecules in human blood leukocytes. Genotoxic testing of terahertz radiation was performed in three different oscillation regimes, the blood leukocytes from healthy donors being irradiated for 20 minutes with the mean intensity of 8 – 200 μW cm{sup -2} within the frequency range of 0.1 – 6.5 THz. Using the comet assay it is shown that in the selected regimes such radiation does not induce a direct DNA damage in viable human blood leukocytes. (biophotonics)