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Sample records for ginsan diminished radiation-induced

  1. Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response

    SciTech Connect

    Shim, Ji-Young; Kim, Mi-Hyoung; Kim, Hyung-Doo; Ahn, Ji-Yeon; Yun, Yeon-Sook; Song, Jie-Young

    2010-02-01

    The aim of the present study was to evaluate immunomodulator ginsan, a polysaccharide extracted from Panax ginseng, on carbon tetrachloride (CCl{sub 4})-induced liver injury. BALB/c mice were injected i.p. with ginsan 24 h prior to CCl{sub 4} administration. Serum liver enzyme levels, histology, expression of antioxidant enzymes, and several cytokines/chemokines were subsequently evaluated. Ginsan treatment markedly suppressed the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and hepatic histological necrosis increased by CCl{sub 4} treatment. Ginsan inhibited CCl{sub 4} induced lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation. The hepatoprotective effect of ginsan was attributed to induction of anti-oxidant protein contents, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) as well as restoration of the hepatic glutathione (GSH) concentration. The marked increase of proinflammatory cytokines (IL-1beta, IFN-gamma) and chemokines (MCP-1, MIP-2beta, KC) in CCl{sub 4} treated mice was additionally attenuated by ginsan, thereby preventing leukocyte infiltration and local inflammation. Our results suggest that ginsan effectively prevent liver injury, mainly through downregulation of oxidative stress and inflammatory response.

  2. 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

  3. 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.

  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. 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.

  6. 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

  7. [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

  8. 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.

  9. Disorders of diminished motivation.

    PubMed

    Marin, Robert S; Wilkosz, Patricia A

    2005-01-01

    Disorders of diminished motivation occur frequently in individuals with traumatic brain injury. Motivation is an ever-present, essential determinant of behavior and adaptation. The major syndromes of diminished motivation are apathy, abulia, and akinetic mutism. Depending on their etiology, disorders of diminished motivation may be a primary clinical disturbance, a symptom of another disorder, or a coexisting second disorder. This article presents a biopsychosocial approach to the assessment and management of motivational impairments in patients with traumatic brain injury. The recognition and differential diagnosis of disorders of diminished motivation, as well as the mechanism and clinical pathogenesis, are discussed. PMID:16030444

  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. The Diminishing Apple.

    ERIC Educational Resources Information Center

    Kelly, Catherine

    2002-01-01

    Introduces the Apple Ocean activity which teaches about the diminishing natural resources of the earth including drinkable water, habitable land, and productive areas while working with fractions, ratios, and proportions. (YDS)

  12. 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.

  13. 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.

  14. [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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Sociable Sequences and Diminishing Functions.

    ERIC Educational Resources Information Center

    Sprows, David

    1989-01-01

    A FORTRAN program is provided for use with computer projects for a course in number theory. Uses diminishing functions and the speed of the computer to quickly determine possible solutions to problems. (MVL)

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Diminishing Returns in Humanities Research

    ERIC Educational Resources Information Center

    Bauerlein, Mark

    2009-01-01

    The author discusses the shift from criticism-as-explanation to criticism-as-performance that has taken place in literary criticism over the past five decades, and the resultant surge in published offerings to what has become a diminishing audience. The question of supersaturation applies to the institutions that demand and reward humanities…

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  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. 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.

  6. 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.

  7. 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.

  8. 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

  9. Nicaraven Attenuates Radiation-Induced Injury in Hematopoietic Stem/Progenitor Cells in Mice

    PubMed Central

    Kawakatsu, Miho; Urata, Yoshishige; Imai, Ryo; Goto, Shinji; Ono, Yusuke; Nishida, Noriyuki; Li, Tao-Sheng

    2013-01-01

    Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been demonstrated to protect against ischemia-reperfusion injury in various organs. We investigated whether nicaraven can attenuate radiation-induced injury in hematopoietic stem/progenitor cells, which is the conmen complication of radiotherapy and one of the major causes of death in sub-acute phase after accidental exposure to high dose radiation. C57BL/6 mice were exposed to 1 Gy γ-ray radiation daily for 5 days in succession (a total of 5 Gy), and given nicaraven or a placebo after each exposure. The mice were sacrificed 2 days after the last radiation treatment, and the protective effects and relevant mechanisms of nicaraven in hematopoietic stem/progenitor cells with radiation-induced damage were investigated by ex vivo examination. We found that post-radiation administration of nicaraven significantly increased the number, improved the colony-forming capacity, and decreased the DNA damage of hematopoietic stem/progenitor cells. The urinary levels of 8-oxo-2′-deoxyguanosine, a marker of DNA oxidation, were significantly lower in mice that were given nicaraven compared with those that received a placebo treatment, although the levels of intracellular and mitochondrial reactive oxygen species in the bone marrow cells did not differ significantly between the two groups. Interestingly, compared with the placebo treatment, the administration of nicaraven significantly decreased the levels of the inflammatory cytokines IL-6 and TNF-α in the plasma of mice. Our data suggest that nicaraven effectively diminished the effects of radiation-induced injury in hematopoietic stem/progenitor cells, which is likely associated with the anti-oxidative and anti-inflammatory properties of this compound. PMID:23555869

  10. Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor cells in mice.

    PubMed

    Kawakatsu, Miho; Urata, Yoshishige; Imai, Ryo; Goto, Shinji; Ono, Yusuke; Nishida, Noriyuki; Li, Tao-Sheng

    2013-01-01

    Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been demonstrated to protect against ischemia-reperfusion injury in various organs. We investigated whether nicaraven can attenuate radiation-induced injury in hematopoietic stem/progenitor cells, which is the conmen complication of radiotherapy and one of the major causes of death in sub-acute phase after accidental exposure to high dose radiation. C57BL/6 mice were exposed to 1 Gy γ-ray radiation daily for 5 days in succession (a total of 5 Gy), and given nicaraven or a placebo after each exposure. The mice were sacrificed 2 days after the last radiation treatment, and the protective effects and relevant mechanisms of nicaraven in hematopoietic stem/progenitor cells with radiation-induced damage were investigated by ex vivo examination. We found that post-radiation administration of nicaraven significantly increased the number, improved the colony-forming capacity, and decreased the DNA damage of hematopoietic stem/progenitor cells. The urinary levels of 8-oxo-2'-deoxyguanosine, a marker of DNA oxidation, were significantly lower in mice that were given nicaraven compared with those that received a placebo treatment, although the levels of intracellular and mitochondrial reactive oxygen species in the bone marrow cells did not differ significantly between the two groups. Interestingly, compared with the placebo treatment, the administration of nicaraven significantly decreased the levels of the inflammatory cytokines IL-6 and TNF-α in the plasma of mice. Our data suggest that nicaraven effectively diminished the effects of radiation-induced injury in hematopoietic stem/progenitor cells, which is likely associated with the anti-oxidative and anti-inflammatory properties of this compound. PMID:23555869

  11. Diminishing Marginal Utility in Economics Textbooks

    ERIC Educational Resources Information Center

    Dittmer, Timothy

    2005-01-01

    Many introductory microeconomics textbook authors derive the law of demand from the assumption of diminishing marginal utility. Authors of intermediate and graduate textbooks derive demand from diminishing marginal rate of substitution and ordinal preferences. These approaches are not interchangeable; diminishing marginal utility for all goods is…

  12. Antihistamines block radiation-induced increased intestinal blood flow in canines

    SciTech Connect

    Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Gossett-Hagerman, C.J.

    1985-06-01

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H1 and H2 histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H1 and H2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systemic plasma histamine levels were determined simultaneously. Data obtained indicated that the H1 and H2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure.

  13. Antihistamines block radiation-induced increased intestinal blood flow in canines

    SciTech Connect

    Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Gossett-Hagerman, C.J.

    1985-01-01

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H/sub 1/ and H/sub 2/ histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H sub 1 and H sub 2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systematic plasma histamine levels were determined simultaneously. Data obtained indicated that the H sub 1 and H sub 2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure. (Author)

  14. 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

  15. Excision repair of UV radiation-induced DNA damage in Caenorhabditis elegans

    SciTech Connect

    Hartman, P.S.; Hevelone, J.; Dwarakanath, V.; Mitchell, D.L. )

    1989-06-01

    Radioimmunoassays were used to monitor the removal of antibody-binding sites associated with the two major UV radiation-induced DNA photoproducts (cyclobutane dimers and (6-4) photoproducts). Unlike with cultured human cells, where (6-4) photoproducts are removed more rapidly than cyclobutane dimers, the kinetics of repair were similar for both lesions. Repair capacity in wild type diminished throughout development. The radioimmunoassays were also employed to confirm the absence of photoreactivation in C. elegans. In addition, three radiation-sensitive mutants (rad-1, rad-2, rad-7) displayed normal repair capacities. An excision defect was much more pronounced in larvae than embryos in the fourth mutant tested (rad-3). This correlates with the hypersensitivity pattern of this mutant and suggests that DNA repair may be developmentally regulated in C. elegans. The mechanism of DNA repair in C. elegans as well as the relationship between the repair of specific photoproducts and UV radiation sensitivity during development are discussed.

  16. 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.

  17. 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

  18. Lycopene as A Carotenoid Provides Radioprotectant and Antioxidant Effects by Quenching Radiation-Induced Free Radical Singlet Oxygen: An Overview

    PubMed Central

    Pirayesh Islamian, Jalil; Mehrali, Habib

    2015-01-01

    Radio-protectors are agents that protect human cells and tissues from undesirable effects of ionizing radiation by mainly scavenging radiation-induced free radicals. Although chemical radio-protectors diminish these deleterious side effects they induce a number of unwanted effects on humans such as blood pressure modifications, vomiting, nausea, and both local and generalized cutaneous reactions. These disadvantages have led to emphasis on the use of some botanical radio-protectants as alternatives. This review has collected and organized studies on a plant-derived radio-protector, lycopene. Lycopene protects normal tissues and cells by scavenging free radicals. Therefore, treatment of cells with lycopene prior to exposure to an oxidative stress, oxidative molecules or ionizing radiation may be an effective approach in diminishing undesirable effects of radiation byproducts. Studies have designated lycopene to be an effective radio-protector with negligible side effects. PMID:25685729

  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. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. Adenosine A2A receptor plays an important role in radiation-induced dermal injury.

    PubMed

    Perez-Aso, Miguel; Mediero, Aránzazu; Low, Yee Cheng; Levine, Jamie; Cronstein, Bruce N

    2016-01-01

    Ionizing radiation is a common therapeutic modality and following irradiation dermal changes, including fibrosis and atrophy, may lead to permanent changes. We have previously demonstrated that occupancy of A2A receptor (A2AR) stimulates collagen production, so we determined whether blockade or deletion of A2AR could prevent radiation-induced fibrosis. After targeted irradiation (40 Gy) of the skin of wild-type (WT) or A2AR knockout (A2ARKO) mice, the A2AR antagonist ZM241385 was applied daily for 28 d. In irradiated WT mice treated with the A2AR antagonist, there was a marked reduction in collagen content and skin thickness, and ZM241385 treatment reduced the number of myofibroblasts and angiogenesis. After irradiation, there is an increase in loosely packed collagen fibrils, which is significantly diminished by ZM241385. Irradiation also induced an increase in epidermal thickness, prevented by ZM241385, by increasing the number of proliferating keratinocytes. Similarly, in A2ARKO mice, the changes in collagen alignment, skin thickness, myofibroblast content, angiogenesis, and epidermal hyperplasia were markedly reduced following irradiation. Radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2ARKO mice. Radiation therapy is administered to a significant number of patients with cancer, and radiation reactions may limit this therapeutic modality. Our findings suggest that topical application of an A2AR antagonist prevents radiation dermatitis and may be useful in the prevention or amelioration of radiation changes in the skin. PMID:26415936

  14. Amifostine Reduces Radiation-Induced Complications in a Murine Model of Expander-Based Breast Reconstruction

    PubMed Central

    Felice, Peter A.; Nelson, Noah S.; Page, Erin E.; Deshpande, Sagar S.; Donneys, Alexis; Rodriguez, José; Buchman, Steven R.

    2014-01-01

    Background Immediate expander-based breast reconstruction after mastectomy is a prevalent option for many women with breast cancer. When coupled with adjuvant radiation, however, radiation-induced skin and soft tissue injury diminish the success of this reconstructive technique. We hypothesize that prophylactic administration of the cytoprotectant Amifostine will reduce soft tissue complications from irradiation, aiding expander-based reconstruction for women battling this disease. Methods Sprague Dawley rats were divided into two experimental groups, Operative Expander Placement (Expander) and Operative Sham (Sham). Expander specimens received a sub-latissimus tissue expander with a 15cc fill volume; Shams underwent identical procedures without expander placement. Experimental groups were further divided into Control specimens receiving no further intervention, XRT specimens receiving human-equivalent radiation, and AMF-XRT specimens receiving both Amifostine and human-equivalent radiation. Animals underwent a 45-day recovery period and were evaluated grossly and via ImageJ analysis for skin and soft tissue complications. Results None of the Control, XRT, or AMF-XRT Sham specimens showed skin and soft tissue complications. For Expander animals, significantly fewer AMF-XRT specimens (4 of 13, 30%) demonstrated skin and soft tissue complications compared to XRT specimens (9 of 13, 69%; p = 0.041). ImageJ evaluation of Expander specimens demonstrated a significant increase in skin and soft tissue necrosis for XRT specimens (12.94%), compared with AMF-XRT animals (6.96%, p = 0.019). Conclusions Amifostine pre-treatment significantly reduced skin and soft-tissue complications in both gross inspection and ImageJ analysis. These findings demonstrate that Amifostine prophylaxis provides protection against radiation-induced skin and soft tissue injury in a murine model of expander-based breast reconstruction. Level of Evidence Animal study, not gradable for level of

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    PubMed

    Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

    2010-07-01

    Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia. PMID:20558844

  8. Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis

    SciTech Connect

    Avila, Jennifer L.; Grundmann, Oliver; Burd, Randy; Limesand, Kirsten H.

    2009-02-01

    Purpose: Radiotherapy for head-and-neck cancer causes adverse secondary side effects in the salivary glands and results in diminished quality of life for the patient. A previous in vivo study in parotid salivary glands demonstrated that targeted head-and-neck irradiation resulted in marked increases in phosphorylated p53 (serine{sup 18}) and apoptosis, which was suppressed in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Methods and Materials: Transgenic and knockout mouse models were exposed to irradiation, and p53-mediated transcription, apoptosis, and salivary gland dysfunction were analyzed. Results: The proapoptotic p53 target genes PUMA and Bax were induced in parotid salivary glands of mice at early time points after therapeutic radiation. This dose-dependent induction requires expression of p53 because no radiation-induced expression of PUMA and Bax was observed in p53-/- mice. Radiation also induced apoptosis in the parotid gland in a dose-dependent manner, which was p53 dependent. Furthermore, expression of p53 was required for the acute and chronic loss of salivary function after irradiation. In contrast, apoptosis was not induced in p53-/- mice, and their salivary function was preserved after radiation exposure. Conclusions: Apoptosis in the salivary glands after therapeutic head-and-neck irradiation is mediated by p53 and corresponds to salivary gland dysfunction in vivo.

  9. Ionizing radiation-induced XRCC4 phosphorylation is mediated through ATM in addition to DNA-PK

    PubMed Central

    SHARMA, Mukesh Kumar; KAMDAR, Radhika Pankaj; FUKUCHI, Mikoto; MATSUMOTO, Yoshihisa

    2014-01-01

    XRCC4 (X-ray cross-complementation group 4) is a protein associated with DNA ligase IV, which is thought to join two DNA ends at the final step of DNA double-strand break repair through non-homologous end-joining. It has been shown that, in response to irradiation or treatment with DNA damaging agents, XRCC4 undergoes phosphorylation, requiring DNA-PK. Here we explored possible role of ATM, which is structurally related to DNA-PK, in the regulation of XRCC4. The radiosensitizing effects of DNA-PK inhibitor and/or ATM inhibitor were dependent on XRCC4. DNA-PK inhibitor and ATM inhibitor did not affect the ionizing radiation-induced chromatin recruitment of XRCC4. Ionizing radiation-induced phosphorylation of XRCC4 in the chromatin-bound fraction was largely inhibited by DNA-PK inhibitor but further diminished by the combination with ATM inhibitor. The present results indicated that XRCC4 phosphorylation is mediated through ATM as well as DNA-PK, although DNA-PK plays the major role. We would propose a possible model that DNA-PK and ATM acts in parallel upstream of XRCC4, regulating through phosphorylation. PMID:25391321

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  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 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.

  20. Does Public Employee Unionism Diminish Democracy?

    ERIC Educational Resources Information Center

    Cohen, Sanford

    1979-01-01

    The author considers charges that public sector unionism diminishes democracy by requiring a sharing of public authority with private bodies that too often exerts disproportionate influence on government decisions. He questions these charges in view of declining public unionism and unrealistic assumptions about the nature of local government…

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Radiation-induced hypomethylation triggers urokinase plasminogen activator transcription in meningioma cells.

    PubMed

    Velpula, Kiran Kumar; Gogineni, Venkateswara Rao; Nalla, Arun Kumar; Dinh, Dzung H; Rao, Jasti S

    2013-02-01

    Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H(2)O(2) or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers u

  10. Radiation-Induced Hypomethylation Triggers Urokinase Plasminogen Activator Transcription in Meningioma Cells1

    PubMed Central

    Velpula, Kiran Kumar; Gogineni, Venkateswara Rao; Nalla, Arun Kumar; Dinh, Dzung H; Rao, Jasti S

    2013-01-01

    Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H2O2 or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers u

  11. 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

  12. 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.

  13. 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.

  14. 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).

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. [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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. [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

  12. 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.

  13. Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma.

    PubMed

    Gordon, Ira K; Lu, Jie; Graves, Christian A; Huntoon, Kristin; Frerich, Jason M; Hanson, Ryan H; Wang, Xiaoping; Hong, Christopher S; Ho, Winson; Feldman, Michael J; Ikejiri, Barbara; Bisht, Kheem; Chen, Xiaoyuan S; Tandle, Anita; Yang, Chunzhang; Arscott, W Tristram; Ye, Donald; Heiss, John D; Lonser, Russell R; Camphausen, Kevin; Zhuang, Zhengping

    2015-07-01

    Protein phosphatase 2A (PP2A) is a tumor suppressor whose function is lost in many cancers. An emerging, though counterintuitive, therapeutic approach is inhibition of PP2A to drive damaged cells through the cell cycle, sensitizing them to radiotherapy. We investigated the effects of PP2A inhibition on U251 glioblastoma cells following radiation treatment in vitro and in a xenograft mouse model in vivo. Radiotherapy alone augmented PP2A activity, though this was significantly attenuated with combination LB100 treatment. LB100 treatment yielded a radiation dose enhancement factor of 1.45 and increased the rate of postradiation mitotic catastrophe at 72 and 96 hours. Glioblastoma cells treated with combination LB100 and radiotherapy maintained increased γ-H2AX expression at 24 hours, diminishing cellular repair of radiation-induced DNA double-strand breaks. Combination therapy significantly enhanced tumor growth delay and mouse survival and decreased p53 expression 3.68-fold, compared with radiotherapy alone. LB100 treatment effectively inhibited PP2A activity and enhanced U251 glioblastoma radiosensitivity in vitro and in vivo. Combination treatment with LB100 and radiation significantly delayed tumor growth, prolonging survival. The mechanism of radiosensitization appears to be related to increased mitotic catastrophe, decreased capacity for repair of DNA double-strand breaks, and diminished p53 DNA-damage response pathway activity. PMID:25939762

  14. Protection of Radiation-Induced Damage to the Hematopoietic System, Small Intestine and Salivary Glands in Rats by JNJ7777120 Compound, a Histamine H4 Ligand

    PubMed Central

    Martinel Lamas, Diego J.; Carabajal, Eliana; Prestifilippo, Juan P.; Rossi, Luis; Elverdin, Juan C.; Merani, Susana; Bergoc, Rosa M.; Rivera, Elena S.; Medina, Vanina A.

    2013-01-01

    Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG) function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01). This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01). JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy. PMID:23922686

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Diminishing returns in bovine tuberculosis control.

    PubMed

    Hone, J

    2013-07-01

    Mycobacterium bovis causes bovine tuberculosis (bTB) in many mammals including cattle, deer and brushtail possum. The aim of this study was to estimate the strength of association, using model selection (AICc) regression analyses, between the proportion of cattle and farmed deer herds with bTB in New Zealand and annual costs of TB control, namely disease control in livestock, in wildlife or in a combination of the two. There was more support for curved (concave up) than linear models which related the proportion of cattle and farmed deer herds with bTB to the annual control costs. The curved, concave-up, best-fitting relationships showed diminishing returns with no positive asymptote and implied TB eradication is feasible in New Zealand. PMID:23632097

  4. Protective effect of an antithyroid compound against γ-radiation-induced damage in human colon cancer cells.

    PubMed

    Perona, Marina; Dagrosa, Maria A; Pagotto, Romina; Casal, Mariana; Pignataro, Omar; Pisarev, Mario A; Juvenal, Guillermo J

    2014-08-01

    We have previously reported the radioprotective effect of propylthiouracil (PTU) on thyroid cells. The aim of the present study was to analyze whether tumor cells and normal cells demonstrate the same response to PTU. Human colon carcinoma cells were irradiated with γ-irradiation with or without PTU. We evaluated the clonogenic survival, intracellular reactive oxygen species levels, catalase, superoxide dismutase and glutathione peroxidase activities, and apoptosis by nuclear cell morphology and caspase-3 activity assays. Cyclic AMP (cAMP) levels were measured by radioimmunoassay. PTU treatment increased surviving cell fraction at 2 Gy (SF2) from 56.9 ± 3.6 in controls to 75.0 ± 3.5 (p < 0.05) and diminished radiation-induced apoptosis. In addition, we observed that the level of antioxidant enzymes' activity was increased in cells treated with PTU. Moreover, pretreatment with PTU increased intracellular levels of cAMP. Forskolin (p < 0.01) and dibutyryl cAMP (p < 0.05) mimicked the effect of PTU on SF2. Co-treatment with H89, an inhibitor of protein kinase A, abolished the radioprotective effect of PTU. PTU reduces the toxicity of ionizing radiation by increasing cAMP levels and also possibly through a reduction in apoptosis levels and in radiation-induced oxidative stress damage. We therefore conclude that PTU protects both normal and cancer cells during exposure to radiation in conditions mimicking the radiotherapy. PMID:24811726

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  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 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  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. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  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. 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.

  5. 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

  6. 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.

  7. 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.

  8. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence.

    PubMed

    Zhang, Chen; Zhao, Kuaile; Bu, Wenbo; Ni, Dalong; Liu, Yanyan; Feng, Jingwei; Shi, Jianlin

    2015-02-01

    Strong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing-radiation-induced PDT agent, achieving synchronous radiotherapy and depth-insensitive PDT with diminished oxygen dependence. In the core-shell Ce(III)-doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the Ce(III)-doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron-hole (e(-)-h(+)) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type I PDT process for enhanced antitumor therapeutic efficacy. PMID:25483028

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. [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

  5. 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.

  6. Experimental Study on Radiation Induced Boiling Enhancement for Stainless Steel Plate

    SciTech Connect

    Koji Okamoto; Hiroshi Akiyama; Haruki Madarame; Tomoji Takamasa

    2002-07-01

    The Radiation Induced Boiling Enhancement phenomena (RIBE) were confirmed using the SUS304 foil. The SUS304 with plasma oxidized surface shows higher CHF, i.e., about 20% improvement. While, the natural and mixed gas oxidized surface does not show the boiling enhancement. The RIBE has been highly related to the surface conditions. (authors)

  7. 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.

  8. 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

  9. 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.

  10. Inactivation of Kupffer Cells by Gadolinium Chloride Protects Murine Liver From Radiation-Induced Apoptosis

    SciTech Connect

    Du Shisuo; Qiang Min; Zeng Zhaochong; Ke Aiwu; Ji Yuan; Zhang Zhengyu; Zeng Haiying; Liu Zhongshan

    2010-03-15

    Purpose: To determine whether the inhibition of Kupffer cells before radiotherapy (RT) would protect hepatocytes from radiation-induced apoptosis. Materials and Methods: A single 30-Gy fraction was administered to the upper abdomen of Sprague-Dawley rats. The Kupffer cell inhibitor gadolinium chloride (GdCl3; 10 mg/kg body weight) was intravenously injected 24 h before RT. The rats were divided into four groups: group 1, sham RT plus saline (control group); group 2, sham RT plus GdCl3; group 3, RT plus saline; and group 4, RT plus GdCl3. Liver tissue was collected for measurement of apoptotic cytokine expression and evaluation of radiation-induced liver toxicity by analysis of liver enzyme activities, hepatocyte micronucleus formation, apoptosis, and histologic staining. Results: The expression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha was significantly attenuated in group 4 compared with group 3 at 2, 6, 24, and 48 h after injection (p <0.05). At early points after RT, the rats in group 4 exhibited significantly lower levels of liver enzyme activity, apoptotic response, and hepatocyte micronucleus formation compared with those in group 3. Conclusion: Selective inactivation of Kupffer cells with GdCl3 reduced radiation-induced cytokine production and protected the liver against acute radiation-induced damage.

  11. 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

  12. 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.

  13. Extracellular Adenosine Production by ecto-5'-Nucleotidase (CD73) Enhances Radiation-Induced Lung Fibrosis.

    PubMed

    Wirsdörfer, Florian; de Leve, Simone; Cappuccini, Federica; Eldh, Therese; Meyer, Alina V; Gau, Eva; Thompson, Linda F; Chen, Ning-Yuan; Karmouty-Quintana, Harry; Fischer, Ute; Kasper, Michael; Klein, Diana; Ritchey, Jerry W; Blackburn, Michael R; Westendorf, Astrid M; Stuschke, Martin; Jendrossek, Verena

    2016-05-15

    Radiation-induced pulmonary fibrosis is a severe side effect of thoracic irradiation, but its pathogenesis remains poorly understood and no effective treatment is available. In this study, we investigated the role of the extracellular adenosine as generated by the ecto-5'-nucleotidase CD73 in fibrosis development after thoracic irradiation. Exposure of wild-type C57BL/6 mice to a single dose (15 Gray) of whole thorax irradiation triggered a progressive increase in CD73 activity in the lung between 3 and 30 weeks postirradiation. In parallel, adenosine levels in bronchoalveolar lavage fluid (BALF) were increased by approximately 3-fold. Histologic evidence of lung fibrosis was observed by 25 weeks after irradiation. Conversely, CD73-deficient mice failed to accumulate adenosine in BALF and exhibited significantly less radiation-induced lung fibrosis (P < 0.010). Furthermore, treatment of wild-type mice with pegylated adenosine deaminase or CD73 antibodies also significantly reduced radiation-induced lung fibrosis. Taken together, our findings demonstrate that CD73 potentiates radiation-induced lung fibrosis, suggesting that existing pharmacologic strategies for modulating adenosine may be effective in limiting lung toxicities associated with the treatment of thoracic malignancies. Cancer Res; 76(10); 3045-56. ©2016 AACR. PMID:26921334

  14. 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

  15. 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).

  16. 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...

  17. 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...

  18. 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

  19. 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

  20. 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

  1. Radiation-induced conductivity and high-temperature Q changes in quartz resonators

    SciTech Connect

    Koehler, D R

    1981-01-01

    While high temperature electrolysis has proven beneficial as a technique to remove interstitial impurities from quartz, reliable indices to measure the efficacy of such a processing step are still under development. The present work is directed toward providing such an index. Two techniques have been investigated - one involves measurement of the radiation induced conductivity in quartz along the optic axis, and the second involves measurement of high temperature Q changes. Both effects originate when impurity charge compensators are released from their traps, in the first case resulting in ionic conduction and in the second case resulting in increased acoustic losses. Radiation induced conductivity measurements have been carried out with a 200 kV, 14 mA x-ray machine producing 5 rads/s. With electric fields of the order of 10/sup 4/ V/cm, the noise level in the current measuring system is equivalent to an ionic current generated by quartz impurities in the 1 ppB range. The accuracy of the high temperature ( 300 to 800/sup 0/K) Q/sup -1/ measurement technique will be determined. A number of resonators constructed of quartz material of different impurity contents have been tested and both the radiation induced conductivity and the high temperature Q/sup -1/ results compared with earlier radiation induced frequency and resonator resistance changes. 10 figures.

  2. 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.

  3. 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

  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. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. Physiology of Hormone Autonomous Tissue Lines Derived From Radiation-Induced Tumors of Arabidopsis thaliana.

    PubMed

    Campell, B R; Town, C D

    1991-11-01

    gamma-Radiation-induced tumors of Arabidopsis thaliana L. have been produced as a novel approach to isolation of genes that regulate plant development. Tumors excised from irradiated plants are hormone autonomous in culture and have been maintained on hormone-free medium for up to 4 years. Five tumor tissue lines having different morphologies and growth rates were analyzed for auxin, cytokinin, and 1-aminocyclopropane-1-carboxylic acid (ACC) content, ethylene production, and response to exogenous growth regulators. Normal tissues and two crown gall tissue lines were analyzed for comparison. Rosettes and whole seedlings each contained approximately 30 nanograms. (gram fresh weight)(-1) free indoleacetic acid (IAA), 150 nanograms. (gram fresh weight)(-1) ester-conjugated IAA, and 10 to 20 micrograms. (gram fresh weight)(-1) amide-conjugated IAA. The crown gall lines contained similar amounts of free and ester-conjugated IAA but less amide conjugates. Whereas three of the radiation-induced tumor lines had IAA profiles similar to normal tissues, one line had 10- to 100-fold more free IAA and three- to 10-fold less amide-conjugated IAA. The fifth line had normal free IAA levels but more conjugated IAA than control tissues. Whole seedlings contained approximately 2 nanograms. (gram fresh weight)(-1) of both zeatin riboside and isopentenyladenosine. The crown gall lines had 100- to 1000-fold higher levels of each cytokinin. In contrast, the three radiation-induced tumor lines analyzed contained cytokinin levels similar to the control tissue. The radiation-induced tumor tissues produced very little ethylene, although each contained relatively high levels of ACC. Normal callus contained similar amounts of ACC but produced several times more ethylene than the radiation-induced tumor lines. Each of the radiation-induced tumor tissues displayed a unique set of responses to exogenously supplied growth regulators. Only one tumor line showed the same response as normal callus to

  11. Physiology of Hormone Autonomous Tissue Lines Derived From Radiation-Induced Tumors of Arabidopsis thaliana 1

    PubMed Central

    Campell, Bruce R.; Town, Christopher D.

    1991-01-01

    γ-Radiation-induced tumors of Arabidopsis thaliana L. have been produced as a novel approach to isolation of genes that regulate plant development. Tumors excised from irradiated plants are hormone autonomous in culture and have been maintained on hormone-free medium for up to 4 years. Five tumor tissue lines having different morphologies and growth rates were analyzed for auxin, cytokinin, and 1-aminocyclopropane-1-carboxylic acid (ACC) content, ethylene production, and response to exogenous growth regulators. Normal tissues and two crown gall tissue lines were analyzed for comparison. Rosettes and whole seedlings each contained approximately 30 nanograms· (gram fresh weight)−1 free indoleacetic acid (IAA), 150 nanograms· (gram fresh weight)−1 ester-conjugated IAA, and 10 to 20 micrograms· (gram fresh weight)−1 amide-conjugated IAA. The crown gall lines contained similar amounts of free and ester-conjugated IAA but less amide conjugates. Whereas three of the radiation-induced tumor lines had IAA profiles similar to normal tissues, one line had 10- to 100-fold more free IAA and three- to 10-fold less amide-conjugated IAA. The fifth line had normal free IAA levels but more conjugated IAA than control tissues. Whole seedlings contained approximately 2 nanograms· (gram fresh weight)−1 of both zeatin riboside and isopentenyladenosine. The crown gall lines had 100- to 1000-fold higher levels of each cytokinin. In contrast, the three radiation-induced tumor lines analyzed contained cytokinin levels similar to the control tissue. The radiation-induced tumor tissues produced very little ethylene, although each contained relatively high levels of ACC. Normal callus contained similar amounts of ACC but produced several times more ethylene than the radiation-induced tumor lines. Each of the radiation-induced tumor tissues displayed a unique set of responses to exogenously supplied growth regulators. Only one tumor line showed the same response as normal callus to

  12. [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

  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. Blocking HMGB1 signal pathway protects early radiation-induced lung injury

    PubMed Central

    Wang, Liping; Zhang, Jing; Wang, Baozhong; Wang, Guifu; Xu, Junlong

    2015-01-01

    It has been reported that HMGB1 participated in various types of lung injury. In this study, we explored whether blocking HMGB1 has a preventive effect on the early radiation-induced lung injury and investigate the mechanism. Mice model of radiation-induced lung injury were accomplished by a single dose irradiation (15 Gy) to the whole thorax. Irradiated mice were treated with HMGB1-neutralizing antibody intraperitoneally dosed 10 μg, 50 μg, 100 μg/mouse respectively and were sacrificed after one week post-irradiation. Lung tissue slices were stained by H&E, and alveolitis was quantified by Szapiel scoring system. The level of cytokines TNF-γ in bronchoalveolar lavage fluid was detected by ELISA method. And p65NF-κB, p50NF-κB protein expression in mice lung tissues was detected by Western blot analysis. The results showed that blocking HMGB1 inhibited the inflammatory response, and thereby decreased the degree of alveolitis of irradiated lung tissue. In addition, HMGB1 antagonist can restrain the expression of type Th2 or Th17 derived inflammatory cytokines TNF-α, IL-6 and IL-17A, promote the expression of Th1 type cytokines INF-γ, and inhibit p65 NF-κB but promote p50 NF-κB activation, which promoted the resolution of the radiation-induced inflammatory response. In conclusion, blocking HMGB1 can reduce the degree of early radiation-induced lung injury, and its mechanism may be related to the promotion of p50NF-κB activation and its downstream molecules expression. Inhibiting HMGB1 may be a new target to deal with early radiation-induced lung injury. PMID:26191172

  15. 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.

  16. On the mechanism of radiation-induced emesis: The role of serotonin

    SciTech Connect

    Scarantino, C.W.; Ornitz, R.D.; Hoffman, L.G.

    1994-11-15

    The aim of this study was to determine the mechanism of action of radiation-induced emesis by determining the incidence of radiation-induced emesis following hemibody irradiation; the effects of specific antiemetics especially ondansetron, a 5-hydroxytryptamine receptor antagonist, and to determine the relationship between radiation-induced emesis and serotonin (5-hydroxytryptamine) through its active metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Forty-one patients received 53 hemibody treatments of 5-8 Gy following intravenous hydration. The patients were divided into three groups according to prehemibody irradiation treatment: Group A: no pretreatment antiemetics, 30 patients; Group B: nonondansetron antiemetics (metoclopramide, dexamethasone, prochlorperazine), ten patients; and Group C: ondansetron, 13 patient. The incidence of radiation-induced emesis was determined prehemibody irradiation or baseline and at 1 h posthemibody irradiation in 38 patients and the results expressed as the percent change in 5-HIAA (ng/ug creatinine). The incidence of radiation-induced emesis was 82% (14/17) following upper/mid hemibody irradiation and 15% (2/11) following lower hemibody irradiation in Group A; 50% (3/6) and 25% (1/4) following upper/mid and lower hemibody irradiation respectively, in Group B/; and 0% (p/13) after upper/mid hemibody irradiation in Group C. The incidence of emesis was significantly different (p<0.001) between the patients of Group A and C who received upper/mid hemibody irradiation. The percent change in 5-HIAA excretion following upper/mid hemibody irradiation were greatest in Group A and smallest in Group C (p<0.002). The degree of change following lower hemibody irradiation (15% incidence of emesis) in Group A was lower than upper/mid hemibody irradiation of the same group. 17 refs., 3 figs., 2 tabs.

  17. Blocking HMGB1 signal pathway protects early radiation-induced lung injury.

    PubMed

    Wang, Liping; Zhang, Jing; Wang, Baozhong; Wang, Guifu; Xu, Junlong

    2015-01-01

    It has been reported that HMGB1 participated in various types of lung injury. In this study, we explored whether blocking HMGB1 has a preventive effect on the early radiation-induced lung injury and investigate the mechanism. Mice model of radiation-induced lung injury were accomplished by a single dose irradiation (15 Gy) to the whole thorax. Irradiated mice were treated with HMGB1-neutralizing antibody intraperitoneally dosed 10 μg, 50 μg, 100 μg/mouse respectively and were sacrificed after one week post-irradiation. Lung tissue slices were stained by H&E, and alveolitis was quantified by Szapiel scoring system. The level of cytokines TNF-γ in bronchoalveolar lavage fluid was detected by ELISA method. And p65NF-κB, p50NF-κB protein expression in mice lung tissues was detected by Western blot analysis. The results showed that blocking HMGB1 inhibited the inflammatory response, and thereby decreased the degree of alveolitis of irradiated lung tissue. In addition, HMGB1 antagonist can restrain the expression of type Th2 or Th17 derived inflammatory cytokines TNF-α, IL-6 and IL-17A, promote the expression of Th1 type cytokines INF-γ, and inhibit p65 NF-κB but promote p50 NF-κB activation, which promoted the resolution of the radiation-induced inflammatory response. In conclusion, blocking HMGB1 can reduce the degree of early radiation-induced lung injury, and its mechanism may be related to the promotion of p50NF-κB activation and its downstream molecules expression. Inhibiting HMGB1 may be a new target to deal with early radiation-induced lung injury. PMID:26191172

  18. 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

  19. Journal of Nuclear Materials - Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91

    SciTech Connect

    Jiao, Zhijie; Busby, Jeremy T; Was, Gary S; Jiao, Zhijie

    2010-01-01

    Radiation-induced segregation in ferritic martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni Si Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures. 2010 Elsevier B.V. All rights reserved

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

    SciTech Connect

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

    1995-03-01

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

  1. Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.

    PubMed

    Weigel, Christoph; Veldwijk, Marlon R; Oakes, Christopher C; Seibold, Petra; Slynko, Alla; Liesenfeld, David B; Rabionet, Mariona; Hanke, Sabrina A; Wenz, Frederik; Sperk, Elena; Benner, Axel; Rösli, Christoph; Sandhoff, Roger; Assenov, Yassen; Plass, Christoph; Herskind, Carsten; Chang-Claude, Jenny; Schmezer, Peter; Popanda, Odilia

    2016-01-01

    Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy. PMID:26964756

  2. Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis

    PubMed Central

    Weigel, Christoph; Veldwijk, Marlon R.; Oakes, Christopher C.; Seibold, Petra; Slynko, Alla; Liesenfeld, David B.; Rabionet, Mariona; Hanke, Sabrina A.; Wenz, Frederik; Sperk, Elena; Benner, Axel; Rösli, Christoph; Sandhoff, Roger; Assenov, Yassen; Plass, Christoph; Herskind, Carsten; Chang-Claude, Jenny; Schmezer, Peter; Popanda, Odilia

    2016-01-01

    Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy. PMID:26964756

  3. 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.

  4. 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.

  5. A case of radiation-induced mucosal melanoma in an immunohistochemically S-100-negative patient.

    PubMed

    Rodriguez, Michael; Patil, Yash; Gupta, Arun

    2016-08-01

    We report a case of radiation-induced mucosal melanoma in a 41-year-old woman with a history of childhood rhabdomyosarcoma of the nasal cavity that had been treated with radiotherapy. During the workup for the melanoma, the patient was found to be negative for S-100 protein on immunostaining. While many melanotic markers for the histologic confirmation of melanoma exist, they can be negative in some cases, such as ours. To the best of our knowledge, only 1 case of radiation-induced melanoma has been previously reported in the English-language literature, and in that case the patient was S-100-positive. Although our case is rare, it suggests another possible long-term adverse effect of radiotherapy. We also describe the morphologies and histology associated with diagnosing melanoma in an S-100-negative patient. PMID:27551844

  6. Protective effect of α-lipoic acid against radiation-induced fibrosis in mice.

    PubMed

    Ryu, Seung-Hee; Park, Eun-Young; Kwak, Sungmin; Heo, Seung-Ho; Ryu, Je-Won; Park, Jin-Hong; Choi, Kyung-Chul; Lee, Sang-Wook

    2016-03-29

    Radiation-induced fibrosis (RIF) is one of the most common late complications of radiation therapy. We found that α-lipoic acid (α-LA) effectively prevents RIF. In RIF a mouse model, leg contracture assay was used to test the in vivo efficacy of α-LA. α-LA suppressed the expression of pro-fibrotic genes after irradiation, both in vivo and in vitro, and inhibited the up-regulation of TGF-β1-mediated p300/CBP activity. Thus, α-LA prevents radiation-induced fibrosis (RIF) by inhibiting the transcriptional activity of NF-κB through inhibition of histone acetyltransferase activity. α-LA is a new therapeutic methods that can be used in the prevention-treatment of RIF. PMID:26799284

  7. Protective effect of α-lipoic acid against radiation-induced fibrosis in mice

    PubMed Central

    Ryu, Seung-Hee; Park, Eun-Young; Kwak, Sungmin; Heo, Seung-Ho; Ryu, Je-Won; Park, Jin-hong

    2016-01-01

    Radiation-induced fibrosis (RIF) is one of the most common late complications of radiation therapy. We found that α-lipoic acid (α-LA) effectively prevents RIF. In RIF a mouse model, leg contracture assay was used to test the in vivo efficacy of α-LA. α-LA suppressed the expression of pro-fibrotic genes after irradiation, both in vivo and in vitro, and inhibited the up-regulation of TGF-β1-mediated p300/CBP activity. Thus, α-LA prevents radiation-induced fibrosis (RIF) by inhibiting the transcriptional activity of NF-κB through inhibition of histone acetyltransferase activity. α-LA is a new therapeutic methods that can be used in the prevention-treatment of RIF. PMID:26799284

  8. 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).

  9. Hyperbaric oxygen in the treatment of radiation-induced optic neuropathy

    SciTech Connect

    Guy, J.; Schatz, N.J.

    1986-08-01

    Four patients with radiation-induced optic neuropathies were treated with hyperbaric oxygen. They had received radiation therapy for treatment of pituitary tumors, reticulum cell sarcoma, and meningioma. Two presented with amaurosis fugax before the onset of unilateral visual loss and began hyperbaria within 72 hours after development of unilateral optic neuropathy. Both had return of visual function to baseline levels. The others initiated treatment two to six weeks after visual loss occurred in the second eye and had no significant improvement of vision. Treatment consisted of daily administration of 100% oxygen under 2.8 atmospheres of pressure for 14-28 days. There were no medical complications of hyperbaria. While hyperbaric oxygen is effective in the treatment of radiation-induced optic neuropathy, it must be instituted within several days of deterioration in vision for restoration of baseline function.

  10. 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.

  11. Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

    SciTech Connect

    Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E. )

    1989-08-01

    This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

  12. [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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

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

    SciTech Connect

    Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C.

    2013-11-01

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

  19. Blockade of Kv1.3 channels ameliorates radiation-induced brain injury

    PubMed Central

    Peng, Ying; Lu, Kui; Li, Zichen; Zhao, Yaodong; Wang, Yiping; Hu, Bin; Xu, Pengfei; Shi, Xiaolei; Zhou, Bin; Pennington, Michael; Chandy, K. George; Tang, Yamei

    2014-01-01

    Background Tumors affecting the head, neck, and brain account for significant morbidity and mortality. The curative efficacy of radiotherapy for these tumors is well established, but radiation carries a significant risk of neurologic injury. So far, neuroprotective therapies for radiation-induced brain injury are still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)–170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel, protected mice from radiation-induced brain injury. Methods Mice were treated with ShK-170 for 3 days immediately after brain irradiation. Radiation-induced brain injury was assessed by MRI scans and a Morris water maze. Pathophysiological change of the brain was measured by immunofluorescence. Gene and protein expressions of Kv1.3 and inflammatory factors were measured by quantitative real-time PCR, reverse transcription PCR, ELISA assay, and western blot analyses. Kv currents were recorded in the whole-cell configuration of the patch-clamp technique. Results Radiation increased Kv1.3 mRNA and protein expression in microglia. Genetic silencing of Kv1.3 by specific short interference RNAs or pharmacological blockade with ShK-170 suppressed radiation-induced production of the proinflammatory factors interleukin-6, cyclooxygenase-2, and tumor necrosis factor–α by microglia. ShK-170 also inhibited neurotoxicity mediated by radiation-activated microglia and promoted neurogenesis by increasing the proliferation of neural progenitor cells. Conclusions The therapeutic effect of ShK-170 is mediated by suppression of microglial activation and microglia-mediated neurotoxicity and enhanced neurorestoration by promoting proliferation of neural progenitor cells. PMID:24305723

  20. Gamma knife radiosurgery of radiation-induced intracranial tumors: Local control, outcomes, and complications

    SciTech Connect

    Jensen, Ashley W.; Brown, Paul D.; Pollock, Bruce E.; Stafford, Scott L.; Link, Michael J.; Garces, Yolanda I.; Foote, Robert L.; Gorman, Deborah A.; Schomberg, Paula J.

    2005-05-01

    Purpose: To determine local control (LC) and complication rates for patients who underwent radiosurgery for radiation-induced intracranial tumors. Methods and Materials: Review of a prospectively maintained database (2,714 patients) identified 16 patients (20 tumors) with radiation-induced tumors treated with radiosurgery between 1990 and 2004. Tumor types included typical meningioma (n = 17), atypical meningioma (n = 2), and schwannoma (n 1). Median patient age at radiosurgery was 47.5 years (range, 27-70 years). The median tumor margin dose was 16 Gy (range, 12-20 Gy). Median follow-up was 40.2 months (range, 10.8-146.2 months). Time-to-event outcomes were calculated with Kaplan-Meier estimates. Results: Three-year and 5-year LC rates were 100%. Three-year and 5-year overall survival rates were 92% and 80%, respectively. Cause-specific survival rates at 3 and 5 years were 100%. Three patients died: 1 had in-field progression 65.1 months after radiosurgery and later died of the tumor, 1 died of progression of a preexisting brain malignancy, and 1 died of an unrelated cause. One patient had increased seizure activity that correlated with development of edema seen on neuroimaging. Conclusions: LC, survival, and complication rates in our series are comparable to those in previous reports of radiosurgery for intracranial meningiomas. Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas. Radiosurgery is a safe and effective treatment option for radiation-induced intracranial tumors, most of which are typical meningiomas.

  1. Radiation-induced intermediates in irradiated glassy ionic liquids at low temperature

    NASA Astrophysics Data System (ADS)

    Saenko, Elizaveta V.; Lukianova, Mariia A.; Shiryaeva, Ekaterina S.; Takahashi, Kenji; Feldman, Vladimir I.

    2016-07-01

    The primary radiation-induced processes in irradiated low-temperature pyrrolidinium- and piperidinium-type ionic liquids were investigated by EPR and optical absorption spectroscopy. A narrow singlet signal in the EPR spectra of irradiated ionic liquids was attributed to the physically stabilized electron. Broad absorption band in visible region was ascribed to "hole" species. Aromatic scavengers react with "hole" species in glassy irradiated ionic liquids at 77 K.

  2. Gamma-Tocotrienol Modulates Radiation-Induced MicroRNA Expression in Mouse Spleen.

    PubMed

    Ghosh, Sanchita P; Pathak, Rupak; Kumar, Parameet; Biswas, Shukla; Bhattacharyya, Sharmistha; Kumar, Vidya P; Hauer-Jensen, Martin; Biswas, Roopa

    2016-05-01

    Ionizing radiation causes depletion of hematopoietic cells and enhances the risk of developing secondary hematopoietic malignancies. Vitamin E analog gamma-tocotrienol (GT3), which has anticancer properties, promotes postirradiation hematopoietic cell recovery by enhancing spleen colony-forming capacity, and provides protection against radiation-induced lethality in mice. However, the underlying molecular mechanism involved in GT3-mediated postirradiation survival is not clearly understood. Recent studies have shown that natural dietary products including vitamin E provide a benefit to biological systems by modulating microRNA (miR) expression. In this study, we show that GT3 differentially modulates the miR footprint in the spleen of irradiated mice compared to controls at early times (day 1), as well as later times (day 4 and 15) after total-body irradiation. We observed that miR expression was altered in a dose- and time-dependent manner in GT3-pretreated spleen tissues from total-body irradiated mice. GT3 appeared to affect the expression of a number of radiation-modulated miRs known to be involved in hematopoiesis and lymphogenesis. Moreover, GT3 pretreatment also suppressed the upregulation of radiation-induced p53, suggesting the function of GT3 in the prevention of radiation-induced damage to the spleen. In addition, we have shown that GT3 significantly reduced serum levels of Flt3L, a biomarker of radiation-induced bone marrow aplasia. Further in silico analyses of the effect of GT3 implied the association of p38 MAPK, ERK and insulin signaling pathways. Our study provides initial insight into the mechanism by which GT3 mediates protection of spleen after total-body irradiation. PMID:27128741

  3. 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

  4. Radiatively induced Lorentz-violating operator of mass dimension five in QED

    SciTech Connect

    Mariz, T.

    2011-02-15

    The first higher derivative term of the photon sector of Lorentz-violating QED, with an operator of mass dimension d=5, is radiatively induced from the fermion sector, which contains a derivative term with the dimensionless coefficient g{sup {lambda}{mu}{nu}}. The calculation is performed perturbatively in the coefficient for Lorentz violation, and, due to the fact that the contributions are quadratically divergent, we adopt dimensional regularization.

  5. Multidisciplinary approach to treatment of radiation-induced chest wall sarcoma.

    PubMed

    Kara, H Volkan; Gandolfi, Brad M; Williams, Judson B; D'Amico, Thomas A; Zenn, Michael R

    2016-08-01

    Radiation-induced sarcoma (RIS) is a rare complication following therapeutic external irradiation for lung cancer patients. Patients with RIS may develop recurrence or metastasis of the previous disease and also at high risk for early chest wall complications following operation, which requires close follow-up and multidisciplinary approach. We present a challenging case of RIS with a multidisciplinary teamwork in the decision-making and successful management. PMID:25663293

  6. 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.

  7. 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

  8. Diminishing Adult Egocentrism when Estimating What Others Know

    ERIC Educational Resources Information Center

    Thomas, Ruthann C.; Jacoby, Larry L.

    2013-01-01

    People often use what they know as a basis to estimate what others know. This egocentrism can bias their estimates of others' knowledge. In 2 experiments, we examined whether people can diminish egocentrism when predicting for others. Participants answered general knowledge questions and then estimated how many of their peers would know the…

  9. The Changing Black Teacher and Diminishing Opportunities for Black Teachers.

    ERIC Educational Resources Information Center

    Hilliard, Asa G., III

    Racism remains a distinct factor in problems faced by black teachers and teacher educators. The number of black teachers in the public schools is diminishing, especially in the southern states, where the black student population is the highest. The higher education environment has been undergoing drastic changes in faculty and student body…

  10. Loss of Matrix Metalloproteinase-13 Attenuates Murine Radiation-Induced Pulmonary Fibrosis

    SciTech Connect

    Flechsig, Paul; Hartenstein, Bettina; Teurich, Sybille; Dadrich, Monika; Hauser, Kai; Abdollahi, Amir; Groene, Hermann-Josef; Angel, Peter; Huber, Peter E.

    2010-06-01

    Purpose: Pulmonary fibrosis is a disorder of the lungs with limited treatment options. Matrix metalloproteinases (MMPs) constitute a family of proteases that degrade extracellular matrix with roles in fibrosis. Here we studied the role of MMP13 in a radiation-induced lung fibrosis model using a MMP13 knockout mouse. Methods and Materials: We investigated the role of MMP13 in lung fibrosis by investigating the effects of MMP13 deficiency in C57Bl/6 mice after 20-Gy thoracic irradiation (6-MV Linac). The morphologic results in histology were correlated with qualitative and quantitative results of volume computed tomography (VCT), magnetic resonance imaging (MRI), and clinical outcome. Results: We found that MMP13 deficient mice developed less pulmonary fibrosis than their wildtype counterparts, showed attenuated acute pulmonary inflammation (days after irradiation), and a reduction of inflammation during the later fibrogenic phase (5-6 months after irradiation). The reduced fibrosis in MMP13 deficient mice was evident in histology with reduced thickening of alveolar septi and reduced remodeling of the lung architecture in good correlation with reduced features of lung fibrosis in qualitative and quantitative VCT and MRI studies. The partial resistance of MMP13-deficient mice to fibrosis was associated with a tendency towards a prolonged mouse survival. Conclusions: Our data indicate that MMP13 has a role in the development of radiation-induced pulmonary fibrosis. Further, our findings suggest that MMP13 constitutes a potential drug target to attenuate radiation-induced lung fibrosis.

  11. Effect of top electrode material on radiation-induced degradation of ferroelectric thin film structures

    NASA Astrophysics Data System (ADS)

    Brewer, Steven J.; Deng, Carmen Z.; Callaway, Connor P.; Paul, McKinley K.; Fisher, Kenzie J.; Guerrier, Jonathon E.; Rudy, Ryan Q.; Polcawich, Ronald G.; Jones, Jacob L.; Glaser, Evan R.; Cress, Cory D.; Bassiri-Gharb, Nazanin

    2016-07-01

    The effects of gamma irradiation on the dielectric and piezoelectric responses of Pb[Zr0.52Ti0.48]O3 (PZT) thin film stacks were investigated for structures with conductive oxide (IrO2) and metallic (Pt) top electrodes. The samples showed, generally, degradation of various key dielectric, ferroelectric, and electromechanical responses when exposed to 2.5 Mrad (Si) 60Co gamma radiation. However, the low-field, relative dielectric permittivity, ɛr, remained largely unaffected by irradiation in samples with both types of electrodes. Samples with Pt top electrodes showed substantial degradation of the remanent polarization and overall piezoelectric response, as well as pinching of the polarization hysteresis curves and creation of multiple peaks in the permittivity-electric field curves post irradiation. The samples with oxide electrodes, however, were largely impervious to the same radiation dose, with less than 5% change in any of the functional characteristics. The results suggest a radiation-induced change in the defect population or defect energy in PZT with metallic top electrodes, which substantially affects motion of internal interfaces such as domain walls. Additionally, the differences observed for stacks with different electrode materials implicate the ferroelectric-electrode interface as either the predominant source of radiation-induced effects (Pt electrodes) or the site of healing for radiation-induced defects (IrO2 electrodes).

  12. Radiation-induced emesis in the dog: effects of lesions and drugs

    SciTech Connect

    Carpenter, D.O.; Briggs, D.B.; Knox, A.P.; Strominger, N.L.

    1986-12-01

    Dogs exposed to 8 Gy /sup 60/Co gamma mid-abdominal irradiation exhibited emesis with an average latency of 102 min and an average of 7.4 episodes over 96 min. There were no significant changes in dogs subjected to a chronic bilateral subdiaphragmatic vagotomy, but emesis was prevented by ablation of the area postrema. Indomethacin pretreatment also prevented radiation-induced emesis in two of seven dogs and in the remainder reduced the average number of episodes. Domperidone pretreatment prevented radiation-induced emesis in all of four dogs tested. In electrophysiological studies recording from the area postrema the chemosensitive neurons were found to be normally silent in anesthetized preparations but excitable by a variety of emetic agents. After irradiation of the abdomen spontaneously active neurons were found with a discharge pattern that mirrored the behavioral pattern of postirradiation emesis. These studies are consistent with radiation-induced emesis being humorally mediated in the dog and implicate dopamine and/or prostaglandins as possible mediators.

  13. The role of secretory granules in radiation-induced dysfunction of rat salivary glands

    SciTech Connect

    Peter, B.; Van Waarde, M.A.W.H.; Konings, A.W.T.; Vissink, A. |; `s-Gravenmade, E.J.

    1995-02-01

    To investigate the possible role of secretory granules in radiation-induced salivary gland dysfunction, rats were pretreated with isoproterenol (5 mg/kg intraperitoneally) to degranulate salivary gland acini. At maximal depletion, salivary glands were locally irradiated with a single dose of 15 Gy of X rays. Parotid and submandibular/sublingual saliva samples were collected before and 1-10 days after irradiation. The lag phase, flow rate, concentrations of potassium and sodium, and amylase secretion were determined. Sham-treated, isoproterenol-treated and irradiated animals provided reference data. In the parotid gland, but not in the submandibular gland, protection against radiation-induced changes in flow rate and composition of saliva occurred after pretreatment with isoproterenol. Combining morphological data from a previous study with data from the current study, it is suggested that improvement of parotid gland function is attributed predominantly to a proliferative stimulus on acinar cells by isoproterenol and not to its degranulation effect. After pretreatment with isoproterenol, an earlier expression of radiation-induced acinar cell damage leading to death was observed, followed by a faster tissue recovery. Thus the proliferative stimulus on acinar cells may accelerate the unmasking of latent lethal damage, resulting in the earlier replacement of dead cells by new, functionally intact cells. 33 refs., 2 figs.

  14. 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

  15. Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

    PubMed Central

    Kang, Bong Gu; Lee, Se Jeong; Kim, Kang Ho; Yang, Heekyoung; Lee, Young-Ae; Cho, Yu Jin; Im, Yong-Seok; Lee, Dong-Sup; Lim, Do-Hoon; Kim, Dong Hyun; Um, Hong-Duck; Lee, Sang-Hun; Lee, Jung-II; Nam, Do-Hyun

    2012-01-01

    Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases. PMID:22347993

  16. Radiation-induced normal tissue injury: role of adhesion molecules in leukocyte-endothelial cell interactions.

    PubMed

    Quarmby, S; Kumar, P; Kumar, S

    1999-07-30

    The late onset of necrosis and fibrosis in normal tissues can be a serious consequence of radiotherapy in cancer patients. Because radiation-induced vascular injury precedes the tissue damage, vascular injury is regarded as crucial in the pathogenesis of tissue damage. An understanding of the processes responsible is essential to develop strategies for the amelioration of radiation-induced normal tissue damage. Leukocyte infiltration is commonly observed at sites of irradiation and is likely to lead to the acceleration and/or induction of parenchymal atrophy, fibrosis and necrosis in normal tissues following radiotherapy. The molecular mechanisms mediating leukocyte infiltration of tissues during inflammation have been studied extensively. It is now well established that cell adhesion molecules (CAMs) expressed on leukocytes and endothelial cells control the trafficking of leukocytes from the blood vessel lumen in these conditions. CAMs including E (endothelial), P (platelet) and L (leukocyte)-selectins, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), beta1 and beta2 integrins and CD31 are involved in the cascade of events resulting in rolling, arrest and transmigration of leukocytes through the inflamed endothelium. Whether a similar sequence of molecular events induces leukocyte sequestration in irradiated normal tissues is not known. This review is focussed on the role of CAMs in radiation-induced leukocyte infiltration of normal tissues and the therapeutic implications of these findings. PMID:10399956

  17. NADPH oxidase mediates radiation-induced oxidative stress in rat brain microvascular endothelial cells.

    PubMed

    Collins-Underwood, J Racquel; Zhao, Weiling; Sharpe, Jessica G; Robbins, Mike E

    2008-09-15

    The need to both understand and minimize the side effects of brain irradiation is heightened by the ever-increasing number of patients with brain metastases that require treatment with whole brain irradiation (WBI); some 200,000 cancer patients/year receive partial or WBI. At the present time, there are no successful treatments for radiation-induced brain injury, nor are there any known effective preventive strategies. Data support a role for chronic oxidative stress in radiation-induced late effects. However, the pathogenic mechanism(s) involved remains unknown. One candidate source of reactive oxygen species (ROS) is nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase, which converts molecular oxygen (O(2)) to the superoxide anion (O(2)(-)) on activation. We hypothesize that brain irradiation leads to activation of NADPH oxidase. We report that irradiating rat brain microvascular endothelial cells in vitro leads to increased (i) intracellular ROS generation, (ii) activation of the transcription factor NFkappaB, (iii) expression of ICAM-1 and PAI-1, and (iv) expression of Nox4, p22(phox), and p47(phox). Pharmacologic and genetic inhibition of NADPH oxidase blocked the radiation-mediated upregulation of intracellular ROS, activation of NFkappaB, and upregulation of ICAM-1 and PAI-1. These results suggest that activation of NADPH oxidase may play a role in radiation-induced oxidative stress. PMID:18640264

  18. Role of the area postrema in radiation-induced taste aversion learning and emesis in cats

    SciTech Connect

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

    1986-01-01

    The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved in the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.

  19. 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

  20. 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.

  1. 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

  2. Altered gastric emptying and prevention of radiation-induced vomiting in dogs. [Cobalt 60 irradiation

    SciTech Connect

    Dubois, A.; Jacobus, J.P.; Grissom, M.P.; Eng, R.R.; Conklin, J.J.

    1984-03-01

    The relation between radiation-induced vomiting and gastric emptying is unclear and the treatment of this condition is not established. We explored, therefore, (a) the effect of cobalt 60 irradiation on gastric emptying of solids and liquids and (b) the possibility of preventing radiation-induced vomiting with the dopamine antagonist, domperidone. Twenty dogs were studied on two separate days, blindly and in random order, after i.v. injection of either a placebo or 0.06 mg/kg domperidone. On a third day, they received 8 Gy (800 rads) whole body irradiation with cobalt 60 gamma-rays after either placebo (n . 10) or domperidone (n . 10). Before each study, each dog was fed chicken liver tagged in vivo with 99mTc-sulfur colloid (solid marker), and water containing 111In-diethylenetriamine pentaacetic acid (liquid marker). Dogs were placed in a Pavlov stand for the subsequent 3 h and radionuclide imaging was performed at 10-min intervals. Irradiation produced vomiting in 9 of 10 dogs given placebo but only in 1 of 10 dogs pretreated with domperidone (p less than 0.01). Gastric emptying of liquids and solids was significantly suppressed by irradiation (p less than 0.01) after both placebo and domperidone. These results demonstrate that radiation-induced vomiting is accompanied by suppression of gastric emptying. Furthermore, domperidone prevents vomiting produced by ionizing radiation but does not alter the accompanying delay of gastric emptying.

  3. 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

  4. Effects of NOX1 on fibroblastic changes of endothelial cells in radiation-induced pulmonary fibrosis

    PubMed Central

    CHOI, SEO-HYUN; KIM, MISEON; LEE, HAE-JUNE; KIM, EUN-HO; KIM, CHUN-HO; LEE, YOON-JIN

    2016-01-01

    Lung fibrosis is a major complication in radiation-induced lung damage following thoracic radiotherapy, while the underlying mechanism has remained to be elucidated. The present study performed immunofluorescence and immunoblot assays on irradiated human pulmonary artery endothelial cells (HPAECs) with or without pre-treatment with VAS2870, a novel NADPH oxidase (NOX) inhibitor, or small hairpin (sh)RNA against NOX1, -2 or -4. VAS2870 reduced the cellular reactive oxygen species content induced by 5 Gy radiation in HPAECs and inhibited phenotypic changes in fibrotic cells, including increased alpha smooth muscle actin and vimentin, and decreased CD31 and vascular endothelial cadherin expression. These fibrotic changes were significantly inhibited by treatment with NOX1 shRNA, but not by NOX2 or NOX4 shRNA. Next, the role of NOX1 in pulmonary fibrosis development was assessed in the lung tissues of C57BL/6J mice following thoracic irradiation using trichrome staining. Administration of an NOX1-specific inhibitor suppressed radiation-induced collagen deposition and fibroblastic changes in the endothelial cells (ECs) of these mice. The results suggested that radiation-induced pulmonary fibrosis may be efficiently reduced by specific inhibition of NOX1, an effect mediated by reduction of fibrotic changes of ECs. PMID:27053172

  5. Basic Fibroblast Growth Factor Ameliorates Endothelial Dysfunction in Radiation-Induced Bladder Injury

    PubMed Central

    Zhang, Shiwei; Qiu, Xuefeng; Zhang, Yanting; Fu, Kai; Zhao, Xiaozhi; Wu, Jinhui; Hu, Yiqiao; Zhu, Weiming; Guo, Hongqian

    2015-01-01

    This study was designed to explore the effect of basic fibroblast growth factor (bFGF) on radiation-induced endothelial dysfunction and histological changes in the urinary bladder. bFGF was administrated to human umbilical vein cells (HUVEC) or urinary bladder immediately after radiation. Reduced expression of thrombomodulin (TM) was indicated in the HUVEC and urinary bladder after treatment with radiation. Decreased apoptosis was observed in HUVEC treated with bFGF. Administration of bFGF increased the expression of TM in HUVEC medium, as well as in the urinary bladder at the early and delayed phases of radiation-induced bladder injury (RIBI). At the early phase, injection of bFGF increased the thickness of urothelium and reduced inflammation within the urinary bladder. At the delayed phase, bFGF was effective in reducing fibrosis within the urinary bladder. Our results indicate that endothelial dysfunction is a prominent feature of RIBI. Administration of bFGF can ameliorate radiation-induced endothelial dysfunction in urinary bladder and preserve bladder histology at early and delayed phases of RIBI. PMID:26351640

  6. Combined inhibition of TGFβ and PDGF signaling attenuates radiation-induced pulmonary fibrosis

    PubMed Central

    Dadrich, Monika; Nicolay, Nils H.; Flechsig, Paul; Bickelhaupt, Sebastian; Hoeltgen, Line; Roeder, Falk; Hauser, Kai; Tietz, Alexandra; Jenne, Jürgen; Lopez, Ramon; Roehrich, Manuel; Wirkner, Ute; Lahn, Michael; Huber, Peter E.

    2016-01-01

    ABSTRACT Background: Radiotherapy (RT) is a mainstay for the treatment of lung cancer, but the effective dose is often limited by the development of radiation-induced pneumonitis and pulmonary fibrosis. Transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF) play crucial roles in the development of these diseases, but the effects of dual growth factor inhibition on pulmonary fibrosis development remain unclear. Methods: C57BL/6 mice were treated with 20 Gy to the thorax to induce pulmonary fibrosis. PDGF receptor inhibitors SU9518 and SU14816 (imatinib) and TGFβ receptor inhibitor galunisertib were applied individually or in combinations after RT. Lung density and septal fibrosis were measured by high-resolution CT and MRI. Lung histology and gene expression analyses were performed and Osteopontin levels were studied. Results: Treatment with SU9518, SU14816 or galunisertib individually attenuated radiation-induced pulmonary inflammation and fibrosis and decreased radiological and histological signs of lung damage. Combining PDGF and TGFβ inhibitors showed to be feasible and safe in a mouse model, and dual inhibition significantly attenuated radiation-induced lung damage and extended mouse survival compared to blockage of either pathway alone. Gene expression analysis of irradiated lung tissue showed upregulation of PDGF and TGFβ-dependent signaling components by thoracic irradiation, and upregulation patterns show crosstalk between downstream mediators of the PDGF and TGFβ pathways. Conclusion: Combined small-molecule inhibition of PDGF and TGFβ signaling is a safe and effective treatment for radiation-induced pulmonary inflammation and fibrosis in mice and may offer a novel approach for treatment of fibrotic lung diseases in humans. Translational statement: RT is an effective treatment modality for cancer with limitations due to acute and chronic toxicities, where TGFβ and PDGF play a key role. Here, we show that a combined

  7. Combined inhibition of TGFβ and PDGF signaling attenuates radiation-induced pulmonary fibrosis.

    PubMed

    Dadrich, Monika; Nicolay, Nils H; Flechsig, Paul; Bickelhaupt, Sebastian; Hoeltgen, Line; Roeder, Falk; Hauser, Kai; Tietz, Alexandra; Jenne, Jürgen; Lopez, Ramon; Roehrich, Manuel; Wirkner, Ute; Lahn, Michael; Huber, Peter E

    2016-05-01

    Background : Radiotherapy (RT) is a mainstay for the treatment of lung cancer, but the effective dose is often limited by the development of radiation-induced pneumonitis and pulmonary fibrosis. Transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF) play crucial roles in the development of these diseases, but the effects of dual growth factor inhibition on pulmonary fibrosis development remain unclear. Methods : C57BL/6 mice were treated with 20 Gy to the thorax to induce pulmonary fibrosis. PDGF receptor inhibitors SU9518 and SU14816 (imatinib) and TGFβ receptor inhibitor galunisertib were applied individually or in combinations after RT. Lung density and septal fibrosis were measured by high-resolution CT and MRI. Lung histology and gene expression analyses were performed and Osteopontin levels were studied. Results : Treatment with SU9518, SU14816 or galunisertib individually attenuated radiation-induced pulmonary inflammation and fibrosis and decreased radiological and histological signs of lung damage. Combining PDGF and TGFβ inhibitors showed to be feasible and safe in a mouse model, and dual inhibition significantly attenuated radiation-induced lung damage and extended mouse survival compared to blockage of either pathway alone. Gene expression analysis of irradiated lung tissue showed upregulation of PDGF and TGFβ-dependent signaling components by thoracic irradiation, and upregulation patterns show crosstalk between downstream mediators of the PDGF and TGFβ pathways. Conclusion : Combined small-molecule inhibition of PDGF and TGFβ signaling is a safe and effective treatment for radiation-induced pulmonary inflammation and fibrosis in mice and may offer a novel approach for treatment of fibrotic lung diseases in humans. Translational statement : RT is an effective treatment modality for cancer with limitations due to acute and chronic toxicities, where TGFβ and PDGF play a key role. Here, we show that a combined inhibition of

  8. 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

  9. 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

  10. Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

    SciTech Connect

    Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R. . E-mail: akennedy@mail.med.upenn.edu

    2006-04-01

    Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, {alpha}-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, {gamma}-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects.

  11. High-frequency detection of the formation and stabilization of a radiation-induced defect cluster in semiconductor structures

    SciTech Connect

    Puzanov, A. S.; Obolenskiy, S. V. Kozlov, V. A.; Volkova, E. V.; Paveliev, D. G.

    2015-12-15

    The processes of the formation and stabilization of a radiation-induced defect cluster upon the arrival of a fast neutron to the space-charge region of a semiconductor diode are analyzed. The current pulse formed by secondary electrons is calculated and the spectrum of the signal generated by the diode (detector) under the action of an instantaneous neutron flux of the fission spectrum is determined. The possibility of experimental detection of the picosecond radiation-induced transition processes is discussed.

  12. Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes

    PubMed Central

    Chang, Jae Won; Park, Keun Hyung; HWANG, Hye Sook; Shin, Yoo Seob; Oh, Young-Taek; Kim, Chul-Ho

    2014-01-01

    Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways. PMID:24078877

  13. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia

    PubMed Central

    2014-01-01

    Background Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy. Results We observed reduced glycolytic flux in tumor cells upon treatment with ketone bodies. Ketone bodies also diminished glutamine uptake, overall ATP content, and survival in multiple pancreatic cancer cell lines, while inducing apoptosis. A decrease in levels of c-Myc, a metabolic master regulator, and its recruitment on glycolytic gene promoters, was in part responsible for the metabolic phenotype in tumor cells. Ketone body-induced intracellular metabolomic reprogramming in pancreatic cancer cells also leads to a significantly diminished cachexia in cell line models. Our mouse orthotopic xenograft models further confirmed the effect of a ketogenic diet in diminishing tumor growth and cachexia. Conclusions Thus, our studies demonstrate that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss. PMID:25228990

  14. Oxygen radicals diminish dopamine transporter function in rat striatum.

    PubMed

    Fleckenstein, A E; Metzger, R R; Beyeler, M L; Gibb, J W; Hanson, G R

    1997-09-01

    Incubation of striatal synaptosomes with the oxygen radical generating enzyme, xanthine oxidase, decreased [3H]dopamine uptake: an effect attributable to a decreased Vmax. Concurrent incubation with the superoxide radical scavenger, superoxide dismutase, abolished the xanthine oxidase-induced decrease. These results indicate that, like methamphetamine administration in vivo, reactive oxygen species diminish dopamine transporter function in vitro. The significance of these findings to mechanisms responsible for effects of methamphetamine is discussed. PMID:9346337

  15. Diminished Reality Based on Image Inpainting Considering Background Geometry.

    PubMed

    Kawai, Norihiko; Sato, Tomokazu; Yokoya, Naokazu

    2016-03-01

    Diminished reality aims to remove real objects from video images and fill in the missing regions with plausible background textures in real time. Most conventional methods based on image inpainting achieve diminished reality by assuming that the background around a target object is almost planar. This paper proposes a new diminished reality method that considers background geometries with less constraints than the conventional ones. In this study, we approximate the background geometry by combining local planes, and improve the quality of image inpainting by correcting the perspective distortion of texture and limiting the search area for finding similar textures as exemplars. The temporal coherence of texture is preserved using the geometries and camera pose estimated by visual-simultaneous localization and mapping (SLAM). The mask region that includes a target object is robustly set in each frame by projecting a 3D region, rather than tracking the object in 2D image space. The effectiveness of the proposed method is successfully demonstrated using several experimental environments. PMID:26829239

  16. SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation.

    PubMed

    Xie, Yuexia; Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen; Shao, Chunlin

    2015-02-01

    Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved. PMID:25772107

  17. Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

    SciTech Connect

    Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

    2010-08-01

    Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-{alpha}, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-{alpha}, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

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

    SciTech Connect

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

    2012-02-17

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

  19. 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

  20. Radiation-induced brain injury: low-hanging fruit for neuroregeneration.

    PubMed

    Burns, Terry C; Awad, Ahmed J; Li, Matthew D; Grant, Gerald A

    2016-05-01

    Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system. PMID:27132524

  1. 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

  2. Radiation-induced formation, annealing and ordering of voids in crystals: Theory and experiment

    NASA Astrophysics Data System (ADS)

    Dubinko, V. I.; Guglya, A. G.; Donnelly, S. E.

    2011-07-01

    Void ordering has been observed in very different radiation environments ranging from metals to ionic crystals bombarded with energetic particles. The void ordering is often accompanied by a saturation of the void swelling with increasing irradiation dose, which makes an understanding of the underlying mechanisms to be both of scientific significance and of practical importance for nuclear engineering. We show that both phenomena can be explained by the original mechanism based on the anisotropic energy transfer provided by self-focusing discrete breathers or quodons (energetic, mobile, highly localized lattice solitons that propagate great distances along close-packed crystal directions). The interaction of quodons with voids can result in radiation-induced “annealing” of selected voids, which results in the void ordering under special irradiation conditions. We observe experimentally radiation-induced void annealing by lowering the irradiation temperature of nickel and copper samples pre-irradiated to produce voids or gas bubbles. The bulk recombination of Frenkel pairs increases with decreasing temperature resulting in suppression of the production of freely migrating vacancies (the driving force of the void growth). On the other hand, the rate of radiation-induced vacancy emission from voids due to the void interaction with quodons remains essentially unchanged, which results in void dissolution. The experimental data on the void shrinkage and void lattice formation obtained for different metals and irradiating particles are explained by the present model assuming the quodon propagation length to be in the micron range, which is consistent with independent data on the irradiation-induced diffusion of interstitial ions in austenitic stainless steel.

  3. Role of Ferulic Acid in the Amelioration of Ionizing Radiation Induced Inflammation: A Murine Model

    PubMed Central

    Das, Ujjal; Manna, Krishnendu; Sinha, Mahuya; Datta, Sanjukta; Das, Dipesh Kr; Chakraborty, Anindita; Ghosh, Mahua; Saha, Krishna Das; Dey, Sanjit

    2014-01-01

    Ionizing radiation is responsible for oxidative stress by generating reactive oxygen species (ROS), which alters the cellular redox potential. This change activates several redox sensitive enzymes which are crucial in activating signaling pathways at molecular level and can lead to oxidative stress induced inflammation. Therefore, the present study was intended to assess the anti-inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation-induced oxidative stress with a novel mechanistic viewpoint. FA was administered (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to exposing them to a single dose of 10 Gy 60Co γ-irradiation. The dose of FA was optimized from the survival experiment and 50 mg/kg body wt dose showed optimum effect. FA significantly ameliorated the radiation induced inflammatory response such as phosphorylation of IKKα/β and IκBα and consequent nuclear translocation of nuclear factor kappa B (NF-κB). FA also prevented the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase-2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum. It was observed that exposure to radiation results in decreased activity of superoxide dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH) content. However, FA treatment prior to irradiation increased the activities of the same endogenous antioxidants. Thus, pretreatment with FA offers protection against gamma radiation induced inflammation. PMID:24854039

  4. Proteomic overview and perspectives of the radiation-induced bystander effects.

    PubMed

    Chevalier, François; Hamdi, Dounia Houria; Saintigny, Yannick; Lefaix, Jean-Louis

    2015-01-01

    Radiation proteomics is a recent, promising and powerful tool to identify protein markers of direct and indirect consequences of ionizing radiation. The main challenges of modern radiobiology is to predict radio-sensitivity of patients and radio-resistance of tumor to be treated, but considerable evidences are now available regarding the significance of a bystander effect at low and high doses. This "radiation-induced bystander effect" (RIBE) is defined as the biological responses of non-irradiated cells that received signals from neighboring irradiated cells. Such intercellular signal is no more considered as a minor side-effect of radiotherapy in surrounding healthy tissue and its occurrence should be considered in adapting radiotherapy protocols, to limit the risk for radiation-induced secondary cancer. There is no consensus on a precise designation of RIBE, which involves a number of distinct signal-mediated effects within or outside the irradiated volume. Indeed, several cellular mechanisms were proposed, including the secretion of soluble factors by irradiated cells in the extracellular matrix, or the direct communication between irradiated and neighboring non-irradiated cells via gap junctions. This phenomenon is observed in a context of major local inflammation, linked with a global imbalance of oxidative metabolism which makes its analysis challenging using in vitro model systems. In this review article, the authors first define the radiation-induced bystander effect as a function of radiation type, in vitro analysis protocols, and cell type. In a second time, the authors present the current status of protein biomarkers and proteomic-based findings and discuss the capacities, limits and perspectives of such global approaches to explore these complex intercellular mechanisms. PMID:25795126

  5. 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

  6. Radiation induced bystander effect by GAP junction channels in human fibroblast cell

    NASA Astrophysics Data System (ADS)

    Furusawa, Y.; Shao, C.; Aoki, M.; Kobayashi, Y.; Funayama, T.; Ando, K.

    The chemical factor involved in bystander effect and its transfer pathway were investigated in a confluent human fibroblast cell (AG1522) population. Micronuclei (MN) and G1-phase arrest were detected in cells irradiated by carbon (~100 keV/μm) ions at HIMAC. A very low dose irradiation showed a high effectiveness in producing MN, suggesting a bystander effect. This effectiveness was enhanced by 8-Br-cAMP treatment that increases gap junctional intercellular communication (GJIC). On the other hand, the effect was reduced by 5% DMSO treatment, which reduce the reactive oxygen species (ROS), and suppressed by 100 μM lindane treatment, an inhibitor of GJIC. In addition, the radiation-induced G1-phase arrest was also enhanced by cAMP, and reduced or suppressed by DMSO or lindane. A microbeam device (JAERI) was also used for these studies. It was found that exposing one single cell in a confluent cell population to exactly one argon (~1260 keV/μm) or neon (~430 keV/ μm) ion, additional MN could be detected in many other unirradiated cells. The yield of MN increased with the number of irradiated cells. However, there was no significant difference in the MN induction when the cells were irradiated by increasing number of particles. MN induction by bystander effect was partly reduced by DMSO, and effectively suppressed by lindane. Our results obtained from both random irradiation and precise numbered irradiation indicate that both GJIC and ROS contributed to the radiation-induced bystander effect, but the cell gap junction channels likely play an essential role in the release and transfer of radiation-induced chemical factors.

  7. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    PubMed Central

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Luijk, Peter Van

    2014-01-01

    Abstract Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for restoring functionality to the irradiated tissue bed. Recent Advances: Preclinical studies presented in this review provide encouraging proof of concept regarding the therapeutic potential of stem cells for treating the adverse side effects associated with radiotherapy in different organs. Early-stage clinical data for radiation-induced lung, bone, and skin complications are promising and highlight the importance of selecting the appropriate stem cell type to stimulate tissue regeneration. Critical Issues: While therapeutic efficacy has been demonstrated in a variety of animal models and human trials, a range of additional concerns regarding stem cell transplantation for ameliorating radiation-induced normal tissue sequelae remain. Safety issues regarding teratoma formation, disease progression, and genomic stability along with technical issues impacting disease targeting, immunorejection, and clinical scale-up are factors bearing on the eventual translation of stem cell therapies into routine clinical practice. Future Directions: Follow-up studies will need to identify the best possible stem cell types for the treatment of early and late radiation-induced normal tissue injury. Additional work should seek to optimize cellular dosing regimes, identify the best routes of administration, elucidate optimal transplantation windows for introducing cells into more receptive host tissues, and improve immune tolerance for longer-term engrafted cell survival into the irradiated microenvironment. Antioxid. Redox Signal. 21: 338–355. PMID:24147585

  8. Perturbed angular correlation study of radiation-induced defects in Rh metal

    NASA Astrophysics Data System (ADS)

    Chawda, M.; Patel, N.; Sebastian, K. C.; Somayajulu, D. R. S.; Sarkar, M.; Singh, R. P.; Murlithar, S.; Awasthi, D. K.

    2006-06-01

    Radiation-induced defects are studied in cubic rhodium metal, using the local probe technique 'Time differential perturbed angular correlation (TDPAC) at liquid N-2 temperature. Isochronal annealing was done at 300, 1073 and 1473 K temperatures. The irradiated sample showed two quadrupole interaction frequencies at 1150 and 93 MHz. The low frequency disappeared at room-temperature annealing, which was assigned to In trapped at a vacancy, whereas the higher frequency remained up to high temperatures and was attributed to In trapped at Rh-C complexes in the Rh matrix.

  9. 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.

  10. Remote sensor response study in the regime of the microwave radiation-induced magnetoresistance oscillations

    SciTech Connect

    Ye, Tianyu; Mani, R. G.; Wegscheider, W.

    2013-11-04

    A concurrent remote sensing and magneto-transport study of the microwave excited two dimensional electron system (2DES) at liquid helium temperatures has been carried out using a carbon detector to remotely sense the microwave activity of the 2D electron system in the GaAs/AlGaAs heterostructure during conventional magneto-transport measurements. Various correlations are observed and reported between the oscillatory magnetotransport and the remotely sensed reflection. In addition, the oscillatory remotely sensed signal is shown to exhibit a power law type variation in its amplitude, similar to the radiation-induced magnetoresistance oscillations.

  11. Radiation-induced meningiomas after BNCT in patients with malignant glioma.

    PubMed

    Kageji, T; Sogabe, S; Mizobichi, Y; Nakajima, K; Shinji, N; Nakagawa, Y

    2015-12-01

    Of the 180 patients with malignant brain tumors whom we treated with boron neutron capture therapy (BNCT) since 1968, only one (0.56%) developed multiple radiation-induced meningiomas. The parasagittal meningioma that had received 42 Gy (w) for BNCT showed more rapid growth on Gd-enhanced MRI scans and more atypical features on histopathologic studies than the temporal convexity tumor that had received 20 Gy (w). Long-term follow up MRI studies are necessary in long-survivors of malignant brain tumors treated by BNCT. PMID:26122975

  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. β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury.

    PubMed

    Liu, Z; Tian, H; Jiang, J; Yang, Y; Tan, S; Lin, X; Liu, H; Wu, B

    2016-09-01

    Intestinal crypt progenitor/stem (ICPS) cell apoptosis and vascular endothelial cell apoptosis are responsible for the initiation and development of ionizing radiation (IR)-evoked gastrointestinal syndrome. The signaling mechanisms underlying IR-induced ICPS cell apoptosis remain largely unclear. Our findings provide evidence that β-arrestin-2 (βarr2)-mediated ICPS cell apoptosis is crucial for IR-stimulated intestinal injury. βArr2-deficient mice exhibited decreased ICPS cell and intestinal Lgr5(+) (leucine-rich repeat-containing G-protein-coupled receptor 5-positive) stem cell apoptosis, promoted crypt proliferation and reproduction, and protracted survival following lethal doses of radiation. Radioprotection in the ICPS cells isolated from βarr2-deficient mice depended on prolonged nuclear factor-κB (NF-κB) activation via direct interaction of βarr2 with IκBα and subsequent inhibition of p53-upregulated modulator of apoptosis (PUMA)-mediated mitochondrial dysfunction. Unexpectedly, βarr2 deficiency had little effect on IR-induced intestinal vascular endothelial cell apoptosis in mice. Consistently, βarr2 knockdown also provided significant radioresistance by manipulating NF-κB/PUMA signaling in Lgr5(+) cells in vitro. Collectively, these observations show that targeting the βarr2/NF-κB/PUMA novel pathway is a potential radiomitigator for limiting the damaging effect of radiotherapy on the gastrointestinal system. Significance statement: acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiotherapy. The issue of whether the critical factor for the initiation of radiation-induced intestinal injury is intestinal stem cell apoptosis or endothelial cell apoptosis remains unresolved. βArrs have recently been found to be multifunctional adaptor of apoptosis. Here, we found that β-arrestin-2 (βarr2) deficiency was associated with decreased radiation-induced ICPS cell apoptosis, which prolonged survival in

  14. The application of radiation-induced processed copolymers to biocatalysis immobilisation

    NASA Astrophysics Data System (ADS)

    de Silva, M. Alves; Beddows, C. G.; Gil, M. H.; Guthrie, J. T.; Guiomar, A. J.; Kotov, S.; Piedade, A. P.

    In this paper, some of the work carried out at our laboratories on the immobilisation of biocatalysts onto graft copolymers prepared by radiation induced procedures is reported. The graft copolymers used were based either on hydrophilic natural polymer (agar) or on hydrophobic (polyethylene) supports. The comonomers grafted branches include poly(hydroxyethyl methacrylate) and poly(hydroxyethyl methacrylate) crosslinked with trimethylpropane triacrylata (TMPTA). The suitability of these graft copolymers for immobilising ∝-chymotrypsin, glucose oxidase and trypsin was assessed by determining the amount of biocatalysts coupled to the support and its retention of activity. The Michaelis Mentan constants (K M) for some of the immobilised enzymes were determined.

  15. Radiation induced dechlorination of some chlorinated hydrocarbons in aqueous suspensions of various solid particles

    NASA Astrophysics Data System (ADS)

    Múčka, V.; Buňata, M.; Čuba, V.; Silber, R.; Juha, L.

    2015-07-01

    Radiation induced dechlorination of trichloroethylene (TCE) and tetrachloroethylene (PCE) in aqueous solutions containing the active carbon (AC) or cupric oxide (CuO) as the modifiers was studied. The obtained results were compared to the previously studied dechlorination of polychlorinated biphenyls (PCBs). Both modifiers were found to decrease the efficiency of dechlorination. The AC modifier acts mainly via adsorption of the aliphatic (unlike the aromatic) hydrocarbons and the CuO oxide mainly inhibits the mineralization of the perchloroethylene. The results presented in this paper will be also helpful for the studies of the impact of chlorinated hydrocarbons on the membrane permeability of living cells.

  16. Radiation-Induced Cataractogenesis: A Critical Literature Review for the Interventional Radiologist.

    PubMed

    Seals, Kevin F; Lee, Edward W; Cagnon, Christopher H; Al-Hakim, Ramsey A; Kee, Stephen T

    2016-02-01

    Extensive research supports an association between radiation exposure and cataractogenesis. New data suggests that radiation-induced cataracts may form stochastically, without a threshold and at low radiation doses. We first review data linking cataractogenesis with interventional work. We then analyze the lens dose typical of various procedures, factors modulating dose, and predicted annual dosages. We conclude by critically evaluating the literature describing techniques for lens protection, finding that leaded eyeglasses may offer inadequate protection and exploring the available data on alternative strategies for cataract prevention. PMID:26404628

  17. Radiation-induced cholecystitis after hepatic radioembolization: do we need to take precautionary measures?

    PubMed

    Prince, Jip F; van den Hoven, Andor F; van den Bosch, Maurice A A J; Elschot, Mattijs; de Jong, Hugo W A M; Lam, Marnix G E H

    2014-11-01

    Controversy exists over the need to take precautionary measures during hepatic radioembolization to minimize the risk of radiation-induced cholecystitis. Strategies for a variety of clinical scenarios are discussed on the basis of a literature review. Precautionary measures are unnecessary in the majority of patients and should be taken only when single photon-emission computed tomography (CT; SPECT)/CT shows a significant concentration of technetium-99m macroaggregated albumin in the gallbladder wall. In this case report with quantitative SPECT analysis, it is illustrated how an adjustment of the catheter position can effectively reduce the absorbed dose of radiation delivered to the gallbladder wall by more than 90%. PMID:25442134

  18. Radiation-induced electrical breakdown of helium in fusion reactor superconducting magnet systems

    SciTech Connect

    Perkins, L.J.

    1983-12-02

    A comprehensive theoretical study has been performed on the reduction of the electrical breakdown potential of liquid and gaseous helium under neutron and gamma radiation. Extension of the conventional Townsend breakdown theory indicates that radiation fields at the superconducting magnets of a typical fusion reactor are potentially capable of significantly reducing currently established (i.e., unirradiated) helium breakdown voltages. Emphasis is given to the implications of these results including future deployment choices of magnet cryogenic methods (e.g., pool-boiling versus forced-flow), the possible impact on magnet shielding requirements and the analogous situation for radiation-induced electrical breakdown in fusion RF transmission systems.

  19. Effect of G/M ratio on the radiation-induced degradation of sodium alginate

    NASA Astrophysics Data System (ADS)

    Şen, Murat; Rendevski, Stojan; Kavaklı, Pınar Akkaş; Sepehrianazar, Amir

    2010-03-01

    Radiation-induced degradation of sodium alginate (NaAlg) having different G/M ratios was investigated. NaAlg samples were irradiated with gamma rays in air at ambient temperature in the solid state at low dose rate. Change in their molecular weights was followed by size exclusion chromatography (SEC). Changes in their rheological properties and viscosity values as a function of temperature, shear rate and irradiation dose were also determined. Chain scission yields, G( S), and degradation rates were calculated. It was observed that G/M ratio was an important factor controlling the G( S) and degradation rate of sodium alginate.

  20. 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.

  1. Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in IMRT for Nasopharyngeal Cancer

    SciTech Connect

    Lee, Victor H.F.; Ng, Sherry C.Y.; Leung, T.W.; Au, Gordon K.H.; Kwong, Dora L.W.

    2012-09-01

    Purpose: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC). Methods and Materials: Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR). A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression. Results: Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis. Conclusions: This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive OARs, and

  2. Radiation-induced electron paramagnetic resonance signal and soybean isoflavones content

    NASA Astrophysics Data System (ADS)

    de Oliveira, Marcos R. R.; Mandarino, José M. G.; del Mastro, Nelida L.

    2012-09-01

    Electron Paramagnetic Resonance (EPR) is a well-known spectroscopic technique that detects paramagnetic centers and can detect free radicals with high sensitivity. In food, free radicals can be generated by several commonly used industrial processes, such as radiosterilization or heat treatment. EPR spectroscopy is used to detect radioinduced free radicals in food. In this work the relation between EPR signal induced by gamma irradiation treatment and soybean isoflavones content was investigated. Present results did not show correlation between total isoflavones content and the EPR signal. Nevertheless, some isoflavone contents had a negative correlation with the radiation-induced EPR signal.

  3. 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

  4. Immobilization of yeast cells on hydrogel carriers obtained by radiation-induced polymerization

    NASA Astrophysics Data System (ADS)

    Xin, Lu Zhao; Carenza, Mario; Kaetsu, Isao; Kumakura, Minoru; Yoshida, Masaru; Fujimura, Takashi

    Polymer hydrogels were obtained by radiation-induced copolymerization at -78°C of aqueous solutions of acrylic and methacrylic esters. The matrices were characterized by equilibrium water content measurements, by optical microscopy observations and by scanning electron microscopy analysis. Yeast cells were immobilized on these hydrogels and the ethanol productivity by batch fermentation was determined. Matrix hydrophilicity and porosity were found to deeply influence the adhesion of yeast cells and, hence, the ethanol productivity. The latter as well as other physico-chemical properties were also affected by the presence of a crosslinking agent added in small amounts to the polymerizing mixture.

  5. Summary of round robin measurements of radiation induced conductivity in Wesgo AL995 alumina

    SciTech Connect

    Zinkle, S.J.

    1996-10-01

    This existing data on radiation induced conductivity (RIC) measurements performed on the same heat of the IEA reference ceramic insulator are summarized. Six different sets of RIC measurements have been performed on Wesgo AL995 at dose rates between 10 Gy/s and 1 MGy/s. In general, good agreement was obtained between the different groups of researchers. The data indicate that the RIC at a test temperature of 400-500{degrees}C is approximately linear with ionizing dose rate up to {approximately}1000 Gy/s, and exhibits an approximately square root dependence on dose rate between 1 kGy/s and 1 MGy/s.

  6. 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.

  7. Observation of linear-polarization-sensitivity in the microwave-radiation-induced magnetoresistance oscillations

    SciTech Connect

    Mani, R. G.; Ramanayaka, A. N.; Wegscheider, W.

    2013-12-04

    We examine the linear polarization sensitivity of the radiation- induced magneto-resistance oscillations by investigating the effect of rotating in-situ the electric field of linearly polarized microwaves relative to the current, in the GaAs/AlGaAs system. We find that the frequency and the phase of the photo-excited magneto-resistance oscillations are insensitive to the polarization. On the other hand, the amplitude of the resistance oscillations are strongly sensitive to the relative orientation between the microwave antenna and the current-axis in the specimen.

  8. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    NASA Astrophysics Data System (ADS)

    Pandey, B. N.; Lathika, K. M.; Mishra, K. P.

    2006-03-01

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after γ-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  9. Study of the effect of dose-rate on radiation-induced damage to human erythrocytes

    NASA Astrophysics Data System (ADS)

    Krokosz, Anita; Koziczak, Renata; Gonciarz, Marta; Szweda-Lewandowska, Zofia

    2006-01-01

    Human erythrocytes suspended in an isotonic Na-phosphate buffer, pH 7.4 (hematocrit of 2%) were irradiated with γ-rays at three dose-rates of 66.7, 36.7, 25 Gy min -1 in order to investigate the influence of the dose-rate on radiation-induced membrane damage, hemoglobin oxidation and loss of reduced glutathione. The obtained results showed that such processes as erythrocyte hemolysis, lipid and protein destruction depend on the radiation dose-rate. The parameter values describing these processes showed an inverse dose-rate effect.

  10. Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

    PubMed Central

    Schiller, Daniela; Kanen, Jonathan W.; LeDoux, Joseph E.; Monfils, Marie-H.; Phelps, Elizabeth A.

    2013-01-01

    Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders. PMID:24277809

  11. Diminished KCC2 confounds synapse specificity of LTP during senescence.

    PubMed

    Ferando, Isabella; Faas, Guido C; Mody, Istvan

    2016-09-01

    The synapse specificity of long-term potentiation (LTP) ensures that no interference arises from inputs irrelevant to the memory to be encoded. In hippocampi of aged (21-28 months) mice, LTP was relayed to unstimulated synapses, blemishing its synapse specificity. Diminished levels of the K(+)/Cl(-) cotransporter KCC2 and a depolarizing GABAA receptor-mediated synaptic component following LTP were the most likely causes for the spreading of potentiation, unveiling mechanisms hindering information storage in the aged brain and identifying KCC2 as a potential target for intervention. PMID:27500406

  12. Radiation-induced destruction of hydroxyl-containing amino acids and dipeptides

    NASA Astrophysics Data System (ADS)

    Sladkova, А. А.; Sosnovskaya, А. А.; Edimecheva, I. P.; Shadyro, О. I.

    2012-12-01

    The yields of molecular products resulting from radiolysis of hydroxyl-containing amino acids and dipeptides under various conditions were determined. The possibility of a new radiation-induced destruction pathway has been shown for serine and threonine, as well as for the dipeptides having residues of these amino acids at the N-terminal part of the respective molecule. This process includes formation of N-centered radicals from the starting molecules followed by their decomposition with elimination of side substituents. On radiolysis, serine and threonine were also shown to undergo free-radical destruction to form acetaldehyde and acetone, respectively. A mechanism has been proposed including consecutive stages of fragmentation of α-hydroxyl-containing carbon-centered radicals with elimination of ammonia and decomposition of the secondary radicals with elimination of CO2. The yields of CO2 obtained on radiolysis of serine and threonine were significantly higher (except for solutions at pH 12) than those for alanine and valine, which have no hydroxyl groups in their structures. The obtained data indicate that the hydroxyl-containing amino acids occupy a special place among other amino acids as regards the variety of radiation-induced reactions which they may undergo due to their structural features.

  13. A biological approach to the interspecies prediction of radiation-induced mortality risk

    SciTech Connect

    Carnes, B.A.; Grahn, D.; Olshansky, S.J.

    1997-08-01

    Evolutionary explanations for why sexually reproducing organisms grow old suggest that the forces of natural selection affect the ages when diseases occur that are subject to a genetic influence (referred to here as intrinsic diseases). When extended to the population level for a species, this logic leads to the general prediction that age-specific death rates from intrinsic causes should begin to rise as the force of selection wanes once the characteristic age of sexual maturity is attained. Results consistent with these predictions have been found for laboratory mice, beagles, and humans where, after adjusting for differences in life span, it was demonstrated that these species share a common age pattern of mortality for intrinsic causes of death. In quantitative models used to predict radiation-induced mortality, risks are often expressed as multiples of those observed in a control population. A control population, however, is an aging population. As such, mortality risks related to exposure must be interpreted relative to the age-specific risk of death associated with aging. Given the previous success in making interspecies predictions of age-related mortality, the purpose of this study was to determine whether radiation-induced mortality observed in one species could also be predicted quantitatively from a model used to describe the mortality consequences of exposure to radiation in a different species. Mortality data for B6CF{sub 1} mice and beagles exposed to {sup 60}Co {gamma}-rays for the duration of life were used for analysis.

  14. Radiation-induced complications in prostate cancer patients treated with radiotherapy

    SciTech Connect

    Azuddin, A. Yusof; Rahman, I. Abdul; Mohamed, F.; Siah, N. J.; Saadc, M.; Ismail, F.

    2014-09-03

    The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60{sub rectum}, rectal mean dose and NTCP{sub rectum} with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

  15. Desalination by electrodialysis with the ion-exchange membrane prepared by radiation-induced graft polymerization

    NASA Astrophysics Data System (ADS)

    Choi, Seong-Ho; Han Jeong, Young; Jeong Ryoo, Jae; Lee, Kwang-Pill

    2001-01-01

    Ion-exchange membranes modified with the triethylamine [-N(CH 2CH 3) 3] and phosphoric acid (-PO 3 H) groups were prepared by radiation-induced grafting of glycidyl methacrylate (GMA) onto the polyolefin nonwavon fabric (PNF) and subsequent chemical modification of poly(GMA) graft chains. The physical and chemical properties of the GMA-grafted PNF and the PNF modified with ion-exchange groups were investigated by SEM, XPS, TGA, and DSC. Furthermore, electrochemical properties such as specific electric resistance, transport number of K +, and desalination were examined. The grafting yield increased with increasing reaction time and reaction temperature. The maximum grafting yield was obtained with 40% (vol.%) monomer concentration in dioxane at 60°C. The content of the cation- and anion-exchange group increased with increasing grafting yield. Electrical resistance of the PNF modified with TEA and -PO 3 H group decreased, while the water uptake (%) increased with increasing ion-exchange group capacities. Transport number of the PNF modified with ion-exchange group were the range of ca. 0.82-0.92. The graft-type ion-exchange membranes prepared by radiation-induced graft copolymerization were successfully applied as separators for electrodialysis.

  16. 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.

  17. Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant) Extract

    PubMed Central

    Sharma, Priyanka; Parmar, Jyoti; Sharma, Priyanka; Verma, Preeti; Goyal, P. K.

    2011-01-01

    The primary objective of this investigation is to determine the deleterious effects of sub lethal gamma radiation on testes and their possible inhibition by Tinospora cordifolia extract (TCE). For this purpose, one group of male Swiss albino mice was exposed to 7.5 Gy gamma radiation to serve as the irradiated control, while the other group received TCE (75 mg/kg b. wt./day) orally for 5 consecutive days half an hr before irradiation to serve as experimental. Exposure of animals to 7.5 Gy gamma radiation resulted into significant decrease in body weight, tissue weight, testes- body weight ratio and tubular diameter up to 15 days of irradiation. Cent percent mortality was recorded by day 17th in irradiated control, whereas all animals survived in experimental group. TCE pretreatment rendered significant increase in body weight, tissue weight, testes- body weight ratio and tubular diameter at various intervals as compared to irradiated group. Radiation induced histological lesions in testicular architecture were observed more severe in irradiated control then the experimental. TCE administration before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radio- protective potential of Tinospora cordifolia root extract in testicular constituents against gamma irradiation in mice. PMID:21350610

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

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

  19. H 2O 2 and radiation induced dissolution of UO 2 and SIMFUEL pellets

    NASA Astrophysics Data System (ADS)

    Nilsson, Sara; Jonsson, Mats

    2011-03-01

    Dissolution of the UO 2 matrix is of major importance in the safety assessment of a future deep repository for spent nuclear fuel. The aim of this work is to elucidate if the observed differences in dissolution rates between SIMFUEL and UO 2 can be attributed to differences in oxidant reactivity towards these two materials. To elucidate this, the oxidative dissolution of U(VI) and consumption of H 2O 2 have been studied for UO 2 and SIMFUEL pellets under N 2 and H 2 atmosphere. The H 2O 2 and U(VI) concentrations have been measured as a function of reaction time. In addition, γ-radiation induced dissolution UO 2 and SIMFUEL pellets have been studied. The experiments show that while the reactivity of the two types of pellets towards H 2O 2 is almost identical and in good agreement with the previously determined rate constant for the reaction, the dissolution rates differ considerably. The significantly lower rate of dissolution of the SIMFUEL pellet is attributed to an increased fraction of catalytic decomposition of H 2O 2. The radiation chemical experiments reveal a similar but less pronounced difference between the two types of pellets. This implies that the relative impact of the radiolytic oxidants in radiation induced UO 2 dissolution differs between a pure UO 2 pellet and SIMFUEL.

  20. H 2 inhibition of radiation induced dissolution of spent nuclear fuel

    NASA Astrophysics Data System (ADS)

    Trummer, Martin; Roth, Olivia; Jonsson, Mats

    2009-01-01

    In order to elucidate the effect of noble metal clusters in spent nuclear fuel on the kinetics of radiation induced spent fuel dissolution we have used Pd particle doped UO 2 pellets. The catalytic effect of Pd particles on the kinetics of radiation induced dissolution of UO 2 during γ-irradiation in HCO3- containing solutions purged with N 2 and H 2 was studied in this work. Four pellets with Pd concentrations of 0%, 0.1%, 1% and 3% were produced to mimic spent nuclear fuel. The pellets were placed in 10 mM HCO3- aqueous solutions and γ-irradiated, and the dissolution of UO22+ was measured spectrophotometrically as a function of time. Under N 2 atmosphere, 3% Pd prevent the dissolution of uranium by reduction with the radiolytically produced H 2, while the other pellets show a rate of dissolution of around 1.6 × 10 -9 mol m -2 s -1. Under H 2 atmosphere already 0.1% Pd effectively prevents the dissolution of uranium, while the rate of dissolution for the pellet without Pd is 1.4 × 10 -9 mol m -2 s -1. It is also shown in experiments without radiation in aqueous solutions containing H 2O 2 and O 2 that ɛ-particles catalyze the oxidation of the UO 2 matrix by these molecular oxidants, and that the kinetics of the catalyzed reactions is close to diffusion controlled.

  1. Geraniin down regulates gamma radiation-induced apoptosis by suppressing DNA damage.

    PubMed

    Bing, So Jin; Ha, Danbee; Kim, Min Ju; Park, Eunjin; Ahn, Ginnae; Kim, Dae Seung; Ko, Ryeo Kyeong; Park, Jae Woo; Lee, Nam Ho; Jee, Youngheun

    2013-07-01

    Gamma ray irradiation triggers DNA damage and apoptosis of proliferating stem cells and peripheral immune cells, resulting in the destruction of intestinal crypts and lymphoid system. Geraniin is a natural compound extracts from an aquatic plant Nymphaea tetragona and possesses good antioxidant property. In this study, we demonstrate that geraniin rescues radiosensitive splenocytes and jejunal crypt cells from radiation-induced DNA damage and apoptosis. Isolated splenocytes from C57BL/6 mice treated with geraniin were protected against radiation injury of 2 Gy irradiation through the enhancement of the proliferation and attenuation of DNA damage. Also, geraniin inhibited apoptosis in radiosensitive splenocytes by reducing the expression level and immunoreactivity of proapoptotic p53 and Bax and increasing those of anti-apoptotic Bcl-2. In mice exposed to radiation, geraniin treatment protected splenocytes and intestinal crypt cells from radiation-induced cell death. Our results suggest that geraniin presents radioprotective effects by regulating DNA damage on splenocytes, exerting immunostimulatory capacities and inhibiting apoptosis of radiosensitive immune cells and jejunal crypt cells. Therefore, geraniin can be a radioprotective agent against γ-irradiation exposure. PMID:23541438

  2. A two-mutation model of radiation-induced acute myeloid leukemia using historical mouse data.

    PubMed

    Dekkers, Fieke; Bijwaard, Harmen; Bouffler, Simon; Ellender, Michele; Huiskamp, René; Kowalczuk, Christine; Meijne, Emmy; Sutmuller, Marjolein

    2011-03-01

    From studies of the atomic bomb survivors, it is well known that ionizing radiation causes several forms of leukemia. However, since the specific mechanism behind this process remains largely unknown, it is difficult to extrapolate carcinogenic effects at acute high-dose exposures to risk estimates for the chronic low-dose exposures that are important for radiation protection purposes. Recently, it has become clear that the induction of acute myeloid leukemia (AML) in CBA/H mice takes place through two key steps, both involving the Sfpi1 gene. A similar mechanism may play a role in human radiation-induced AML. In the present paper, a two-mutation carcinogenesis model is applied to model AML in several data sets of X-ray- and neutron-exposed CBA/H mice. The models obtained provide good fits to the data. A comparison between the predictions for neutron-induced and X-ray-induced AML yields an RBE for neutrons of approximately 3. The model used is considered to be a first step toward a model for human radiation-induced AML, which could be used to estimate risks of exposure to low doses. PMID:20842369

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

    PubMed Central

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

    2014-01-01

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

  4. Radiation-induced complications in prostate cancer patients treated with radiotherapy

    NASA Astrophysics Data System (ADS)

    Azuddin, A. Yusof; Rahman, I. Abdul; Siah, N. J.; Mohamed, F.; Saadc, M.; Ismail, F.

    2014-09-01

    The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60rectum, rectal mean dose and NTCPrectum with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

  5. Radiation-induced malignant fibrous histiocytoma of the occipital: a case report.

    PubMed

    Zhang, Guo-Bin; Li, Jian; Zhang, Peng-Fei; Han, Li-Jiang; Zhang, Jun-Ting

    2014-01-01

    Malignant fibrous histiocytoma (MFH) is a rare neoplasm exhibiting a propensity for aggressive clinical behavior. Effective treatment modality is surgical resection with wide margins, but its rate of recurrence and metastasis is still high. Early detection and complete excision of the tumor is necessary. A MFH of the occipital developed in a 51-year-old woman eight years after surgery and radiation for medulloblastoma of the cerebellar vermis. The secondary neoplasm arose at the site of tumor resection within the irradiated field, and was resected. The development of sarcomas is a recognized complication of radiation therapy. The final diagnosis after the operation was MFH. Radiation-induced sarcoma (RIS) is well known, but radiation-induced MFH is relatively rare in the head and neck region, especially in the occipital. The imaging findings are not diagnosis specific, but strict follow-up within the radiation field by computerized tomography (CT) and magnetic resonance imaging (MRI) and appreciation of the expected latency period may help in providing the diagnosis of RIS. PMID:24742094

  6. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients

    PubMed Central

    Clavo, Bernardino; Santana-Rodriguez, Norberto; Llontop, Pedro; Gutierrez, Dominga; Ceballos, Daniel; Méndez, Charlin; Rovira, Gloria; Suarez, Gerardo; Rey-Baltar, Dolores; Garcia-Cabrera, Laura; Martínez-Sánchez, Gregorio; Fiuza, Dolores

    2015-01-01

    Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52–119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7–14) g/dL to 13 (10–15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation. PMID:26357522

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

    SciTech Connect

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

    1989-04-01

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

  8. Apigenin ameliorates gamma radiation-induced cytogenetic alterations in cultured human blood lymphocytes.

    PubMed

    Begum, Naziya; Prasad, N Rajendra; Kanimozhi, G; Hasan, Annie Q

    2012-08-30

    The aim of the present study was to assess the protective effect of apigenin, a dietary flavone, against cytogenetic alterations in human peripheral blood lymphocytes (HPBL) induced by Cobalt-60 radiation (3Gy). Results of MTT [3-(4, 5-dimethyl-2-thiaozolyl)-2,5-diphenyl-2H tetrazolium bromide] assay revealed that 37.2μM of apigenin was found to be non-toxic in HPBL. At this dose (37.2μM) of apigenin, the LD(50) radiation dose of HPBL increased from 2.9Gy to 3.4Gy, which resulted in a DMF of 1.17. Apigenin (37.2μM) treatment 1h before irradiation significantly (p<0.05) reduced DNA damage in irradiated HPBL as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment). Moreover, apigenin treatment significantly decreased the frequencies of dicentric (DC), acentric fragments (AF), and acentric rings (AR) in irradiated HPBL. Apigenin pretreatment also reduced the radiation-induced CBMN (cytokinesis blocked micronuclei) anomalies such as micronuclei (MNi), nucleoplasmic bridges (NPB) and nuclear buds (NBUD) in HPBL. These results also showed that there was a significant correlation between NPB and DC frequencies and MNi and AF+AR. Treatment with apigenin alone had no significant effect on DNA damage and chromosomal aberrations in HPBL. Thus, the current studies indicate that apigenin protects HPBL from radiation-induced cytogenetic alterations. PMID:22516036

  9. Punica granatum peel extract protects against ionizing radiation-induced enteritis and leukocyte apoptosis in rats.

    PubMed

    Toklu, Hale Z; Sehirli, Ozer; Ozyurt, Hazan; Mayadağli, A Alpaslan; Ekşioğlu-Demiralp, Emel; Cetinel, Sule; Sahin, Hülya; Yeğen, Berrak C; Ulusoylu Dumlu, Melek; Gökmen, Vural; Sener, Göksel

    2009-07-01

    Radiation-induced enteritis is a well-recognized sequel of therapeutic irradiation. Therefore we examined the radioprotective properties of Punica granatum peel extract (PPE) on the oxidative damage in the ileum. Rats were exposed to a single whole-body X-ray irradiation of 800 cGy. Irradiated rats were pretreated orally with saline or PPE (50 mg/kg/day) for 10 days before irradiation and the following 10 days, while control rats received saline or PPE but no irradiation. Then plasma and ileum samples were obtained. Irradiation caused a decrease in glutathione and total antioxidant capacity, which was accompanied by increases in malondialdehyde levels, myeloperoxidase activity, collagen content of the tissue with a concomitant increase 8-hydroxy-2'-deoxyguanosine (an index of oxidative DNA damage). Similarly, pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Furthermore, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in irradiated animals, while PPE reversed these effects. PPE supplementation reduced oxidative damage in the ileal tissues, probably by a mechanism that is associated with the decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. Adjuvant therapy of PPE may have a potential to support a successful radiotherapy by protecting against radiation-induced enteritis. PMID:19478462

  10. [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

  11. Cytokine profiling for prediction of symptomatic radiation-induced lung injury

    SciTech Connect

    Hart, Justin P.; Broadwater, Gloria; Rabbani, Zahid; Moeller, Benjamin J.; Clough, Robert; Huang, Dale; Sempowski, Gregory A.; Dewhirst, Mark; Pizzo, Salvatore V.; Vujaskovic, Zeljko; Anscher, Mitchell S. . E-mail: anscher@radonc.duke.edu

    2005-12-01

    Purpose: To analyze plasma cytokine profiles before the initiation of radiation therapy to define a cytokine phenotype that correlates with risk of developing symptomatic radiation-induced lung injury (SRILI). Methods and Materials: Symptomatic radiation-induced lung injury was evaluated in 55 patients (22 with SRILI and 33 without SRILI), according to modified National Cancer Institute common toxicity criteria. These plasma samples were analyzed by the multiplex suspension bead array system (Bio-Rad Laboratories; Hercules, CA), which included the following cytokines: interleukin (IL)-1{beta}, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17, granulocyte/macrophage colony-stimulating factor, interferon-{gamma}, monocyte chemotactic protein 1, macrophage inflammatory protein 1{beta}, tumor necrosis factor {alpha}, and granulocyte colony-stimulating factor. Results: Significant differences in the median values of IL-8 were observed between patients with and without SRILI. Patients who did not develop SRILI had approximately fourfold elevated levels of IL-8 as compared with patients who did subsequently develop SRILI. Significant correlations were not found for any other cytokine in this study, including transforming growth factor {beta}1. Conclusions: Patients with lower levels of plasma IL-8 before radiation therapy might be at increased risk for developing SRILI. Further studies are necessary to determine whether IL-8 levels are predictive of SRILI in a prospective trial and whether this marker might be used to determine patient eligibility for dose escalation.

  12. Enhanced radiation-induced cell killing by Herbimycin A pre-treatment

    NASA Astrophysics Data System (ADS)

    Noguchi, Miho; Hirayama, Ryoichi; Druzhinin, Sergey; Okayasu, Ryuichi

    2009-12-01

    Herbimycin A (HA), as in Geldanamycin, binds to conserved pockets of heat shock protein 90 (Hsp90) and inhibits its chaperone functions. Hsp90 plays an integral role in cancer cell growth and survival, because it maintains the stability of several key proteins by its chaperone's activity. It is known that some of the proteins associated with radiation responses are functionally stabilized by Hsp90. In this study, we investigated the effect of HA on radiosensitivity in human cancer cells and the mechanism related to the sensitization. In order to gain a mechanistic insight of this sensitization, we examined repair of DNA double-strand breaks (DSBs) in irradiated human cancer cells pre-treated with HA, as unrepaired DSBs are thought to be the main cause of radiation-induced cell death. Cellular radiosensitivity was determined by clonogenic assay, and the DSB rejoining kinetics was examined by constant field gel electrophoresis. SQ-5, a lung squamous carcinoma cell line, showed synergistic increase in radiosensitivity when cells were pre-treated with HA. In addition, HA significantly inhibited repair of radiation-induced DSBs. These results suggest that the combination of HA and ionizing radiation may be a useful therapeutic strategy for treating certain cancer cells.

  13. Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data?

    SciTech Connect

    Schultz-Hector, Susanne . E-mail: susanne.schultz-hector@helmholtz.de; Trott, Klaus-Ruediger Prof.

    2007-01-01

    The Life Span Study of Japanese atomic bomb survivors demonstrates that radiation exposure significantly increased the risk of developing ischemic heart disease, in particular myocardial infarction. Similarly, epidemiologic investigations in very large populations of patients who had received postoperative radiotherapy for breast cancer or for peptic ulcer demonstrate that radiation exposure of the heart with an average equivalent single dose of approximately 2 Gy significantly increased the risk of developing ischemic heart disease more than 10 years after irradiation. These epidemiologic findings are compatible with radiobiologic data on the pathogenesis of radiation-induced heart disease in experimental animals. The critical target structure appears to be the endothelial lining of blood vessels, in particular arteries, leading to early functional alterations such as pro-inflammatory responses and other changes, which are slowly progressive. Research should concentrate on the interaction of these radiation-induced endothelial changes with the early stages of age-related atherosclerosis to develop criteria for optimizing treatment plans in radiotherapy and also potential interventional strategies.

  14. Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis

    PubMed Central

    Han, Gangwen; Bian, Li; Li, Fulun; Cotrim, Ana; Wang, Donna; Lu, Jian Bo; Deng, Yu; Bird, Gregory; Sowers, Anastasia; Mitchell, James B.; Gutkind, J. Silvio; Zhao, Rui; Raben, David; Dijke, Peter ten; Refaeli, Yosef; Zhang, Qinghong; Wang, Xiao-Jing

    2013-01-01

    We report that K5.Smad7 mice, which express Smad7 transgene by a keratin-5 promoter, were resistant to radiation-induced oral mucositis, a painful oral ulceration. In addition to NF-κB activation known to contribute to oral mucositis, we found activated TGF-β signaling in oral mucositis. Smad7 dampened both pathways to attenuate inflammation, growth inhibition and apoptosis. Additionally, Smad7 promoted oral epithelial migration to close the wound. Further analyses revealed that TGF-β signaling Smads and their co-repressor CtBP1 transcriptionally repressed Rac1, and Smad7 abrogated this repression. Knocking down Rac1 in mouse keratinocytes abrogated Smad7-induced migration. Topically applying Smad7 protein with a cell permeable Tat-tag (Tat-Smad7) to oral mucosa showed preventive and therapeutic effects on radiation-induced oral mucositis in mice. Thus, we have identified novel molecular mechanisms involved in oral mucositis pathogenesis and our data suggest an alternative therapeutic strategy to block multiple pathological processes of oral mucositis. PMID:23475202

  15. Protective effect of esculentoside A on radiation-induced dermatitis and fibrosis

    SciTech Connect

    Xiao Zhenyu; Su Ying; Yang Shanmin; Yin Liangjie; Wang Wei; Yi Yanghua; Fenton, Bruce M.; Zhang Lurong; Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu

    2006-07-01

    Purpose: To investigate the effect of esculentoside A (EsA) on radiation-induced cutaneous and fibrovascular toxicity and its possible molecular mechanisms, both in vivo and in vitro. Methods and Materials: Mice received drug intervention 18 hours before 30 Gy to the right hind leg. Alterations in several cytokines expressed in skin tissue 2 days after irradiation were determined by ELISA. Early skin toxicity was evaluated 3 to 4 weeks after irradiation by skin scoring, and both tissue contraction and expression of TGF-{beta}1 were determined for soft-tissue fibrosis 3 months after irradiation. In vitro, the effect of EsA on radiation-induced nitric oxide (NO) and cytokine production in different cell types was measured by application of 2, 4, and 8 Gy. Results: In vivo, EsA reduced levels of IL-1{alpha}, MCP-1, VEGF, and TGF-{beta}1 in cutaneous tissue and reduced soft-tissue toxicity. In vitro, EsA inhibited the IL-1{alpha} ordinarily produced after 4 Gy in A431 cells. In Raw264.7 cells, EsA reduced levels of IL-1{alpha}, IL-1{beta}, and NO production costimulated by radiation and lipopolysaccharide (LPS). In L-929 cells, EsA inhibited VEGF, TNF, and MCP-1 production at 2, 4, and 8 Gy. Conclusions: Esculentoside A protects soft tissues against radiation toxicity through inhibiting the production of several proinflammatory cytokines and inflammatory mediators in epithelial cells, macrophages, fibroblasts, and skin tissue.

  16. Radiofrequency radiation-induced calcium ion efflux enhancement from human and other neuroblastoma cells in culture

    SciTech Connect

    Dutta, S.K.; Ghosh, B.; Blackman, C.F.

    1989-01-01

    To test the generality of radiofrequency radiation-induced changes in /sup 45/Ca2+ efflux from avian and feline brain tissues, human neuroblastoma cells were exposed to electromagnetic radiation at 147 MHz, amplitude-modulated (AM) at 16 Hz, at specific absorption rates (SAR) of 0.1, 0.05, 0.01, 0.005, 0.001, and 0.0005 W/kg. Significant /sup 45/Ca2+ efflux was obtained at SAR values of 0.05 and 0.005 W/kg. Enhanced efflux at 0.05 W/kg peaked at the 13-16 Hz and at the 57.5-60 Hz modulation ranges. A Chinese hamster-mouse hybrid neuroblastoma was also shown to exhibit enhanced radiation-induced /sup 45/Ca2+ efflux at an SAR of 0.05 W/kg, using 147 MHz, AM at 16 Hz. These results confirm that amplitude-modulated radiofrequency radiation can induce responses in cells of nervous tissue origin from widely different animal species, including humans. The results are also consistent with the reports of similar findings in avian and feline brain tissues and indicate the general nature of the phenomenon.

  17. Paradoxical Relationship between Mn Superoxide Dismutase Deficiency and Radiation-Induced Cognitive Defects

    PubMed Central

    Corniola, Rikki; Zou, Yani; Leu, David; Fike, John R.; Huang, Ting-Ting

    2012-01-01

    Radiation therapy of the CNS, even at low doses, can lead to deficits in neurocognitive functions. Reduction in hippocampal neurogenesis is usually, but not always, associated with cognitive deficits resulting from radiation therapy. Generation of reactive oxygen species is considered the main cause of radiation-induced tissue injuries, and elevated levels of oxidative stress persist long after the initial cranial irradiation. Consequently, mutant mice with reduced levels of the mitochondrial antioxidant enzyme, Mn superoxide dismutase (MnSOD or Sod2), are expected to be more sensitive to radiation-induced changes in hippocampal neurogenesis and the related functions. In this study, we showed that MnSOD deficiency led to reduced generation of immature neurons in Sod2−/+ mice even though progenitor cell proliferation was not affected. Compared to irradiated Sod2+/+ mice, which showed cognitive defects and reduced differentiation of newborn cells towards the neuronal lineage, irradiated Sod2−/+ mice showed normal hippocampal-dependent cognitive functions and normal differentiation pattern for newborn neurons and astroglia. However, we also observed a disproportional decrease in newborn neurons in irradiated Sod2−/+ following behavioral studies, suggesting that MnSOD deficiency may render newborn neurons more sensitive to stress from behavioral trainings following cranial irradiation. A positive correlation between normal cognitive functions and normal dendritic spine densities in dentate granule cells was observed. The data suggest that maintenance of synaptic connections, via maintenance of dendritic spines, may be important for normal cognitive functions following cranial irradiation. PMID:23145165

  18. Anti-apoptotic peptides protect against radiation-induced cell death.

    PubMed

    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

    2007-04-01

    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 15Gy radiation. In mice exposed to 5Gy 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. PMID:17307150

  19. Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis.

    PubMed

    Noronha, Vladimir R A S; Araujo, Gustavo S; Gomes, Rafael T; Iwanaga, Samara H; Barbosa, Maralice C; Abdo, Evandro N; Ferreira e Ferreira, Efigenia; Viana Campos, Ana C; Souza, Alexandre A; Abreu, Sheila R L; Santos, Vagner R

    2014-01-01

    The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Twenty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast(®) Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. However, comparative phase III study with larger number of patients should be done for confirmation of the efficacy of the product. PMID:24502424

  20. Imaging of dose distributions using polymer gels based on radiation induced changes in stiffness

    NASA Astrophysics Data System (ADS)

    Crescenti, Remo A.; Bamber, Jeffrey C.; Oberai, Assad A.; Barbone, Paul E.; Richter, Joseph P.; Rivas, Carlos; Bush, Nigel L.; Webb, Steve

    2009-05-01

    Previously, dose determination based on radiation induced stiffness difference measurements has received no or very little attention. Here, a preliminary evaluation of a combined system for dosimetry based on radiation sensitive gels, ultrasonic elastography and a plane strain inverse algorithm is presented. A block of gel was irradiated along one of its axes producing stiff rod-like regions. The dose distribution found with quantitative ultrasound elastography was compared with a reference dose distribution measured with magnetic resonance imaging. In these early results, the high dose areas were clearly detected, while noise in the ultrasound measurement and strong regularisation in the inverse computing introduced shape distortions, noise in the dose estimates and problems estimating the correct dose contrast. Improvements in the experimental setup and inverse computing are possible, for example by acquisition of transversal ultrasound data, which could essentially reduce the noise and restrict direct influence of the experimental boundary condition on the dose estimation by providing additional information for inverse computing. Based on the preliminary results and the potential for improvement it is concluded that further investigations should follow to establish the potential of the rapidly developing field of elastography for measuring radiation dose based on radiation induced changes in stiffness.

  1. The Role of Alveolar Epithelium in Radiation-Induced Lung Injury

    PubMed Central

    Almeida, Celine; Nagarajan, Devipriya; Tian, Jian; Leal, Sofia Walder; Wheeler, Kenneth; Munley, Michael; Blackstock, William; Zhao, Weiling

    2013-01-01

    Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11–13 Gy) and fractionated doses (24–36 Gy) of 137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis. PMID:23326473

  2. Development of small-molecule PUMA inhibitors for mitigating radiation-induced cell death.

    PubMed

    Mustata, Gabriela; Li, Mei; Zevola, Nicki; Bakan, Ahmet; Zhang, Lin; Epperly, Michael; Greenberger, Joel S; Yu, Jian; Bahar, Ivet

    2011-01-01

    PUMA (p53 upregulated modulator of apoptosis) is a Bcl-2 homology 3 (BH3)-only Bcl-2 family member and a key mediator of apoptosis induced by a wide variety of stimuli. PUMA is particularly important in initiating radiation-induced apoptosis and damage in the gastrointestinal and hematopoietic systems. Unlike most BH3-only proteins, PUMA neutralizes all five known antiapoptotic Bcl-2 members though high affinity interactions with its BH3 domain to initiate mitochondria-dependent cell death. Using structural data on the conserved interactions of PUMA with Bcl-2-like proteins, we developed a pharmacophore model that mimics these interactions. In silico screening of the ZINC 8.0 database with this pharmacophore model yielded 142 compounds that could potentially disrupt these interactions. Thirteen structurally diverse compounds with favorable in silico ADME/Toxicity profiles have been retrieved from this set. Extensive testing of these compounds using cell-based and cell-free systems identified lead compounds that confer considerable protection against PUMA-dependent and radiation-induced apoptosis, and inhibit the interaction between PUMA and Bcl-xL. PMID:21320058

  3. Development of Small-Molecule PUMA Inhibitors for Mitigating Radiation-Induced Cell Death

    PubMed Central

    Mustata, Gabriela; Li, Mei; Zevola, Nicki; Bakan, Ahmet; Zhang, Lin; Epperly, Michael; Greenberger, Joel S.; Yu, Jian; Bahar, Ivet

    2011-01-01

    PUMA (p53 upregulated modulator of apoptosis) is a Bcl-2 homology 3 (BH3)-only Bcl-2 family member and a key mediator of apoptosis induced by a wide variety of stimuli. PUMA is particularly important in initiating radiation-induced apoptosis and damage in the gastrointestinal and hematopoietic systems. Unlike most BH3-only proteins, PUMA neutralizes all five known antiapoptotic Bcl-2 members through high affinity interactions with its BH3 domain to initiate mitochondria-dependent cell death. Using structural data on the conserved interactions of PUMA with Bcl-2-like proteins, we developed a pharmacophore model that mimics these interactions. In silico screening of the ZINC 8.0 database with this pharmacophore model yielded 142 compounds that could potentially disrupt these interactions. Thirteen structurally diverse compounds with favorable in silico ADME/Toxicity profiles have been retrieved from this set. Extensive testing of these compounds using cell-based and cell-free systems identified lead compounds that confer considerable protection against PUMA-dependent and radiation-induced apoptosis, and inhibit the interaction between PUMA and Bcl-xL. PMID:21320058

  4. Does altered fractionation influence the risk of radiation-induced optic neuropathy?

    SciTech Connect

    Bhandare, Niranjan; Monroe, Alan T.; Morris, Christopher G.; Bhatti, M. Tariq; Mendenhall, William M. . E-mail: mendewil@shands.ufl.edu

    2005-07-15

    Purpose: To analyze the parameters that influence the risk of radiation-induced optic neuropathy (RION) after radiotherapy for head-and-neck tumors. Methods and Materials: Between 1964 and 2000, 273 patients with tumors of the nasopharynx, paranasal sinuses, nasal cavity, and hard palate adenoid cystic carcinomas were treated with curative intent and had radiation fields that included the optic nerves and/or chiasm. Patients were followed for at least 1 year after radiotherapy. Results: Radiation-induced optic neuropathy developed in 32 eyes of 24 patients (9%). The 5-year rates of freedom from RION according to the total dose and once- vs. twice-daily fractionation were as follows: {<=}63 Gy once daily, 95%; {<=}63 Gy twice daily, 98%; >63 Gy once daily, 78%; and >63 Gy twice daily, 91%. Multivariate analysis revealed that the total dose affected the risk of RION (p = 0.0047), with patient age (p = 0.0909), once-daily vs. twice-daily fractionation (p = 0.0684), and overall treatment time (p = 0.0972) were marginally significant. The use of adjuvant chemotherapy did not significantly influence the likelihood of developing RION. Conclusion: The likelihood of developing RION is primarily influenced by the total dose. Hyperfractionation may reduce the risk of experiencing this complication.

  5. Assessment of acute radiation-induced pulmonary changes using computed tomography.

    PubMed

    Mah, K; Poon, P Y; Van Dyk, J; Keane, T; Majesky, I F; Rideout, D F

    1986-01-01

    In a prospective study of acute radiation-induced pulmonary changes, CT scans of 54 patients were performed before and at preselected times during the 6 months following fractionated radiation therapy of the thorax. The CT films were evaluated independently by three diagnostic radiologists and 36 patients were scored as having postirradiation pulmonary findings. The average interobserver agreement for this scoring was approximately 85%. The end point was observed as an increase in lung density within the irradiated volume on a follow-up CT examination. All 36 patients demonstrated lung opacities in an irregular, homogeneous, or nonhomogeneous pattern within the radiation beam boundaries. In addition, the following characteristics were observed at various frequencies in these 36 patients: extension of the changes across anatomic tissue boundaries (50%), air bronchograms (25%), loss of lung volume (15%), and pleural thickening (15%). Confinement of the findings within the irradiated volume was the only specific characteristic of postirradiation changes. In two patients the changes appeared as sharply defined, nodular opacities and were considered to be atypical of radiation damage. These were subsequently confirmed to be metastases. Prospective assessment of an adequate number of patients has helped to establish the CT appearance of acute radiation-induced pulmonary effects and, hence, to minimize its confusion with malignancies and other abnormalities. PMID:3745541

  6. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse.

    PubMed

    Cheng, Joseph C; Bai, Aiping; Beckham, Thomas H; Marrison, S Tucker; Yount, Caroline L; Young, Katherine; Lu, Ping; Bartlett, Anne M; Wu, Bill X; Keane, Barry J; Armeson, Kent E; Marshall, David T; Keane, Thomas E; Smith, Michael T; Jones, E Ellen; Drake, Richard R; Bielawska, Alicja; Norris, James S; Liu, Xiang

    2013-10-01

    Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy. PMID:24091326

  7. Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells.

    PubMed

    Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio; Nakayama, Toshiyuki; Nakashima, Masahiro; Uemura, Takashi; Niino, Daisuke; Sekine, Ichiro

    2008-07-01

    Polaprezinc, an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. Polaprezinc has been shown to prevent gastric mucosal injury. The anti ulcer effects of polaprezinc have been ascribed to its antioxidative property. The effect of polaprezinc on ionizing radiation-induced apoptosis was studied in the jejunal epithelial crypt cells of rats. Seven-to eight week-old Wistar rats, which were treated with 100 mg/kg of polaprezinc orally 1h before irradiation or 2% carboxymethyl cellulose sodium in controls, were exposed to whole body X-ray irradiation at 2 Gy. The number of apoptotic cells per jejunum crypt was counted in haematoxylin and eosin stained sections at 0-6 h after irradiation. TUNEL positive cells and immunopositive cells for active caspase-3 per crypt were also counted. Accumulation of p53, p21(WAF1/CIP1) and Bax expression in the jejunum after irradiation were examined by Western blot analyses. Polaprezinc treatment given prior to radiation resulted in a significant reduction in numbers of apoptotic cells, TUNEL positive cells and active caspase-3 immunopositive cells in jejunal crypt cells. Polaprezinc treatment resulted in decreases of p53 accumulation, p21(WAF1/CIP1) and Bax expression after irradiation. Polaprezinc has a protective effect against ionizing radiation induced apoptosis in rat jejunal crypt cells. PMID:18413982

  8. Preclinical evaluation of erythropoietin administration in a model of radiation-induced kidney dysfunction

    SciTech Connect

    Andratschke, Nicolaus; Schnaitera, Andrea; Weber, Wolfgang A.; Caia, Lu; Schill, Sabine; Wiedenmann, Nicole; Schwaiger, Markus; Molls, Michael; Nieder, Carsten . E-mail: cnied@hotmail.com

    2006-04-01

    Purpose: To test whether the clinically available growth factor erythropoietin (EPO) influences radiation-induced normal-tissue damage in a model of kidney dysfunction. Methods: Animal experiments were conducted to test the role of EPO administration in a C3H mouse model of unilateral kidney irradiation with 6, 8, and 10 Gy and to assess the effects of 2 different dose levels of EPO. The kidney function was assessed before radiotherapy, as well as 19, 25, 31, and 37 weeks thereafter by means of {sup 99m}Tc-dimercaptosuccinat scans (static scintigraphy). Results: Concomitant EPO administration significantly increased the degree of radiation-induced kidney dysfunction. A dose of 2,000 IU/kg body weight per injection tended to cause more damage than the lower dose of 500 IU/kg. Conclusion: Administration of growth factors concomitant to radiotherapy might modify the development of kidney dysfunction. Although insulin-like growth factor-1 has previously been shown to protect the kidney, such an effect could not be demonstrated for EPO. The latter agent even increased the development of nephropathy.

  9. Proximity within interphase chromosome contributes to the breakpoint distribution in radiation-induced intrachromosomal exchanges

    NASA Astrophysics Data System (ADS)

    Zhang, Ye; Uhlemeyer, Jimmy; Hada, Megumi; Asaithamby, A.; Chen, David J.; Wu, Honglu

    2014-07-01

    Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome 3 in human mammary epithelial cells after exposures to either low- or high-LET radiation. In particular, breaks in certain regions of the chromosome tended to rejoin with each other to form an intrachromosome exchange event. This study tests the hypothesis that proximity within a single chromosome in interphase cell nuclei contributes to the distribution of radiation-induced chromosome breaks. Chromosome 3 in G1 human mammary epithelial cells was hybridized with the multicolor banding in situ hybridization (mBAND) probes that distinguish the chromosome in six differently colored regions, and the location of these regions was measured with a laser confocal microscope. Results of the study indicated that, on a multi-mega base pair scale of the DNA, the arrangement of chromatin was non-random. Both telomere regions tended to be located towards the exterior of the chromosome domain, whereas the centromere region towards the interior. In addition, the interior of the chromosome domain was preferentially occupied by the p-arm of the chromatin, which is consistent with our previous finding of intrachromosome exchanges involving breaks on the p-arm and in the centromere region of chromosome 3. Other factors, such as the fragile sites in the 3p21 band and gene regulation, may also contribute to the breakpoint distribution in radiation-induced chromosome aberrations.

  10. Sorafenib Enhances Radiation-Induced Apoptosis in Hepatocellular Carcinoma by Inhibiting STAT3

    SciTech Connect

    Huang, Chao-Yuan; Lin, Chen-Si; Tai, Wei-Tien; Hsieh, Chi-Ying; Shiau, Chung-Wai; Cheng, Ann-Lii; Chen, Kuen-Feng

    2013-07-01

    Purpose: Hepatocellular carcinoma (HCC) is one of the most common and lethal human malignancies. Lack of efficient therapy for advanced HCC is a pressing problem worldwide. This study aimed to determine the efficacy and mechanism of combined sorafenib and radiation therapy treatment for HCC. Methods and Materials: HCC cell lines (PLC5, Huh-7, Sk-Hep1, and Hep3B) were treated with sorafenib, radiation, or both, and apoptosis and signal transduction were analyzed. Results: All 4 HCC cell lines showed resistance to radiation-induced apoptosis; however, this resistance could be reversed in the presence of sorafenib. Inhibition of phospho-STAT3 was found in cells treated with sorafenib or sorafenib plus radiation and subsequently reduced the expression levels of STAT3-related proteins, Mcl-1, cyclin D1, and survivin. Silencing STAT3 by RNA interference overcame apoptotic resistance to radiation in HCC cells, and the ectopic expression of STAT3 in HCC cells abolished the radiosensitizing effect of sorafenib. Moreover, sorafenib plus radiation significantly suppressed PLC5 xenograft tumor growth. Conclusions: These results indicate that sorafenib sensitizes resistant HCC cells to radiation-induced apoptosis via downregulating phosphorylation of STAT3 in vitro and in vivo.

  11. A non-human primate model of radiation-induced cachexia

    PubMed Central

    Cui, Wanchang; Bennett, Alexander W.; Zhang, Pei; Barrow, Kory R.; Kearney, Sean R.; Hankey, Kim G.; Taylor-Howell, Cheryl; Gibbs, Allison M.; Smith, Cassandra P.; MacVittie, Thomas J.

    2016-01-01

    Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20–25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease. PMID:27029502

  12. Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly

    PubMed Central

    Shimada, Mikio; Matsuzaki, Fumio; Kato, Akihiro; Kobayashi, Junya; Matsumoto, Tomohiro; Komatsu, Kenshi

    2016-01-01

    The embryonic brain is one of the tissues most vulnerable to ionizing radiation. In this study, we showed that ionizing radiation induces apoptosis in the neural progenitors of the mouse cerebral cortex, and that the surviving progenitor cells subsequently develop a considerable amount of supernumerary centrosomes. When mouse embryos at Day 13.5 were exposed to γ-rays, brains sizes were reduced markedly in a dose-dependent manner, and these size reductions persisted until birth. Immunostaining with caspase-3 antibodies showed that apoptosis occurred in 35% and 40% of neural progenitor cells at 4 h after exposure to 1 and 2 Gy, respectively, and this was accompanied by a disruption of the apical layer in which mitotic spindles were positioned in unirradiated mice. At 24 h after 1 Gy irradiation, the apoptotic cells were completely eliminated and proliferation was restored to a level similar to that of unirradiated cells, but numerous spindles were localized outside the apical layer. Similarly, abnormal cytokinesis, which included multipolar division and centrosome clustering, was observed in 19% and 24% of the surviving neural progenitor cells at 48 h after irradiation with 1 and 2 Gy, respectively. Because these cytokinesis aberrations derived from excess centrosomes result in growth delay and mitotic catastrophe-mediated cell elimination, our findings suggest that, in addition to apoptosis at an early stage of radiation exposure, radiation-induced centrosome overduplication could contribute to the depletion of neural progenitors and thereby lead to microcephaly. PMID:27367050

  13. The role of protein kinase C alpha translocation in radiation-induced bystander effect

    PubMed Central

    Fang, Zihui; Xu, An; Wu, Lijun; Hei, Tom K.; Hong, Mei

    2016-01-01

    Ionizing radiation is a well known human carcinogen. Evidence accumulated over the past decade suggested that extranuclear/extracellular targets and events may also play a critical role in modulating biological responses to ionizing radiation. However, the underlying mechanism(s) of radiation-induced bystander effect is still unclear. In the current study, AL cells were irradiated with alpha particles and responses of bystander cells were investigated. We found out that in bystander AL cells, protein kinase C alpha (PKCα) translocated from cytosol to membrane fraction. Pre-treatment of cells with PKC translocation inhibitor chelerythrine chloride suppressed the induced extracellular signal-regulated kinases (ERK) activity and the increased cyclooxygenase 2 (COX-2) expression as well as the mutagenic effect in bystander cells. Furthermore, tumor necrosis factor alpha (TNFα) was elevated in directly irradiated but not bystander cells; while TNFα receptor 1 (TNFR1) increased in the membrane fraction of bystander cells. Further analysis revealed that PKC activation caused accelerated internalization and recycling of TNFR1. Our data suggested that PKCα translocation may occur as an early event in radiation-induced bystander responses and mediate TNFα-induced signaling pathways that lead to the activation of ERK and up-regulation of COX-2. PMID:27165942

  14. The nucleus is the target for radiation-induced chromosomal instability

    NASA Technical Reports Server (NTRS)

    Kaplan, M. I.; Morgan, W. F.

    1998-01-01

    We have previously described chromosomal instability in cells of a human-hamster hybrid cell line after exposure to X rays. Chromosomal instability in these cells is characterized by the appearance of novel chromosomal rearrangements multiple generations after exposure to ionizing radiation. To identify the cellular target(s) for radiation-induced chromosomal instability, cells were treated with 125I-labeled compounds and frozen. Radioactive decays from 125I cause damage to the cell primarily at the site of their decay, and freezing the cells allows damage to accumulate in the absence of other cellular processes. We found that the decay of 125I-iododeoxyuridine, which is incorporated into the DNA, caused chromosomal instability. While cell killing and first-division chromosomal rearrangements increased with increasing numbers of 125I decays, the frequency of chromosomal instability was independent of dose. Chromosomal instability could also be induced from incorporation of 125I-iododeoxyuridine without freezing the cells for accumulation of decays. This indicates that DNA double-strand breaks in frozen cells resulting from 125I decays failed to lead to instability. Incorporation of an 125I-labeled protein (125I-succinyl-concanavalin A), which was internalized into the cell and/or bound to the plasma membrane, neither caused chromosomal instability nor potentiated chromosomal instability induced by 125I-iododeoxyuridine. These results show that the target for radiation-induced chromosomal instability in these cells is the nucleus.

  15. Protective Role of Rheum Tanguticum Polysaccharide 1 in Radiation- induced Intestinal Mucosal Injury

    PubMed Central

    Liu, Lin-Na; Shi, Lei; Li, Shi-Cao; Zhang, Wen-Juan; Zhang, Yan; Zhang, Zhi-Pei

    2015-01-01

    The protective effects of Rheum tanguticum polysaccharide 1 (RTP1), which is extracted from the Chinese traditional medicine Rheum tanguticum, on radiation-induced intestinal mucosal injury was investigated. Rat intestinal crypt epithelial cells (IEC-6 cells) and Sprague-Dawley rats were each divided into control, irradiated and RTP1-pretreated irradiated groups. After irradiation, cell survival was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide). assay, and the intracellular reactive oxygen species (ROS) was detected by fluorescent probe method. Apoptosis was observed by acridine orange staining, and cell cycle was analysed by flow cytometry. Histological analysis of the rat intestinal mucosa was conducted by haematoxylin and eosin staining. Irradiation at 8 Gy(Gray) decreased cell survival rate to only 54%, significantly increased intracellular ROS levels and induced apoptosis. RTP1 pretreatment significantly inhibited cell death, reduced the formation of intracellular ROS and partially inhibited apoptosis. Irradiation markedly reduced the height and quantity of rat intestinal villi, but it could be antagonised by RTP1 pretreatment. RTP1 can promote the recovery of intestinal mucosa damage, possibly by inhibiting radiation-induced intestinal epithelial apoptosis and intracellular ROS production. PMID:26330871

  16. 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

  17. Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1.

    PubMed

    Bronova, Irina; Smith, Brett; Aydogan, Bulent; Weichselbaum, Ralph R; Vemuri, Kiran; Erdelyi, Katalin; Makriyannis, Alex; Pacher, Pal; Berdyshev, Evgeny V

    2015-10-01

    Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis. Female C57BL/6 mice and CB1 knockout mice generated on C57BL/6 background received 20 Gy (2 Gy/min) single-dose thoracic irradiation that resulted in pulmonary fibrosis and animal death within 15 to 18 weeks. Some C57BL/6 animals received the CB1 peripherally restricted antagonist AM6545 at 1 mg/kg intraperitoneally three times per week. Animal survival and parameters of pulmonary inflammation and fibrosis were evaluated. Thoracic irradiation (20 Gy) was associated with marked pulmonary inflammation and fibrosis in mice and high mortality within 15 to 18 weeks after exposure. Genetic deletion or pharmacological inhibition of CB1 receptors with a peripheral CB1 antagonist AM6545 markedly attenuated or delayed the lung inflammation and fibrosis and increased animal survival. Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation. PMID:26426981

  18. 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

  19. Relief of radiation-induced oral mucositis in head and neck cancer.

    PubMed

    Putwatana, Panwadee; Sanmanowong, Phichanee; Oonprasertpong, Ladawal; Junda, Tiraporn; Pitiporn, Supaporn; Narkwong, Ladawan

    2009-01-01

    This study was a prospective, randomized clinical trial carried out to explore the efficacy of payayor in the prevention and relief of radiation-induced oral mucositis compared with benzydamine. Sixty patients with head and neck cancer, who have started to receive radiotherapy and met predetermined criteria, were randomly assigned into each group to use assigned products 3 times a day from the first to the last day of radiation. The first group used glycerin payayor, a Thai prepared herbal product, by dripping it into the mouth. Another group rinsed their mouths with benzydamine hydrochloride. The World Health Organization Mucositis Grading System was used to assess oral status every week and 2 weeks after radiation. Comparison of time to the onset, pain, severity, xerostomia, postponement of treatment, satisfaction of the solution, and body weight between the 2 groups was performed by t test. The average time to the onset of oral mucositis in the payayor group was significantly later, and its severity and pain score were less than those of the benzydamine group throughout the study period. Significantly higher satisfaction with the solution and higher body weight at the end of the study were shown in the payayor group. Payayor seemed to be superior to benzydamine for preventing and relieving radiation-induced oral mucositis. PMID:19104205

  20. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

  1. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

    SciTech Connect

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.

  2. Investigation of radiation-induced free radicals and luminescence properties in fresh pomegranate fruits.

    PubMed

    Shahbaz, Hafiz M; Akram, Kashif; Ahn, Jae-Jun; Kwon, Joong-Ho

    2013-05-01

    Radiation-induced free radicals and luminescence properties were investigated in γ-irradiated (0-3 kGy) pomegranate ( Punica granatum L.) fruits. Photostimulated luminescence (PSL) analysis showed limited applicability, and only 3 kGy-irradiated pomegranates showed positive PSL values (>5000 PCs). Thermoluminescence (TL) glow curve features, such as intensity and the presence of maximum glow peak in radiation-specific temperature range (150-250 °C), provided definite proof of irradiation, and the TL ratios (TL1/TL2) also confirmed the reliability of TL results. Scanning electron microscopy energy dispersive X-ray (SEM-EDX) analysis of the separated minerals showed that feldspar and quartz minerals were responsible for the luminescence properties. Radiation-induced cellulose radicals were detected in the seeds and rinds by ESR analysis. The ESR results were better in freeze-dried samples than in alcohol-extracted ones. A positive correlation was found between the ESR and TL signal intensities and irradiation doses; however, the most promising detection of the irradiation status was possible through TL analysis. PMID:23565691

  3. Radiation-induced attenuation self-compensating effect in super-fluorescent fiber source

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Hong; Suo, Xin-Xin; Yang, Wei

    2014-09-01

    The compact super-fluorescent fiber source (SFS) output spectra variations at different pump currents and under different dose of gamma-ray radiation were measured and compared respectively. The radiation-induced attenuation (RIA) self-compensating effect in SFS based on photo-bleaching was found and the general mathematic model of SFS output spectra variations was made. The radiation-induced background attenuation (RIBA) at the pump wavelength was identified to be the main cause of the total output power and spectra variations and the variations can then be compensated by active control of the pump power to enhance the self-compensating effect. With closed-loop feedback control of pump current, double-pass backward (DPB) configuration and spectrum re-shaping technology, an SFS prototype was made and tested. The mean-wavelength stability of about 87.4 ppm and output power instability of less than 5% were achieved under up to 200 krad (Si) gamma-ray irradiation.

  4. Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment

    NASA Technical Reports Server (NTRS)

    Durante, M.; George, K.; Wu, H. L.; Yang, T. C.

    1998-01-01

    It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

  5. Sialylation of Integrin beta1 is Involved in Radiation-Induced Adhesion and Migration in Human Colon Cancer Cells

    SciTech Connect

    Lee, Minyoung; Lee, Hae-June; Seo, Woo Duck; Park, Ki Hun; Lee, Yun-Sil

    2010-04-15

    Purpose: Previously, we reported that radiation-induced ST6 Gal I gene expression was responsible for an increase of integrin beta1 sialylation. In this study, we have further investigated the function of radiation-mediated integrin beta1 sialylation in colon cancer cells. Methods and Materials: We performed Western blotting and lectin affinity assay to analyze the expression and level of sialylated integrin beta1. After exposure to ionizing radiation (IR), adhesion and migration of cells were measured by in vitro adhesion and migration assay. Results: IR increased sialylation of integrin beta1 responsible for its increased protein stability and adhesion and migration of colon cancer cells. However, for cells with an N-glycosylation site mutant of integrin beta1 located on the I-like domain (Mu3), these effects were dramatically inhibited. In addition, integrin beta1-mediated radioresistance was not observed in cells containing this mutant. When sialylation of integrin beta1 was targeted with a sulfonamide chalcone compound, inhibition of radiation-induced sialylation of integrin beta1 and inhibition of radiation-induced adhesion and migration occurred. Conclusion: The increase of integrin beta1 sialylation by ST6 Gal I is critically involved in radiation-mediated adhesion and migration of colon cancer cells. From these findings, integrin beta1 sialylation may be a novel target for overcoming radiation-induced survival, especially radiation-induced adhesion and migration.

  6. Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs.

    PubMed

    Linard, Christine; Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-11-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. PMID:24068742

  7. Radiation-induced brachial plexopathy: Neurological follow-up in 161 recurrence-free breast cancer patients

    SciTech Connect

    Olsen, N.K.; Pfeiffer, P.; Johannsen, L.; Schroder, H.; Rose, C. )

    1993-04-30

    The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients, treated according to the Danish Breast Cancer Cooperative Group protocols. One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months (13-99 months). After total mastectomy and axillary node sampling, high-risk patients were randomized to adjuvant therapy. One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks. In addition, 82 of these patients received cytotoxic therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and 46 received tamoxifen. Five percent and 9% of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy, respectively. Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy (p = 0.04) and in younger patients (p = 0.04). The clinical manifestations were paraesthesia (100%), hypaesthesia (74%), weakness (58%), decreased muscle stretch reflexes (47%), and pain (47%). The brachial plexus is more vulnerable to large fraction size. Fractions of 2 Gy or less are advisable. Cytotoxic therapy adds to the damaging effect of radiotherapy. Peripheral nerves in younger patients seems more vulnerable. Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus. 24 refs., 9 tabs.

  8. The suppression of radiation-induced NF-{kappa}B activity by dexamethasone correlates with increased cell death in vivo

    SciTech Connect

    Nam, Seon Young; Chung, Hee-Yong . E-mail: hychung@hanyang.ac.kr

    2005-10-21

    In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory {kappa}B{alpha} (I{kappa}B{alpha}) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and {gamma}-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents in bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases I{kappa}B{alpha} expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-{kappa}B in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing I{kappa}B{alpha} expression in hematopoietic organs such as spleen and bone marrow.

  9. Inactivation of NADPH Oxidases NOX4 and NOX5 Protects Human Primary Fibroblasts from Ionizing Radiation-Induced DNA Damage

    PubMed Central

    Weyemi, Urbain; Redon, Christophe E.; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R.; Bonner, Michael Y.; Arbiser, Jack L.; Bonner, William M.

    2015-01-01

    Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year. PMID:25706776

  10. Radioprotector WR1065 reduces radiation-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells

    SciTech Connect

    Grdina, D.J.; Hill, C.K.; Peraino, C. ); Biserka, N. ); Wells, R.L. . Dept. of Radiology and Radiation Biology)

    1985-06-01

    N-(2-mercaptoethyl)-1,3-diaminopropane (WR1065) protects against radiation-induced cell killing and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster lung fibroblast cells. WR1065 (4 mm) was found to be effective in protecting against radiation-induced cell lethality only if present during irradiation. No protective effect was observed if the protector was added within 5 min after irradiation or 3 h later. The effect of WR1065 on radiation-induced mutation, expressed as resistance to the cytotoxic purine analogue 6-thioguanine (HGPRT), was also investigated. This agent was effective in reducing radiation-induced mutations regardless of when it was administered. Following 10 Gy of /sup 60/Co ..gamma..-rays, the mutation frequencies observed per 10/sup 6/ survivors were 77 +- 8, 27 +- 6, 42 +- 7, and 42 +- 7 for radiation only, and WR1065 present during, immediately after, or 3 h after irradiation. These data suggest that although a segment of radiation-induced damage leading to reproductive death cannot be modulated through the postirradiation action of WR1065, processes leading to the fixation of gross genetic damage and mutation induction in surviving cells can be effectively altered and interfered with leading to a marked reduction in mutation frequency.

  11. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR)

    PubMed Central

    2011-01-01

    Background With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances with DOR, and is now utilized by approximately one third of all IVF centers world-wide. Increasing DHEA utilization and publication of a first prospectively randomized trial now warrants a systematic review. Methods PubMed, Cochrane and Ovid Medline were searched between 1995 and 2010 under the following strategy: [ and diminished ovarian reserve or ovarian function >]. Bibliographies of relevant publications were further explored for additional relevant citations. Since only one randomized study has been published, publications, independent of evidence levels and quality assessment, were reviewed. Results Current best available evidence suggests that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. DHEA over time also appears to objectively improve ovarian reserve. Recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia. Discussion Improvement of oocyte/embryo quality with DHEA supplementation potentially suggests a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. DHEA may, thus, represent a first agent beneficially affecting aging ovarian environments. Others can be expected to follow. PMID:21586137

  12. Targeting heparanase overcomes chemoresistance and diminishes relapse in myeloma.

    PubMed

    Ramani, Vishnu C; Zhan, Fenghuang; He, Jianbo; Barbieri, Paola; Noseda, Alessandro; Tricot, Guido; Sanderson, Ralph D

    2016-01-12

    In most myeloma patients, even after several rounds of intensive therapy, drug resistant tumor cells survive and proliferate aggressively leading to relapse. In the present study, gene expression profiling of tumor cells isolated from myeloma patients after sequential rounds of chemotherapy, revealed for the first time that heparanase, a potent promoter of myeloma growth and progression, was elevated in myeloma cells that survived therapy. Based on this clinical data, we hypothesized that heparanase was involved in myeloma resistance to drug therapy. In several survival and viability assays, elevated heparanase expression promoted resistance of myeloma tumor cells to chemotherapy. Mechanistically, this enhanced survival was due to heparanase-mediated ERK signaling. Importantly, use of the heparanase inhibitor Roneparstat in combination with chemotherapy clearly diminished the growth of disseminated myeloma tumors in vivo. Moreover, use of Roneparstat either during or after chemotherapy diminished regrowth of myeloma tumors in vivo following therapy. These results provide compelling evidence that heparanase is a promising, novel target for overcoming myeloma resistance to therapy and that targeting heparanase has the potential to prevent relapse in myeloma and possibly other cancers. PMID:26624982

  13. Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex

    PubMed Central

    Hurlemann, René; Arndt, Stephan; Schlaepfer, Thomas E.; Reul, Juergen; Maier, Wolfgang; Scheele, Dirk

    2015-01-01

    From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress. PMID:25752944

  14. Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

    PubMed

    Hurlemann, René; Arndt, Stephan; Schlaepfer, Thomas E; Reul, Juergen; Maier, Wolfgang; Scheele, Dirk

    2015-01-01

    From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress. PMID:25752944

  15. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

  16. Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

    PubMed

    Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

    2015-05-25

    The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. PMID:25824410

  17. Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Schnegg, Caroline Isabel

    As a result of improvements in cancer therapy and health care, the population of long-term cancer survivors is growing. For these approximately 12 million long-term cancer survivors, brain metastases are a significant risk. Fractionated partial or whole-brain irradiation (fWBI) is often required to treat both primary and metastatic brain cancer. Radiation-induced normal tissue injury, including progressive cognitive impairment, however, can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year. Recent reports indicate that radiation-induced brain injury is associated with chronic inflammatory and oxidative stress responses, as well as increased microglial activation in the brain. Anti-inflammatory drugs may, therefore, be a beneficial therapy to mitigate radiation-induced brain injury. We hypothesized that activation of peroxisomal proliferator activated receptor delta (PPARō) would prevent or ameliorate radiation-induced brain injury, including cognitive impairment, in part, by alleviating inflammatory responses in microglia. For our in vitro studies, we hypothesized that PPARō activation would prevent the radiation-induced inflammatory response in microglia following irradiation. Incubating BV-2 murine microglial cells with the (PPAR)ō agonist, L-165041, prevented the radiation-induced increase in: i) intracellular ROS generation, ii) Cox-2 and MCP-1 expression, and iii) IL-1β and TNF-α message levels. This occured, in part, through PPARō-mediated modulation of stress activated kinases and proinflammatory transcription factors. PPARō inhibited NF-κB via transrepression by physically interacting with the p65 subunit, and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular ROS generation. These data support the hypothesis that PPARō activation can modulate the radiation-induced oxidative stress and inflammatory

  18. Successful Treatment of Intractable Bleeding Caused by Radiation-Induced Hemorrhagic Gastritis Using Oral Prednisolone: A Case Report

    PubMed Central

    Yun, Hyong Geun; Kim, Hong Yong; Kim, Do Yeun; Lim, Yun Jeong

    2015-01-01

    Radiation-induced hemorrhagic gastritis is an intractable and dangerous condition. We describe a 59-year-old female patient with radiation-induced hemorrhagic gastritis. The patient underwent postoperative radiation therapy with a dose of 54 Gy in 30 fractions after a radical operation for a Klatskin tumor. Radiation volume included the gastric antrum. Approximately three months after radiation therapy, she was admitted for melena and anemia. Esophagogastroduodenoscopy showed an area of bleeding in the gastric antrum that was so diffuse that effective laser coagulation was not feasible. After failure of various treatments and transfusion of 7,040 mL of packed red blood cells, we successfully stopped the hemorrhage using oral prednisolone treatment. Based on this case, we think that oral prednisolone treatment can be tried as a first treatment for potentially life-threatening radiation-induced hemorrhagic gastritis. PMID:25327495

  19. Diminished dose minimally invasive radioguided parathyroidectomy: a case for radioguidance.

    PubMed

    You, Christopher J; Zapas, John L

    2007-07-01

    Minimally invasive radioguided parathyroidectomy (MIRP) has been established as an alternative to bilateral neck exploration (BNE) for primary hyperparathyroidism. We investigate whether a diminished dose of technetium-99m sestamibi gives similar results to the standard dose. One hundred one patients were offered MIRP or diminished-dose MIRP (ddMIRP). Patients received intravenous Tc-99m sestamibi at a dose of either 25 mCi 1.5 hours or 5 mCi 1 hour preoperatively. The procedure was terminated when the 20 per cent rule was satisfied. All tissue was confirmed to be parathyroid tissue by frozen section analysis. In addition, intraoperative parathyroid hormone levels were measured in a majority of patients. Patients who failed IOM underwent BNE. Frozen section analysis and intraoperative parathyroid hormone monitoring were also performed in the BNEs. Postoperatively, serum calcium levels were measured at 1 week and 6 months. Fifteen per cent of patients were male and 85 per cent were female. The median age was 63 years (range, 25-89 years). The first 58 patients had the standard dose of 25 mCi, whereas 43 patients had ddMIRP. Six patients (10%) failed intraoperative mapping in the MIRP group and were found to have single-gland disease. Five patients (12%) failed intraoperative mapping in the ddMIRP group. However, two patients were identified to have multigland disease making the true failure rate of intraoperative mapping 7 per cent (three patients). Median operative times for MIRP, ddMIRP, and BNE were 40 minutes, 46 minutes, and 105 minutes, respectively. The 20 per cent rule was satisfied in 96 per cent of patients undergoing MIRP and 98 per cent of patients undergoing ddMIRP. Frozen section analysis and intraoperative parathyroid hormone monitoring did not result in a change in management. Median follow up was 193 days and serum calcium levels at 6 months were normal. Diminished-dose MIRP is a feasible alternative to standard-dose MIRP without compromising

  20. The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity.

    PubMed

    Adhikari, Manish; Arora, Rajesh

    2016-06-01

    The main focus of this study is evaluation of radioprotective efficacy of silymarin, a flavonolignan, against γ-radiation-induced damage to hematological, vital organs (liver and intestine), and immune system. Survival studies revealed that silymarin (administered orally for 3 days) provided maximum protection (67%) at 70 mg/kg body weight (b.wt.) against lethal 9 Gy γ-irradiation (dose reduction factor = 1.27). The study revealed significant (p < 0.05) changes in levels of catalase (12.57 ± 2.58 to 30.24 ± 4.89 units), glutathione peroxidase (6.23 ± 2.95 to 13.26 ± 1.36 µg of reduced glutathione consumed/min/mg protein), glutathione reductase (0.25 ± 5.6 to 11.65 ± 2.83 pM NADPH consumed/min/mg protein), and superoxide dismutase (11.74 ± 0.2 to 16.09 ± 3.47 SOD U/mg of protein) activity at 30th day. Silymarin pretreated irradiated group exhibited increased proliferation in erythrocyte count (1.76 ± 0.41 × 10(6) to 9.25 ± 0.24 × 10(6) ), hemoglobin (2.15 ± 0.48g/dL to 14.77 ± 0.25g/dL), hematocrit (4.55 ± 0.24% to 37.22 ± 0.21%), and total leucocyte count (1.4 ± 0.15 × 10(6) to 8.31 ± 0.47 × 10(6) ) as compared with radiation control group on 15th day. An increase in CD4:CD8 ratio was witnessed (0.2-1%) at 30th day time interval using flow cytometry. Silymarin also countered radiation-induced decrease (p < 0.05) in regulatory T-cells (Tregs ) (11.23% in radiation group at 7th day versus 0.1% in pretreated silymarin irradiated group at 15th day). The results of this study indicate that flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity and might prove useful in management of nuclear and radiological emergencies. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 641-654, 2016. PMID:25411116

  1. Resolving the H 2 effect on radiation induced dissolution of UO 2-based spent nuclear fuel

    NASA Astrophysics Data System (ADS)

    Trummer, Martin; Jonsson, Mats

    2010-01-01

    In recent years, the impact of H2 on α-radiation induced dissolution of UO2-based spent nuclear fuel has been studied and debated extensively. Experimental results on the effect of H2 on the concentration of H2O2 during α-radiolysis have been shown to disagree with numerical simulations. For this reason, the reaction scheme used in simulations of aqueous radiation chemistry has sometimes been questioned. In this work, we have studied the impact of H2 on the H2O2 concentration in α-irradiated aqueous solution using numerical simulations. The effects of H2 pressure, α-dose rate and HCO3- concentration were investigated by performing systematic variations in these parameters. The simulations show that the discrepancy between the previously published experimental result and numerical simulations is due to the use of a homogeneous dose rate (the energy is assumed to be equally distributed in the whole volume). Taking the actual dose rate of the α-irradiated volume into account, the simulation is in perfect agreement with the experimental results. This shows that the H2 effect is strongly α-dose rate dependent, and proves the reliability of the reaction scheme used in the simulations. The simulations also show that H2 influences the H2O2 concentration under α-radiolysis. The magnitude of the effect depends on the dose rate and the H2 pressure as well as on the concentration of HCO 3-. The impact of the radiolytic H2 effect on the rate of α-radiation induced dissolution of spent nuclear fuel is discussed along with other (α- and γ-) radiation induced processes capable of reducing the concentration of uranium in solution. The radiolytic H2 effect is quantitatively compared to the previously presented noble metal catalyzed H2 effect. This comparison shows that the noble metal catalyzed H2 effect is far more efficient than the radiolytic H2 effect. Reduction of U(VI) in solution due to low dose rate γ-radiolysis in the presence of H2 is proposed to be the cause of

  2. The use of radiation-induced graft polymerization for modification of polymer track membranes

    NASA Astrophysics Data System (ADS)

    Shtanko, N. I.; Kabanov, V. Ya.; Apel, P. Yu.; Yoshida, M.

    1999-05-01

    Track membranes (TM) made of poly(ethylene terephtalate) (PET) and polypropylene (PP) films have a number of peculiarities as compared with other ones. They have high mechanical strength at a low thickness, narrow pore size distribution, low content of extractables. However, TM have some disadvantages such as low chemical resistance in alkaline media (PET TM), the low water flow rate due to the hydrophobic nature of their surface. The use of radiation-induced graft polymerization makes it possible to improve the basic characteristics of TM. In this communication our results on the modification of PET and PP TM are presented. The modified membranes were prepared by radiation-induced graft polymerization from the liquid phase. Three methods of grafting were used: (a) the direct method in argon atmosphere; (b) the pre-irradiation of TM in air followed by grafting in argon atmosphere; (c) pre-irradiation in vacuum followed by grafting in vacuum without contacting oxygen. The aim of the work was to investigate some properties of TM modified by grafted poly(methylvinyl pyridine) (PMVP) and poly(N-isopropylacrylamide) (PNIPAAM). It was shown that the modification of TM with hydrophilic polymer results in the growth of the water flow rate. In the past few years many works have been devoted to the synthesis of new polymers - the so-called "intelligent" materials - such as PNIPAAM. However, it is very difficult to make thin membranes of this polymer. Recently, it has been proposed to manufacture composite membranes by grafting stimulus-responsive polymers onto TM. Following this principle, we prepared thermosensitive membranes by the radiation-induced graft polymerization of N-isopropylacrylamide (NIPAAM) onto PET TM. PET TM with the pore size of about 1 μm and pore density of 10 6 cm -2 were first inserted into a solution of NIPAAM containing inhibitor of homopolymerization (CuCl 2) and then exposed to the γ-rays from a 60Co source. The transport properties of the grafted

  3. Alpha Lipoic Acid Attenuates Radiation-Induced Thyroid Injury in Rats

    PubMed Central

    Jung, Jung Hwa; Jung, Jaehoon; Kim, Soo Kyoung; Woo, Seung Hoon; Kang, Ki Mun; Jeong, Bae-Kwon; Jung, Myeong Hee; Kim, Jin Hyun; Hahm, Jong Ryeal

    2014-01-01

    Exposure of the thyroid to radiation during radiotherapy of the head and neck is often unavoidable. The present study aimed to investigate the protective effect of α-lipoic acid (ALA) on radiation-induced thyroid injury in rats. Rats were randomly assigned to four groups: healthy controls (CTL), irradiated (RT), received ALA before irradiation (ALA + RT), and received ALA only (ALA, 100 mg/kg, i.p.). ALA was treated at 24 h and 30 minutes prior to irradiation. The neck area including the thyroid gland was evenly irradiated with 2 Gy per minute (total dose of 18 Gy) using a photon 6-MV linear accelerator. Greater numbers of abnormal and unusually small follicles in the irradiated thyroid tissues were observed compared to the controls and the ALA group on days 4 and 7 after irradiation. However, all pathologies were decreased by ALA pretreatment. The quantity of small follicles in the irradiated rats was greater on day 7 than day 4 after irradiation. However, in the ALA-treated irradiated rats, the numbers of small and medium follicles were significantly decreased to a similar degree as in the control and ALA-only groups. The PAS-positive density of the colloid in RT group was decreased significantly compared with all other groups and reversed by ALA pretreatment. The high activity index in the irradiated rats was lowered by ALA treatment. TGF-ß1 immunoreactivity was enhanced in irradiated rats and was more severe on the day 7 after radiation exposure than on day 4. Expression of TGF-ß1 was reduced in the thyroid that had undergone ALA pretreatment. Levels of serum pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) did not differ significantly between the all groups. This study provides that pretreatment with ALA decreased the severity of radiation-induced thyroid injury by reducing inflammation and fibrotic infiltration and lowering the activity index. Thus, ALA could be used to ameliorate radiation-induced thyroid injury. PMID:25401725

  4. EGR1 regulates radiation-induced apoptosis in head and neck squamous cell carcinoma.

    PubMed

    Yoon, Tae Mi; Kim, Sun-Ae; Lee, Dong Hoon; Lee, Joon Kyoo; Park, Young-Lan; Lee, Kyung-Hwa; Chung, Ik-Joo; Joo, Young-Eun; Lim, Sang Chul

    2015-04-01

    The transcription factor, early growth response 1 (EGR1) belongs to the early growth response family. EGR1 regulates the transactivation of genes involved in growth inhibition and apoptosis by ionizing radiation. The aims of the present study were to evaluate the expression of EGR1, and its relationship to prognosis, in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) receiving chemoradiation therapy, and to observe the effect of EGR1 on the apoptosis of head and neck squamous cell carcinoma (HNSCC) cells treated with ionizing radiation. Expression of the EGR1 protein in tissue samples from patients with LHSCC was detected by immunohistochemistry. A high expression of the EGR1 protein was observed in 37 (67.3%) of the 55 LHSCC tissue samples examined. A high EGR1 protein expression in patients with LHSCC who were treated with chemoradiation was significantly associated with improved larynx-preservation survival (p=0.04). The 5-year disease-specific survival rate with larynx preservation was 59% in patients with a high EGR1 protein expression vs. 30% in those with a low EGR1 protein expression. In the human HNSCC cell line, PCI50, EGR1 mRNA expression was induced at 30-60 min, and EGR1 protein expression was induced at 60-120 min, after exposure to a 5 Gy dose of ionizing radiation. To evaluate the impact of EGR1 on radiation-induced apoptosis, we used small‑interfering RNA to knock down endogenous EGR1 gene expression. Cleaved caspase 3, cleaved caspase 7, and cleaved PARP were decreased, while XIAP was increased, in EGR1-knockdown PCI50 cells compared to negative control PCI50 cells, at all observed post-irradiation time points. These findings suggested that EGR1 knockdown inhibits radiation-induced apoptosis. In conclusion, EGR1 may be associated with larynx-preservation survival, through the regulation of radiation-induced apoptosis in patients with LHSCC treated with chemoradiation. Although further investigations are

  5. 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

  6. A Survey of Radiation-Induced Bronchiolitis Obliterans Organizing Pneumonia Syndrome After Breast-Conserving Therapy in Japan

    SciTech Connect

    Ogo, Etsuyo Komaki, Ritsuko; Fujimoto, Kiminori; Uchida, Masafumi; Abe, Toshi; Nakamura, Katsumasa; Mitsumori, Michihide; Sekiguchi, Kenji; Kaneyasu, Yuko; Hayabuchi, Naofumi

    2008-05-01

    Purpose: We observed a rare and unique occurrence of radiation-induced pulmonary injury outside the tangential field for early breast cancer treatment. The findings appeared to be idiopathic and were called radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome. We surveyed major hospitals in Japan to review their findings of radiation-induced BOOP, in particular the clinical and pictorial characteristics of the entity. Methods and Materials: We reviewed surveys completed and returned by 20 institutions. The survey responses were based on a total of 37 cases of BOOP syndrome. We also reviewed X-ray and computed tomography scans provided by these institutions. We discussed the information derived from the questionnaire and analyzed patients' characteristics, methods used in the treatment of BOOP syndrome, and prognosis. Results: The incidence of the radiation-induced BOOP syndrome was about 1.8% (37 of 2,056). We did not find a relationship between the characteristics of patients and the occurrence of radiation-induced BOOP syndrome. The pulmonary findings were classified into four patterns on chest computed tomography scans. Progression of the pulmonary lesions observed on chest X-ray was classified into three patterns. Pneumonitis appeared within 6 months after radiotherapy was completed and disappeared within 6-12 months after its onset. At 5-year follow-up, 2 patients had died, 1 of breast cancer and the other of interstitial pneumonitis, which seemed to be idiopathic and unrelated to the radiation-induced BOOP syndrome. Conclusions: Although the incidence of BOOP syndrome and its associated prognosis are not significant, the patients' clinical condition must be carefully followed.

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

    SciTech Connect

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

    2009-07-01

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

  8. HSPB1 polymorphisms might be associated with radiation-induced damage risk in lung cancer patients treated with radiotherapy.

    PubMed

    Li, Xiaofeng; Xu, Sheng; Cheng, Yu; Shu, Jun

    2016-05-01

    Several studies investigating the association between heat shock protein beta-1 (HSPB1) polymorphisms and radiation-induced damage in lung cancer patients administrated with radiotherapy have derived conflicting results. This meta-analysis aimed to assess the association between the HSPB1 genes' (rs2868370 and rs2868371) polymorphisms and the risk of radiation-induced damage in lung cancer patients. After an electronic literature search, four articles including six studies were found to be eligible for this meta-analysis. No association was observed between rs2868370 genotypes and radiation-induced damage risk. However, rs2868371 showed a statistically increased risk of radiation-induced damage under CC vs. CG/GG model (OR = 1.59, 95 % CI = 1.10-2.29). Subgroup analysis by ethnicity showed that the genotypes of rs2868371 were also associated with a significantly increased risk of radiation-induced damage in CC vs. CG/GG model (OR = 1.86, 95 % CI = 1.21-2.83) among mixed ethnicities which are mainly comprised of white people. When the data was stratified by organ-damaged, a significant association was only observed in the esophagus group (OR = 2.94, 95 % CI = 1.35-6.37, for CC vs. CG/GG model). In conclusion, the present study demonstrated that the rs2868371 genotypes of HSPB1 might be associated with radiation-induced esophagus damage risk, especially in Caucasians but not in the Asian population. PMID:26874728

  9. Assessment of Total Variation Diminishing schemes in combustion instability problems

    NASA Technical Reports Server (NTRS)

    Wang, Z. J.; Yang, H. Q.; Przekwas, A. J.

    1993-01-01

    Numerical simulations of acoustic waves in a shear layer and in an idealized combustion chamber using high resolution Total Variation Diminishing (TVD) schemes has been carried out to study the effects of inherent scheme dissipation and dispersion errors of this class of problems. The numerical results are compared against available exact solutions to quantify these errors. Several popular TVD limiters widely used in the Computational Fluid Dynamics (CFD) community have been assessed. Osher-Chakravarthy limiters are modified so that they can be used in explicit schemes. Among all the limiters investigated, Osher-Chakravarthy third-order limiter is identified as having performed the best. It is also found that all TVD schemes have exceptionally small dispersive errors.

  10. Social Presence Diminishes Contagious Yawning in the Laboratory

    PubMed Central

    Gallup, Andrew; Church, Allyson M.; Miller, Heather; Risko, Evan F.; Kingstone, Alan

    2016-01-01

    Contagious yawning may be a useful measure of social psychological functioning, and thus it is important to evaluate the variables influencing its expression in laboratory settings. Previous research has documented that humans yawn less frequently in crowded environments and when under direct observation, but the impact of social presence on contagious yawning remains unknown. Here we present the first study to systematically alter the degree of social presence experienced by participants in the laboratory to determine its effect on contagious yawning frequency. Our results demonstrate that both implied and actual social presence significantly diminish yawn contagion in comparison to a control condition, indicating a key social component to contagious yawning. These findings provide a framework for pursuing additional research investigating the social factors influencing contagious yawning, while also offering applications for measuring this response in laboratory settings. PMID:27112374

  11. 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

  12. Reduction of radiation-induced cell cycle blocks by caffeine does not necessarily lead to increased cell killing

    SciTech Connect

    Musk, S.R. )

    1991-03-01

    The effect of caffeine upon the radiosensitivities of three human tumor lines was examined and correlated with its action upon the radiation-induced S-phase and G2-phase blocks. Caffeine was found to reduce at least partially the S-phase and G2-phase blocks in all the cell lines examined but potentiated cytotoxicity in only one of the three tumor lines. That reductions have been demonstrated to occur in the absence of increased cell killing provides supporting evidence for the hypothesis that reductions may not be causal in those cases when potentiation of radiation-induced cytotoxicity is observed in the presence of caffeine.

  13. 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

  14. Measurements of growth and decay of radiation induced attenuation during the irradiation and recovery of plastic optical fibres

    NASA Astrophysics Data System (ADS)

    Kovačević, M. S.; Savović, S.; Djordjevich, A.; Bajić, J.; Stupar, D.; Kovačević, M.; Simić, S.

    2013-04-01

    In this work, we present the experimental study of the radiation-induced attenuation in step-index polymethyl-methacrylate based plastic optical fibre by exposure to low dose rate ionizing radiation. The low dose exposure has been found to induce significant permanent attenuation in plastic optical fibres. Based on the experimental results, the formula between radiation-induced attenuation and radiation dose is obtained accordingly. The recovery properties of plastic optical fibre also were investigated. The fibre begins to recover immediately after irradiation, but it does not fully recover, i.e. the irradiation leads to permanent damage of polymer.

  15. 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.

  16. Beneficial effects of sucralphate in radiation induced diarrhea. An open randomized study in gynecological cancer patients.

    PubMed

    Henriksson, R; Arevärn, M; Franzén, L; Persson, H; Stendahl, U

    1990-01-01

    In an open randomized study including 51 consecutive patients with gynaecological malignancies sucralphate was daily administered to patients receiving pelvic irradiation. Sucralphate, an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer, seems to be of value in preventing radiation-induced bowel discomfort. The most objective parameter, frequency of diarrhoea was almost 50% less in the sucralphate groups as compared to the controls. The patients receiving sucralphate in general displayed only minor alterations in bowel habits even at the end of the radiation treatment. The number of patients requiring symptomatic therapy with loperamide were markedly lower in the sucralphate group. Subjective discomfort such as nausea, vomiting, loss of appetite were also less common. A reduction in acute reactions to irradiation increases the possibility of carrying through planned treatment and avoids unfavourable intermissions, and thus curing the patient with cancer in the pelvis by means of radiotherapy. PMID:2245814

  17. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    SciTech Connect

    Chiolo, Irene; Georgescu, Walter; Tang, Jonathan; Costes, Sylvain V.

    2013-09-03

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  18. Endogenous retrovirus and radiation-induced leukemia in the RMF mouse

    SciTech Connect

    Tennant, R.W.; Boone, L.R.; Lalley, P.; Yang, W.K.

    1982-01-01

    The induction of myeloid leukemia in irradiated RFM/Un mice has been associated with retrovirus infection. However, two characteristics of this strain complicate efforts to define the role of the virus. This strain possesses only one inducible host range class of endogenous virus and a unique gene, in addition to the Fv-1/sup n/ locus, which specifically restricts exogenous infection by endogenous viruses. These characteristics possibly account for absence of recombinant viruses in this strain, even though virus is amply expressed during most of the animal's life span. We have examined further the distribution of retrovirus sequences and the chromosomal locus of the inducible virus in this strain. This report describes evidence for additional viral sequences in cells of a radiation-induced myeloid leukemia line and discusses the possible origin of these added copies.

  19. Retrograde dilation of a complex radiation-induced esophageal stricture through percutaneous gastrostomy.

    PubMed

    Eminler, A T; Uslan, M I; Köksal, A Ş; Guven, M; Parlak, E

    2015-06-01

    Upper esophageal strictures occur in approximately 3-4% of patients who receive radiotherapy for head and neck cancers. The standart initial treatment is dilation by using bougie or through-the-scope balloon dilators. Endoscopic treatment requires the passage of a guidewire through the stricture which cannot be accomplished in some of the patients with complex strictures. Retrograde dilation of esophageal strictures through a mature percutaneous gastrostomy tract have been reported in a limited number of cases and small case series up to date and can be considered as a rescue treatment before considering surgery in such patients. Herein we report retrograde dilatation of a radiation-induced complex esophageal stricture through the percutaneous gastrostomy tract in a patient with operated larynx cancer. PMID:26151697

  20. Radiation-induced softening of Fe-Mo alloy under high- temperature electron irradiation

    NASA Astrophysics Data System (ADS)

    Tsepelev, A.

    2016-04-01

    Effect of radiation-induced change of mechanical properties of Fe-5 wt.% Mo alloy irradiated with electrons (2 MeV) at room temperature and 400°C has been investigated. Mechanical properties were estimated by Miniaturized Disk Bend Test technique. Effect of radiation softening of the alloy is ascertained the value of which was increased with temperature rise. With the purpose of separation of thermal and radiation contributions into the effects, the tests were carried out for specimens annealed in the same thermal conditions (temperature and duration of annealing) just as during irradiation. Thermal annealing and electron irradiation at 400°C is found to bring to multidirectional effects of the alloy strengthening and softening respectively. It is concluded that irradiation suppresses the effect of thermal-induced strengthening and stimulates a softening of the alloy due to more significant changes in the structure and phase composition of it.

  1. 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

  2. The correlation between swelling and radiation-induced segregation in iron-chromium-nickel alloys.

    SciTech Connect

    Allen, T. R.; Busby, J. T.; Kenik, E. A.; Was, G. S.

    1998-03-05

    The magnitudes of both void swelling and radiation-induced segregation (RIS) in iron-chromium-nickel alloys are dependent on bulk alloy composition. Because the diffusivity of nickel via the vacancy flux is slow relative to chromium, nickel enriches and chromium depletes at void surfaces during irradiation. This local composition change reduces the subsequent vacancy flux to the void, thereby reducing void swelling. In this work, the resistance to swelling from major element segregation is estimated using diffusivities derived from grain boundary segregation measurements in irradiated iron-chromium-nickel alloys. The resistance to void swelling in iron- and nickel-base alloys correlates with the segregation and both are functions of bulk alloy composition. Alloys that display the greatest amount of nickel enrichment and chromium depletion are found to be most resistant to void swelling, as predicted. Additionally, swelling is shown to be greater in alloys in which the RIS profiles are slow to develop.

  3. In vitro radiation induced alterations in heavy metals and metallothionein content in Plantago ovata Forsk.

    PubMed

    Saha, Priyanka; Mishra, Debadutta; Chakraborty, Anindita; Sudarshan, Mathummal; Raychaudhuri, Sarmistha Sen

    2008-09-01

    Proton Induced X-ray emission (PIXE) and fluorescence-activated cell sorting (FACS) have been used to study the effects of gamma irradiation on heavy metal accumulation in callus tissue of Plantago ovata-an important cash crop of India. PIXE analysis revealed radiation-induced alteration in trace element profile during developmental stages of the callus of P. ovata. Subsequent experiments showed antagonism between Fe and Cu and also Cu and Zn and synergistic effect between Fe and Zn. FACS analysis showed significant induction of the metallothionein (MT) protein following gamma-irradiation, and maximum induction was noted at the 50-Gy absorbed dose. This indicated a progressive increment of MTs as a measure for protection against gamma-rays, to combat alteration in the homeostasis of heavy metals like Fe, Cu, Zn, and Mn. PMID:18493724

  4. Radiation-Induced Decomposition of PETN and TATB under Extreme Conditions

    SciTech Connect

    Giefers, Hubertus; Pravica, Michael

    2008-11-03

    We conducted a series of experiments investigating decomposition of secondary explosives PETN and TATB at varying static pressures and temperatures using synchrotron radiation. As seen in our earlier work, the decomposition rate of TATB at ambient temperature slows systematically with increasing pressure up to at least 26 GPa but varies little with pressure in PETN at ambient temperature up to 15.7 GPa, yielding important information pertaining to the activation complex volume in both cases. We also investigated the radiation-induced decomposition rate as a function of temperature at ambient pressure and 26 GPa for TATB up to 403 K, observing that the decomposition rate increases with increasing temperature as expected. The activation energy for the TATB reaction at ambient temperature was experimentally determined to be 16 {+-} 3 kJ/mol.

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

    SciTech Connect

    Nordal, Robert A.; Wong, C. Shun . E-mail: shun.wang@sw.ca

    2005-05-01

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

  6. A computational approach to the relationship between radiation induced double strand breaks and translocations

    NASA Technical Reports Server (NTRS)

    Holley, W. R.; Chatterjee, A.

    1994-01-01

    A theoretical framework is presented which provides a quantitative analysis of radiation induced translocations between the ab1 oncogene on CH9q34 and a breakpoint cluster region, bcr, on CH 22q11. Such translocations are associated frequently with chronic myelogenous leukemia. The theory is based on the assumption that incorrect or unfaithful rejoining of initial double strand breaks produced concurrently within the 200 kbp intron region upstream of the second abl exon, and the 16.5 kbp region between bcr exon 2 and exon 6 interact with each other, resulting in a fusion gene. for an x-ray dose of 100 Gy, there is good agreement between the theoretical estimate and the one available experimental result. The theory has been extended to provide dose response curves for these types of translocations. These curves are quadratic at low doses and become linear at high doses.

  7. Radiation induced damage and recovery in poly(3-hexyl thiophene) based polymer solar cells.

    PubMed

    Li, Gang; Yang, Yang; Devine, R A B; Mayberry, Clay

    2008-10-22

    Polymer solar cells have been characterized during and after x-ray irradiation. The open circuit voltage, dark current and power conversion efficiency show degradation consistent with the generation of defect states in the polymer semiconductor. The polymer solar cell device remained functional with exposure to a considerable dose (500 krad (SiO(2))) and showed clear signs of recovery upon removal of the irradiation source (degraded from 4.1% to 2.2% and recovered to 2.9%). Mobility-relaxation time variation, derived from J-V measurement, clearly demonstrates that radiation induced defect generation mechanisms in the organic semiconductor are active and need to be further studied. Optical transmission results ruled out the possibility of reduced light absorption and/or polymer crystallinity. The results suggest that organic solar cells are sufficiently radiation tolerant to be useful for space applications. PMID:21832674

  8. Toxicogenomic Effects in Rat Blood Leukocytes and Chemoprophylaxis of Radiation-Induced Carcinogenesis.

    PubMed

    Ivanov, S D; Bespalov, V G; Semenov, A L; Kovan'ko, E G; Aleksandrov, V A

    2016-03-01

    Toxicogenomic parameters were studied in the blood of female rats after exposure to ionizing γ-radiation in a dose of 4 Gy and chemoprophylaxis with α-difluoromethylornithine, eleutherococcus or leuzea extracts, which were used in animals with morphological manifestations of tumor growth under conditions of radiation-induced carcinogenesis. Life-time evaluation of toxicogenomic effects was carried out by express method for measurements of blood nucleotid DNA - fluorescent indication. The level of hyperaneu/polyploidy increased in the blood leukocytes of control rats 30 days after radiation exposure. A significant decrease of genotoxicity as a result of drug treatment in comparison with the number and multiplicity of tumors in irradiated animals was found only in the endocrine and reproductive organs of rats treated by eleutherococcus extract. PMID:27021083

  9. Thermal effusivity: a promising imaging biomarker to predict radiation-induced skin injuries.

    SciTech Connect

    Chu, J. C. H.; Templeton, A.; Yao, R.; Griem, K. L.; Sun, J. G.

    2012-01-01

    An effective screening technology is needed to triage individuals at the time of radiation incidents involving a large population. Three-dimensional thermal tomography is a relatively new development in active thermal imaging technology that produces cross-sectional images based on the subject's ability to transfer heat thermal effusivity at the voxel level. This noninvasive imaging modality has been used successfully in nondestructive examination of complex materials; also it has been shown to predict the severity of radiation-induced skin injuries several days before the manifestation of severe moist desquamations or blister formation symptoms in mice at 40 Gy. If these results are confirmed at lower dose levels in human subjects, a thermal tomography imaging device may be an ideal screening tool in radiation emergencies. This imaging method is non-invasive, relatively simple, easily adaptable for field use, and when properly deployed, it will enhance public emergency preparedness for incidents involving unexpected radiation exposure.

  10. Radiation-induced electrical degradation experiments in the Japan materials testing reactor

    SciTech Connect

    Farnum, E.; Scharborough, K.; Shikama, Tatsuo

    1995-04-01

    The objective of this experiment is to determine the extent of degradation during neutron irradiation of electrical and optical properties of candidate dielectric materials. The goals are to identify promising dielectrics for ITER and other fusion machines for diagnostic applications and establish the basis for optimization of candidate materials. An experiment to measure radiation-induced electrical degradation (REID) in sapphire and MgO-insulated cables was conducted at the JMTR light water reactor. The materials were irradiated at about 260 {degree}C to a fluence of 3{times}10{sup 24} n/m{sup 2} (E>1 MeV) with an applied DC electric field between 100 kV/m and 500 kV/m.

  11. A Human Espophageal Epithelial Cell Model for Study of Radiation Induced Cancer and DNA Damage Repair

    NASA Technical Reports Server (NTRS)

    Huff, Janice L.; Patel, Zarana S.; Hada, Megumi; Cucinotta, Francis A.

    2008-01-01

    For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma, a type of cancer found to have a significant enhancement in incidence in the survivors of the atomic bomb detonations in Japan. Here we present the results of our preliminary characterization of both normal and hTERT immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of - H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron).

  12. Characterization of Network Structure of Polyacrylamide Based Hydrogels Prepared By Radiation Induced Polymerization

    SciTech Connect

    Mahmudi, Naim; Sen, Murat; Gueven, Olgun; Rendevski, Stojan

    2007-04-23

    In this study network structure of polyacrylamide based hydrogels prepared by radiation induced polymerization has been investigated. Polyacrylamide based hydrogels in the rod form were prepared by copolymerization of acrylamide(AAm) with hydroxyl ethyl methacrylate(HEMA) and methyl acrylamide(MAAm) in the presence of cross-linking agent and water by gamma rays at ambient temperature. Molecular weight between cross-links and effective cross-link density of hydrogels were calculated from swelling as well as shear modulus data obtained from compression tests. The results have shown that simple compression analyses can be used for the determination of effective cross-link density of hydrogels without any need to some polymer-solvent based parameters as in the case of swelling based determinations. Diffusion of water into hydrogels was examined by analyzing water absorption kinetics and the effect of network, structure on the diffusion type and coefficient was discussed.

  13. Bioinformatics methods for learning radiation-induced lung inflammation from heterogeneous retrospective and prospective data.

    PubMed

    Spencer, Sarah J; Bonnin, Damian Almiron; Deasy, Joseph O; Bradley, Jeffrey D; El Naqa, Issam

    2009-01-01

    Radiotherapy outcomes are determined by complex interactions between physical and biological factors, reflecting both treatment conditions and underlying genetics. Recent advances in radiotherapy and biotechnology provide new opportunities and challenges for predicting radiation-induced toxicities, particularly radiation pneumonitis (RP), in lung cancer patients. In this work, we utilize datamining methods based on machine learning to build a predictive model of lung injury by retrospective analysis of treatment planning archives. In addition, biomarkers for this model are extracted from a prospective clinical trial that collects blood serum samples at multiple time points. We utilize a 3-way proteomics methodology to screen for differentially expressed proteins that are related to RP. Our preliminary results demonstrate that kernel methods can capture nonlinear dose-volume interactions, but fail to address missing biological factors. Our proteomics strategy yielded promising protein candidates, but their role in RP as well as their interactions with dose-volume metrics remain to be determined. PMID:19704920

  14. Polymeric nanocomposite proton exchange membranes prepared by radiation-induced polymerization for direct methanol fuel cell

    NASA Astrophysics Data System (ADS)

    Kim, Young-Seok; Seo, Kwang-Seok; Choi, Seong-Ho

    2016-01-01

    The vinyl group-modified montmorillonite clay (F-MMT), vinyl group-modified graphene oxide (F-GO), and vinyl group-modified multi-walled carbon nanotube (F-MWNT) were first prepared by ion exchange reaction of 1-[(4-ethylphenyl)methyl]-3-butyl-imidazolium chloride in order to use the materials for protection against methanol cross-over in direct methanol fuel cell (DMFC) membrane. Then polymeric nanocomposite membranes with F-MMT, F-GO, and F-MWNT were prepared by the solvent casting method after radiation-induced polymerization of vinyl monomers in water-methanol mixture solvents. The proton conductivity, water uptake, ion-exchange capacity, methanol permeability, and DMFC performance of the polymeric nanocomposite membranes with F-MMT, F-GO, and F-MWNT were evaluated.

  15. Radiation-induced changes in the dielectric response of poly(vinylidene fluoride) type polymers

    NASA Astrophysics Data System (ADS)

    Hilczer, B.; Smogor, H.; Goslar, J.; Warchol, S.

    2003-01-01

    High and dispersive dielectric response, characteristic of the relaxor state, was observed in ferroelectric P(VDF/TrFE)(50/50) copolymers irradiated with 1.0 MeV and 1.5 MeV electrons. Relaxor-like behaviour of the copolymer is a result of overlapping of the dielectric anomaly characteristic of the glass transition and that related to the Curie point, which is shifted downwards by electron irradiation. The results of ESR, IR and NIR Raman spectroscopy studies of the radiation damage to P(VDF/TrFE)(50/50) show that radiation-induced irreversible transformation of the ferroelectric copolymer to the relaxor state is related to the existence of polar clusters, consisting of a variety of short range coherence of trans-conformation, stabilized by random fields of C=C and conjugated C=C bonds.

  16. Semi-interpenetrating polymer networks of poly(3-hydroxybutyrate) prepared by radiation-induced polymerization

    NASA Astrophysics Data System (ADS)

    Martellini, Flavia; Innocentini Mei, Lúcia H.; Lora, Silvano; Carenza, Mario

    2004-09-01

    Semi-interpenetrating polymer networks (IPNs) based on bacterial poly(3-hydroxy butyrate) with a hydrophilic monomer at different compositions were prepared by radiation-induced polymerization using γ-rays from a 60Co source with a total dose of 10-100 kGy. The swelling behaviour was determined by water content at equilibrium, while thermal properties and crystallinity were studied by differential scanning calorimetry. Extraction of the soluble part of PHB from the films at low and high temperature with water or chloroform as well as FTIR data indicate the occurrence of the crosslinking reaction in the hydrogels. The results show a water uptake increasing with the hydrophilic component until 25%.

  17. Bioinformatics Methods for Learning Radiation-Induced Lung Inflammation from Heterogeneous Retrospective and Prospective Data

    PubMed Central

    Spencer, Sarah J.; Almiron Bonnin, Damian; Deasy, Joseph O.; Bradley, Jeffrey D.; El Naqa, Issam

    2009-01-01

    Radiotherapy outcomes are determined by complex interactions between physical and biological factors, reflecting both treatment conditions and underlying genetics. Recent advances in radiotherapy and biotechnology provide new opportunities and challenges for predicting radiation-induced toxicities, particularly radiation pneumonitis (RP), in lung cancer patients. In this work, we utilize datamining methods based on machine learning to build a predictive model of lung injury by retrospective analysis of treatment planning archives. In addition, biomarkers for this model are extracted from a prospective clinical trial that collects blood serum samples at multiple time points. We utilize a 3-way proteomics methodology to screen for differentially expressed proteins that are related to RP. Our preliminary results demonstrate that kernel methods can capture nonlinear dose-volume interactions, but fail to address missing biological factors. Our proteomics strategy yielded promising protein candidates, but their role in RP as well as their interactions with dose-volume metrics remain to be determined. PMID:19704920

  18. Tight-binding molecular dynamics simulations of radiation-induced fragmentation of C60

    NASA Astrophysics Data System (ADS)

    Horváth, Lóránd; Beu, Titus A.

    2008-02-01

    The fragmentation of the C60 fullerene was investigated using tight-binding molecular dynamics simulations based on the parametrization of Papaconstantopoulos [MRS Symposia Proceedings No. 491 (Materials Research Society, Pittsburgh, 1998), p. 221]. Averaged fragment size distributions over random sets of initial configurations were obtained from simulations of radiation-induced fragmentation in the 50-500eV excitation energy range. The excitation caused by the radiation was simulated simply by ascribing suddenly random velocities to each atom of the fullerene cage. For low excitation energies, the size distributions are peaked for dimers (reflecting a preferential C2 emission) and a bimodal size dependence characterizes the distributions of the complementary small and large fragments. For high excitation energies, predominantly multifragmentation occurs, but a genuine power-law dependence of small fragments is not yet observable. A phase transition is found for rather low excitation energies (100-120eV) .

  19. Graft polymerization using radiation-induced peroxides and application to textile dyeing

    NASA Astrophysics Data System (ADS)

    Enomoto, Ichiro; Katsumura, Yosuke; Kudo, Hisaaki; Soeda, Shin

    2011-02-01

    To improve the dyeing affinity of ultra high molecular weight polyethylene (UHMWPE) fiber, surface treatment by radiation-induced graft polymerization was performed. Methyl methacrylate (MMA), acrylic acid (AA) and styrene (St) were used as the monomers. The grafting yields as a function of storage time after irradiation were examined. Although the grafting yield of St after the sulfonation processing was quite low compared with those of MMA and AA, it was successfully dyed to a dark color with a cationic dye. Some acid dyes can dye the grafted fiber with AA. The acid dye is distributed to the amorphous domains of the AA grafted fiber. The dyeing concentration depended on the grafting yield, and the higher the grafting yield the darker the dye color.

  20. Molecular mechanisms of radiation-induced genomic instability in human cells

    SciTech Connect

    Liber, Howard L.

    2003-02-13

    The overall strategy was to create a series of isogenic human cell lines that differ in key elements of cell cycle checkpoint, apoptosis, or DNA repair in response to radiation-induced damage. The goal then was to quantify the fractions of cells within a population that exhibit reduced telomere lengths and relate this to the genetic background of the cell, as well as to the response to ionizing radiation. Association between telomere length and degree of genomic instability in the population is being examined for seven closely related cell lines, that vary in p53 status, bcl-2 status, or ability to repair double strand breaks. Experiments utilize gamma rays at doses of 0, 10, and 200 cGy. During this time period the effort concentrated on generating data with two cell lines. Approximately one-third of the required clones were isolated, and analyses for mutagenesis and chromosome aberrations were undertaken.

  1. Propagating self-sustained annealing of radiation-induced interstitial complexes

    NASA Astrophysics Data System (ADS)

    Bokov, P. M.; Selyshchev, P. A.

    2016-02-01

    A propagating self-sustained annealing of radiation induced defects as a result of thermal-concentration instability is studied. The defects that are considered in the model are complexes. Each of them consists of one atom of impunity and of one interstitial atom. Crystal with defects has extra energy which is transformed into heat during defect annealing. Simulation of the auto-wave of annealing has been performed. The front and the speed of the auto-wave have been obtained. It is shown that annealing occurs in a narrow region of time and space. There are two kinds of such annealing behaviour. In the first case the speed of the auto-wave oscillates near its constant mean value and the front of temperature oscillates in a complex way. In the second case the speed of propagation is constant and fronts of temperature and concentration look like sigmoid functions.

  2. Prompt radiation-induced conductivity in polyurethane foam and glass microballoons

    SciTech Connect

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

    2014-06-01

    We performed measurements and analyses of the prompt radiation-induced conductivity (RIC) in thin samples of polyurethane foam and glass microballoon foam at the Little Mountain Medusa LINAC facility in Ogden, UT. The RIC coefficient was non-linear with dose rate for polyurethane foam; however, typical values at 1E11 rad(si)/s dose rate was measured as 0.8E-11 mho/m/rad/s for 5 lb./cu ft. foam and 0.3E-11 mho/m/rad/s for 10 lb./cu ft. density polyurethane foam. For encapsulated glass microballoons (GMB) the RIC coefficient was approximately 1E-15 mho/m/rad/s and was not a strong function of dose rate.

  3. Radiation-induced breast cancer: the question of early breast cancer screening in Hodgkin's lymphoma survivors

    PubMed Central

    Hilal, Talal; Rudy, David W.

    2016-01-01

    Chest irradiation is associated with numerous early and late complications that arise from ionizing radiation-induced damage to cellular structures within the field of therapy. In patients exposed to chest irradiation at an early age as part of the treatment of childhood cancer, specifically Hodgkin's lymphoma, the increased risk of breast cancer in the long run should be considered. A case of a 35-year-old woman who exposed to chest irradiation as part of the treatment of Hodgkin's lymphoma at the age of 20 years is presented here and serves as a reminder of this somewhat overlooked complication. The article presents the evidence available for and against breast cancer screening in this particular patient population. PMID:26949536

  4. A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation induced death

    PubMed Central

    Atkinson, Jeffrey; Kapralov, Alexandr A.; Yanamala, Naveena; Tyurina, Yulia Y.; Amoscato, Andrew A.; Pearce, Linda; Peterson, Jim; Huang, Zhentai; Jiang, Jianfei; Samhan-Arias, Alejandro K.; Maeda, Akihiro; Feng, Weihong; Wasserloos, Karla; Belikova, Natalia A.; Tyurin, Vladimir A.; Wang, Hong; Fletcher, Jackie; Wang, Yongsheng; Vlasova, Irina I.; Klein-Seetharaman, Judith; Stoyanovsky, Detcho A.; Bayîr, Hülya; Pitt, Bruce R.; Epperly, Michael W.; Greenberger, Joel S.; Kagan, Valerian E.

    2013-01-01

    The risk of radionuclide release in terrorist acts or exposure of healthy tissue during radiotherapy demand potent radioprotectants/radiomitigators. Ionizing radiation induces cell death by initiating the selective peroxidation of cardiolipin in mitochondria by the peroxidase activity of its complex with cytochrome c leading to release of hemoprotein into the cytosol and commitment to the apoptotic program. Here we design and synthesize mitochondria-targeted triphenylphosphonium-conjugated imidazole-substituted oleic and stearic acids which blocked peroxidase activity of cytochrome c/cardiolipin complex by specifically binding to its heme-iron. We show that both compounds inhibit pro-apoptotic oxidative events, suppress cyt c release, prevent cell death, and protect mice against lethal doses of irradiation. Significant radioprotective/radiomitigative effects of imidazole-substituted oleic acid are observed after pretreatment of mice from 1 hr before through 24 hrs after the irradiation. PMID:21988913

  5. A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death.

    PubMed

    Atkinson, Jeffrey; Kapralov, Alexandr A; Yanamala, Naveena; Tyurina, Yulia Y; Amoscato, Andrew A; Pearce, Linda; Peterson, Jim; Huang, Zhentai; Jiang, Jianfei; Samhan-Arias, Alejandro K; Maeda, Akihiro; Feng, Weihong; Wasserloos, Karla; Belikova, Natalia A; Tyurin, Vladimir A; Wang, Hong; Fletcher, Jackie; Wang, Yongsheng; Vlasova, Irina I; Klein-Seetharaman, Judith; Stoyanovsky, Detcho A; Bayîr, Hülya; Pitt, Bruce R; Epperly, Michael W; Greenberger, Joel S; Kagan, Valerian E

    2011-01-01

    The risk of radionuclide release in terrorist acts or exposure of healthy tissue during radiotherapy demand potent radioprotectants/radiomitigators. Ionizing radiation induces cell death by initiating the selective peroxidation of cardiolipin in mitochondria by the peroxidase activity of its complex with cytochrome c leading to release of haemoprotein into the cytosol and commitment to the apoptotic program. Here we design and synthesize mitochondria-targeted triphenylphosphonium-conjugated imidazole-substituted oleic and stearic acids that blocked peroxidase activity of cytochrome c/cardiolipin complex by specifically binding to its haem-iron. We show that both compounds inhibit pro-apoptotic oxidative events, suppress cyt c release, prevent cell death, and protect mice against lethal doses of irradiation. Significant radioprotective/radiomitigative effects of imidazole-substituted oleic acid are observed after pretreatment of mice from 1 h before through 24 h after the irradiation. PMID:21988913

  6. Functional properties of nisin-carbohydrate conjugates formed by radiation induced Maillard reaction

    NASA Astrophysics Data System (ADS)

    Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

    2012-12-01

    Nisin-carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin-carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin-dextran conjugates possessed better antioxidant potential than nisin-glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry.

  7. A review on radiation-induced nucleation and growth of colloidal metallic nanoparticles

    PubMed Central

    2013-01-01

    This review presents an introduction to the synthesis of metallic nanoparticles by radiation-induced method, especially gamma irradiation. This method offers some benefits over the conventional methods because it provides fully reduced and highly pure nanoparticles free from by-products or chemical reducing agents, and is capable of controlling the particle size and structure. The nucleation and growth mechanism of metallic nanoparticles are also discussed. The competition between nucleation and growth process in the formation of nanoparticles can determine the size of nanoparticles which is influenced by certain parameters such as the choice of solvents and stabilizer, the precursor to stabilizer ratio, pH during synthesis, and absorbed dose. PMID:24225302

  8. Ionizing radiations induce apoptosis in TRAIL resistant cancer cells: in vivo and in vitro analysis.

    PubMed

    Silva, Marcela Fernandes; Khokhar, Abdur Rehman; Qureshi, Muhammad Zahid; Farooqi, Ammad Ahmad

    2014-01-01

    Increasingly it is being realized that despite considerable advancements in therapeutic interventions related to treatment of cancer, satisfactory results are still difficult to achieve. Rapidly accumulating evidence has started to shed light on the fact that cancer cells escape from death via constitutive activation of pro-survival signaling cascades. Cell biology and genetics have extensively enhanced our current understanding of the molecular mechanisms that underlie loss of apoptosis in cancer cells. This review is focused on ionizing radiation mediated restoration of TRAIL mediated apoptosis as evidenced by cell culture and animal model studies. Moreover, we also bring to the limelight radiation induced expression of miRNAs and how miRNAs further control response of cancer cells to radiation. PMID:24716909

  9. Radiation-induced breast cancer: the question of early breast cancer screening in Hodgkin's lymphoma survivors.

    PubMed

    Hilal, Talal; Rudy, David W

    2016-02-01

    Chest irradiation is associated with numerous early and late complications that arise from ionizing radiation-induced damage to cellular structures within the field of therapy. In patients exposed to chest irradiation at an early age as part of the treatment of childhood cancer, specifically Hodgkin's lymphoma, the increased risk of breast cancer in the long run should be considered. A case of a 35-year-old woman who exposed to chest irradiation as part of the treatment of Hodgkin's lymphoma at the age of 20 years is presented here and serves as a reminder of this somewhat overlooked complication. The article presents the evidence available for and against breast cancer screening in this particular patient population. PMID:26949536

  10. 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.

  11. Radiation-Induced Centers in Lead Silicate Glasses Irradiated by Stationary and Pulsed Electron Beams

    NASA Astrophysics Data System (ADS)

    Zhidkov, I. S.; Zatsepin, A. F.; Konev, S. F.; Cholakh, S. O.

    2015-08-01

    Radiation-induced centers formed in heavy flint glasses irradiated by electron beams are investigated by the methods of optical and EPR spectroscopy. It is revealed that stable and short-living optical absorption centers of close natures are formed under irradiation by fast electrons. A correlation is established between the stable optical absorption bands and the EPR signals interpreted as signals of the (Pb2+)/h+ hole centers. The shortliving color centers are formed due to short-term distortion of the O-Pb bonds, and the stable centers are formed due to the spatial separation, thermalization, and subsequent stabilization of excited electrons and holes in tails of the localized states. Irradiation by electron beams leads to a change in the spectral characteristics of the fundamental absorption edge and, in particular, of the Urbach energy that determines the degree of structural disorder.

  12. Investigation of radiation-induced yellow color in tourmaline by magnetic resonance

    NASA Astrophysics Data System (ADS)

    Krambrock, K.; Pinheiro, M. V. B.; Medeiros, S. M.; Guedes, K. J.; Schweizer, S.; Spaeth, J.-M.

    2002-05-01

    Tourmaline is known as a gemstone with great variety in color and composition. Some color centers are related to transition metal ions, others to radiation-induced electron-hole traps. The knowledge concerning the microscopic structure of the color centers is very poor. Therefore, color enhancing processes by irradiation and/or thermal treatments in tourmaline are performed empirically. By electron paramagnetic resonance and electron nuclear double resonance a yellow color center produced by γ-irradiation in colorless Li-bearing tourmaline (elbaite) has been identified. The color center is proposed to be a hole trap of type O - showing mainly superhyperfine interaction with two Al nuclei. During the irradiation process atomic hydrogen H 0 is also produced which shows the same thermal stability as the hole trap (250 °C).

  13. Influence of matrix porosity on the immobilization of penicillin acylase by radiation-induced polymerization

    NASA Astrophysics Data System (ADS)

    Carenza, M.; Lora, S.; Palma, G.; Boccù, E.; Largajolli, R.; Veronese, F. M.

    Penicillin acylase was immobilized by low temperature radiation-induced polymerization into polymer matrices obtained from monomers of different hydrophilicities, at various ratios of monomer to enzyme solution and at different polymerization conversions. It was found that the penicillin acylase retention (60-85% of the starting enzyme) is independent of the monomer used in thepolymerization, of the polymerization conversion and of the porosity of the polymer matrix. On the other hand, the penicillin acylase retention strongly depends on the presence in the irradiation mixture of the hydrophobic crosslinking agent, trimethylolpropane trimethacrylate, even in low amounts. The data suggest that the enzyme is bound to the polymer matrix by hydrophobic interactions through crosslinking agent molecules.

  14. Experimental investigation of the factors influencing temperature dependence of radiation-induced attenuation in optical fiber

    NASA Astrophysics Data System (ADS)

    Jin, Jing; Xu, Raomei; Liu, Jixun; Song, Ningfang

    2014-03-01

    The effects of transmission wavelength, total dose and light source power on temperature dependence of radiation-induced attenuation (RIA) in Ge-P co-doped fibers were investigated. Three fibers irradiated up to total dose of 100 Gy and 10,000 Gy were used as test samples. A test system for temperature dependence of RIA was built up. The influence of transmission wavelength, total dose and light power on temperature sensitivity and linearity of RIA in three irradiated fibers were researched. The test results show that temperature sensitivity and linearity of RIA in optical fibers could be improved by adjusting total dose and selecting transmission wavelength. The light source power does not have obvious influence on temperature sensitivity and linearity. The Ge-P co-doped fiber at 850 nm transmission wavelength with higher total dose is a very promising candidate for fiber-optic temperature sensor.

  15. Radiation-induced decomposition of trace amounts of 17 β-estradiol in water

    NASA Astrophysics Data System (ADS)

    Kimura, Atsushi; Taguchi, Mitsumasa; Arai, Hidehiko; Hiratsuka, Hiroshi; Namba, Hideki; Kojima, Takuji

    2004-03-01

    The radiation-induced decomposition of trace amounts of 17 β-estradiol (E2) in water was studied as a function of the dose of 60Co γ-rays. The rate constant of the reaction of the OH radicals with E2 was estimated to be 1.6×10 10 mol dm -3 s -1 by a comparison with the known rate constant for the reaction with phenol. Both E2 and E2-equivalent concentrations were estimated by LC-MS and ELISA, and decreased with an increase in γ-rays dose. E2 (1.8 nmol dm -3) in water was degraded almost completely by irradiations up to 10 Gy. The estrogen activity of the same sample solution still remained at a dose of 10 Gy, but decreased at 30 Gy to the lower than the threshold level of contamination to induce some estrogenic effects on the environmental ecology.

  16. Radiation induced modifications on microstructure and related properties of high temperature superconductor YBCO

    NASA Astrophysics Data System (ADS)

    Marhas, Manmeet Kaur; Balakrishnan, K.; Saravanan, P.; Ganesan, V.; Srinivasan, R.; Kanjilal, D.; Mehta, G. K.; Vedwyas, M.; Ogale, S. B.; Pai, S. P.; Ramachandra Rao, M. S.; Pinto, R.; Mohan Rao, G.; Senthilnathan, S.; Mohan, S.

    Role of swift heavy ion irradiation on the modification of transport and structural properties of high temperature superconductors is studied. Good quality YBCO thin films prepared by high pressure oxygen sputtering and laser ablation were used in this investigation. Resistivity and atomic force microscopy (AFM) were mainly used to probe superconducting and microstructural modifications resulted from the irradiation of high energy and heavy ions like 100 MeV oxygen and 200 MeV silver. Radiation induced sputtering or erosion is likely to be a major disastrous component of such high energy irradiation that could be powerful in masking phase coherence effects, atleast in grain boundaries. The extent of damage/nature of defects other than columnar defects produced by swift heavy ions is discussed in the light of AFM measurements. The effect of high energy oxygen ion irradiation is anomalous. A clear annealing effect at higher doses is seen.

  17. The complex interactions between radiation induced non-targeted effects and cancer.

    PubMed

    Campa, Alessandro; Balduzzi, Maria; Dini, Valentina; Esposito, Giuseppe; Tabocchini, Maria Antonella

    2015-01-01

    Radiation induced non-targeted effects have been widely investigated in the last two decades for their potential impact on low dose radiation risk. In this paper we will give an overview of the most relevant aspects related to these effects, starting from the definition of the low dose scenarios. We will underline the role of radiation quality, both in terms of mechanisms of interaction with the biological matter and for the importance of charged particles as powerful tools for low dose effects investigation. We will focus on cell communication, representing a common feature of non-targeted effects, giving also an overview of cancer models that have explicitly considered such effects. PMID:24139968

  18. Quantitative Ultrasonic Evaluation of Radiation-Induced Late Tissue Toxicity: Pilot Study of Breast Cancer Radiotherapy

    SciTech Connect

    Liu Tian; Zhou Jun; Yoshida, Emi J.; Woodhouse, Shermian A.; Schiff, Peter B.; Wang, Tony J.C.; Lu Zhengfeng; Pile-Spellman, Eliza; Zhang Pengpeng; Kutcher, Gerald J.

    2010-11-01

    Purpose: To investigate the use of advanced ultrasonic imaging to quantitatively evaluate normal-tissue toxicity in breast-cancer radiation treatment. Methods and Materials: Eighteen breast cancer patients who received radiation treatment were enrolled in an institutional review board-approved clinical study. Radiotherapy involved a radiation dose of 50.0 to 50.4 Gy delivered to the entire breast, followed by an electron boost of 10.0 to 16.0 Gy delivered to the tumor bed. Patients underwent scanning with ultrasound during follow-up, which ranged from 6 to 94 months (median, 22 months) postradiotherapy. Conventional ultrasound images and radio-frequency (RF) echo signals were acquired from treated and untreated breasts. Three ultrasound parameters, namely, skin thickness, Pearson coefficient, and spectral midband fit, were computed from RF signals to measure radiation-induced changes in dermis, hypodermis, and subcutaneous tissue, respectively. Ultrasound parameter values of the treated breast were compared with those of the untreated breast. Ultrasound findings were compared with clinical assessment using Radiation Therapy Oncology Group (RTOG) late-toxicity scores. Results: Significant changes were observed in ultrasonic parameter values of the treated vs. untreated breasts. Average skin thickness increased by 27.3%, from 2.05 {+-} 0.22mm to 2.61 {+-} 0.52mm; Pearson coefficient decreased by 31.7%, from 0.41 {+-} 0.07 to 0.28 {+-} 0.05; and midband fit increased by 94.6%, from -0.92 {+-} 7.35 dB to 0.87 {+-} 6.70 dB. Ultrasound evaluations were consistent with RTOG scores. Conclusions: Quantitative ultrasound provides a noninvasive, objective means of assessing radiation-induced changes to the skin and subcutaneous tissue. This imaging tool will become increasingly valuable as we continue to improve radiation therapy technique.

  19. 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

  20. Inhibition of radiation induced dissolution of UO2 by sulfide - A comparison with the hydrogen effect

    NASA Astrophysics Data System (ADS)

    Yang, Miao; Barreiro Fidalgo, Alexandre; Sundin, Sara; Jonsson, Mats

    2013-03-01

    In this work we have studied the influence of H2S on radiation induced dissolution of spent nuclear fuel using simple model systems. The reaction between H2O2 and H2S/HS- has been studied experimentally as well as the effect of H2S/HS- on γ-radiation induced dissolution of a UO2 pellet. The experiments clearly show that the reaction of H2O2 and H2S/HS- is fairly rapid and that H2O2 and H2S/HS- stoichiometry is favorable for inhibition. Radiolysis experiments show that H2S/HS- can effectively protect UO2 from oxidative dissolution. The effect depends on sulfide concentration in combination with dose rate. Autoclave experiments were also conducted to study the role of H2S/HS- in the reduction of U(VI) in the presence and absence of H2 and Pd particles in anoxic aqueous solution. The aqueous solutions were pressurized with H2 or N2 and two different concentrations of H2S/HS- were used in the presence and absence of Pd. No catalytic effect of Pd on the U(VI) reduction by H2S/HS- could be found in N2 atmosphere. U(VI) reduction was found to be proportional to H2S/HS- concentration in H2 and N2 atmosphere. It is clearly shown the Pd catalyzed H2 effect is more powerful than the effect of H2S/HS-. H2S/HS- poisoning of the Pd catalyst is not observed under the present conditions.

  1. BK K+ channel blockade inhibits radiation-induced migration/brain infiltration of glioblastoma cells

    PubMed Central

    Klumpp, Lukas; Haehl, Erik; Schilbach, Karin; Lukowski, Robert; Kühnle, Matthias; Bernhardt, Günther; Buschauer, Armin; Zips, Daniel; Ruth, Peter; Huber, Stephan M.

    2016-01-01

    Infiltration of the brain by glioblastoma cells reportedly requires Ca2+ signals and BK K+ channels that program and drive glioblastoma cell migration, respectively. Ionizing radiation (IR) has been shown to induce expression of the chemokine SDF-1, to alter the Ca2+ signaling, and to stimulate cell migration of glioblastoma cells. Here, we quantified fractionated IR-induced migration/brain infiltration of human glioblastoma cells in vitro and in an orthotopic mouse model and analyzed the role of SDF-1/CXCR4 signaling and BK channels. To this end, the radiation-induced migratory phenotypes of human T98G and far-red fluorescent U-87MG-Katushka glioblastoma cells were characterized by mRNA and protein expression, fura-2 Ca2+ imaging, BK patch-clamp recording and transfilter migration assay. In addition, U-87MG-Katushka cells were grown to solid glioblastomas in the right hemispheres of immunocompromised mice, fractionated irradiated (6 MV photons) with 5 × 0 or 5 × 2 Gy, and SDF-1, CXCR4, and BK protein expression by the tumor as well as glioblastoma brain infiltration was analyzed in dependence on BK channel targeting by systemic paxilline application concomitant to IR. As a result, IR stimulated SDF-1 signaling and induced migration of glioblastoma cells in vitro and in vivo. Importantly, paxilline blocked IR-induced migration in vivo. Collectively, our data demonstrate that fractionated IR of glioblastoma stimulates and BK K+ channel targeting mitigates migration and brain infiltration of glioblastoma cells in vivo. This suggests that BK channel targeting might represent a novel approach to overcome radiation-induced spreading of malignant brain tumors during radiotherapy. PMID:26893360

  2. Mitigation and Treatment of Radiation-Induced Thoracic Injury With a Cyclooxygenase-2 Inhibitor, Celecoxib

    SciTech Connect

    Hunter, Nancy R.; Valdecanas, David; Liao Zhongxing; Milas, Luka; Thames, Howard D.; Mason, Kathy A.

    2013-02-01

    Purpose: To test whether a cyclooxygenase-2 inhibitor (celecoxib) could reduce mortality resulting from radiation-induced pneumonitis. Methods and Materials: Celecoxib was given to mice twice daily for 40 consecutive days starting on the day of local thoracic irradiation (LTI) or 40 or 80 days later. C3Hf/KamLaw mice were observed for morbidity, and time to death was determined. Results were analyzed using the Cox proportional hazards model. Results: Timing of celecoxib relative to LTI determined efficacy. A significant reduction in time to death was achieved only when celecoxib was started 80 days after LTI, corresponding to the time when pneumonitis is expressed. For these mice the reduction in mortality was quantified as a hazard ratio for mortality of treated vs untreated of 0.36 (95% confidence interval [CI] 0.24-0.53), thus significantly less than 1.0. Correspondingly, the median lethal dose for treated mice (12.9 Gy; 95% CI 12.55-13.25 Gy) was significantly (P=.026) higher than for untreated mice (12.4 Gy; 95% CI 12.2-12.65 Gy). Conclusions: Celecoxib significantly reduced lung toxicity when administered months after LTI when the deleterious effects of radiation were expressed. The schedule-dependent reduction in fatal pneumonitis suggests that celecoxib could be clinically useful by reintroduction of treatment months after completion of radiation therapy. These findings may be important for designing clinical trials using cyclooxygenase-2 inhibitors to treat radiation-induced lung toxicity as a complement to concurrent radiation therapy of lung cancers.

  3. Radiation-induced functional connectivity alterations in nasopharyngeal carcinoma patients with radiotherapy.

    PubMed

    Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun

    2016-07-01

    The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale.The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores.Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA.The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment. PMID:27442663

  4. The Role of Platelet Factor 4 in Radiation-Induced Thrombocytopenia

    SciTech Connect

    Lambert, Michele P.; Xiao Liqing; Nguyen, Yvonne; Kowalska, M. Anna; Poncz, Mortimer

    2011-08-01

    Purpose: Factors affecting the severity of radiation-induced thrombocytopenia (RIT) are not well described. We address whether platelet factor 4 (PF4; a negative paracrine for megakaryopoiesis) affects platelet recovery postradiation. Methods and Materials: Using conditioned media from irradiated bone marrow (BM) cells from transgenic mice overexpressing human (h) PF4 (hPF4+), megakaryocyte colony formation was assessed in the presence of this conditioned media and PF4 blocking agents. In a model of radiation-induced thrombocytopenia, irradiated mice with varying PF4 expression levels were treated with anti-hPF4 and/or thrombopoietin (TPO), and platelet count recovery and survival were examined. Results: Conditioned media from irradiated BM from hPF4+ mice inhibited megakaryocyte colony formation, suggesting that PF4 is a negative paracrine released in RIT. Blocking with an anti-hPF4 antibody restored colony formation of BM grown in the presence of hPF4+ irradiated media, as did antibodies that block the megakaryocyte receptor for PF4, low-density lipoprotein receptor-related protein 1 (LRP1). Irradiated PF4 knockout mice had higher nadir platelet counts than irradiated hPF4+/knockout litter mates (651 vs. 328 x 106/mcL, p = 0.02) and recovered earlier (15 days vs. 22 days, respectively, p <0.02). When irradiated hPF4+ mice were treated with anti-hPF4 antibody and/or TPO, they showed less severe thrombocytopenia than untreated mice, with improved survival and time to platelet recovery, but no additive effect was seen. Conclusions: Our studies show that in RIT, damaged megakaryocytes release PF4 locally, inhibiting platelet recovery. Blocking PF4 enhances recovery while released PF4 from megakaryocytes limits TPO efficacy, potentially because of increased release of PF4 stimulated by TPO. The clinical value of blocking this negative paracrine pathway post-RIT remains to be determined.

  5. 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

  6. Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse

    PubMed Central

    Kondo, Hisataka; Yumoto, Kenji; Alwood, Joshua S.; Mojarrab, Rose; Wang, Angela; Almeida, Eduardo A. C.; Searby, Nancy D.; Limoli, Charles L.

    2010-01-01

    Exposure of astronauts in space to radiation during weightlessness may contribute to subsequent bone loss. Gamma irradiation of postpubertal mice rapidly increases the number of bone-resorbing osteoclasts and causes bone loss in cancellous tissue; similar changes occur in skeletal diseases associated with oxidative stress. Therefore, we hypothesized that increased oxidative stress mediates radiation-induced bone loss and that musculoskeletal disuse changes the sensitivity of cancellous tissue to radiation exposure. Musculoskeletal disuse by hindlimb unloading (1 or 2 wk) or total body gamma irradiation (1 or 2 Gy of 137Cs) of 4-mo-old, male C57BL/6 mice each decreased cancellous bone volume fraction in the proximal tibiae and lumbar vertebrae. The extent of radiation-induced acute cancellous bone loss in tibiae and lumbar vertebrae was similar in normally loaded and hindlimb-unloaded mice. Similarly, osteoclast surface in the tibiae increased 46% as a result of irradiation, 47% as a result of hindlimb unloading, and 64% as a result of irradiation + hindlimb unloading compared with normally loaded mice. Irradiation, but not hindlimb unloading, reduced viability and increased apoptosis of marrow cells and caused oxidative damage to lipids within mineralized tissue. Irradiation also stimulated generation of reactive oxygen species in marrow cells. Furthermore, injection of α-lipoic acid, an antioxidant, mitigated the acute bone loss caused by irradiation. Together, these results showed that disuse and gamma irradiation, alone or in combination, caused a similar degree of acute cancellous bone loss and shared a common cellular mechanism of increased bone resorption. Furthermore, irradiation, but not disuse, may increase the number of osteoclasts and the extent of acute bone loss via increased reactive oxygen species production and ensuing oxidative damage, implying different molecular mechanisms. The finding that α-lipoic acid protected cancellous tissue from the

  7. Using Drosophila Larval Imaginal Discs to Study Low-Dose Radiation-Induced Cell Cycle Arrest

    PubMed Central

    Yan, Shian-Jang; Li, Willis X.

    2012-01-01

    Under genotoxic stress, activation of cell cycle checkpoint responses leads to cell cycle arrest, which allows cells to repair DNA damage before continuing to cycle. Drosophila larval epithelial sacs, called imaginal discs, are an excellent in vivo model system for studying radiation-induced cell cycle arrest. Larval imaginal discs go into cell cycle arrest after being subjected to low-dose irradiation, are subject to easy genetic manipulation, are not crucial for survival of the organism, and can be dissected easily for further molecular or cellular analysis. In this chapter, we describe methods for assessing low-dose irradiation-induced cell cycle arrest. Mitotic cells are identified by immunofluorescence staining for the mitotic marker phosphorylated histone H3 (phospho-histone H3 or pH3). When wandering third-instar control larvae, without transgene expression, are exposed to 500 rads of X-ray or γ-ray irradiation, the number of pH3-positive cells in wing imaginal discs is reduced from hundreds before irradiation to approximately 30 after irradiation, with an equal distribution between the anterior and posterior compartments (Yan et al., 2011, FASEB J). Using the GAL4/UAS system, RNAi, cDNA, or microRNA sponge transgenes can be expressed in the posterior compartment of the wing disc using drivers such as engrailed (en)-Gal4, while the anterior compartment serves as an internal control. This approach makes it possible to do genome-wide genetic screening for molecules involved in radiation-induced cell cycle arrest. PMID:21870287

  8. Proximity Within Interphase Chromosome Contributes to the Breakpoint Distribution in Radiation-Induced Intrachromosomal Exchanges

    NASA Technical Reports Server (NTRS)

    Zhang, Ye; Uhlemeyer, Jimmy; Hada, Megumi; Asaithamby, A.; Chen, David J.; Wu, Honglu

    2015-01-01

    Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome3 in human mammary epithelial cells after exposures to either low-or high-LET radiation. In particular, breaks in certain regions of the chromosome tended to rejoin with each other to form an intrachromosome exchange event. This study tests the hypothesis that proximity within a single chromosome in interphase cell nuclei contributes to the distribution of radiation-induced chromosome breaks. Chromosome 3 in G1 human mammary epithelial cells was hybridized with the multicolor banding in situ hybridization (mBAND) probes that distinguish the chromosome in six differently colored regions, and the location of these regions was measured with a laser confocal microscope. Results of the study indicated that, on a multi-mega base pair scale of the DNA, the arrangement of chromatin was non-random. Both telomere regions tended to be located towards the exterior of the chromosome domain, whereas the centromere region towards the interior. In addition, the interior of the chromosome domain was preferentially occupied by the p-arm of the chromatin, which is consistent with our previous finding of intrachromosome exchanges involving breaks on the p-arm and in the centromere region of chromosome3. Other factors, such as the fragile sites in the 3p21 band and gene regulation, may also contribute to the breakpoint distribution in radiation-induced chromosome aberrations. Further investigations suggest that the 3D chromosome folding is cell type and culture condition dependent.

  9. Radiation-induced reactions of COH 2 gas mixtures over various solid catalysts

    NASA Astrophysics Data System (ADS)

    Nagai, S.; Arai, H.; Hatada, M.

    Studies have been carried out of radiation-induced reactions of COH 2 gas mixtures in the presence of various solid catalysts in order to find possibilities of synthesizing organic raw materials from COH 2 by radiation for the future. The solid catalysts studied include Fischer-Tropsch catalyst (FeCu supported by diatomaceous earth), titania(TiO 2), and silica gel. Analysis of the reaction products over Fischer-Tropsch catalyst or semiconductors such as TiO 2 and ZnOCr 2O 3 reveals that these solid catalysts do not sensitize the radiation chemical reaction of COH 2 but show the secondary effects on the reaction so as to induce the hydrogenation of olefins produced by the catalytic reaction and of aldehydes produced in gas phase by radiation. On the other hand, silica gel and other insulators such as alumina have been found to exhibit high catalytic activity in the formation of hydrocarbons from COH 2 under electron beam irradiation at 300°C. It has been shown experimentally that secondary reactions between H 2 and carbonaceous solid produced from CO make a substantial contribution to the formation of hydrocarbons from COH 2 over silica gel. In an attempt to find the role of silica gel in the reaction to produce hydrocarbons, radiation-induced reactions have been studied of H 2 with the carbonaceous solid that had been produced by irradiation of CO in the absence of solid catalyst, over TiO 2, or over silica gel. The results indicate that silica gel not only enhances the yields of CO 2 and carbonaceous solid from CO but also promotes hydrogenation reactions of the carbonaceous solid under electron beam irradiation.

  10. Recombinant human neuregulin-1β is protective against radiation-induced myocardial cell injury.

    PubMed

    Zhou, Qiang; Hu, Wenbing; Fei, Xinxiong; Huang, Xuqun; Chen, Xi; Zhao, Deqing; Huang, Jun; Jiang, Lan; Wang, Gangsheng

    2016-07-01

    The aim of the present study was to investigate the role of recombinant human neuregulin-1β (rhNRG-1β) in the repair of the radiation-induced damage of myocardial cells and the underlying mechanism. Rats were divided into the radiotherapy alone group, the rhNRG-1β group (radiotherapy with rhNRG‑1β treatment) and the Herceptin group (radiotherapy with Herceptin treatment), and their myocardial cells were analyzed. The morphology of the myocardial cells was observed under an optical microscope, and the expression of γ‑H2AX and p53 was analyzed using immunohistochemistry and western blot analysis. Damage to the myocardial cells was identified in the three groups following radiation treatment, which was identified by cell swelling and altered morphology. The integrated optical density values of γ‑H2AX in the radiotherapy alone, rhNRG‑1β and Herceptin groups were 50.96±5.548, 27.63±10.61 and 76.12±2.084, respectively. The OD of the radiotherapy alone group was significantly higher than that of the rhNRG‑1β treated group (P<0.0001), and the value of the Herceptin group was significantly higher than that of the radiotherapy alone group (P<0.0001). The p53 level in the rhNRG‑1β group was less than that of the radiotherapy alone group (P<0.001), and was higher in the Herceptin group compared with the radiotherapy alone group (P<0.0001). Thus, rhNRG‑1β can ameliorate radiotherapy-induced myocardial cell injury, predominantly by enhancing myocardial cell DNA repair, inhibiting cell apoptosis and improving myocardial function. The results of this study in myocardial cells suggest that patients with thoracic cancer may benefit from treatment with rhNRG‑1β for the repair of the radiation-induced damage of myocardial cells. PMID:27150576

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

    SciTech Connect

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

    2009-09-15

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

  12. Radiation-Inducible Caspase-8 Gene Therapy for Malignant Brain Tumors

    SciTech Connect

    Tsurushima, Hideo Yuan Xuan; Dillehay, Larry E.; Leong, Kam W.

    2008-06-01

    Purpose: Patients with malignant gliomas have a poor prognosis. To explore a novel and more effective approach for the treatment of patients with malignant gliomas, we designed a strategy that combines caspase-8 (CSP8) gene therapy and radiation treatment (RT). In addition, the specificity of the combined therapy was investigated to decrease the unpleasant effects experienced by the surrounding normal tissue. Methods and Materials: We constructed the plasmid pEGR-green fluorescence protein that included the radiation-inducible early growth response gene-1 (Egr-1) promoter and evaluated its characteristics. The pEGR-CSP8 was constructed and included the Egr-1 promoter and CSP8 complementary DNA. Assays that evaluated the apoptosis inducibility and cytotoxicity caused by CSP8 gene therapy combined with RT were performed using U251 and U87 glioma cells. The pEGR-CSP8 was transfected into the subcutaneous U251 glioma cells of nude mice by means of in vivo electroporation. The in vivo effects of CSP8 gene therapy combined with RT were evaluated. Results: The Egr-1 promoter yielded a better response with fractionated RT than with single-dose RT. In the assay of apoptosis inducibility and cytotoxicity, pEGR-CSP8 showed response for RT. The pEGR-CSP8 combined with RT is capable of inducing cell death effectively. In mice treated with pEGR-CSP8 and RT, apoptotic cells were detected in pathologic sections, and a significant difference was observed in tumor volumes. Conclusions: Our results indicate that radiation-inducible gene therapy may have great potential because this can be spatially or temporally controlled by exogenous RT and is safe and specific.

  13. Honey and Radiation-Induced Stomatitis in Patients With Head and Neck Cancer

    PubMed Central

    Bahramnezhad, Fatemeh; Dehghan Nayeri, Nahid; Bassampour, Shiva Sadat; Khajeh, Mahboobeh; Asgari, Parvaneh

    2015-01-01

    Background: Stomatitis is a common oral complication which affects 100% of patients undergoing head and neck radiotherapy. Acute stomatitis might cause failure and delay radiotherapy. Attention to mouth hygiene, particularly using mouthwash, has a fundamental importance for these patients. Objectives: The current study came to addresses the effects of pure natural honey on radiation-induced stomatitis in patients with a variety of head and neck cancers. Patients and Methods: The present single-blinded nonrandomized controlled trial was conducted on 105 patients undergoing radiotherapy due to head and neck cancer at the radiation unit of Shafa hospital in Kerman, Iran, from October 2012 to March 2012. The research groups were selected by writing the names of the protocols (the mouthwashes of chamomile, honey and the common caring protocol at ward which uses water) on three cubes. The first extracted cube was related to the chamomile mouthwash (Matrica), the second to the honey mouthwash and the last cube to the water mouthwash. The first experimental group (n = 35) gurgled a solution containing 20 mL diluted honey, the second group gurgled a solution containing German chamomile, and the 35 patients in the control group were advised to gurgle 20 mL water (the ward routine). Results: The results showed that severe stomatitis in groups of honey, chamomile and control was 0, 5.7%, and 17.6%, respectively. On the 14th day, it was 0, 0, and 17.6%, respectively. There were significant differences between the three groups regarding the severity of stomatitis in the 14th day (P < 0.001). Conclusions: The application of natural honey is effective in managing and preventing radiation-induced stomatitis in patients with head and neck cancers. PMID:26568850

  14. Mitigation of radiation-induced lung injury by Genistein and EUK-207

    PubMed Central

    Mahmood, J; Jelveh, S; Calveley, V; Zaidi, A; Doctrow, SR; Hill, RP

    2011-01-01

    Purpose We examined the effects of genistein and/or Eukarion (EUK)-207 on radiation-induced lung damage and investigated whether treatment for 0–14 weeks (wks) post-irradiation (PI) would mitigate late lung injury. Materials and Methods The lungs of female Sprague-Dawley (SD) rats were irradiated with 10 Gy. EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (PI) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1β, IL-6, Tumor necrotic factor (TNF)-α and Transforming growth factor (TGF)-β1, and macrophage activation were analysed by immunohistochemistry. Results Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4–14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines. Conclusion Genistein, and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI. PMID:21675818

  15. 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

  16. Polaprezinc reduces the severity of radiation-induced mucositis in head and neck cancer patients

    PubMed Central

    DOI, HIROSHI; FUJIWARA, MASAYUKI; SUZUKI, HITOMI; NIWA, YASUE; NAKAYAMA, MASAHIRO; SHIKATA, TOSHIYUKI; ODAWARA, SOICHI; TAKADA, YASUHIRO; KIMURA, TAKESHI; KAMIKONYA, NORIHIKO; HIROTA, SHOZO

    2015-01-01

    Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant properties. The aim of the present study was to assess the feasibility and efficacy of administering PZ for radiation-induced mucositis in head and neck cancer patients. Patients with newly diagnosed head and neck cancer were enrolled in this prospective study. PZ was prepared as an oral rinse. The PZ oral rinse was used four times per day during the course of radiotherapy. Sequential changes in radiation mucositis were assessed during and after radiotherapy according to the Common Terminology Criteria for Adverse Events, version 3.0. Furthermore, a retrospective comparison analysis was performed to assess the efficacy of PZ for radiation-induced mucositis. A total of 32 patients were enrolled in the prospective study of the PZ oral rinse. Radiotherapy was performed up to a total dose of 60–66 Gy using a conventional schedule combined with chemotherapy. Of the 32 patients, 30 (93.8%) reported no complaints due to the PZ oral rinse. In addition, PZ was not associated with severe adverse effects. Among the patients who received PZ, grade 3 mucositis was observed in 29.0% based on the mucosal findings and in 39.3% based on the symptoms. In the patients who did not receive PZ, the incidence of grade 3 mucositis was 40.0% based on the mucosal findings and 60.7% based on the symptoms. Moreover, PZ promoted the recovery from mucositis caused by chemoradiotherapy and was not associated with reduced tumor response to radiotherapy. Therefore, the PZ oral rinse was well tolerated and proved to be efficient for the treatment of radiotherapy-induced oral mucositis. PMID:25798271

  17. Treatment of radiation-induced acute intestinal injury with bone marrow-derived mesenchymal stem cells

    PubMed Central

    ZHENG, KAI; WU, WEIZHEN; YANG, SHUNLIANG; HUANG, LIANGHU; CHEN, JIN; GONG, CHUNGUI; FU, ZHICHAO; LIN, RUOFEI; TAN, JIANMING

    2016-01-01

    The aim of the present study was to investigate the ability of bone marrow-derived mesenchymal stem cells (BMSCs) to repair radiation-induced acute intestinal injury, and to elucidate the underlying repair mechanism. Male Sprague-Dawley rats were subjected to whole abdominal irradiation using a single medical linear accelerator (12 Gy) and randomly assigned to two groups. Rats in the BMSC-treated group were injected with 1 ml BMSC suspension (2×106 cells/ml) via the tail vein, while the control group rats were injected with normal saline. BMSCs were identified by detecting the expression of CD29, CD90, CD34 and CD45 using flow cytometry. The expression of the cytokines stromal cell-derived factor 1 (SDF-1), prostaglandin E2 (PGE2) and interleukin (IL)-2 was detected using immunohistochemical techniques. Plasma citrulline concentrations were evaluated using an ELISA kit. Rat general conditions, including body weight, and changes in cellular morphology were also recorded. The results suggested that BMSCs exerted a protective effect on radiation-induced acute intestinal injury in rats. The histological damage was rapidly repaired in the BMSC-treated group. In addition, the BMSC-treated group showed significantly reduced radiation injury scores (P<0.01), mildly reduced body weight and plasma citrulline levels, significantly more rapid recovery (P<0.01), significantly reduced expression of the cytokines PGE2 and IL-2 (P<0.05) and significantly increased SDF-1 expression (P<0.01) compared with the control group. In summary, the present results indicate that BMSCs are able to effectively reduce inflammation and promote repair of the structure and function of intestinal tissues damaged by radiation exposure, suggesting that they may provide a promising therapeutic agent. PMID:27284330

  18. 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

  19. Persistence of Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts

    NASA Technical Reports Server (NTRS)

    George, Kerry; Cucinotta, Francis A.

    2008-01-01

    Cytogenetic damage in astronaut's peripheral blood lymphocytes is a useful in vivo marker of space radiation induced damage. Moreover, if radiation induced chromosome translocations persist in peripheral blood lymphocytes for many years, as has been assumed, they could potentially be used to measure retrospective doses or prolonged low dose rate exposures. However, as more data becomes available, evidence suggests that the yield of translocations may decline with time after exposure, at least in the case of space radiation exposures. We present our latest follow-up measurements of chromosome aberrations in astronauts blood lymphocytes assessed by FISH painting and collected a various times beginning directly after return from space to several years after flight. For most individuals the analysis of individual time-courses for translocations revealed a temporal decline of yields with different half-lives. Since the level of stable aberrations depends on the interplay between natural loss of circulating T-lymphocytes and replenishment from the stem or progenitor cells, the differences in the rates of decay could be explained by inter-individual variation in lymphocyte turn over. Biodosimetry estimates derived from cytogenetic analysis of samples collected a few days after return to earth lie within the range expected from physical dosimetry. However, a temporal decline in yields may indicate complications with the use of stable aberrations for retrospective dose reconstruction, and the differences in the decay time may reflect individual variability in risk from space radiation exposure. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from one crewmember who has participated in two separate long-duration space missions and has been followed up for over 10 years provides limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

  20. Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction

    PubMed Central

    Zhao, Sanhu; Yang, Yanyong; Liu, Wen; Xuan, Zhiqiang; Wu, Shouming; Yu, Shunfei; Mei, Ke; Huang, Yijuan; Zhang, Pei; Cai, Jianming; Ni, Jin; Zhao, Yaoxian

    2014-01-01

    Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. This study was undertaken to evaluate the radioprotective effects of hydrogen on immune system in mice. H2 was dissolved in physiological saline using an apparatus produced by our department. Spleen index and histological analysis were used to evaluate the splenic structural damage. Spleen superoxide dismutase, GSH, MDA were measured to appraise the antioxidant capacity and a DCF assay for the measurement of radical oxygen species. Cell apoptosis was evaluated by an Annexin V-FITC and propidium iodide staining method as well as the apoptotic proteins such as Bcl-2, Bax, caspase-3 and c-caspase-3. CD4+ and CD8+ T cells subtypes were detected by flow cytometry with FITC-labelled antimouse CD4 and PE antimouse CD8 staining. Real-time PCR was utilized to determine the CD4+ T cell subtypes and related cytokines. Our study demonstrated that pre-treatment with H2 could increase the spleen index and attenuate the radiation damage on splenic structure. Radical oxygen species level was also reduced by H2 treatment. H2 also inhibited radiation-induced apoptosis in splenocytes and down-regulated pro-apoptotic proteins in living mice. Radiation-induced imbalance of T cells was attenuated by H2. Finally, we found that H2 could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H2 as an effective radioprotective agent on immune system by scavenging reactive oxygen species. PMID:24618260

  1. Using Drosophila larval imaginal discs to study low-dose radiation-induced cell cycle arrest.

    PubMed

    Yan, Shian-Jang; Li, Willis X

    2011-01-01

    Under genotoxic stress, activation of cell cycle checkpoint responses leads to cell cycle arrest, which allows cells to repair DNA damage before continuing to cycle. Drosophila larval epithelial sacs, called imaginal discs, are an excellent in vivo model system for studying radiation-induced cell cycle arrest. Larval imaginal discs go into cell cycle arrest after being subjected to low-dose irradiation, are subject to easy genetic manipulation, are not crucial for survival of the organism, and can be dissected easily for further molecular or cellular analysis. In this chapter, we describe methods for assessing low-dose irradiation-induced cell cycle arrest. Mitotic cells are identified by immunofluorescence staining for the mitotic marker phosphorylated histone H3 (phospho-histone H3 or pH3). When wandering third-instar control larvae, without transgene expression, are exposed to 500 rads of X-ray or γ-ray irradiation, the number of pH3-positive cells in wing imaginal discs is reduced from hundreds before irradiation to approximately 30 after irradiation, with an equal distribution between the anterior and posterior compartments (Yan et al., 2011, FASEB J). Using the GAL4/UAS system, RNAi, cDNA, or microRNA sponge transgenes can be expressed in the posterior compartment of the wing disc using drivers such as engrailed (en)-Gal4, while the anterior compartment serves as an internal control. This approach makes it possible to do genome-wide genetic screening for molecules involved in radiation-induced cell cycle arrest. PMID:21870287

  2. Whole Brain Radiation-Induced Cognitive Impairment: Pathophysiological Mechanisms and Therapeutic Targets

    PubMed Central

    Lee, Yong Woo; Cho, Hyung Joon; Lee, Won Hee; Sonntag, William E.

    2012-01-01

    Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tu-mor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cel-lular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the iden-tification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defin-ing a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy. PMID:24009822

  3. Radiation-induced diamond crystallization: Origin of carbonados and its implications on meteorite nano-diamonds

    USGS Publications Warehouse

    Ozima, M.; Tatsumoto, M.

    1997-01-01

    Ten carbonados from Central Africa were studied for U-Th-Pb systematics. To extract U, Th, and Pb from the samples, we developed a cold combustion technique wherein diamond was burnt in liquid oxygen. The technique gave low blanks; 25-50 pg for Pb, 3 pg for U, and 5 pg for Th. After very thorough acid treatments of the carbonados with hot HNO3, HF, and HCl over one week, most of U, Th, and Pb were removed from the samples. Lead in the acid-leached diamonds was highly radiogenic (206Pb/204Pb up to 470). However, the amounts of U and Th in the acid-leached diamonds are too low to account for the radiogenic Pb even if we assume 4.5 Ga for the age of the diamonds. Therefore, we conclude that the radiogenic Pb was implanted into the diamonds from surroundings by means of recoil energy of radioactive decays of U and Th. From the radiogenic lead isotopic composition, we estimate a minimum age of 2.6 Ga and a maximum age of 3.8 Ga for the formation of the carbonados. The above findings of the implantation of recoiled radiogenic Pb into carbonados is consistent with the process of radiation-induced crystallization which was proposed for carbonado by Kaminsky (1987). We show from some theoretical considerations that when highly energetic particles, such as those emitted from radioactive decay of U and Th, interact with carbonaceous materials, they give rise to cascades of atomic disturbance (over regions of about a few nanometer), and the disturbed atoms are likely to recrystallize to form micro-diamonds because of increasing surface energy due to small size. The radiation-induced diamond formation mechanism may be relevant to the origin of nano-diamonds in primitive meteorites. Copyright ?? 1997 Elsevier Science Ltd.

  4. BK K+ channel blockade inhibits radiation-induced migration/brain infiltration of glioblastoma cells.

    PubMed

    Edalat, Lena; Stegen, Benjamin; Klumpp, Lukas; Haehl, Erik; Schilbach, Karin; Lukowski, Robert; Kühnle, Matthias; Bernhardt, Günther; Buschauer, Armin; Zips, Daniel; Ruth, Peter; Huber, Stephan M

    2016-03-22

    Infiltration of the brain by glioblastoma cells reportedly requires Ca2+ signals and BK K+ channels that program and drive glioblastoma cell migration, respectively. Ionizing radiation (IR) has been shown to induce expression of the chemokine SDF-1, to alter the Ca2+ signaling, and to stimulate cell migration of glioblastoma cells. Here, we quantified fractionated IR-induced migration/brain infiltration of human glioblastoma cells in vitro and in an orthotopic mouse model and analyzed the role of SDF-1/CXCR4 signaling and BK channels. To this end, the radiation-induced migratory phenotypes of human T98G and far-red fluorescent U-87MG-Katushka glioblastoma cells were characterized by mRNA and protein expression, fura-2 Ca2+ imaging, BK patch-clamp recording and transfilter migration assay. In addition, U-87MG-Katushka cells were grown to solid glioblastomas in the right hemispheres of immunocompromised mice, fractionated irradiated (6 MV photons) with 5 × 0 or 5 × 2 Gy, and SDF-1, CXCR4, and BK protein expression by the tumor as well as glioblastoma brain infiltration was analyzed in dependence on BK channel targeting by systemic paxilline application concomitant to IR. As a result, IR stimulated SDF-1 signaling and induced migration of glioblastoma cells in vitro and in vivo. Importantly, paxilline blocked IR-induced migration in vivo. Collectively, our data demonstrate that fractionated IR of glioblastoma stimulates and BK K+ channel targeting mitigates migration and brain infiltration of glioblastoma cells in vivo. This suggests that BK channel targeting might represent a novel approach to overcome radiation-induced spreading of malignant brain tumors during radiotherapy. PMID:26893360

  5. Radiation-Induced Segregation and Phase Stability in Candidate Alloys for the Advanced Burner Reactor

    SciTech Connect

    Gary S. Was; Brian D. Wirth

    2011-05-29

    Major accomplishments of this project were the following: 1) Radiation induced depletion of Cr occurs in alloy D9, in agreement with that observed in austenitic alloys. 2) In F-M alloys, Cr enriches at PAG grain boundaries at low dose (<7 dpa) and at intermediate temperature (400°C) and the magnitude of the enrichment decreases with temperature. 3) Cr enrichment decreases with dose, remaining enriched in alloy T91 up to 10 dpa, but changing to depletion above 3 dpa in HT9 and HCM12A. 4) Cr has a higher diffusivity than Fe by a vacancy mechanism and the corresponding atomic flux of Cr is larger than Fe in the opposite direction to the vacancy flux. 5) Cr concentration at grain boundaries decreases as a result of vacancy transport during electron or proton irradiation, consistent with Inverse Kirkendall models. 6) Inclusion of other point defect sinks into the KLMC simulation of vacancy-mediated diffusion only influences the results in the low temperature, recombination dominated regime, but does not change the conclusion that Cr depletes as a result of vacancy transport to the sink. 7) Cr segregation behavior is independent of Frenkel pair versus cascade production, as simulated for electron versus proton irradiation conditions, for the temperatures investigated. 8) The amount of Cr depletion at a simulated planar boundary with vacancy-mediated diffusion reaches an apparent saturation value by about 1 dpa, with the precise saturation concentration dependent on the ratio of Cr to Fe diffusivity. 9) Cr diffuses faster than Fe by an interstitial transport mechanism, and the corresponding atomic flux of Cr is much larger than Fe in the same direction as the interstitial flux. 10) Observed experimental and computational results show that the radiation induced segregation behavior of Cr is consistent with an Inverse Kirkendall mechanism.

  6. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway.

    PubMed

    Delanian, Sylvie; Lefaix, Jean-Louis

    2004-11-01

    The radiation-induced fibroatrophic process (RIF) constitutes a late, local and unavoidable sequela to high-dose radiotherapy, traditionally considered irreversible. Today, this process is partly reversible, thanks to recent progress in understanding the physiopathology of the lesions it causes and the results of recent clinical trials using antioxidant therapy. This review includes a synthetic description of the static and dynamic features of the RIF process, as reflected by its clinical, instrumental and histopathological characteristics, and by its cellular and molecular regulation. Schematically, three successive clinical and histopathological phases can be distinguished: a pre-fibrotic aspecific inflammatory phase, a constitutive fibrotic cellular phase, and a matrix densification and remodelling phase, possibly ending in terminal tissular necrosis. The respective roles of the chief actors in the RIF process are defined, as well as their development with time. A fibroblastic stromal hypothesis is suggested revolving around a 'gravitational effect' exerted by the couple ROS (reactive oxygen species)--fibroblasts, and partly mediated by TGF-beta1. A variety of strategies have been tested for the management of RIF. In the light of the mechanisms described, a curative procedure has been proposed via the antioxidant pathway. In particular, it was showed that superoxide dismutase and combined pentoxifylline-tocopherol treatment enables the process of established radiation-induced fibroatrophy to be greatly reduced or even reversed, both in clinical practice and animal experiments. The efficacy of combined pentoxifylline-tocopherol treatment in superficial RIF was confirmed in a randomised clinical trial, and then in successful phase II trials especially in uterine fibroatrophy and osteoradionecrosis. It is of critical importance to evaluate these new management approaches in larger clinical trials and to improve the recording of results for better outcome analysis

  7. Dragon's blood and its extracts attenuate radiation-induced oxidative stress in mice.

    PubMed

    Ran, Yuanyuan; Wang, Ran; Gao, Qian; Jia, Qiutian; Hasan, Murtaza; Awan, Muhammad Umer Farooq; Tang, Bo; Zhou, Rui; Dong, Yiming; Wang, Xiao; Li, Qiang; Ma, Hong; Deng, Yulin; Qing, Hong

    2014-07-01

    Dragon's blood (DB) possesses great medicinal values due to the presence of several phenolic compounds. This study was designed to investigate the effects of DB and its extracts (DBEs) on oxidative stress in mice exposed to whole body (60)Co-γ irradiation (4 Gy). DB and DBEs were intragastrically administered to mice for 5 d prior to radiation. The antioxidant activities, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels in liver and spleen were measured using kits. Furthermore, DB and DBE effects were determined by organ indices and histology of liver and spleen. Our results indicated that the DB and DBE-treated groups showed a significant decrease (P < 0.05) in levels of MDA in liver and spleen compared with the irradiation-only group. Moreover, the activity of SOD, CAT and the level of GSH in liver and spleen tissue were enhanced significantly (P < 0.05) in the DB and DBE groups. DB and DBE also had a significant effect on the recovery of thymus indices. The histological observations of groups having treatment with DB and DBE indicated significant reduction in the radiation-induced damage to the liver and spleen, together with improvement in the morphology of the liver and spleen. These results suggest that DB and DBE treatment prevents radiation-induced oxidative stress injury and restores antioxidant status and histopathological changes in the liver and spleen, but there is need for further study to explore the precise molecular mechanism and strategy for optimal practical application of DB and DBE. PMID:24634306

  8. Potential prevention: Aloe vera mouthwash may reduce radiation-induced oral mucositis in head and neck cancer patients.

    PubMed

    Ahmadi, Amirhossein

    2012-08-01

    In recent years, more head and neck cancer patients have been treated with radiotherapy. Radiation-induced mucositis is a common and dose limiting toxicity of radiotherapy among patients with head and neck cancers. Patients undergoing radiation therapy for head and neck cancer are also at increased risk of developing oral candidiasis. A number of new agents applied locally or systemically to prevent or treat radiation-induced mucositis have been investigated, but there is no widely accepted prophylactic or effective treatment for mucositis. Topical Aloe vera is widely used for mild sunburn, frostbites, and scalding burns. Studies have reported the beneficial effects of Aloe gel for wound healing, mucous membrane protection, and treatment of oral ulcers, in addition to antiinflammatory, immunomudulation, antifungal, scavenging free radicals, increasing collagen formation and inhibiting collagenase. Herein the author postulates that oral Aloe vera mouthwash may not only prevent radiation-induced mucositis by its wound healing and antiinflammatory mechanism, but also may reduce oral candidiasis of patients undergoing head and neck radiotherapy due to its antifungal and immunomodulatory properties. Hence, Aloe vera mouthwash may provide an alternative agent for treating radiation-induced oral mucositis and candidiasis in patients with head and neck cancers. PMID:22855041

  9. Contribution of endogenous and exogenous damage to the total radiation-induced damage in the bacterial spore

    SciTech Connect

    Jacobs, G.P.; Samuni, A.; Czapski, G.

    1980-01-01

    Radical scavengers such as polyethylene glycol 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous damage to the total radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous.

  10. Oxidative lipidomics of γ-radiation-induced lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation.

    PubMed

    Tyurina, Yulia Y; Tyurin, Vladimir A; Kapralova, Valentyna I; Wasserloos, Karla; Mosher, Mackenzie; Epperly, Michael W; Greenberger, Joel S; Pitt, Bruce R; Kagan, Valerian E

    2011-05-01

    Oxidative damage plays a significant role in the pathogenesis of γ-radiation-induced lung injury. Endothelium is a preferred target for early radiation-induced damage and apoptosis. Given the newly discovered role of oxidized phospholipids in apoptotic signaling, we performed oxidative lipidomics analysis of phospholipids in irradiated mouse lungs and cultured mouse lung endothelial cells. C57BL/6NHsd female mice were subjected to total-body irradiation (10 Gy, 15 Gy) and euthanized 24 h thereafter. Mouse lung endothelial cells were analyzed 48 h after γ irradiation (15 Gy). We found that radiation-induced apoptosis in vivo and in vitro was accompanied by non-random oxidation of phospholipids. Cardiolipin and phosphatidylserine were the major oxidized phospholipids, while more abundant phospholipids (phosphatidylcholine, phosphatidylethanolamine) remained non-oxidized. Electrospray ionization mass spectrometry analysis revealed the formation of cardiolipin and phosphatidylserine oxygenated molecular species in the irradiated lung and cells. Analysis of fatty acids after hydrolysis of cardiolipin and phosphatidylserine by phospholipase A(2) revealed the presence of mono-hydroperoxy and/or mono-hydroxy/mono-epoxy, mono-hydroperoxy/mono-oxo molecular species of linoleic acid. We speculate that cyt c-driven oxidations of cardiolipin and phosphatidylserine associated with the execution of apoptosis in pulmonary endothelial cells are important contributors to endothelium dysfunction in γ-radiation-induced lung injury. PMID:21338246

  11. Oxidative Lipidomics of γ-Radiation-Induced Lung Injury: Mass Spectrometric Characterization of Cardiolipin and Phosphatidylserine Peroxidation

    PubMed Central

    Tyurina, Yulia Y.; Tyurin, Vladimir A.; Kapralova, Valentyna I.; Wasserloos, Karla; Mosher, Mackenzie; Epperly, Michael W.; Greenberger, Joel S.; Pitt, Bruce R.; Kagan, Valerian E.

    2011-01-01

    Oxidative damage plays a significant role in the pathogenesis of γ-radiation-induced lung injury. Endothelium is a preferred target for early radiation-induced damage and apoptosis. Given the newly discovered role of oxidized phospholipids in apoptotic signaling, we performed oxidative lipidomics analysis of phospholipids in irradiated mouse lungs and cultured mouse lung endothelial cells. C57BL/6NHsd female mice were subjected to total-body irradiation (10 Gy, 15 Gy) and euthanized 24 h thereafter. Mouse lung endothelial cells were analyzed 48 h after γ irradiation (15 Gy). We found that radiation-induced apoptosis in vivo and in vitro was accompanied by non-random oxidation of phospholipids. Cardiolipin and phosphatidylserine were the major oxidized phospholipids, while more abundant phospholipids (phosphatidylcholine, phosphatidylethanolamine) remained non-oxidized. Electrospray ionization mass spectrometry analysis revealed the formation of cardiolipin and phosphatidylserine oxygenated molecular species in the irradiated lung and cells. Analysis of fatty acids after hydrolysis of cardiolipin and phosphatidylserine by phospholipase A2 revealed the presence of mono-hydroperoxy and/or mono-hydroxy/mono-epoxy, mono-hydroperoxy/mono-oxo molecular species of linoleic acid. We speculate that cyt c-driven oxidations of cardiolipin and phosphatidylserine associated with the execution of apoptosis in pulmonary endothelial cells are important contributors to endothelium dysfunction in γ-radiation-induced lung injury. PMID:21338246

  12. RADIOFREQUENCY RADIATION-INDUCED CALCIUM-ION-EFFLUX ENHANCEMENT FROM HUMAN AND OTHER NEUROBLASTOMA CELLS IN CULTURE

    EPA Science Inventory

    In order to test the generality of radiofrequency-radiation-induced change in alteration 45Ca2+ efflux from avian and feline brain tissues, human neuroblastoma cells were exposed to electromagnetic radiation at 147 MHz, amplitude modulated (AM) at 16 Hz, at specific absorption ra...

  13. Overeducation and depressive symptoms: diminishing mental health returns to education.

    PubMed

    Bracke, Piet; Pattyn, Elise; von dem Knesebeck, Olaf

    2013-11-01

    In general, well-educated people enjoy better mental health than those with less education. As a result, some wonder whether there are limits to the mental health benefits of education. Inspired by the literature on the expansion of tertiary education, this article explores marginal mental health returns to education and studies the mental health status of overeducated people. To enhance the validity of the findings we use two indicators of educational attainment - years of education and ISCED97 categories - and two objective indicators of overeducation (the realised matches method and the job analyst method) in a sample of the working population of 25 European countries (unweighted sample N = 19,089). Depression is measured using an eight-item version of the CES-D scale. We find diminishing mental health returns to education. In addition, overeducated people report more depression symptoms. Both findings hold irrespective of the indicators used. The results must be interpreted in the light of the enduring expansion of education, as our findings show that the discussion of the relevance of the human capital perspective, and the diploma disease view on the relationship between education and modern society, is not obsolete. PMID:23909439

  14. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins

    PubMed Central

    Yao, Chunxiang; Behring, Jessica B.; Shao, Di; Sverdlov, Aaron L.; Whelan, Stephen A.; Elezaby, Aly; Yin, Xiaoyan; Siwik, Deborah A.; Seta, Francesca; Costello, Catherine E.; Cohen, Richard A.; Matsui, Reiko; Colucci, Wilson S.; McComb, Mark E.; Bachschmid, Markus M.

    2015-01-01

    Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2), react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat), an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a ‘Tandem Mass Tag’ (TMT) labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg) mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation. PMID:26642319

  15. Evidence for microRNA-31 dependent Bim-Bax interaction preceding mitochondrial Bax translocation during radiation-induced apoptosis.

    PubMed

    Kumar, Ashish; Ghosh, Soma; Chandna, Sudhir

    2015-01-01

    Downregulation of microRNA-31 has been linked with enhanced stress resistance, while its overexpression leads to cell death. In this study, we found mediatory role of microRNA-31 in γ-radiation-induced apoptosis in a model insect cell line Sf9 carrying well-conserved apoptotic machinery. Mature microRNA-31 is perfectly conserved amongst insects; hence we used biotinylated probes designed from Bombyx mori sequence for its successful detection in Sf9 cells. Target identification using Bombyx mori 3'UTRs predicted miR-31's potential role in Lepidopteran apoptosis, which prompted us to investigate alterations in its expression during radiation-induced cell death. We found significant overexpression of Sf-miR-31 following lethal dose (1,000Gy-3,000Gy) irradiation. Its mediatory role was finally confirmed as antisense-microRNA-31 could successfully inhibit radiation-induced cytochrome-c release, caspase-3 activation and apoptosis. While Bax/Bcl-2 expression remained unchanged, lethal radiation doses induced Bim overexpression and direct Bim-Bax interaction (co-immunoprecipitation) which is not yet unequivocally demonstrated during apoptosis. Quite important, these events were found to be dependent on radiation-induced miR-31 overexpression, as antisense-miR-31 inhibited both the responses and resulted in significant inhibition of cell death. Pro-apoptotic role of miR-31 was further confirmed when miR-31 mimic induced apoptosis involving similar Bim/Bax alterations. Therefore, our study reveals an important mediatory role of miR-31 in radiation-induced cell death. PMID:26514984

  16. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    SciTech Connect

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua; Guo, Renfeng; Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun; Zhu, Maoxiang

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  17. Silymarin Protects Epidermal Keratinocytes from Ultraviolet Radiation-Induced Apoptosis and DNA Damage by Nucleotide Excision Repair Mechanism

    PubMed Central

    Katiyar, Santosh K.; Mantena, Sudheer K.; Meeran, Syed M.

    2011-01-01

    Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK) with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells. PMID:21731736

  18. Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism.

    PubMed

    Katiyar, Santosh K; Mantena, Sudheer K; Meeran, Syed M

    2011-01-01

    Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK) with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells. PMID:21731736

  19. Radiation-induced refraction artifacts in the optical CT readout of polymer gel dosimeters

    SciTech Connect

    Campbell, Warren G.; Jirasek, Andrew; Wells, Derek M.

    2014-11-01

    Purpose: The objective of this work is to demonstrate imaging artifacts that can occur during the optical computed tomography (CT) scanning of polymer gel dosimeters due to radiation-induced refractive index (RI) changes in polyacrylamide gels. Methods: A 1 L cylindrical polyacrylamide gel dosimeter was irradiated with 3 × 3 cm{sup 2} square beams of 6 MV photons. A prototype fan-beam optical CT scanner was used to image the dosimeter. Investigative optical CT scans were performed to examine two types of rayline bending: (i) bending within the plane of the fan-beam and (ii) bending out the plane of the fan-beam. To address structured errors, an iterative Savitzky–Golay (ISG) filtering routine was designed to filter 2D projections in sinogram space. For comparison, 2D projections were alternatively filtered using an adaptive-mean (AM) filter. Results: In-plane rayline bending was most notably observed in optical CT projections where rays of the fan-beam confronted a sustained dose gradient that was perpendicular to their trajectory but within the fan-beam plane. These errors caused distinct streaking artifacts in image reconstructions due to the refraction of higher intensity rays toward more opaque regions of the dosimeter. Out-of-plane rayline bending was observed in slices of the dosimeter that featured dose gradients perpendicular to the plane of the fan-beam. These errors caused widespread, severe overestimations of dose in image reconstructions due to the higher-than-actual opacity that is perceived by the scanner when light is bent off of the detector array. The ISG filtering routine outperformed AM filtering for both in-plane and out-of-plane rayline errors caused by radiation-induced RI changes. For in-plane rayline errors, streaks in an irradiated region (>7 Gy) were as high as 49% for unfiltered data, 14% for AM, and 6% for ISG. For out-of-plane rayline errors, overestimations of dose in a low-dose region (∼50 cGy) were as high as 13 Gy for

  20. 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