Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats

International Nuclear Information System (INIS)

Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

2013-01-01

Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-α levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. (author)

Effect of aqueous extract of saffron (crocus sativus L.) against gamma radiation-induced skeletal muscles damage in rats

International Nuclear Information System (INIS)

El-Tahawy, N.A; Said, U.Z

2010-01-01

Muscular strength is important in sport as well as in daily activities. Reactive oxygen species (ROS) and oxidative damage are the most important factors in radiation-induced acute damage to muscle tissue. Saffron, obtained from dried stigmas of Crocus sativus L. (Iridaceae), is a highly valued spice, commonly used in flavouring and food colouring in different parts of the world and is known to possess the richest source of carotenoids. The present study was designed to investigate the efficacy of an aqueous extract of saffron to protect against radiation-induced oxidative damage in rat's skeletal muscle. Saffron was supplemented orally, via gavages to rats at a dose of 80 mg/ kg body wt/ day for 2 week pre- and 1 week post-exposure to 5 Gy (one shot dose) of whole body gamma-irradiation. Animals were sacrificed 1, 2 and 3 weeks post radiation exposure. The results revealed that whole body gamma-irradiation of rats induce oxidative stress in skeletal muscles obvious by significant elevation in the level of thiobarbituric acid reactive substances associated with significant decreases in superoxide dismutase and catalase activities. Also, radiation-induces skeletal muscles damage evidenced by significant decreases in the level of pyruvic acid, creatine phosphokinase, glutamate dehydrogenase and glucose-6-phosphate dehydrogenase activities as well as significant increases in lactic acid, total iron, and copper and calcium levels. Saffron treated-irradiated rats showed significantly less severe damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that saffron by attenuating radiation-induced oxidative stress might play a role in maintaining skeletal muscle integrity.

Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

International Nuclear Information System (INIS)

Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G.; Castiglione, F.; Vanzi, E.; Bottoncetti, A.; Pupi, A.

2011-01-01

Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

Energy Technology Data Exchange (ETDEWEB)

Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

2011-10-15

Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

Pathomorphologic observation on treatment of radiation-induced lung damage in rats with

International Nuclear Information System (INIS)

Ye Jiangfeng; Qi Haowen; Zhao Feng; Fan Fengyun; Shi Mei; Zhao Yiling; Meng Yulin

2004-01-01

Objective: To inquire into the means of preventing lung damage induced by thoracic irradiation. Methods: SD rats were divided randomly into 3 groups: normal control, irradiated control (Group IC) and irradiated and fluvastatin (Flu)-treated group (Group F). The later two groups of rats were irradiated with X-rays at a dose of 20 Gy thoracically. Beginning from the seventh day before irradiation the rats in the Group F were treated with Flu at a dose of 20 mg per day by garaging until the end of the experiment. Animals from each group were sacrificed on days 5, 15, 30, 60 respectively after irradiation. Sections of lung were examined with light microscopy, electron microscopy and morphometry. Results: The rats in the Group IC suffered from typical radiation pneumonitis (P<0.01). Electron microscopy indicated type II pneumonocytes and capillary endothelial cells were injured in rats of Group IC on days 30, 60. There were increase of collagen and a great quantity of mast cells in irradiated control rats. In rats of the Group F there was slight reaction in the lung. Conclusion: Fluvastatin could reduce radiation pneumonitis and inhibit increase of collagen. The treatment and prevention of radiation-induced lung injury in rats with fluvastatin is effective

Alleviation of acute radiation damages by post-irradiation treatments

International Nuclear Information System (INIS)

Kurishita, A.; Ono, T.

1992-01-01

Radiation induced hematopoietic and gastro-intestinal damages in mice were tried to alleviate experimentally by post-treatment. Combined treatment of OK-432 and aztreonam clearly prevented the radiation induced sepsis and elevated the survival rate in mice; the survival was 80% in the OK-432 plus aztreonam group while it was 55% in the group treated with OK-432 alone and 0% with saline. Irsogladine maleate, an anti-ulcer drug, increased the survival rate of jejunal crypt stem cells with a clear dose-related trend. The D 0 for irsogladine maleate was 2.8 Gy although it was 2.3 Gy for saline, These findings suggest that some conventional drugs are effective for radiation induced hematopoietic and gastro-intestinal damages and the possibility that they can be applied for people exposed to radiation accidentally. (author)

Action of the chlorophyllin before genetic damage induced by gamma radiation in germinal cells of Drosophila

International Nuclear Information System (INIS)

Moreno B, R.

2004-01-01

The chlorophyllin (CHLN) is a porphyrin of nutritious grade and soluble in water, derived of the chlorophyll. It has been reported that this pigment is a good anti mutagen since it reduces the damage to the DNA caused by physical or chemical agents of direct or indirect action. Their anti carcinogenic action has also been demonstrated when it is administered itself during the induced post-initiation phase by aflatoxins and heterocyclic amines. However in the last decade it has been reported that it also has promoter activity against the genetic damage induced by diverse agents like the alkyl ants of direct and indirect action, the gamma radiation and some heterocyclic amines. This effect has been observed in testing systems like Salmonella, Drosophila, rainbow trout and rodents. In the mouse spermatogonia it has been reported that it reduces the damage to the DNA but with the test of lethal dominant in Drosophila increment the damage induced by gamma radiation. The present study consisted on evaluating the effect of the CHLN in the line germinal masculine of Drosophila by means of the lethal recessive test bound to the sex (LRLS) with the stump Muller 5 and a litters system. Its were pretreated wild males with CHLN and 24 h later were irradiated with 0, 10, 20 and 40 Gy of gamma radiation immediately later were crossed with virgin females of the stump Basc and at 72 h the male was transferred to a cultivation media with three new virgin females, this process repeated three times until completing 3 litters. The F1 it was crossed among itself and in the F2 it was analysed the presence or absence of lethals. The results indicated that the CHLN per se incremented the basal frequency of damage due to the pigment can act as an agent that is inserted to the ADN causing pre mutagenic leisure. Nevertheless with the groups treated with the different doses of gamma radiation the CHLN does not present any protector action, neither promoter except in the litter I of the group

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

International Nuclear Information System (INIS)

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

UV and ionizing radiations induced DNA damage, differences and similarities

Science.gov (United States)

Ravanat, Jean-Luc; Douki, Thierry

2016-11-01

Both UV and ionizing radiations damage DNA. Two main mechanisms, so-called direct and indirect pathways, are involved in the degradation of DNA induced by ionizing radiations. The direct effect of radiation corresponds to direct ionization of DNA (one electron ejection) whereas indirect effects are produced by reactive oxygen species generated through water radiolysis, including the highly reactive hydroxyl radicals, which damage DNA. UV (and visible) light damages DNA by again two distinct mechanisms. UVC and to a lesser extend UVB photons are directly absorbed by DNA bases, generating their excited states that are at the origin of the formation of pyrimidine dimers. UVA (and visible) light by interaction with endogenous or exogenous photosensitizers induce the formation of DNA damage through photosensitization reactions. The excited photosensitizer is able to induce either a one-electron oxidation of DNA (type I) or to produce singlet oxygen (type II) that reacts with DNA. In addition, through an energy transfer from the excited photosensitizer to DNA bases (sometime called type III mechanism) formation of pyrimidine dimers could be produced. Interestingly it has been shown recently that pyrimidine dimers are also produced by direct absorption of UVA light by DNA, even if absorption of DNA bases at these wavelengths is very low. It should be stressed that some excited photosensitizers (such as psoralens) could add directly to DNA bases to generate adducts. The review will described the differences and similarities in terms of damage formation (structure and mechanisms) between these two physical genotoxic agents.

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

Science.gov (United States)

Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

2002-01-01

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

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

Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

International Nuclear Information System (INIS)

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

1989-01-01

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

Feasibility of OCT to detect radiation-induced esophageal damage in small animal models (Conference Presentation)

Science.gov (United States)

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.

Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis

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Ifigeneia V. Mavragani

2017-07-01

Full Text Available Cellular effects of ionizing radiation (IR are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs, single strand breaks (SSBs and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1 repair resistant, increasing genomic instability (GI and malignant transformation and (2 can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity. Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.

The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation

International Nuclear Information System (INIS)

Shikazono, Naoya; Noguchi, Miho; Fujii, Kentaro; Urushibara, Ayumi; Yokoya, Akinari

2009-01-01

After living cells are exposed to ionizing radiation, a variety of chemical modifications of DNA are induced either directly by ionization of DNA or indirectly through interactions with water-derived radicals. The DNA lesions include single strand breaks (SSB), base lesions, sugar damage, and apurinic/apyrimidinic sites (AP sites). Clustered DNA damage, which is defined as two or more of such lesions within one to two helical turns of DNA induced by a single radiation track, is considered to be a unique feature of ionizing radiation. A double strand break (DSB) is a type of clustered DNA damage, in which single strand breaks are formed on opposite strands in close proximity. Formation and repair of DSBs have been studied in great detail over the years as they have been linked to important biological endpoints, such as cell death, loss of genetic material, chromosome aberration. Although non-DSB clustered DNA damage has received less attention, there is growing evidence of its biological significance. This review focuses on the current understanding of (1) the yield of non-DSB clustered damage induced by ionizing radiation (2) the processing, and (3) biological consequences of non-DSB clustered DNA damage. (author)

Protective Effect of HSP25 on Radiation Induced Tissue Damage

International Nuclear Information System (INIS)

Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Bae, Sang-Woo; Lee, Yun-Sil; Kim, Sung Ho

2007-01-01

Control of cancer by irradiation therapy alone or in conjunction with combination chemotherapy is often limited by organ specific toxicity. Ionizing irradiation toxicity is initiated by damage to normal tissue near the tumor target and within the transit volume of radiotherapy beams. Irradiation-induced cellular, tissue, and organ damage is mediated by acute effects, which can be dose limiting. A latent period follows recovery from the acute reaction, then chronic irradiation fibrosis (late effects) pose a second cause of organ failure. HSP25/27 has been suggested to protect cells against apoptotic cell death triggered by hyperthermia, ionizing radiation, oxidative stress, Fas ligand, and cytotoxic drugs. And several mechanisms have been proposed to account for HSP27-mediated apoptotic protection. However radioprotective effect of HSP25/27 in vivo system has not yet been evaluated. The aim of this study was to evaluate the potential of exogenous HSP25 expression, as delivered by adenoviral vectors, to protect animal from radiation induced tissue damage

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

International Nuclear Information System (INIS)

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

2013-01-01

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. (author)

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

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

Radiation-induced neuropathies: collateral damage of improved cancer prognosis

International Nuclear Information System (INIS)

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

2012-01-01

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

Protection from ionizing radiation induced damages by phytoceuticals and nutraceuticals

International Nuclear Information System (INIS)

Nair, C.K.K.

2012-01-01

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

Radiation damage

CERN Document Server

Heijne, Erik H M; CERN. Geneva

1998-01-01

a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

Radiation-induced hyperprolactinaemia in a treated acromegalic

International Nuclear Information System (INIS)

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

1979-01-01

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

Radiation induced crystallinity damage in poly(L-lactic acid)

CERN Document Server

Kantoglu, O

2002-01-01

The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

Protection from radiation-induced damage to spermatogenesis by hormone treatment

International Nuclear Information System (INIS)

Kurdoglu, B.; Wilson, G.; Parchuri, N.; Ye, W.; Meistrich, M.L.

1994-01-01

Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism. 32 refs., 3 figs

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

International Nuclear Information System (INIS)

Rannou, Emilie

2015-01-01

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

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

International Nuclear Information System (INIS)

Angermeier, Marita; Moertl, Simone

2012-01-01

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

Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

International Nuclear Information System (INIS)

Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

2009-01-01

Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

Science.gov (United States)

Schroeder, P; Calles, C; Benesova, T; Macaluso, F; Krutmann, J

2010-01-01

Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage. 2010 S. Karger AG, Basel.

Radioprotective effects saffron and its combination with green tea against γ-radiation-induced DNA damage in Swiss albino mice

International Nuclear Information System (INIS)

Koul, Apurva; Abraham, Suresh K.

2016-01-01

Protective effects of aqueous extract of saffron (dried stigmas of Crocus sativus L.) alone and its combination with green tea against γ-radiation-induced genotoxicity and oxidative stress were investigated in Swiss albino mice. Saffron (40 mg/kg bw) alone and in combination with green tea (40 mg/kg bw) were orally administered to mice for six consecutive days, followed by exposure to γ-radiation (2.25 Gy) on 6 th day after final feeding. Antigenotoxic effect of saffron was assayed using micronucleus test in bone marrow cells which showed a significant decrease in the number of micronucleated PCEs in saffron alone and its combination with green tea pre-treated animals when compared with the radiation alone treated animals. Saffron alone and its combination with green tea pre-treated animals showed a significant decrease in lipid peroxidation levels with a significant increase in the activity of antioxidant defense system enzymes, viz. acetylcholine esterase, glutathione-S-transferase, catalase, glutathione peroxidase, glutathione reductase and non-enzymatic antioxidant (GSH), when compared with the radiation alone treated animals. Our results suggested that saffron in combination with green tea exhibits radioprotective effects against γ-radiation induced DNA damage and oxidative stress in Swiss albino mice. (author)

Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.

Directory of Open Access Journals (Sweden)

Grace Hill

Full Text Available Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1 normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage.

Does Statin Modulate Oxidative Damage Induced by ionizing Radiation in Mouse?

International Nuclear Information System (INIS)

Tawfik, S.S.; Zahran, A.M.; Salama, S.F.

2007-01-01

HMG-CoA (3-Hydroxy-3-methylglutaryl coenzyme-A) reductase inhibitors commonly referred to as the statins family. The aim of the present work was to evaluate the role of statins on oxidative stress, endothelial function, inflammatory response and bleeding time in gamma irradiated mice. Irradiated mice received 6 Gy y-rays, instilled as 2 fractions (I Gy each/week) for 3 weeks. Treated irradiated animals received by gavage atorvastatin; a synthetic form of statins (10 mg/kg body wt, 3-times/week for 3 weeks) within the same schedule of irradiation. In irradiated mice group, the results revealed significant increases of thiobarbituric acid reactive substances (TBARS), protein carbonyl values, creatine phosphokinase (CPK) activity, C-reactive protein (CRP) level as well as bleeding time. While, there was significant decreases of reduced glutathione (GSH) and nitric oxide (NO) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. In treated-irradiated mice group, atorvastatin application has significantly improved the radiation-induced changes in all these tested parameters. It could be concluded that, atorvastatin may be applied to minimize radiation damage and attenuate the side effects of radiotherapy. These results observed in mice need to be confirmed in other experimental models, but could become a part of the rationale of further randomised clinical trails in patients treated by radiotherapy

Does Statin Modulate Oxidative Damage Induced by ionizing Radiation in Mouse?

Energy Technology Data Exchange (ETDEWEB)

Tawfik, S S [Health Rad. Research Dept, National Centre for Radiation Research and Technology (NCRRT), Nasr City (Egypt); Zahran, A M; Salama, S F [Biology Dept., National Centre for Radiation Research and Technology (NCRRT), Nasr City (Egypt)

2007-07-01

HMG-CoA (3-Hydroxy-3-methylglutaryl coenzyme-A) reductase inhibitors commonly referred to as the statins family. The aim of the present work was to evaluate the role of statins on oxidative stress, endothelial function, inflammatory response and bleeding time in gamma irradiated mice. Irradiated mice received 6 Gy y-rays, instilled as 2 fractions (I Gy each/week) for 3 weeks. Treated irradiated animals received by gavage atorvastatin; a synthetic form of statins (10 mg/kg body wt, 3-times/week for 3 weeks) within the same schedule of irradiation. In irradiated mice group, the results revealed significant increases of thiobarbituric acid reactive substances (TBARS), protein carbonyl values, creatine phosphokinase (CPK) activity, C-reactive protein (CRP) level as well as bleeding time. While, there was significant decreases of reduced glutathione (GSH) and nitric oxide (NO) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. In treated-irradiated mice group, atorvastatin application has significantly improved the radiation-induced changes in all these tested parameters. It could be concluded that, atorvastatin may be applied to minimize radiation damage and attenuate the side effects of radiotherapy. These results observed in mice need to be confirmed in other experimental models, but could become a part of the rationale of further randomised clinical trails in patients treated by radiotherapy.

The protective effect of DNA on the rat cell membrane damage induced by ultraviolet radiation

International Nuclear Information System (INIS)

Ma Shouxiang; Zhong Jinyan

1988-01-01

The protective effect of DNA on the cell membrane damage induced by ultra-violet radiation was studied. Rat erythrocytes were used as experimental materials. Blood samples were taken from the rat, and centrifuged to separate the plasma. The cells were washed twice with isotonic saline, resuspended in normal saline solution and then irradiated by ultra-violet radiation. The DNA was added before or after irradiation. THe cell suspensions were kept at 5 deg C for 20 hours after irradiation, and then centrifuged. The supernatants were used for hemoglobin determination. The main results obtained may summarized as follows: the cell suspension of erythrocytes were irradiated for 5, 10 and 20 min. The amount of hemolysis induced by irradiation dosage revealed a direct proportional relationship. If DNA (20-40μg/ml) was applied before irradiation, the amount of hemolysis induced apparently decreased. The differences between the control and DNA treated were statistically significant, P<0.01, but insignificant for DNA added after irradiation

Curcumin Attenuates Gamma Radiation Induced Intestinal Damage in Rats

International Nuclear Information System (INIS)

EI-Tahawy, N.A.

2009-01-01

Small Intestine exhibits numerous morphological and functional alterations during radiation exposure. Oxidative stress, a factor implicated in the intestinal injury may contribute towards some of these alterations. The present work was designed to evaluate the efficacy of curcumin, a yellow pigment of turmeric on y-radiation-induced oxidative damage in the small intestine by measuring alterations in the level of thiobarbituric acid reactive substances (TSARS), serotonin metabolism, catecholamine levels, and monoamine oxidase (MAO) activity in parallel to changes in the architecture of intestinal tissues. In addition, monoamine level, MAO activity and TSARS level were determined in the serum. Curcumin was supplemented orally via gavages, to rats at a dose of (45 mg/ Kg body wt/ day) for 2 weeks pre-irradiation and the last supplementation was 30 min pre exposure to 6.5 Gy gamma radiations (applied as one shot dose). Animals were sacrificed on the 7th day after irradiation. The results demonstrated that, whole body exposure of rats to ionizing radiation has induced oxidative damage in small intestine obvious by significant increases of TSARS content, MAO activity and 5-hydroxy indole acetic acid (5-HIAA) and by significant decreases of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) levels. In parallel histopathological studies of the small intestine of irradiated rats through light microscopic showed significant decrease in the number of villi, villus height, mixed sub mucosa layer with more fibres and fibroblasts. Intestinal damage was in parallel to significant alterations of serum MAO activity, TBARS, 5-HT, DA, NE and EPI levels. Administration of curcumin before irradiation has significantly improved the levels of monoamines in small intestine and serum of irradiated rats, which was associated with significant amelioration in MAO activity and TBARS contents

Defense mechanisms against radiation induced teratogenic damage in mice

International Nuclear Information System (INIS)

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

2002-01-01

Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair

Analytical studies into radiation-induced starch damage in black and white peppers

International Nuclear Information System (INIS)

Farkas, J.; Sharif, M.M.; Barabassy, S.

1990-01-01

In order to develop detection methods of radiation treatment, ground black pepper samples equilibrated to water activity levels of 0.25, 0.50 and 0.75 a w , respectively, were irradiated with gamma radiation doses of 0, 4, 8, 16 or 32 kGy, and their damaged starch content, reduced sugar content and alcohol induced turbidity of their aqueous extracts were investigated. The colorimetric method and the alcohol-induced turbidity showed statistically significant increase of starch damage at 4 kGy or higher dose levels. However, all investigated analytical indices of starch radio-depolymerization were changed less dramatically by irradiation than the apparent viscosity of the gelatinized suspensions of spices reported previously. (author) 15 refs.; 4 tabs

DNA damage caused by ionizing radiation

International Nuclear Information System (INIS)

Sachs, R.K.; Peili Chen; Hahnfeldt, P.J.; Klatky, L.R.

1992-01-01

A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions. 51 refs., 5 figs

Protective Effects of Polysaccharides from Soybean Meal Against X-ray Radiation Induced Damage in Mouse Spleen Lymphocytes

Directory of Open Access Journals (Sweden)

Xin Yang

2011-11-01

Full Text Available The aim of this study was to investigate radioprotective effect of the polysaccharides from soybean meal (SMP against X-ray radiation-induced damage in mouse spleen lymphocytes. MTT and comet assay were performed to evaluate SMP’s ability to prevent cell death and DNA damage induced by radiation. The results show that, X-ray radiation (30 KV, 10 mA, 8 min (4 Gy can significantly increase cell death and DNA fragmentation of mouse spleen lymphocytes. Pretreatment with SMP for 2 h before radiation could increase cell viability, moreover, the SMP can reduce X-ray radiation-induced DNA damage. The percentage of tail DNA and the tail moment of the SMP groups were significantly lower than those of the radiation alone group (p < 0.05. These results suggest SMP may be a good candidate as a radioprotective agent.

The alteration of chromatin domains during damage repair induced by ionizing radiation

International Nuclear Information System (INIS)

Cress, A.E.; Olson, K.M.; Olson, G.B.

1995-01-01

Several groups previously have reported the ability of chromatin structure to influence the production of damage induced by ionizing radiation. The authors' interest has been to determine whether chromatin structural alterations exist after ionizing radiation during a repair interval. The earlier work investigated this question using biochemical techniques. The crosslinking of nuclear structural proteins to DNA after ionizing radiation was observed. In addition, they found that the chromatin structure in vitro as measured by sucrose density gradient sedimentation, was altered after ionizing radiation. These observations added to earlier studies in which digital imaging techniques showed an alteration in feulgen-positive DNA after irradiation prompted the present study. The object of this study was to detect whether the higher order structure of DNA into chromatin domains within interphase human cells was altered in interphase cells in response to a radiation induced damage. The present study takes advantage of the advances in the detection of chromatin domains in situ using DNA specific dyes and digital image processing of established human T and B cell lines

Effects of ionizing radiation on laser-induced damage in SiO/sub 2/

Energy Technology Data Exchange (ETDEWEB)

Soileau, M J; Mansour, N; Canto, E; Griscom, D L

1988-05-01

The effects of radiation damage on bulk laser-induced damage in SiO/sub 2/ were investigated. Samples studied included Spectrasil A, B, and WF (water free). Measurements of laser-induced breakdown were conducted with 532 and 1064 nm laser pulses of approximately 20 ns duration. Reductions of up to 40% in the laser-induced breakdown threshold were observed at 532 nm for samples exposed to 10/sup 8/ rad of ..gamma..-radiation. The decrease in breakdown threshold for irradiated SiO/sub 2/ samples at 532 nm was found to be proportional to the linear absorption of the specimen at 266 nm. These results are in good agreement with a proposed model which suggests that two-photon absorption initiated avalanche process is responsible for laser-induced breakdown for these materials.

Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

NARCIS (Netherlands)

Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

International Nuclear Information System (INIS)

Pinar, Beatriz; Henríquez-Hernández, Luis Alberto; Lara, Pedro C; Bordon, Elisa; Rodriguez-Gallego, Carlos; Lloret, Marta; Nuñez, Maria Isabel; De Almodovar, Mariano Ruiz

2010-01-01

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. 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. 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. An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity

Radiation Damage in Scintillating Crystals

CERN Document Server

Zhu Ren Yuan

1998-01-01

Crystal Calorimetry in future high energy physics experiments faces a new challenge to maintain its precision in a hostile radiation environment. This paper discusses the effects of radiation damage in scintillating crystals, and concludes that the predominant radiation damage effect in crystal scintillators is the radiation induced absorption, or color center formation, not the loss of the scintillation light yield. The importance of maintaining crystal's light response uniformity and the feasibility to build a precision crystal calorimeter under radiation are elaborated. The mechanism of the radiation damage in scintillating crystals is also discussed. While the damage in alkali halides is found to be caused by the oxygen or hydroxyl contamination, it is the structure defects, such as oxygen vacancies, cause damage in oxides. Material analysis methods used to reach these conclusions are presented in details.

Protective role of Carica papaya (Linn.) in electron beam radiation induced hematological and cytogenetic damages in Swiss albino mice

International Nuclear Information System (INIS)

Yogish Somayaji, T.; Suchetha Kumari, N.

2014-01-01

Carica papaya (Linn.) is known to possess various biomedical applications. It has remarkable antioxidant properties. The main objective of the study was to evaluate the leaf extracts of Carica papaya (Linn.) on hematologic and cytogenetic changes occurring due to irradiation of mice to sub-lethal doses of Electron Beam Radiation (EBR). Analysis of hematological changes occurring due to irradiation of mice to sub-lethal doses of EBR, and the effects of Carica papaya (Linn.) extract on the same. The Assessment of hematopoietic stress by spleen colony forming unit and spleen body weight index. The analysis of cell proliferation and immunomodulation with response to the effects of Carica papaya (Linn.) extract by estimation of IL-6. The estimation of serum total antioxidants, lipid peroxidation and analyzing the activities of enzymes like SOD, ALP, and AST. Male Swiss albino mice were fed orally with papaya aqueous leaf extract for 15 days. They were irradiated with a whole body dose of 6 Gy Electron Beam radiation. The mice were dissected for liver, kidney, bone marrow, spleen and brain. The hematological studies were done using blood cell count in an automated cell counter. The biochemical estimations like urea, creatinine, SGOT, SGPT, Total Protein, Albumin, Bilirubin were done using the serum and homogenates. The total antioxidant capacity, the antioxidant enzymes were estimated. The Interleukin-6 levels were estimated in serum to assess immune modulation. The results show a decrease in the hematological parameters in radiated animals. The papaya treated groups have shown modulation in the hematological parameters. The extract has also reduced the suppression of the bone marrow induced by radiation. The radiation induced liver damage is also reduced in papaya treated groups. The aqueous extract of Carica papaya (Linn.) has shown protective effects in electron beam radiation induced tissue damages in Swiss Albino mice (author)

Biomarkers of DNA and cytogenetic damages induced by environmental chemicals or radiation

International Nuclear Information System (INIS)

1999-01-01

This paper presents and discusses results from the studies on various biomarkers of the DNA and cytogenetic damages induced by environmental chemicals or radiation. Results of the biomonitoring studies have shown that particularly in the condition of Poland, health hazard from radiation exposure is overestimated in contradistinction to the environmental hazard

Delayed repair of radiation induced clustered DNA damage: Friend or foe?

International Nuclear Information System (INIS)

Eccles, Laura J.; O'Neill, Peter; Lomax, Martine E.

2011-01-01

A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a 'friend', leading to cell killing in tumour cells or as a 'foe', resulting in the formation of mutations and genetic instability in normal tissue.

Electron Beam Induced Radiation Damage of the Semiconductor Radiation Detector based on Silicon

International Nuclear Information System (INIS)

Kim, Han Soo; Kim, Yong Kyun; Park, Se Hwan; Haa, Jang Ho; Kang, Sang Mook; Chung, Chong Eun; Cho, Seung Yeon; Park, Ji Hyun; Yoon, Tae Hyung

2005-01-01

A Silicon Surface Barrier (SSB) semiconductor detector which is generally used to detect a charged particle such as an alpha particle was developed. The performance of the developed SSB semiconductor detector was measured with an I-V curve and an alpha spectrum. The response for an alpha particle was measured by Pu-238 sources. A SSB semiconductor detector was irradiated firstly at 30sec, at 30μA and secondly 40sec, 40μA with a 2MeV pulsed electron beam generator in KAERI. And the electron beam induced radiation damage of a homemade SSB detector and the commercially available PIN photodiode were investigated. An annealing effect of the damaged SSB and PIN diode detector were also investigated using a Rapid Thermal Annealing (RTA). This data may assist in designing the silicon based semiconductor radiation detector when it is operated in a high radiation field such as space or a nuclear power plant

Gymnemagenin-a triterpene saponin prevents γ-radiation induced cellular DNA damage

International Nuclear Information System (INIS)

Arunachalam, Kantha Deivi; Arun, Lilly Baptista; Annamalai, Sathesh Kumar; Hari, Shanmugasundaram

2014-01-01

Gymnema sylvestre an ethno-medicinally important plant was investigated for its protecting activity against radiation induced DNA damage. The major bioactive component present in Gymnema sylvestre such as gymnemic acid and gymnemagenin a triterpene saponin, were tested for its radioprotective effects against 60 Co irradiation induced DNA damage in fish model using fresh water fish Pangasius sutchi. Fishes subjected to a dose of 133 Gy of gamma radiation and observed for eight days. The genotoxic assessment by micronucleus assay showed us that that the plant extract helped in reducing the frequency of micronucleated and binucleated erythrocytes compared to the irradiated control group. The genotoxic assessment by alkaline comet assay by single gel electrophoresis shows that pretreatment with the plant extract appreciably decreased the percentage of tail DNA towards the levels close to those of normal control group. The gradual increase in the level of the antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT) during the course of the experiment indicates that the antioxidant enzyme activities play an important role in protecting organisms against gamma radiation-induced cellular oxidative stress. In conclusion the leaf extracts of Gymnema sylvstre exerts its radio protective potential by suppressing the toxic assault of ROS generated by the ionizing radiation through its ability to boost the levels of antioxidant enzymes (CAT and SOD) due to the presence of its phytochemicals like gymnemgenenin- a Triterpene Saponin. (author)

High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

International Nuclear Information System (INIS)

Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

2012-01-01

Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

Longitudinal diffusion tensor magnetic resonance imaging study of radiation-induced white matter damage in a rat model.

Science.gov (United States)

Wang, Silun; Wu, Ed X; Qiu, Deqiang; Leung, Lucullus H T; Lau, Ho-Fai; Khong, Pek-Lan

2009-02-01

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

Solar ultraviolet radiation-induced DNA damage in aquatic organisms: potential environmental impact

International Nuclear Information System (INIS)

Haeder, Donat-P.; Sinha, Rajeshwar P.

2005-01-01

Continuing depletion of stratospheric ozone and subsequent increases in deleterious ultraviolet (UV) radiation at the Earth's surface have fueled the interest in its ecological consequences for aquatic ecosystems. The DNA is certainly one of the key targets for UV-induced damage in a variety of aquatic organisms. UV radiation induces two of the most abundant mutagenic and cytotoxic DNA lesions, cyclobutane pyrimidine dimers (CPDs) and pyrimidine pyrimidone photoproducts (6-4PPs) and their Dewar valence isomers. However, aquatic organisms have developed a number of repair and tolerance mechanisms to counteract the damaging effects of UV on DNA. Photoreactivation with the help of the enzyme photolyase is one of the most important and frequently occurring repair mechanisms in a variety of organisms. Excision repair, which can be distinguished into base excision repair (BER) and nucleotide excision repair (NER), also play an important role in DNA repair in several organisms with the help of a number of glycosylases and polymerases, respectively. In addition, mechanisms such as mutagenic repair or dimer bypass, recombinational repair, cell-cycle checkpoints, apoptosis and certain alternative repair pathways are also operative in various organisms. This review deals with the UV-induced DNA damage and repair in a number of aquatic organisms as well as methods of detecting DNA damage

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

Science.gov (United States)

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

2016-06-01

The link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR-induced non-epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR-induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR-induced DNA damage. IR partly reversed the pro-apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR-induced DNA damage and thereby might contribute to melanomagenesis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

International Nuclear Information System (INIS)

Averbeck, D.; Boucher, D.

2006-01-01

Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using 137 Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage into

The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Averbeck, D.; Boucher, D. [Institut Curie-Section de Recherche, UMR2027 CNRS, LCR-V28 du CEA, Centre Universitaire, 91405 Orsay Cedex (France)

2006-07-01

Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using {sup 137}Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage

Protective Effect of Curcumin on γ - radiation Induced Chromosome Aberrations in Human Blood Lymphocytes

International Nuclear Information System (INIS)

AlSuhaibani, E.S

2008-01-01

The present work is aimed at evaluating the radioprotective effect of curcumin on γ radiation induced genetic toxicity. The DNA damage was analyzed by the frequencies of chromosome aberrations assay. Human lymphocytes were treated in vitro with 5.0 γg/ml of curcumin for 30 min at 37 degree C then exposed to 1, 2 and 4 Gy gamma-radiation. The lymphocytes which were pre-treated with curcumin exhibited a significant decrease in the frequency of chromosome aberration at 1 and 2 Gy radiation-induced chromosome damage as compared with the irradiated cells which did not receive the curcumin pretreatment. Thus, pretreatment with curcumin gives protection to lymphocytes against γ-radiation induced chromosome aberration at certain doses. (author)

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma.

Science.gov (United States)

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-19

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased ( P histogram parameters increased (all P histogram parameters. Early mean change rates for bilateral parotid SD and ADC max could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 ( P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

Delayed repair of radiation induced clustered DNA damage: Friend or foe?

Science.gov (United States)

Eccles, Laura J.; O’Neill, Peter; Lomax, Martine E.

2011-01-01

A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a “friend”, leading to cell killing in tumour cells or as a “foe”, resulting in the formation of mutations and genetic instability in normal tissue. PMID:21130102

Amelioration of radiation induced DNA damage and biochemical alterations by Punica Granatum (L) extracts and synthetic ellagic acid in Swiss albino mice

International Nuclear Information System (INIS)

Satheesh Kumar Bhandary, B.; Sharmila, K.P.; Suchetha Kumari, N.; Vadisha Bhat, S.; Sherly, Sharmila; Sanjeev, Ganesh

2013-01-01

Radiation therapy has been used in cancer treatment for many decades; Although effective in killing tumor cells, ROS produced in radiotherapy threaten the integrity and survival of surrounding normal cells. ROS are scavenged by radioprotectors before they can interact with biochemical molecules, thus reducing harmful effects of radiation. The pomegranate, Punica granatum L., an ancient, mystical, and highly distinctive fruit, is the predominant member of the Punicaceae family. It is used in several systems of medicine for a variety of ailments. The objective of the present study was to investigate the protective effects of ethanolic extracts of pomegranate whole fruit (EPWF) and seeds (EPS) and Synthetic Ellagic acid (EA) against Electron Beam Radiation (EBR) induced DNA damage and biochemical alterations in Swiss Albino mice. The extracts and synthetic compound were assessed for its radical scavenging property by DPPH radical scavenging and Ferric Reducing Antioxidant Power assays. The animals were treated with 200 mg/kg body wt. of pomegranate extracts and Ellagic acid for 15 days before exposure to 6 Gy of EBR. Radiation induced DNA damage was assessed by comet assay in the peripheral blood lymphocytes of mice. The biochemical estimations were carried out in the serum and RBC lysate of the animals. The plant extracts and synthetic compound exhibited good radical scavenging and reducing properties.The pretreated animals before irradiation caused a reduction in the comet length, olive tail moment, % DNA in tail when compared to irradiated group. The biochemical parameters such as lipid peroxidation was significantly depleted in the treated groups when compared to irradiated group followed by significant elevation in reduced glutathione. Our findings indicate the ameliorating effects of pomegranate extracts and synthetic ellagic acid on radiation induced DNA damage and biochemical changes in mice may be due to its free radical scavenging and increased antioxidant

Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, tempol

International Nuclear Information System (INIS)

Mitchell, J.B.; DeGraff, W.; Kaufman, D.; Krishna, M.C.; Samuni, A.; Finkelstein, E.; Ahn, M.S.; Hahn, S.M.; Gamson, J.; Russo, A.

1991-01-01

Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)2 mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mM Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress

Particle interaction and displacement damage in silicon devices operated in radiation environments

International Nuclear Information System (INIS)

Leroy, Claude; Rancoita, Pier-Giorgio

2007-01-01

Silicon is used in radiation detectors and electronic devices. Nowadays, these devices achieving submicron technology are parts of integrated circuits of large to very large scale integration (VLSI). Silicon and silicon-based devices are commonly operated in many fields including particle physics experiments, nuclear medicine and space. Some of these fields present adverse radiation environments that may affect the operation of the devices. The particle energy deposition mechanisms by ionization and non-ionization processes are reviewed as well as the radiation-induced damage and its effect on device parameters evolution, depending on particle type, energy and fluence. The temporary or permanent damage inflicted by a single particle (single event effect) to electronic devices or integrated circuits is treated separately from the total ionizing dose (TID) effect for which the accumulated fluence causes degradation and from the displacement damage induced by the non-ionizing energy-loss (NIEL) deposition. Understanding of radiation effects on silicon devices has an impact on their design and allows the prediction of a specific device behaviour when exposed to a radiation field of interest

The effect of dithiothreitol on radiation-induced genetic damage in Arabidopsis thaliana (L) Heynh

International Nuclear Information System (INIS)

Dellaert, L.M.W.

1980-01-01

A study was made on the effect of dithiothreitol (DTT; present during irradiation) on M 1 ovule sterility, M 2 embryonic lethals, M 2 chlorophyll mutants and M 2 viable mutants induced with fast neutrons or X-rays in Arabidopsis thaliana. DTT provides considerable protection against both fast-neutron and X-ray induced genetic damage. However, a higher protection was observed against M 1 ovule sterility, than against embryonic lethals, chlorophylls and viable mutants. This implies a significant DTT-induced spectral shift (0.01 < p < 0.05), i.e. a shift in the relative frequencies of the different genetic parameters. This spectral shift is explained on the basis of a specific DTT protection against radiation-induced strand breaks, and by differences in the ratio strand breaks/base damage for the genetic parameters concerned, i.e. a higher ratio for ovule sterility than for the other parameters. The induction of the genetic damage by ionizing radiation, either with or without DTT, is described by a mathematical model, which includes both strand breaks and base damage. The model shows that the resolving power of a test for a 'mutation'spectral shift depends on the relative values of the strandbreak reduction factor of -SH compounds and on the ratio strand breaks/base damage of the genetic parameters. For each genetic parameter the DTT damage reduction factor (DRF) is calculated per irradiation dose, and in addition the average (over-all doses) ratio strand breaks/base damage. (orig.)

Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model.

Science.gov (United States)

Zuo, Wen-Qi; Hu, Yu-Juan; Yang, Yang; Zhao, Xue-Yan; Zhang, Yuan-Yuan; Kong, Wen; Kong, Wei-Jia

2015-05-29

With the increasing popularity of mobile phones, the potential hazards of radiofrequency electromagnetic radiation (RF-EMR) on the auditory system remain unclear. Apart from RF-EMR, humans are also exposed to various physical and chemical factors. We established a lipopolysaccharide (LPS)-induced inflammation in vitro model to investigate whether the possible sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation (at specific absorption rates: 2, 4 W/kg) will increase. Spiral ganglion neurons (SGN) were obtained from neonatal (1- to 3-day-old) Sprague Dawley® (SD) rats. After the SGN were treated with different concentrations (0, 20, 40, 50, 100, 200, and 400 μg/ml) of LPS, the Cell Counting Kit-8 (CCK-8) and alkaline comet assay were used to quantify cellular activity and DNA damage, respectively. The SGN were treated with the moderate LPS concentrations before RF-EMR exposure. After 24 h intermittent exposure at an absorption rate of 2 and 4 W/kg, DNA damage was examined by alkaline comet assay, ultrastructure changes were detected by transmission electron microscopy, and expression of the autophagy markers LC3-II and Beclin1 were examined by immunofluorescence and confocal laser scanning microscopy. Reactive oxygen species (ROS) production was quantified by the dichlorofluorescin-diacetate assay. LPS (100 μg/ml) induced DNA damage and suppressed cellular activity (P 0.05); therefore, 40 μg/ml was used to pretreat the concentration before exposure to RF-EMR. RF-EMR could not directly induce DNA damage. However, the 4 W/kg combined with LPS (40 μg/ml) group showed mitochondria vacuoles, karyopyknosis, presence of lysosomes and autophagosome, and increasing expression of LC3-II and Beclin1. The ROS values significantly increased in the 4 W/kg exposure, 4 W/kg combined with LPS (40 μg/ml) exposure, and H2O2 groups (P spiral ganglion neurons, but it could cause the changes of cellular ultrastructure at special SAR 4

Study of terahertz-radiation-induced DNA damage in human blood leukocytes

Energy Technology Data Exchange (ETDEWEB)

Angeluts, A A; Esaulkov, M N; Kosareva, O G; Solyankin, P M; Shkurinov, A P [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation); Gapeyev, A B; Pashovkin, T N [Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region (Russian Federation); Matyunin, S N [Section of Applied Problems at the Presidium of the Russian Academy of Sciences, Moscow (Russian Federation); Nazarov, M M [Institute on Laser and Information Technologies, Russian Academy of Sciences, Shatura, Moscow Region (Russian Federation); Cherkasova, O P [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation)

2014-03-28

We have carried out the studies aimed at assessing the effect of terahertz radiation on DNA molecules in human blood leukocytes. Genotoxic testing of terahertz radiation was performed in three different oscillation regimes, the blood leukocytes from healthy donors being irradiated for 20 minutes with the mean intensity of 8 – 200 μW cm{sup -2} within the frequency range of 0.1 – 6.5 THz. Using the comet assay it is shown that in the selected regimes such radiation does not induce a direct DNA damage in viable human blood leukocytes. (biophotonics)

Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

International Nuclear Information System (INIS)

Jiang Erkang; Wu Lijun

2009-01-01

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

Analysis of ionizing radiation-induced foci of DNA damage repair proteins

International Nuclear Information System (INIS)

Veelen, Lieneke R. van; Cervelli, Tiziana; Rakt, Mandy W.M.M. van de; Theil, Arjan F.; Essers, Jeroen; Kanaar, Roland

2005-01-01

Repair of DNA double-strand breaks by homologous recombination requires an extensive set of proteins. Among these proteins are Rad51 and Mre11, which are known to re-localize to sites of DNA damage into nuclear foci. Ionizing radiation-induced foci can be visualized by immuno-staining. Published data show a large variation in the number of foci-positive cells and number of foci per nucleus for specific DNA repair proteins. The experiments described here demonstrate that the time after induction of DNA damage influenced not only the number of foci-positive cells, but also the size of the individual foci. The dose of ionizing radiation influenced both the number of foci-positive cells and the number of foci per nucleus. Furthermore, ionizing radiation-induced foci formation depended on the cell cycle stage of the cells and the protein of interest that was investigated. Rad51 and Mre11 foci seemed to be mutually exclusive, though a small subset of cells did show co-localization of these proteins, which suggests a possible cooperation between the proteins at a specific moment during DNA repair

Common genomic signaling among initial DNA damage and radiation-induced apoptosis in peripheral blood lymphocytes from locally advanced breast cancer patients

DEFF Research Database (Denmark)

Henríquez-Hernández, Luis Alberto; Pinar, Beatriz; Carmona-Vigo, Ruth

2013-01-01

PURPOSE: To investigate the genomic signaling that defines sensitive lymphocytes to radiation and if such molecular profiles are consistent with clinical toxicity; trying to disclose the radiobiology mechanisms behind these cellular processes. PATIENTS AND METHODS: Twelve consecutive patients...... suffering from locally advanced breast cancer and treated with high-dose hyperfractionated radiotherapy were recruited. Initial DNA damage was measured by pulsed-field gel electrophoresis and radiation-induced apoptosis was measured by flow cytometry. Gene expression was assessed by DNA microarray. RESULTS...

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

Directory of Open Access Journals (Sweden)

Jiamin Zhang

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

Flow cytometric determination of radiation-induced chromosome damage and its correlation with cell survival

International Nuclear Information System (INIS)

Welleweerd, J.; Wilder, M.E.; Carpenter, S.G.; Raju, M.R.

1984-01-01

Chinese hamster M3-1 cells were irradiated with several doses of x rays or α particles from 238 Pu. Propidium iodide-stained chromosome suspensions were prepared at different times after irradiation; cells were also assayed for survival. The DNA histograms of these chromosomes showed increased background counts with increased doses of radiation. This increase in background was cell-cycle dependent and was correlated with cell survival. The correlation between radiation-induced chromosome damage and cell survival was the same for X rays and α particles. Data are presented which indicate that flow cytometric analysis of chromosomes of irradiated cell populations can be a useful adjunct to classical cytogenic analysis of irradiation-induced chromosomal damage by virtue of its ability to express and measure chromosomal damage not seen by classical cytogenic methods

Oxidative damage of mitochondrial and nuclear DNA induced by ionizing radiation in human hepatoblastoma cells

International Nuclear Information System (INIS)

Morales, Albert; Miranda, Merce; Sanchez-Reyes, Alberto; Biete, Alberto; Fernandez-Checa, Jose C.

1998-01-01

Purpose: Since reactive oxygen species (ROS) act as mediators of radiation-induced cellular damage, the aim of our studies was to determine the effects of ionizing radiation on the regulation of hepatocellular reduced glutathione (GSH), survival and integrity of nuclear and mitochondrial DNA (mtDNA) in human hepatoblastoma cells (Hep G2) depleted of GSH prior to radiation. Methods and Materials: GSH, oxidized glutathione (GSSG), and generation of ROS were determined in irradiated (50-500 cGy) Hep G2 cells. Clonogenic survival, nuclear DNA fragmentation, and integrity of mtDNA were assessed in cells depleted of GSH prior to radiation. Results: Radiation of Hep G2 cells (50-400 cGy) resulted in a dose-dependent generation of ROS, an effect accompanied by a decrease of reduced GSH, ranging from a 15% decrease for 50 cGy to a 25% decrease for 400 cGy and decreased GSH/GSSG from a ratio of 17 to a ratio of 7 for controls and from 16 to 6 for diethyl maleate (DEM)-treated cells. Depletion of GSH prior to radiation accentuated the increase of ROS by 40-50%. The depletion of GSH by radiation was apparent in different subcellular sites, being particularly significant in mitochondria. Furthermore, depletion of nuclear GSH to 50-60% of initial values prior to irradiation (400 cGy) resulted in DNA fragmentation and apoptosis. Consequently, the survival of Hep G2 to radiation was reduced from 25% of cells not depleted of GSH to 10% of GSH-depleted cells. Fitting the survival rate of cells as a function of GSH using a theoretical model confirmed cellular GSH as a key factor in determining intrinsic sensitivity of Hep G2 cells to radiation. mtDNA displayed an increased susceptibility to the radiation-induced loss of integrity compared to nuclear DNA, an effect that was potentiated by GSH depletion in mitochondria (10-15% intact mtDNA in GSH-depleted cells vs. 25-30% of repleted cells). Conclusion: GSH plays a critical protective role in maintaining nuclear and mtDNA functional

Protective effect of zingerone, a dietary compound against radiation induced damage

International Nuclear Information System (INIS)

Satish Rao, B.S.; Rao, Nageshwar

2012-01-01

The radioprotective potential of phenolic alkanone, Zingerone (ZO) was investigated using human peripheral blood lymphocytes as well as Chinese hamster fibroblast (V79) cells growing in vitro and in vivo by using Swiss albino mice exposed to gamma radiation. In the in vivo studies, mice were administered with ZO (10-100 mg/kg b.wt), once daily for five consecutive days. One hour after the last administration of ZO on the fifth day, animals were whole body exposed to 10 Gy gamma radiations. The radioprotective potential was assessed using animal survival, haemopoietic stem cell survival (CFU) assay, mouse bone marrow micronucleus test, histological observations of intestinal and bone marrow damage. Effect of ZO pretreatment on radiation-induced changes in glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPx) levels was also analyzed. ZO treatment resulted increase in the LD50/30 by 1.8 Gy (dose reduction factor = 1.2). The number of spleen colonies after whole body irradiation of mice (4.5 or 7.5 Gy) was increased when ZO was administered 1 h prior to irradiation. The histological observations indicated a decline in the villus height and crypt number with an increase in goblet and dead cell population in the irradiated group, which was normalized by pretreatment with ZO. A significant (p < 0.001) reduction in micronucleated polychromatic, normochromatic erythrocytes, increased PCE/NCE ratio, increase in the GSH, GST, SOD, CAT and decreased LPx levels were observed in ZO by pretreated group when compared to the irradiated animals. Our in vitro and in vivo studies demonstrate the potential of ZO in mitigating radiation-induced cytotoxic, genotoxicity, apoptosis in cell culture and animal mortality, cytogenetic damage, intestinal and bone marrow protection in vivo. Radioprotective potential of ZO may be attributed to the inhibition radiation-induced decline in the endogenous antioxidant levels

Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

Energy Technology Data Exchange (ETDEWEB)

Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br; Tsutsumi, Shiguetoshi [Amazon Food Ltd., Tokyo (Japan)], e-mail: fwip5138@mb.infoweb.ne.jp

2009-07-01

In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by {sup 60}Co {gamma}-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 {mu}g/ml), 1 h before irradiation, with 1 Gy of {gamma} radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

International Nuclear Information System (INIS)

Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo; Tsutsumi, Shiguetoshi

2009-01-01

In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by 60 Co γ-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 μg/ml), 1 h before irradiation, with 1 Gy of γ radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

Cytogenetic methods for the detection of radiation-induced chromosome damage in aquatic organisms

International Nuclear Information System (INIS)

Kligerman, A.D.

1979-01-01

One means of evaluating the genetic effects of radiation on the genomes of aquatic organisms is to screen radiation-exposed cells for chromosome aberrations. A brief literature review of studies dealing with radiation-induced chromosome damage in aquatic organisms is presented, and reasons are given detailing why most previous studies are of little quantitative value. Suggestions are made for obtaining adequate qualitative and quantitative data through the use of modern cytogenetic methods and a model systems approach to the study of cytogenetic radiation damage in aquatic organisms. Detailed procedures for both in vivo and in vitro cytogenetic methods are described, and experimental considerations are discussed. Finally, suggestions for studies that could be of value in establishing protective guidelines for aquatic ecosystems are presented. (author)

Differences in inhibition by beta-arabinofuranosyladenine (araA) of radiation induced DNA damage repair in exponentially growing and plateau-phase CHO-cells

International Nuclear Information System (INIS)

Iliakis, G.; Seaner, R.

1988-01-01

The effect of beta-arabinofuranosyladenine (araA) on the repair of radiation induced DNA damage, as measured by the DNA unwinding technique, was studied in exponentially growing and plateau-phase CHO-cells after exposure to X-rays. Induction of DNA damage by radiation was found to be similar in exponentially growing and plateau-phase cells. In the absence of araA, repair of radiation induced DNA damage proceeded with similar kinetics in exponentially growing and plateau-phase cells. AraA at concentrations between 0-1500 μM inhibited DNA repair both in exponentially growing and in plateau-phase cells. However, the degree of inhibition was significantly higher (by a factor of 3) in plateau-phase cells. A similar degree of repair inhibition by araA was observed in plateau-phase cells treated in their conditioned medium, as well as in plateau-phase cells that were transferred in fresh growth medium just before treatment initiation. These results indicate the importance of biochemical parameters associated with alterations in the growth state of the cells for the inhibitory effect of araA and may help in the elucidation of the molecular mechanism(s) underlying repair inhibition by inhibitors of DNA replication. (orig.)

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

International Nuclear Information System (INIS)

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

1993-01-01

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

Imitation of radiation-induced damages to DNA with a radionuclide incorporated into polynucleotides

International Nuclear Information System (INIS)

Korolev, V.G.

1984-01-01

Because of a great variety and different reparability of radiation-induced DNA lesions it is difficult to evaluate the radiobiologacal significance of certain individual alterations. It is suggested that the radionuclides incorporated anto DNA can be used to imitate different types of radiation damages to DNA. Both qualitative and quantitative aspects of the problem are discussed

Radiation damage in barium fluoride detector materials

International Nuclear Information System (INIS)

Levey, P.W.; Kierstead, J.A.; Woody, C.L.

1988-01-01

To develop radiation hard detectors, particularly for high energy physics studies, radiation damage is being studied in BaF 2 , both undoped and doped with La, Ce, Nd, Eu, Gd and Tm. Some dopants reduce radiation damage. In La doped BaF 2 they reduce the unwanted long lifetime luminescence which interferes with the short-lived fluorescence used to detect particles. Radiation induced coloring is being studied with facilities for making optical measurements before, during and after irradiation with 60 C0 gamma rays. Doses of 10 6 rad, or less, create only ionization induced charge transfer effects since lattice atom displacement damage is negligible at these doses. All crystals studied exhibit color center formation, between approximately 200 and 800 nm, during irradiation and color center decay after irradiation. Thus only measurements made during irradiation show the total absorption present in a radiation field. Both undoped and La doped BaF 2 develop damage at minimum detectable levels in the UV---which is important for particle detectors. For particle detector applications these studies must be extended to high dose irradiations with particles energetic enough to cause lattice atom displacement damage. In principle, the reduction in damage provided by dopants could apply to other applications requiring radiation damage resistant materials

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

Directory of Open Access Journals (Sweden)

Santosh K Katiyar

Full Text Available 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.

Radiation damage to DNA: the effect of LET

Energy Technology Data Exchange (ETDEWEB)

Ward, J F; Milligan, J R [California Univ., San Diego, La Jolla, CA (United States). School of Medicine

1997-03-01

Mechanisms whereby ionizing radiation induced damage are introduced into cellular DNA are discussed. The types of lesions induced are summarized and the rationale is presented which supports the statement that radiation induced singly damaged sites are biologically unimportant. The conclusion that multiply damaged sites are critical is discussed and the mechanisms whereby such lesions are formed are presented. Structures of multiply damaged sites are summarized and problems which they present to cellular repair systems are discussed. Lastly the effects of linear energy transfer on the complexity of multiply damaged sites are surveyed and the consequences of this increased complexity are considered in terms of cell survival and mutation. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-05-08

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

Development of radiation biological dosimetry and treatment of radiation-induced damaged tissue

Energy Technology Data Exchange (ETDEWEB)

Cho, Chul Koo; Kim, Tae Hwan; Lee, Yun Sil [and others

2000-04-01

Util now, only a few methods have been developed for radiation biological dosimetry such as conventional chromosome aberration and micronucleus in peripheral blood cell. However, because these methods not only can be estimated by the expert, but also have a little limitation due to need high technique and many times in the case of radiation accident, it is very difficult to evaluate the absorbed dose of victims. Therefore, we should develop effective, easy, simple and rapid biodosimetry and its guideline(triage) to be able to be treated the victims as fast as possible. We established the apoptotic fragment assay, PCC, comet assay, and micronucleus assay which was the significant relationship between dose and cell damages to evaluate the irradiated dose as correct and rapid as possible using lymphocytes and crypt cells, and compared with chromosome dosimetry and micronucleus assay.

Development of radiation biological dosimetry and treatment of radiation-induced damaged tissue

International Nuclear Information System (INIS)

Cho, Chul Koo; Kim, Tae Hwan; Lee, Yun Sil

2000-04-01

Util now, only a few methods have been developed for radiation biological dosimetry such as conventional chromosome aberration and micronucleus in peripheral blood cell. However, because these methods not only can be estimated by the expert, but also have a little limitation due to need high technique and many times in the case of radiation accident, it is very difficult to evaluate the absorbed dose of victims. Therefore, we should develop effective, easy, simple and rapid biodosimetry and its guideline(triage) to be able to be treated the victims as fast as possible. We established the apoptotic fragment assay, PCC, comet assay, and micronucleus assay which was the significant relationship between dose and cell damages to evaluate the irradiated dose as correct and rapid as possible using lymphocytes and crypt cells, and compared with chromosome dosimetry and micronucleus assay

Early mechanisms in radiation-induced biological damage

International Nuclear Information System (INIS)

Powers, E.L.

1983-01-01

An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical

Radiation-induced normal tissue damage: implications for radiotherapy

International Nuclear Information System (INIS)

Prasanna, Pataje G.

2014-01-01

Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

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

Science.gov (United States)

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Micronuclei: sensitivity for the detection of radiation induced damage

International Nuclear Information System (INIS)

Di Giorgio, M.; Nasazzi, N.B.; Taja, M.R.

1998-01-01

The in vitro cytokinesis-block (CB) micronucleus (MN) assay for human peripheral blood has been used extensively for the assessment of chromosomal damage induced by ionizing radiation and chemicals and considered a suitable biological dosimeter for estimating in vivo whole body exposures, particularly in the case of large scale radiation accidents. One of the major drawbacks of the MN assay is its reduced sensitivity for the detection of damage induced by low doses of low LET radiation, due to the high variability among the spontaneous MN frequencies. It is suggested that age, smoking habit and sex are the main confounding factors that contribute to the observed variability. Previous work in our laboratory, shows a significant positive correlation of the spontaneous and radiation induced MN frequencies with age and smoking habit, the latter being the strongest confounder. These findings led to in vitro studies of the dose-response relationships for smoking and non smoking donors evaluated separately, using 60 Co γ rays. The objectives of the present work are: 1-To increase the amount of data of the dose-response relationships, using γ rays from a 60 Co source, for smoking and non smoking donors, in order to find, if applicable, a correction factor for the calibration curve that takes into account the smoking habit of the individual in the case of accidental overexposure dose assessment, particularly in the low dose range. 2-To establish general conclusions on the current state of the technique. The sample for smoking and non smoking calibration curves was enlarged in the range of 0Gy to 2Gy. The fitting of both curves, performed up to the 2Gy dose, resulted in a linear quadratic model. MN distribution among bi nucleated cells was found to be over dispersed with respect to Poisson distribution, the average ratio of variance to mean being 1.13 for non smokers and 1.17 for smokers. Each fitted calibration curve, for smoking and non smoking donors, fell within the 95

Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay

International Nuclear Information System (INIS)

Praveen Kumar, M.K.; Shyama, S.K.; Sonaye, B.S.; Naik, U Roshini; Kadam, S.B.; Bipin, P.D.; D’costa, A.; Chaubey, R.C.

2014-01-01

Highlights: • Possible genotoxic effect of accidental exposure of aquatic fauna to γ radiation. • Relative sensitivity of bivalves to γ radiation is also analyzed using comet assay. • γ radiation induced significant genetic damage in both the species of bivalves. • P. malabarica and M. casta exhibited a similar level of sensitivity to γ radiation. • Comet assay may be used as a biomarker for the environmental biomonitoring. - Abstract: Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of ‘Comet assay’ for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in

Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay

Energy Technology Data Exchange (ETDEWEB)

Praveen Kumar, M.K., E-mail: here.praveen@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Shyama, S.K., E-mail: skshyama@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Sonaye, B.S. [Department of Radiation Oncology, Goa Medical College, Goa (India); Naik, U Roshini; Kadam, S.B.; Bipin, P.D.; D’costa, A. [Department of Zoology, Goa University, Goa 403206 (India); Chaubey, R.C. [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

2014-05-01

Highlights: • Possible genotoxic effect of accidental exposure of aquatic fauna to γ radiation. • Relative sensitivity of bivalves to γ radiation is also analyzed using comet assay. • γ radiation induced significant genetic damage in both the species of bivalves. • P. malabarica and M. casta exhibited a similar level of sensitivity to γ radiation. • Comet assay may be used as a biomarker for the environmental biomonitoring. - Abstract: Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of ‘Comet assay’ for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in

Radiation-Induced Astrogliosis and Blood-Brain Barrier Damage Can Be Abrogated Using Anti-TNF Treatment

International Nuclear Information System (INIS)

Wilson, Christy M.; Gaber, M. Waleed; Sabek, Omaima M.; Zawaski, Janice A.; Merchant, Thomas E.

2009-01-01

Purpose: In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors. Methods and Materials: Intravital microscopy and a closed cranial window technique were used to measure quantitatively BBB permeability to FITC-dextran 4.4-kDa molecules, leukocyte adhesion (Rhodamine-6G) and vessel diameters before and after 20-Gy cranial radiation with and without treatment with anti-TNF. Immunohistochemistry was used to quantify astrogliosis post-RT and immunofluorescence was used to visualize protein expression of TNF and ICAM-1 post-RT. Recombinant TNF (rTNF) was used to elucidate the role of TNF in leukocyte adhesion and vessel diameter. Results: Mice treated with anti-TNF showed significantly lower permeability and leukocyte adhesion at 24 and 48 h post-RT vs. RT-only animals. We observed a significant decrease in arteriole diameters at 48 h post-RT that was inhibited in TNF-treated animals. We also saw a significant increase in activated astrocytes following RT that was significantly lower in the anti-TNF-treated group. In addition, immunofluorescence showed protein expression of TNF and ICAM-1 in the cerebral cortex that was inhibited with anti-TNF treatment. Finally, administration of rTNF induced a decrease in arteriole diameter and a significant increase in leukocyte adhesion in venules and arterioles. Conclusions: TNF plays a significant role in acute changes in BBB permeability, leukocyte adhesion, arteriole diameter, and astrocyte activation following cranial radiation. Treatment with anti-TNF protects the brain's microvascular network from the acute damage following RT.

Repair of endogenous and ionizing radiation-induced DNA damages: mechanisms and biological functions

International Nuclear Information System (INIS)

Boiteux, S.

2002-01-01

The cellular DNA is continuously exposed to endogenous and exogenous stress. Oxidative stress due to cellular metabolism is the major cause of endogenous DNA damage. On the other hand, ionizing radiation (IR) is an important exogenous stress. Both induce similar DNA damages: damaged bases, abasic sites and strand breakage. Most of these lesions are lethal and/or mutagenic. The survival of the cell is managed by efficient and accurate DNA repair mechanisms that remove lesions before their replication or transcription. DNA repair pathways involved in the removal of IR-induced lesions are briefly described. Base excision repair (BER) is mostly involved in the removal of base damage, abasic sites and single strand breaks. In contrast, DNA double strand breaks are mostly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). How DNA repair pathways prevent cancer process is also discussed. (author)

Radiation induced damage to the lipid contents of bacteria and cultured mammalian cells

International Nuclear Information System (INIS)

Gholipour Khalili, K.

1993-01-01

In this study, exponentially growing phase of E. Coli. K12-N167 and cultured mouse leukemic L5178Y were used to study the effect of gamma irradiation on phospholipid contents. Following irradiation, both bacteria and cultured cells were incubated with either 14 C or 32 P labelled precursors for periods of cell division time. Phospholipid composition and their contents were detected in both the bacteria and cultured cells by using liquid scintillation counting and autoradiography methods. In contrast, as radiation dose increased, the Phospholipid contents were decreased in the both bacteria and cultured cells. It was concluded that the changes of phospholipid contents may result to altered activities of phospholipid pathway enzymes damaged by a radiation dose. The results of this investigation would be helpful in control of induced radiation damages in cell killings in radiation workers and radiation treatment of human cancer in the clinics. (author). 35 refs, 3 figs, 4 tabs

Stem cell therapy for the treatment of radiation-induced normal tissue damage

International Nuclear Information System (INIS)

Chapel, A.; Benderitter, M.; Gourmelon, P.; Lataillade, J.J.; Gorin, N.C.

2013-01-01

Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. In Europe, per year, 1.5 million patients undergo external radiotherapy. Acute adverse effect concern 80% of patients. The late adverse effect of radiotherapy concern 5 to 10% of them, which could be life threatening. Eradication of these manifestations is crucial. The French Institute of Radioprotection and Nuclear Safety (IRSN) contribute to understand effect of radiation on healthy tissue. IRSN is strongly implicated in the field of regeneration of healthy tissue after radiotherapy or radiological accident and in the clinical use of cell therapy in the treatment of irradiated patients. Our first success in cell therapy was the correction of deficient hematopoiesis in two patients. The intravenous injection of Mesenchymal Stem Cells (MSC) has restored bone marrow micro-environment after total body irradiation necessary to sustain hematopoiesis. Cutaneous radiation reactions play an important role in radiation accidents, but also as a limitation in radiotherapy and radio-oncology. We have evidenced for the first time, the efficiency of MSC therapy in the context of acute cutaneous and muscle damage following irradiation in five patients. Concerning the medical management of gastrointestinal disorder after irradiation, we have demonstrated the promising approach of the MSC treatment. We have shown that MSC migrate to damaged tissues and restore gut functions after radiation damage. The evaluation of stem cell therapy combining different sources of adult stem cells is under investigation

The Effect of a Grape Seed Extract on Radiation-Induced DNA Damage in Human Lymphocytes

Science.gov (United States)

Dicu, Tiberius; Postescu, Ion D.; Foriş, Vasile; Brie, Ioana; Fischer-Fodor, Eva; Cernea, Valentin; Moldovan, Mircea; Cosma, Constantin

2009-05-01

Plant-derived antioxidants due to their phenolic compounds content are reported as potential candidates for reducing the levels of oxidative stress in living organisms. Grape seed extracts are very potent antioxidants and exhibit numerous interesting pharmacologic activities. Hydroethanolic (50/50, v/v) standardized extract was obtained from red grape seed (Vitis vinifera, variety Burgund Mare—BM). The total polyphenols content was evaluated by Folin-Ciocalteu procedure and expressed as μEq Gallic Acid/ml. The aim of this study was to evaluate the potential antioxidant effects of different concentrations of BM extract against 60Co γ-rays induced DNA damage in human lymphocytes. Samples of human lymphocytes were incubated with BM extract (12.5, 25.0 and 37.5 μEq GA/ml, respectively) administered at 30 minutes before in vitro irradiation with γ-rays (2 Gy). The DNA damage and repair in lymphocytes were evaluated using alkaline comet assay. Using the lesion score, the radiation-induced DNA damage was found to be significantly different (pextract (except the lymphocytes treated with 37.5 μEq GA/ml BM extract). DNA repair analyzed by incubating the irradiated cells at 37° C and 5% CO2 atmosphere for 2 h, indicated a significant difference (pextract, immediately and two hours after irradiation. These results suggest radioprotective effects after treatment with BM extract in human lymphocytes.

Radiation damage and its repair in non-sporulating bacteria

International Nuclear Information System (INIS)

Moseley, B.E.B.

1984-01-01

A review is given of radiation damage and its repair in non-sporulating bacteria. The identification and measurement of radiation damage in the DNA of the bacteria after exposure to ultraviolet radiation and ionizing radiation is described. Measuring the extent of DNA repair and ways of isolating repair mutants are also described. The DNA repair mechanisms for UV-induced damage are discussed including photoreactivation repair, excision repair, post-replication recombination repair and induced error-prone repair. The DNA repair mechanisms for ionizing radiation damage are also discussed including the repair of both single and double-strand breaks. Other aspects discussed include the effects of growth, irradiation medium and recovery medium on survival, DNA repair in humans, the commercial use of UV and ionizing radiations and the future of ionizing irradiation as a food treatment process. (U.K.)

Influence of the complexity of radiation-induced DNA damage on enzyme recognition

International Nuclear Information System (INIS)

Palmer, Philip

2002-01-01

Ionising radiation is unique in inducing DNA clustered damage together with the simple isolated lesions. Understanding how these complex lesions are recognised and repaired by the cell is key to understanding the health risks associated with radiation exposure. This study focuses on whether ionising radiation-induced complex single-strand breaks (SSB) are recognised by DNA-PK and PARP, and whether the complexity of DSB influence their ligation by either DNA ligase lV/XRCC4 (LX) complex or T4 DNA ligase. Plasmid DNA, irradiated in aqueous solution using sparsely ionising γ-rays and densely ionising α-particles produce different yields of complex DNA damages, used as substrates for in vitro DNA-PK and PARP activity assays. The activity of DNA-PK to phosphorylate a peptide was determined using HF19 cell nuclear extracts as a source of DNA-PK. PARP ADP-ribosylation activity was determined using purified PARP enzyme. The activation of DNA-PK and PARP by irradiated DNA is due to SSB and not the low yield of DSB (linear plasmid DNA <10%). A ∼2 fold increase in DNA-PK activation and a ∼3-fold reduction in PARP activity seen on increasing the ionising density of the radiation (proportion of complex damage) are proposed to reflect changes in the complexity of SSB and may relate to damage signalling. Complex DSB synthesised as double-stranded oligonucleotides, with a 2 bp 5'-overhang, and containing modified lesions, 8-oxoguanine and abasic sites, at known positions relative to the termini were used as substrates for in vitro ligation by DNA ligase IV/XRCC4 or T4 ligase. The presence of a modified lesion 2 or 3 bp but not 4 bp from the 3'-termini and 2 or 6 bp from the 5'-termini caused a drastic reduction in the extent of ligation. Therefore, the presence of modified lesions near to the termini of a DSB may compromise their rejoining by non-homologous end-joining (NHEJ) involving the LX complex. (author)

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature

Directory of Open Access Journals (Sweden)

Abbaszadeh A.

2017-06-01

Full Text Available Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/ biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses

The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

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Arpita Chatterjee

2018-01-01

Full Text Available Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs, ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

Lycopene: An antioxidant and radioprotector against γ-radiation-induced cellular damages in cultured human lymphocytes

International Nuclear Information System (INIS)

Srinivasan, M.; Devipriya, N.; Kalpana, K.B.; Menon, Venugopal P.

2009-01-01

The present study aimed to evaluate the radioprotective effect of lycopene, a naturally occurring dietary carotenoid on γ-radiation-induced toxicity. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analyzed by cytokinesis blocked micronucleus assay (CBMN), dicentric aberration (DC) and translocation frequency. The γ-radiation at different doses (1, 2 and 4 Gy) resulted in a significant increase in the number of micronuclei (MN), DC, translocation frequency, TBARS and HP level, whereas the levels of GSH and antioxidant enzymes were significantly decreased when compared with normal control. The maximum damage to lymphocytes was observed at 4 Gy irradiation. Lycopene pretreatment (1, 5 and 10 μg/ml) significantly decreased the frequency of MN, DC and translocation when compared with γ-radiation control. The levels of TBARS, HP were also decreased and activities of SOD, CAT and GPx were significantly increased along with GSH levels when compared with γ-radiation control. The dose of 5 μg/ml of lycopene was found to be more effective than the other two doses. Thus, our result shows that pretreatment with lycopene offers protection to normal lymphocytes against γ-radiation-induced cellular damage.

Compound Poisson Processes and Clustered Damage of Radiation Induced DNA Double Strand Breaks

International Nuclear Information System (INIS)

Gudowska-Nowak, E.; Ritter, S.; Taucher-Scholz, G.; Kraft, G.

2000-01-01

Recent experimental data have demonstrated that DNA damage induced by densely ionizing radiation in mammalian cells is distributed along the DNA molecule in the form of clusters. The principal constituent of DNA damage are double-strand breaks (DSB) which are formed when the breaks occur in both DNA strands and are directly opposite or separated by only a few base pairs. DSBs are believed to be most important lesions produced in chromosomes by radiation; interaction between DSBs can lead to cell killing, mutation or carcinogenesis. The paper discusses a model of clustered DSB formation viewed in terms of compound Poisson process along with the predictive essay of the formalism in application to experimental data. (author)

Action of the chlorophyllin on the genetic damage induced by gamma radiation in germinal cells of Drosophila Melanogaster

International Nuclear Information System (INIS)

Cruces, M.P.; Pimentel, A.E.; Moreno, A.; Moreno, R.

2003-01-01

The obtained results using somatic cells, they have evidenced that the chlorophyllin (CHLN) it can act inhibiting or increasing the damage caused by different mutagens. The objective of this investigation is to evaluate the effect of the CHLN on the damage induced by gamma radiation in germinal cells of Drosophila. Two tests were used, the lost of the X chromosome and the conventional test of lethal recessive bound to the sex (LRLS); both with a system of litters. The obtained results in both essays, indicated that the CHLN doesn't reduce the damage induced by the gamma radiation in none of the cellular monitored states. (Author)

Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay.

Science.gov (United States)

Praveen Kumar, M K; Shyama, S K; Sonaye, B S; Naik, U Roshini; Kadam, S B; Bipin, P D; D'costa, A; Chaubey, R C

2014-05-01

Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in both bivalve species. This showed a dose-dependent increase of genetic damage induced in bivalves by EMS as well as gamma radiation. Further, the highest DNA damage was observed at 24h. The damage gradually decreased with time, i.e. was smaller at 48 and 72 h than at 24h post irradiation in both species of bivalves. This may indicate repair of the damaged DNA and/or loss of heavily damaged cells as the post irradiation time advanced. The present study

Protective Effect of Diphlorethohydroxycarmalol against Ultraviolet B Radiation-Induced DNA Damage by Inducing the Nucleotide Excision Repair System in HaCaT Human Keratinocytes

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Mei Jing Piao

2015-09-01

Full Text Available We investigated the protective properties of diphlorethohydroxycarmalol (DPHC, a phlorotannin, against ultraviolet B (UVB radiation-induced cyclobutane pyrimidine dimers (CPDs in HaCaT human keratinocytes. The nucleotide excision repair (NER system is the pathway by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV radiation-induced CPDs and 6-4 photoproducts. CPDs levels were elevated in UVB-exposed cells; however, this increase was reduced by DPHC. Expression levels of xeroderma pigmentosum complementation group C (XPC and excision repair cross-complementing 1 (ERCC1, which are essential components of the NER pathway, were induced in DPHC-treated cells. Expression of XPC and ERCC1 were reduced following UVB exposure, whereas DPHC treatment partially restored the levels of both proteins. DPHC also increased expression of transcription factor specificity protein 1 (SP1 and sirtuin 1, an up-regulator of XPC, in UVB-exposed cells. DPHC restored binding of the SP1 to the XPC promoter, which is reduced in UVB-exposed cells. These results indicate that DPHC can protect cells against UVB-induced DNA damage by inducing the NER system.

Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

Energy Technology Data Exchange (ETDEWEB)

Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

2013-06-01

Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin.

Science.gov (United States)

Jelveh, Salomeh; Kaspler, Pavel; Bhogal, Nirmal; Mahmood, Javed; Lindsay, Patricia E; Okunieff, Paul; Doctrow, Susan R; Bristow, Robert G; Hill, Richard P

2013-08-01

Radioprotection and mitigation effects of the antioxidants, Eukarion (EUK)-207, curcumin, and the curcumin analogs D12 and D68, on radiation-induced DNA damage or lipid peroxidation in murine skin were investigated. These antioxidants were studied because they have been previously reported to protect or mitigate against radiation-induced skin reactions. DNA damage was assessed using two different assays. A cytokinesis-blocked micronucleus (MN) assay was performed on primary skin fibroblasts harvested from the skin of C3H/HeJ male mice 1 day, 1 week and 4 weeks after 5 Gy or 10 Gy irradiation. Local skin or whole body irradiation (100 kVp X-rays or caesium (Cs)-137 γ-rays respectively) was performed. DNA damage was further quantified in keratinocytes by immunofluorescence staining of γ-histone 2AX (γ-H2AX) foci in formalin-fixed skin harvested 1 hour or 1 day post-whole body irradiation. Radiation-induced lipid peroxidation in the skin was investigated at the same time points as the MN assay by measuring malondialdehyde (MDA) with a Thiobarbituric acid reactive substances (TBARS) assay. None of the studied antioxidants showed significant mitigation of skin DNA damage induced by local irradiation. However, when EUK-207 or curcumin were delivered before irradiation they provided some protection against DNA damage. In contrast, all the studied antioxidants demonstrated significant mitigating and protecting effects on radiation-induced lipid peroxidation at one or more of the three time points after local skin irradiation. Our results show no evidence for mitigation of DNA damage by the antioxidants studied in contrast to mitigation of lipid peroxidation. Since these agents have been reported to mitigate skin reactions following irradiation, the data suggest that changes in lipid peroxidation levels in skin may reflect developing skin reactions better than residual post-irradiation DNA damage in skin cells. Further direct comparison studies are required to confirm

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

International Nuclear Information System (INIS)

Thacker, J.

1986-01-01

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

REC-2006-A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo.

Science.gov (United States)

Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

2011-01-01

Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg(-1) body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair.

New concept of damage evaluation method for core internal materials considering radiation induced stress relaxation (1). Experiments and modeling of radiation effects

International Nuclear Information System (INIS)

Miwa, Yukio; Kondo, Keietsu; Okubo, Nariaki; Kaji, Yoshiyuki; Tsukada, Takashi

2009-01-01

In order to build the new concept of material damage evaluation method, synergistic effect of radiation and residual stress on material degradation was estimated experimentally, and the effect of radiation induced stress relaxation on retardation of material degradation was observed. (author)

Molecular mechanisms in radiation damage to DNA: Final report

International Nuclear Information System (INIS)

Osman, R.

1996-01-01

The objectives of this work were to elucidate the molecular mechanisms that were responsible for radiation-induced DNA damage. The studies were based on theoretical explorations of possible mechanisms that link initial radiation damage in the form of base and sugar damage to conformational changes in DNA

Microfabricated electrochemical sensor for the detection of radiation-induced DNA damage

Energy Technology Data Exchange (ETDEWEB)

Wang, J.; Rivas, G.; Ozsoz, M.; Grant, D.H.; Cai, X.; Parrado, C. [New Mexico State Univ., Las Cruces, NM (United States)

1997-04-01

An electrochemical biosensor protocol for the detection of radiation-induced DNA damage is described. The procedure employs a dsDNA-coated screen-printed electrode and relies on changes in the guanine-DNA oxidation signal upon exposure to ultraviolet radiation. The decreased signal is ascribed primarily to conformational changes in the DNA and to the photoconversion of the guanine-DNA moiety to a nonelectroactive monomeric base product. Factors influencing the response of these microfabricated DNA sensors, such as irradiation time, wavelength, and distance, are explored, and future prospects are discussed. Similar results are given for the use of bare strip electrodes in connection with irradiated DNA solutions. 8 refs., 4 figs.

Radiation damage in biomolecular systems

CERN Document Server

Fuss, Martina Christina

2012-01-01

Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection. Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada,  the USA and Australia. This book summarizes the advances achieved by these...

Reduction of radiation-induced damage to salivary gland by bone marrow derived stem cells

International Nuclear Information System (INIS)

Coppes, R.P.; Wierenga, P.K.; Kampinga, H.H.; De Hann, G.

2003-01-01

Irradiation of the salivary glands can result in severe side effects that reduce the patient's quality of life. Late damage to the salivary glands is mainly caused by exhaustion of the tissue's stem cells. Post-irradiation replacement of salivary gland stem cells with healthy donor stem cells may reduce complications. Bone marrow derived stem cells (BMSC) have been show to be multipotent and engraft in many tissue after injury. In this study we assessed the potential of BMSC to reduce irradiation-induced salivary gland damage. The salivary glands of wild type C57Bl/6 mice were locally irradiated with 20 Gy. Thirty days later, BMSC from transgenic eGFP+ C57Bl/6 mice were transplanted by i.v. injection or by direct injection into the salivary glands. In addition, animals were transplanted with eGFP + bone marrow after 9.5 Gy TBI excluding the salivary glands. Subsequently, the animals were locally irradiated to the salivary gland with 20 Gy. Thirty days later i.v. G-CSF mobilised eGFP + bone marrow derived stem cells to the peripheral blood. Again thirty days after mobilisation, the salivary gland were harvested. eGFP + cells were detected by confocal laser fluorescence scanning microscopy and flow cytometry and H and E histology was performed. eGFP + cells were detected in the salivary gland after all protocols. The number of eGFP + cells in irradiated salivary glands was highest in animals treated with G-CSF. Intraglandular transplantation, in contrast, was successful only in 1 out of 8 attempts. Immuno-histochemistry using a-SM-actin antibodies showed the close vicinity of actin and eGFP within the cells, demonstrating the occurrence of BMSC derived myoepithelial cells in irradiated salivary gland. Further, cell-type specific antibodies will reveal the nature of all eGFP + cells. H and E histology revealed improved gland morphology in animals treated with G-CSF after irradiation when compared to the non-treated animals. These preliminary results indicate that bone

Protection of vanillin derivative VND3207 on plasmid DNA damage induced by different LET ionizing radiation

International Nuclear Information System (INIS)

Xu Huihui; Wang Li; Sui Li; Guan Hua; Wang Yu; Liu Xiaodan; Zhang Shimeng; Xu Qinzhi; Wang Xiao; Zhou Pingkun

2011-01-01

Objective: To evaluate the radioprotective effect of vanillin derivative VND3207 on DNA damage induced by different LET ionizing radiation. Methods: The plasmid DNA in liquid was irradiated by 60 Co γ-rays, proton or 7 Li heavy ion with or without VND3207. The conformation changes of plasmid DNA were assessed by agarose gel electrophoresis and the quantification was done using gel imaging system. Results: The DNA damage induced by proton and 7 Li heavy ion was much more serious as compared with that by 60 Co γ-rays, and the vanillin derivative VND3207 could efficiently decrease the DNA damage induced by all three types of irradiation sources, which was expressed as a significantly reduced ratio of open circular form (OC) of plasmid DNA. The radioprotective effect of VND3207 increased with the increasing of drug concentration. The protective efficiencies of 200 μmol/L VND3207 were 85.3% (t =3.70, P=0.033), 73.3% (t=10.58, P=0.017) and 80.4% (t=8.57, P=0.008) on DNA damage induction by 50 Gy of γ-rays, proton and 7 Li heavy ion, respectively. It seemed that the radioprotection of VND3207 was more effective on DNA damage induced by high LET heavy ion than that by proton. Conclusions: VND3207 has a protective effect against the genotoxicity of different LET ionizing radiation, especially for γ-rays and 7 Li heavy ion. (authors)

Characterization of radiation damage induced by swift heavy ions in graphite

Energy Technology Data Exchange (ETDEWEB)

Hubert, Christian

2016-05-15

Graphite is a classical material in neutron radiation environments, being widely used in nuclear reactors and power plants as a moderator. For high energy particle accelerators, graphite provides ideal material properties because of the low Z of carbon and its corresponding low stopping power, thus when ion projectiles interact with graphite is the energy deposition rather low. This work aims to improve the understanding of how the irradiation with swift heavy ions (SHI) of kinetic energies in the range of MeV to GeV affects the structure of graphite and other carbon-based materials. Special focus of this project is given to beam induced changes of thermo-mechanical properties. For this purpose the Highly oriented pyrolytic graphite (HOPG) and glassy carbon (GC) (both serving as model materials), isotropic high density polycrystalline graphite (PG) and other carbon based materials like carbon fiber carbon composites (CFC), chemically expanded graphite (FG) and molybdenum carbide enhanced graphite composites (MoC) were exposed to different ions ranging from {sup 131}Xe to {sup 238}U provided by the UNILAC accelerator at GSI in Darmstadt, Germany. To investigate structural changes, various in-situ and off-line measurements were performed including Raman spectroscopy, x-ray diffraction and x-ray photo-electron spectroscopy. Thermo-mechanical properties were investigated using the laser-flash-analysis method, differential scanning calorimetry, micro/nano-indentation and 4-point electrical resistivity measurements. Beam induced stresses were investigated using profilometry. Obtained results provided clear evidence that ion beam-induced radiation damage leads to structural changes and degradation of thermal, mechanical and electrical properties of graphite. PG transforms towards a disordered sp2 structure, comparable to GC at high fluences. Irradiation-induced embrittlement is strongly reducing the lifetime of most high-dose exposed accelerator components. For

Radiation damage to nucleoprotein complexes in macromolecular crystallography

International Nuclear Information System (INIS)

Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary; Ravelli, Raimond B. G.; Carmichael, Ian; Kneale, Geoff; McGeehan, John E.

2015-01-01

Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N 1 —C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses

Molecular mechanisms in radiation damage to DNA

International Nuclear Information System (INIS)

Osman, R.

1991-01-01

The objectives of this work are to elucidate the molecular mechanisms that are responsible for radiation-induced DNA damage. The overall goal is to understand the relationship between the chemical and structural changes produced by ionizing radiation in DNA and the resulting impairment of biological function expressed as carcinogenesis or cell death. The studies are based on theoretical explorations of possible mechanisms that link initial radiation damage in the form of base and sugar damage to conformational changes in DNA. These mechanistic explorations should lead to the formulation of testable hypothesis regarding the processes of impairment of regulation of gene expression, alternation in DNA repair, and damage to DNA structure involved in cell death or cancer

Programmed cellular response to ionizing radiation damage

International Nuclear Information System (INIS)

Crompton, N.E.A.

1998-01-01

Three forms of radiation response were investigated to evaluate the hypothesis that cellular radiation response is the result of active molecular signaling and not simply a passive physicochemical process. The decision whether or not a cell should respond to radiation-induced damage either by induction of rescue systems, e.g. mobilization of repair proteins, or induction of suicide mechanisms, e.g. programmed cell death, appears to be the expression of intricate cellular biochemistry. A cell must recognize damage in its genetic material and then activate the appropriate responses. Cell type is important; the response of a fibroblast to radiation damage is both quantitatively and qualitatively different form that of a lymphocyte. The programmed component of radiation response is significant in radiation oncology and predicted to create unique opportunities for enhanced treatment success. (orig.)

REC-2006—A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo

Science.gov (United States)

Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

2011-01-01

Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg−1 body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair. PMID:20008078

Effect of proton and electron-irradiation intensity on radiation-induced damages in silicon bioolar transistors

International Nuclear Information System (INIS)

Bannikov, Yu.A.; Gorin, B.M.; Kozhevnikov, V.P.; Mikhnovich, V.V.; Gusev, L.I.

1981-01-01

The increase of radiation-induced damages of bipolar n-p-n transistors 8-12 times with the irradiation intensity decrease by protons from 4.07x1010 to 2.5x107 cm-2 x c-1 has been found experimentally. damages of p-n-p transistors vary in the opposite way - they are decreased 2-3 times with the irradiation intensity decrease within the same limits. the dependence of damages on intansity of proton irradiation occurs at the dose rate by three orders less than it has been observed for electron irradiation. the results obtained are explained by the dependence of radiation defectoformation reactions on charge state of defects with account for the role of formation of disordering regions upon proton irradiation [ru

Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells.

Directory of Open Access Journals (Sweden)

Luca A Petruccelli

Full Text Available Histone deacetylase inhibitors (HDACi are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents.

Vorinostat Induces Reactive Oxygen Species and DNA Damage in Acute Myeloid Leukemia Cells

Science.gov (United States)

Pettersson, Filippa; Retrouvey, Hélène; Skoulikas, Sophia; Miller, Wilson H.

2011-01-01

Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML) cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC) reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents. PMID:21695163

The contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore

International Nuclear Information System (INIS)

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

1985-01-01

Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia. (author)

Quinacrine pretreatment reduces microwave-induced neuronal damage by stabilizing the cell membrane

Science.gov (United States)

Ding, Xue-feng; Wu, Yan; Qu, Wen-rui; Fan, Ming; Zhao, Yong-qi

2018-01-01

Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine (20 and 40 mM) and irradiated them with 50 mW/cm2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation. PMID:29623929

Histamine protects bone marrow against cellular damage induced by Ionizing radiation

International Nuclear Information System (INIS)

Medina, Vanina; Sambuco, Lorena; Massari, Noelia; Cricco, Graciela; Martin, Gabriela; Bergoc, Rosa; Rivera, Elena S.

2008-01-01

After surgery, radiotherapy is arguably one of the most important treatments for cancer, especially for localized disease that has not spread. However, ionizing radiation is toxic not only to tumor cells but also to healthy tissues causing serious adverse effects to patients. We have recently reported that histamine prevents ionizing radiation-induced toxicity on mouse small intestine. The aim of the present work was to determine whether histamine is able to protect bone marrow cells against ionizing radiation damage. For that purpose 56 mice were divided into 4 groups. Histamine and Histamine-10Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued till the end of experimental period; untreated group received saline. Histamine-10Gy and untreated-10Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Bone marrow was removed, fixed and stained with hematoxylin and eosin. The number of megacariocytes per 40x field, bone marrow tropism, edema, vascular damage, and other histological characteristics of bone marrow cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA) and cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Results indicate that histamine treatment substantially reduced the grade of aplasia, the edema and the vascular damage induced by ionizing radiation on bone marrow. Additionally, histamine preserved medullar components increasing significantly the number of megacariocytes per field (5.4 ± 0.4 vs. 2.8 ± 0.4 in Control-10 Gy, P<0.01). This effect was associated with an increased proliferation rate determined by the augmented PCNA expression and BrdU incorporation of bone marrow cells. On the basis of these results, we conclude that histamine

Concurrent Transient Activation of Wnt/{beta}-Catenin Pathway Prevents Radiation Damage to Salivary Glands

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Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States); Boyer, Arthur [Department of Radiology, Scott and White Hospital, Temple, Texas (United States); Liu, Fei, E-mail: fliu@medicine.tamhsc.edu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States)

2012-05-01

Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/{beta}-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/{beta}-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/{beta}-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/{beta}-catenin pathway could prevent radiation-induced salivary gland dysfunction.

Concurrent Transient Activation of Wnt/β-Catenin Pathway Prevents Radiation Damage to Salivary Glands

International Nuclear Information System (INIS)

Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu; Boyer, Arthur; Liu, Fei

2012-01-01

Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/β-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/β-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/β-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/β-catenin pathway could prevent radiation-induced salivary gland dysfunction.

Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones

Directory of Open Access Journals (Sweden)

Matthew D Fountain

2016-11-01

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

Radiation-induced apoptosis

International Nuclear Information System (INIS)

Ohyama, Harumi

1995-01-01

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

Radiation damage for the spallation target of ADS

International Nuclear Information System (INIS)

Fan Sheng; Ye Yanlin; Xu Chuncheng; Chen Tao; Sobolevsky, N.M.

2000-01-01

By using SHIELD codes system, the authors investigate the radiation damage, such as radiation damage cross section, displacement atom cross section and the rate of displacement atom, gas production cross section, the rate of gas production and the ratio, R, of the helium and displacement production rates in target, container window and spallation neutron source materials as W and Pb induced from intermediate energy proton and neutron incident. And the study of radiation damage in the thick Pb target with long 60 cm, radius 20 cm is presented

Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

International Nuclear Information System (INIS)

Camats, Nuria; Garcia, Francisca; Parrilla, Juan Jose; Calaf, Joaquim; Martin, Miguel; Caldes, Montserrat Garcia

2008-01-01

Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

Energy Technology Data Exchange (ETDEWEB)

Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

2008-04-02

Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

Effects of an Amifostine analogue on radiation induced lung inflammation and fibrosis

International Nuclear Information System (INIS)

Arora, Aastha; Bhuria, Vikas; Soni, Ravi; Singh, Saurabh; Hazari, Puja Panwar; Bhatt, Anant Narayan; Dwarakanath, B.S.; Pathak, Uma; Mathur, Shweta; Sandhir, Rajat

2014-01-01

Radiation-induced pulmonary toxicity causes significant morbidity and mortality in patients irradiated for thoracic malignancies as well as in victims of accidental radiation exposure. We have recently established the efficacy of an analogue of Amifostine (DRDE-30) in reducing the mortality of whole body irradiated mice. The widely used radioprotector Amifostine has been found to reduce the incidence of radiation induced pneumonitis during radiation therapy for non small cell lung carcinoma. In the present study, we investigated the potential of DRDE-30 in ameliorating the radiation induced lung damage. Intra-peritoneal administration of DRDE-30 at 220 mg/kg b.wt 30 min. prior to 13.5 Gy thoracic radiation enhanced the 24-month survival of C57BL/6 mice to 80% compared to 0% with radiation alone. Reduced protein content and cell number in the broncheo-alveolar lavage fluid suggested reduction in radiation induced vascular permeability in DRDE-30 treated mice. Higher levels of MnSOD and Catalase observed under these conditions indicated that strengthening of the anti-oxidant defense system by DRDE-30 could also contribute to the protection against radiation induced lung damage. Reduced levels of p-p38 observed under these conditions suggested down-regulation of the p38/MAP kinase pathway as one of the plausible mechanisms underlying anti-inflammatory effects of DRDE-30, while lower levels of Vimentin seen, indicated inhibition of epithelial to mesenchymal transition revealing its anti-fibrotic effect as well. Structural analysis with X-ray CT indicated comparable lung architecture in control and drug treated mice in terms of reduced opacity, which correlated well with the lung morphology (H and E staining) and reduced collagen deposition (trichrome staining). These results demonstrate the potential of DRDE-30 in reducing radiation induced pulmonary toxicity by attenuating the inflammatory and fibrotic responses. (author)

Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

International Nuclear Information System (INIS)

Heintz, Desiree Ellen

2012-07-01

The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

Energy Technology Data Exchange (ETDEWEB)

Heintz, Desiree Ellen

2012-07-15

The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

Radiation-induced brain damage in children

International Nuclear Information System (INIS)

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

1990-01-01

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

Grape (Vitis vinifera) extracts protect against radiation-induced oxidative stress and DNA damage

International Nuclear Information System (INIS)

Singha, Indrani; Das, Subir Kumar; Saxena, S.; Gautam, S.

2016-01-01

Ionizing radiation (IR) causes oxidative stress through the overwhelming generation of reactive oxygen species (ROS) in the living cells leading further to the oxidative damage to biomolecules. Grapes (Vitis vinifera) contain several bioactive phytochemicals and are the richest source of antioxidant. In this study, we investigated and compared in vitro antioxidant activity and DNA damage protective property of the grape extracts of four different cultivars, including the Thompson seedless, Flame seedless, Kishmish chorni and Red globe. The activities of ascorbic acid oxidase and catalase significantly (p<0.01) differed among extracts within the same cultivar, while that of peroxidase and polyphenol oxidase did not differ significantly among extracts of any cultivar. In vitro antioxidant activities were assessed by ferric-reducing antioxidant power (FRAP) assay and ABTS. The superoxide radical-scavenging activity was higher in the seed as compared to the skin or pulp of the same cultivar. DNA damage was evaluated in acellular system using pBR322 plasmid relaxation. Grape extract was able to effectively scavenge free radicals in vitro. It could significantly prevent radiation-induced DNA damage. Furthermore, the protective action of grape depends on the source of extract and type of the cultivars. (author)

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

Directory of Open Access Journals (Sweden)

Gholam Hassan Haddadi

2017-01-01

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

Modifier activity of the protoporphyrin IX of the clastogenic damage induced by gamma radiation in Drosophila melanogaster

International Nuclear Information System (INIS)

Martinez A, G.

2007-01-01

It has been demonstrated that the copper sodium chlorophyllin (CCS) it is a potent inhibitor of the one genetic damage induced by physical or chemical agents in systems like: bacteria, Drosophila, rainbow trout and mammals. Nevertheless it has been observed that under certain conditions it promotes it. In the laboratory of Drosophila of the ININ evidences have been obtained that the CCS increases the percentage of lethal embryonic dominant and post-embryonic induced by gamma radiation. One of the probable causes of this effect promoter, is the oxidizer stress that it could cause the metallic center of the CCS. The objective of this investigation it was the evaluation of the inhibitory action of the protoporphyrin IX (PP-IX) of the genetic damage induced by gamma radiation in the germinal line of Drosophila melanogaster. For such effect it was used the lethal dominant test by means of two protocols: one in the one that the PP-IX or CCS was administered to the females and the other one to the males. Females of genotype y/y and males of the canton-S stump were used. In both cases the males were treated with 40 Gy of gamma radiation. Its were count the embryonic lethal dominant (L-E) and those post-embryonic (L-PE) of the F1. The results indicated that after the one pretreatment with PP-IX to the crossed females with males treaties increase the percentage of L-E (P ≤ 0.001) and it diminished that of L-PE (P ≤ 0.001) compared with the sucrose control more radiation, however when it was pretreated with CCS also it was observed an increment in the percentage of L-E (P ≤ 0.001), but it doesn't present effect on that of L-PE. In contrast, when the males were pretreated, it was observed that the PP-IX tends to increase those L-E, but diminished the L-PE (P ≤ 0.05), however when it was pretreated with CCS was observed that increased the percentage of L-E (P ≤ 0.001) but diminished that of L-PE (P ≤ 0.001). It was concluded that none of the two pigments act as

Potential biological indicators of multi-organ damage: Application to radiation accident victims

International Nuclear Information System (INIS)

Bertho, J.M.; Souidi, M.; Gourmelon, P.

2009-01-01

Accidental irradiations induce a complex pathological situation, difficult to assess and to treat. However, recent results describing new biological indicators of radiation-induced damages such as Flt3-ligand, citrulline and oxy-sterol concentration in the plasma, together with results obtained in large animal models of high dose irradiation, allowed a better understanding of pathophysiological mechanisms induced by uncontrolled irradiations. This conducted to leave the classical paradigm of the acute radiation syndrome, described as the association of three individual syndromes, the hematopoietic syndrome, the gastro-intestinal syndrome and the cerebrovascular syndrome, in favour of a multiple organ dysfunction syndrome, with the implication of other organs and systems. Follow-up of victims from two recent radiation accidents brings a confirmation of the usefulness of the newly described biological indicators, and also a partial confirmation of this new concept of a multiple organ dysfunction syndrome. (authors)

XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

Science.gov (United States)

Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

2014-03-01

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

Science.gov (United States)

Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

2015-12-01

Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (pmicrowave exposed groups (pmicrowave exposed animal (pmicrowave exposed groups as compared to their corresponding values in sham exposed group (pmicrowave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy of wheat germ oil in modulating radiation-induced heart damage in rats

International Nuclear Information System (INIS)

Said, U.Z.; Azab, Kh.Sh.

2006-01-01

Wheat Germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. This study was designed to investigate the cardio-protective efficacy of wheat germ oil, on radiation-induced oxidative damage in rat's heart. Wheat germ oil was supplemented by gavage to rats at a dose of 81 mg/ kg body wt for 10 successive days pre- and 7 successive days post-exposure to 7 Gy (single dose) of whole body gamma irradiation. The dose of wheat germ oil is equivalent to daily human nutritional supplementation quantity. The results revealed that whole body ?-irradiation of rats produced significant alterations in blood cells picture. The erythrocyte, leucocyte, platelet counts and hemoglobin levels decreased after irradiation. Also, radiation-induced biochemical disorders manifested by significant elevation in xanthine oxidase activity (XO) and thiobarbituric acid reactive substances (TBARS) level, with decrease in reduced glutathione (GSH) content in heart tissues, indicating depression in the antioxidant status. Serum lipid profile as total cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and triglycerides levels (TG) were significantly higher than normal control rats. Radiation exposure produced a significant rise in the activities of serum markers for heart damage as creatine phosphokinase (CPK), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) indicating acute cardiac toxicity. Moreover, the obtained results revealed abnormal electrophoretic pattern of LDH isoenzymes in the 7th day after exposure to gamma rays. Three bands only appear on the agarose film comparing with 4 bands in normal control rats. The rats that received wheat germ oil supplement showed significantly less severe damage and remarkable improvement in all of the measured parameters when compared to

Chromosomal damages and mutagenesis in mammalian and human cells induced by ionizing radiations with different LET

International Nuclear Information System (INIS)

Govorun, R.D.

1997-01-01

On the basis of literature and proper data the inference was made about essential role of structural chromosomal (and gene) damages in spontaneous and radiation-induced mutagenesis of mammalian and human cells on HPRT-loci. The evidences of increasing role of these damages in the mutagenesis after the influence of ionizing radiations with high LET are adduced. The consequences of HPRT-gene damages have been examined hypothetically. The geterogeneity of mutant subclones on their cytogenetical properties were revealed experimentally. The data reflect a phenomenon of the reproductive chromosomal instability in many generations of mutant cell. The mutagenesis of mammalian cells is also accompanied by the impairment of chromosome integrity with high probability as a stage of appropriate genome reorganization because of changed vital conditions

Cytogenetic damages induced in vivo in human lymphocytes by environmental chemicals or radiation

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.

1999-01-01

The importance of various environmental exposures has been evident in variation in cancer incidence and mortality. Benzene is considered to be a human carcinogen, is clastogenic to rodents and humans, and it affects the immune response. Workers in various industrial plants, are exposed to benzene and benzene related compounds as a result of various activities in which benzene is processed, generated or used. Major sources of environmental exposure to benzene related compounds, continue to be active and passive smoking, auto exhaust, and driving or riding in automobiles. Benzene is of a particular interest, not only because of its known toxicity, but also because this was to be the parent compound and a model for extensive programs of metabolism of a variety of aromatic chemicals. Ionizing radiation is an unavoidable physical agent that is presented in environment, and public opinion is well aware against radiation risk and strongly against it. The aim of the presentation was comparison between cytogenetic damages induced in vivo by environmental chemicals with those of radiation. Results from biomonitoring survey on genotoxicity in human blood cells of benzene and benzene related compounds were compared to damages detected in lymphocytes of persons who had been accidentally exposed to gamma radiation. In the groups, that had been occupationally or environmentally exposed to benzene related compound, total aberration frequencies, or percent of aberrant cells ranged between 0 - 0.16 aberrations/cell or 16% of aberrant cells respectively. A multivariate regression analysis confirmed: (i) a significant association between cytogenetic damage and exposure to benzene related compound, (ii) a possible association between cytogenetic damage and cancer, (iii) a significant influence of smoking habit. In 1996 few persons were suspected of accidental exposure to gamma radiation. To estimate the absorbed doses, lymphocytes from their blood have been analyzed for the presence of

UV-induced skin damage

International Nuclear Information System (INIS)

Ichihashi, M.; Ueda, M.; Budiyanto, A.; Bito, T.; Oka, M.; Fukunaga, M.; Tsuru, K.; Horikawa, T.

2003-01-01

Solar radiation induces acute and chronic reactions in human and animal skin. Chronic repeated exposures are the primary cause of benign and malignant skin tumors, including malignant melanoma. Among types of solar radiation, ultraviolet B (290-320 nm) radiation is highly mutagenic and carcinogenic in animal experiments compared to ultraviolet A (320-400 nm) radiation. Epidemiological studies suggest that solar UV radiation is responsible for skin tumor development via gene mutations and immunosuppression, and possibly for photoaging. In this review, recent understanding of DNA damage caused by direct UV radiation and by indirect stress via reactive oxygen species (ROS) and DNA repair mechanisms, particularly nucleotide excision repair of human cells, are discussed. In addition, mutations induced by solar UV radiation in p53, ras and patched genes of non-melanoma skin cancer cells, and the role of ROS as both a promoter in UV-carcinogenesis and an inducer of UV-apoptosis, are described based primarily on the findings reported during the last decade. Furthermore, the effect of UV on immunological reaction in the skin is discussed. Finally, possible prevention of UV-induced skin cancer by feeding or topical use of antioxidants, such as polyphenols, vitamin C, and vitamin E, is discussed

Lack of effect of inhibitors of DNA synthesis/repair on the ionizing radiation-induced chromosomal damage in G[sub 2] stage of ataxia telangiectasia cells

Energy Technology Data Exchange (ETDEWEB)

Antoccia, A. (Univ. ' La Sapienza' , Rome (Italy). Dipt. di Genetica e Biologia Molecolare); Palitti, F.; Raggi, T. (Univ. del Tuscia, Viterbo (Italy). Dipt. di Agrobiologia ed Agrochimica); Catena, C. (ENEA, Casaccia (Italy). Centro Ricerche Energia); Tanzarella, C. (Rome Univ. 3 (Italy). Dipt. di Biologia)

1994-09-01

The relationship between the repair processes occurring at the G[sub 2] phase of the cell cycle and cytogenetic damage in ataxia telangiectasia (AT) cells was studied. Lymphoblastoid cells derived from normal, heterozygote AT (HzAT) and three AT patients were exposed to X-rays or fission neutrons and post-treated with inhibitors of DNA synthesis/repair, such as inhibitors of DNA polymerases [alpha], [sigma] and [epsilon] (cytosine arabinoside, ara-C; aphidicolin, APC; buthylphenyl-guanine, BuPdG) or ribonucleotide reductase (hydroxyurea HU). A strong increase of radiation-induced chromosomal aberrations was observed in normal and HzAT cells post-treated with ara-C, APC and HU, but not in the presence of BuPdG. No enhancing effect was observed in cells derived from AT patients, except for HU post-irradiation treatment. These results suggest that the enzymes that can be inhibited by these agents are not directly involved in the repair of radiation damage induced in G[sub 2] cells from AT patients, indicating that probably the AT cells that we used lack the capability to transform the primary DNA lesions into reparable products, or that AT cells might contain a mutated form of DNA polymerase resistant to the inhibitors. (author).

Evaluation of gamma radiation induced genetic damage in the fish Cyprinus carpio using comet assay

International Nuclear Information System (INIS)

Praveen Kumar, M.K.; Shyama, S.K.; Bhagat, S.S.; Chaubey, R.C.

2013-01-01

Radionuclides released from various sources including the industries, as well as, accidental release during a nuclear disaster can contaminate inland water bodies. Suitable bio-monitoring methods/biomarkers are the need of the day to assess the impact of high/low levels of radiation exposure in aquatic environment. Fishes are very important as a group of ecologically and commercially important non-human biota and are often used as a bioindicators of aquatic pollution. Present work was carried out to assess the genotoxic effect of gamma radiation on fresh water fish Cyprinus carpio (common carp) in vivo using comet assay. Fishes were irradiated with 2, 4, 6, 8 and 10 Gy of gamma rays using a teletherapy machine and comet assay was performed on nucleated erythrocytes after 24, 48 and 72 h of irradiation . A significant increase in % tail DNA was observed at all the doses of gamma radiation as compared to controls indicating radiation induced DNA damage in a dose-dependent manner. Maximum % tail DNA was observed at 24 h which gradually declined till 72 h, in a time-dependent manner. This decrease in damage may indicate repair of the damaged DNA and or loss of heavily damaged cells, over a period of time. The study reveals that the comet assay may be used as a sensitive and rapid method to detect genotoxicity of gamma radiation and other environmental pollutants in sentinel species. (author)

Grape Seed Oil Extract Protects Against Radiation-Induced Oxidative Damage in Rats Eyes

International Nuclear Information System (INIS)

Naguib, N.I.

2011-01-01

The present study was carried out to investigate the beneficial effects of grape seed oil on radiation-induced oxidative stress in the irradiated rat eyes. The rats were divided into three groups; control group that received distilled water, irradiated group (R) that exposed to gamma radiation as a single dose of 6.4 Gy and irradiated + grape seed oil group (R+GSO) that administered grape seed oil for seven consecutive days then exposed to the same single gamma radiation dose followed by grape seed oil for seven additional days. Histopathological results revealed protective effect of grape seed oil on the eye tissues of rat. The results lead to the conclusion that administration of GSO prior to radiation exposure may be a promising attempt in attenuating the extent of oxidative damage accompanying radiotherapy

Pudendal Nerve and Internal Pudendal Artery Damage May Contribute to Radiation-Induced Erectile Dysfunction

Energy Technology Data Exchange (ETDEWEB)

Nolan, Michael W., E-mail: mwnolan@ncsu.edu [Department of Clinical Sciences, and Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina (United States); Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Marolf, Angela J. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Ehrhart, E.J. [Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado (United States); Rao, Sangeeta [Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado (United States); Kraft, Susan L. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Engel, Stephanie [Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado (United States); Yoshikawa, Hiroto; Golden, Anne E. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Wasserman, Todd H. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); LaRue, Susan M. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States)

2015-03-15

Purpose/Objectives: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. Methods and Materials: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. Results: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. Conclusions: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is

The effect of vitamin D prophylaxis on radiation induced pulmonary damage

International Nuclear Information System (INIS)

Yazici, G.; Yildiz, F.; Iskit, A.; Surucu, S.; Firat, P.; Hayran, M.; Ozyigit, G.; Cengiz, M.; Erdemli, E.

2011-01-01

Vitamin D has a selective radio and chemosensitizing effect on tumor cells. In vitro and in vivo studies have shown that vitamin D inhibits collagen gel construction, induces type II pneumocyte proliferation and surfactant synthesis in the lungs, and decreases vascular permeability caused by radiation. The aim of this experimental study was to determine if vitamin D has a protective effect against radiation-induced pulmonary damage. Adult Wistar rats were divided into 4 groups. Group 1 was comprised of control animals. Group 2, which was administered 0.25 μg/kg/day of vitamin D3 for 8 weeks, was the vitamin D control group. Rats in groups 3 and 4 were given 20 Gy right hemithorax radiotherapy, and in addition group 4 was given vitamin D3 treatment, which began the day before the radiotherapy and continued for 8 weeks. At the 8 th and the 12 th weeks of the study 4 rats from each group were sacrificed. Right lungs were dissected for light and electron microscopic study. The electron microscopy examinations revealed statistically significant differences between group 3 and 4, and in group 4 there was less interstitial inflammation and collagen deposition, and the alveolar structure and the cells lining the alveolar walls were protected. These results confirm that vitamin D has a protective effect against radiation-induced pulmonary toxicity. These findings should be evaluated with further clinical studies. (author)

An analysis of radiation-induced damage in the spider mite. Relationship between mortality of haploid and diploid eggs in two successive generations

International Nuclear Information System (INIS)

Leenhouts, H.P.; Chadwick, K.H.

1976-01-01

Unfertilized females of the spider mite (Tetranychus urticae) produce only haploid eggs which develop into a haploid male. Fertilized females produce both haploid eggs (unfertilized), which develop into males, and diploid eggs (fertilized), which develop into females. Radiobiological experiments performed by A.M. Feldmann (Association Euratom-ITAL) made data available on the radiation-induced mortality of haploid and diploid eggs in the F 1 and F 2 generation following irradiation of either males or females with X rays or fast neutrons. The data have been analysed using the molecular theory of cell survival where it is assumed that DNA double strand breaks, induced randomly in the cell, are the critical radiation-induced lesions, which lead to cell death. Theoretical relationships are derived for the dose dependence of hatchability in haploid and diploid eggs in the first and second generations expressed as a function of the radiation damage in the parental genome. These theoretical relationships can be used to derive the inter-relationship between the different hatchabilities, and the results from the spider mite have been analysed using these considerations. It is concluded that the radiation-induced genetic damage arises from one type of initial lesion. The eventual radiobiological implications of this analysis are discussed, expecially with respect to the transmittance of radiation-induced genetic damage after low-level radiation. (author)

Fungal beta glucan protects radiation induced DNA damage in human lymphocytes.

Science.gov (United States)

Pillai, Thulasi G; Maurya, Dharmendra K; Salvi, Veena P; Janardhanan, Krishnankutty K; Nair, Cherupally K K

2014-02-01

Ganoderma lucidum (Ling Zhi), a basidiomycete white rot macrofungus has been used extensively for therapeutic use in China, Japan, Korea and other Asian countries for 2,000 years. The present study is an attempt to investigate its DNA protecting property in human lymphocytes. Beta glucan (BG) was isolated by standard procedure and the structure and composition were studied by infrared radiation (IR) and nuclear magnetic resonance (NMR) spectroscopy, gel filtration chromatography and paper chromatography. The radioprotective properties of BG isolated from the macro fungi Ganoderma lucidum was assessed by single cell gel electrophoresis (comet assay). Human lymphocytes were exposed to 0, 1, 2 and 4 Gy gamma radiation in the presence and absence of BG. The comet parameters were reduced by BG. The results indicate that the BG of G. lucidum possessed significant radioprotective activity with DNA repairing ability and antioxidant activity as the suggestive mechanism. The findings suggest the potential use of this mushroom for the prevention of radiation induced cellular damages.

Reduction of radiation-induced early skin damage (mouse foot) by 0-(β-hydroxyaethyl)-rutoside

International Nuclear Information System (INIS)

Fritz-Niggli, H.; Froehlich, E.

1980-01-01

The effect of a bioflavonoid, 0-(β-hydroxyethyl)-rutoside (HR) on early radiation-induced skin damage was examined, using the mouse foot system; the response to radiation is not species specific and comparison with the clinical situation is therefore possible. The aim was to see whether HR, which is highly effective in protecting against late damage, is also able to reduce early effects. Early reactions were considered to be erythema, swelling and ulceration and occurring up to 30 days after irradiation. It was found that HR significantly reduces early damage, both after a single dose and after fractionated irradiation with low doses. A single pre-treatment dose of HR and pre-treatment together with 30 days post-treatment administration were both found to be effective. The protective effect became more marked with increasing radiation dose (single irradiation). Reduction of late effects is produced iptimally by an interval of 0.25 hours between application of HR and irradiation, and this is also true for early skin damage. The early effects are partly reversible, but there is possibly an interesting correlation between these and irreversible late effects (such as loss of toes); a similar mechanism, presumably affecting the vascular system, may therefore be postulated. The protective action of this well tolesated, highly effective substance, which apparently protects normal tissues from early and late injury, is discussed. (orig.) [de

UV radiation-induced photochemical damage of tryptophan in peptides, proteins and ocular lenses

International Nuclear Information System (INIS)

Hibbard, L.B.

1985-01-01

These studies were undertaken to investigate the possible involvement of the amino acid tryptophan in the near-ultraviolet radiation-induced photochemical alteration of peptides and proteins and the role tryptophan photolysis plays in ocular lens damage. Sample irradiations were performed to determine if tryptophan photolysis occurs with radiation in the UV-A region in comparison to photolysis induced by wavelengths in the normal absorption band of the amino acid (UV-B). Photolysis studies were carried out on free tryptophan and two dipeptides, tryptophyglycine and glycyltryptophan, in aqueous solutions at different pH values in the range 4.5-10.0 under aerated or anaerobic conditions. Rates of photolysis of these 290 nm-irradiated compounds, detected by observing tryptophan fluorescence intensity loss during irradiation, were compared and significant differences were observed for each compound which varied with pH and oxygen environment. Another series of experiments examined the photolysis of tryptophan residues in lens proteins in whole rat lenses induced by 290 nm and 298 nm dye laser radiation. Tryptophan residue photolysis was, once again, monitored by loss in tryptophan fluorescence intensity. A relationship was derived between tryptophan loss and photoproduct buildup during irradiation

Membrane phospholipids and radiation-induced death of mammalian cells

International Nuclear Information System (INIS)

Wolters, H.

1987-01-01

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

Post-irradiation dietary vitamin E does not affect the development of radiation-induced lung damage in rats

International Nuclear Information System (INIS)

Wiegman, Erwin M.; Gameren, Mieke M. van; Kampinga, Harm H.; Szabo, Ben G.; Coppes, Rob P.

2004-01-01

The purpose of this study was to investigate whether application of post-irradiation vitamin E, an anti-oxidant, could prevent the development of radiation induced lung damage. Wistar rats were given vitamin E enriched or vitamin E deprived food starting from 4 weeks after 18 Gy single dose irradiation of the right thorax. Neither breathing frequencies nor CT density measurements revealed differences between the groups. It is concluded that post-irradiation vitamin E does not influence radiation-induced fibrosis to the lung

Radiation damage to DNA: The importance of track structure

International Nuclear Information System (INIS)

Hill, M.A.

1999-01-01

A wide variety of biological effects are induced by ionizing radiation, from cell death to mutations and carcinogenesis. The biological effectiveness is found to vary not only with the absorbed dose but also with the type of radiation and its energy, i.e., with the nature of radiation tracks. An overview is presented of some of the biological experiments using different qualities of radiation, which when compared with Monte Carlo track structure studies, have highlighted the importance of the localized spatial properties of stochastic energy deposition on the nanometer scale at or near DNA. The track structure leads to clustering of damage which may include DNA breaks, base damage etc., the complexity of the cluster and therefore its biological repairability varying with radiation type. The ability of individual tracks to produce clustered damage, and the subsequent biological response are important in the assessment of the risk associated with low-level human exposure. Recent experiments have also shown that biological response to radiation is not always restricted to the 'hit' cell but can sometimes be induced in 'un-hit' cells near by

Ion - biomolecule interactions and radiation damage

International Nuclear Information System (INIS)

Schlathoelter, T.

2004-01-01

Full text: The biological effects of ionizing radiation in living cells are not a mere result of the direct impact of high energy quanta of radiation. Secondary particles such as low energy electrons, radicals and (multiply charged) ions are formed within the track. The interaction of these secondary particles with biologically relevant molecules is responsible for a large fraction of biological radiation damage to a cell, as well. Singly and multiply charged ions can be of importance as both, primary and secondary particles, and are known to cause severe biological damage. For instance, in heavy ion therapy and proton therapy the pronounced Bragg peak of fast (typically a few 100 MeV/u) ions in biological tissue is utilized. The Bragg peak is located at a depth, where the ions (mostly C q+ or protons) are slowed down to about 100 keV/u and have their maximum linear energy transfer (LET) to the medium. This depth is reasonably well defined and depends on the initial ion kinetic energy. Since the ions are rapidly stopped in this energy range, penetration beyond the Bragg peak is weak and it is thus possible to 'scan' the Bragg peak through a malignant tumour without excessive damage of the surrounding tissue by mere variation of the ion kinetic energy (i.e. the penetration depth). Severe biological damage is almost only possible, when the track of a primary quantum of ionizing radiation crosses the nucleus of a cell. Particularly the induction of double strand breaks of DNA or clustered DNA lesions is potentially lethal or mutagenic. A primary particle interacting with individual molecules within this environment leads to molecular excitation, ionization and fragmentation. In the process, the primary particle looses energy and slow secondary electrons and ions are formed, which might induce further damage. For a deep understanding of biological radiation damage on the level of individual molecules it is thus important to quantify excitation, ionization and

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

Science.gov (United States)

George, Kerry

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 irradiation, at least for space radiation exposures. We present our latest follow-up measurements of chromosome aberrations in astronauts' blood lymphocytes assessed by FISH painting and collected at 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 provide limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

Protective Effects of Hydrogen against Low-Dose Long-Term Radiation-Induced Damage to the Behavioral Performances, Hematopoietic System, Genital System, and Splenic Lymphocytes in Mice

Directory of Open Access Journals (Sweden)

Jiaming Guo

2016-01-01

Full Text Available Molecular hydrogen (H2 has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects of H2 on the alterations induced by low-dose long-term radiation (LDLTR. All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM observation, forced swim test (FST, the open field test (OFT, the chromosome aberration (CA, the peripheral blood cells parameters analysis, the sperm abnormality (SA, the lymphocyte transformation test (LTT, and the histopathological studies. And significant differences between the treatment group and the radiation-only groups were observed, showing that H2 could diminish the detriment induced by LDLTR and suggesting the protective efficacy of H2 in multiple systems in mice against LDLTR.

Modification of radiation-induced oxic and anoxic damage by caffeine and potassium permanganate in barley seeds

International Nuclear Information System (INIS)

Kesavan, P.C.; Dodd, N.J.F.

1976-01-01

It has been demonstrated that both the immediate and post-irradiation oxygen effects in barley seeds decrease in magnitude in the presence of potassium permanganate and caffeine. This implied that these two types of oxygen effect have features in common. With the removal of the radiation-induced oxygen-sensitive sites, by anoxic hydration, caffeine potentiated the oxygen-independent component of damage, in seeds irradiated in a dry or pre-soaked state. Potassium permanganate, on the other hand, enhanced the anoxic radiation damage only in seeds irradiated in a dry state. The possible mode of action of KMnO 4 and caffeine in barley seeds is discussed. (author)

Effects of UV-B radiation on tetraspores of Chondrus ocellatus Holm (Rhodophyta), and effects of red and blue light on repair of UV-B-induced damage

Science.gov (United States)

Ju, Qing; Xiao, Hui; Wang, You; Tang, Xuexi

2015-05-01

We evaluated the effects of red and blue light on the repair of UV-B radiation-induced damage in tetraspores of Chondrus ocellatus Holm. Tetraspores of C. ocellatus were treated with different UV-B radiation levels (0, 36, 72, 108, 144 and 180 J/m2), and thereafter subjected to PAR, darkness, or red or blue light during a 2-h repair stage, each day for 48 days. The diameters and cellular contents of cyclobutane pyrimidine dimmers (CPDs), chlorophyll a (Chl a), phycoerythrin, and UV-B-absorbing mycosporinelike amino acids (MAAs) contents of the tetraspores were determined. Our results show that low doses of UV-B radiation (36 and 72 J/m2) promoted the growth of C. ocellatus; however, increased UV-B radiation gradually reduced the C. ocellatus growth (greater than 72 J/m2). The MAAs (palythine and asterina-330) in C. ocellatus were detected and analyzed by LC/MS. Our results suggest that moderate red light could induce the growth of this alga in aquaculture. In addition, photorepair was inhibited by red light, so there may be some other DNA repair mechanism activated by red light. Blue light promoted the activity of DNA photolyase, greatly improving remediation efficiency. Red and blue lights were found to reduce the capacity of C. ocellatus to form MAAs. Therefore, PAR, red light, and blue light play different roles during the repair processes for damage induced by UV-B radiation.

Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

International Nuclear Information System (INIS)

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

1999-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Krokosz, Anita [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland)]. E-mail: krokosz@biol.uni.lodz.pl; Koziczak, Renata [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland); Gonciarz, Marta [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland); Szweda-Lewandowska, Zofia [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland)

2006-01-15

Human erythrocytes suspended in an isotonic Na-phosphate buffer, pH 7.4 (hematocrit of 2%) were irradiated with {gamma}-rays at three dose-rates of 66.7, 36.7, 25 Gy min{sup -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.

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

International Nuclear Information System (INIS)

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

Repair of radiation-induced DNA damage in rat epidermis as a function of age

International Nuclear Information System (INIS)

Sargent, E.V.; Burns, F.J.

1985-01-01

The rate of repair of radiation-induced DNA damage in proliferating rat epidermal cells diminished progressively with increasing age of the animal. The dorsal skin was irradiated with 1200 rad of 0.8 MeV electrons at various ages, and the amount of DNA damage was determined as a function of time after irradiation by the method of alkaline unwinding followed by S 1 nuclease digestion. The amount of DNA damage immediately after irradiation was not age dependent, while the rate of damage removal from the DNA decreased with increasing age. By fitting an exponential function to the relative amount of undamaged DNA as a function of time after irradiation, DNA repair halftimes of 20, 27, 69, and 107 min were obtained for 28, 100-, 200-, and 400-day-old animals, respectively

Clustered DNA damage induced by proton and heavy ion irradiation

International Nuclear Information System (INIS)

Davidkova, M.; Pachnerova Brabcova, K; Stepan, V.; Vysin, L.; Sihver, L.; Incerti, S.

2014-01-01

Ionizing radiation induces in DNA strand breaks, damaged bases and modified sugars, which accumulate with increasing density of ionizations in charged particle tracks. Compared to isolated DNA damage sites, the biological toxicity of damage clusters can be for living cells more severe. We investigated the clustered DNA damage induced by protons (30 MeV) and high LET radiation (C 290 MeV/u and Fe 500 MeV/u) in pBR322 plasmid DNA. To distinguish between direct and indirect pathways of radiation damage, the plasmid was irradiated in pure water or in aqueous solution of one of the three scavengers (coumarin-3-carboxylic acid, dimethylsulfoxide, and glycylglycine). The goal of the contribution is the analysis of determined types of DNA damage in dependence on radiation quality and related contribution of direct and indirect radiation effects. The yield of double strand breaks (DSB) induced in the DNA plasmid-scavenger system by heavy ion radiation was found to decrease with increasing scavenging capacity due to reaction with hydroxyl radical, linearly with high correlation coefficients. The yield of non-DSB clusters was found to occur twice as much as the DSB. Their decrease with increasing scavenging capacity had lower linear correlation coefficients. This indicates that the yield of non-DSB clusters depends on more factors, which are likely connected to the chemical properties of individual scavengers. (authors)

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-09-15

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

The amount of DNA damage needed to activate the radiation-induced G2 checkpoint varies between single cells

International Nuclear Information System (INIS)

Tkacz-Stachowska, Kinga; Lund-Andersen, Christin; Velissarou, Angeliki; Myklebust, June H.; Stokke, Trond; Syljuåsen, Randi G.

2011-01-01

Background and purpose: The radiation-induced G2 checkpoint helps facilitate DNA repair before cell division. However, recent work has revealed that human cells often escape the G2 checkpoint with unrepaired DNA breaks. The purpose was to explore whether G2 checkpoint activation occurs according to a threshold level of DNA damage. Materials and methods: G2 checkpoint activation was assayed at 75–90 min and 24–48 h after X-ray irradiation of BJ diploid fibroblasts and U2OS osteosarcoma cells. Multiparameter flow cytometry with pacific blue barcoding, and flow cytometry-based sorting of phospho-H3 positive cells to microscope slides, were used to examine the DNA damage marker γ-H2AX in individual mitotic cells that had escaped the G2 checkpoint. Results: For all radiation doses and times tested, the number of γ-H2AX foci varied between individual mitotic cells. At 75 min the median levels of γ-H2AX in mitotic cells increased with higher radiation doses. At 24–48 h, following a prolonged G2 checkpoint, cells were more resistant to checkpoint re-activation by a second dose of radiation. Conclusion: Our results suggest that different amounts of DNA damage are needed to activate the G2 checkpoint in individual cells. Such single cell variation in checkpoint activation may potentially contribute to radiation-induced genomic instability.

Radio-oxidative membrane damage and its possible role as an indicator of radiation exposure

International Nuclear Information System (INIS)

Amit Kumar; Pandey, B.N.; Mishra, K.P.

2004-01-01

Cellular membranes have been recognized as a sensitive target in the mechanism of ionizing radiation-induced cell killing. In our laboratory, studies have been devoted to investigations on gamma radiation induced oxidative damage to model and cellular membrane damage by employing fluorescence and electron spin resonance (ESR) methods Considerable evidences has accumulated to suggest that radiation induced oxidative damage was related to apoptotic death of a variety of cells in culture. Radiation induced damage involving lipid peroxidation, altered bilayer fluidity, permeability changes and intracellular generated ROS have been evaluated by chemical and physical methods. Modification of damage by structural modulating agents such as cholesterol and antioxidants such as eugenol, ascorbic acid, ellagic acid, triphala have been extensively investigated. Generation of intracellular ROS in radiation stressed normal cell e.g. mouse thymocytes, tumor cells e.g. Ehrlich ascites cells and human cervical cell line were evaluated after exposure from low to moderate doses of α-radiation. Results suggest that modulation of intracellular ROS level may be an important approach to alter radio-cytotoxicity of cells. This presentation would describe results of our study together with an overview of free radical mediated oxidative damage to cellular membrane as an indicator of radiation exposure. (author)

DNA damages induced by Ar F laser

Energy Technology Data Exchange (ETDEWEB)

Chapel, C.; Rose, S.; Chevrier, L.; Cordier, E.; Courant, D. [CEA Fontenay-aux-Roses, 92 (France). Dept. de Radiobiologie et de Radiopathologie

2006-07-01

over 10 days post irradiation but about 10% of abnormalities remain in irradiated cells. In conclusion this work has shown that 193 nm laser radiation could induce double strand breaks, micronuclei and apoptotic cells; frequencies of such abnormalities are dose related to exposure. These low doses could be considered as genotoxic for stromal cells, close to the ablation area. Surviving cells which have repaired DNA alterations remain fragile. These damages could generate accelerated cell ageing and may be of significance toward the response of treated cornea to ultraviolet radiations. (authors)

Radiation-induced osteosarcoma of the jaw treated with skull base surgery

International Nuclear Information System (INIS)

Yamamoto, Misaki; Asato, Ryo; Torii, Hiroko; Kanda, Tomoko; Tamura, Yoshihiro; Hirano, Shigeru; Ito, Juichi; Tanaka, Shinzou

2009-01-01

Head and neck osteosarcomas are rare. A 33-year-old woman received radiation therapy for lymphoepithelioma of the epipharynx in her childhood. After twenty-two years, she presented with a swelling of the right cheek. We did a work up, and diagnosed her radiation-induced osteosarcoma of the jaw. We treated her with neoadjuvant chemotherapy, surgery including skull base resection, and adjuvant chemo-therapy. A small skin recurrence developed after one year, but it was resected under local anesthesia, and there have been no recurrences since. We think that skull base surgery with a combined approach is a useful method in therapy for osteosarcomas in the skull base region. (author)

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

International Nuclear Information System (INIS)

Santra, Manas Kumar

2017-01-01

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

Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

Science.gov (United States)

Sannino, Anna; Zeni, Olga; Romeo, Stefania; Massa, Rita; Gialanella, Giancarlo; Grossi, Gianfranco; Manti, Lorenzo; Vijayalaxmi; Scarfì, Maria Rosaria

2014-03-01

The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector.

Science.gov (United States)

Jermusek, Frank; Benedict, Chelsea; Dreischmeier, Emma; Brand, Michael; Uder, Michael; Jeffery, Justin J; Ranallo, Frank N; Fahl, William E

2018-05-21

While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P 95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

Radioprotective effect of methanolic root extract of Loeseneriella arnottiana on radiation induced DNA damage in human lymphocytes in vitro

International Nuclear Information System (INIS)

Prajna, P.S.

2012-01-01

Intense exposure to ionization radiation by accidental, occupational or therapeutical purpose causes cellular damage mainly by formation of excessive reactive oxygen species (ROS) or by free radicals. Humans are intentionally exposed to ionising radiation for diagnostic or therapeutic purposes. The use of ionising radiation in cancer therapy may lead to transient and/or permanent injury to normal tissues within the treatment field. To increase the therapeutic index of radiation therapy, various modes of radioprotection have been developed that selectively reduce cytotoxic effects to normal tissues. Because radiation-induced cellular damage is attributed primarily to the harmful effects of free radicals, molecules with radical scavenging properties are particularly promising as radioprotectors. Loeseneriella arnottiana, a member of family Hippocrateaceae, is a climbing shrub used by traditional medicine practitioners. To study the antioxidant activity and radioprotective effect of methanolic root extract of Loeseneriella arnottiana against electron beam radiation induced DNA damage in human lymphocytes. Loeseneriella arnottiana roots were dried and extracted using methanol by solvent extraction method. Antioxidant activity was measured by DPPH method. DNA damage was assessed by comet assay parameters. The lymphocytes were incubated for one hour with two different concentrations 10 μg and 50 μg of root extract before exposure to 2 Gy electron beam radiation. 30 μg of methanolic root extract of Loeseneriella arnottiana exhibited 96% radical scavenging activity comparable to 15 μg of ascorbic acid. In reducing power assay it showed dose dependent increase in absorbance indicating that extract is capable of donating hydrogen atoms. Pretreatment of lymphocytes with 10 μg and 50 μg of root extract before irradiation resulted in reduction in the Comet length, Olive tail moment, percentage of DNA in tail when compared to the radiation control group. Results of this

Comparison of damage induced by mercury chloride and ionizing radiation in the susceptible rat model

International Nuclear Information System (INIS)

Kim, Ji Hyang; Yoon, Yong Dal; Kim, Jin Kyu

2003-01-01

Mercury (Hg), one of the most diffused and hazardous organ-specific environmental contaminants, exists in a wide variety of physical and chemical states. Although the reports indicate that mercury induces a deleterious damage, little has been reported from the investigations of mercury effects in living things. The purpose of this study is to evaluate the effects of mercury chloride and ionizing radiation. Prepubertal male F-344 rats were administered mercury chloride in drinking water throughout the experimental period. Two weeks after whole body irradiation, organs were collected for measuring the induced injury. Serum levels of GOT, GPT, ALP, and LDH were checked in the experimental groups and the hematological analysis was accomplished in plasma. In conclusion, the target organ of mercury chloride seems to be urinary organs and the pattern of damage induced by mercury differs from that of the irradiated group

Radiation-induced lung damage in rats: The influence of fraction spacing on effect per fraction

International Nuclear Information System (INIS)

Haston, C.K.; Hill, R.P.; Newcomb, C.H.; Van Dyk, J.

1994-01-01

When the linear-quadratic model is used to predict fractionated treatments which are isoeffective, it is usually assumed that each (equal size) treatment fraction has an equal effect, independent of the time at which it was delivered during a course of treatment. Previous work has indicated that this assumption may not be valid in the context of radiation-induced lung damage in rats. Consequently the authors tested directly the validity of the assumption that each fraction has an equal effect, independent of the time it is delivered. An experiment was completed in which fractionated irradiation was given to whole thoraces of Sprague-Dawley rats. All treatment schedules consisted of eleven equal dose fractions in 36 days given as a split course, with some groups receiving the bulk of the doses early in the treatment schedule, before a 27-day gap, and others receiving most of the dose toward the end of the treatment schedule, after the time gap. To monitor the incidence of radiation-induced damage, breathing rate and lethality assays were used. The maximum differences in the LD 50 s and breathing rate ED 50 s for the different fractionation schedules were 4.0% and 7.7% respectively. The lethality data and breathing rate data were consistent with results expected from modelling using the linear-quadratic model with the inclusion of an overall time factor, but not the generalized linear-quadratic model which accounted for fraction spacing. For conventional daily fractionation, and within the range of experimental uncertainties, the results indicate that the effect of a treatment fraction does not depend on the time at which it is given (its position) in the treatment. The results indicate no need to extend isoeffect formulae to consider the effect of each fraction separately for radiation-induced lung damage. 21 refs., 6 figs., 3 tabs

Radiation exposure and chromosome damage

International Nuclear Information System (INIS)

Lloyd, D.

1979-01-01

Chromosome damage is discussed as a means of biologically measuring radiation exposure to the body. Human lymphocytes are commonly used for this test since the extent of chromosome damage induced is related to the exposure dose. Several hundred lymphocytes are analysed in metaphase for chromosome damage, particularly dicentrics. The dose estimate is made by comparing the observed dicentric yield against calibration curves, previously produced by in vitro irradiation of blood samples to known doses of different types of radiation. This test is useful when there is doubt that the film badge has recorded a reasonable whole body dose and also when there is an absence of any physical data. A case of deliberate exposure is described where the chromosome damage test estimated an exposure of 152 rads. The life span of cell aberrations is also considered. Regular checks on radiotherapy patients and some accidental overdose cases have shown little reduction in the aberration levels over the first six weeks after which the damage disappears slowly with a half-life of about three years. In conclusion, chromosome studies have been shown to be of value in resolving practical problems in radiological protection. (U.K.)

Molecular mechanisms in radiation damage to DNA. Progress report

International Nuclear Information System (INIS)

Osman, R.

1994-01-01

The objectives of this work are to elucidate the molecular mechanisms that are responsible for radiation-induced DNA damage. The overall goal is to understand the relationship between the chemical and structural changes produced by ionizing radiation in DNA and the resulting impairment of biological function expressed as carcinogenesis or cell death. The studies are based on theoretical explorations of possible mechanisms that link initial radiation damage in the form of base and sugar damage to conformational changes in DNA. These mechanistic explorations should lead to the formulation of testable hypotheses regarding the processes of impairment of regulation of gene expression, alteration in DNA repair, and damage to DNA structure involved in cell death or cancer

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

International Nuclear Information System (INIS)

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

1997-01-01

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

A novel topical protectant for the prevention of β-radiation induced moist desquamation

International Nuclear Information System (INIS)

Ma, L.; Wilcock, S.; Rezvani, M.; Hsia, C.

2003-01-01

Full text: Effective therapies for the prevention of radiation-induced skin burns that could be readily deployed under a nuclear accident or nuclear terrorism scenario are urgently needed. In this report we describe the efficacy of a novel radioprotectant (DMZ911) in a model of b-radiation induced moist desquamation (MD) in pig skin. DMZ911 is a nitroxide-based topical cream that effectively delivers the nitroxide into viable skin cells. Stable nitroxide compounds have been shown to be effective against both X-ray and ?-ray-induced damage in vivo and in vitro. A pig skin model of β-radiation-induced MD was employed in this study. Exposure to 30 Gy was used to induce skin lesions involving >80% moist desquamation in prescribed test sites on flank skin of female Large White pigs. DMZ911 or placebo was applied to various test sites 2 hours prior to radiation exposure. Lesions were scored based on the area of the test site containing 50% MD (severe) as determined by clinical assessment using blinded observers. Treatment with DMZ911 resulted in a 31% net reduction in MD when compared to placebo treated sites following an 8-week study period. This reduction was observed whether all sites or only those with severe MD were considered. Skin damage (as indicated by MD) from radiation exposure was significantly reduced by 31% (p = 0.05) following pretreatment with the novel topical radioprotectant DMZ911. This observation suggests that skin lesion development from radiation-induced oxidative damage cascades may be successfully inhibited by treatment with DMZ911. This topical therapeutic agent represents a novel treatment for nuclear radiation induced skin injury. DMZ911 may have unique applications in radiation oncology, cosmetic and therapeutic UV, laser, glycolic and dermabrasion procedures

Effect of reactor radiation on the thermal conductivity of TREAT fuel

Energy Technology Data Exchange (ETDEWEB)

Mo, Kun, E-mail: kunmo@anl.gov; Miao, Yinbin; Kontogeorgakos, Dimitrios C.; Connaway, Heather M.; Wright, Arthur E.; Yacout, Abdellatif M.

2017-04-15

The Transient Reactor Test Facility (TREAT) at the Idaho National Laboratory is resuming operations after more than 20 years in latency in order to produce high-neutron-flux transients for investigating transient-induced behavior of reactor fuels and their interactions with other materials and structures. A parallel program is ongoing to develop a replacement core in which the fuel, historically containing highly-enriched uranium (HEU), is replaced by low-enriched uranium (LEU). Both the HEU and prospective LEU fuels are in the form of UO{sub 2} particles dispersed in a graphite matrix, but the LEU fuel will contain a much higher volume of UO{sub 2} particles, which may create a larger area of interphase boundaries between the particles and the graphite. This may lead to a higher volume fraction of graphite exposed to the fission fragments escaping from the UO{sub 2} particles, and thus may induce a higher volume of fission-fragment damage on the fuel graphite. In this work, we analyzed the reactor-radiation induced thermal conductivity degradation of graphite-based dispersion fuel. A semi-empirical method to model the relative thermal conductivity with reactor radiation was proposed and validated based on the available experimental data. Prediction of thermal conductivity degradation of LEU TREAT fuel during a long-term operation was performed, with a focus on the effect of UO{sub 2} particle size on fission-fragment damage. The proposed method can be further adjusted to evaluate the degradation of other properties of graphite-based dispersion fuel.

DNA damage-inducible transcripts in mammalian cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Alamo, I. Jr.; Hollander, M.C.

1988-01-01

Hybridization subtraction at low ratios of RNA to cDNA was used to enrich for the cDNA of transcripts increased in Chinese hamster cells after UV irradiation. Forty-nine different cDNA clones were isolated. Most coded for nonabundant transcripts rapidly induced 2- to 10-fold after UV irradiation. Only 2 of the 20 cDNA clones sequenced matched known sequences (metallothionein I and II). The predicted amino acid sequence of one cDNA had two localized areas of homology with the rat helix-destabilizing protein. These areas of homology were at the two DNA-binding sites of this nucleic acid single-strand-binding protein. The induced transcripts were separated into two general classes. Class I transcripts were induced by UV radiation and not by the alkylating agent methyl methanesulfonate. Class II transcripts were induced by UV radiation and by methyl methanesulfonate. Many class II transcripts were induced also by H2O2 and various alkylating agents but not by heat shock, phorbol 12-tetradecanoate 13-acetate, or DNA-damaging agents which do not produce high levels of base damage. Since many of the cDNA clones coded for transcripts which were induced rapidly and only by certain types of DNA-damaging agents, their induction is likely a specific response to such damage rather than a general response to cell injury

Taurine Protects Mouse Spermatocytes from Ionizing Radiation-Induced Damage Through Activation of Nrf2/HO-1 Signaling.

Science.gov (United States)

Yang, Wenjun; Huang, Jinfeng; Xiao, Bang; Liu, Yan; Zhu, Yiqing; Wang, Fang; Sun, Shuhan

2017-01-01

The increasing prevalence of ionizing radiation exposure has inevitably raised public concern over the potential detrimental effects of ionizing radiation on male reproductive system function. The detection of drug candidates to prevent reproductive system from damage caused by ionizing radiation is urgent. We aimed to investigate the protective role of taurine on the injury of mouse spermatocyte-derived cells (GC-2) subjected to ionizing radiation. mouse spermatocytes (GC-2 cells) were exposed to ionizing radiation with or without treatment of Taurine. The effect of ionizing radiation and Taurine treatment on GC-2 cells were evaluated by cell viability assay (CCK8), cell cycle and apoptosis. The relative protein abundance change was determined by Western blotting. The siRNA was used to explore whether Nrf2 signaling was involved in the cytoprotection of Taurine. Taurine significantly inhibited the decrease of cell viability, percentage of apoptotic cells and cell cycle arrest induced by ionizing radiation. Western blot analysis showed that taurine significantly limited the ionizing radiation-induced down-regulation of CyclinB1 and CDK1, and suppressed activation of Fas/FasL system pathway. In addition, taurine treatment significantly increased the expression of Nrf2 and HO-1 in GC-2 cells exposed to ionizing radiation, two components in antioxidant pathway. The above cytoprotection of Taurine was blocked by siNrf2. Our results demonstrate that taurine has the potential to effectively protect GC-2 cells from ionizing radiation- triggered damage via upregulation of Nrf2/HO-1 signaling. © 2017 The Author(s). Published by S. Karger AG, Basel.

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

International Nuclear Information System (INIS)

Feinendegen, L.E.; Sondhaus, C.A.; Altman, K.I.

1998-01-01

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

Energy Technology Data Exchange (ETDEWEB)

Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

1998-12-31

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

Salvia officinalis l. (sage) Ameliorates Radiation-Induced Oxidative Brain Damage In Rats

International Nuclear Information System (INIS)

Osman, N. N.; Abd El Azime, A.Sh.

2013-01-01

The present study was designed to investigate the oxidative stress and the role of antioxidant system in the management of gamma irradiation induced whole brain damage in rats . Also, to elucidate the potential role of Salvia officinalis (sage) in alleviating such negative effects. Rats were subjected to gamma radiation (6 Gy). Sage extract was daily given to rats during 14 days before starting irradiation and continued after radiation exposure for another 14 days. The results revealed that the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and nitric oxide (NO) content were significantly increased, while the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the reduced glutathione (GSH) content were significantly decreased in the brain homogenate of irradiated rats. Additionally, brain acetylcholinesterase (AChE) as well as alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH) activities were significantly increased. On the other hand, the results showed that, administration of sage extract to rats was able to ameliorate the mentioned parameters and the values returned close to the normal ones. It could be concluded that sage extract, by its antioxidant constituents, could modulate radiation induced oxidative stress and enzyme activities in the brain.

DNA Damage Signals and Space Radiation Risk

Science.gov (United States)

Cucinotta, Francis A.

2011-01-01

Space radiation is comprised of high-energy and charge (HZE) nuclei and protons. The initial DNA damage from HZE nuclei is qualitatively different from X-rays or gamma rays due to the clustering of damage sites which increases their complexity. Clustering of DNA damage occurs on several scales. First there is clustering of single strand breaks (SSB), double strand breaks (DSB), and base damage within a few to several hundred base pairs (bp). A second form of damage clustering occurs on the scale of a few kbp where several DSB?s may be induced by single HZE nuclei. These forms of damage clusters do not occur at low to moderate doses of X-rays or gamma rays thus presenting new challenges to DNA repair systems. We review current knowledge of differences that occur in DNA repair pathways for different types of radiation and possible relationships to mutations, chromosomal aberrations and cancer risks.

Kaempferol protects against gamma radiation-induced mortality and damage via inhibiting oxidative stress and modulating apoptotic molecules in vivo and vitro.

Science.gov (United States)

Wang, Jing; Li, Tiejun; Feng, Jingjing; Li, Li; Wang, Rong; Cheng, Hao; Yuan, Yongfang

2018-04-20

To investigate the potential protective effect of kaempferol, a representative flavonoid, against radiation induced mortality and injury in vivo and vitro.C57BL/6 male mice and human umbilical venous endothelial cells (HUVECs) were pretreated with kaempferol before radiation. We found that kaempferol can effectively increase 30-day survival rate after 8.5 Gy lethal total body irradiation (TBI). Mice were sacrificed at 7th day after 7 Gy TBI, we found kaempferol against radiation-induced tissues damage, by inhibiting the oxidative stress, and attenuating morphological changes and cell apoptosis. In vitro, kaempferol increased HUVECs cell viability and decrease apoptosis. It also mitigated oxidative stress and restored the abnormal expression of prx-5, Cyt-c, Caspase9 and Caspase3 in mRNA and protein level in HUVECs after radiation. Taken together, it suggests kaempferol can protect against gamma-radiation induced tissue damage and mortality. The present study is the first report of the radioprotective role of kaempferol in vivo and vitro. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of Lutein Intervention in Mice on the Radiation Induced Clastogenic Changes

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Vidya Vasudeva

2017-10-01

Full Text Available One of the genetic effects of radiation is that it may lead to formation of single or double strand breaks in DNA which can be observed in differentially stained polychromatic or normochromatic erythrocytes (PCE and NCE respectively. In pursuit of finding a natural radioprotector to treat the radiation induced damages; lutein, a carotenoid pigment is one such approach. Swiss albino mice are administered with the compound (lutein/gallic acid/DMSO with respective controls for 15 consecutive days after which they are irradiated. The whole blood is drawn for comet assay and the femur of the leg is removed to flush out the content of the bone marrow in BSA for the micronucleus assay. The comet slides are observed under the fluorescent microscope and the PCE/NCE or micronucleated PCEs or NCEs are scored blindly. Lutein in the present study has effectively reduced the olive moment and the tail moment. However, % DNA in tail has been maintained to normal levels in comparison to its control indicating lesser extent of damage to the genetic material. The percent micronucleated NCE (MnNCE has been decreased in the group treated with lutein prior to radiation. The % MnPCE and the PCE/(PCE + NCE ratio has been increased in all the irradiated groups; however lutein treatment has not drastically increased the formation of micronuclei in comparison to its control. This indicates that lutein shows a protective effect against the radiation induced cytogenetic damages in Swiss albino mice.

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

2015-08-14

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

International Nuclear Information System (INIS)

Dasgupta, Amrita; Katdare, Meena

2015-01-01

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics

Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

Science.gov (United States)

Griko, Y. V.; Yan, Xiaoli

2016-01-01

Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing

Operative treatment of radiation-induced fistulae

International Nuclear Information System (INIS)

Balslev, I.; Harling, H.

1987-01-01

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

Operative treatment of radiation-induced fistulae

Energy Technology Data Exchange (ETDEWEB)

Balslev, I.; Harling, H.

1987-01-01

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

The role of amino acids on the development of radiation-induced damage of central nervous system

International Nuclear Information System (INIS)

Yamatodani, Atsushi; Yamamoto, Kouichi; Nohara, Kyoko; Moriyasu, Saeko; Yamamoto, Takashi

2005-01-01

Radiation impairs some functions of the central nervous system, which is one of the radiation-resistant tissues in the body. However, the underlying mechanisms are still unclear. In this study, we investigated the effects of the effects of high-linear energy transfer (LET) heavy-ions on the release of glutamate, the major excitatory neurotransmitter in the central nervous system, in the hypothalamus of rats measured by in vivo brain microdialysis. Total body and head, but not abdominal, heavy-ion (carbon) irradiation induced a significant increase in glutamate levels to approximately 150% of the basal level at 1.5 h of the irradiation, and the release gradually increased during the observation period. Furthermore, heavy-ion-induced glutamate release was suppressed by pretreatment with the dexamethasone. These results suggested that the central pathways (i.e. the neuronal damage of the brain or inflammatory cytokines which were produced in the brain) are involved in the development of high-LET radiation-induced glutamate release. (author)

Appearance of radiation-induced lesions after radiotherapy for Hodgkin's disease of the mediastinum and lungs

Energy Technology Data Exchange (ETDEWEB)

Zomer-Drozda, J [Instytut Onkologii, Warsaw (Poland)

1976-01-01

The incidence of radiation-induced lesions of lung tissue adjacent to the mediastinum and covered by radiation was established on the basis of a retrospective analysis of radiograms of 245 patients treated at the Institute of Oncology in Warsaw in the years 1951-1968, who received radiotherapy to the mediastinal lymph nodes. The radiation-induced lesions were divided into 4 grades depending on their extent and intensity of pulmonary tissue damage. Criteria for classification of radiation-induced fibrosis into the above mentioned grades were established. The correlation between radiation-induced injury and the doses of X-rays applied to the mediastinal lymph nodes was analysed. The importance of radiation-induced changes in the mediastinum and lungs for the diagnosis of recurrences in the irradiated fields, in the marginal areas and granulomatous infiltrations in pulmonary tissue is discussed.

Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

Science.gov (United States)

Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

2015-01-01

Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to

Consequential late radiation damage in the skin in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Li Wei; Kong Ling; Zhang Youwang; Hu Chaosu; Wu Yongru

2008-01-01

Objective: To evaluate the relationship between early and late radiation damage in skin. Methods: 335 patients with nasopharyngeal carcinoma treated with radical radiotherapy were evaluated. 240 patients had lymph nodes in the neck at initial diagnosis. The median doses were 70 Gy (55-86 Gy) to the nasopharyngeal region by external beam radiotherapy. The median doses were 64 Gy (46-72 Gy) to the neck with lymph node metastases, 55 Gy (21-67 Gy) to the node-negative neck. 71 patients were treated with facial-neck fields, while 264 patients were treated with pre-auricular fields. Chemotherapy was given in 48 patients. According to the 1995 SOMA scales late radiation damage in the skin was evaluated. Results: The median time from the radiotherapy to follow up was 14 years (range, 5-38 years). 63 patients have grade 0 late radiation reactions in the neck skin, the grade 1,2, 3,4 late radiation reactions in the neck skin were 43.9% (147 patients), 20.9% (70 patients), 13.7% (46 patients) and 2.7% (9 patients), respectively. 44 patients had moist desquamation in the medical records. The grade 1,2,3,4 late radiation reactions in the neck skin were 41%, 23%, 30% and 5%, respectively in patients with moist desquamation, while in patients without moist desquamation, the corresponding rates were 44.3%, 20.6%, 11.3% and 2.4%, respectively. The difference were significant between these two groups by chi-square analysis(χ 2 =17.42, P=0.002). Furthermore, whether patients had positive lymph node in the neck or not, the size of facial-neck fields and higher doses to the neck had more severe late radiation reaction in the neck skin, while age, gender and chemotherapy failed to show any effects on the development of late radiation reactions in the neck skin. Conclusion: The severe early radiation damage in the skin possibly increases the late radiation damage in the neck skin. (authors)

Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage recognition and apoptotic cell death

International Nuclear Information System (INIS)

Tomita, Masanori

2010-01-01

Exposure to ionizing radiation and hyperthermia results in important biological consequences, e.g. cell death, chromosomal aberrations, mutations, and DNA strand breaks. There is good evidence that the nucleus, specifically cellular DNA, is the principal target for radiation-induced cell lethality. DNA double-strand breaks (DSBs) are considered to be the most serious type of DNA damage induced by ionizing radiation. On the other hand, verifiable mechanisms which can lead to heat-induced cell death are damage to the plasma membrane and/or inactivation of heat-labile proteins caused by protein denaturation and subsequent aggregation. Recently, several reports have suggested that DSBs can be induced after hyperthermia because heat-induced phosphorylated histone H2AX (γ-H2AX) foci formation can be observed in several mammalian cell lines. In mammalian cells, DSBs are repaired primarily through two distinct and complementary mechanisms: non-homologous end joining (NHEJ), and homologous recombination (HR) or homology-directed repair (HDR). DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) are key players in the initiation of DSB repair and phosphorylate and/or activate many substrates, including themselves. These phosphorylated substrates have important roles in the functioning of cell cycle checkpoints and in cell death, as well as in DSB repair. Apoptotic cell death is a crucial cell suicide mechanism during development and in the defense of homeostasis. If DSBs are unrepaired or misrepaired, apoptosis is a very important system which can protect an organism against carcinogenesis. This paper reviews recently obtained results and current topics concerning the role of DNA-PK and ATM in heat- or radiation-induced apoptotic cell death. (author)

Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

Science.gov (United States)

Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

2008-12-01

To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

International Nuclear Information System (INIS)

Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

2008-01-01

To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD 50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

Protection against radiation induced testicular damage in Swiss albino mice by mentha piperita (Linn)

Energy Technology Data Exchange (ETDEWEB)

Samarth, Ravindra M; Samarth, Meenakshi [Rajasthan Univ., Jaipur (India). Dept. of Zoology, Radiation and Cancer Biology Lab.

2008-07-01

Mentha piperita linn or peppermint (Family - Labiatae) is aromatic and has stimulant and carminative properties. The protective effects of mentha piperita (Linn) extract against radiation induced damage in testis of Swiss albino mice have been studied. Animals (Male Swiss albino mice) were given leaf extract of M. piperita orally (1 g kg{sup -1} day{sup -1}) for three consecutive days prior to radiation exposure (8 Gy gamma radiation). Mice were autopsied at 1, 3, 7, 14 and 30 days of post-irradiation to evaluate the radiomodulatory effect in terms of histological alterations, lipid peroxidation, acid and alkaline phosphatases levels in testis. There was significantly less degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and Leydig cells. Significant decreases in the LPO and acid phosphatase level and increase in level of alkaline phosphatase were observed in testis. The methanolic extract of M. piperita showed high amount of phenolic content, flavonoids content and flavonol. Leaf extract of M. piperita has significant radioprotective effect and the amount of phenolic compounds, flavonoids and flavonol content of extract of M. piperita may be held responsible for its radioprotective effect. (author)

Protection against radiation induced testicular damage in Swiss albino mice by mentha piperita (Linn)

International Nuclear Information System (INIS)

Samarth, Ravindra M.; Samarth, Meenakshi

2008-01-01

Mentha piperita linn or peppermint (Family - Labiatae) is aromatic and has stimulant and carminative properties. The protective effects of mentha piperita (Linn) extract against radiation induced damage in testis of Swiss albino mice have been studied. Animals (Male Swiss albino mice) were given leaf extract of M. piperita orally (1 g kg -1 day -1 ) for three consecutive days prior to radiation exposure (8 Gy gamma radiation). Mice were autopsied at 1, 3, 7, 14 and 30 days of post-irradiation to evaluate the radiomodulatory effect in terms of histological alterations, lipid peroxidation, acid and alkaline phosphatases levels in testis. There was significantly less degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and Leydig cells. Significant decreases in the LPO and acid phosphatase level and increase in level of alkaline phosphatase were observed in testis. The methanolic extract of M. piperita showed high amount of phenolic content, flavonoids content and flavonol. Leaf extract of M. piperita has significant radioprotective effect and the amount of phenolic compounds, flavonoids and flavonol content of extract of M. piperita may be held responsible for its radioprotective effect. (author)

Automated analysis of damages for radiation in plastics surfaces

International Nuclear Information System (INIS)

Andrade, C.; Camacho M, E.; Tavera, L.; Balcazar, M.

1990-02-01

Analysis of damages done by the radiation in a polymer characterized by optic properties of polished surfaces, of uniformity and chemical resistance that the acrylic; resistant until the 150 centigrade grades of temperature, and with an approximate weight of half of the glass. An objective of this work is the development of a method that analyze in automated form the superficial damages induced by radiation in plastic materials means an images analyst. (Author)

Radiation damage in DNA

International Nuclear Information System (INIS)

Lafleur, V.

1978-01-01

A number of experiments are described with the purpose to obtain a better insight in the chemical nature and the biological significance of radiation-induced damage in DNA, with some emphasis on the significance of alkali-labile sites. It is shown that not only reactions of OH radicals but also of H radicals introduce breaks and other inactivating damage in single-standed phiX174 DNA. It is found that phosphate buffer is very suitable for the study of the reactions of H radicals with DNA, as the H 2 PO 4 - ions convert the hydrated electrons into H radicals. The hydrated electron, which does react with DNA, does not cause a detectable inactivation. (Auth.)

Raman study of radiation-damaged zircon under hydrostatic compression

Science.gov (United States)

Nasdala, Lutz; Miletich, Ronald; Ruschel, Katja; Váczi, Tamás

2008-12-01

Pressure-induced changes of Raman band parameters of four natural, gem-quality zircon samples with different degrees of self-irradiation damage, and synthetic ZrSiO4 without radiation damage, have been studied under hydrostatic compression in a diamond anvil cell up to ~10 GPa. Radiation-damaged zircon shows similar up-shifts of internal SiO4 stretching modes at elevated pressures as non-damaged ZrSiO4. Only minor changes of band-widths were observed in all cases. This makes it possible to estimate the degree of radiation damage from the width of the ν3(SiO4) band of zircon inclusions in situ, almost independent from potential “fossilized pressures” or compressive strain acting on the inclusions. An application is the non-destructive analysis of gemstones such as corundum or spinel: broadened Raman bands are a reliable indicator of self-irradiation damage in zircon inclusions, whose presence allows one to exclude artificial color enhancement by high-temperature treatment of the specimen.

Scopolamine methylbromide mitigates radiation induced damage and lethality in zebrafish

International Nuclear Information System (INIS)

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

2014-01-01

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

Modeling DNA?damage-induced pneumopathy in mice: insight from danger signaling cascades

OpenAIRE

Wirsd?rfer, Florian; Jendrossek, Verena

2017-01-01

Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secr...

Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

Directory of Open Access Journals (Sweden)

Kyeung Min Joo

Full Text Available 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.

Scavenging capacity of medicinal plants against free radical-induced cellular damage by radiation and photoactivation

Energy Technology Data Exchange (ETDEWEB)

Gadkar, Shalaka [Ruia College, Mumbai (India); Mohan, H [Chemistry Group, Bhabha Atomic Research Centre, Mumbai (India); Kamat, J P [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

2004-01-01

The scavenging capacity of medicinal plants. Andrographis paniculata (Ap) and Swertia chirata (Sc) was examined against cellular damage, induced by radiation and photo-activation in sub-cellular membranes. The results demonstrated significant radical scavenging capacity of the extracts. The rate constants as evaluated by deoxyribose degradation studies and the pulse radiolysis studies carried in presence of ABTS radical well supported the antioxidant properties of the extracts. (author)

Action of the chlorophyllin before genetic damage induced by gamma radiation in germinal cells of Drosophila; Accion de la clorofilina ante el dano genetico inducido por radiacion gamma en celulas germinales de Drosophila

Energy Technology Data Exchange (ETDEWEB)

Moreno B, R

2004-07-01

The chlorophyllin (CHLN) is a porphyrin of nutritious grade and soluble in water, derived of the chlorophyll. It has been reported that this pigment is a good anti mutagen since it reduces the damage to the DNA caused by physical or chemical agents of direct or indirect action. Their anti carcinogenic action has also been demonstrated when it is administered itself during the induced post-initiation phase by aflatoxins and heterocyclic amines. However in the last decade it has been reported that it also has promoter activity against the genetic damage induced by diverse agents like the alkyl ants of direct and indirect action, the gamma radiation and some heterocyclic amines. This effect has been observed in testing systems like Salmonella, Drosophila, rainbow trout and rodents. In the mouse spermatogonia it has been reported that it reduces the damage to the DNA but with the test of lethal dominant in Drosophila increment the damage induced by gamma radiation. The present study consisted on evaluating the effect of the CHLN in the line germinal masculine of Drosophila by means of the lethal recessive test bound to the sex (LRLS) with the stump Muller 5 and a litters system. Its were pretreated wild males with CHLN and 24 h later were irradiated with 0, 10, 20 and 40 Gy of gamma radiation immediately later were crossed with virgin females of the stump Basc and at 72 h the male was transferred to a cultivation media with three new virgin females, this process repeated three times until completing 3 litters. The F1 it was crossed among itself and in the F2 it was analysed the presence or absence of lethals. The results indicated that the CHLN per se incremented the basal frequency of damage due to the pigment can act as an agent that is inserted to the ADN causing pre mutagenic leisure. Nevertheless with the groups treated with the different doses of gamma radiation the CHLN does not present any protector action, neither promoter except in the litter I of the group

Analytical studies into radiation-induced starch damage in black and white peppers

International Nuclear Information System (INIS)

Sharif, M.M.; Farkas, J.

1993-01-01

Temperature dependence of the apparent viscosity of heat-generalized suspensions of untreated and irradiated pepper samples has been investigated. There was a close linear correlation between the logarithm of ''fluidity'' (reciprocal of the apparent viscosity) and the reciprocal absolute temperature of the measurement. The slope of the regression line (the temperature dependence of fluidity) increased with the radiation dose. Gelatinization thermograms of aqueous suspensions of ground pepper samples were obtained by differential scanning calorimetry. Temperature characteristics of heat-gelatinization endotherms showed no significant differences between untreated and irradiated samples. A calorimetric method for damaged starch, the estimation of reducing power, and the alcohol-induced turbidity of aqueous extracts showed statistically significant increases of starch damage at doses higher than 4 kGy. These indices of starch-depolymerization have been changed less dramatically by irradiation than the apparent viscosity of the heat-gelatinized suspensions. (author)

Post-irradiation dietary vitamin E does not affect the development of radiation-induced lung damage in rats

NARCIS (Netherlands)

Wiegman, EA; van Gameren, MA; Kampinga, HH; Szabo, BG; Coppes, RP

The purpose of this study was to investigate whether application of post-irradiation vitamin E, an anti-oxidant, could prevent the development of radiation induced lung damage. Wistar rats were given vitamin E enriched or vitamin E deprived food starting from 4 weeks after 18 Gy single dose

Radioprotective effect of sesamol on γ-radiation induced DNA damage, lipid peroxidation and antioxidants levels in cultured human lymphocytes

International Nuclear Information System (INIS)

Prasad, N. Rajendra; Menon, Venugopal P.; Vasudev, V.; Pugalendi, K.V.

2005-01-01

Sesamol pretreated (1, 5 and 10 μg/ml) lymphocytes were exposed to different doses of γ-radiation, i.e., 1, 2 and 4 Gray (Gy) and the cellular changes were estimated by using cytokinesis blocked micronucleus assay (MN), dicentric aberration (DC), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Radiation significantly increased MN, DC frequencies, TBARS levels and decreased GSH and antioxidant enzyme levels in a dose dependent manner. The highest damage to lymphocytes was observed at 4 Gy irradiation. On the other hand, sesamol pretreatment significantly decreased MN, DC frequencies, TBARS levels and increased GSH levels and SOD, CAT and GPx activities in a concentration dependent manner. At 1 Gy irradiation all concentrations of sesamol (1, 5 and 10 μg/ml) significantly protects the lymphocytes from radiation damage. At 2 Gy irradiation 5 and 10 μg/ml of sesamol shows significant radioprotection. Since the highest damage was observed at 4 Gy irradiation both 1 and 5 μg/ml of sesamol pretreatment were not sufficient to protect the lymphocytes from radiation damage but 10 μg/ml of sesamol significantly (p < 0.05) protects the lymphocytes from radiation effect. Thus, sesamol pretreatment gives significant protection to cultured human lymphocytes against γ-radiation induced cellular damage. The possible mechanism involved in the radioprotective influence of sesamol is discussed

The Possible Protective Role of Curcumin against Radiation Induced Cytogenetic Damages in Mice

International Nuclear Information System (INIS)

Hassan, M.R.M.

2014-01-01

This study was undertaken to investigate the effect of curcumin on radiation induced damages in albino male mice. Animals were injected intraperitoneally with 20 mg/kg body weight curcumin 30 minutes prior to whole body gamma-irradiation (4Gy). Animals were sacrificed after 1, 3 and 7 days of the irradiation. The possible radioprotective effect of curcumin on bone marrow chromosomes, DNA fragmentation, superoxide dismutase (SOD) activity, reduced glutathione (GSH) content, malondialdehyde (MDA) level, total free radicals in spleen, and peripheral blood differential count was examined at the different time intervals of the experiment. Radiation exposure resulted in a statistically significant elevation in the percentage of the aberrant metaphases, total amount of chromosomal damage, percentage of the DNA fragmentation, (MDA) level, decline in the activities of (SOD) and (GSH) contents, at 1, 3 and 7 days post-irradiation, elevation in the total free radicals one day post-irradiation and percentage of the total number of normal and abnormal white blood cells after 1, 3 days of irradiation specially the abnormal lymphocytes and neutrophils. Curcumin showed a clastogenic effect that it caused elevation of the total number of aberrant cells, structural and numerical aberrant cells after 1 and 3 days of the experiment. Moreover, curcumin caused a decline in the liver (GSH) content after 1, 3 and 7 days of the experiment. On the other hand, intraperitoneal injection of curcumin before irradiation didn‘t show any protective effect on the total aberrant cells and structural aberrant cells induced by irradiation, liver (GSH) content and the percentage of the DNA fragmentation, liver (MDA) level and number of abnormal leukocytes. In contrast, it showed potentiating effect on the numerical type aberrations especially endomitosis after one day post-irradiation. In addition, elevation in the percentage of the total free radicals induced by curcumin 3 and 7 days post

Damage of DNA by radiation and it's recovery, 3

International Nuclear Information System (INIS)

Narita, Noboru; Matsuura, Tomio; Sato, Hiroyuki.

1974-01-01

The damage and recovery of DNA was investigated by the incorporation of thymine derivatives (DHT, I trans, II trans, cis and glycol) into exponentially growing Tetrahymena cells. The strain employed was Tetrahymena pyriformis, Variety I, mating type IV. It is well known that these thymine derivatives are induced in vivo by radiation. The in vivo damage of DNA induced by radiation, and its recovery, were confirmed experimentally by means of gradient separation of sucrose density and by analytical ultra centrifugation (UVC). The recovery of DNA, its excision repair and its recombinational repair were compared with the recovery of Bacillus subtilis whose recovery kinetics were already known. 1) The damage of DNA was more sensitive to glycol than to II trans and cis. On the other hand, DHT is not sensitive for breaking DNA strand. 2) In its recovery damaged DNA was no more sensitive to glycol than to hhp as was true for Bacillus subtilis. (author)

DNA Damage by Ionizing Radiation: Tandem Double Lesions by Charged Particles

Science.gov (United States)

Huo, Winifred M.; Chaban, Galina M.; Wang, Dunyou; Dateo, Christopher E.

2005-01-01

Oxidative damages by ionizing radiation are the source of radiation-induced carcinogenesis, damage to the central nervous system, lowering of the immune response, as well as other radiation-induced damages to human health. Monte Carlo track simulations and kinetic modeling of radiation damages to the DNA employ available molecular and cellular data to simulate the biological effect of high and low LET radiation io the DNA. While the simulations predict single and double strand breaks and base damages, so far all complex lesions are the result of stochastic coincidence from independent processes. Tandem double lesions have not yet been taken into account. Unlike the standard double lesions that are produced by two separate attacks by charged particles or radicals, tandem double lesions are produced by one single attack. The standard double lesions dominate at the high dosage regime. On the other hand, tandem double lesions do not depend on stochastic coincidences and become important at the low dosage regime of particular interest to NASA. Tandem double lesions by hydroxyl radical attack of guanine in isolated DNA have been reported at a dosage of radiation as low as 10 Gy. The formation of two tandem base lesions was found to be linear with the applied doses, a characteristic of tandem lesions. However, tandem double lesions from attack by a charged particle have not been reported.

Studies on protective effects of superoxide dismutase on radiation induced-chromosomal aberrations

International Nuclear Information System (INIS)

Zheng Siying; Jiang Jiagui; Lin Xingcheng

1987-09-01

This study demonstrates that radiation induced-chromosomal aberrations are not only due to the direct effect of radiation h it , but the indirect effect of free radical as well. Therefore, chromosome damage induced by radiation may be reduced by adding exogenous SOD into the radiation exposed lymphocyte culture to eliminate the superoxide free radical which damages DNA. On the other hand, however, the radiosensitivity of lymphocytes can be raised by adding SOD inhibitor (DDC) into the lymphocyte culture, which makes radiation induced-chromosomal damages more severely

Equivalence of displacement radiation damage in superluminescent diodes induced by protons and heavy ions

Energy Technology Data Exchange (ETDEWEB)

Li, Xingji, E-mail: lxj0218@hit.edu.cn [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Liu, Chaoming [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Lan, Mujie; Xiao, Liyi [Center of Micro-electronics, Harbin Institute of Technology, Harbin 150001 (China); Liu, Jianchun; Ding, Dongfa [Beijing Aerospace Times Optical-electronic Technology Co.Ltd, Beijing 100854 (China); Yang, Dezhuang; He, Shiyu [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China)

2013-07-11

The degradation of optical power for superluminescent diodes is in situ measured under exposures of protons with various energies (170 keV, 3 MeV and 5 MeV), and 25 MeV carbon ions for several irradiation fluences. Experimental results show that the optical power of the SLDs decreases with increasing fluence. The protons with lower energies cause more degradation in the optical power of SLDs than those with higher energies at a given fluence. Compared to the proton irradiation with various energies, the 25 MeV carbon ions induce more severe degradation to the optical power. To characterize the radiation damage of the SLDs, the displacement doses as a function of chip depth in the SLDs are calculated by SRIM code for the protons and carbon ions. Based on the irradiation testing and calculation results, an approach is given to normalize the equivalence of displacement damage induced by various charged particles in SLDs.

Characteristics of the chrome-tanned sheep leather treated by radiation-induced graft of BA

International Nuclear Information System (INIS)

Zhou Dezhong; Deng Yongzhen; Li Ying

1986-01-01

The characteristics of the chrome-tanned sheep leather treated by radiation-induced graft of BA is presented. Using the method of radiation-induced graft of BA instead of the chrome-retanning, the leather has been obviously improved not only in the surface, such as the brightness, fullness, uniformity of the thickness but also in the physical characteristics such as retaining of tensile strength, decreasing of water absorption after being immersed in water for 2h, and 24h, enhancement of tearing strength and stitch tear strength. Although the air permeability and water vapor permeability are a bit worse than the control, however is still in the range of the standard issued by Light Industry Ministry of China

Caffeine and D2O medium interact in affecting the expression of radiation-induced potentially lethal damage

International Nuclear Information System (INIS)

Utsumi, H.; Elkind, M.M.

1991-01-01

Earlier work has been extended to compare the killing of long-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D 2 O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D 2 O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D 2 O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D 2 O medium is similar. For example, the kinetic of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D 2 O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. Thus, although caffeine and D 2 O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect. (author)

Long term radiological features of radiation-induced lung damage.

Science.gov (United States)

Veiga, Catarina; Landau, David; McClelland, Jamie R; Ledermann, Jonathan A; Hawkes, David; Janes, Sam M; Devaraj, Anand

2018-02-01

To describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation. Baseline and 12-month CT scans of 33 patients were reviewed from a phase I/II clinical trial of isotoxic chemoradiation (IDEAL CRT). CT findings were scored in three categories derived from eleven sub-categories: (1) parenchymal change, defined as the presence of consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or reticulation; (2) lung volume reduction, identified through reduction in lung height and/or distortions in fissures, diaphragm, anterior junction line and major airways anatomy, and (3) pleural changes, either thickening and/or effusion. Six patients were excluded from the analysis due to anatomical changes caused by partial lung collapse and abscess. All remaining 27 patients had radiological evidence of lung damage. The three categories, parenchymal change, shrinkage and pleural change were present in 100%, 96% and 82% respectively. All patients had at least two categories of change present and 72% all three. GGOs, reticulation and traction bronchiectasis were present in 44%, 52% and 37% of patients. Parenchymal change, lung shrinkage and pleural change are present in a high proportion of patients and are frequently identified in RILD. GGOs, reticulation and traction bronchiectasis are common at 12 months but not diagnostic. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation Damage in Silicon Detectors Caused by Hadronic and Electromagnetic Irradiation

CERN Document Server

Fretwurst, E.; Stahl, J.; Pintilie, I.

2002-01-01

The report contains various aspects of radiation damage in silicon detectors subjected to high intensity hadron and electromagnetic irradiation. It focuses on improvements for the foreseen LHC applications, employing oxygenation of silicon wafers during detector processing (result from CERN-RD48). An updated survey on hadron induced damage is given in the first article. Several improvements are outlined especially with respect to antiannealing problems associated with detector storage during LHC maintenance periods. Open questions are outlined in the final section, among which are a full understanding of differences found between proton and neutron induced damage, process related effects changing the radiation tolerance in addition to the oxygen content and the lack of understanding the changed detector properties on the basis of damage induced point and cluster defects. In addition to float zone silicon, so far entirely used for detector fabrication,Czochralski silicon was also studied and first promising re...

Study on preventive and therapeutic function of compound white peony root oral liquids in treating radiation-induced esophagitis

International Nuclear Information System (INIS)

Shen Li; Shan Baoen; Zhang Li; Li Wei; Gong Yanjun; Gao Haixiang

2007-01-01

Wistar rats were divided into seven groups: the normal group, the irradiated group, the preventive group treated with the normal dose of compound white peony root oral liquids (cWPROL) (immediately administered on the day after rats were irradiated), the preventive group treated with the high dose of cWPROL (immediately administered on the day after rats were irradiated), the group treated with normal dose of cWPROL (administered on the 7th day after rats were irradiated), the group treated with high dose of cWPROL (administered on the 7th day after rats were irradiated), the group treated with Western medicine administered from the seventh day after irradiation. The radiation esophagitis of rats was induced by single irradiation of 43 Gy gamma ray locally. Then the rats with radiation esophagitis were treated in different ways. The food weight, water volume intaked by the rats and its body weight change were observed; The rats were killed on the 14th day after irradiation and the leucocyte count and DIFF were analyzed and the esophageal pathological sections were made. The pathological change of rats' esophageal mucosa and ultrastructure change of cells were observed for different groups. The results showed all the cWPROL and Western medicine have therapeutic function of treating radiation-induced esophagitis of rats. The ultrastructure of cells of rats in the group treated with normal dose of cWPROL recovered. The food weight and water volume intaked by the rats had increased in the group infused with cWPROL compared with purely irradiated groups, especially in the preventive group treated with high dose of cWPROL. The weight of food, the WBC count, the lymphocyte differential count in the group which was treated with Western medicine decreased compared with the purely irradiated group. Lymphocyte differential count increased in the groups administered cWPROL compared with the purely irradiated group. The compound white peony root oral liquids serves the function

Ultraviolet Radiations: Skin Defense-Damage Mechanism.

Science.gov (United States)

Mohania, Dheeraj; Chandel, Shikha; Kumar, Parveen; Verma, Vivek; Digvijay, Kumar; Tripathi, Deepika; Choudhury, Khushboo; Mitten, Sandeep Kumar; Shah, Dilip

2017-01-01

UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations. Certain heredity diseases have been found susceptible to UV-induced skin cancer. UV radiations activate the cutaneous immune system, which led to an inflammatory response by different mechanisms. The first line of defense mechanism against UV radiation is melanin (an epidermal pigment), and UV absorbing pigment of skin, which dissipate UV radiation as heat. Cell surface death receptor (e.g. Fas) of keratinocytes responds to UV-induced injury and elicits apoptosis to avoid malignant transformation. In addition to the formation of photo-dimers in the genome, UV also can induce mutation by generating ROS and nucleotides are highly susceptible to these free radical injuries. Melanocortin 1 receptor (MC1R) has been known to be implicated in different UV-induced damages such as pigmentation, adaptive tanning, and skin cancer. UV-B induces the formation of pre-vitamin D3 in the epidermal layer of skin. UV-induced tans act as a photoprotection by providing a sun protection factor (SPF) of 3-4 and epidermal hyperplasia. There is a need to prevent the harmful effects and harness the useful effects of UV radiations.

Radiation damage of nonmetallic solids

International Nuclear Information System (INIS)

Goland, A.N.

1975-01-01

A review of data and information on radiation damage in nonmetallic solids is presented. Discussions are included on defects in nonmetals, radiation damage processes in nonmetals, electronic damage processes, physical damage processes, atomic displacement, photochemical damage processes, and ion implantation

Radiation damage in nonmetallic solids under dense electronic excitation

International Nuclear Information System (INIS)

Itoh, Noriaki; Tanimura, Katsumi; Nakai, Yasuo

1992-01-01

Basic processes of radiation damage of insulators by dense electronic excitation are reviewed. First it is pointed out that electronic excitation of nonmetallic solids produces the self-trapped excitons and defect-related metastable states having relatively long lifetimes, and that the excitation of these metastable states, produces stable defects. The effects of irradiation with heavy ions, including track registration, are surveyed on the basis of the microscopic studies. It is pointed out also that the excitation of the metastable states plays a role in laser-induced damage at relatively low fluences, while the laser damage has been reported to be governed by heating of free electrons produced by multiphoton excitation. Difference in the contributions of the excitation of metastable defects to laser-induced damage of surfaces, or laser ablation, and laser-induced bulk damage is stressed. (orig.)

Intensification of ultraviolet-induced dermal damage by infrared radiation

International Nuclear Information System (INIS)

Kligman, L.H.

1982-01-01

To assess the role of IR in actinic damage to the dermis, albino guinea pigs were irradiated for 45 weeks with UV-B and UV-A, with and without IR. Control animals received IR only or no irradiation at all. Unirradiated dermis contains small amounts of elastic fibers in the upper dermis with greater depositions around follicles and sebaceous glands. After irradiation with UV, the fibers became more numerous, thicker, and more twisted; IR alone producd many fine, feathery fibers. The addition of IR to UV resulted in dense matlike elastic fiber depositions that exceeded what was observed with either irradiation alone. In combination or alone UV and IR radiation produced a large increase in ground substance, a finding also seen in actinically damaged human skin. Infrared radiation, in the physiologic range, though pleasant is not innocuous. (orig./MG) [de

The cellular environment in computer simulations of radiation-induced damage to DNA

International Nuclear Information System (INIS)

Moiseenko, V.V.; Waker, A.J.; Prestwich, W.V.

1998-01-01

Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in a cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3 x 10 9 dm 3 mol -1 s -1 . Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10 -9 s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage. (orig.)

The cellular environment in computer simulations of radiation-induced damage to DNA

International Nuclear Information System (INIS)

Moiseenko, V.V.; Hamm, R.N.; Waker, A.J.; Prestwich, W.V.

1988-01-01

Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3x10 9 dm 3 mol -1 s-1. Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10 -9 s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage. (author)

Thioredoxin mitigates radiation-induced hematopoietic stem cell injury in mice

Directory of Open Access Journals (Sweden)

Pasupathi Sundaramoorthy

2017-11-01

Full Text Available Abstract Background Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs from radiation injury is an important goal in the development of medical countermeasure agents (MCM. We recently identified thioredoxin (TXN as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI and in enhancing hematopoietic reconstitution following a lethal dose of irradiation. Methods We used in-vivo and in-vitro methods to understand the biological and molecular mechanisms of TXN on radiation mitigation. BABL/c mice were used for the survival study and a flow cytometer was used to quantify the HSC population and cell senescence. A hematology analyzer was used for the peripheral blood cell count, including white blood cells (WBCs, red blood cells (RBCs, hemoglobin, and platelets. Colony forming unit (CFU assay was used to study the colongenic function of HSCs. Hematoxylin and eosin staining was used to determine the bone marrow cellularity. Senescence-associated β-galactosidase assay was used for cell senescence. Western blot analysis was used to evaluate the DNA damage and senescence protein expression. Immunofluorescence staining was used to measure the expression of γ-H2AX foci for DNA damage. Results We found that administration of TXN 24 h following irradiation significantly mitigates BALB/c mice from TBI-induced death: 70% of TXN-treated mice survived, whereas only 25% of saline-treated mice survived. TXN administration led to enhanced recovery of peripheral blood cell counts, bone marrow cellularity, and HSC population as measured by c-Kit+Sca-1+Lin– (KSL cells, SLAM + KSL cells and CFUs. TXN treatment reduced cell senescence and radiation-induced

Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

International Nuclear Information System (INIS)

Stoilov, L.M.; Mullenders, L.H.F.; Natarajan, A.T.

1994-01-01

The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations

Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

Energy Technology Data Exchange (ETDEWEB)

Stoilov, L.M. (Department of Molecular Genetics, Institute of Genetics, Sofia (Bulgaria)); Mullenders, L.H.F.; Natarajan, A.T. (J.A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection, Leiden (Netherlands))

1994-12-01

The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations.

Protective effects of melatonin on damage of thymocytes in mice induced by ionizing radiation

International Nuclear Information System (INIS)

Zhang Xuan; Wang Zhenqi; Liu Yang; Gong Shouliang; Zhang Ming; Liu Shuzheng

2004-01-01

Objective: To explore the effects of melatonin (MLT) on the damage of mouse thymocytes in vivo induced by ionizing radiation and its mechanism. Methods: The exogenous MLT was given to Kunming mice to establish the animal models of single and successive administration of MLT through intraperitoneal injection before whole-body irradiation with 1 Gy X-rays. For single administration of MLT, the apoptotic body percentage (ABP) and DNA lytic rate (DLR) in the thymocytes were determined with flow cytometry and fluorospectrophotometry, respectively, 12 h after irradiation. For successive administration of MLT, 3 H-TdR incorporative rate (HTIR ) was determined 24 h after irradiation. Results: The number of thymocytes in single administration group was significantly lower than that in the sham-irradiation group 12 h after irradiation with 1 Gy X-rays (P -1 MLT group was significantly higher, while the ABP and DLR were significantly lower than those in 0 mg·kg -1 MLT group (simple irradiation, P -1 MLT were significantly higher than that in 0 mg·kg -1 MLT group (P -1 MLT group was also significantly higher (P<0.05). Conclusion: The administration of exogenous MLT before irradiation can decrease the damage of mouse thymocytes induced by ionizing radiation, and has the protective effect on immune functions in mice. (authors)

Thermal annealing of natural, radiation-damaged pyrochlore

Energy Technology Data Exchange (ETDEWEB)

Zietlow, Peter; Mihailova, Boriana [Hamburg Univ. (Germany). Dept. of Earth Sciences; Beirau, Tobias [Hamburg Univ. (Germany). Dept. of Earth Sciences; Stanford Univ., CA (United States). Dept. of Geological Sciences; and others

2017-03-01

Radiation damage in minerals is caused by the α-decay of incorporated radionuclides, such as U and Th and their decay products. The effect of thermal annealing (400-1000 K) on radiation-damaged pyrochlores has been investigated by Raman scattering, X-ray powder diffraction (XRD), and combined differential scanning calorimetry/thermogravimetry (DSC/TG). The analysis of three natural radiation-damaged pyrochlore samples from Miass/Russia [6.4 wt% Th, 23.1.10{sup 18} α-decay events per gram (dpg)], Panda Hill/Tanzania (1.6 wt% Th, 1.6.10{sup 18} dpg), and Blue River/Canada (10.5 wt% U, 115.4.10{sup 18} dpg), are compared with a crystalline reference pyrochlore from Schelingen (Germany). The type of structural recovery depends on the initial degree of radiation damage (Panda Hill 28%, Blue River 85% and Miass 100% according to XRD), as the recrystallization temperature increases with increasing degree of amorphization. Raman spectra indicate reordering on the local scale during annealing-induced recrystallization. As Raman modes around 800 cm{sup -1} are sensitive to radiation damage (M. T. Vandenborre, E. Husson, Comparison of the force field in various pyrochlore families. I. The A{sub 2}B{sub 2}O{sub 7} oxides. J. Solid State Chem. 1983, 50, 362, S. Moll, G. Sattonnay, L. Thome, J. Jagielski, C. Decorse, P. Simon, I. Monnet, W. J. Weber, Irradiation damage in Gd{sub 2}Ti{sub 2}O{sub 7} single crystals: Ballistic versus ionization processes. Phys. Rev. 2011, 84, 64115.), the degree of local order was deduced from the ratio of the integrated intensities of the sum of the Raman bands between 605 and 680 cm{sup -1} divided by the sum of the integrated intensities of the bands between 810 and 860 cm{sup -1}. The most radiation damaged pyrochlore (Miass) shows an abrupt recovery of both, its short- (Raman) and long-range order (X-ray) between 800 and 850 K, while the weakly damaged pyrochlore (Panda Hill) begins to recover at considerably lower temperatures (near 500 K

Enhancement of radiation damage in germinating wheat seeds by hyperthermia

International Nuclear Information System (INIS)

Guo Fangqing; Gu Ruiqi

1994-01-01

Enhancement of X-ray induced radiation damage in germinating wheat seeds by heat treatment (44 degree C or 41 degree C, 20 min) has been investigated. The enhancement effect of heat treatment after irradiation was more significant than that of heat treatment before irradiation at dose range of 4.3-8.6 Gy. It was observed that germinating wheat seeds were very sensitive to heat treatment within 15 min after irradiation, which indicated that the repair of radiation damage was very active and rapid in a short period after irradiation. The repair of radiation damage in interval of fractionated irradiation was severely inhibited by heat treatment. The sensitivity of seeds to heat treatment corresponded with the levels of their repair activities. The more active the repairs of the seeds are, the more sensitive to heat treatment the seeds show. It was assumed that the enhancement of radiation damage by heat treatment in germinating wheat seeds was attributed to the inhibition of radiation damage repair by heat treatment, which is similar to the results of animal experiments

Cataracts induced by microwave and ionizing radiation

International Nuclear Information System (INIS)

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

1988-01-01

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

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

Science.gov (United States)

Lorimore, S A; Wright, E G

2003-01-01

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

Radiation damage to DNA: The importance of track structure

CERN Document Server

Hill, M A

1999-01-01

A wide variety of biological effects are induced by ionizing radiation, from cell death to mutations and carcinogenesis. The biological effectiveness is found to vary not only with the absorbed dose but also with the type of radiation and its energy, i.e., with the nature of radiation tracks. An overview is presented of some of the biological experiments using different qualities of radiation, which when compared with Monte Carlo track structure studies, have highlighted the importance of the localized spatial properties of stochastic energy deposition on the nanometer scale at or near DNA. The track structure leads to clustering of damage which may include DNA breaks, base damage etc., the complexity of the cluster and therefore its biological repairability varying with radiation type. The ability of individual tracks to produce clustered damage, and the subsequent biological response are important in the assessment of the risk associated with low-level human exposure. Recent experiments have also shown that...

DNA damage in leukocytes from fanconi anemia patients and heterozygotes induced by mitomycin C and ionizing radiation as assessed by the comet and comet - FISH assay

International Nuclear Information System (INIS)

Mohseni Meybodi, A.; Mozdarani, H.

2009-01-01

Lymphocytes of Fanconi anemia (FA) show an increased sensitivity to the alkylating agents such as mitomycin C (MMC), but their responses to gamma-irradiation is controversial. The extent of DNA damage in leukocytes of FA patients following irradiation and MMC treatment was studied at cellular and single chromosome level. Methods: DNA damage induced by gamma-rays and MMC was measured in leukocytes of FA patients and carriers at whole genome level using the comet assay. Also, at the DNA level of specific chromosome involved in this disease using a modified comet-FISH protocol with whole chromosome painting probes (chromosomes 16 and 13), DNA damage in leukocytes of FA patients and heterozygotes were compared to healthy individuals. Results: Baseline DNA damage in leukocytes of patients and heterozygotes was higher than in controls. Net induced DNA damage by gamma-rays in leukocytes of FA cases was not significantly different from that of healthy donors and heterozygotes. Net induced DNA damage by MMC was statistically higher and significantly different (P<0.05) in patients than other groups. Hybridization of chromosome 16 reveals more signals in the tail but the number of spots in the tail was not significantly higher than the hybridization spots for chromosome 13 in both gamma-irradiated and MMC treated samples. Conclusion: Results indicate that DNA damage induced by MMC could be a better index for diagnosis of FA patients compared to gamma-rays. Results of comet-FISH showed no difference between the sensitivity of chromosome 16 and 13 to MMC and radiation. It may indicate that, although the FA-A gene is located on chromosome 16, this chromosome might have a similar sensitivity as other chromosomes

Damaging and protective cell signalling in the untargeted effects of ionizing radiation

International Nuclear Information System (INIS)

Coates, Philip J.; Lorimore, Sally A.; Wright, Eric G.

2004-01-01

The major adverse consequences of radiation exposures are attributed to DNA damage in irradiated cells that has not been correctly restored by metabolic repair processes. However, the dogma that genetic alterations are restricted to directly irradiated cells has been challenged by observations in which effects of ionizing radiation arise in non-irradiated cells. These, so called, untargeted effects are demonstrated in cells that are the descendants of irradiated cells either directly or via media transfer (radiation-induced genomic instability) or in cells that have communicated with irradiated cells (radiation-induced bystander effects). Radiation-induced genomic instability is characterized by a number of delayed responses including chromosomal abnormalities, gene mutations and cell death. Bystander effects include increases or decreases in damage-inducible and stress-related proteins, increases or decreases in reactive oxygen and nitrogen species, cell death or cell proliferation, cell differentiation, radioadaptation, induction of mutations and chromosome aberrations and chromosomal instability. The phenotypic expression of untargeted effects and the potential consequences of these effects in tissues reflect a balance between the type of bystander signals produced and the responses of cell populations to such signals, both of which may be significantly influenced by cell type and genotype. Thus, in addition to targeted effects of damage induced directly in cells by irradiation, a variety of untargeted effects may also make important short-term and long-term contributions to determining overall outcome after radiation exposures

Use of 2-color flow cytometry to assess radiation induced geotoxic damage on CHO-KI cells

Energy Technology Data Exchange (ETDEWEB)

Carvalho, Luma Ramirez de; Bonfim, Leticia; Vieira, Daniel Perez, E-mail: lrcarvalho@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2017-11-01

The micronucleus assay is an important technique used to evaluate genotoxic damage of chemical or physical agents (as ionizing radiations) on cells, based on quantification of cells bearing micronuclei, which are fragments derived from damage (breakage) of the DNA. Currently, this technique was updated to an automated approach that relies on plasma membrane dissolution to analyze fluorescent dye-labelled nuclei and micronuclei by flow cytometry. Cell suspensions were irradiated in PBS by a {sup 60}Co source in doses between 0 and 16Gy, and incubated by 48h. Cell membranes were lysed in the presence of SYTOX Green and EMA dyes, so EMA-stained nuclei could be discriminated as from dead cells, and nuclei and micronuclei could be quantified. Amounts of micronuclei (percent of events) in the samples, were found to be proportional to radiation doses, and could be fitted to a linear-quadratic model (R² = 0.993). Only higher doses (8 and 16Gy) and positive control could induce relevant increases in micronucleus amounts. The incorporation EMA showed an increase in irradiated cells. Mid to high doses (4, 8 and 16Gy) induced reduction of cell proliferation. Experiments showed the suitability of the technique to replace traditional microscopy analysis in evaluation of the effects of ionizing radiations on cells, with possibility to use in biological dosimetry. (author)

Enhancement of chemically induced reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells by 872 MHz radiofrequency radiation

Energy Technology Data Exchange (ETDEWEB)

Luukkonen, Jukka [Department of Environmental Science, University of Kuopio, Bioteknia 2, P.O. Box 1627, FI-70211 Kuopio (Finland)], E-mail: Jukka.Luukkonen@uku.fi; Hakulinen, Pasi; Maeki-Paakkanen, Jorma [Department of Environmental Health, National Public Health Institute, P.O. Box 95, FI-70701 Kuopio (Finland); Juutilainen, Jukka; Naarala, Jonne [Department of Environmental Science, University of Kuopio, Bioteknia 2, P.O. Box 1627, FI-70211 Kuopio (Finland)

2009-03-09

The objective of the study was to investigate effects of 872 MHz radiofrequency (RF) radiation on intracellular reactive oxygen species (ROS) production and DNA damage at a relatively high SAR value (5 W/kg). The experiments also involved combined exposure to RF radiation and menadione, a chemical inducing intracellular ROS production and DNA damage. The production of ROS was measured using the fluorescent probe dichlorofluorescein and DNA damage was evaluated by the Comet assay. Human SH-SY5Y neuroblastoma cells were exposed to RF radiation for 1 h with or without menadione. Control cultures were sham exposed. Both continuous waves (CW) and a pulsed signal similar to that used in global system for mobile communications (GSM) mobile phones were used. Exposure to the CW RF radiation increased DNA breakage (p < 0.01) in comparison to the cells exposed only to menadione. Comparison of the same groups also showed that ROS level was higher in cells exposed to CW RF radiation at 30 and 60 min after the end of exposure (p < 0.05 and p < 0.01, respectively). No effects of the GSM signal were seen on either ROS production or DNA damage. The results of the present study suggest that 872 MHz CW RF radiation at 5 W/kg might enhance chemically induced ROS production and thus cause secondary DNA damage. However, there is no known mechanism that would explain such effects from CW RF radiation but not from GSM modulated RF radiation at identical SAR.

Enhancement of chemically induced reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells by 872 MHz radiofrequency radiation

International Nuclear Information System (INIS)

Luukkonen, Jukka; Hakulinen, Pasi; Maeki-Paakkanen, Jorma; Juutilainen, Jukka; Naarala, Jonne

2009-01-01

The objective of the study was to investigate effects of 872 MHz radiofrequency (RF) radiation on intracellular reactive oxygen species (ROS) production and DNA damage at a relatively high SAR value (5 W/kg). The experiments also involved combined exposure to RF radiation and menadione, a chemical inducing intracellular ROS production and DNA damage. The production of ROS was measured using the fluorescent probe dichlorofluorescein and DNA damage was evaluated by the Comet assay. Human SH-SY5Y neuroblastoma cells were exposed to RF radiation for 1 h with or without menadione. Control cultures were sham exposed. Both continuous waves (CW) and a pulsed signal similar to that used in global system for mobile communications (GSM) mobile phones were used. Exposure to the CW RF radiation increased DNA breakage (p < 0.01) in comparison to the cells exposed only to menadione. Comparison of the same groups also showed that ROS level was higher in cells exposed to CW RF radiation at 30 and 60 min after the end of exposure (p < 0.05 and p < 0.01, respectively). No effects of the GSM signal were seen on either ROS production or DNA damage. The results of the present study suggest that 872 MHz CW RF radiation at 5 W/kg might enhance chemically induced ROS production and thus cause secondary DNA damage. However, there is no known mechanism that would explain such effects from CW RF radiation but not from GSM modulated RF radiation at identical SAR

Radiation damage in BaF2 crystals

International Nuclear Information System (INIS)

Woody, C.L.; Kierstead, J.A.; Levy, P.W.; Stoll, S.

1991-01-01

The effects of radiation damage and recovery have been studied in BaF 2 crystals exposed to 60 Co radiation. The change in optical transmission and scintillation light output have been measured as a function of dose up to 4.7 x 10 6 rad. Although some crystals exhibit a small change in transmission, a greater change in scintillation light output is observed. Several 25 cm long crystals whichhave been irradiated show large changes in both transmission and light output. Recovery from radiation damage has been studied as a function of time and exposure to UV light. A long lived radiation induced phosphorescence has been observed in all irradiated samples which is distinct from the standard fast and slow scintillation emissions. The emission spectrum of the phosphorescence has been measured and shown a peakat ∼330 nm, near the region of the slow scintillation component. Results are given on the dependence of the decay time of the phosphorescence with dose

Hydration-annealing of chemical radiation damage in calcium nitrate

International Nuclear Information System (INIS)

Nair, S.M.K.; James, C.

1984-01-01

The effect of hydration on the annealing of chemical radiation damage in anhydrous calcium nitrate has been investigated. Rehydration of the anhydrous irradiated nitrate induces direct recovery of the damage. The rehydrated salt is susceptible to thermal annealing but the extent of annealing is small compared to that in the anhydrous salt. The direct recovery of damage on rehydration is due to enhanced lattice mobility. The recovery process is unimolecular. (author)

Radiation damage effect on avalanche photodiodes

CERN Document Server

Baccaro, S; Cavallari, F; Da Ponte, V; Deiters, K; Denes, P; Diemoz, M; Kirn, Th; Lintern, A L; Longo, E; Montecchi, M; Musienko, Y; Pansart, J P; Renker, D; Reucroft, S; Rosi, G; Rusack, R; Ruuska, D; Stephenson, R; Torbet, M J

1999-01-01

Avalanche Photodiodes have been chosen as photon sensors for the electromagnetic calorimeter of the CMS experiment at the LHC. These sensors should operate in the 4T magnetic field of the experiment. Because of the high neutron radiation in the detector extensive studies have been done by the CMS collaboration on the APD neutron radiation damage. The characteristics of these devices after irradiation have been analized, with particular attention to the quantum efficiency and the dark current. The recovery of the radiation induced dark current has been studied carefully at room temperature and at slightly lower and higher temperatures. The temperature dependence of the defects decay-time has been evaluated.

Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation

Energy Technology Data Exchange (ETDEWEB)

Asaithamby, Aroumougame, E-mail: Aroumougame.Asaithamy@UTsouthwestern.edu [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 (United States); Chen, David J., E-mail: David.Chen@UTsouthwestern.edu [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 (United States)

2011-06-03

Low-linear energy transfer (LET) radiation (i.e., {gamma}- and X-rays) induces DNA double-strand breaks (DSBs) that are rapidly repaired (rejoined). In contrast, DNA damage induced by the dense ionizing track of high-atomic number and energy (HZE) particles is slowly repaired or is irreparable. These unrepaired and/or misrepaired DNA lesions may contribute to the observed higher relative biological effectiveness for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in HZE particle irradiated cells compared to those treated with low-LET radiation. The types of DNA lesions induced by HZE particles have been characterized in vitro and usually consist of two or more closely spaced strand breaks, abasic sites, or oxidized bases on opposing strands. It is unclear why these lesions are difficult to repair. In this review, we highlight the potential of a new technology allowing direct visualization of different types of DNA lesions in human cells and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal characterization of complex DNA damage. We focus on the recent insights into the molecular pathways that participate in the repair of HZE particle-induced DSBs. We also discuss recent advances in our understanding of how different end-processing nucleases aid in repair of DSBs with complicated ends generated by HZE particles. Understanding the mechanism underlying the repair of DNA damage induced by HZE particles will have important implications for estimating the risks to human health associated with HZE particle exposure.

Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation

International Nuclear Information System (INIS)

Asaithamby, Aroumougame; Chen, David J.

2011-01-01

Low-linear energy transfer (LET) radiation (i.e., γ- and X-rays) induces DNA double-strand breaks (DSBs) that are rapidly repaired (rejoined). In contrast, DNA damage induced by the dense ionizing track of high-atomic number and energy (HZE) particles is slowly repaired or is irreparable. These unrepaired and/or misrepaired DNA lesions may contribute to the observed higher relative biological effectiveness for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in HZE particle irradiated cells compared to those treated with low-LET radiation. The types of DNA lesions induced by HZE particles have been characterized in vitro and usually consist of two or more closely spaced strand breaks, abasic sites, or oxidized bases on opposing strands. It is unclear why these lesions are difficult to repair. In this review, we highlight the potential of a new technology allowing direct visualization of different types of DNA lesions in human cells and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal characterization of complex DNA damage. We focus on the recent insights into the molecular pathways that participate in the repair of HZE particle-induced DSBs. We also discuss recent advances in our understanding of how different end-processing nucleases aid in repair of DSBs with complicated ends generated by HZE particles. Understanding the mechanism underlying the repair of DNA damage induced by HZE particles will have important implications for estimating the risks to human health associated with HZE particle exposure.

The use of the SRIM code for calculation of radiation damage induced by neutrons

Science.gov (United States)

Mohammadi, A.; Hamidi, S.; Asadabad, Mohsen Asadi

2017-12-01

Materials subjected to neutron irradiation will being evolve to structural changes by the displacement cascades initiated by nuclear reaction. This study discusses a methodology to compute primary knock-on atoms or PKAs information that lead to radiation damage. A program AMTRACK has been developed for assessing of the PKAs information. This software determines the specifications of recoil atoms (using PTRAC card of MCNPX code) and also the kinematics of interactions. The deterministic method was used for verification of the results of (MCNPX+AMTRACK). The SRIM (formely TRIM) code is capable to compute neutron radiation damage. The PKAs information was extracted by AMTRACK program, which can be used as an input of SRIM codes for systematic analysis of primary radiation damage. Then the Bushehr Nuclear Power Plant (BNPP) radiation damage on reactor pressure vessel is calculated.

Ion irradiation and biomolecular radiation damage II. Indirect effect

OpenAIRE

Wang, Wei; Yu, Zengliang; Su, Wenhui

2010-01-01

It has been reported that damage of genome in a living cell by ionizing radiation is about one-third direct and two-thirds indirect. The former which has been introduced in our last paper, concerns direct energy deposition and ionizing reactions in the biomolecules; the latter results from radiation induced reactive species (mainly radicals) in the medium (mainly water) surrounding the biomolecules. In this review, a short description of ion implantation induced radical formation in water is ...

Radiation damage in silicon detectors

CERN Document Server

Lindström, G

2003-01-01

Radiation damage effects in silicon detectors under severe hadron and gamma-irradiation are surveyed, focusing on bulk effects. Both macroscopic detector properties (reverse current, depletion voltage and charge collection) as also the underlying microscopic defect generation are covered. Basic results are taken from the work done in the CERN-RD48 (ROSE) collaboration updated by results of recent work. Preliminary studies on the use of dimerized float zone and Czochralski silicon as detector material show possible benefits. An essential progress in the understanding of the radiation-induced detector deterioration had recently been achieved in gamma irradiation, directly correlating defect analysis data with the macroscopic detector performance.

Polyhydroxylated fatty alcohols derived from avocado suppress inflammatory response and provide non-sunscreen protection against UV-induced damage in skin cells.

Science.gov (United States)

Rosenblat, Gennady; Meretski, Shai; Segal, Joseph; Tarshis, Mark; Schroeder, Avi; Zanin-Zhorov, Alexandra; Lion, Gilead; Ingber, Arieh; Hochberg, Malka

2011-05-01

Exposing skin to ultraviolet (UV) radiation contributes to photoaging and to the development of skin cancer by DNA lesions and triggering inflammatory and other harmful cellular cascades. The present study tested the ability of unique lipid molecules, polyhydroxylated fatty alcohols (PFA), extracted from avocado, to reduce UVB-induced damage and inflammation in skin. Introducing PFA to keratinocytes prior to their exposure to UVB exerted a protective effect, increasing cell viability, decreasing the secretion of IL-6 and PGE(2), and enhancing DNA repair. In human skin explants, treating with PFA reduced significantly UV-induced cellular damage. These results support the idea that PFA can play an important role as a photo-protective agent in UV-induced skin damage.

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

Science.gov (United States)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2017-11-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

Science.gov (United States)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2018-05-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.

Caffeine and D sub 2 O medium interact in affecting the expression of radiation-induced potentially lethal damage

Energy Technology Data Exchange (ETDEWEB)

Utsumi, H. (Kyoto Univ. (Japan). Radiation Biology Center); Elkind, M.M. (Colorado State Univ., Fort Collins, CO (United States). Dept. of Radiological Health Sciences)

1991-10-01

Earlier work has been extended to compare the killing of long-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D{sub 2}O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D{sub 2}O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D{sub 2}O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D{sub 2}O medium is similar. For example, the kinetic of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D{sub 2}O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. Thus, although caffeine and D{sub 2}O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect. (author).

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Radiation damage to DNA constituents

International Nuclear Information System (INIS)

Bergene, R.

1977-01-01

The molecular changes of the DNA molecule, in various systems exposed to inoizing radiation, have been the subject of a great number of studies. In the present work electron spin resonance spectroscopy (ESR) has been applied to irradiated crystalline systems, in particular single crystals of DNA subunits and their derivatives. The main conclusions about the molecular damage are based on this technique in combination with molecular orbital calculations. It should be emphasized that the ESR technique is restricted to damage containing unpaired electrons. These unstable intermediates called free radicals seem, however, to be involved in all molecular models describing the action of radiation on DNA. One of the premises for a detailed theory of the radiation induced reactions at the physico-chemical level seems to involve exact knowledge of the induced free radicals as well as the modes of their formation and fate. For DNA, as such, it is hardly possible to arrive at such a level of knowledge since the molecular complexity prevents selective studies of the many different radiation induced products. One possible approach is to study the free radicals formed in the constituents of DNA. In the present work three lines of approach should be mentioned. The first is based on the observation that radical formation in general causes only minor structural alterations to the molecule in question. The use of isotopes with different spin and magnetic moment (in particular deuterium) may also serve a source of information. Deuteration leads to a number of protons, mainly NH - and OH, becoming substituted, and if any of these are involved in interactions with unpaired protons the resonance pattern is influeneed. The third source of information is molecular orbital calculation. The electron spin density distribution is a function in the three dimensional space based on the system's electronic wave functions. This constitutes the basis for the idea that ESR data can be correlated with

Study of radiation damage in solid materials by simulating physical processes

International Nuclear Information System (INIS)

Pinnera Hernandez, Ibrahin

2006-12-01

Nowadays the damage induced by different types of radiation in advanced materials is widely studied. Especially those materials involved in experiments and developing of new technologies, such as high critical temperature superconductors, semiconductors, metals. These materials are the basis constituents of radiation detectors, particle accelerators, etc. One way of studying this kind of damage is through the determination of the displacements per atom (dpa) induced by the radiation in these materials. This magnitude is one of the measures of the provoked radiation damage. On this direction, the present thesis deals with the study of two types of materials through mathematical simulation of physical processes taking place in the radiation transport. Ceramic superconductor Yba 2 Cu 3 O 7-x and metal Fe are the selected materials. The energy range of the incident gamma radiation goes from a few keV to 15 MeV. The MCNPX version 2.6b is used to determine the physical magnitudes required to calculate the distribution of displacements per atom within these materials, using an algorithm implemented for this purpose. Finally, a comparison between the obtained dpa profiles and the corresponding of energy deposition by radiation in these same materials and the possible linear dependence between both quantities is discussed. (Author)

Low dose radiation prevents doxorubicin-induced cardiotoxicity.

Science.gov (United States)

Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

2018-01-02

This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic.

Science.gov (United States)

Maini, Sabia; Fahlman, Brian M; Krol, Ed S

2015-01-01

Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage. EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m(2) at 365 nm) and UVB (9000 J/m(2) at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS. EpiDerm™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation. Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Protective effects of extracts of Vernonia amygdalina, Hibiscus sabdariffa and vitamin C against radiation-induced liver damage in rats

International Nuclear Information System (INIS)

Adaramoye, Oluwatosin; Ogungbenro, Bayo; Anyaegbu, Oluchi; Fafunso, Michael

2008-01-01

catalase were obtained in animals treated with VIT C and extracts at 5 weeks. Taken together, the results suggest that the extracts of VA and HS, and VIT C could increase the antioxidant defense systems and may probably protect animals from radiation-induced liver damage. (author)

Ciliary derived neurotrophic factor protects oligodendrocytes against radiation induced damage in vitro by a mechanism independent of a proliferative effect

International Nuclear Information System (INIS)

Evans, Andrew J.; Mabie, Peter C.; Kessler, Jack A.; Vikram, Bhadrasain

1997-01-01

Purpose/Objective: Radiation-induced damage to the central nervous system in the from of myelopathy is a dose-limiting complication in the treatment of tumors situated in or close to the spinal cord. The target cell for this damage is not definitively identified, but demyelination due to oligodendrocyte damage is strongly implicated. Multiple neurotrophic factors have recently been identified which demonstrate a survival effect on oligodendrocytes. We investigated the effect of Ciliary Derived Neurotrophic Factor (CNTF), Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) on the radiosensitivity of oligodendrocytes in vitro to determine if this may ameliorate radiation damage, as a model for reducing myelopathy in vivo. Materials and Methods: Mature oligodendrocytes were cultured from the cortex of newborn Sprague-Dawley white rats and maintained on poly-d-lysine plates. The experimental arm was exposed to CNTF (0.01-100ng/ml), NGF (100ng/ml) or NT-3 (20ng/ml) for 24 hours prior to radiation, and control and experimental arms radiated using a cobalt 60 irradiator at a dose rate of .87 Gy/min with doses from 2 Gy to 10 Gy. Oligodendrocytes were identified using an O4 antibody, assessed for viability at 5 days using an MTT assay and counted using a phase contrast microscope. Combination studies of CNTF and NT-3 were also performed. BrdU studies were performed to determine if the various neurotrophins induced proliferation, with BrdU added for the 24 hour period prior to radiation only, for the 5 day period following radiation only, or for both periods combined. Results: The proportion of mature oligodendrocytes surviving 5 days after irradiation was not significantly increased by NGF, and was only modestly increased by NT-3. However, CNTF significantly increased the surviving proportion at all doses The addition of NT-3 to CNTF did not further increase the proportion of oligodendrocytes surviving. CNTF dose escalation studies confirmed 20ng/ml as an optimal dose. Brd

A protective effect of anthocyanins and xanthophylls on UVB-induced damage in retinal pigment epithelial cells.

Science.gov (United States)

Silván, Jose Manuel; Reguero, Marina; de Pascual-Teresa, Sonia

2016-02-01

Increased exposure to solar ultraviolet B (UVB) radiation causes oxidative damage that may promote age related macular degeneration (AMD) and other ocular pathologies. This study is aimed to demonstrate the protective effects of some anthocyanins and xanthophylls against the UVB-induced oxidative damage to retinal pigment epithelial (RPE) cells. ARPE-19 cells were treated with 5 μM cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, lutein, zeaxanthin or a mixture of cyanidin-3-O-glucoside:zeaxanthin prior to UVB exposure (500 J m(-2)). Cell viability and mitogen-activated protein kinase (MAPK) phosphorylation were determined by MTT assay and western blot analysis, respectively. Oxidative damage was evaluated by measuring the intracellular reactive oxygen species (ROS). The data showed that UVB irradiation reduces the cell viability to 46% with increasing of intracellular ROS levels and phosphorylation of MAPKs. However, pre-treatment (60 min) with 5 μM cyanidin-3-O-glucoside, lutein or zeaxanthin significantly reduced cellular ROS levels and phosphorylation of MAPKs (JNK1/2 and p38) mediated by UVB irradiation and subsequently increased cell viability. Thus, results show that UVB irradiation is able to induce apoptosis in ARPE-19 cells through oxidative stress; however anthocyanins and xanthophylls pre-treatment can attenuate this damage. This suggests that cyanidin-3-O-glucoside, lutein and zeaxanthin are effective in preventing UVB-induced damage in RPE cells and may be suitable as chemoprotective factors for the prevention of ocular damage. The use of natural dietary antioxidants might reduce ocular oxidative damage caused by UVB radiation.

Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

Energy Technology Data Exchange (ETDEWEB)

Cebulska-Wasilewska, A. [Institute of Nuclear Physics, Cracow (Poland)

1997-12-31

Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.

1997-01-01

Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

Heavy-ion radiation induced bystander effect in mice

Science.gov (United States)

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

2012-07-01

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

Glutathione requirement for the rejoining of radiation-induced DNA breaks in misonidazole-treated cells

International Nuclear Information System (INIS)

Edgren, M.; Revesz, L.

1985-01-01

The role of glutathione (GSH) in the rejoining of radiation-induced single-strand DNA breaks (ssb) was studied in human fibroblast cultures sensitized to radiation by a 30 min treatment with 1 mM misonidazole (MISO). Hypoxically irradiated cells, deficient in GSH, either inherently, or due to a 16 h incubation with 1 mM buthionine sulphoximine (BSO), rejoined the breaks after MISO treatment at a lower rate and to a lesser extent than did GSH-proficient cells. Without MISO treatment, the hypoxically induced ssb were rejoined in the GSH-deficient cells as effectively as in the proficient cells. It is concluded that a large proportion of the breaks which arise after hypoxic irradiation in the presence of MISO are of a different type to those which arise in the absence of the drug, and require a particular GSH-dependent, enzymatic repair system. This requirement for rejoining in hypoxically irradiated, MISO-treated cells is similar to that seen earlier in MISO-untreated, oxically irradiated cells, and suggests that the ssb induced by radiation in the presence of MISO or oxygen are of a similar nature. (author)

Radiation damage in nuclear waste materials

International Nuclear Information System (INIS)

Jencic, I.

2000-01-01

Final disposal of high-level radioactive nuclear waste is usually envisioned in some sort of ceramic material. The physical and chemical properties of host materials for nuclear waste can be altered by internal radiation and consequently their structural integrity can be jeopardized. Assessment of long-term performance of these ceramic materials is therefore vital for a safe and successful disposal. This paper presents an overview of studies on several possible candidate materials for immobilization of fission products and actinides, such as spinel (MgAl 2 O 4 ), perovskite (CaTiO 3 ), zircon (ZrSiO 4 ), and pyrochlore (Gd 2 Ti 2 O 7 and Gd 2 Zr 2 O 7 ). The basic microscopic picture of radiation damage in ceramics consists of atomic displacements and ionization. In many cases these processes result in amorphization (metaminctization) of irradiated material. The evolution of microscopic structure during irradiation leads to various macroscopic radiation effects. The connection between microscopic and macroscopic picture is in most cases at least qualitatively known and studies of radiation induced microscopic changes are therefore an essential step in the design of a reliable nuclear waste host material. The relevance of these technologically important results on our general understanding of radiation damage processes and on current research efforts in Slovenia is also addressed. (author)

Radiation damage to mushrooms

International Nuclear Information System (INIS)

Sattler, P.W.

1986-01-01

This document contains newspaper cuttings and correspondence with various ministries in Hessen on the subject of radiation damage to mushrooms from the Odenwald area. The reader is given, amongst other things, detailed information on radiation damage to different types of mushroom in 1986. (MG) [de

Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

Science.gov (United States)

M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra

2017-10-01

The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

Correlated analysis of 2 MeV proton-induced radiation damage in CdZnTe crystals using photoluminescence and thermally stimulated current techniques

Energy Technology Data Exchange (ETDEWEB)

Gu, Yaxu [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); Jie, Wanqi, E-mail: jwq@nwpu.edu.cn [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); Rong, Caicai [Institute of Modern Physics, Applied Ion Beam Physics Laboratory, Fudan University, Shanghai 200433 (China); Wang, Yuhan; Xu, Lingyan; Xu, Yadong [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); Lv, Haoyan; Shen, Hao [Institute of Modern Physics, Applied Ion Beam Physics Laboratory, Fudan University, Shanghai 200433 (China); Du, Guanghua [Materials Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Fu, Xu [State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an 710072 (China); Key Laboratory of Radiation Detection Materials and Devices of Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an 710072 (China); and others

2016-11-01

Highlights: • 2 MeV proton-induced radiation damage in CdZnTe crystals is investigated by PL and TSC techniques. • The influence of radiation damage on the luminescent and electrical properties of CdZnTe crystals is studied. • Intensity of PL spectrum is found to decrease significantly in irradiated regions, suggesting the increase of non-radiative recombination centers. • A correlated analysis of PL and TSC spectra suggests that the density of dislocations and A-centers increase after proton irradiation. - Abstract: Radiation damage induced by 2 MeV protons in CdZnTe crystals has been studied by means of photoluminescence (PL) and thermally stimulated current (TSC) techniques. A notable quenching of PL intensity is observed in the regions irradiated with a fluence of 6 × 10{sup 13} p/cm{sup 2}, suggesting the increase of non-radiative recombination centers. Moreover, the intensity of emission peak D{sub complex} centered at 1.48 eV dominates in the PL spectrum obtained from irradiated regions, ascribed to the increase of interstitial dislocation loops and A centers. The intensity of TSC spectra in irradiated regions decreases compared to the virgin regions, resulting from the charge collection inefficiency caused by proton-induced recombination centers. By comparing the intensity of identified traps obtained from numerical fitting using simultaneous multiple peak analysis (SIMPA) method, it suggests that proton irradiation under such dose can introduce high density of dislocation and A-centers in CdZnTe crystals, consistent with PL results.

Radiation damage to DNA-protein complexes

Czech Academy of Sciences Publication Activity Database

Spotheim-Maurizot, M.; Davídková, Marie

2011-01-01

Roč. 261, zima (2011), s. 1-10 ISSN 1742-6588. [COST Chemistry CM0603-MELUSYN Joint Meeting Damages Induced in Biomolecules by Low and High Energy Radiations. Paříž, 09.03.2010-12.03.2010] R&D Projects: GA AV ČR IAA1048103; GA AV ČR KJB4048401; GA MŠk 1P05OC085; GA MŠk OC09012; GA AV ČR IAB1048901 Institutional research plan: CEZ:AV0Z10480505 Keywords : radiolysis * molecular-dynamics simulation * hydroxyl radical attack * induced strand breakage Subject RIV: BO - Biophysics

Mechanism for radiation-induced damage via TLR3 on the intestinal epithelium

International Nuclear Information System (INIS)

Takemura, Naoki; Uematsu, Satoshi

2014-01-01

When the small-intestinal epithelium is injured due to high-dose radiation exposure, radiation-induced gastrointestinal syndrome (GIS) such as absorption inhibition and intestinal bacterial infection occurs, and lead to subacute death. The authors immunologically analyzed the disease onset mechanism of GIS. In the small-intestinal mucosal epithelium, the intestinal epithelial stem cells of crypt structure and their daughter cells are renewed through proliferation and differentiation in the cycle of 3 or 4 days. When DNA is damaged by radiation, although p53 gene stops cell cycle and repairs DNA, cell death is induced if the repair is impossible. When stem cells perish, cell supply stops resulting in epithelial breakdown and fatal GIS. The authors analyzed the involvement in GIS of toll-like receptor (TLR) with the function of natural immunity, based on lethal γ-ray irradiation on KO mice and other methods. The authors found the mechanism, in which RNA that was leaked due to cell death caused by p53 gene elicits inflammation by activating TLR3, and leads to GIS through a wide range of cell death induction and stem cell extinction. The administration of a TLR3/RNA binding inhibitor before the irradiation of mice decreased crypt cell death and greatly improved survival rate. The administration one hour after the irradiation also showed improvement. The administration of the TLR3 specific inhibitor within a fixed time after the exposure is hopeful for the prevention of GIS, without affecting the DNA repair function of p53 gene. (A.O.)

Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand.

Directory of Open Access Journals (Sweden)

Diego J Martinel Lamas

Full Text Available 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.

Sweet potato Ipomoea Batatas Modulates Radiation-induced Oxidative damage in Liver and kidney of Male Albino Rats

International Nuclear Information System (INIS)

Darwish, M. M.; Farag, M. F. S.; Osman, N. N.

2010-01-01

Sweet potato Ipomoea Batatas, one of the major vegetable crops consumed worldwide, is rich in phytochemicals, which displayed antioxidant activities. This work aims at assessing the radio-protective properties of sweet potato tubers on liver and kidney tissues. Male albino rats were whole body exposed to 0.5 Gy day after day for a period of 20 days. Animal received orally prepared aqueous extract of sweet potato tubers (100 mg kg/body weight), one week before irradiation and during the period of radiation exposure. The results demonstrated that irradiation of rats induced a significant increase in lipid peroxides level measured as thiobarbituric acid reactive substances (TBARS) concomitant with a significant decrease in superoxide dismutase (SOD), and catalase (CAT) activity and glutathione (GSH) content in liver and kidney tissues. Administration of a freshly prepared aqueous extract of sweet potato tubers to rats, one week pre-irradiation and during the period of radiation exposure has significantly of ameliorated the oxidative stress in both tissues. The significant amelioration in oxidative stress was substantiated by improvement of liver and kidney enzymes Treatment of rats with sweet potato has significantly reduced the increase in serum alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase (LDH) activity, serum creatinine and urea levels. Furthermore, hyperglycemia and alteration in lipid profile manifested by a significant increase in triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), and a significant decrease in high density lipoprotein cholesterol (HDL-C), were improved in sweet potato-treated irradiated rats compared to those only irradiated. According to the results obtained in the present study, it could be concluded that sweet potato through its antioxidant activities could protect cellular membrane from radiation induced oxidative damage in animals and preserve the

Protective Effects of Resveratrol against UVA-Induced Damage in ARPE19 Cells

Directory of Open Access Journals (Sweden)

Chi-Ming Chan

2015-03-01

Full Text Available Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD. Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2 expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD.

Protective Effects of Resveratrol against UVA-Induced Damage in ARPE19 Cells

Science.gov (United States)

Chan, Chi-Ming; Huang, Cheng-Hua; Li, Hsin-Ju; Hsiao, Chien-Yu; Su, Ching-Chieh; Lee, Pei-Lan; Hung, Chi-Feng

2015-01-01

Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD. PMID:25775159

Damage pattern as a function of radiation quality and other factors.

Science.gov (United States)

Burkart, W; Jung, T; Frasch, G

1999-01-01

An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex

Multi-scale approach to radiation damage induced by ion beams: complex DNA damage and effects of thermal spikes

International Nuclear Information System (INIS)

Surdutovich, E.; Yakubovich, A.V.; Solov'yov, A.V.; Surdutovich, E.; Yakubovich, A.V.; Solov'yov, A.V.

2010-01-01

We present the latest advances of the multi-scale approach to radiation damage caused by irradiation of a tissue with energetic ions and report the calculations of complex DNA damage and the effects of thermal spikes on biomolecules. The multi-scale approach aims to quantify the most important physical, chemical, and biological phenomena taking place during and following irradiation with ions and provide a better means for clinically-necessary calculations with adequate accuracy. We suggest a way of quantifying the complex clustered damage, one of the most important features of the radiation damage caused by ions. This quantification allows the studying of how the clusterization of DNA lesions affects the lethality of damage. We discuss the first results of molecular dynamics simulations of ubiquitin in the environment of thermal spikes, predicted to occur in tissue for a short time after an ion's passage in the vicinity of the ions' tracks. (authors)

Understanding the role of p53 in adaptive response to radiation-induced germline mutations

International Nuclear Information System (INIS)

Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

2003-01-01

Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

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

Science.gov (United States)

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

2006-09-01

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

Moderate acute intake of de-alcoholised red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo-Results of a comparative in vivo intervention study in younger men

Energy Technology Data Exchange (ETDEWEB)

Greenrod, W. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Stockley, C.S. [Australian Wine Research Institute, South Australia (Australia); Burcham, P. [Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Abbey, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Fenech, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia)]. E-mail: michael.fenech@hsn.csiro.au

2005-12-11

Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, dealcoholised red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of dealcoholised red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R = -0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

Moderate acute intake of de-alcoholised red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo-Results of a comparative in vivo intervention study in younger men

International Nuclear Information System (INIS)

Greenrod, W.; Stockley, C.S.; Burcham, P.; Abbey, M.; Fenech, M.

2005-01-01

Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, dealcoholised red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of dealcoholised red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R = -0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin

Criteria for the Evaluation and Selection of Radiation-Induced Metabolic Changes as Biochemical Indicators of Radiation Damage

Energy Technology Data Exchange (ETDEWEB)

Altman, K. I. [Departments of Experimental Radiology, Radiation Biology, Biophysics and Biochemistry, University of Rochester, School of Medicine and Dentistry, Rochester, NY (United States)

1971-03-15

There are several reasons which prompt a search for suitable biochemical indicators of radiation damage in man. Perhaps the most compelling of these reasons is the urgent need for estimates of exposure doses in cases of accidental exposures of human subjects to ionizing radiations under conditions which preclude a reliable assessment of the exposure dose by the usual physical means. At worst, a biochemical estimate of the dose would provide an independent means of obtaining information otherwise based solely on physical considerations and assumptions. In addition, a biochemical estimate of radiation injury may also, under ideal circumstances, serve as a guide to the attending physician in chosing the type of therapy most efficacious and least likely to lead to complications in the near as well as more distant future. The availability of biochemical indicators capable of revealing with some degree of accuracy the impairment of function of a particular organ would be a helpful adjunct in making decisions concerning the therapeutic approach to be adopted. The latter aspect would be of considerable interest in acute, accidental radiation exposures since under these circumstances radiation exposures are frequently of the partial-body type. An estimate of radiation injury by means of biochemical indicators should also prove useful in cases of protracted or chronic exposures to radiation, the source of which may be either external or internal. The use of biochemical indicators under these conditions of radiation exposure may, in general, aid 'case-finding' efforts and, in a more specific way, may help in pin-pointing discrete organ dysfunctions. In evaluating the suitability of radiation-induced metabolic changes for application as biochemical indicators of radiation damage, the following general criteria may be set forth: (1) the biochemical response to irradiation must be dose-dependent within a certain, sufficiently wide range in order to be useful; (2) the sensitivity

Quercitrin protects skin from UVB-induced oxidative damage

Energy Technology Data Exchange (ETDEWEB)

Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

2013-06-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

Quercitrin protects skin from UVB-induced oxidative damage

International Nuclear Information System (INIS)

Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-01-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries

Mild hyperthermia can induce adaptation to cytogenetic damage caused by subsequent X irradiation

International Nuclear Information System (INIS)

Cai, Lu.; Jiang, Jie.

1995-01-01

Many low-level environmental agents are able to induce an increased resistance to subsequent mutagenic effects induced by ionizing radiation. In this paper, an induced cytogenetic adaptation to radiation in human lymphocytes was studied with mild hyperthermia as the adaptive treatment and compared with that induced by low-dose radiation. We found that this adaptation could be induced not only in PHA-stimulated human lymphocytes (at 14, 38 and 42 h after addition of PHA), but also in unstimulated G 0 -phase cells (before addition of PHA) by mild hyperthermia (41 degrees C for 1 h) as well as 50 mGy X rays. When the two adaptive treatments were combined, no additive effects on the magnitude of the adaptation induced were observed, suggesting that low-dose radiation and hyperthermia may share one mechanism of induction of adaptation to cytogenetic damage. Some mechanisms which may be involved in the induction of adaptation to cytogenetic damage by low-dose radiation are discussed and compared with the effects of mild hyperthermia in inducing thermotolerance and radioresistance. 56 refs., 4 figs., 3 tabs

Electromagnetic noise inhibits radiofrequency radiation-induced DNA damage and reactive oxygen species increase in human lens epithelial cells

Science.gov (United States)

Wu, Wei; Wang, KaiJun; Ni, Shuang; Ye, PanPan; Yu, YiBo; Ye, Juan; Sun, LiXia

2008-01-01

Purpose The goal of this study was to investigate whether superposing of electromagnetic noise could block or attenuate DNA damage and intracellular reactive oxygen species (ROS) increase of cultured human lens epithelial cells (HLECs) induced by acute exposure to 1.8 GHz radiofrequency field (RF) of the Global System for Mobile Communications (GSM). Methods An sXc-1800 RF exposure system was used to produce a GSM signal at 1.8 GHz (217 Hz amplitude-modulated) with the specific absorption rate (SAR) of 1, 2, 3, and 4 W/kg. After 2 h of intermittent exposure, the ROS level was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). DNA damage to HLECs was examined by alkaline comet assay and the phosphorylated form of histone variant H2AX (γH2AX) foci formation assay. Results After exposure to 1.8 GHz RF for 2 h, HLECs exhibited significant intracellular ROS increase in the 2, 3, and 4 W/kg groups. RF radiation at the SAR of 3 W/kg and 4 W/kg could induce significant DNA damage, examined by alkaline comet assay, which was used to detect mainly single strand breaks (SSBs), while no statistical difference in double strand breaks (DSBs), evaluated by γH2AX foci, was found between RF exposure (SAR: 3 and 4 W/kg) and sham exposure groups. When RF was superposed with 2 μT electromagnetic noise could block RF-induced ROS increase and DNA damage. Conclusions DNA damage induced by 1.8 GHz radiofrequency field for 2 h, which was mainly SSBs, may be associated with the increased ROS production. Electromagnetic noise could block RF-induced ROS formation and DNA damage. PMID:18509546

High dose radiation damage in nuclear energy structural materials investigated by heavy ion irradiation simulation

International Nuclear Information System (INIS)

Zheng Yongnan; Xu Yongjun; Yuan Daqing

2014-01-01

Structural materials in ITER, ADS and fast reactor suffer high dose irradiations of neutrons and/or protons, that leads to severe displacement damage up to lOO dpa per year. Investigation of radiation damage induced by such a high dose irradiation has attracted great attention along with the development of nuclear energy facilities of new generation. However, it is deeply hampered for the lacking of high dose neutron and proton sources. Irradiation simulation of heavy ions produced by accelerators opens up an effective way for laboratory investigation of high dose irradiation induced radiation damage encountered in the ITER, ADS, etc. Radiation damage is caused mainly by atomic displacement in materials. The displacement rate of heavy ions is about lO 3 ∼10 7 orders higher than those of neutrons and protons. High displacement rate of heavy ions significantly reduces the irradiation time. The heavy ion irradiation simulation technique (HIIS) technique has been developed at China Institute of Atomic Energy and a series of the HIIS experiments have been performed to investigate radiation damage in stainless steels, tungsten and tantalum at irradiation temperatures from room temperature to 800 ℃ and in the irradiation dose region up to 100 dpa. The experimental results show that he radiation swelling peak for the modified stainless steel appears in the temperature region around 580 ℃ and the radiation damage is more sensitive to the temperature, the size of the radiation induced vacancy cluster or void increase with the increasing of the irradiation dose, and among the three materials the home-made modified stainless steel has the best radiation resistant property. (authors)

Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

Science.gov (United States)

Rao, Bola Sadashiva Satish; Upadhya, Dinesh; Adiga, Satish Kumar

2008-01-01

The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (p<0.001) reduction in micronucleated binucleate cells (MNBNC%) after various doses of CDE treatment in V79 cells and HPBLs. The optimum dose of CDE (40 and 50 microg/ml in HPBLs and V79 cells, respectively) with the greatest reduction in micronuclei was further used in combination with various doses of gamma radiation (0.5, 1, 2, 3, and 4 Gy) exposed 1 h after CDE treatment. A linear dose-dependent MNBNC% increase in radiation alone group was observed, while 40/50 microg/ml CDE significantly resulted in the reduction of MNBNC%, compared to the respective radiation alone groups. CDE resulted in a dose-dependent increase in free radical scavenging ability against various free radicals, viz., 2, 2-diphenyl-2-picryl-hydrazyl (DPPH); 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE.

Damage-induced DNA repair processes in Escherichia coli cells

International Nuclear Information System (INIS)

Slezarikova, V.

1986-01-01

The existing knowledge is summed up of the response of Escherichia coli cells to DNA damage due to various factors including ultraviolet radiation. So far, three inducible mechanisms caused by DNA damage are known, viz., SOS induction, adaptation and thermal shock induction. Greatest attention is devoted to SOS induction. Its mechanism is described and the importance of the lexA recA proteins is shown. In addition, direct or indirect role is played by other proteins, such as the ssb protein binding the single-strand DNA sections. The results are reported of a study of induced repair processes in Escherichia coli cells repeatedly irradiated with UV radiation. A model of induction by repeated cell irradiation discovered a new role of induced proteins, i.e., the elimination of alkali-labile points in the daughter DNA synthetized on a damaged model. The nature of the alkali-labile points has so far been unclear. In the adaptation process, regulation proteins are synthetized whose production is induced by the presence of alkylation agents. In the thermal shock induction, new proteins synthetize in cells, whose function has not yet been clarified. (E.S.)

Electronic-excitation induced radiation damage in glasses

Energy Technology Data Exchange (ETDEWEB)

Vigouroux, J P

1985-01-01

In order to understand the microscopic nature of radiation induced defects in insulators, we have studied localization of negative and positive charges in amorphous and monocrystalline SiO2. The behaviour of these charges is linked to creation of point defects by electronic excitation. The role of intense electric fields under irradiation is pointed out.

Radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (Family: Poaceae), against radiation-induced cytogenetic damage

International Nuclear Information System (INIS)

Satish Rao, B.S.; Upadhya, D.; Adiga, S.K.

2007-01-01

The exposure of humans to ionizing radiations may be advertently by routine diagnostic and therapeutic purposes or inadvertently during natural, occupational and nuclear accident situations. Therefore, in order to overcome the deleterious biological effects of radiation several chemical agents have been studied for their radioprotective potential. The medicinal plants being one of the resources for such clinically important natural agents, used extensively in several drug discovery related research. Here the radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (Family: Poaceae), against radiation-induced cytogenetic damage was analyzed using Chinese hamster fibroblast cells (V79) and human peripheral blood lymphocytes (HPBLs) growing in vitro is reported

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

International Nuclear Information System (INIS)

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

2003-01-01

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

Radiation-induced chromosomal instability

International Nuclear Information System (INIS)

Ritter, S.

1999-01-01

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

Acemannan (a polysaccharides of Aloe vera gel) protects against radiation induced mortality by modulation of immunosuppression

International Nuclear Information System (INIS)

Kumar, Sumit; Tiku, Ashu Bhan

2014-01-01

Acemannan (poly-acetylated mannose) is an active component of Aloe vera gel and has been reported to have anticancerous, antimicrobial and shown to stimulate the development and proliferation of the hematopoietic cells. The anticancerous properties of acemannan have been attributed to the modulation of immune system rather then cytotoxicity. Therefore objective of the present study was to evaluate radioprotective efficacy of acemannan against radiation induced immune suppression using Swiss albino mice as a model system. For In-vivo studies mice were treated for 7 days orally prior to irradiation (5 Gy). Animals were sacrificed at different time point to study the effect on cellular proliferation, DNA damage, apoptosis and ROS level, cytokines level, antioxidant enzymes, nitric oxide and protein expression. For survival studies mice were treated with acemannan for 7 days pre or post irradiation and survival was monitored for 30 days. Acemannan showed a significant induction of proliferation of splenocytes in radiation treated groups. Beside a decrease in radiation induced ROS and DNA damage resulted in the reduction of apoptosis in murine splenocytes. Acemannan restored the antioxidant enzyme level (catalase, SOD, DTD and GST) and maintained the proper redox status via GSH, in irradiated mice. Further acemannan was shown to induce the hematopoiesis (peripheral lymphocytes cells, spleen colony cells, spleen index) by increasing the level of the pro-hematopoiesis cytokines (IL-1, TNF-α). Being an immunomodulator, acemannan reduced the level of the inflammation (IL-6, nitric oxide). Also the multiple mechanisms operational at cellular and molecule levelled to the reduction of radiation induced mortality of mice in both pre and post-irradiation studies. On the basis of the above results it can be concluded that radioprotective effects of the acemannan was due to its immunomodulatory activity and could have application for radio-therapeutic purposes. (author)

Radiation damage of DNA. Model for direct ionization of DNA

International Nuclear Information System (INIS)

Kobayashi, Kazuo; Tagawa, Seiichi

2004-01-01

Current aspects of radiation damage of DNA, particularly induced by the direct effect of radiation, and author's method of pulse radiolysis are described in relation to behavior of ions formed by radiation and active principles to induce the strand break. In irradiation of DNA solution in water, the direct effect of radiation is derived from ionization of DNA itself and indirect one, from the reaction between DNA and radicals generated from water molecules and the former direct one has been scarcely investigated due to difficulty of experimental approach. Radicals generated in sugar moiety of DNA are shown important in the strand break by recent studies on crystalline DNA irradiated by X-ray, DNA solution by electron and photon beams, hydrated DNA by γ-ray and by high linear energy transfer (LET) ion. Author's pulse radiolysis studies have revealed behaviors of guanine and adenine radical cations in dynamics of DNA oxidation. Since reactions described are the model, the experimental approach is thought necessary for elucidation of the actually occurring DNA damage in living cells. (N.I.)

Radiation Damage Mechanism in PbWO4 Crystal and Radiation Hardness Quality Control of PWO Scintillators for CMS

CERN Document Server

Baccaro, Stefania; Borgia, Bruno; Cavallari, Francesca; Cecilia, Angelica; Dafinei, Ioan; Diemoz, Marcella; Lecoq, Paul; Longo, Egidio; Montecchi, Marco; Organtini, Giovanni; Salvatori, S

1997-01-01

The optical damage induced by UV light in PbWO4 crystals is found to be similar to that induced by g radiation. Due to the peculiarities of optical absorption in PbWO4, the damage induced by UV light is a bulk process. This fact has important consequences for the approach to be adopted both for the use of the crystal as scintillator and for the qualification methods foreseen in the Regional Centres of the ECAL CMS Collaboration.

Radiation effects on testes. XI. Studies on glycogen and its metabolizing enzymes following radiation-induced atrophy

International Nuclear Information System (INIS)

Gupta, G.S.; Bawa, S.R.

1977-01-01

Effect of radiation on enzymes of carbohydrate metabolism has been studied. It is observed that hexokinase of testis is highly sensitive to radiation damage. Reduced hexokinase activity seems to be related to those parts of the testis (spermatocytes and spermatids) which depend upon glucose for their functioning. Radiation-induced atrophic testis is rich in glycogen content. The observations on the inhibition of gluocose-6-phosphatase and phosphorylase may explain the higher levels of the polysaccharide although a possibility of enhanced glycogenesis due to the activation of glycogen synthetase has also been suggested. The presence of glucose-6-phosphate isomerase and glycogen in atrophied testis in 11-month-treated rats indicate the higher glycolytic activity with hyperplastic testicular interstitium. The results suggest that the accumulated glycogen is acting as a reserve substrate in nongerminal cells

Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes

Directory of Open Access Journals (Sweden)

A. Montoro

2011-01-01

Full Text Available Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP, including 20, 40, 120, 250, 500, 750, 1000, and 2000 μg mL−1 and then exposed to 2 Gy γ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 μg mL−1 of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation.

A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage

Energy Technology Data Exchange (ETDEWEB)

Palma, Giuseppe [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Monti, Serena [IRCCS SDN, Naples (Italy); D' Avino, Vittoria [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Conson, Manuel [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Liuzzi, Raffaele [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Pressello, Maria Cristina [Department of Health Physics, S. Camillo-Forlanini Hospital, Rome (Italy); Donato, Vittorio [Department of Radiation Oncology, S. Camillo-Forlanini Hospital, Rome (Italy); Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY (United States); Quarantelli, Mario [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Pacelli, Roberto [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Cella, Laura, E-mail: laura.cella@cnr.it [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy)

2016-09-01

Purpose: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). Methods and Materials: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. The coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. Results: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose of the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. Conclusions: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose–RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high

Influence of cigarette smoke and green tea on radiation-induced micronucleated polychromatic erythrocytes

International Nuclear Information System (INIS)

Gao Yong; Hao Enzhu; Ni Yanbo

2006-01-01

Objective: To observe the effects of cigarette smoke and green tea on radiation-induced bone marrow cell mutation, and to provide scientific information for prevention and treatment of radiation damage. Methods: There were 8 groups in the factorial experiment design with 3 factors at 2 levels. Mice were randomly divided into each group. There were 8 mice in each group. Mice in seven experimental groups were exposed to cigarette smoke, green tea, radiation or their mixtures respectively. One group was treated as the blank control group. The frequencies of micrnucleated polychromatic erythrocytes (MPCE) were scored by single blinded method. The data were analyzed with factorial experiments analysis of variance using SAS 8.0. Results: Analysis of variance showed that radiation, cigarette smoke and green tea were independently significant factors (P<0.01). Interactions between cigarette smoke and radiation or between green tea and radiation were statistically significant (P<0.01). Conclusion: Radiation and cigarette smoke can cause bone marrow cell mutations independently. There is synergistic effect between cigarette smoke and radiation. Green tea can inhibit radiation-induced cell mutation. (authors)

Moderate acute intake of de-alcoholized red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo -- results of a comparative in vivo intervention study in younger men.

Science.gov (United States)

Greenrod, W; Stockley, C S; Burcham, P; Abbey, M; Fenech, M

2005-12-11

Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, de-alcoholized red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of de-alcoholized red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R=-0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

Use of lectin-induced lymphocyte stimulation as a biodosimeter of radiation damage

International Nuclear Information System (INIS)

Shifrine, M.; Taylor, N.J.; DeRock, E.W.; Wiger, N.; Wilson, F.D.

1979-01-01

The purpose of this study was to determine the feasibility of utilizing an in vitro test to determine whether an individual has suffered radiation damage. It was not our purpose to develop a test capable of detecting low doses but rather to determine possible damage due to a radiation accident at medium to high doses. In a pilot study using the whole blood lymphocyte stimulation test (WB/LST), we pretested six dogs weekly for three weeks. One was sham irradiated and is referred to as the control and one each received an acute whole body dose of 10, 25, 50, 75, or 100 R. The dogs were tested one day post-irradiation and then weekly for 56 days. Our data indicate that, using Con-A and PHA in the WB/LST, a biodosimeter can be developed to determine recovery of lymphocyte function after suspected radiation exposure to confirm accidental radiation and estimate the magnitude of the dose

Catalase inhibits ionizing radiation-induced apoptosis in hematopoietic stem and progenitor cells.

Science.gov (United States)

Xiao, Xia; Luo, Hongmei; Vanek, Kenneth N; LaRue, Amanda C; Schulte, Bradley A; Wang, Gavin Y

2015-06-01

Hematologic toxicity is a major cause of mortality in radiation emergency scenarios and a primary side effect concern in patients undergoing chemo-radiotherapy. Therefore, there is a critical need for the development of novel and more effective approaches to manage this side effect. Catalase is a potent antioxidant enzyme that coverts hydrogen peroxide into hydrogen and water. In this study, we evaluated the efficacy of catalase as a protectant against ionizing radiation (IR)-induced toxicity in hematopoietic stem and progenitor cells (HSPCs). The results revealed that catalase treatment markedly inhibits IR-induced apoptosis in murine hematopoietic stem cells and hematopoietic progenitor cells. Subsequent colony-forming cell and cobble-stone area-forming cell assays showed that catalase-treated HSPCs can not only survive irradiation-induced apoptosis but also have higher clonogenic capacity, compared with vehicle-treated cells. Moreover, transplantation of catalase-treated irradiated HSPCs results in high levels of multi-lineage and long-term engraftments, whereas vehicle-treated irradiated HSPCs exhibit very limited hematopoiesis reconstituting capacity. Mechanistically, catalase treatment attenuates IR-induced DNA double-strand breaks and inhibits reactive oxygen species. Unexpectedly, we found that the radioprotective effect of catalase is associated with activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway and pharmacological inhibition of STAT3 abolishes the protective activity of catalase, suggesting that catalase may protect HSPCs against IR-induced toxicity via promoting STAT3 activation. Collectively, these results demonstrate a previously unrecognized mechanism by which catalase inhibits IR-induced DNA damage and apoptosis in HSPCs.

Radiation damage in molybdenum and tungsten in high neutron fluxes

International Nuclear Information System (INIS)

Veljkovic, S.; Milasin, N.

1964-01-01

The effects of radiation on molybdenum and tungsten in high neutron fluxes are presented. The changes induced, particularly defects with a high migration activation energy, are analyzed. The correlation of these changes with the basic concepts of radiation damage in solids is considered. An attempt is made to relate the defects studied with the changes in macroscopic properties (author)

Radiation damage in molybdenum and tungsten in high neutron fluxes

Energy Technology Data Exchange (ETDEWEB)

Veljkovic, S; Milasin, N [Institute of Nuclear Sciences Boris Kidric, Department of Reactor Materials, Vinca, Beograd (Serbia and Montenegro)

1964-04-15

The effects of radiation on molybdenum and tungsten in high neutron fluxes are presented. The changes induced, particularly defects with a high migration activation energy, are analyzed. The correlation of these changes with the basic concepts of radiation damage in solids is considered. An attempt is made to relate the defects studied with the changes in macroscopic properties (author)

Chromatin damage induced by fast neutrons or UV laser radiation

Energy Technology Data Exchange (ETDEWEB)

Radu, L.; Constantinescu, B.; Gazdaru, D.; Mihailescu, I

2002-07-01

Chromatin samples from livers of Wistar rats were subjected to fast neutron irradiation in doses of 10-100 Gy or to a 248 nm excimer laser radiation, in doses of 0.5-3 MJ.m{sup -2}. The action of the radiation on chromatin was monitored by chromatin intrinsic fluorescence and fluorescence lifetimes (of bound ethidium bromide to chromatin) and by analysing fluorescence resonance energy transfer between dansyl chloride and acridine orange coupled to chromatin. For the mentioned doses of UV excimer laser radiation, the action on chromatin was more intense than in the case of fast neutrons. The same types of damage are produced by the two radiations: acidic and basic destruction of chromatin protein structure, DNA strand breaking and the increase of the distance between DNA and proteins in chromatin. (author)

Chromatin damage induced by fast neutrons or UV laser radiation

International Nuclear Information System (INIS)

Radu, L.; Constantinescu, B.; Gazdaru, D.; Mihailescu, I.

2002-01-01

Chromatin samples from livers of Wistar rats were subjected to fast neutron irradiation in doses of 10-100 Gy or to a 248 nm excimer laser radiation, in doses of 0.5-3 MJ.m -2 . The action of the radiation on chromatin was monitored by chromatin intrinsic fluorescence and fluorescence lifetimes (of bound ethidium bromide to chromatin) and by analysing fluorescence resonance energy transfer between dansyl chloride and acridine orange coupled to chromatin. For the mentioned doses of UV excimer laser radiation, the action on chromatin was more intense than in the case of fast neutrons. The same types of damage are produced by the two radiations: acidic and basic destruction of chromatin protein structure, DNA strand breaking and the increase of the distance between DNA and proteins in chromatin. (author)

Nonuniform radiation damage in permanent magnet quadrupoles.

Science.gov (United States)

Danly, C R; Merrill, F E; Barlow, D; Mariam, F G

2014-08-01

We present data that indicate nonuniform magnetization loss due to radiation damage in neodymium-iron-boron Halbach-style permanent magnet quadrupoles. The proton radiography (pRad) facility at Los Alamos uses permanent-magnet quadrupoles for magnifying lenses, and a system recently commissioned at GSI-Darmsdadt uses permanent magnets for its primary lenses. Large fluences of spallation neutrons can be produced in close proximity to these magnets when the proton beam is, intentionally or unintentionally, directed into the tungsten beam collimators; imaging experiments at LANL's pRad have shown image degradation with these magnetic lenses at proton beam doses lower than those expected to cause damage through radiation-induced reduction of the quadrupole strength alone. We have observed preferential degradation in portions of the permanent magnet quadrupole where the field intensity is highest, resulting in increased high-order multipole components.

Nonuniform radiation damage in permanent magnet quadrupoles

International Nuclear Information System (INIS)

Danly, C. R.; Merrill, F. E.; Barlow, D.; Mariam, F. G.

2014-01-01

We present data that indicate nonuniform magnetization loss due to radiation damage in neodymium-iron-boron Halbach-style permanent magnet quadrupoles. The proton radiography (pRad) facility at Los Alamos uses permanent-magnet quadrupoles for magnifying lenses, and a system recently commissioned at GSI-Darmsdadt uses permanent magnets for its primary lenses. Large fluences of spallation neutrons can be produced in close proximity to these magnets when the proton beam is, intentionally or unintentionally, directed into the tungsten beam collimators; imaging experiments at LANL’s pRad have shown image degradation with these magnetic lenses at proton beam doses lower than those expected to cause damage through radiation-induced reduction of the quadrupole strength alone. We have observed preferential degradation in portions of the permanent magnet quadrupole where the field intensity is highest, resulting in increased high-order multipole components

Nonuniform radiation damage in permanent magnet quadrupoles

Energy Technology Data Exchange (ETDEWEB)

Danly, C. R.; Merrill, F. E.; Barlow, D.; Mariam, F. G. [Los Alamos National Laboratory, Los Alamos, New Mexico 87544 (United States)

2014-08-15

We present data that indicate nonuniform magnetization loss due to radiation damage in neodymium-iron-boron Halbach-style permanent magnet quadrupoles. The proton radiography (pRad) facility at Los Alamos uses permanent-magnet quadrupoles for magnifying lenses, and a system recently commissioned at GSI-Darmsdadt uses permanent magnets for its primary lenses. Large fluences of spallation neutrons can be produced in close proximity to these magnets when the proton beam is, intentionally or unintentionally, directed into the tungsten beam collimators; imaging experiments at LANL’s pRad have shown image degradation with these magnetic lenses at proton beam doses lower than those expected to cause damage through radiation-induced reduction of the quadrupole strength alone. We have observed preferential degradation in portions of the permanent magnet quadrupole where the field intensity is highest, resulting in increased high-order multipole components.

Radiation damage in nanostructured metallic films

Science.gov (United States)

Yu, Kaiyuan

High energy neutron and charged particle radiation cause microstructural and mechanical degradation in structural metals and alloys, such as phase segregation, void swelling, embrittlement and creep. Radiation induced damages typically limit nuclear materials to a lifetime of about 40 years. Next generation nuclear reactors require materials that can sustain over 60 - 80 years. Therefore it is of great significance to explore new materials with better radiation resistance, to design metals with favorable microstructures and to investigate their response to radiation. The goals of this thesis are to study the radiation responses of several nanostructured metallic thin film systems, including Ag/Ni multilayers, nanotwinned Ag and nanocrystalline Fe. Such systems obtain high volume fraction of boundaries, which are considered sinks to radiation induced defects. From the viewpoint of nanomechanics, it is of interest to investigate the plastic deformation mechanisms of nanostructured films, which typically show strong size dependence. By controlling the feature size (layer thickness, twin spacing and grain size), it is applicable to picture a deformation mechanism map which also provides prerequisite information for subsequent radiation hardening study. And from the viewpoint of radiation effects, it is of interest to explore the fundamentals of radiation response, to examine the microstructural and mechanical variations of irradiated nanometals and to enrich the design database. More importantly, with the assistance of in situ techniques, it is appealing to examine the defect generation, evolution, annihilation, absorption and interaction with internal interfaces (layer interfaces, twin boundaries and grain boundaries). Moreover, well-designed nanostructures can also verify the speculation that radiation induced defect density and hardening show clear size dependence. The focus of this thesis lies in the radiation response of Ag/Ni multilayers and nanotwinned Ag

An extract of Polygonum multiflorum protects against free radical damage induced by ultraviolet B irradiation of the skin

Directory of Open Access Journals (Sweden)

I.K. Hwang

Full Text Available Over the last decades, the incidence of ultraviolet B (UVB-related skin problems has been increasing. Damages induced by UVB radiation are related to mutations that occur as a result of direct DNA damage and/or the production of reactive oxygen species. We investigated the anti-oxidant effects of a Polygonum multiflorum thumb extract against skin damage induced by UVB irradiation. Female SKH-1 hairless mice were divided into three groups: control (N = 7, distilled water- (N = 10, and P. multiflorum extract-treated (PM, N = 10 groups. The PM (10 g was extracted with 100 mL distilled water, cryo-dried and 9.8 g was obtained. The animals received a topical application of 500 µL distilled water or PM extract (1, 2, 4, 8, and 16%, w/v, dissolved in distilled water for 30 min after UVB irradiation (wavelength 280-320 nm, 300 mJ/cm²; 3 min of the dorsal kin for 14 days, and skin immunohistochemistry and Cu,Zn-superoxide dismutase (SOD1 activity were determined. SOD1 immunoreactivity, its protein levels and activities in the skin were significantly reduced by 70% in the distilled water-treated group after UVB irradiation compared to control. However, in the PM extract-treated groups, SOD1 immunoreactivity and its protein and activity levels increased in a dose-dependent manner (1-16%, w/v, PM extract compared to the distilled water-treated group. SOD1 protein levels and activities in the groups treated with 8 and 16%, w/v, PM extract recovered to 80-90% of the control group levels after UVB. These results suggest that PM extract strongly inhibits the destruction of SOD1 by UV radiation and probably contains anti-skin photoaging agents.

Near-ultraviolet radiation-induced damage using an actinic reticuloid strain as a possible sensitive model

International Nuclear Information System (INIS)

Kralli, A.

1987-01-01

The introduction to this thesis consists of a review of current concepts regarding the effects of ultraviolet radiation on living cells. Actinic reticuloid, a disease condition for which a near-ultraviolet radiation cellular sensitivity has been proposed as an underlying cause, is described. The experimental work, the broad aim of which is to expand existing knowledge of the effects of near-ultraviolet radiation that may lead to cell lethality, has centred upon the irradiation of a normal human skin fibroblast strain, GM730, and a strain derived from an actinic reticuloid patient, AR6LO. Parts 1 and 2 examine the effects of the irradiation on both normal and actinic fibroblast sensitivities to a range of ultraviolet wavelengths. The next two sections include observations on the protective effect of Trolox-C, a vitamin E analogue and the sensitization resulting from the replacement of the irradiation medium by a deuterated one, using both normal and actinic reticuloid fibroblasts. The final part examines broad-band near- and far-ultraviolet radiation induced membrane damage by the use of radioactively labelled rubidium as a potassium analogue. (author)

Targeting the Renin–Angiotensin System Combined With an Antioxidant Is Highly Effective in Mitigating Radiation-Induced Lung Damage

Energy Technology Data Exchange (ETDEWEB)

Mahmood, Javed [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Jelveh, Salomeh [Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Zaidi, Asif [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Doctrow, Susan R. [Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts (United States); Medhora, Meetha [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Hill, Richard P., E-mail: hill@uhnres.utoronto.ca [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

2014-07-15

Purpose: To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. Methods and Materials: The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. Results: The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Conclusion: Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

A new analysis of radiation-induced cytogenetic damage in human lymphocytes using the PCC technique, and its implications for biological dosimetry and the understanding of cell-cycle-dependent radiosensitivity fluctuations

International Nuclear Information System (INIS)

Zannos, A.; Pantelias, G.E.

1993-01-01

The objectives of the project are: to develop a sensitive biological dosemeter, based on the analysis of C-banded peripheral blood lymphocyte prematurely condensed chromosomes (PCCs), for the early assessment of radiation injury and the establishment of absorbed dose estimates in accidental overexposures; and to elucidate the mechanisms of radiation action at the molecular, chromosomal and cellular levels by the study of the effects of DNA repair inhibitors on the repair of radiation damage, effects of BrdUrd incorporation on radiation damage, effects of hyperthermia on the induction and repair of radiation-induced damage, and induction and repair of radiation damage in an X-ray sensitive CHO mutant cell line. (authors) 16 refs., 1 fig

Chromatin structure influence the sensitivity of DNA to ionizing radiation induced DNA damage

International Nuclear Information System (INIS)

Gupta, Sanjay

2016-01-01

Chromatin acts as a natural hindrance in DNA-damage recognition, repair and recovery. Histone and their variants undergo differential post-translational modification(s) and regulate chromatin structure to facilitate DNA damage response (DDR). During the presentation we will discuss the importance of chromatin organization and histone modification(s) during IR-induced DNA damage response in human liver cells. Our data shows G1-phase specific decrease of H3 serine10 phosphorylation in response to DNA damage is coupled with chromatin compaction in repair phase of DDR. The loss of H3Ser10P during DNA damage shows an inverse correlation with gain of γH2AX from a same mono-nucleosome in a dose-dependent manner. The loss of H3Ser10P is a universal phenomenon as it is independent of origin of cell lines and nature of genotoxic agents in G1 phase cells. The reversible reduction of H3Ser10P is mediated by opposing activities of phosphatase, MKP1 and kinase, MSK1 of the MAP kinase pathway. The present study suggests distinct reversible histone marks are associated with G1-phase of cell cycle and plays a critical role in chromatin organization which may facilitate differential sensitivity against radiation. Thus, the study raises the possibility of combinatorial modulation of H3Ser10P and histone acetylation with specific inhibitors to target the radio-resistant cancer cells in G1-phase and thus may serve as promising targets for cancer therapy. (author)

Acetylation dynamics of human nuclear proteins during the ionizing radiation-induced DNA damage response

DEFF Research Database (Denmark)

Bennetzen, Martin; Andersen, J.S.; Lasen, D.H.

2013-01-01

Genotoxic insults, such as ionizing radiation (IR), cause DNA damage that evokes a multifaceted cellular DNA damage response (DDR). DNA damage signaling events that control protein activity, subcellular localization, DNA binding, protein-protein interactions, etc. rely heavily on time...

Study on the damage effect of 131I-iodinated oil internal radiation in SMMC-7721 hepatoma model in rat

International Nuclear Information System (INIS)

Wu Shuyan; Zhang Xuguang; Wang Xiangying; Li Su'an; Mao Dihua

2004-01-01

Objective: To investigate the damage effect of 131 I-iodinated oil internal radiation in hepatoma. Methods: SMMC-7721 rat hepatoma model was used to evaluate the damage of 131 I-iodinated oil internal radiation in carcinoma. 131 I-iodinated oil was injected sector-shapely into tumor model of SMMC-7721 hepatoma with arc-needle, matched with routine straight-needle injection. Tumor damage induced by 131 I-iodinated oil intralesion radiation in the carcinoma models are recorded through survival time, weight of rat, local carcinoma, pathology, electron microscopy. Results: Arc-needle injection 131 I-iodinated oil in SMMC-7721 hepatoma at subcutis could increase rat's survival time, the body weight kept less descent, the lumps necrosed wholly. Pathology and ultrastructure detection revealed cell necrosis and collapse, sever nuclear damage was observed in the death cells. The early characteristics of necrosis such as margination of heterochromatin was also found in some tumor cells. Besides, well differentiated tumor cells, degenerative tumor cells and some lymphocytes were seen. Conclusion: Arc-needle injection 131 I-iodinated oil step-by step sector-shapely into tumor is a better method and necrosis is the major effect of 131 I-iodinated oil internal radiation in carcinoma at the level of treated dosage

Radiation-Induced Bystander Response: Mechanism and Clinical Implications

OpenAIRE

Suzuki, Keiji; Yamashita, Shunichi

2014-01-01

Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure.

Radioprotection by WR-151327 against the late normal tissue damage in mouse hind legs from gamma ray radiation

International Nuclear Information System (INIS)

Matsushita, Satoru; Ando, Koichi; Koike, Sachiko

1994-01-01

To evaluate the protective effect of WR-151327 on late radiation-induced damaged to normal tissues in mice, the right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137 Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined. Latae damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice. WR-151327 has the potential to protect against radiation-induced late normal tissue damage. 17 refs., 6 figs., 2 tabs

Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

International Nuclear Information System (INIS)

Maga, J.A.

1983-01-01

The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

Radiation-induced bone neoplasma in facial cranium

Energy Technology Data Exchange (ETDEWEB)

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

1976-01-01

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

Radiation damage to DNA-binding proteins

International Nuclear Information System (INIS)

Culard, G.; Eon, S.; DeVuyst, G.; Charlier, M.; Spotheim-Maurizot, M.

2003-01-01

The DNA-binding properties of proteins are strongly affected upon irradiation. The tetrameric lactose repressor (a dimer of dimers) losses its ability to bind operator DNA as soon as at least two damages per protomer of each dimer occur. The monomeric MC1 protein losses its ability to bind DNA in two steps : i) at low doses only the specific binding is abolished, whereas the non-specific one is still possible; ii) at high doses all binding vanishes. Moreover, the DNA bending induced by MC1 binding is less pronounced for a protein that underwent the low dose irradiation. When the entire DNA-protein complexes are irradiated, the observed disruption of the complexes is mainly due to the damage of the proteins and not to that of DNA. The doses necessary for complex disruption are higher than those inactivating the free protein. This difference, larger for MC1 than for lactose repressor, is due to the protection of the protein by the bound DNA. The oxidation of the protein side chains that are accessible to the radiation-induced hydroxyl radicals seems to represent the inactivating damage

Activity of the protector chlorophyllin or promoter of the genetic damage induced by the 1,2 dimethyl hydrazine

International Nuclear Information System (INIS)

Guerrero M, M.G.

2004-01-01

The chlorophyllin (CHLN) it is a porphyrin of soluble nutritious grade in water, derived of the chlorophyll that includes in their structure a copper atom. It has been reported that this pigment can act as anti mutagen, reducing the damage to the DNA caused by physical or chemical agents of direct or indirect action. Their anti carcinogen action has also been studied during the initiation phase induced for carcinogen as the aflatoxins and heterocyclic amines. In contrast the reports have increased on a probable promoter activity of the CHLN on the induced genetic damage. This effect was seen for the first time before the damage induced by alkylating agents in Salmonella. Recently it has been observed with the damage induced by gamma radiation, ENU and CrO 3 in somatic cells of the wing of Drosophila and in the induction of tumors for 1,2-dimethylhydrazine (DMH) in mice. Presently study is evaluated the protective effect or promoter of the CHLN before the genetic damage induced by 1,2-dimethylhydrazine, by means of the bioassay mutation and somatic recombination (SMART) in the wing of Drosophila melanogaster. Its were pretreated with CHLN or SAC to transheterocygotes larvas for two locus of the chromosome three mwh+/+flr 3 ; later on they are retarded the chronic treatment with DMH 0, 1, 2 and 3 days. It was measured the toxicity and the speed of development of the treated individuals. The wings of those adults that emerged were analyzed to register the number and the size of stains. The results indicated: differences in the viability of the individuals of the groups SAC + DMH vs CHLN + DMH only in the treated immediately after the pretreatment (DRT-0) that the CHLN doesn't modify the rate of the treated individuals development. The results of somatic mutation indicated that the CHLN has a protective effect only immediately after the pretreatment (DRT-0) however in DRT-1, 2 and 3 showed a promoter effect of genetic damage. (Author)

Influence of Hot Implantation on Residual Radiation Damage in Silicon Carbide

International Nuclear Information System (INIS)

Rawski, M.; Zuk, J.; Kulik, M.; Drozdziel, A.; Pyszniak, K.; Turek, M.; Lin, L.; Prucnal, S.

2011-01-01

Remarkable thermomechanical and electrical properties of silicon carbide (SiC) make this material very attractive for high-temperature, high-power, and high-frequency applications. Because of very low values of diffusion coefficient of most impurities in SiC, ion implantation is the best method to selectively introduce dopants over well-defined depths in SiC. Aluminium is commonly used for creating p-type regions in SiC. However, post-implantation radiation damage, which strongly deteriorates required electric properties of the implanted layers, is difficult to anneal even at high temperatures because of remaining residual damage. Therefore implantation at elevated target temperatures (hot implantation) is nowadays an accepted method to decrease the level of the residual radiation damage by avoiding ion beam-induced amorphization. The main objective of this study is to compare the results of the Rutherford backscattering spectroscopy with channeling and micro-Raman spectroscopy investigations of room temperature and 500 o C Al + ion implantation-induced damage in 6H-SiC and its removal by high temperature (up to 1600 o C) thermal annealing. (author)

Radiation damage in CTR magnet components

International Nuclear Information System (INIS)

Ullmaier, H.

1976-01-01

Data are reviewed (already existing or to be acquired) which should allow prediction of the behavior of large superconducting coils in the radiation field of a future fusion reactor. The electrical and mechanical stability of such magnets is determined by the irradiation induced deterioration of the magnet components, i.e., (a) changes in critical current, field and temperature of the superconductor (NbTi, A-15 phases), (b) resistivity increase in the stabilizer (Cu, Al), and (c) changes in mechanical and dielectric properties of insulators and spacers. Recent low temperature simulation experiments (with fission neutrons and heavy ions) show that the superconductor will not be the critical component of a fusion magnet--at least as far as radiation damage is concerned. Much more severe is the loss of stability due to the resistivity increase of the stabilizing material. It seems, however, that the magnitude of this effect can be predicted rather reliably and therefore taken into account in the coil design. Almost no data exist about the low temperature behavior of insulator and spacer materials in a radiation field. Furthermore, very little is known about the nature of the radiation damage in non-metals, which makes extrapolations of the few existing data to other materials or to other doses highly speculative. Only future experiments can decide if the insulators will be the limiting component of a CTR magnet or not

DNA damage induced by radiation plasmodial mixed + gamma thermal neutrons in the presence and absence of free radical scavenger

International Nuclear Information System (INIS)

Rodriguez Gual, Maritza; Mas Milian, Felix; Gouveia, Andreia; Deppman, Airton

2010-01-01

In this work is quantified the damage in DNA plasmid induced by mixed radiation (thermal neutron and gamma rays) for first time. For the study was used the pBs KS+ plasmid of 2961 bp in aqueous solution of the 88 ng/μL with 0, 2 and 20 mmol/L of glycerol which acts as a free radicals scavenger. This plasmid changes its form of supercoiled to circular when a simple strand break is produced, and passes to a linear form when a double strand break is produced in the chain. Quantifying the fractions that exist in each of these forms is possible to estimate the effect of radiation on DNA. The irradiations were carried out in the radial channel 3 at IEA-R1 research reactor of the Instituto de Pesquisas Energeticas y Nucleares in Sao Paulo, Brazil. DNA forms were separated by agarose gel electrophoresis. For quantification the program GelAnalis was used. The values of the fractions of DNA in various forms were plotted as a function of dose and fitted to exponential and linear functions to obtaining the probabilities of simple and double strand breaks normalized by dose and molecular mass. The results showed the protective action of free radical scavenger against damage induced for radiation which corroborates the previous results found with other ionizing radiations. Yields of SSB and DSB will be of interest for the validation of the different models that attempt to reproduce the experimental results

Radiation-induced heart injury

International Nuclear Information System (INIS)

Suzuki, Yoshihiko; Niibe, Hideo

1975-01-01

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

Enhancement of Temozolomide and radiation induced damage in malignant glioma cell lines by 2-deoxy-D-glucose

International Nuclear Information System (INIS)

Kumari, Kalyani; Shyam, Sai; Chandrasekhar Sagar, B.K.; Jagath Lal, G.; Kalia, Vijay Kumar

2014-01-01

Malignant Gliomas are the most common and aggressive CNS tumors. The current standard treatment includes surgery, followed by Temozolomide (TMZ)-Radiotherapy. It leads to increased survival as compared to radiotherapy alone. However hematological toxicities are also increased by the combination treatments. Therefore, it is important to carry out further preclinical studies, to develop more effective treatment for these tumors. 2-deoxy-D-Glucose (2-DG), an inhibitor of glycolytic energy metabolism, has been shown earlier to differentially inhibit growth and survival of tumor cells in vitro. It also increases tumor regression in experimental models; and has been used in a few clinical studies as radiosensitizer. In the present study, effects of combining 2-DG with TMZ on radiation induced damage were studied in established malignant glioma cell lines (U251MG and U87MG); and primary cultures derived from malignant glioma biopsies. Exponentially growing cells were exposed to drugs and radiation. Drugs were removed 4 hours later and cultures were processed further for different assays of damage. Effects on proliferation response, viability and total cellular damage (TCD; micronuclei + apoptosis) were studied after post-treatment growth for 1, 2, 4 or 6 days. Our results showed that combination of 2-DG with TMZ ± Radiation significantly inhibited tumor cell proliferation up to 6 days, at low drug concentrations in primary as well as in established cell lines. The TCD at 24 and 48 hours after Gamma irradiation was also significantly increased by the combination of drugs as compared to individual treatments. Experiments to study proliferation kinetics by flow cytometry and cell survival are in progress. These studies suggest that 2-DG significantly enhances the cytotoxic effect of TMZ + radiation without increasing toxic side effects. Therefore, combining 2-DG with TMZ+ radiation therapy could be a potential strategy to improve the therapeutic outcome for Malignant

The study on the immunity restoring function of cWPROL in treating experimental radiation esophagitis

International Nuclear Information System (INIS)

Shen Li; Shan Baoen; Zhang Li; Lu Fuhe; Guo Xiujuan

2007-01-01

Objective: To study the restorative function of compound white peony root oral liquids (cWPROL) in treating rats' experimental acute radiation-induced esophagitis from the aspect of immunodeficiency. Methods: 128 Wistar rats were divided into eight groups. The radiation esophagitis was induced by 43 Gy 60 Co. Then the rats were treated with medicine in different ways. On every experimental point the absolute number and percentage of T lymphocyte subsets were analyzed by flow cytometry. The changes of the leukocyte in number and differential count were detected by haemocyte counting instrument. IgG and C3 in rats' serum were analyzed by immunological turbidimetry. Results: Radiation brought on decrease of experimental rats 'leukocyte count, the lymphocyte differential count, absolute count and absolute T lymphocyte subsets in the blood and the content of IgG and C3 with radiation esophagitis. cWPROL could increase the lymphocyte percentage compared that in with the radiated group 2. The preventive (high dose) could increase lymphocyte count while Western medicine decreased rats' leukocyte count, lymphocyte percentage and absolute count (P<0.05). The absolute T lymphocyte subsets in rats' peripheral blood increased in the group infused with cWPROL (high dose) (P<0.001). Compared with the radiated group 2 the absolute T lymphocyte subsets decreased significantly(P<0.001), and the content of complement C3 increased in the group infused with cWPROL (high dose) (P<0.05) but decreased in the group infused with Western medicine (P<0.01). Conclusion: cWPROL plays the role of restoring the cytoimmunity and immunity damaged by radiation in rats with radiation esophagitis. (authors)

Radiation- induced aneuploidy in mammalian germ cells

International Nuclear Information System (INIS)

Tease, C.

1989-01-01

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

Relation of radiation damage of metallic solids to electronic structure. Pt. 5

International Nuclear Information System (INIS)

Shalaev, A.M.; Adamenko, A.A.

1977-01-01

The problem of relating a damage in metal solids to the parameters of radiation fluxes and the physical nature of a target is considered. Basing upon experimental and theoretical investigations into the processes of interaction of particle fluxes with solids, the following conclusions have been reached. Threshold energy of ion displacement in the crystal lattice of a metal solid is dependent on the energy of a bombarding particle, which is due to ionization and electroexcitation stimulated by energy transfer from a fast particle to a system of collectivized electrons. The rate of metal solid damage by radiation depends on the state of the crystal lattice, in particular on its defectness. Variations of local electron density in the vicinity of a defect are related with changing thermodynamic characteristics of radiation-induced defect formation. A type of atomic bond in a solid affects the rate of radiation damage. The greatest damage occurs in materials with a covalent bond

Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Hasegawa, Tatsuya, E-mail: tatsuya.hasegawa@to.shiseido.co.jp; Nakashima, Masaya; Suzuki, Yoshiharu

2016-08-26

Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE{sub 2}. In addition, inhibition of DNA damage repair by knockdown of XPA, which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.

Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

International Nuclear Information System (INIS)

Hasegawa, Tatsuya; Nakashima, Masaya; Suzuki, Yoshiharu

2016-01-01

Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE_2. In addition, inhibition of DNA damage repair by knockdown of XPA, which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.

Radiation-induced DNA damage and repair in radiosensitive and radioresistant human tumour cells measured by field inversion gel electrophoresis

International Nuclear Information System (INIS)

Smeets, M.F.M.A.; Mooren, E.H.M.; Begg, A.C.

1993-01-01

Radiation-induced DNA damage induction and repair was measured in two human squamous carcinoma cell lines with differing radiosensitivities. Experiments were carried out with field inversion gel electrophoresis (FIGE), adapted to measure DNA double strand break (DSB) induction and repair in unlabelled cells. The sensitivity of the method was increased by introducing a hybridization membrane into the agarose gel. Damaged DNA accumulated on one spot on the membrane resulting in high local concentrations. This DNA was quantified using radioactively-labelled total human DNA as a probe. Radiosensitivity differences at physiological temperatures could not be explained by differences in either induction or repair of DNA damage as measured by pulsed field gel electrophoresis. (author)

Perinatal radiation-induced renal damage in the beagle

International Nuclear Information System (INIS)

Jaenke, R.S.; Angleton, G.M.

1990-01-01

The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated