Radiation sensitizations at DNA-level by chemical and biological agents. Coordinated programme on improvement of radiotherapy of cancer using modifiers of radiosensitivity of cells

International Nuclear Information System (INIS)

Altmann, H.

1982-01-01

Radiation sensitization by chemical agents at DNA level is discussed. Procaine, Halothan and Metronidazole showed no significant effect on unscheduled DNA synthesis (UDS) in mouse spleen cells, investigated by autoradiography and no effect on rejoining of DNA single strand breaks after gamma or UV irradiation. Oxyphenbutazon and prednisolone reduced the replicative DNA synthesis in vitro and in vivo but there was only little effect on DNA repair in the in vivo experiments. These two substances showed also a small reduction in poly(ADP-ribose) synthesis (PAR synthesis). 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) in combination with UV irradiation showed that 5-MOP was more toxic than mutagen, but induced much less DNA crosslinks than 8-MOP. Autoradiographic studies of radiation sensitization by biological agents showed significant inhibition of UDS in Yoshida tumor cells after acute mycoplasma infection in rats. Nucleoid sedimentation studies showed only in the case of Yoshida tumor cells after mycoplasma infection a dramatic effect in the sedimentation behaviour. Sensitization of cells by changing chromatin structure was also studied. Benzamide, 3-NH 2 -benzamide, 3-Methoxybenzamide, Spermine, Theophyllin and Caffeine were tested in different concentrations on replicative DNA synthesis, UDS after UV irradiation and PAR synthesis Chinese hamster ovary cells. 5-Methoxybenzamide was the strongest sensitizer and inhibitor of the PAR synthesis, and was used in further experiments. Results of KFA Juelich on sensitization of a mamma-adenocarcinoma EO 771 on C57 B1 mice are given. Replicative DNA synthesis, DNA repair and PAR synthesis were compared in spleen cells and adenocarcinoma cells after treatment with 5-Methoxybenzamide. An inhibitory effect on UDS could be shown only in adenocarcinoma cells but not in the mice spleen cells

Radiation sensitivity and DNA repair in Caenorhabditis elegans strains with different mean life spans

Energy Technology Data Exchange (ETDEWEB)

Hartman, P S; Simpson, V J; Johnson, T; Mitchell, D

1988-06-01

The sensitivities to three DNA damaging agents (UV and ..gamma..-radiation, methyl methanesulfonate) were measured in four recombinant inbred (RI) strains of Caenorhabditis elegans with mean life spans ranging from 13 to 30.9 days, as well as in the wild-type strains used to derive these RI's. Sensitivities at several stages in the developmental cycle were tested. There were no significant correlations between mean life span and the lethal effects of these 3 agents. Excision of two UV-radiation-induced DNA photoproducts was also measured. Long-lived strains were no more repair competent than shorter-lived strains. These data indicate that DNA repair plays at best a minor role in the aging process of C. elegans. 33 refs.; 4 figs.

pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

Science.gov (United States)

Li, Wenyan (Inventor); Buhrow, Jerry W. (Inventor); Jolley, Scott T. (Inventor); Calle, Luz M. (Inventor)

2014-01-01

Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

Andrographolide Sensitizes Ras-Transformed Cells to Radiation in vitro and in vivo

International Nuclear Information System (INIS)

Hung, Shih-Kai; Hung, Ling-Chien; Kuo, Cheng-Deng

2010-01-01

Purpose: Increasing the sensitivity of tumor cells to radiation is a major goal of radiotherapy. The present study investigated the radiosensitizing effects of andrographolide and examined the molecular mechanisms of andrographolide-mediated radiosensitization. Methods and Materials: An H-ras-transformed rat kidney epithelial (RK3E) cell line was used to measure the radiosensitizing effects of andrographolide in clonogenic assays, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assays, and a xenograft tumor growth model. The mechanism of andrographolide-sensitized cell death was analyzed using annexin V staining, caspase 3 activity assays, and terminal transferase uridyl nick end labeling assays. The roles of nuclear factor kappa B (NF-κB) and Akt in andrographolide-mediated sensitization were examined using reporter assays, electrophoretic mobility shift assays, and Western blotting. Results: Concurrent andrographolide treatment (10 μM, 3 h) sensitized Ras-transformed cells to radiation in vitro (sensitizer enhancement ratio, 1.73). Andrographolide plus radiation (one dose of 300 mg/kg peritumor andrographolide and one dose of 6 Gy radiation) resulted in significant tumor growth delay (27 ± 2.5 days) compared with radiation alone (22 ± 1.5 days; p <.05). Radiation induced apoptotic markers (e.g., caspase-3, membrane reversion, DNA fragmentation), and andrographolide treatment did not promote radiation-induced apoptosis. However, the protein level of activated Akt was significantly reduced by andrographolide. NF-κB activity was elevated in irradiated Ras-transformed cells, and andrographolide treatment significantly reduced radiation-induced NF-κB activity. Conclusion: Andrographolide sensitized Ras-transformed cells to radiation both in vitro and in vivo. Andrographolide-mediated radiosensitization was associated with downregulation of Akt and NF-κB activity. These observations indicate that andrographolide is a novel radiosensitizing agent

How far is cancer cured by radiation sensitization?

International Nuclear Information System (INIS)

Ando, Koichi; Sasaki, Takehito; Ikeda, Hiroshi

1990-01-01

Some types of cancer are not cured by radiation alone in view of histology, location, and size. In facing so-called radioresistant cancer, antineoplastic agents, hypoxic cell sensitizers, biological response modifiers, or hyperthermia are used in combination with radiation, with the aim of cancer cure. First of all, this chapter discusses the subject of 'what is tumor cure by radiation therapy'. Current conditions of the aforementioned combined modalities and the future perspectives are presented. The following subjects are covered: (1) tumor control - significance of the number of stem cells; (2) biological evaluation of chemo-radiotherapy with cisplatin; (3) clinical results and experience with combination of radiotherapy and radiosensitizers; (4) radiosensitization with hypoxic cell radiosensitizers - present status (5) hypoxic cell radiosensitizers - present status and problems from the viewpoint of clinical radiotherapy; (6) thermal radiosensitization in vitro and its implications for radiotherapy; (7) clinical assessment of thermoradiotherapy for breast cancer and cancer of the urinary bladder; (8) interactions of radiation and biological response modifiers in the treatment of malignant tumor; (9) improvement in the effects of radiation therapy with biological response modifiers. (N.K.)

Toxic clinical hypoxic radiation sensitizers plus radiation-induced toxicity

International Nuclear Information System (INIS)

Richmond, R.C.

1984-01-01

The operational definition espoused twelve years ago that clinical hypoxic radiation sensitizers should be nontoxic interferes with the recognition and research of useful radiation sensitizers. Eight years ago the toxic antitumor drug cis-dichlorodiammineplatinum(II) was reported to be a hypoxic radiation sensitizer and the selective antitumor action of this drug was stressed as potentially creating tumor-targeted radiation sensitization. This rationale of oxidative antitumor drugs as toxic and targeted clinical sensitizers is useful, and has led to the study reported here. The antitumor drug cis-(1,1-cyclobutane-dicarboxylato)diammineplatinum(II), or JM-8, is being tested in clinical trials. Cells of S. typhimurium in PBS in the presence of 0.2mM JM-8 are found to be sensitized to irradiation under hypoxic, but not oxic, conditions. JM-8 is nontoxic to bacteria at this concentration, but upon irradiation the JM-8 solution becomes highly toxic. This radiation induced toxicity of JM-8 preferentially develops from hypoxic solution, and thus contributes to the rationale of hypoxic tumor cell destruction

Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours

International Nuclear Information System (INIS)

Horsman, M.

1996-01-01

Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitize murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms. However, recent studies in mouse tumours have shown that these drugs prevent transient cessations in blood flow, thus inhibiting the development of acute hypoxia. This novel discovery led to the suggestion that the potential role of these agents as radiosensitizers would be when combined with treatments that overcame chronic hypoxia. The combined nicotinamide with hyperthermia proved that the enhancement of radiation damage by both agents together was greater than that seen with each agent alone. Similar results were later seen for nicotinamide combined with a perfluorochemical emulsion, carbogen breathing, and pentoxifylline, and in all these studies the effects in tumours were always greater than those seen in appropriate normal tissues. Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically, with daily doses of up to 6 g, associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to

Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

Science.gov (United States)

Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

2005-11-15

One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

A Culture-Sensitive Agent in Kirman's Ant Model

Science.gov (United States)

Chen, Shu-Heng; Liou, Wen-Ching; Chen, Ting-Yu

The global financial crisis brought a serious collapse involving a "systemic" meltdown. Internet technology and globalization have increased the chances for interaction between countries and people. The global economy has become more complex than ever before. Mark Buchanan [12] indicated that agent-based computer models will prevent another financial crisis and has been particularly influential in contributing insights. There are two reasons why culture-sensitive agent on the financial market has become so important. Therefore, the aim of this article is to establish a culture-sensitive agent and forecast the process of change regarding herding behavior in the financial market. We based our study on the Kirman's Ant Model[4,5] and Hofstede's Natational Culture[11] to establish our culture-sensitive agent based model. Kirman's Ant Model is quite famous and describes financial market herding behavior from the expectations of the future of financial investors. Hofstede's cultural consequence used the staff of IBM in 72 different countries to understand the cultural difference. As a result, this paper focuses on one of the five dimensions of culture from Hofstede: individualism versus collectivism and creates a culture-sensitive agent and predicts the process of change regarding herding behavior in the financial market. To conclude, this study will be of importance in explaining the herding behavior with cultural factors, as well as in providing researchers with a clearer understanding of how herding beliefs of people about different cultures relate to their finance market strategies.

γ-radiation induces cellular sensitivity and aberrant methylation in human tumor cell lines.

Science.gov (United States)

Kumar, Ashok; Rai, Padmalatha S; Upadhya, Raghavendra; Vishwanatha; Prasada, K Shama; Rao, B S Satish; Satyamoorthy, Kapettu

2011-11-01

Ionizing radiation induces cellular damage through both direct and indirect mechanisms, which may include effects from epigenetic changes. The purpose of this study was to determine the effect of ionizing radiation on DNA methylation patterns that may be associated with altered gene expression. Sixteen human tumor cell lines originating from various cancers were initially tested for radiation sensitivity by irradiating them with γ-radiation in vitro and subsequently, radiation sensitive and resistant cell lines were treated with different doses of a demethylating agent, 5-Aza-2'-Deoxycytidine (5-aza-dC) and a chromatin modifier, Trichostatin-A (TSA). Survival of these cell lines was measured using 3-(4, 5-Dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium (MTT) and clonogenic assays. The effect of radiation on global DNA methylation was measured using reverse phase high performance liquid chromatography (RP-HPLC). The transcription response of methylated gene promoters, from cyclin-dependent kinase inhibitor 2A (p16(INK4a)) and ataxia telangiectasia mutated (ATM) genes, to radiation was measured using a luciferase reporter assay. γ-radiation resistant (SiHa and MDAMB453) and sensitive (SaOS2 and WM115) tumor cell lines were examined for the relationship between radiation sensitivity and DNA methylation. Treatment of cells with 5-aza-dC and TSA prior to irradiation enhanced DNA strand breaks, G2/M phase arrest, apoptosis and cell death. Exposure to γ-radiation led to global demethylation in a time-dependent manner in tumor cells in relation to resistance and sensitivity to radiation with concomitant activation of p16(INK4a) and ATM gene promoters. These results provide important information on alterations in DNA methylation as one of the determinants of radiation effects, which may be associated with altered gene expression. Our results may help in delineating the mechanisms of radiation resistance in tumor cells, which can influence diagnosis, prognosis and

Radiation sensitivity of different citric pectins

Energy Technology Data Exchange (ETDEWEB)

Inamura, Patricia Y.; Mastro, Nelida L. del [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: patyoko@yahoo.com; nlmastro@ipen.br

2007-07-01

Pectic substances are important soluble polysaccharides of plant origin of considerable interest for food industry as gelling agent and stabilizer in jams, fruit jellies, yogurt drinks and lactic acid beverages. Polysaccharides can be degraded by ionizing radiation due to the free radical induced scission of the glycosidic bonds. Viscosity methods had been used to determine the efficiency of hydroxyl radical induced chain breaks generation in macromolecules. In the present work samples of pectin with different degree of methoxylation were employed in order to study their radiation sensitivity by means of viscosity measurements. Samples of citric pectin 1% solutions were irradiated with gamma rays at different doses, ranging from 0 to 15 kGy, using a {sup 60}Co Gammacell 220 (AECL), dose rate about 2 kGy/h. After irradiation the viscosity was measured on the viscometer Brookfield model LV-DVIII at 50, 60 and 70 deg C within a period of 48h. Pectin viscosity with high degree of methoxylation decreased sharply with the radiation dose remaining almost constant from 10 kGy. Pectin with low degree of methoxylation presented initially higher values of viscosity and the radiation induced decrease was also pronounced. Viscosity measurements decreased with the increase of the temperature applied for both kind of samples. The effect of radiation induced chain breaks generation in pectin molecules was evident through the viscosity reduction of irradiated pectin solutions although the viscosity presented diverse values depending of the degree of methoxylation of carboxyl groups in the backbone of polysaccharide macromolecules. (author)

Radiation sensitivity of different citric pectins

International Nuclear Information System (INIS)

Inamura, Patricia Y.; Mastro, Nelida L. del

2007-01-01

Pectic substances are important soluble polysaccharides of plant origin of considerable interest for food industry as gelling agent and stabilizer in jams, fruit jellies, yogurt drinks and lactic acid beverages. Polysaccharides can be degraded by ionizing radiation due to the free radical induced scission of the glycosidic bonds. Viscosity methods had been used to determine the efficiency of hydroxyl radical induced chain breaks generation in macromolecules. In the present work samples of pectin with different degree of methoxylation were employed in order to study their radiation sensitivity by means of viscosity measurements. Samples of citric pectin 1% solutions were irradiated with gamma rays at different doses, ranging from 0 to 15 kGy, using a 60 Co Gammacell 220 (AECL), dose rate about 2 kGy/h. After irradiation the viscosity was measured on the viscometer Brookfield model LV-DVIII at 50, 60 and 70 deg C within a period of 48h. Pectin viscosity with high degree of methoxylation decreased sharply with the radiation dose remaining almost constant from 10 kGy. Pectin with low degree of methoxylation presented initially higher values of viscosity and the radiation induced decrease was also pronounced. Viscosity measurements decreased with the increase of the temperature applied for both kind of samples. The effect of radiation induced chain breaks generation in pectin molecules was evident through the viscosity reduction of irradiated pectin solutions although the viscosity presented diverse values depending of the degree of methoxylation of carboxyl groups in the backbone of polysaccharide macromolecules. (author)

SEM probe of IC radiation sensitivity

Science.gov (United States)

Gauthier, M. K.; Stanley, A. G.

1979-01-01

Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

Radiation sensitivity of bacteria and virus in porcine xenoskin for dressing agent

International Nuclear Information System (INIS)

Jo, Eu-Ri; Jung, Pil-Mun; Choi, Jong-il; Lee, Ju-Woon

2012-01-01

In this study, gamma irradiation sensitivities of bacteria and viruses in porcine skin were evaluated to establish the optimum sterilization condition for the dressing material and a xenoskin graft. Escherichia coli and Bacillus subtilis were used as model pathogens and inoculated at 10 6 –10 7 log CFU/g. As model viruses, porcine parvovirus (PPV), bovine viral diarrhea virus (BVDV), and poliovirus were used and inoculated at 10 5 –10 6 TCID 50 /g into porcine skin. The D 10 value of E. coli was found to be 0.25±0.1 kGy. B. subtilis endospores produced under stressful environmental conditions showed lower radiation sensitivity as D 10 was 3.88±0.3 kGy in porcine skin. The D 10 values of PPV, BVDV, and poliovirus were found to be 1.73±0.2, 3.81±0.2, and 6.88±0.3 kGy, respectively. These results can offer the basic information required for inactivating pathogens by gamma irradiation and achieving dressing material and porcine skin grafts.

Synthesis and characterization of a smart contrast agent sensitive to calcium.

Science.gov (United States)

Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K

2008-08-07

A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.

Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents

International Nuclear Information System (INIS)

Lohrer, H.; Robson, T.

1989-01-01

Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1-2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cd 1 ), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-nitro-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals. (author)

Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents

Energy Technology Data Exchange (ETDEWEB)

Lohrer, H.; Robson, T. (Newcastle upon Tyne Univ. (UK). Cancer Research Unit)

1989-12-01

Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1-2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cd{sup 1}), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-nitro-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals. (author).

Radiation-sensitive material and method of recording information upon radiation-sensitive material

International Nuclear Information System (INIS)

Petrov, V.V.; Krjuchin, A.A.

1981-01-01

The invention can be employed for recording binary information in memory units of electronic computers, in video-recording equipment, laser recording devices and other recording means. The proposed radiation-sensitive material comprises a metallic layer made of silver, or copper, or nickel, or thallium, or alloy thereof, an inorganic material layer made of arsenic chalcogenide, or antimony chalcogenide, or bismuth chalcogenide, and a separation layer disposed between the metallic layer and the inorganic material layer made of a material which is inert relative to said layers, which separation layer has a thickness sufficient for preventing interaction between the metallic layer and the inorganic material layer when the radiation-sensitive materials is exposed to electromagnetic or corpuscular radiation having a power density lower than a threshold value required for the breakdown of the separation layer in the area exposed to radiation. The separation layer can be made from As, Sb, Si or Ge or their oxides, metallic oxides of e.g. Al, Ti, V or Fe, or from polyorganosiloxane films. (author)

Lethal and mutagenic effects of radiation and alkylating agents on two strains of mouse L5178Y cells

International Nuclear Information System (INIS)

Evans, H.H.; Horng, M.; Beer, J.Z.

1986-01-01

The two closely related strains of L5178Y (LY) mouse lymphoma cells, LY-R and LY-S, have been shown to differ in their sensitivity to UV and ionizing radiation. In the present work, the lethal and mutagenic effects of ethyl methanesulfonate (EMS), methyl nitrosourea (MNU) and UV radiation (254 nm) were compared in the two strains. Mutability at the Na + /K + -ATPase locus as well as the HGPRT locus was determined. The authors found strain LY-S to be more resistant than strain LY-R to the lethal effects of UV radiation. In contrast, strain LY-S was more sensitive to the cytotoxic effects of the two alkylating agents. In spite of these differences in sensitivity, the authors found strain LY-S to be less mutable than strain LY-R by all 3 agents at the HGPRT locus. At the Na + /K + -ATPase locus, strain LY-S was also less mutable than strain LY-R by equal concentrations of EMS and UV radiation and by equitoxic concentrations of MNU. However, the difference between the strains was much more pronounced at the HGPRT locus than at the Na + /K + -ATPase locus. The authors have suggested that the interaction of unrepaired lesions in strain LY-S tends to cause an excess of deletions and multilocus effects, which in turn result in a locus-dependent decrease in the recovery of viable LY-S mutant cells. (Auth.)

Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

International Nuclear Information System (INIS)

Bree, Chris van; Kreder, Natasja Castro; Loves, Willem J.P.; Franken, Nicolaas A.P.; Peters, Godefridus J.; Haveman, Jaap

2002-01-01

Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5-fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000 were determined by clonogenic assay. Bivariate flowcytometry was performed to study cell cycle changes. Results: In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level. This was accompanied by a 10-fold decrease in dCK activity which resulted in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50-100 μM dFdC) induced radioenhancement in the dFdC-resistant cell lines similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in the parental lines. An early S-phase arrest was found in all cell lines after dFdC treatment where radioenhancement was achieved. Conclusions: In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. No cross-resistance was observed to other anti-tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing radiation was not altered in two different dFdC-resistant cell lines. Resistance to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation

Combined radiation-protective and radiation-sensitizing agents. III. Radiosensitization by misonidazole as a function of concentrations of endogenous glutathione or exogenous thiols

International Nuclear Information System (INIS)

Koch, C.J.; Stobbe, C.C.; Baer, K.A.

1986-01-01

Radiosensitization of V79 Chinese hamster fibroblasts by 0.5 mM misonidazole is a smooth function of endogenous glutathione (GSH) levels as modulated upwards by pre-incubation in medium containing cysteamine, or downwards by pre-incubation in medium containing buthionine sulfoximine. The enhancement ratio (radiation sensitivity in nitrogen/radiation sensitivity in nitrogen +/- sensitizer or thiol) varies from 1.3 at 12 mM to 2.25 at less than 0.1 mM endogenous GSH. The enhanced radiosensitivity of thiol-depleted hypoxic cells is reversed when exogenous thiols are added, and for equivalent ER, the exogenous thiol concentrations are much lower than the endogenous GSH concentrations. Measurement of intracellular drug concentrations amplified rather than diminished the above discrepancy, since intracellular concentrations of cysteamine were lower and glutathione much lower than the extracellular concentrations. Three possible explanations are addressed: an external membrane component of damage is involved, long-range protection to DNA target radicals is possible from outside the cell (e.g., donation of electrons), and (c) endogenous glutathione is not in a free or exchangeable state (e.g., bound)

Antibiotic Sensitivity Patterns of Aerobic Bacterial Agents in Post ...

African Journals Online (AJOL)

Antibiotic Sensitivity Patterns of Aerobic Bacterial Agents in Post-Surgical ... those commonly used to treat orofacial infections were tested for sensitivity against the ... were the augmented Penicillins and newer generations Cephalosporins.

In vitro study of cytotoxicity by U.V. radiation and differential sensitivity in combination with alkylating agents on established cell systems

International Nuclear Information System (INIS)

Ramudu, K.

1991-01-01

The effect of U.V. radiation or alkylating agents, such as actinomycin-D, cycloheximide and mitomycin-C (MMC), was studied on CHO, BHK and HeLa cells. U.V. radiation caused DNA ssb and dsb and were prevented by cycloheximide and actinomycin-D. MMC is known to be cytotoxic in CHO/BHK cells by forming free radical generation. MMC in combination with U.V. radiation enhanced DNA ssb ampersand dsb in these cell types. However, HeLa cells were insensitive to U.V. radiation. This insensitivity to U.V. radiation could be ascribed to the presence of glutathione transferase which is absent in CHO/BHK cell line

Evaluation of the radiation-sensitizer/protector and/or antioxidant efficiencies using Fricke and PAG dosimeters

International Nuclear Information System (INIS)

Meesat, Ridthee; Jay-Gerin, Jean-Paul; Khalil, Abdelouahed; Lepage, Martin

2009-01-01

In this study, our aim is to assess the potential of Fricke and polyacrylamide gel (PAG) dosimeters to quantitatively evaluate the efficiency of potential radiation sensitizers/protectors and antioxidants. These compounds are of importance in radiotherapy as well as in disease prevention and promotion of health. The basic principle of the Fricke dosimeter is the radiation-induced oxidation of Fe 2+ to Fe 3+ in an aerated aqueous 0.4 M H 2 SO 4 . The production of ferric ions is most sensitive to the radical species produced in the radiolysis of water. Using this method, we observed that cystamine (one of the best of the known radioprotectors) can prevent oxydation of Fe 2+ from reactive radiolysis species. However, one obvious disadvantage of the Fricke dosimeter is that it operates under highly acidic conditions (pH 0.46), which may degrade biological compounds. In contrast, the pH of the polyacrylamide gel (PAG) dosimeter is almost neutral, such that degradation of compounds is less probable. A change in R 2 -dose sensitivity was observed in the presence of radiosensitizers/radioprotectors and antioxidants. The protective effect of Trolox (a well-known antioxidant) and thiourea (a radioprotector) was readily observed using the PAG dosimeter. Incorporation of iodinated radiation sensitizers such as NaI and an iodine contrast agent led to a quantifiable sensitizer enhancement ratio. These studies suggest that the Fricke and the PAG dosimeters have the potential to evaluate the efficiency of radiation sensitizers/protectors and antioxidants.

Radiation sensitive solid state devices

International Nuclear Information System (INIS)

Shannon, J.M.; Ralph, J.E.

1975-01-01

A solid state radiation sensitive device is described employing JFETs as the sensitive elements. Two terminal construction is achieved by using a common conductor to capacitively couple to the JFET gate and to one of the source and drain connections. (auth)

Combined radiation-protective and radiation-sensitizing agents. IV. Measurement of intracellular protector concentrations

International Nuclear Information System (INIS)

Koch, C.J.; Stobbe, C.C.; Hettiaratchi, P.

1989-01-01

Radiosensitization of hypoxic V79 Chinese hamster cells by 0.5 mM misonidazole at approximately 0-4 degrees C is substantially enhanced by pretreating the cells overnight with 0.1 mM buthionine sulfoximine, which lowers the cellular glutathione content to 5% of control values (from 4 mM to approximately 0.2 mM). The enhanced sensitization is reversed by concentrations of exogenous cysteine that are much lower (0.02 mM) than the original glutathione content. Reduced Co-enzyme A affords reversal of the enhancing effect at concentrations of about 1 mM. Sodium ascorbate gives no protection at all even at concentrations of 2 mM. The intracellular concentration of the reducing agents was measured using a spin-through oil technique. There was no diffusion of Co-A (MW greater than 750) or ascorbate (excluded by charge) into the cells. In contrast, cysteine was rapidly concentrated by factors of 4-10, even at the low temperatures used. Extracellular ascorbate's inability to radioprotect argues against electron transfer across the cell membrane as a mechanism for radioprotection. This mechanism could have explained the ability of exogenous thiols to radioprotect in former studies using glutathione, and in the present studies using Co-A. The potential of cysteine to be concentrated by cells poses a problem in the interpretation of exogenous protection by non-diffusing thiols, since trace contamination by cysteine could lead to the actual protection observed. Cysteine could also be formed by exchange reactions of exogenous thiols with the disulfide of cysteine, present in all media formulations

Synthesis and mechanistic studies of phosphoraziridines as radiation sensitizers

International Nuclear Information System (INIS)

Perlman, M.E.

1982-01-01

Ethyl bis(2,2-dimethyl-1-aziridinyl)phosphinyl carbamate (AB-132) and ethyl bis(2,2-dimethyl-1-aziridinyl)phosphinate (AB-163) are potent antitumor agents which have also been demonstrated to be radiation sensitizers in experimental and clinical studies. Monophenyl aziridines and various isomers of diphenylaziridines were utilized. Optically active 2-phenyl aziridine was also employed in order to prepare diastereomerically homogeneous compounds. Para-substituted phenylaziridines were prepared as well and converted to the corresponding phosphoraziridines in order to probe electronic effects of such substituents on biological activity and chemical reactivity. The hydrolysis of 2,2-dimethylaziridine-type compounds including AB-132 and AB-163 was studied by NMR in order to gain further insight into the hydrolytic intermediates which may be responsible for the known cholinesterase inhibition and the suspected phosphorylation of radiation-damaged DNA. Comparative reactivities of the compounds prepared in this study with p-nitrobenzylpyridine were investigated so as to provide some indication of potential alkylating activity, in the hope of obtaining a correlation with biological activity. Electron spin resonance was utilized to study the effects of radiation on phosphoraziridine crystals

Radiation-sensitive diacrylates

International Nuclear Information System (INIS)

Demajistre, R.

1976-01-01

Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysts to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials. 6 claims, no drawings

[Insulin-sensitizing agents: metformin and thiazolidinedione derivatives].

Science.gov (United States)

Satoh, Jo

2003-07-01

Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, there has been indicated that these agents ameliorate metabolic syndrome beyond glucose-level lowering. Molecular targets of these agents have recently been revealed; AMP-activated protein kinase (AMPK) for metformin and adiponectin, while PPAR gamma for TZDs which induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin-sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs.

Development of an efficient process for radiation vulcanization of natural rubber latex using hydroperoxide with sensitizer

International Nuclear Information System (INIS)

Siri-upathum, C.; Sonsuk, M.

1996-01-01

An attempt was made to reduce irradiation dose for radiation vulcanization of natural rubber latex. A promising method was to partially crosslink the latex by radiation vulcanization using n-butyl acrylate (n-BA) as sensitizer and t-butyl hydroperoxide (BHPO) as a co-sensitizer followed by redox vulcanization using residual BHPO as an oxidant and either fructose or tetra ethylene penta mine as reducing agents. It was found that the irradiation dose was reduced to 4 kGy with 5 phr n-BA as sensitizer and 0.1 phr BHPO as co-sensitizer. Successive crosslinking to full vulcanization was done by redox vulcanization using either 4 phr fructose at 60 degree C for 3 hours of 0.4 phr tetra-ethylene penta mine at room temperature for 1 hour. The rubber films obtained had tensile strength of about 25 MPa, modulus 300% of 0.9 MPa and crosslink density of about 1.5 x 10 19 crosslink/cm 3 . It was noted that the rubber film from the co-vulcanization was the average value of the values obtained by radiation vulcanization and redox vulcanization

Comparative study of different surrogate markers for individual radiation sensitivity

International Nuclear Information System (INIS)

Hoffmann, Nele Julia

2013-01-01

Radiotherapy is an important part of therapeutic tumor treatment concept. The applied total dose is limited by the unavoidable radiation effect on the surrounding normal tissue and the risk of radiation induced acute or chronic side effects. The clinical radiation sensitivity, i.e. the risk of radiogenic side effects is strongly coupled to the cellular radiation sensitivity. The contribution is focused on the development of a predictive tool for the individual radiation sensitivity for individual radiotherapeutic planning using lymphocytes. Residual foci, i.e. accumulated repair associated proteins at the residual double strand break are supposed to be surrogate markers of the cellular radiation sensitivity. No relation between the foci detection and the G(0)/G(1) was found assay with respect to the individual radiation sensitivity.

Enhancement of the photo-electric effect with pharmacological agents in synchrotron radiation based anti-cancer radiotherapy: a methodological study

International Nuclear Information System (INIS)

Corde, Stephanie

2002-01-01

Anti-cancer therapy rests on three main principles: 1) anatomic confinement of irradiation; 2) temporal fractioning of treatment; 3) treatment of tissues that are more sensitive to radiation than surrounding healthy tissue. Under those principles hides the goal of radiotherapy: to deposit more of the X-ray energy in the tumor while preserving the surrounding healthy tissues. This goal is hard to reach since one of the causes of the failures in radiotherapy is the continuing evolution of the tumor. Could synchrotron radiation be more effective as an X-ray source for radiotherapy? The variation of the radiation-matter interaction cross-sections as a function of X-ray energy and atomic number of the medium show that certain energies and certain elements are more suitable to obtain the largest number of interactions and the largest amount of deposited energy. Synchrotron radiation allows to select precisely those energies because of its high spectral intensity. Its spectral characteristics (energy of the photons between 10 and 100 keV) allow to trigger the photoelectric effect with a maximum of probability on heavy elements introduced close to cancerous cells. It has been shown that: 1) synchrotron radiation based tomodensitometry is a quantitative imaging technique, potentially powerful for radiotherapy since it insures in-vivo the measurement of intra-tumoral concentration of contrast agent (I or Gd); 2) in the presence of iodinated contrast agent the lethal effect of X-rays on cell survival is increased and the gain in radio sensitivity depends on X-ray energy; 3) at the cellular scale the lethality of irradiation can be optimised again by transporting heavy atoms (I, Pt) inside the DNA, which is the biological target of the irradiation. This reinforcement of the killing efficiency of low energy X-rays using a physical mechanism aimed at a pharmacological agent is an original concept in anti-cancer radiotherapy. (author) [fr

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.

Superoxide dismutase amplifies organismal sensitivity to ionizing radiation

International Nuclear Information System (INIS)

Scott, M.D.; Meshnick, S.R.; Eaton, J.W.

1989-01-01

Although increased superoxide dismutase (SOD) activity is often associated with enhanced resistance of cells and organisms to oxidant challenges, few direct tests of the antioxidant importance of this enzyme have been carried out. To assess the importance of SOD in defending against gamma-radiation, we employed Escherichia coli with deficient, normal, and super-normal enzyme activities. Surprisingly, the radiation sensitivity of E. coli actually increases as bacterial SOD activity increases. Elevated intracellular SOD activity sensitizes E. coli to radiation-induced mortality, whereas SOD-deficient bacteria show normal or decreased radiosensitivity. Toxic effects of activated oxygen species are involved in this phenomenon; bacterial SOD activity has no effect on radiation sensitivity under anaerobic conditions or on the lethality of other, non-oxygen-dependent, toxins such as ultraviolet radiation

Sensitivity Analysis of an Agent-Based Model of Culture's Consequences for Trade

NARCIS (Netherlands)

Burgers, S.L.G.E.; Jonker, C.M.; Hofstede, G.J.; Verwaart, D.

2010-01-01

This paper describes the analysis of an agent-based model’s sensitivity to changes in parameters that describe the agents’ cultural background, relational parameters, and parameters of the decision functions. As agent-based models may be very sensitive to small changes in parameter values, it is of

Radiation-induced Genomic Instability and Radiation Sensitivity

Energy Technology Data Exchange (ETDEWEB)

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

2013-01-19

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

Radiation sensitivity of human lung cancer cell lines

International Nuclear Information System (INIS)

Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

1989-01-01

X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

Radiation sensitive devices and systems for detection of radioactive materials and related methods

Science.gov (United States)

Kotter, Dale K

2014-12-02

Radiation sensitive devices include a substrate comprising a radiation sensitive material and a plurality of resonance elements coupled to the substrate. Each resonance element is configured to resonate responsive to non-ionizing incident radiation. Systems for detecting radiation from a special nuclear material include a radiation sensitive device and a sensor located remotely from the radiation sensitive device and configured to measure an output signal from the radiation sensitive device. In such systems, the radiation sensitive device includes a radiation sensitive material and a plurality of resonance elements positioned on the radiation sensitive material. Methods for detecting a presence of a special nuclear material include positioning a radiation sensitive device in a location where special nuclear materials are to be detected and remotely interrogating the radiation sensitive device with a sensor.

Radiation sensitivity of mammalian cells

International Nuclear Information System (INIS)

Koch, C.J.

1985-01-01

The authors tested various aspects of the so-called ''competition'' model for radiation sensitization/protection. In this model, sensitizers and/or protectors react in first order chemical reactions with radiation-induced target radicals in the cell, producing damage fixation or repair respectively. It is only because of these parallel, first-order competing reactions that they may assign net amounts of damage on the basis of the chemical reactivity of the sentiziers/protectors with the radicals. It might be expected that such a simple model could not explain all aspects of cellular radiosensitivity and this has indeed been found to be true. However, one is able, with the simple model, to pose quite specific questions, and obtain quantitative information with respect to the relative agreement between experiment and theory. Many experiments by several investigators have found areas of disagreement with the competition theory, particularly with respect to the follow items: 1) role of cellular glutathione as the most important endogeneous radiation protector 2) characteristics of various sensitizers which cause them to behave differently from each other 3) methods relating to the quantitative kinetic analysis of experimenal results. This paper addresses these specific areas of disagreement from both an experimental and theoretical basis

Training strategic community agents in health effects of ionizing radiation

International Nuclear Information System (INIS)

Leite, Teresa C.S.B.; Silva, IIson P.M. da; Jannuzzi, Denise M.S.; Maurmo, Alexandre M.

2013-01-01

The main motivation for the development of training was the need to train agents (opinion makers) with proximity and credibility among the population, to clarify the most frequently asked questions in relation to ionizing radiation, the operation of nuclear power plants, emergency plans and about the possibility of there effects of radiation on the health of inhabitants in regions close to the central Nuclear Almirante Alvaro Alberto - CNAAA. The project has a target audience of 420 agents, 60 of them have already been trained in a pilot project . The results indicate that the topics of training were adequate and the agents have expanded their knowledge. On the other hand, the information passed on to communities by agents, recognized by this population as ' the most reliable people', is of greater credibility and likelihood of success in communicating important issues for the population living in the vicinity of the CNAAA. (author)

Influence of catalase on the radiation sensitizing effect of misonidazole

International Nuclear Information System (INIS)

Gazso, G.L.; Dam, A.

1985-01-01

The radiation modifying action of misonidazole and catalase was investigated in Bacillus megaterium spores at various oxygen concentrations. Catalase (120 μg/ml) decreased the radiation sensitizing action of misonidazole. Misonidazole as an electron affinic radiation sensitizer enhanced the build up of H 2 O 2 , thus promoting the reaction with catalase. Protection by catalase was not enough to eliminate the total radiation sensitizing effect of misonidazole. (orig.)

Evaluation of texaphyrins as tumor selective radiation sensitizers

International Nuclear Information System (INIS)

Qing Fan; Woodburn, Kathryn W.; Young, Stuart W.

1997-01-01

Texaphyrins are expanded porphyrin macrocycles that selectively localize and are retained in cancerous lesions. The function of the texaphyrin can be manipulated by the incorporation of different metal ions into the macrocycle's central cavity. Gadolinium texaphyrin (Gd-Tex) and lutetium texaphyrin (Lu-Tex) were evaluated as radiation sensitizers. Radiation sensitization studies were performed using SMT-F and EMT6 mammary tumor-bearing mice. Single and multifraction dose regimens were performed. SMT-F bearing DBA/2N mice and EMT6 bearing Balb/c mice were intravenously administered with Gd-Tex of Lu-Tex (5-40 μmol/kg) 30 minutes to 5 hours prior to radiation (10-50 Gray) for the single fraction studies. The more radioresistant EMT-6 sarcoma model was used for the multifraction studies. The tumor bearing animals were injected with Gd-Tex (5, 20, or 40 μmol/kg) to 2 hours prior radiation (1, 2, or 4 Gray), this regimen was performed for five consecutive days. Gd-Tex is paramagnetic and has a strong fluorescence signal. Tumor selectivity was determined by MRI and fluorescence spectral imaging before and up to 24 hours following the administration of Gd-Tex. Gd-Tex but not Lu-Tex, proved to be an effective radiation sensitizer. Administration of Gd-Tex (40 μmol/kg) prior to a single dose of 30 Gray radiation provided a significant improvement in survival in SMT-F-bearing DBA/2N mice as compared to animals receiving radiation alone (p = 0.0034). A significant radiation sensitization effect was also found in multiple fraction studies (five consecutive days) with Balb/C mice bearing EMT-6 neoplasma-- following 1 Gray of radiation for 5 days there was a significant difference between the 20 and 40 μmol/kg group and controls (p = 0.003, p = 0.005 respectively). MRI and fluorescence spectral imaging studies of tumor bearing animals revealed excellent contrast enhancement of the tumor which persisted up to 24 hours. Texaphyrins localize in neoplasms as visualized using MRI

Tumor progression: analysis of the instability of the metastatic phenotype, sensitivity to radiation and chemotherapy

International Nuclear Information System (INIS)

Welch, D.R.

1984-01-01

The major complications for tumor therapy are 1) tumor spread (metastasis); 2) the mixed nature of tumors (heterogeneity); and 3) the capacity of tumors to evolve (progress). To study these tumor characteristics, the rat 13762NF mammary adenocarcinoma was cloned and studied for metastatic properties and sensitivities to therapy (chemotherapy, radiation and hyperthermia). The cell clones were heterogeneous and no correlation between metastatic potential and therapeutic sensitivities was observed. Further, these phenotypes were unstable during pasage in vitro; yet, the changes were clone dependent and reproducible using different cryoprotected cell stocks. To understand the phenotypic instability, subclones were isolated from low and high passage cell clones. The results demonstrated that 1) tumor cells are heterogeneous for multiple phenotypes; 2) tumor cells are unstable for multiple phenotypes; 3) the magnitude, direction and time of occurrence of phenotypic drift is clone dependent; 4) the sensitivity of cell clones to ionizing radiation (γ or heat) and chemotherapy agents is independent of their metastatic potential; 5) shifts in metastatic potential and sensitivity to therapy may occur simultaneously but are not linked; and 6) tumor cells independently diverge to form several subpopulations with unique phenotypic profiles

Relationship between intrinsic radiation sensitivity and metastatic potential

International Nuclear Information System (INIS)

Lewis, Anne M.; Mei, Su; Doty, Jay; Chen Yi; Pardo, Francisco S.

1996-01-01

Purpose: Prior studies emphasized genetic modulation of tumorigenicity, and experimental metastatic potential in cells transfected with oncogenes. Whether the intrinsic radiation sensitivity of cells might correlate with parallel changes in metastatic potential is unknown. Methods and Materials: Rat embryo cells (REC) were transfected with the following oncogenes, and where appropriate, with corresponding selection markers: pCMV neopEJ6.6ras, pEJ6.6ras/v-myc, pE1a, and pEJ6-.6ras/E1a. Individual transfectant clones and corresponding pooled cellular populations were propagated in selective medium. In vitro cellular radiation sensitivity was determined via clonogenic assays, a minimum of three, by standard techniques and individual SF 2 and MID parameters determined. Tumorigenicity was defined as the number of tumors forming following the injection of 1 x 10 5 - 1 x 10 6 cells into the axillary pouch of three different strains of immune-deficient mice. Animals were killed once resultant tumors reached a maximum size of 1.5-2.0 cm in maximum diameter. For determination of experimental metastatic potential, between 1 x 10 5 -1 x 10 6 cells were injected into the tail veins of litter-matched sibling mice in parallel to the tumorigenicity studies. Results: Radiobiologic studies indicate similar levels of radiation sensitivity among REC, mock-transfected REC, E1a, and combined E1a/ras transfectants. pEJ6.6ras, and combined ras/myc transfected pooled cellular populations demonstrated increases in radiation resistance when compared to the pooled radiobiologic data from untransfected and mock-transfected corresponding pooled cellular populations (p 2 , MID). Rat embryo cells, E1a, and mock-transfectants were relatively radiation sensitive and nontumorigenic. pE1a/ras was tumorigenic but demonstrated relatively low experimental metastatic potential. Ras, and ras/myc transfectants, demonstrated similar levels of experimental metastatic potential on lung colonization assays

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

Science.gov (United States)

Raso, Alessandro; Vecchio, Donatella; Cappelli, Enrico; Ropolo, Monica; Poggi, Alessandro; Nozza, Paolo; Biassoni, Roberto; Mascelli, Samantha; Capra, Valeria; Kalfas, Fotios; Severi, Paolo; Frosina, Guido

2012-09-01

Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Radiation-sensitive genetically susceptible pediatric sub-populations

Energy Technology Data Exchange (ETDEWEB)

Kleinerman, Ruth A. [National Cancer Institute, NIH, DHHS, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Rockville, MD (United States)

2009-02-15

Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation. (orig.)

In vivo radiation sensitivity of glioblastoma multiforme

International Nuclear Information System (INIS)

Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

1995-01-01

Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF 2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD 50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD 50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD 50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD 50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 ± 13.1 Gy. The TCD 50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 ± 6.4. The difference between the average TCD 50 of GBM and SCC was not significant. The STS and CC xenografts had TCD 50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD 50 in vivo and the SF 2 or D 0 in vitro. Conclusions: Our data on GBM xenografts showed a wide range of sensitivities to single dose

In vivo radiation sensitivity of glioblastoma multiforme

Energy Technology Data Exchange (ETDEWEB)

Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

1995-04-30

Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF{sub 2} values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD{sub 50} (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD{sub 50} of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD{sub 50} assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD{sub 50} values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 {+-} 13.1 Gy. The TCD{sub 50} values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 {+-} 6.4. The difference between the average TCD{sub 50} of GBM and SCC was not significant. The STS and CC xenografts had TCD{sub 50} values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD{sub 50} in vivo and the SF{sub 2} or D{sub 0} in vitro. Conclusions: Our data on GBM

Sensitivities in synchrotron radiation TXRF

International Nuclear Information System (INIS)

Pianetta, P.; Baur, K.; Brennan, S.

2000-01-01

This work describes the progress we achieved at the Stanford Synchrotron Radiation Laboratory (SSRL) in improving the sensitivity for both the transition metals and light elements such as Al and Na. The transition metal work has matured to the point where a facility exists at SSRL in which semiconductor companies are able to perform industrially relevant measurements at state of the art detection limits. This facility features clean wafer handling and automated data acquisition making routine analytical measurements possible. The best sensitivity demonstrated so far is 3.4 E7 atoms/cm 2 for a 5000 second count time corresponding to 7.6 E7 atoms/cm 2 for a standard 1000 second count time. This is more than a factor of 100 better than what can be achieved with conventional TXRF systems. The detection of light elements such as Al and Na is challenging due to the presence of the h stronger Si fluorescence peak. For traditional energy-dispersive detection only the tunability of synchrotron radiation to excitation energies below the Si-K absorption edge leads to an acceptable sensitivity for Al detection which is limited by a large background due to inelastic x-ray Raman scattering. An alternative approach to overcome the Raman contribution and the strong Si fluorescence is to use a wavelength-dispersive spectrometer for fluorescence detection. The benefits of such a multilayer spectrometer over a solid state detector are its higher energy resolution and greater dynamic range. This strategy allows primary excitation above the Si K absorption edge, eliminating the background due to Raman scattering, and a gracing emission geometry to guarantee high surface sensitivity. Studies testing this concept in combination with high flux synchrotron radiation are underway and first results will be presented. (author)

Correlation of radiation sensitivity and nitrofurantoin sensitivity of Escherichia coli K-12

International Nuclear Information System (INIS)

Kloeck, K.

1981-01-01

The Uvr- and rec-mutants of E.coli K-12 have been tested with a view to their radiation- and nitrofuration sensitivity. The tests showed that all mutants tested were more radiation- and NF-sensitive than the wild type AB 1157. When the NF-sensitivity had been compared to the UV- and X-ray sensitivity it became obvious that the NF-sensitivity is correlated to the UV-sensitivity. Studies carried out with regard to the time dependence of the NF-effect on E.coli showed that the effect of NF on E. Coli became weaker after about 1 1/2 to 2 hours. That is possibly caused by the fact that the E. coli bacteria succeed in reducing the NF to an inactive form. By means of nitrosoguanidine mutants of E-coli AB 1157 had been induced and by means of the Replicite Plating Method, NF-sensible mutants had been isolated from the plutonium mixture. Among the mutants which had been isolated by this method, 74% had been more UV-sensitive than the wild type and 55% more X-ray sensitive. Thus NF-sensitive mutants have not necessarily to be considered as rec-mutants as there are also uvr-mutants in the mixture. (orig.) [de

SU-E-QI-13: Predictable Models for Radio-Sensitizing Agent Kinetics: Application to Stereotactic Synchrotron Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Obeid, L; Schmitt, M; Esteve, F; Adam, J [Grenoble Institut des Neurosciences, La Tronche, RHONE-ALPES (France)

2014-06-15

Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The radiation dose enhancement depends on the time course of iodine in the tumors. A prolonged CT scanning (∼30 min) is required to follow-up iodine kinetics for recruited patients. This protocol could lead to substantial radiation dose to the patient. A novel method is proposed to reduce the acquisition time. Methods: 12 patients received an intravenous bolus of iodinated contrast agent, followed by a steady-state infusion to ensure stable intra-tumoral amounts of iodine during the treatment. Absolute iodine concentrations (IC) were derived from 40 multi-slice dynamic conventional CT images of the brain. The impulse response function (IRF) to the bolus was estimated using the adiabatic approximation of the Johnson and Wilson's model. The arterial input function (AIF) of the steady-state infusion was fitted with several models: Gamma, Gamma with recirculation and hybrid. Estimated IC were calculated by convolving the IRF with the modeled AIF and were compared to the measured data. Results: The gamma variate function was not relevant to model the AIF due to high differences with the measured AIF. The hybrid and the gamma with recirculation models provided differences below 8% during the whole acquisition time. The absolute difference between the measured and the estimated IC was lower than 0.5 mg/ml, which corresponds to 5% of dose enhancement error. Conclusion: The proposed method allows a good estimation of the iodine time course with reduced scanning delays (3 instead of 30 min) and dose to the patient. The results suggest that the dose errors may stay within the radiotherapy standards.

Oyster radiation sensitivity

International Nuclear Information System (INIS)

Marchese, Sandra R.M.; Mastro, Nelida L. del

1996-01-01

Various food products like oysters, crabs and shrimps have been described as possible Vibrio spp. transmitting agents. Seafood irradiation is been presented as an alternative among the different public health intervention measures to control food borne diseases. The objective of this work was to establish, firstly, the radioresistance of Crassostrea brasiliana oysters. The oysters were irradiated with Co-60 radiation with doses of 0, 1.5,3 and 6 kGy. Survival curves a function of time showed that 100% of samples irradiated with 3 kGy survived at least 6 days; among those irradiated with 6 kGy, 100% survived 3 days. These results are encouraging since a dose of 2 kGy is already effective in diminishing oyster bioburden. (author)

Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization

Energy Technology Data Exchange (ETDEWEB)

Schuemann, Jan, E-mail: jschuemann@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Berbeco, Ross [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Chithrani, Devika B. [Department of Physics, Ryerson University, Toronto, Ontario (Canada); Cho, Sang Hyun [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kumar, Rajiv [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); McMahon, Stephen J. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); Sridhar, Srinivas [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Krishnan, Sunil [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-01-01

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Augmentation of radiation response with the vascular targeting agent ZD6126

International Nuclear Information System (INIS)

Hoang Tien; Huang Shyhmin; Armstrong, Eric; Eickhoff, Jens C.; Harari, Paul M.

2006-01-01

Purpose: To examine the antivascular and antitumor activity of the vascular targeting agent ZD6126 in combination with radiation in lung and head-and-neck (H and N) cancer models. The overall hypothesis was that simultaneous targeting of tumor cells (radiation) and tumor vasculature (ZD6126) might enhance tumor cell killing. Methods and Materials: A series of in vitro studies using human umbilical vein endothelial cells (HUVEC) and in vivo studies in athymic mice bearing human lung (H226) and H and N (squamous cell carcinoma [SCC]1, SCC6) tumor xenografts treated with ZD6126 and/or radiation were performed. Results: ZD6126 inhibited the capillary-like network formation in HUVEC. Treatment of HUVEC with ZD6126 resulted in cell cycle arrest in G2/M, with decrease of cells in S phase and proliferation inhibition in a dose-dependent manner. ZD6126 augmented the cell-killing effect of radiation and radiation-induced apoptosis in HUVEC. The combination of ZD6126 and radiation further decreased tumor vascularization in an in vivo Matrigel angiogenesis assay. In tumor xenografts, ZD6126 enhanced the antitumor activity of radiation, resulting in tumor growth delay. Conclusions: These preclinical studies suggest that ZD6126 can augment the radiation response of proliferating endothelial H and N and lung cancer cells. These results complement recent reports suggesting the potential value of combining radiation with vascular targeting/antiangiogenic agents

Individual radiation sensitivity: implications in medical practice

Energy Technology Data Exchange (ETDEWEB)

Gisone, P.; Dubner, D.; Perez, M.D.R.; Michelin, S.; Di Giogio, M. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Bourguignon, M. [Direction Generale de la Surete Nucleaire et de la Radioprotection, Paris (France)

2006-07-01

Important advances in radiotherapy and nuclear medicine towards better treatment modalities and safer applications have taken place in recent years. Progress in medical imaging, better tumour targeting and optimization of radiation delivery have allowed for dose escalation and improved patient outcome. However, the tolerance of normal tissues constitutes the limiting factor for dose escalation in therapeutical uses of ionizing radiation (IR). Patients vary considerably in their normal tissue response to IR even after similar treatments. As many as 5% of cancer patients develop severe effects to external radiation therapy in normal tissues within the treatment field: they may include acute effects such as erythema and desquamation of the exposed skin and mucosa that appear during or directly after radiotherapy, late effects developed months or years later, such as fibrosis and telangiectasia and cancer induction. Several patient and treatment related factors are known to influence the variability of side effects, however up to a 70% of the total variance of normal tissue radiation response remained unexplained. Thus, individual sensitivity to IR, i.e. hypersensitivity to carcinogenic risks (stochastic effects) and hypersensitivity to deterministic effects, is becoming an important issue in oncology and raises questions regarding the underlying mechanisms. The mechanisms of DNA repair, the signalling pathways involved in radiation sensitivity and non-targeted effects are key aspects, essential to understanding radiation effects at genetic level. Moreover, human genetic diseases that combine higher incidence of cancer and hypersensitivity to IR are associated with defects in cell response to DNA damage. Therefore, much interest has raised during the last years in the developing of predictive tests capable to detect in advance such hypersensitive conditions. The goal of this presentation is to review the possible mechanisms involved in genetic and epigenetic

Individual radiation sensitivity: implications in medical practice

International Nuclear Information System (INIS)

Gisone, P.; Dubner, D.; Perez, M.D.R.; Michelin, S.; Di Giogio, M.; Bourguignon, M.

2006-01-01

Important advances in radiotherapy and nuclear medicine towards better treatment modalities and safer applications have taken place in recent years. Progress in medical imaging, better tumour targeting and optimization of radiation delivery have allowed for dose escalation and improved patient outcome. However, the tolerance of normal tissues constitutes the limiting factor for dose escalation in therapeutical uses of ionizing radiation (IR). Patients vary considerably in their normal tissue response to IR even after similar treatments. As many as 5% of cancer patients develop severe effects to external radiation therapy in normal tissues within the treatment field: they may include acute effects such as erythema and desquamation of the exposed skin and mucosa that appear during or directly after radiotherapy, late effects developed months or years later, such as fibrosis and telangiectasia and cancer induction. Several patient and treatment related factors are known to influence the variability of side effects, however up to a 70% of the total variance of normal tissue radiation response remained unexplained. Thus, individual sensitivity to IR, i.e. hypersensitivity to carcinogenic risks (stochastic effects) and hypersensitivity to deterministic effects, is becoming an important issue in oncology and raises questions regarding the underlying mechanisms. The mechanisms of DNA repair, the signalling pathways involved in radiation sensitivity and non-targeted effects are key aspects, essential to understanding radiation effects at genetic level. Moreover, human genetic diseases that combine higher incidence of cancer and hypersensitivity to IR are associated with defects in cell response to DNA damage. Therefore, much interest has raised during the last years in the developing of predictive tests capable to detect in advance such hypersensitive conditions. The goal of this presentation is to review the possible mechanisms involved in genetic and epigenetic

FANCG knockout CHO cells display sensitivity to diverse DNA damaging agents and possible genomic instability

International Nuclear Information System (INIS)

Hinz, J.M.; Tebbs, R.S.; Yamada, N.A.; Salazar, E.P.; Kopf, V.L.; Thompson, L.H.

2003-01-01

Full text: The function of the proteins encoded by the genes responsible for the disease Fanconi anemia (FA) have not been elucidated. Several of these proteins (FancA, C, E, F, and G) form a complex in the nucleus, and cells deficient in any one of these proteins are sensitive to crosslinking agents, suggesting a possible role for these proteins in some aspect of DNA repair, chromosomal maintenance, or replication. We constructed a FancG knockout mutant (FGKO40) in CHO AA8 cells, as well as FancG-corrected FGKO40 cells (KO40BP6, which is a pool of six BAC-clone transformants). FGKO40 cells are sensitive to a wide variety of DNA damaging agents. Sensitivity to the cross-linking agents MMC (3x) and chloroethyl-nitrosourea (3x) does not exceed that of methyl methanesulfonate (MMS) (4x), methyl-nitrosourea (4x), or ethyl-nitrosourea (3x), or the purine analog 6-thioguanine (5x). Other agents show mild sensitivity in FGKO40 cells: ionizing radiation (1.2x), UV-C (1.5x), hydroxyurea (1.2x), camptothecin (1.2x), and excess thymidine (normal). The length of S phase was carefully measured by monitoring the progression of highly synchronous G1 cells obtained by centrifugal elutriation. FGKO40 cells traversed S phase normally but had a slightly longer G2 phase than parental cells. Treatment of synchronized G1 cells with MMS did not increase S phase in parental or mutant cells, but again G2 was slightly longer for FGKO40. Mutation rates were measured at the hrpt and aprt loci, where gene inactivation confers resistance to 6-thioguanine or 8-azaadenine, respectively. FGKO40 had a slightly reduced mutation rate for hprt mutants, suggesting reduced recovery of large deletions at this locus. Moreover, the rate of methotrexate resistance was elevated 2.5-fold in mutant cells compared to controls. Resistance to this drug is generally associated with amplification of the dhfr locus, suggesting FancG plays a role in this aspect of genome stability. We suggest that the defect in FGKO

Relative radiation sensitivity of insulators, stabilizers, and superconductors

International Nuclear Information System (INIS)

Van Konynenburg, R.A.; Guinan, M.W.

1980-12-01

The operating conditions of the magnets including temperature and radiation fields are discussed. Comments were made on the nuclear heating. Components of the magnet system, including the materials used, the important properties, the atomic structure, the damage mechanism, and the effects of room temperature warmup are described. Some failure criteria for the various components are suggested. Available data concerning radiation effects on each component are discussed. Their radiation sensitivities are compared using the conditions calculated for the ETF toroidal field magnet inboard leg, and ranked in order of sensitivity. Comments were made on the implications of this ranking for the directions of future applied materials research

Effect of troglitazone on radiation sensitivity in cervix cancer cells

International Nuclear Information System (INIS)

An, Zheng Zhe; Liu, Xian Guang; Song, Hye Jin; Choi, Chi Hwan; Kim, Won Dong; Park, Woo Yoon; Yu, Jae Ran

2012-01-01

Troglitazone (TRO) is a peroxisome proliferator-activated receptor γ (PPARγ ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu 2+ /Zn 2+ -superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro. Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 μM of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay. By 5 μM TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0- G1 phase cells were increased in HeLa and Me180 by 5 μM TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 μM TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 μM TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO. TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalasemediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPAR γ expression level.

Radiation sensitivity of integrated circuits Pt. 1

International Nuclear Information System (INIS)

Bereczkine Kerenyi, Ilona

1986-01-01

The cosmic ray sensitivity of CMOS integrated circuits are overviewed in three parts. The aim is to analyze the effects of ionizing radiation on the degradation of electronic parameters, the effects of the electric state during irradiation, and the radiation hardening of ICs. In this Part 1 a general introduction of the response of semiconductors to cosmic radiation is given, and the radiation tolerance and hardening of small-scale integrated CMOS ICs is analyzed in detail. The devices include various basic inverters and simple gate ICs. (R.P.)

Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy?

Science.gov (United States)

Harrison, Louis; Blackwell, Kimberly

2004-01-01

Hypoxia is a common feature of solid tumors that occurs across a wide variety of malignancies. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. These effects, in turn, can lead to increased invasiveness and metastatic potential, loss of apoptosis, and chaotic angiogenesis, thereby further increasing treatment resistance. Investigations of the prognostic significance of pretreatment tumor oxygenation status have shown that hypoxia (oxygen tension [pO(2)] value effect of hypoxia on standard cancer treatment, a variety of hypoxia- and anemia-targeted therapies have been studied in an effort to improve therapeutic effectiveness and patient outcomes. Early evidence from experimental and clinical studies suggests the administration of recombinant human erythropoietin (rHuEPO) may enhance the effectiveness of radiation therapy and chemotherapy by increasing hemoglobin levels and ameliorating anemia in patients with disease- or treatment-related anemia. However, further research is needed in the area of hypoxia-related treatment resistance and its reversal.

Radiation hardenable impregnating agents for the consolidating conservation of wooden objects

International Nuclear Information System (INIS)

Schaudy, R.

1985-01-01

Radiation hardenable impregnating agents offer some advantages over the conventional agents. At the author's institution objects up to 110 cm length can be impregnated for conservation. More than 200 monomers and resins have been investigated. The procedure of impregnation is outlined and some kinds of wooden objects conserved in this way listed. (G.W.)

Selective enhancement of radiation response of herpes simplex virus thymidine kinase transduced 9L gliosarcoma cells in vitro and in vivo by antiviral agents

International Nuclear Information System (INIS)

Kim, Jae Ho; Kim, Sang Hie; Kolozsvary, A.

1995-01-01

The purpose of this investigation was to demonstrate in a well-characterized tumor model that the radiosensitivity of tumor cells transduced with a herpes simplex virus thymidine kinase gene (HS-tk) would be selectively enhanced by antiviral agents. Rat 9L gliosarcoma cells transduced with a retroviral vector containing an HS-tk gene, 9L-tk cells were exposed to various doses or irradiation under either in vitro or in vivo conditions. The radiation sensitizing potential of two antiviral drugs, bromovinyl deoxyuridine (BVdU) and dihydroxymethyl ethyl methyl guanine (acyclovir), was evaluated in vitro. The radiosensitizing ability of BVdU was also evaluated with a 9L-tk tumor growing in the rat brain. Tumors growing in the right hemisphere of rat brains were irradiated stereotactically with single-dose irradiation. The radiation response of 9L-tk cells was selectively enhanced by antiviral agents relative to nontransduced cells. In the cell culture, when a 24-h drug exposure (20 μg/ml) preceded radiation, the sensitizer enhancement ratio (SER) for BVdU and acyclovir was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. Exposure of cells to 10 μg/ml acyclovir for two 24-h periods both pre- and postirradiation resulted in a SER of 1.6 ± 0.1. In vivo, a significant increase in median survival time of rats with 9L-tk tumors was found when BVdU was administered prior to single-dose irradiation relative to the survival time of similar rats receiving radiation alone. An antiviral agent can enhance cell killing by radiation with selective action in cells transduced with the herpes simplex virus thymidine kinase gene. The results suggest that the three-pronged therapy of HS-tk gene transduction, systemically administered antiviral drug, and stereotactically targeted radiation therapy will improve the effectiveness of radiation therapy for the treatment of radioresistant tumors. 25 refs., 6 figs

Selective enhancement of radiation response of herpes simplex virus thymidine kinase transduced 9L gliosarcoma cells in vitro and in vivo by antiviral agents

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Ho; Kim, Sang Hie; Kolozsvary, A. [Henry Ford Hospital, Detroit, MI (United States)] [and others

1995-11-01

The purpose of this investigation was to demonstrate in a well-characterized tumor model that the radiosensitivity of tumor cells transduced with a herpes simplex virus thymidine kinase gene (HS-tk) would be selectively enhanced by antiviral agents. Rat 9L gliosarcoma cells transduced with a retroviral vector containing an HS-tk gene, 9L-tk cells were exposed to various doses or irradiation under either in vitro or in vivo conditions. The radiation sensitizing potential of two antiviral drugs, bromovinyl deoxyuridine (BVdU) and dihydroxymethyl ethyl methyl guanine (acyclovir), was evaluated in vitro. The radiosensitizing ability of BVdU was also evaluated with a 9L-tk tumor growing in the rat brain. Tumors growing in the right hemisphere of rat brains were irradiated stereotactically with single-dose irradiation. The radiation response of 9L-tk cells was selectively enhanced by antiviral agents relative to nontransduced cells. In the cell culture, when a 24-h drug exposure (20 {mu}g/ml) preceded radiation, the sensitizer enhancement ratio (SER) for BVdU and acyclovir was 1.4 {plus_minus} 0.1 and 1.3 {plus_minus} 0.1, respectively. Exposure of cells to 10 {mu}g/ml acyclovir for two 24-h periods both pre- and postirradiation resulted in a SER of 1.6 {plus_minus} 0.1. In vivo, a significant increase in median survival time of rats with 9L-tk tumors was found when BVdU was administered prior to single-dose irradiation relative to the survival time of similar rats receiving radiation alone. An antiviral agent can enhance cell killing by radiation with selective action in cells transduced with the herpes simplex virus thymidine kinase gene. The results suggest that the three-pronged therapy of HS-tk gene transduction, systemically administered antiviral drug, and stereotactically targeted radiation therapy will improve the effectiveness of radiation therapy for the treatment of radioresistant tumors. 25 refs., 6 figs.

Selective enhancement of radiation response of herpes simplex virus thymidine kinase transduced 9L gliosarcoma cells in vitro and in vivo by antiviral agents

International Nuclear Information System (INIS)

Jae, Ho Kim; Sang, Hie Kim; Kolozsvary, Andrew; Brown, Stephen L.; Ok, Bae Kim; Freytag, Svend O.

1995-01-01

Purpose: To demonstrate in a well-characterized tumor model that the radiosensitivity of tumor cells transduced with a herpes simplex virus thymidine kinase gene (HS-tk) would be selectively enhanced by antiviral agents. Methods and Materials: Rat 9L gliosarcoma cells transduced with a retroviral vector containing an HS-tk gene, 9L-tk cells were exposed to various doses of irradiation under either in vitro or in vivo conditions. The radiation sensitizing potential of two antiviral drugs, bromovinyl deoxyuridine (BVdU) and dihydroxymethyl ethyl methyl guanine (acyclovir), was evaluated in vitro. The radiosensitizing ability of BVdU was also evaluated with a 9L-tk tumor growing in the rat brain. Tumors growing in the right hemisphere of rat brains were irradiated stereotactically with single-dose irradiation. Results: The radiation response of 9L-tk cells was selectively enhanced by antiviral agents relative to nontransduced cells. In the cell culture, when a 24-h drug exposure (20 μg/ml) preceded radiation, the sensitizer enhancement ratio (SER) for BVdU and acyclovir was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. Exposure of cells to 10 μg/ml acyclovir for two 24-h periods both pre- and postirradiation resulted in a SER of 1.6 ± 0.1. In vivo, a significant increase in median survival time of rats with 9L-tk tumors was found when BVdU was administered prior to single-dose irradiation relative to the survival time of similar rats receiving radiation alone. Conclusion: An antiviral agent can enhance cell killing by radiation with selective action in cells transduced with the herpes simplex virus thymidine kinase gene. The results suggest that the three-pronged therapy of HS-tk gene transduction, systemically administered antiviral drug, and stereotactically targeted radiation therapy will improve the effectiveness of radiation therapy for the treatment of radioresistant tumors

Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex.

Science.gov (United States)

Hagberg, Gisela E; Mamedov, Ilgar; Power, Anthony; Beyerlein, Michael; Merkle, Hellmut; Kiselev, Valerij G; Dhingra, Kirti; Kubìček, Vojtĕch; Angelovski, Goran; Logothetis, Nikos K

2014-01-01

Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look-Locker-based quantitative T(1) mapping, and T(1) -weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2-4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration. Copyright © 2014 John Wiley & Sons, Ltd.

Herbal radiation countermeasure agents: promising role in the management of radiological/nuclear exigencies

International Nuclear Information System (INIS)

Arora, Rajesh; Sharma, A.; Kumar, R.; Tripathi, R.P.

2008-01-01

In the future, there is a need to substantially boost biomass production and employ elicitors/precursors for improving the production of radioprotective compounds from such alternative sources for ensuring a sustainable supply of the high-value, low volume radioprotective molecules. Chemical fingerprinting, identification and characterization of bioactive constituents using modem analytical techniques and evaluation of their multifaceted mode of action at genomic/proteomic level is also the need of the hour. Such data will help in the development of novel, safe and effective radiation countermeasure agents for human use. Herbal radiation countermeasure agents, including several dietary agents, are likely to find large-scale acceptance in most countries in view of their widespread acceptance, holistic mode of action, less toxicity and economical nature. Endeavours made at INMAS in this direction are likely to fructify in coming years and radiation countermeasure agents from several of these herbal sources would become available, possibly several would be obtainable over-the-counter, for use by civilians, military personnel, first emergency responders and other rescue and recovery personnel. (author)

DNA repair and radiation sensitivity in mammalian cells

International Nuclear Information System (INIS)

Chen, D.J.C.; Stackhouse, M.; Chen, D.S.

1993-01-01

Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population

HeLa Cells Containing a Truncated Form of DNA Polymerase Beta are More Sensitized to Alkylating Agents than to Agents Inducing Oxidative Stress.

Science.gov (United States)

Khanra, Kalyani; Chakraborty, Anindita; Bhattacharyya, Nandan

2015-01-01

The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta (polβ Δ208-304) specific for ovarian cancer. Pol β Δ208-304 has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. Polβ Δ208-304 cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards H2O2 and UV when compared with HeLa cells alone. It has been shown that cell death in Pol β Δ208-304 transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

Mutagenic effect of ionizing radiation and chemical and environmental agents in Tradescantia

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.

1988-01-01

The studies covered the following problems: an influence of some environmental agents on the mutagenic effectiveness of ionizing radiation, interaction between ionizing radiation and chemical mutagens in the induction of somatic mutations and also an application of Tradescantia model system for biological monitoring. The studies showed that the pretreatment of Tradescantia plants with sodium fluoride or the modification of the soil composition with dolomite admixture, visibly influences plants radiosensitivity. The analysis of the changes in the dose-response curves suggested that the employed agents were influencing in different ways the repair processes of the DNA. The studies on the interaction between agents proved that the synergistic effect occurs in case of combined action of ionizing radiation with such chemical mutagens as ethyl methansulfonate or 1,2 dibromomethane. It was also discovered that in the range of low doses the effect was proportional to radiation dose and total exposition to chemical mutagen. The field application of Tradescantia method defined the mutagenicity of air pollution in the Cracow area. The highest frequencies of mutations were detected after the Chernobyl accident and after the damage of the filters in the Pharmaceutical Plant. The applied method was evaluated in respect of its usefulness for biological monitoring of environmental pollution. 163 refs. (author)

Applying radiation approaches to the control of public risks from chemical agents

International Nuclear Information System (INIS)

Alexander, R.E.

1989-01-01

IF a hazardous agent has a threshold, prevention is the obvious measure of success. To the eyes of this author, success is also achieveable for a hazardous agent that may have no threshold and that causes its effects in a probabilistic manner. First, the technical people responsible for protection must be given a reasonable, well defined risk objective by governmental authorities. To the extent that they meet that objective (1) without unnecessarily increasing operational costs, (2) without interfering unnecessarily with operational activities, and (3) without diverting resources away from greater risks, they are successful. Considering these three qualifications, radiation protection for members of the public can hardly be presented as the panacea for other hazardous agents. It would be an error to dismiss the improvement opportunities discussed above as being of acdemic interest only. Decades of experience with radiation have demonstrated that these problems are both real adn significant. In the US the axioms discussed above are accepted as scientific fact for radiation by many policy makers, the news media and the public. For any operation the collective dose is calculated using zero dose as the lower limit of integration, the results are converted to cancer deaths using the risk coefficients, and decisions are made as though these deaths would actually occur without governmental intervention. As a result, billions of dollars and a very large number of highly skilled persons are being expended to protect against radiation doses far smaller than geographical variations in the natural radiation background. These expenditures are demanded by, and required for well-meaning, nontechnical people who have been misled. It is often stated by knowledgeable people that if the degree of protection required for radiation were also to be requested for the other hazards, human progress would come to a halt. If the radiation approaches are to be used in the control of public

Training strategic community agents in health effects of ionizing radiation; Capacitacao de agentes comunitarios de saude em efeitos das radiacoes ionizantes

Energy Technology Data Exchange (ETDEWEB)

Leite, Teresa C.S.B.; Silva, IIson P.M. da; Jannuzzi, Denise M.S. [Fundacao Eletronuclear de Assistencia Medica (CIRA/FEAM), Angra dos Reis, RJ (Brazil). Centro de Informacoes em Radioepidemiologia; Maurmo, Alexandre M., E-mail: ammaurmo@gmail.com [Fundacao Eletronuclear de Assistencia Medica (CMRl/CTNV/FEAM), Angra dos Reis, RJ (Brazil). Centro de Treinamento Prof. Nelson Valverde. Centro de Medicina das Radiacoes Ionizantes

2013-11-01

The main motivation for the development of training was the need to train agents (opinion makers) with proximity and credibility among the population, to clarify the most frequently asked questions in relation to ionizing radiation, the operation of nuclear power plants, emergency plans and about the possibility of there effects of radiation on the health of inhabitants in regions close to the central Nuclear Almirante Alvaro Alberto - CNAAA. The project has a target audience of 420 agents, 60 of them have already been trained in a pilot project . The results indicate that the topics of training were adequate and the agents have expanded their knowledge. On the other hand, the information passed on to communities by agents, recognized by this population as ' the most reliable people', is of greater credibility and likelihood of success in communicating important issues for the population living in the vicinity of the CNAAA. (author)

Antiangiogenic Agent Might Upgrade tumor Cell Sensitivity to Ionizing Radiation

International Nuclear Information System (INIS)

Badr, N.M.S.A.

2013-01-01

The understanding of the fundamental role of angiogenesis and metastasis in cancer growth has led to tremendous interest in research regarding its regulatory mechanisms and clinical implications in the management of cancer. The present study was conducted to evaluate the influence of the angiogenic regulators modification on the tumor growth and the cell sensitivity to ionizing radiation targeting the improvement of cancer therapeutic protocols. Accordingly, the antiangiogenic activity of apigenin and selenium was tested in vitro via MTT assay. The action of Apigenin and or Selenium was examined in vivo by using a model of solid tumor carcinoma (EAC). The growth rate of solid tumor in all experimental groups was measured by Caliper. The irradiated mice were exposed to 6.5 Gy of gamma rays. Apigenin 50 mg/kg body weight and selenium 5 μg per mice were daily administrated for 14 consecutive days after tumor volume reached 1mm 3 . The angiogenic activators TNF-α (key cytokine) in spleen, serum MMP 2 and MMP 9, liver and tumor NO, the lipid peroxidation (LPx) and angiogenic inhibitor TIMP-1 in spleen as well as, antioxidant markers (CAT, SOD, GPX) in tumor and liver tissue and DNA fragmentation in splenocytes were estimated to monitor efficacy of Apigenin and selenium in cancer treatment strategy. All parameters were determined as a time course on days 16 and 22 after tumor volume reached 1mm 3 . The using of MTT assay on EAC cells shows inhibition in EAC cell proliferation after the incubation with apigenin and /or selenium. The administration of apigenin and /or selenium to mice bearing tumor and to irradiated mice bearing tumor reduce significantly the TNF-α expression, MMP 2,9 , NO , LPx level and increased the antioxidant enzymes (GPx , SOD and CAT) activities. The DNA fragmentation and the antiangiogenic factors TIMP-1 were significantly increased when compared with their values in mice bearing tumor or in irradiated mice bearing tumor. From the results

191 bacterial agents of otitis media and their sensitivity to some ...

African Journals Online (AJOL)

DR. AMINU

2010-06-01

Shamsuddeen, U., Usman A. D., Bukar, ... Key Words: Bacterial agents, otitis media, sensitivity, antibiotics, AKTH. INTRODUCTION. Otitis media is an .... Atlas R.M (1998) Microbiology Fundamentals and. Applications. Second edition ...

Non-nitro radiation sensitizers

International Nuclear Information System (INIS)

Jacobs, G.P.

1986-01-01

This short communication aims to update the review of non-nitro radiation sensitizers (Shenoy and Singh 1985) and correct omissions. Work is mentioned and bibliography given for studied of cis-platinum, potassium permanganate, cobalt hexammine, sodium bromide, dimethylsulphoxide, zinc and copper ions, organic nitroxyl free radicals (TAN,TMPN and NPPN + PNAP), halogenated pyrimidines, organic and inorganic iodine containing compounds, diacetyl, acetone and acetophenone, rho-hydrobenzoic acid and its esters, pentobarbitone and secobarbitone, heparin and 9-anilinoacridines, dehydropiandosterone and paraquat. (U.K.)

Radiation sensitivity of human malignant lymphocytes

International Nuclear Information System (INIS)

Seshadri, R.; Matthews, C.; Morley, A.A.

1985-01-01

A simple and rapid in vitro technique to assess the sensitivity of human malignant lymphocytes to roentgen irradiation is described. A variety of established malignant lymphocyte cell lines were cloned in microwells and clone survival was used as the end-point. The survival of the clonogenic malignant lymphocyte down to a fraction of approximately 0.001 could be measured accurately. Except for a T-cell line, the radiation sensitivities of the cell lines were similar to that of normal T-lymphocytes. (orig.)

The radiation-induced inactivation of microorganisms in non-aqueous suspension: The effect of selective alcohols and paraffins on the radiation sensitivity of aerated Bacillus pumilus spores

International Nuclear Information System (INIS)

Jacobs, G.P.

1981-01-01

The effect of model compounds comprising alcohols and paraffins on the radiation sensitivity of B. pumilus spores has been studied with the aim of understanding the radiation-induced inactivation of microorganisms when suspended in non-aqueous medium. This study is a prerequisite to the undertaking of radiation sterilization of non-aqueous pharmaceuticals. Spores of B. pumilus E601 mounted on kaolin powder were suspended in the appropriate organic agent and gamma irradiated under oxic conditions. Spores suspended in paraffins displayed increased radiation response over that for aerated buffered suspensions. Values of inactivation constant ranged between 2 x and 5 x that for buffer. Less pronounced modification of response was obtained for the alcohols. The results reveal a marked tendency for response to increase with decreasing polarity of the supending fluid. The partial miscibility of the alcohols in water enabled the examining of the transition from the response characteristic of aerated buffered suspensions to those of the spores in pure organic liquids. (orig./MG) [de

Physical determinants of radiation sensitivity in bacterial spores

International Nuclear Information System (INIS)

Powers, E.L.

1982-01-01

Several factors modifying radiation sensitivity in dry bacterial spores are described and discussed. Vacuum inducing the loss of critical structural water, very low dose rates of radiation from which the cell may recover, radiations of high linear energy transfer, and the action of temperature over long periods of time on previously irradiated cells are recognized from extensive laboratory work as important in determining survival of spores exposed to low radiation doses at low temperatures for long periods of time. Some extensions of laboratory work are proposed

Toward the elucidation of factors concerning the individual difference of radiation sensitivity, and the reduction of radiation risks

International Nuclear Information System (INIS)

Nenoi, Mitsuru; Nakajima, Tetsuo; Wang, Bing

2013-01-01

This article describes studies aiming at the title subject and contains 2 topics of genetic and non-genetic factors modifying the radiation sensitivity. The ultimate purposes of those studies are the introduction of individual weighting factor to correct the individual differences of the sensitivity (IDS) and the practical control of the sensitivity-concerned factors, in the field of medical exposure. For genetic factors, described are studies on factors modifying the sensitivity at DNA repair and on the control of the sensitivity through the DNA repairing factors. The former, using cultured cells, aims at identifying protein (gene) of possible biomarker for IDS in non-homologous end-joining (NHEJ), an important mechanism in repairing the double strand break of DNA. Ku protein is found as the candidate. The latter has revealed that cells lacking Artemis, XRCC4 or MDC1 gene are highly sensitive, and are planning to suppress Artemis activity artificially, which may lead to the reduction of radiation cancer formation due to the death of highly sensitive cells. For non-genetic factors, described are studies on the life habits modifying the sensitivity, on the control of the sensitivity through the radiation-induced adaptive response and with steroid hormone. In the first, in mice treated with high-calorie diet and X-irradiation, a possible radiation response is suggested in the hepatic DNA-methylation and micro-RNA. Second, the combination of radiation adaptive response in the genome damage and restriction of diet ingestion is shown to lower the sensitivity of mice with use of C, Ne ion or X-ray irradiation. Third, in studies on the radiation-induced formation and condensation of breast cancer stem cells in the presence of progesterone, the hormone is found to produce micro-RNA molecules relating with the suppression of cellular senescence and repressed carcinogenesis with over-expression of apoptosis inhibitory molecules. (T.T.)

Investigation of graphene-based nanoscale radiation sensitive materials

Science.gov (United States)

Robinson, Joshua A.; Wetherington, Maxwell; Hughes, Zachary; LaBella, Michael, III; Bresnehan, Michael

2012-06-01

Current state-of-the-art nanotechnology offers multiple benefits for radiation sensing applications. These include the ability to incorporate nano-sized radiation indicators into widely used materials such as paint, corrosion-resistant coatings, and ceramics to create nano-composite materials that can be widely used in everyday life. Additionally, nanotechnology may lead to the development of ultra-low power, flexible detection systems that can be embedded in clothing or other systems. Graphene, a single layer of graphite, exhibits exceptional electronic and structural properties, and is being investigated for high-frequency devices and sensors. Previous work indicates that graphene-oxide (GO) - a derivative of graphene - exhibits luminescent properties that can be tailored based on chemistry; however, exploration of graphene-oxide's ability to provide a sufficient change in luminescent properties when exposed to gamma or neutron radiation has not been carried out. We investigate the mechanisms of radiation-induced chemical modifications and radiation damage induced shifts in luminescence in graphene-oxide materials to provide a fundamental foundation for further development of radiation sensitive detection architectures. Additionally, we investigate the integration of hexagonal boron nitride (hBN) with graphene-based devices to evaluate radiation induced conductivity in nanoscale devices. Importantly, we demonstrate the sensitivity of graphene transport properties to the presence of alpha particles, and discuss the successful integration of hBN with large area graphene electrodes as a means to provide the foundation for large-area nanoscale radiation sensors.

Low environmental radiation background impairs biological defence of the yeast Saccharomyces cerevisiae to chemical radiomimetic agents

International Nuclear Information System (INIS)

Satta, L.; Augusti-Tocco, G.; Ceccarelli, R.; Paggi, P.; Scarsella, G.; Esposito, A.; Fiore, M.; Poggesi, I.; Ricordy, R.; Cundari, E.

1995-01-01

Background radiation is likely to constitute one of the factors involved in biological evolution since radiations are able to affect biological processes. Therefore, it is possible to hypothesize that organisms are adapted to environmental background radiation and that this adaptation could increase their ability to respond to the harmful effects of ionizing radiations. In fact, adaptive responses to alkylating agents and to low doses of ionizing radiation have been found in many organisms. In order to test for effects of adaptation, cell susceptibility to treatments with high doses of radiomimetic chemical agents has been studied by growing them in a reduced environmental radiation background. The experiment has been performed by culturing yeast cells (Saccharomyces cerevisiae D7) in parallel in a standard background environment and in the underground Gran Sasso National Laboratory, with reduced environmental background radiation. After a conditioning period, yeast cells were exposed to recombinogenic doses of methyl methanesulfonate. The yeast cells grown in the Gran Sasso Laboratory showed a higher frequency of radiomimetic induced recombination as compared to those grown in the standard environment. This suggests that environmental radiation may act as a conditioning agent

Gamma response study of radiation sensitive MOSFETs for their use as gamma radiation sensor

Energy Technology Data Exchange (ETDEWEB)

Srivastava, Saurabh; Kumar, A. Vinod [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai (India); Aggarwal, Bharti; Singh, Arvind; Topkar, Anita, E-mail: anita@barc.gov.in [Electronics Division, Bhabha Atomic Research Centre, Mumbai (India)

2016-05-23

Continuous monitoring of gamma dose is important in various fields like radiation therapy, space-related research, nuclear energy programs and high energy physics experiment facilities. The present work is focused on utilization of radiation-sensitive Metal-Oxide-Semiconductor Field Effect Transistors (MOSFETs) to monitor gamma radiation doses. Static characterization of these detectors was performed to check their expected current-voltage relationship. Threshold voltage and transconductance per unit gate to source voltage (K factor) were calculated from the experimental data. The detector was exposed to gamma radiation in both, with and without gate bias voltage conditions, and change in threshold voltage was monitored at different gamma doses. The experimental data was fitted to obtain equation for dependence of threshold voltage on gamma dose. More than ten times increase in sensitivity was observed in biased condition (+3 V) compared to the unbiased case.

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

International Nuclear Information System (INIS)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-01-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5–20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10 −2 , 1.48×10 −2 , 4.14×10 −2 , and 6.03×10 −2 , 9.44×10 −2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose. - Highlights: • Radiation sensitivity of gallic acid and its esters were studied in intermediate and low radiation dose range using EPR. • While the irradiated samples of GA were presented complex EPR spectra the esters presented singlet ESR spectra. • Samples were compared to alanine in terms of the dosimetric point of view. • The radiation sensitivities of the investigated materials were very low at intermediate doses. • Lauryl ester of gallic acid was found to present a good sensitivity below 10 Gy

A yeast mutant specifically sensitive to bifunctional alkylation

International Nuclear Information System (INIS)

Ruhland, A.; Kircher, M.; Wilborn, F.; Brendel, M.

1981-01-01

A mutation that specifically confers sensitivity to bi- and tri-functional alkylating agents is presented. No or little cross-sensitivity to radiation or monofunctional agents could be detected. Sensitivity does not seem to be due to preferential alkylation of mutant DNA as parent and mutant strain exhibit the same amount of DNA alkylation and the same pattern of DNA lesions including interstrand crosslinks. The mutation is due to a defect in a nuclear gene which has been designated SNM1 (sensitive to nitrogen mustard); it may control an important step in the repair of DNA interstrand crosslinks (orig.(AJ)

Sensitivity of pathogenic and free-living Leptospira spp. to UV radiation and mitomycin C

International Nuclear Information System (INIS)

Stamm, L.V.; Charon, N.W.

1988-01-01

The habitats for the two major Leptospira spp. differ. The main habitat of L. biflexa is soil and water, whereas L. interrogans primarily resides in the renal tubules of animals. We investigated whether these two species, along with L. illini (species incertae sedis), differ with respect to their sensitivity to UV radiation. The doses of UV resulting in 37, 10 and 1% survival were determined for representive serovars from each species. L. interrogans serovar pomona was 3.0 to 4.8 times more sensitive to UV than the other Leptospira species under the 37, 10, and 1% survival parameters. In comparison to other bacteria, L. interrogans serovar pomona is among the most sensitive to UV. In a qualitative UV sensitivity assay., L. interrogans serovars were found to be in general more sensitive than L. biflexa serovars. All three species were found to have a photoreactivation DNA repair mechanism. Since organisms that are resistant to UV are often resistant to the DNA cross-linking agent mitomycin C, we tested the relative sensitivity of several Leptospira serovars to this compound. With few exceptions, L. biflexa and L. illini serovars were considerably more resistant to mitomycin C than the L. interrogans serovars. The mitomycin C sensitivity assay could be a useful addition to current characterization tests used to differentiate the Leptospira species

Sensitivity of pathogenic and free-living Leptospira spp. to UV radiation and mitomycin C

Energy Technology Data Exchange (ETDEWEB)

Stamm, L.V.; Charon, N.W.

1988-03-01

The habitats for the two major Leptospira spp. differ. The main habitat of L. biflexa is soil and water, whereas L. interrogans primarily resides in the renal tubules of animals. We investigated whether these two species, along with L. illini (species incertae sedis), differ with respect to their sensitivity to UV radiation. The doses of UV resulting in 37, 10 and 1% survival were determined for representive serovars from each species. L. interrogans serovar pomona was 3.0 to 4.8 times more sensitive to UV than the other Leptospira species under the 37, 10, and 1% survival parameters. In comparison to other bacteria, L. interrogans serovar pomona is among the most sensitive to UV. In a qualitative UV sensitivity assay., L. interrogans serovars were found to be in general more sensitive than L. biflexa serovars. All three species were found to have a photoreactivation DNA repair mechanism. Since organisms that are resistant to UV are often resistant to the DNA cross-linking agent mitomycin C, we tested the relative sensitivity of several Leptospira serovars to this compound. With few exceptions, L. biflexa and L. illini serovars were considerably more resistant to mitomycin C than the L. interrogans serovars. The mitomycin C sensitivity assay could be a useful addition to current characterization tests used to differentiate the Leptospira species.

Sensitivity of transient synchrotron radiation to tokamak plasma parameters

International Nuclear Information System (INIS)

Fisch, N.J.; Kritz, A.H.

1988-12-01

Synchrotron radiation from a hot plasma can inform on certain plasma parameters. The dependence on plasma parameters is particularly sensitive for the transient radiation response to a brief, deliberate, perturbation of hot plasma electrons. We investigate how such a radiation response can be used to diagnose a variety of plasma parameters in a tokamak. 18 refs., 13 figs

In vitro method determing sensitivity of anticancer agents by incorporation of radioactive precursors

International Nuclear Information System (INIS)

Sakakibara, Satoshi

1983-01-01

A new sensitivity test of anticancer agents was developed to measure the lethal effects of cancer cells by the incorporation of radioactive precursors. The thousand cancer cells were cultured in a microplate in the presence of anticancer agents. These cells were exposed to radioactive precursors. Two or three days later, the cancer cells were harvested on a glass fiver filter by a multiple automatic cell-harvester and the incorporation of precursors was counted by a liquid scintillation counter. In this study, the in vivo results of drug testing in animal model systems were compared with drug sensitivities. Mice inoculated Ehrlich ascites cells were treated with various kinds of anticancer drugs. The development of the cells was compatible with the result of the sensitivity test. The growths of Lauson and ME-180 cells derived from human cancers implanted subcutaneously to nude mice were also well correlated with this sensitivity test. (author)

Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden.

Science.gov (United States)

Lope, Virginia; Pérez-Gómez, Beatriz; Aragonés, Nuria; López-Abente, Gonzalo; Gustavsson, Per; Plato, Nils; Zock, Jan-Paul; Pollán, Marina

2008-11-01

This study sought to identify occupations with high incidence of multiple myeloma and to investigate possible excess risk associated with occupational exposure to chemicals and sensitizing agents in Sweden. A historical cohort of 2,992,166 workers was followed up (1971--1989) through record linkage with the National Cancer and Death Registries. For each job category, age and period standardized incidence ratios and age and period adjusted relative risks of multiple myeloma were calculated using Poisson models. Exposure to chemicals and to sensitizing agents was also assessed using two job-exposure matrices. Men and women were analyzed separately. During follow-up, 3,127 and 1,282 myelomas were diagnosed in men and women, respectively. In men, excess risk was detected among working proprietors, agricultural, horticultural and forestry enterprisers, bakers and pastry cooks, dental technicians, stone cutters/carvers, and prison/reformatory officials. In women, this excess was observed among attendants in psychiatric care, metal workers, bakers and pastry cooks, and paper/paperboard product workers. Workers, particularly bakers and pastry cooks, exposed to high molecular weight sensitizing agents registered an excess risk of over 40% across the sexes. Occasional, although intense, exposure to pesticides was also associated with risk of myeloma in our cohort. Our study supports a possible etiologic role for farming and use of pesticides in myeloma risk. The high incidence found in both female and male bakers and pastry cooks has not been described previously. Further research is required to assess the influence of high molecular weight sensitizing agents on risk of multiple myeloma.

Plastic for indicating a radiation dose

International Nuclear Information System (INIS)

Hori, Y.; Yoshikawa, N.; Ohmori, S.

1975-01-01

A plastic film suitable for indicating radiation dose contains a chlorine polymer, at least one acid sensitive coloring agent and a plasticizer. The film undergoes a distinct change of color in response to a given radiation dose, the degree of change proportional to the total change. These films may be stored for a long period without loss of sensitivity, and have good color stability after irradiation. (auth)

Quantitation of MRI sensitivity to quasi-monodisperse microbubble contrast agents for spatially resolved manometry.

Science.gov (United States)

Bencsik, Martin; Al-Rwaili, Amgad; Morris, Robert; Fairhurst, David J; Mundell, Victoria; Cave, Gareth; McKendry, Jonathan; Evans, Stephen

2013-11-01

The direct in-vivo measurement of fluid pressure cannot be achieved with MRI unless it is done with the contribution of a contrast agent. No such contrast agents are currently available commercially, whilst those demonstrated previously only produced qualitative results due to their broad size distribution. Our aim is to quantitate then model the MR sensitivity to the presence of quasi-monodisperse microbubble populations. Lipid stabilised microbubble populations with mean radius 1.2 ± 0.8 μm have been produced by mechanical agitation. Contrast agents with increasing volume fraction of bubbles up to 4% were formed and the contribution the bubbles bring to the relaxation rate was quantitated. A periodic pressure change was also continuously applied to the same contrast agent, until MR signal changes were only due to bubble radius change and not due to a change in bubble density. The MR data compared favourably with the prediction of an improved numerical simulation. An excellent MR sensitivity of 23 % bar(-1) has been demonstrated. This work opens up the possibility of generating microbubble preparations tailored to specific applications with optimised MR sensitivity, in particular MRI based in-vivo manometry. Copyright © 2012 Wiley Periodicals, Inc.

Radiation-curable impregnating agents for the conservation of archaeologic wooden objects. Part 2

International Nuclear Information System (INIS)

Schaudy, R.; Wendrinsky, J.; Kalteis, H.; Grienauer, W.

1982-12-01

As a continuation of the work described in OEFZS Ber. No. 4165, impregnating agents curable by ionizing radiation, such as free radical polymerizable monomers or artificial resins, have been investigated. Specific weight and viscosity of the liquid mixtures have been as well determined as the specific weight and gel content of the gamma radiation-cured samples. Hardness and elastic behaviour have been estimated only. The shrinkage during hardening was found to be 5 to 12 % for low viscous mixtures (up to 600 mPa.s) and 3 to 8 % for higher viscous impregnating agents. The results are to be discussed. (Author) [de

Characterization of new radiation-sensitive mutant, Escherichia coli K-12 radC102

International Nuclear Information System (INIS)

Felzenszwalb, I.; Sargentini, N.J.; Smith, K.C.

1984-01-01

A new radiation-sensitive mutant, radC, has been isolated. The radC gene is located at 81.0 min on the Escherichia coli K-12 linkage map. The radC mutation sensitized cells to uv radiation, but unlike most DNA repair mutations, sensitization to X rays was observed only for rich medium-grown cells. For cells grown in rich medium, the radC mutant was normal for γ radiation mutagenesis, but showed less uv-radiation mutagenesis than the wild-type strain; it showed normal amount of X- and uv-radiation-induced DNA degradation, and it wasapprox. =60% deficient in recombination ability. The radC strain was normal for host cell reactivation of γ and uv-irradiated bacteriophage the radC mutation did not sensitize a recA strain, but did sensitize a radA and a polA strain to X and uv radiation and a uvrA strain to uv radiation. Therefore, it is suggested that the radC gene product plays a role in the growth medium-dependent, recA gene-dependent repair of DNA single-strand breaks after X irradiation, and in postreplication repair after uv irradiation

WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Callens, M; Verboven, E; Van Den Abeele, K [Department of Physics, Wave Propagation and Signal Processing, KU Leuven KULAK, Kortrijk (Belgium); D’Agostino, E [DoseVue NV, Hasselt (Belgium); Pfeiffer, H [Department of Materials Engineering, KU Leuven, Leuven (Belgium); D’hooge, J [Department of Cardiovascular Sciences, Bio-Medical Science Group, KU Leuven, Leuven (Belgium)

2015-06-15

Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at the location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are

Cross-sensitivity of X-ray-hypersensitive cells derived from LEC strain rats to DNA-damaging agents

International Nuclear Information System (INIS)

Okui, T.; Endoh, D.; Arai, S.; Isogai, E.; Hayashi, M.

1996-01-01

The cross-sensitivity of X-ray-hypersensitive lung fibroblasts from LEC strain (LEC) rats to other DNA-damaging agents was examined. The LEC cells were 2- to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks, and to a cross-linking agent, mitomycin C, than the cells from WKAH strain (WKAH) rats, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine, but not to UV-irradiation. Although no difference was observed in the initial yields of DNA double-strand breaks induced by BLM between LEC and WKAH cells, the repair process of DNA double-strand breaks was significantly slower in LEC cells than in WKAH cells

Epicatechin stimulates mitochondrial activity and selectively sensitizes cancer cells to radiation.

Directory of Open Access Journals (Sweden)

Hosam A Elbaz

Full Text Available Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (--epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (--epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and Western blot analyses. (--Epicatechin stimulated mitochondrial respiration and oxygen consumption in Panc-1 cells. Human normal fibroblasts were not affected. (--Epicatechin sensitized Panc-1, U87, and MIA PaCa-2 cells with an average radiation enhancement factor (REF of 1.7, 1.5, and 1.2, respectively. (--Epicatechin did not sensitize normal fibroblast cells to ionizing radiation with a REF of 0.9, suggesting cancer cell selectivity. (--Epicatechin enhanced Chk2 phosphorylation and p21 induction when combined with radiation in cancer, but not normal, cells. Taken together, (--epicatechin radiosensitized cancer cells, but not normal cells, and may be a promising candidate for pancreatic cancer treatment when combined with radiation.

Toxic agent and radiation control: meeting the 1990 objectives for the nation

International Nuclear Information System (INIS)

Rall, D.P.

1984-01-01

Toxic agent and radiation control is 1 of the 15 health priority areas addressed through the Public Health Service's Objectives for the Nation. Several gains in moving toward the 1990 goals for toxic agent and radiation control have been recorded. Research and technical assistance, combined with legislation to reduce the amount of lead in gasoline, have contributed to a decrease in the mean blood lead level of the general population. New testing procedures have been developed to evaluate both reproductive and developmental toxicities of chemicals. Educational implementation of pelvimetry referral criteria in a multiyear study involving approximately 200 U.S. hospitals has resulted in a 50 percent reduction in the number of pelvimetries performed. Health-related responses have been given to environmental problems such as exposures to polychlorinated biphenyls (PCBs) in Massachusetts and Florida and exposures to dioxin in Missouri and New Jersey. Chemical records for some 1000 compounds likely to occur in chemical dumps or in bulk transit are being either created or updated to enhance online data retrieval services. For the foreseeable future, however, improvement of knowledge of the potential health risk posed by toxic chemicals and radiation must remain one of the most important priorities. To control toxic agents, development of surveillance systems and data bases are equally important

Interactions of radiation with novel chemotherapeutic agents: Taxanes and nucleoside analogs

International Nuclear Information System (INIS)

Milas, Luka

1997-01-01

The combination of chemotherapeutic agents and radiotherapy is an appealing approach to improving the results of cancer treatment. By their independent action or interactive action chemotherapeutic drugs reduce cell burden in tumors undergoing radiotherapy, thereby increasing the chances of tumor control. In addition, the drugs may spatially cooperate with radiotherapy through their systemic action on metastatic disease. Recently, a number of new chemotherapeutic agents have been introduced for cancer treatment, which in addition have high potential to increase therapeutic ratio of radiotherapy. These agents include taxanes (paclitaxel and docetaxel) and the nucleoside analogs fludarabine and gemcitabine. Paclitaxel is a natural product isolated from the bark of Taxus brevifolia and taxotere is a semisynthetic analogue of paclitaxel prepared from needle extracts of Taxus baccata. By binding to cellular tubulin structures, taxanes interfere with tubulin polymerization and promote microtubule assembly, resulting in accumulation of cells in the radiosensitive G2 and M phases of the cell cycle. In vivo studies have demonstrated two major mechanisms of tumor radioenhancement by taxanes: mitotic arrest and tumor reoxygenation. Fludarabine and gemcitabine inhibit DNA synthesis and the repair of radiation-induced chromosome breaks. The mechanism of their radioenhancing activity include inhibition of repair of radiation induced damage, apoptosis induction and cell cycle synchronization. Because both classes of these agents affect radioresponse of normal dose-limiting tissues much less than that of tumors, they can greatly increase therapeutic ratio of radiotherapy. The objective of this course is to overview the rationale for using these drugs as radioenhancing agents, the experimental findings in preclinical studies, the mechanisms of their interaction, and the clinical application of these agents

Uncertainty and Sensitivity Analysis of Afterbody Radiative Heating Predictions for Earth Entry

Science.gov (United States)

West, Thomas K., IV; Johnston, Christopher O.; Hosder, Serhat

2016-01-01

The objective of this work was to perform sensitivity analysis and uncertainty quantification for afterbody radiative heating predictions of Stardust capsule during Earth entry at peak afterbody radiation conditions. The radiation environment in the afterbody region poses significant challenges for accurate uncertainty quantification and sensitivity analysis due to the complexity of the flow physics, computational cost, and large number of un-certain variables. In this study, first a sparse collocation non-intrusive polynomial chaos approach along with global non-linear sensitivity analysis was used to identify the most significant uncertain variables and reduce the dimensions of the stochastic problem. Then, a total order stochastic expansion was constructed over only the important parameters for an efficient and accurate estimate of the uncertainty in radiation. Based on previous work, 388 uncertain parameters were considered in the radiation model, which came from the thermodynamics, flow field chemistry, and radiation modeling. The sensitivity analysis showed that only four of these variables contributed significantly to afterbody radiation uncertainty, accounting for almost 95% of the uncertainty. These included the electronic- impact excitation rate for N between level 2 and level 5 and rates of three chemical reactions in uencing N, N(+), O, and O(+) number densities in the flow field.

Multiparametric assessment of radiation effects for the individual radiation sensitivity estimation

International Nuclear Information System (INIS)

2006-01-01

The effects of low dose irradiation are highly relevant for radiation protection in the public. The sensitivity to clastogenic and tumorigenic effects of ionizing radiation (IR) varies considerably amongst individuals. Examples for genetically determined enhanced sensitivity are well known in some hereditary diseases: patients with chromosomal instability syndromes, Ataxia telangiectasia (A-T), Nijmegen Breakage Syndrome (NBS) and Bloom Syndrome (BS) show strongly enhanced sensitivity towards IR, severe immunodeficiencies, and a high incidence for developing leukemias and lymphomas. This obvious coincidence of enhanced radiosensitivity and tumor risk, and the frequently observed enhanced radiosensitivity of genetically non-defined tumor patients indicate that tumor patients may constitute a subpopulation with enriched genetical predisposition for enhanced radiosensitivity. Furthermore, a subpopulation of radiosensitive individuals may be part of the probably inconspicuous total population. For example, individuals heterozygous for the above mentioned genes (and possibly some other genes) show enhanced radiosensitivity if compared with the normal population. In general, heterozygous carriers of those hereditary deficiencies are clinically inconspicuous, but due an haploinsufficiency their tumour risk may be enhanced. This has been shown for mice carrying an heterozygous Nbs1 mutation (J.-Q. Wang, Lyon, pers. Communication). Our findings concerning enhanced radiation-induced chromosomal aberrations in heterozygous Nbs1 cell lines support this notion. The identification of high risk groups with enhanced radiosensitivity is therefore an important task for radioprotection. This project aimed at establishing a procedure which allows to test various cellular parameters as indicators for effects of radiation. A standard protocol for the isolation and cryoconservation of primary blood cells was developed. DNA repair analysis (Comet Assay) and radiation-induced apoptosis

Butyrate down regulates BCL-XL and sensitizes human fibroblasts to radiation and chemotherapy induced apoptosis

International Nuclear Information System (INIS)

Chung, Diana H.; Ljungman, Mats; Zhang Fenfen; Chen Feng; McLaughlin, William P.

1997-01-01

Purpose/Objective: Butyrate is a short chain fatty acid that has been implicated in the induction of cell cycle arrest, cell differentiation and apoptosis. The purpose of this study was to determine if butyrate treatment sensitizes cells to radiation or chemotherapy induced apoptosis. Materials and Methods: Normal neonatal human diploid fibroblasts were used throughout this study. Apoptosis was scored and quantified using three different methods. First, cell morphology using propidium iodide and fluorescence microscopy was used to qualitatively determine apoptosis and to quantify the percentage of cells undergoing apoptosis. Second, apoptosis induced DNA degradation was scored by quantifying the amount of cells appearing in a sub-G1 peak using fixed and PI-stained cells and flow cytometry. Third, apoptosis-induced DNA degradation was examined by using an assay involving direct lysis of cells in the wells of agarose gels followed by conventional gel electrophoresis. Western blotting was used to quantify the cellular levels of the apoptosis regulators, Bcl-2, Bcl-XL and Bax. Results: Human diploid fibroblasts, which were resistant to radiation induced apoptosis, were found to undergo massive apoptosis when radiation was combined with butyrate treatment. Sensitization was obtained when butyrate was added before or after radiation although the combination of both pre and post-treatment was the most effective. Butyrate was also found to enhance UV light and cisplatin-induced apoptosis. These findings correlated with a reduction of the apoptosis antagonist Bcl-XL. Bcl-XL levels significantly dropped in a time and dose dependent manner. In addition, butyrate effectively blocked UV-induced accumulation of p53. Conclusion: Our results suggest that butyrate may be an attractive agent to use in combination with radiation or chemotherapy to lower the apoptotic threshold of tumor cells, regardless of the p53 status of the tumor cells

Radiation-sensitive switching circuits

Energy Technology Data Exchange (ETDEWEB)

Moore, J.H.; Cockshott, C.P.

1976-03-16

A radiation-sensitive switching circuit has a light emitting diode which supplies light to a photo-transistor, the light being interrupted from time to time. When the photo-transistor is illuminated, current builds up and when this current reaches a predetermined value, a trigger circuit changes state. The peak output of the photo-transistor is measured and the trigger circuit is arranged to change state when the output of the device is a set proportion of the peak output, so as to allow for aging of the components. The circuit is designed to control the ignition system in an automobile engine.

Radiation-sensitive switching circuits

Energy Technology Data Exchange (ETDEWEB)

Moore, J.H.; Cockshott, C.P.

1976-03-16

A radiation-sensitive switching circuit includes a light emitting diode which from time to time illuminates a photo-transistor, the photo-transistor serving when its output reaches a predetermined value to operate a trigger circuit. In order to allow for aging of the components, the current flow through the diode is increased when the output from the transistor falls below a known level. Conveniently, this is achieved by having a transistor in parallel with the diode, and turning the transistor off when the output from the phototransistor becomes too low. The circuit is designed to control the ignition system in an automobile engine.

Ca2+ sensitizers: An emerging class of agents for counterbalancing weakness in skeletal muscle diseases?

Science.gov (United States)

Ochala, Julien

2010-02-01

Ca(2+) ions are key regulators of skeletal muscle contraction. By binding to contractile proteins, they initiate a cascade of molecular events leading to cross-bridge formation and ultimately, muscle shortening and force production. The ability of contractile proteins to respond to Ca(2+) attachment, also known as Ca(2+) sensitivity, is often compromised in acquired and congenital skeletal muscle disorders. It constitutes, undoubtedly, a major physiological cause of weakness for patients. In this review, we discuss recent studies giving strong molecular and cellular evidence that pharmacological modulators of some of the contractile proteins, also termed Ca(2+) sensitizers, are efficient agents to improve Ca(2+) sensitivity and function in diseased skeletal muscle cells. In fact, they compensate for the impaired contractile proteins response to Ca(2+) binding. Currently, such Ca(2+) sensitizing compounds are successfully used for reducing problems in cardiac disorders. Therefore, in the future, under certain conditions, these agents may represent an emerging class of agents to enhance the quality of life of patients suffering from skeletal muscle weakness. Copyright 2009 Elsevier B.V. All rights reserved.

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 vulcanization of natural rubber latex sensitized with commercial gases

International Nuclear Information System (INIS)

Chirinos, H.; Lugao, A.

2002-01-01

The industrial activities using natural rubber latex are fully compatible with rural areas in Amazon and other places in Brazil, as well as in other tropical countries. However the classical sulfur vulcanization presents many occupational problems for the workers in rural areas. Radiation vulcanization of natural rubber latex is a much more friendly process as sulfur compounds are not needed for crosslinking, although chemicals as acrylate monomers, particularly multifunctional acrylates are still used as sensitizers for radiation processes. Two commercial gases, acetylene and butadiene, were selected as sensitizers for the radiation vulcanization of natural rubber latex instead of acrylates. These gases accelerate the crosslinking rates of the cure process and lower the radiation dose required to achieve vulcanization of natural rubber latex and improve the mechanical properties to reduce the tackiness of rubber goods. (author)

Radiation vulcanization of natural rubber latex sensitized with commercial gases

Energy Technology Data Exchange (ETDEWEB)

Chirinos, H.; Lugao, A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

2002-07-01

The industrial activities using natural rubber latex are fully compatible with rural areas in Amazon and other places in Brazil, as well as in other tropical countries. However the classical sulfur vulcanization presents many occupational problems for the workers in rural areas. Radiation vulcanization of natural rubber latex is a much more friendly process as sulfur compounds are not needed for crosslinking, although chemicals as acrylate monomers, particularly multifunctional acrylates are still used as sensitizers for radiation processes. Two commercial gases, acetylene and butadiene, were selected as sensitizers for the radiation vulcanization of natural rubber latex instead of acrylates. These gases accelerate the crosslinking rates of the cure process and lower the radiation dose required to achieve vulcanization of natural rubber latex and improve the mechanical properties to reduce the tackiness of rubber goods. (author)

Modification of radiation damage by naturally occurring substances

International Nuclear Information System (INIS)

Prasad, K.N.

1984-01-01

The major objectives of studying the modification of radiation sensitivity have been (1) to identify a compound that will produce a differential protection or sensitization of the effect of irradiation on normal and tumor tissue, and (2) to understand more about the mechanisms of radiation damage. In spite of massive research on this particular problem since World War II, the first objective remains elusive. During this period, numerous radioprotective and radiosensitizing agents have been identified. These agents have served as important biologic tools for increasing our understanding of radiation injuries. Most of these substances are synthetic compounds and are very toxic to humans. In addition, very few of the compounds provide differential modifications of the effect of radiation on tumor and normal cells. This chapter presents objectives for identifying naturally occurring substances that modify the effect of x-radiation on mammalian cells and discusses the role of physiologic substances in modifying radiation injuries on mammalian normal and tumor cells

In vivo assay of the radiation sensitivity of hypoxic tumour cells. Influence of radiation quality and hypoxic sensitization

International Nuclear Information System (INIS)

Porschen, W.; Bosiljanoff, P.; Gewehr, K.; Muehlensiepen, H.; Feinendegen, L.E.

1977-01-01

In order to measure quantitatively tumour cell kinetics in living mice, tumour bearing animals (sarcoma-180) received intravenously 5-iodo-2'-deoxyuridine (IUdR), a thymidine analogue, which was labelled with 125 I or with 131 I, both of which can be easily externally counted by their gamma emission. IUdR is stably bound to DNA, reutilization is minimal and the measured activity loss from the tumour later than 50 hours after injection signals cell loss or cell death. The effect of irradiation on euoxic and average tumour cells was studied by sequentially labelling the tumour bearing animals first with 125 IUdR and, 70 hours later, with 131 IUdR. At the time of the second injection the average tumour cell population is labelled by the first injection of 125 IUdR, and the second injection of 131 IUdR nearly exclusively tags the perivascular tumour cells; these are euoxic in contrast to the average tumour cell, a large proportion of which is hypoxic. The radiation-induced activity loss rates from the two labelled tumour cell populations indicate the sensitivities of the two populations. At dose levels that cause identical effects on euoxic cells, the ratio of radiation-induced enhancement of cell loss rates for euoxic cells to average cells was 2.6 for 60 Co gamma radiation, 1.4 for 15MeV neutron irradiation, and 1.0 for alpha irradiation (1.5.MeV). The effect of five hypoxic cell sensitizers was analysed. The sensitization was limited to hypoxic cells, and the most effective drug was Ro-07-0582, showing at the 50% level of maximum effect a dose modifying factor of 1.5. Sensitization was highest when the drug was given 15 min prior to irradiation. Hyperthermia affected nearly exclusively hypoxic cells and showed a dose modifying factor of about 2 when the tumours were heated at 42 0 C for 30 min immediately after irradiation. The resulting enhancement of effect was reduced when hyperthermia was applied prior to irradiation. (author)

Biochemical reasoning for radiation protection and screening methods for radiation sensitivity and potential carcinogenicity

International Nuclear Information System (INIS)

Riklis, Emanuel; Emerit, Ingrid

1994-01-01

Cells of different genetic characteristics respond differently to agents that modify radiation effects. When the modification is a result of chemical repair, reduction of the amount of damage by radical scavenging, production of hypoxia, or any other such mechanism, then the modification of the response will be the same for all types of cells, but not the same when biological or biochemical parameters are involved, because the differences between the cells affect the final outcome, and the genetic traits obviously become affected by chemical modifying agents. Some of these agents directly affect the repair of deoxyribonucleic acid (DNA) by mechanisms not yet understood. Another agent nicotinamide (NA), is directly linked to a repair pathway. Thus, a system that uses NA as a precursor of nicotinamide adenine dinucleotide (NAD) + , and uses NAD + to produce the polymer polyadenosine diphosphate ribose (PADPR) appears to be an interesting and important factor in the biochemical events that may be linked to improved radioprotection. (author). 36 refs., 5 figs

Radiation curable pressure sensitive adhesive composition

International Nuclear Information System (INIS)

Steuben, K.C.

1978-01-01

Radiation curable pressure sensitive adhesive composition comprises: a polyoxyalkylene homo- or copolymer which is either a polyoxyethylene homopolymer or a poly (oxyethylene-oxypropylene) copolymer, or mixture thereof, having a molecular weight of from 1,700 to 90,000, in which at least 40 percent by weight of the oxyalkylene units are oxyethylene units; a liquid carbamyloxy alkyl acrylate; and, optionally, a photoinitiator

Role of mitochondria in radiation sensitivity

International Nuclear Information System (INIS)

Indo, Hiroko; Tomita, Kazuo; Majima, Hideyuki; Matsui, Hirofumi; Ozawa, Toshihiko

2007-01-01

This paper describes mainly the role of mitochondrial (Mt) manganese superoxide dismutase (MnSOD) for deciding the radiation sensitivity of cells. The fact that Mt concerns with apoptosis has been shown by the finding that change in Mt membrane potential relates with the cell death. Mt has the electron transport system to yield the cellular energy molecule (ATP) and from which electrons are leaked out in 2-3%, a considerably large proportion in a cell. The electrons react with oxygen nearby to yield SO (O 2 ·- ), which in turn induces apoptosis through oxidation stress (OS). On the other hand, MnSOD is transported in Mt from cytoplasm and excludes the reactive oxygen species (ROS) like SO. Studies by MnSOD gene-deletion, knockout, cDNA-transfection, and transgenesis have indicated MnSOD is essential for keeping life and resistance to OS. Authors have shown that overexpression of Mt MnSOD protects against radiation-induced cell death, suggesting that Mt participates in radiation sensitivity where SO is involved. Interestingly, MnSOD activity is low in cancer cells, its overexpression results in tumor suppression and MnSOD is a target in leukemia therapy. When MTS (Mt targeting sequence, necessary for the enzyme to enter Mt)-deleted MnSOD is transfected, cells lack resistance to radiation, indicating the enzyme must be present in Mt. Mt DNA damage leading to electron transport system impairment is found to increase ROS, and to be reversed by the transfection of MnSOD gene. Studies of Mt DNA damage in cancer cells where aerobic glycolysis is actively operated, are currently in progress lively, and are thought to promote the development of diagnosis and treatment of cancer. (R.T.)

Radiation Chemistry Studies on Chemotherapeutic Agents

DEFF Research Database (Denmark)

Gohn, M.; Getoff, N.; Bjergbakke, Erling

1977-01-01

Adrenalin has been studied as a model radiation protective agent by means of pulse radiolysis in aqueous solutions. The rate constants for the reactions of adrenalin with e–aq and OH were determined : k(e–aq+ adr—NH+2)= 7.5 × 108 dm3 mol–1 s–1, k(e–aq+ adr—NH)= 2.5 × 108 dm3 mol–1 s–1, and k......(OH + adr)= 2.2 × 1010 dm3 mol–1 s–1(pH = 9.2). e–aq attacks the amino group by splitting off methylamine, whereas OH and O–aq lead to the formation of the corresponding adducts of the cyclohexadienyl type. OH radicals can also abstract an electron from an O– group at pH > 8....

On the instability effects in radiation-sensitive chalcogenide glasses

International Nuclear Information System (INIS)

Balitska, V.; Kovalskiy, A.; Shpotyuk, O.; Vakiv, M.

2007-01-01

The features of application of radiation-sensitive media based on chalcogenide glasses of As-Ge-S system for registration of high-energy γ-radiation are analysed. It is shown that compositional features of the observed time-instability effect should be taken into account in order to ensure a higher accuracy of the developed dosimeters

On the instability effects in radiation-sensitive chalcogenide glasses

Energy Technology Data Exchange (ETDEWEB)

Balitska, V. [Lviv State University for Vital Activity Safety, 35 Kleparivska str., Lviv, UA-79007 (Ukraine); Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); Kovalskiy, A. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); International Materials Institute for New Functionality in Glass, Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States); Shpotyuk, O. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); International Materials Institute for New Functionality in Glass, Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States)], E-mail: shpotyuk@novas.lviv.ua; Vakiv, M. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine)

2007-04-15

The features of application of radiation-sensitive media based on chalcogenide glasses of As-Ge-S system for registration of high-energy {gamma}-radiation are analysed. It is shown that compositional features of the observed time-instability effect should be taken into account in order to ensure a higher accuracy of the developed dosimeters.

The Visualization of Infrared Radiation Using Thermal Sensitive Foils

Science.gov (United States)

Bochnícek, Zdenek

2013-01-01

This paper describes a set of demonstration school experiments where infrared radiation is detected using thermal sensitive foils. The possibility of using standard glass lenses for infrared imaging is discussed in detail. It is shown that with optic components made from glass, infrared radiation up to 2.5 µm of wavelength can be detected. The…

Effect of ionizing radiation on properties of acrylic pressure sensitive adhesives

International Nuclear Information System (INIS)

Panta, P.P.; Zimek, Z.A.; Giuszewski, W.; Kowalewski, R.; Wojtynska, E.; Wnuk, A.

1998-01-01

Pressure-sensitive adhesives for technical application are widely produced. The biological properties of adhesives depend on the type of monomers used. The available literature data as experience of the authors of this study in the area of pressure-sensitive acrylic adhesive, polymers used in medicine, polymerisation in aqueous media, radiation sterilization, permit to make an assumption that it is possible to elaborate the technology of production of pressure-sensitive adhesives in aqueous emulsion for medical applications. Identification of phenomena influencing the adhesive properties, especially its adhesion, cohesion, tack and durability is of great importance. The control of polymer structure is performed by means of adequate selection of conditions of synthesis and parameters of radiation processing. The authors investigate the influence on the final products of such factors as the type and amount of monomers used, their mutual ratio, as well as the ratio monomers and the dose of ionising radiation. There is no available literature information concerning the investigation of resistance of acrylic emulsion adhesive to sterilisation by electron beam. It is known from unpublished research that some adhesives are resistant to radiation, while others undergo destruction. It probably depends on the composition of emulsion, specifically on the additives which modify adhesives. Simultaneous achievement of good cohesion and adhesion in the case of such types of pressure sensitive adhesives is very difficult pressure sensitive adhesives is very difficult

Characterization of the response of a human breast carcinoma cell line (T-47D) to radiation and chemotherapeutic agents

International Nuclear Information System (INIS)

Prager, A.; Ben-Hur, E.; Riklis, E.

1981-01-01

The response of a human breast carcinoma cell line (T-47D) to various antitumour agents, gamma irradiation, UV light and heat was studied, using the colony-forming ability technique. Combinations of radiation with drugs and heat were also tested. The resulting survival curves corresponded to one of five patterns: simple exponential, biphasic exponential, threshold exponential, exponential plateau and ineffectual. Whereas the cells were particularly sensitive to gamma irradiation, the response to UV light was normal. The patient from whom this cell line originated did not respond to METHOTREXATEsup(R) therapy. The in vitro results correlated with this observation. (author)

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

International Nuclear Information System (INIS)

Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R.

2006-01-01

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

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

Science.gov (United States)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-02-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

Sensitivity of surface temperature to radiative forcing by contrail cirrus in a radiative-mixing model

Directory of Open Access Journals (Sweden)

U. Schumann

2017-11-01

Full Text Available Earth's surface temperature sensitivity to radiative forcing (RF by contrail cirrus and the related RF efficacy relative to CO2 are investigated in a one-dimensional idealized model of the atmosphere. The model includes energy transport by shortwave (SW and longwave (LW radiation and by mixing in an otherwise fixed reference atmosphere (no other feedbacks. Mixing includes convective adjustment and turbulent diffusion, where the latter is related to the vertical component of mixing by large-scale eddies. The conceptual study shows that the surface temperature sensitivity to given contrail RF depends strongly on the timescales of energy transport by mixing and radiation. The timescales are derived for steady layered heating (ghost forcing and for a transient contrail cirrus case. The radiative timescales are shortest at the surface and shorter in the troposphere than in the mid-stratosphere. Without mixing, a large part of the energy induced into the upper troposphere by radiation due to contrails or similar disturbances gets lost to space before it can contribute to surface warming. Because of the different radiative forcing at the surface and at top of atmosphere (TOA and different radiative heating rate profiles in the troposphere, the local surface temperature sensitivity to stratosphere-adjusted RF is larger for SW than for LW contrail forcing. Without mixing, the surface energy budget is more important for surface warming than the TOA budget. Hence, surface warming by contrails is smaller than suggested by the net RF at TOA. For zero mixing, cooling by contrails cannot be excluded. This may in part explain low efficacy values for contrails found in previous global circulation model studies. Possible implications of this study are discussed. Since the results of this study are model dependent, they should be tested with a comprehensive climate model in the future.

CHEMICAL VAPOUR DEPOSITION FROM A RADIATION-SENSITIVE PRECURSOR

DEFF Research Database (Denmark)

2017-01-01

The present invention relates in one aspect to a method of depositing a thin film on a substrate by chemical vapour deposition (CVD) from a radiation-sensitive precursor substance. The method comprises the steps of: (i) placing the substrate in a reaction chamber of a CVD system; (ii) heating...... heating pulse followed by an idle period; (iii) during at least one of the idle periods, providing a pressure pulse of precursor substance inside the reaction chamber by feeding at least one precursor substance to the reaction chamber so as to establish a reaction partial pressure for thin film deposition...... is formed. According to a further aspect, the invention relates to a chemical vapour deposition (CVD) system for depositing a thin film onto a substrate using precursor substances containing at least one radiation sensitive species....

Guide for use of radiation-sensitive indicators. 2. ed.

International Nuclear Information System (INIS)

2002-01-01

This guide covers the use of radiation-sensitive indicators in radiation processing. These indicators may be labels, papers, inks or packaging materials which undergo a color change or become colored when exposed to ionizing radiation. The purpose of these indicators is to determine visually whether or not a product has been irradiated, rather than to measure different dose levels. Such materials are not dosimeters and should not be used as a substitute for proper dosimetry. Information about dosimetry systems for ionizing radiation is provided in other ASTM and ISO/ASTM documents (see ISO/ASTM Guide 51261

Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation

International Nuclear Information System (INIS)

Fuma, S.; Ishii, N.; Takeda, H.; Miyamoto, K.; Yanagisawa, K.; Ichimasa, Y.; Saito, M.; Kawabata, Z.; Polikarpov, G.G.

2003-01-01

The purpose of this study was an evaluation of the effect levels of various toxic agents compared with acute doses of ionizing radiation for the experimental model ecosystem, i.e., microcosm mimicking aquatic microbial communities. For this purpose, the authors used the microcosm consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Escherichia coli as a decomposer. Effects of aluminum and copper on the microcosm were investigated in this study, while effects of γ-rays, ultraviolet radiation, acidification, manganese, nickel and gadolinium were reported in previous studies. The microcosm could detect not only the direct effects of these agents but also the community-level effects due to the interspecies interactions or the interactions between organisms and toxic agents. The authors evaluated doses or concentrations of each toxic agent which had the following effects on the microcosm: (1) no effects; (2) recognizable effects, i.e., decrease or increase in the cell densities of at least one species; (3) severe effects, i.e., extinction of one or two species; and (4) destructive effects, i.e., extinction of all species. The resulting effects data will contribute to an ecological risk assessment of the toxic agents compared with acute doses of ionizing radiation

Radiation chemistry studies on chemotherapeutic agents

International Nuclear Information System (INIS)

Gohn, M.; Getoff, N.; Bjergbakke, E.

1977-01-01

Adrenalin has been studied as a model radiation protective agent by means of pulse radiolysis in aqueous solutions. The rate constants for the reactions of adrenalin with e - sub(aq) and OH were determined: k(e - sub(aq) + adr -NH + 2 ) = 7.5 x 10 8 dm 3 mol -1 s -1 , k(e - sub(aq) + adr - NH) = 2.5 x 10 8 dm 3 mol -1 s -1 , and k(OH + adr) = 2.2 x 10 -10 dm 3 mol -1 s -1 (pH = 9.2). e - sub(aq) attacks the amino group by splitting off methylamine, whereas OH and O - sub(aq) lead to the formation of the corresponding adducts of the cyclohexadienyl type. OH radicals can also abstract an electron from an 0 - group at pH > 8. (author)

[Variability of the sensitivity of human lymphocytes to the antiproliferative action of alkylating agents].

Science.gov (United States)

Veremko, L N; Telegin, L Iu; Pevnitskii, L A

1983-05-01

A study was made of variability of the sensitivity of peripheral blood lymphocytes from different donors to an antiproliferative action of cyclophosphamide and thiophosphamide. A similar degree of the sensitivity was revealed to alkylating agents differing in the action mode, with this degree being independent of the "stimulation index" magnitude.

Radiation sensitivity of T-lymphocytes from immunodeficient wasted mice

International Nuclear Information System (INIS)

Padilla, M.; Libertin, C.; Krco, C.; Woloschak, G.E.

1990-01-01

Mice with the autosomal recessive gene wasted (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thyl + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thyl + cells were observed. Furthermore, when cells were treated with gamma-rays in combination with Con A, Thyl + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies

Conservation experiments applying radiation-curable impregnating agents to intact and artifically decayed wood samples

International Nuclear Information System (INIS)

Schaudy, R.; Slais, E.

1983-02-01

Conservation experiments have been performed applying 10 selected impregnating agents to intact and chemically as well as biologically decayed wood samples. The quality of the radiation-curable impregnating agents could be valued by determination of the monomer uptake, the alteration of dimensions and volume and the deformation of the samples. The results are to be discussed. (Author) [de

Expression of Ku correlates with radiation sensitivities in the head and neck cancer cell lines

International Nuclear Information System (INIS)

Lee, Sang Wook; Yu, Eun Sil; Yi, So Lyoung; Son, Se Hee; Kim, Jong Hoon; Ahn, Seung Do; Shin, Seong Soo; Choi, Eun Kyung

2004-01-01

DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase consisting of a 470 kDa catalytic subunit (DNA-PKcs) and a heterodimeric regulatory complex, called Ku, which is composed of 70 kDa (Ku 70) and 86 kDa (Ku 80) proteins. The DNA-PK has been shown to play a pivotal role in rejoining DNA double-strand-breaks (dsb) in mammalian cells. The purpose of this study is to examine the relationship between the level of Ku expression and radiation sensitivity. Nine head and neck, cancer cell lines showed various intrinsic radiation sensitivities. Among the nine, AMC-HN-3 cell was the most sensitive for X-ray irradiation and AMC-HN-9 cell was the most resistance. The most sensitive and resistant cell lines were selected and the test sensitivity of radiation and expression of Ku were measured. Radiation sensitivity was obtained by colony forming assay and Ku protein expression using Western blot analysis. Ku80 increased expression by radiation, wheras Ku70 did not. Overexpression of Ku80 protein increased radiation resistance in AMC-HN9 cell line. There was a correlation between Ku80 expression and radiation resistance. Ku80 was shown to play an important role in radiation damage response. Induction of Ku80 expression had an important role in DNA damage repair by radiation. Ku80 expression may be an effective predictive assay of radiosensitivity on head and neck cancer

Changes in bacterial radiation sensitivity due to deuterium substitution

International Nuclear Information System (INIS)

Strauss, A.; Weiss, H.

1985-01-01

The influence of deuterium substitution for hydrogen on radiation sensitivity was measured under various conditions for E. coli B/r irradiated by 450 kev electrons in single intense pulses. Cells were grown in a nutrient medium made from a deuterium oxide based solution. They were suspended in a D/sub 2/O based buffered saline and plated in thin aqueous layers on membrane filters and irradiated in 100% N/sub 2/ or 100% O/sub 2/. Comparisons were made to cells similarly plated and irradiated but grown instead in a water based nutrient medium and suspended in either a water based or a D/sub 2/O based buffered saline. For the conventionally grown cells, D/sub 2/O increased the radiation sensitivity in both gases by about 10%. For cells grown and suspended with D/sub 2/O based media, a 50% reduction of radiation sensitivity was found with both gas and an increased extrapolation number was observed. In this latter method, deuterium is more fully substituted for hydrogen in the molecular substrate of the cell. These cells were also irradiated over a temperature range of 2 0 C to 43 0 C after being suspended in deuterated ethanol. Speculations for the changes induced by the substitution are presented

Synergism in mutations induction in Tradescantia by plants protection agents acting jointly with ionizing radiation

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Smagala, J.

1990-01-01

Tradescantia was first treated by plants protection agents such as: Ambusz, Afalton, Ripcord, Decis, deltametryne and after that irradiated with X radiation. The synergism of both factors was observed. The mutation frequency dependence on radiation doses was studied. 7 figs., 4 refs. (A.S.)

Genetic and epigenetic features in radiation sensitivity. Part I: Cell signalling in radiation response

International Nuclear Information System (INIS)

Bourguignon, Michel H.; Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di; Carosella, Edgardo D.

2005-01-01

Recent progress especially in the field of gene identification and expression has attracted greater attention to genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. It has been proposed that the occurrence and severity of the adverse reactions to radiation therapy are also influenced by such genetic susceptibility. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation offering a better likelihood of cure for malignant tumours. This paper, the first of two parts, reviews the main mechanisms involved in cell response to ionising radiation. DNA repair machinery and cell signalling pathways are considered and their role in radiosensitivity is analysed. The implication of non-targeted and delayed effects in radiosensitivity is also discussed. (orig.)

Highly sensitive microcalorimeters for radiation research

International Nuclear Information System (INIS)

Avaev, V.N.; Demchuk, B.N.; Ioffe, L.A.; Efimov, E.P.

1984-01-01

Calorimetry is used in research at various types of nuclear-physics installations to obtain information on the quantitative and qualitative composition of ionizing radiation in a reactor core and in the surrounding layers of the biological shield. In this paper, the authors examine the characteristics of highly sensitive microcalorimeters with modular semiconductor heat pickups designed for operation in reactor channels. The microcalorimeters have a thin-walled aluminum housing on whose inner surface modular heat pickups are placed radially as shown here. The results of measurements of the temperature dependence of the sensitivity of the microcalorimeters are shown. The results of measuring the sensitivity of a PMK-2 microcalorimeter assembly as a function of integrated neutron flux for three energy intervals and the adsorbed gamma energy are shown. In order to study specimens with different shapes and sizes, microcalorimeters with chambers in the form of cylinders and a parallelepiped were built and tested

Radiation and thermal characteristics of mouse lymphoma cells and their radiation-sensitive mutant

International Nuclear Information System (INIS)

Baba, Yuji; Yasunaga, Tadamasa; Uozumi, Hideaki; Takahashi, Mutsumasa; Sawada, Shozo.

1988-01-01

Radiation and thermal characteristics of L5178Y cells and their radiation-sensitive mutant M10 cells were studied by the colony-forming method and the dye-exclusion method using eosin-Y. Although M10 cells were remarkably radiation-sensitive compared with L5178Y cells, it was diffcult to cause interphase death of M10 after a large dose of irradiation. After heat treatments, L5178Y cells revealed more cell destruction and were stained well by eosin-Y, but it was relatively difficult to produce cell destruction of M10 cells, which showed poor staining by eosin-Y. When assayed by the colony-forming method, M10 cells were also heat-resistant compared to L5178Y. The dye-exclusion rate was closely correlated with cell survival after hyperthermia of L5178Y cells, suggesting that this is a simple method of detecting the thermosensitivity and thermotolerance of cancer cells. The difference in survival of L5178Y cells and M10 cells after combined treatment with gamma irradiation and hyperthermia was smaller than with gamma irradiation alone. It was also found that there was a relationship between radiation-induced interphase death and hyperthermia-induced interphase death, and that interphase death accounted for a major part of cell death caused by hyperthermia in mouse leukemia cells. (author)

Familial melanoma associated with dominant ultraviolet radiation sensitivity

International Nuclear Information System (INIS)

Ramsay, R.G.; Chen, P.; Imray, F.P.; Kidson, C.; Lavin, M.F.; Hockey, A.

1982-01-01

Sensitivity to ultraviolet radiation was studied in lymphoblastoid cell lines derived from 32 members of two families with histories of multiple primary melanomas in several generations. As assayed by colony formation in agar or by trypan blue exclusion following irradiation, cellular sensitivity showed a bimodal distribution. All persons with melanoma or multiple moles were in the sensitive group, while some family members exhibited responses similar to those of controls. Cells from four cases of sporadic melanoma showed normal levels of sensitivity. The data are consistent with a dominantly inherited ultraviolet light sensitivity associated with these examples of familial melanoma. Spontaneous and ultraviolet light-induced sister chromatid exchange frequencies were similar to those in control cell lines. No defect in excision repair was detected in any of the above cell lines, but the sensitive group showed postirradiation inhibition of DNA replication intermediate between controls and an excision-deficient xeroderma pigmentosum cell line

Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents

International Nuclear Information System (INIS)

Hohmann, J.; Albrecht, T.; Hoffmann, C.W.; Wolf, K.-J.

2003-01-01

Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet

Biological monitoring of radiation exposure

Science.gov (United States)

Horneck, G.

1998-11-01

Complementary to physical dosimetry, biological dosimetry systems have been developed and applied which weight the different components of environmental radiation according to their biological efficacy. They generally give a record of the accumulated exposure of individuals with high sensitivity and specificity for the toxic agent under consideration. Basically three different types of biological detecting/monitoring systems are available: (i) intrinsic biological dosimeters that record the individual radiation exposure (humans, plants, animals) in measurable units. For monitoring ionizing radiation exposure, in situ biomarkers for genetic (e.g. chromosomal aberrations in human lymphocytes, germ line minisatellite mutation rates) or metabolic changes in serum, plasma and blood (e.g. serum lipids, lipoproteins, lipid peroxides, melatonin, antibody titer) have been used. (ii) Extrinsic biological dosimeters/indicators that record the accumulated dose in biological model systems. Their application includes long-term monitoring of changes in environmental UV radiation and its biological implications as well as dosimetry of personal UV exposure. (iii) Biological detectors/biosensors for genotoxic substances and agents such as bacterial assays (e.g. Ames test, SOS-type test) that are highly sensitive to genotoxins with high specificity. They may be applicable for different aspects in environmental monitoring including the International Space Station.

Significance of genetic predisposition and genomic instability for individual sensitivity to radiation. Implications for radiation protection

International Nuclear Information System (INIS)

Heller, H.

2001-01-01

At its closed-door meeting on 20/21 January 2000 the Radiation Protection Committee dedicated much of its attention to the significance of genetic predisposition and genetic instability for individual radiation sensitivity and to the implication of this for radiation protection. The statements and contributions to the closing plenary discussion touched on many aspects of ethics, personal rights, occupational medicine and insurance issues relating to this subject, all of which extend far beyond the purely technical issues of radiation protection. The present volume contains the lecture manuscripts of the meeting as well as a summarising assessment by the Radiation Protection Committee [de

166Ho-chitosan as a radiation synovectomy agent - biocompatibility study of 166Ho-chitosan in rabbits

International Nuclear Information System (INIS)

Kim, Sug Jun; Lee, Soo Yong; Jeon, Dae Geun; Lee Jong Seok

1997-01-01

Radiation synovectomy is a noninvasive therapy that has been investigated as an alternative to surgical synovectomy. It is been successfully employed in the treatment of synovitis in rheumatoid arthrits and other inflammatory arthropathies. We developed the 166 Ho-chitosan complex for possible use as a radiation synovectomy agent. Holmium is the more practical isotope based on its higher radioactivity and logner half-life. And isotope based on its higher radioactivity and logner half-life. And chitosan is ideal and suitable particles based on its soluble and biodegradable characteristics. So we investigated the biocompatibility of the 166 Ho-chitosan complex to evaluated the suitability as a radiation synovectomy agent. In this study, we performed in vivo and in vitro stability test and biodistribution test. Our results indicate that 166 Ho-chitosan may be an effective radiopharmaceutical for radiation synovectomy. (author). 30 refs., 7 tabs

Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

Directory of Open Access Journals (Sweden)

Richard C Wang

Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

Energy Technology Data Exchange (ETDEWEB)

Northway, M.G.; Scobey, M.W.; Geisinger, K.R.

1988-11-01

Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man.

Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

International Nuclear Information System (INIS)

Northway, M.G.; Scobey, M.W.; Geisinger, K.R.

1988-01-01

Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man

Sensitivity of hyperthermia-treated human cells to killing by ultraviolet or gamma radiation

International Nuclear Information System (INIS)

Mitchel, R.E.; Smith, B.P.; Wheatly, N.; Chan, A.; Child, S.; Paterson, M.C.

1985-01-01

Human xeroderma pigmentosum (XP) or Fanconi anemia (FA) fibroblasts displayed shouldered 45 0 C heat survival curves not significantly different from normal fibroblasts, a result similar to that previously found for ataxia telangiectasia (AT) cells, indicating heat resistance is not linked to either uv or low-LET ionizing radiation resistance. Hyperthermia (45 0 C) sensitized normal and XP fibroblasts to killing by gamma radiation but failed to sensitize the cells to the lethal effects of 254 nm uv radiation. Thermal inhibition of repair of ionizing radiation lesions but not uv-induced lesions appears to contribute synergistically to cell death. The thermal enhancement ratio (TER) for the synergistic interaction of hyperthermia (45 0 C, 30 min) and gamma radiation was significantly lower in one FA and two strains (TER = 1.7-1.8) than that reported previously for three normal strains (TER = 2.5-3.0). These XP and FA strains may be more gamma sensitive than normal human fibroblasts. Since hyperthermia treatment only slightly increases the gamma-radiation sensitivity of ataxia telangiectasia (AT) fibroblasts compared to normal strains, it is possible that the degree of thermal enhancement attainable reflects the genetically inherent ionizing radiation repair capacity of the cells. The data indicate that both repair inhibition and particular lesion types are required for lethal synergism between heat and radiation. We therefore postulate that the transient thermal inhibition of repair results in the conversion of gamma-induced lesions to irrepairable lethal damage, while uv-type damage can remain unaltered during this period

DNA-nuclear matrix interactions and ionizing radiation sensitivity

International Nuclear Information System (INIS)

Schwartz, J.L.; Vaughan, A.T.M.

1993-01-01

The association between inherent ionizing radiation sensitivity and DNA supercoil unwinding in mammalian cells suggests that the organization of the DNA in chromosomes plays an important role in radiation responses. In this paper, a model is proposed which suggests that these DNA unwinding alterations reflect differences in the attachment of DNA to the nuclear matrix. In radioresistant cells, the MAR structure might exist in a more stable, open configuration, limiting DNA unwinding following strand break induction and influencing the rate and nature of DNA double-strand break rejoining

Clinical effect of Cystenosine on leukocytopenia at the time of therapy with radiation and antineoplastic agents

International Nuclear Information System (INIS)

Sato, Kazuhide; Usui, Ryu; Inoue, Hiroshi; Mihashi, Norio; Niibe, Hideo.

1977-01-01

Out of 62 cases, 25 cases received only radiotherapy, 11 cases received both radiotherapy and antineoplastic agents, and 26 cases received only antineoplastic agents. Total dose of x-ray ranges from 3000 to 6200 rad in 18 of 36 cases of the former two groups, and 2600 to 6260 rad of 60 Co dose were irradiated to 18 cases of the rest. This agent was administered 9 tablets per a day (one tablet contains 200 mg of inosine and 20 mg of cystine) for 19 to 142 days. Its effects on leukocytopenia showed marked effectiveness in 9 out of 25 cases treated with only radiation, effectiveness in 8 cases, and ineffectiveness in 3 cases. Its effective rate was 72.8%. The effective rate was 65.4% in the cases treated with only antineoplastic agents, and was 67.7% in all cases. A certain relationship between dose and the effective rate was not recognized. Radiation sickness, such as loss of appetite general fatigue and mausea, decreased gradually by using this agent. Side effect was not recognized particularly. (Kanao. N.)

Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

Science.gov (United States)

Ayars, Michael; Eshleman, James; Goggins, Michael

2017-05-19

Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.

Study on intraoperative radiotherapy applying hyperthermia together with radiation sensitizers for progressive local carcinoma

Energy Technology Data Exchange (ETDEWEB)

Abe, M; Takahashi, M; Ono, K; Hiraoka, M [Kyoto Univ. (Japan). Faculty of Medicine

1980-08-01

Intraoperative radiotherapy for gastric cancer, colonic cancer, pancreatic cancer, cancer of the biliary tract, prostatic carcinoma, cerebral tumor, tumor of soft tissues, and osteosarcoma and its clinical results were described. Basic and clinical studies on effects of both hyperthermia and radiation sensitizers to elevate radiation sensitivity were also described, because effects of intraoperative radiotherapy were raised by applying hyperthermia and hypoxic cell sensitizers.

Radiation polymerized hot melt pressure sensitive adhesives

International Nuclear Information System (INIS)

Pastor, S.D.; Skoultchi, M.M.

1977-01-01

Hot melt pressure sensitive adhesive compositions formed by copolymerizing at least one 3-(chlorinated aryloxy)-2-hydroxypropyl ester of an alpha, beta unsaturated carboxylic acid with acrylate based copolymerizable monomers, are described. The resultant ethylenically saturated prepolymer is heated to a temperature sufficient to render it fluid and flowable. This composition is coated onto a substrate and exposed to ultraviolet radiation

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

Reduction of radiation injury of fresh agricultural products by saccharide

International Nuclear Information System (INIS)

Hayashi, Toru; Todoroki, Setsuko

1998-01-01

To establish irradiation technologies as one of alternative technology of methyl bromide fumigation, radiation sensitivities for each kind of fresh agricultural products and reduction of radiation injury were investigated. Fresh vegetables and flowers such as cabbage, sprouts, asparagus, lettuce, chrysanthemum, carnation, rose, etc. were used and irradiated with 750 Gy γ-ray. Flowers received radiation injury were soaked into various kinds of solutions for one night, then they were irradiated with 500 Gy γ-ray. They showed different radiation sensitivities. Cruciferae plant showed radioresistance and Compositae plant radiosensitivity. A keeping quality agent for cut flowers indicated protection effect on radiation injury. (S.Y.)

Reduction of radiation injury of fresh agricultural products by saccharide

Energy Technology Data Exchange (ETDEWEB)

Hayashi, Toru; Todoroki, Setsuko [National Food Research Inst., Tsukuba, Ibaraki (Japan)

1998-02-01

To establish irradiation technologies as one of alternative technology of methyl bromide fumigation, radiation sensitivities for each kind of fresh agricultural products and reduction of radiation injury were investigated. Fresh vegetables and flowers such as cabbage, sprouts, asparagus, lettuce, chrysanthemum, carnation, rose, etc. were used and irradiated with 750 Gy {gamma}-ray. Flowers received radiation injury were soaked into various kinds of solutions for one night, then they were irradiated with 500 Gy {gamma}-ray. They showed different radiation sensitivities. Cruciferae plant showed radioresistance and Compositae plant radiosensitivity. A keeping quality agent for cut flowers indicated protection effect on radiation injury. (S.Y.)

Radiation, hypoxia and genetic stimulation: implications for future therapies

International Nuclear Information System (INIS)

Adams, Gerald E.; Hasan, Na'il M.; Joiner, Michael C.

1997-01-01

The cellular stress response, whereby very low doses of cytotoxic agents induce resistance to much higher doses, is an evolutionary defence mechanism and is stimulated following challenges by numerous chemical, biological and physical agents including particularly radiation, drugs, heat and hypoxia. There is much homology in the effects of these agents which are manifest through the up-regulation of various genetic pathways. Low-dose radiation stress influences processes involved in cell-cycle control, signal transduction pathways, radiation sensitivity, changes in cell adhesion and cell growth. There is also homology between radiation and other cellular stress agents, particularly hypoxia. Whereas traditionally, hypoxia was regarded mainly as an agent conferring resistance to radiation, there is now much evidence illustrating the cytokine-like properties of hypoxia as well as radiation. Stress phenomena are likely to be important in risks arising from low doses of radiation. Conversely, exploitation of the stress response in settings appropriate to therapy can be particularly beneficial not only in regard to radiation alone but in combinations of radiation and drugs. Similarly, tissue hypoxia can be exploited in novel ways of enhancing therapeutic efficacy. Bioreductive drugs, which are cytotoxically activated in hypoxic regions of tissue, can be rendered even more effective by hypoxia-induced increased expression of enzyme reductases. Nitric oxide pathways are influenced by hypoxia thereby offering possibilities for novel vascular based therapies. Other approaches are discussed

Sensitivity of radiation methods of diagnosis of electric potentials in dielectric materials

International Nuclear Information System (INIS)

Sapozhkov, Yu.I.; Smekalin, L.F.; Yagushkin, N.I.

1985-01-01

On the base of the albedo method the characteristics of radiation methods of diagnosis of electric potentials inside dielectrics, such as sensitivity and resolution are considered. Investigations are carried out for electron energies of tens keV. It is shown that with energy growth the sensitivity to electric field in the dielectrics volume drops. The target atomic number growth reduces the sensitivity approximately 1/lnz. The albedo method resolution in the investigated energy range is constant. The results obtained testify to the usability radiation methods of the diagnosis for control of electric fields of dielectric structural materials in the course of their operation

Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

International Nuclear Information System (INIS)

Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

1987-01-01

This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation

Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

Energy Technology Data Exchange (ETDEWEB)

Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

1987-01-01

This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation.

Radiation-sensitive compounds and methods of using same

International Nuclear Information System (INIS)

DeMajistre, R.

1977-01-01

Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysis to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials

Gamma radiation induced sensitization and photo-transfer in Mg2SiO4:Tb TLD phosphor

International Nuclear Information System (INIS)

Lakshmanan, A.R.; Vohra, K.G.

1979-01-01

Mg 2 SiO 4 :Tb TLD phosphor was found to show enhanced TL sensitivity to both gamma and UV radiations after high pre-gamma exposures (>100 R) and a post-annealing treatment at 300 0 C for 1 h. Maximum sensitization factors of 2.8 and 55 were obtained at the pre-expsoure levels of 5.2x10 1 C/kg and 1.3x10 3 C/kg for gamma and UV test radiations respectively. The near constancy of the intensity of the residual TL (RTL) peak at 500 0 C for the sensitized sample with increasing test-gamma exposures has ruled out the re-trapping model proposed earlier for the gamma radiation induced sensitization in this phosphor. The Tsub(max) for the sensitized phosphor was found to occur at a higher temperature compared to that for the virgin phosphor. The dependence of sensitization on RTL was explained qualitatively on the basis of competition between sensitization traps (having higher energy than the dosimetry traps) and RTL traps while capturing the charge carriers generated during the test-gamma exposure. The sensitization observed in this phosphor to UV test radiation was found to be a consequence of the photo-transfer of charge carriers from deep (RTL) traps to the shallow (dosimetry) traps. The reduction in RTL peak (500 0 C) intensity of the sensitized sample with increasing test-UV exposure has demonstrated the photo-transfer mechanism in this phosphor. The TL response of the virgin Mg 2 SiO 4 :Tb phosphor was found to be supralinear to both gamma and UV radiations. The TL response of the sensitized phosphor was found to be linear to gamma radiation and sublinear to UV radiation. (Auth.)

DNA-nuclear matrix interactions and ionizing radiation sensitivity

International Nuclear Information System (INIS)

Schwartz, J.L.; Chicago Univ., IL; Vaughan, A.T.M.

1993-01-01

The association between inherent ionizing radiation sensitivity and DNA supercoil unwinding in mammalian cells suggests that the DNA-nuclear matrix attachment region (MAR) plays an important role in radiation response. In radioresistant cells, the MAR structure may exist in a more stable, open configuration, limiting DNA unwinding following strand break induction and maintaining DNA ends in close proximity for more rapid and accurate rejoining. In addition, the open configuration at these matrix attachment sites may serve to facilitate rapid DNA processing of breaks by providing (1) sites for repair proteins to collect and (2) energy to drive enzymatic reactions

Mechanisms of UVB-resistance in rice: Cultivar differences in the sensitivity to UVB radiation in rice

International Nuclear Information System (INIS)

Hidema, J.

2001-01-01

In a study on the sensitivity to UVB radiation of rice cultivars of 5 Asian rice ecotypes, results showed that the rice cultivars widely varied in UVB sensitivity; among the Japanese rice cultivars, Sasanishiki was more resistant to UVB, while Norin 1 was less resistant; UV-sensitive Norin 1 was deficient in photorepair of cyclobutane pyrimidine dimers (UV-induced DNA damage), and the sensitivity to UVB radiation significantly correlated with deficient CPD photorepair; and that this deficiency in Norin 1 resulted from a functionally altered photolyase. The results suggest that photorepair capacity is a principal factor in determining UVB sensitivity in rice. The effects of supplemental UVB radiation on the growth and yield of Japanese rice cultivars under field conditions were also studied in Japan since 1993. The results indicate that supplemental UVB radiation had inhibitory effects on the growth and yield of rice. Furthermore, grain size was smaller with supplemental UVB radiation

Improvements to a neutral radiation detection and position sensitive process and devices

International Nuclear Information System (INIS)

Charpak, Georges; Nguyen, N.H.; Policarpo, Armando.

1977-01-01

This invention aims to provide a neutral radiation position sensitive process and device providing a spatial radiation satisfactory for most medical applications and an energy radiation that cannot be reached by gas detectors based on proportional counters or by scintillation counters. Only solid state detectors can compete with respect to energy resolution. The detector described enables large areas to be covered which cannot be reached at accessible costs by solid state detectors. With this aim in view, the invention suggests an incident neutral radiation and position sensitive process, particularly soft gamma and X radiations, whereby photoelectrons are made to form by incident radiation action on gas atoms contained in an enclosure. By means of an electric field, the electrons are diverted towards a space undergoing an electric field high enough in value to create photons by exciting gas atoms and returning them to the de-excited state. The photons are collected, through a transparent window, on a layer of a material for converting such photons into scintillations in the near or visible UV spectrum and the barycentre of the scintillations is positioned on the layer, for instance by photomultipliers or ionization detectors. According to another aspect of the invention, it suggests a detection and position sensitive device comprising (generally downstream of a collimator with a grid of inlet holes) a leak tight containment fitted with an inlet window transparent to incident radiations, filled with a gas producing electrons by interaction with the incident radiation, and fitted with electrodes for generating an electric field to divert the electrons to a space for creating secondary photons [fr

The sensitivity testing of Wilms' tumors to cytostatic agents with an autoradiographic in vitro short-term test

International Nuclear Information System (INIS)

Willnow, U.

1984-01-01

Sensitivity of 15 Wilms' tumors in children was tested towards cytostatic agents in vitro by means of an autoradiographic short-term test. Sensitivity was measured as the magnitude of the inhibition of 3 H-thymidine or 3 H-uridine incorporation. The test was performed with Adriamycin, Actinomycin D, Daunomycin, Bleomycin, Cyclophosphamide, Ifosfamide, Trenimon, and Arabinosylcytosine. None of the tumors is resistant to all substances, they are responsive against 2 or more drugs. The most effective drugs tested are Adriamycin, Actinomycin D and Cyclophosphamide. The tumors show a marked individual sensitivity pattern. This behavior is explained mainly by the usually high proliferative activity of Wilms' tumors. The possibilities and limits of long-term and short-term methods for sensitivity testing are discussed critically. For the evaluation of the results of in vitro testing and in vivo effectiveness the close correlation should be considered between the type of cytostatic agent and proliferation kinetics of the tumor, cytostatic agent and effect on tumor metabolism as well as the effect of the cytostatics and the nucleic acid precursors used for the short-term test. Despite the methodological limitations preclinical testing should be preferred to unselected chemotherapy. (author)

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.

In vitro sensitivity of Trichomonas vaginalis and Candida albicans to chemotherapeutic agents.

Science.gov (United States)

Lövgren, T; Salmela, I

1978-06-01

Strains of fresh clinical isolates of Trichomonas vaginalis and Candida albicans have been tested in vitro for their sensitivity to eight drugs used in the therapy of monilial and trichomonal vaginitis. Three of the chemotherapeutic agents, chlorchinaldol, clotrimazole and broxyquinoline were effective against both organisms. Tinidazole and metronidazole were active against T. vaginalis. The strains of C. albicans were also sensitive to trichomycin, natamycin and nystatin. Tinidazole was the most effective trichomonacide, clotrimazole and chlorchinaldol were most effective against C. albicans, while chlorchinaldol had the best in vitro effect against both organisms. The ranges of the MICs are compared to values previously reported.

Sea urchin coelomocytes are resistant to a variety of DNA damaging agents

International Nuclear Information System (INIS)

Loram, Jeannette; Raudonis, Renee; Chapman, Jecar; Lortie, Mae; Bodnar, Andrea

2012-01-01

Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H 2 O 2 ), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD 50 values determined for coelomocytes after 24 h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H 2 O 2 , MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.

Gamma radiation effect on sisal / polyurethane composites without coupling agents

Energy Technology Data Exchange (ETDEWEB)

Vasco, Marina Cardoso; Claro Neto, Salvador; Nascimento, Eduardo Mauro; Azevedo, Elaine, E-mail: marina.mcv@gmail.com [University of Patras (Greece); Universidade de Sao Paulo (USP) Sao Carlos, SP (Brazil); Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil)

2017-04-15

Natural fibers and polyurethane based composites may present chemical bonding between the components of the polymer and the lignin of the fiber. The incidence of radiation can cause degradation of the polymeric material and alter its mechanical properties. The objective of this study was to obtain and characterize cold pressed composites from polyurethane derived from castor oil and sisal fibers, without coupling agents, through thermogravimetric and mechanical tests, before and after the incidence of 25 kGy dose of gamma radiation. Woven composites that were not irradiated had maximum values of 4.40 GPa for flexural elastic modulus on three point flexural test and dispersed fiber composite that were not irradiated had maximum values of 2.25 GPa. These materials are adequate for use in non-structural applications in radiotherapy and radiodiagnostic rooms. (author)

TmDOTA-tetraglycinate encapsulated liposomes as pH-sensitive LipoCEST agents.

Directory of Open Access Journals (Sweden)

Ana Christina L Opina

Full Text Available Lanthanide DOTA-tetraglycinate (LnDOTA-(gly₄⁻ complexes contain four magnetically equivalent amide protons that exchange with protons of bulk water. The rate of this base catalyzed exchange process has been measured using chemical exchange saturation transfer (CEST NMR techniques as a function of solution pH for various paramagnetic LnDOTA-(gly₄⁻ complexes to evaluate the effects of lanthanide ion size on this process. Complexes with Tb(III, Dy(III, Tm(III and Yb(III were chosen because these ions induce large hyperfine shifts in all ligand protons, including the exchanging amide protons. The magnitude of the amide proton CEST exchange signal differed for the four paramagnetic complexes in order, Yb>Tm>Tb>Dy. Although the Dy(III complex showed the largest hyperfine shift as expected, the combination of favorable chemical shift and amide proton CEST linewidth in the Tm(III complex was deemed most favorable for future in vivo applications where tissue magnetization effects can interfere. TmDOTA-(gly₄⁻ at various concentrations was encapsulated in the core interior of liposomes to yield lipoCEST particles for molecular imaging. The resulting nanoparticles showed less than 1% leakage of the agent from the interior over a range of temperatures and pH. The pH versus amide proton CEST curves differed for the free versus encapsulated agents over the acidic pH regions, consistent with a lower proton permeability across the liposomal bilayer for the encapsulated agent. Nevertheless, the resulting lipoCEST nanoparticles amplify the CEST sensitivity by a factor of ∼10⁴ compared to the free, un-encapsulated agent. Such pH sensitive nano-probes could prove useful for pH mapping of liposomes targeted to tumors.

Investigation of the interaction of radiation and cardiotoxic anticancer agents using a fetal mouse heart organ culture system

International Nuclear Information System (INIS)

Kimler, B.F.; Rethorst, R.D.; Cox, G.G.

1985-01-01

The fetal mouse heart organ culture was utilized in an attempt to predict the cardiotoxic effects of combinations of radiation, Adriamycin (ADR), and Dihydroxyanthraquinone (DHAQ), antineoplastic agents which have been shown to produce clinical cardiomyopathy. Seventeen-day fetal hearts were removed and placed in a culture system of micro-titer plates. A single heart was placed in each well on a piece of aluminum mesh to keep the heart above the culture medium but bathed by capillary action. The plates were then placed in a 100% oxygen environment at 37 0 C. Treatments were performed on day 1 after culture: radiation doses (Cs-137) of 10, 20, or 40 Gy; drug treatment with 10, 30, or 100 μg/ml of ADR; 5, 20, or 50 μg/ml of DHAQ; and combinations and sequences of drug and radiation. Hearts were checked every day for functional activity as evidenced by a continuous heart beat. Untreated hearts beat rhythmically for up to 9 days; treated hearts stopped beating earlier. Using an endpoint of functional retention time, dose response curves were obtained for all individual agents and for combinations of agents. This system may help to predict the cardiotoxic effects that result from the use of these drugs and radiation. It may also aid in the development of new anthracycline chemotherapeutic agents that lack cardiotoxicity

Effects of peroxide and catalase on near ultraviolet radiation sensitivity in Escherichia coli strains

International Nuclear Information System (INIS)

Coombs, A.M.L.; Moss, S.H.

1987-01-01

The role of peroxide and catalase on NUV radiation sensitivity was examined in two repair competent E. coli strains, AB1157 and B/r. Exponential phase B/r is considerably more sensitive to NUV radiation than exponential phase AB1157. However, resistance to 5 mmol dm -3 H 2 O 2 was induced in both AB1157 and B/r by pretreating growing cells with 30 μmol dm -3 H 2 O 2 . Pretreatment also induced resistance to broad-band NUV radiation in these strains. The addition of catalase to the post-irradiation plating medium increased survival to the same extent as that provided by pretreatment with 30 μmol dm -3 H 2 O 2 , in both strains. The NUV radiation sensitivity seen in B/r does not appear to be due to a deficiency in enzymes that scavenge H 2 O 2 , as a catalase deficient mutant, E. coli UM1, is more resistant to NUV radiation than B/r. Also, assays for H 2 O 2 scavenging ability show little difference between AB1157 and B/r in this respect. Two hypotheses are put forward to account for the sensitivity of exponential phase B/r. Whilst it is apparent that peroxides and catalase do have a role in NUV radiation damage, it is clear that other factors also influence survival under certain conditions. (author)

High sensitive radiation detector for radiology dosimetry

Energy Technology Data Exchange (ETDEWEB)

Valente, M.; Malano, F. [Instituto de Fisica Enrique Gaviola, Oficina 102 FaMAF - UNC, Av. Luis Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Molina, W.; Vedelago, J., E-mail: valente@famac.unc.edu.ar [Laboratorio de Investigaciones e Instrumentacion en Fisica Aplicada a la Medicina e Imagenes por Rayos X, Laboratorio 448 FaMAF - UNC, Ciudad Universitaria, 5000 Cordoba (Argentina)

2014-08-15

Fricke solution has a wide range of applications as radiation detector and dosimetry. It is particularly appreciated in terms of relevant comparative advantages, like tissue equivalence when prepared in aqueous media like gel matrix, continuous mapping capability, dose rate recorded and incident direction independence as well as linear dose response. This work presents the development and characterization of a novel Fricke gel system, based on modified chemical compositions making possible its application in clinical radiology. Properties of standard Fricke gel dosimeter for high dose levels are used as starting point and suitable chemical modifications are introduced and carefully investigated in order to attain high resolution for low dose ranges, like those corresponding to radiology interventions. The developed Fricke gel radiation dosimeter system achieves the expected typical dose dependency, actually showing linear response in the dose range from 20 up to 4000 mGy. Systematic investigations including several chemical compositions are carried out in order to obtain a good enough dosimeter response for low dose levels. A suitable composition among those studied is selected as a good candidate for low dose level radiation dosimetry consisting on a modified Fricke solution fixed to a gel matrix containing benzoic acid along with sulfuric acid, ferrous sulfate, xylenol orange and ultra-pure reactive grade water. Dosimeter samples are prepared in standard vials for its in phantom irradiation and further characterization by spectrophotometry measuring visible light transmission and absorbance before and after irradiation. Samples are irradiated by typical kV X-ray tubes and calibrated Farmer type ionization chamber is used as reference to measure dose rates inside phantoms in at vials locations. Once sensitive material composition is already optimized, dose-response curves show significant improvement regarding overall sensitivity for low dose levels. According to

High sensitive radiation detector for radiology dosimetry

International Nuclear Information System (INIS)

Valente, M.; Malano, F.; Molina, W.; Vedelago, J.

2014-08-01

Fricke solution has a wide range of applications as radiation detector and dosimetry. It is particularly appreciated in terms of relevant comparative advantages, like tissue equivalence when prepared in aqueous media like gel matrix, continuous mapping capability, dose rate recorded and incident direction independence as well as linear dose response. This work presents the development and characterization of a novel Fricke gel system, based on modified chemical compositions making possible its application in clinical radiology. Properties of standard Fricke gel dosimeter for high dose levels are used as starting point and suitable chemical modifications are introduced and carefully investigated in order to attain high resolution for low dose ranges, like those corresponding to radiology interventions. The developed Fricke gel radiation dosimeter system achieves the expected typical dose dependency, actually showing linear response in the dose range from 20 up to 4000 mGy. Systematic investigations including several chemical compositions are carried out in order to obtain a good enough dosimeter response for low dose levels. A suitable composition among those studied is selected as a good candidate for low dose level radiation dosimetry consisting on a modified Fricke solution fixed to a gel matrix containing benzoic acid along with sulfuric acid, ferrous sulfate, xylenol orange and ultra-pure reactive grade water. Dosimeter samples are prepared in standard vials for its in phantom irradiation and further characterization by spectrophotometry measuring visible light transmission and absorbance before and after irradiation. Samples are irradiated by typical kV X-ray tubes and calibrated Farmer type ionization chamber is used as reference to measure dose rates inside phantoms in at vials locations. Once sensitive material composition is already optimized, dose-response curves show significant improvement regarding overall sensitivity for low dose levels. According to

Effect of Long Term Low-Level Gamma Radiation on Thermal Sensitivity of RDX/HMX Mixtures

Science.gov (United States)

1976-11-01

1.1x10 R. It was concluded that the slight exothermic reaction before the 3^6 HMX polymorphic transition could be caused by a radiation-induced...Radiation on Thermal Sensitivity of RDX / HMX Mixtures 5. TYPE OF REPORT 4 PERIOD COVERED Final Report 6. PERFORMING ORG. REPORT NUMBER 7...and Identity by block number) Gamma radiation Weight loss HMX Impact sensitivity test RDX Vacuum stability test DTA Infrared spectrometry TGA

Gamma radiation effect on sisal / polyurethane composites without coupling agents

Directory of Open Access Journals (Sweden)

Marina Cardoso Vasco

Full Text Available Abstract Natural fibers and polyurethane based composites may present chemical bonding between the components of the polymer and the lignin of the fiber. The incidence of radiation can cause degradation of the polymeric material and alter its mechanical properties. The objective of this study was to obtain and characterize cold pressed composites from polyurethane derived from castor oil and sisal fibers, without coupling agents, through thermogravimetric and mechanical tests, before and after the incidence of 25 kGy dose of gamma radiation. Woven composites that were not irradiated had maximum values of 4.40 GPa for flexural elastic modulus on three point flexural test and dispersed fiber composite that were not irradiated had maximum values of 2.25 GPa. These materials are adequate for use in non-structural applications in radiotherapy and radiodiagnostic rooms.

Sensitivity of glaciation in the arid subtropical Andes to changes in temperature, precipitation, and solar radiation

Science.gov (United States)

Vargo, L. J.; Galewsky, J.; Rupper, S.; Ward, D. J.

2018-04-01

The subtropical Andes (18.5-27 °S) have been glaciated in the past, but are presently glacier-free. We use idealized model experiments to quantify glacier sensitivity to changes in climate in order to investigate the climatic drivers of past glaciations. We quantify the equilibrium line altitude (ELA) sensitivity (the change in ELA per change in climate) to temperature, precipitation, and shortwave radiation for three distinct climatic regions in the subtropical Andes. We find that in the western cordillera, where conditions are hyper-arid with the highest solar radiation on Earth, ELA sensitivity is as high as 34 m per % increase in precipitation, and 70 m per % decrease in shortwave radiation. This is compared with the eastern cordillera, where precipitation is the highest of the three regions, and ELA sensitivity is only 10 m per % increase in precipitation, and 25 m per % decrease in shortwave radiation. The high ELA sensitivity to shortwave radiation highlights the influence of radiation on mass balance of high elevation and low-latitude glaciers. We also consider these quantified ELA sensitivities in context of previously dated glacial deposits from the regions. Our results suggest that glaciation of the humid eastern cordillera was driven primarily by lower temperatures, while glaciations of the arid Altiplano and western cordillera were also influenced by increases in precipitation and decreases in shortwave radiation. Using paleoclimate records from the timing of glaciation, we find that glaciation of the hyper-arid western cordillera can be explained by precipitation increases of 90-160% (1.9-2.6× higher than modern), in conjunction with associated decreases in shortwave radiation of 7-12% and in temperature of 3.5 °C.

Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection

International Nuclear Information System (INIS)

Bourguignon, Michel H.; Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di; Carosella, Edgardo D.

2005-01-01

Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are ''hypersensitive'' to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed. (orig.)

Sensitivity to plant modelling uncertainties in optimal feedback control of sound radiation from a panel

DEFF Research Database (Denmark)

Mørkholt, Jakob

1997-01-01

Optimal feedback control of broadband sound radiation from a rectangular baffled panel has been investigated through computer simulations. Special emphasis has been put on the sensitivity of the optimal feedback control to uncertainties in the modelling of the system under control.A model...... in terms of a set of radiation filters modelling the radiation dynamics.Linear quadratic feedback control applied to the panel in order to minimise the radiated sound power has then been simulated. The sensitivity of the model based controller to modelling uncertainties when using feedback from actual...

Effects of peroxide and catalase on near ultraviolet radiation sensitivity in Escherichia coli strains

Energy Technology Data Exchange (ETDEWEB)

Coombs, A.M.L.; Moss, S.H.

1987-03-01

The role of peroxide and catalase on NUV radiation sensitivity was examined in two repair competent E. coli strains, AB1157 and B/r. Exponential phase B/r is considerably more sensitive to NUV radiation than exponential phase AB1157. However, resistance to 5 mmol dm/sup -3/ H/sub 2/O/sub 2/ was induced in both AB1157 and B/r by pretreating growing cells with 30 ..mu..mol dm/sup -3/ H/sub 2/O/sub 2/. Pretreatment also induced resistance to broad-band NUV radiation in these strains. The addition of catalase to the post-irradiation plating medium increased survival to the same extent as that provided by pretreatment with 30 ..mu..mol dm/sup -3/ H/sub 2/O/sub 2/, in both strains. The NUV radiation sensitivity seen in B/r does not appear to be due to a deficiency in enzymes that scavenge H/sub 2/O/sub 2/, as a catalase deficient mutant, E. coli UM1, is more resistant to NUV radiation than B/r. Also, assays for H/sub 2/O/sub 2/ scavenging ability show little difference between AB1157 and B/r in this respect. Two hypotheses are put forward to account for the sensitivity of exponential phase B/r. Whilst it is apparent that peroxides and catalase do have a role in NUV radiation damage, it is clear that other factors also influence survival under certain conditions.

Chinese insurance agents in "bad barrels": a multilevel analysis of the relationship between ethical leadership, ethical climate and business ethical sensitivity.

Science.gov (United States)

Zhang, Na; Zhang, Jian

2016-01-01

The moral hazards and poor public image of the insurance industry, arising from insurance agents' unethical behavior, affect both the normal operation of an insurance company and decrease applicants' confidence in the company. Contrarily, these scandals may demonstrate that the organizations were "bad barrels" in which insurance agents' unethical decisions were supported or encouraged by the organization's leadership or climate. The present study brings two organization-level factors (ethical leadership and ethical climate) together and explores the role of ethical climate on the relationship between the ethical leadership and business ethical sensitivity of Chinese insurance agents. Through the multilevel analysis of 502 insurance agents from 56 organizations, it is found that organizational ethical leadership is positively related to the organizational ethical climate; organizational ethical climate is positively related to business ethical sensitivity, and organizational ethical climate fully mediates the relationship between organizational ethical leadership and business ethical sensitivity. Organizational ethical climate plays a completely mediating role in the relationship between organizational ethical leadership and business ethical sensitivity. The integrated model of ethical leadership, ethical climate and business ethical sensitivity makes several contributions to ethics theory, research and management.

Enhanced sensitivity of the RET proto-oncogene to ionizing radiation in vitro.

Science.gov (United States)

Volpato, Claudia Béu; Martínez-Alfaro, Minerva; Corvi, Raffaella; Gabus, Coralie; Sauvaigo, Sylvie; Ferrari, Pietro; Bonora, Elena; De Grandi, Alessandro; Romeo, Giovanni

2008-11-01

Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia and thyroid cancer. It has been known for a long time that exposure of cells to radiation results in extensive DNA damage; however, a small number of studies have tried to explain the mechanisms of radiation-induced carcinogenesis. The high prevalence of RET/PTC rearrangements in patients who have received external radiation, and the evidence of in vitro induction of RET rearrangements in human cells, suggest an enhanced sensitivity of the RET genomic region to damage by ionizing radiation. To assess whether RET is indeed more sensitive to radiations than other genomic regions, we used a COMET assay coupled with fluorescence in situ hybridization, which allows the measurement of DNA fragmentation in defined genomic regions of single cells. We compared the initial DNA damage of the genomic regions of RET, CXCL12/SDF1, ABL, MYC, PLA2G2A, p53, and JAK2 induced by ionizing radiation in both a lymphoblastoid and a fetal thyroid cell line. In both cell lines, RET fragmentation was significantly higher than in other genomic regions. Moreover, a differential distribution of signals within the COMET was associated with a higher percentage of RET fragments in the tail. RET was more susceptible to fragmentation in the thyroid-derived cells than in lymphoblasts. This enhanced susceptibility of RET to ionizing radiation suggests the possibility of using it as a radiation exposure marker.

Charge-coupled devices as positron sensitive detectors of x-radiation

International Nuclear Information System (INIS)

Volkov, G.S.; Zazhivikhin, V.V.; Zajtsev, V.I.; Mishevskij, V.O.

1996-01-01

Results of theoretical and experimental studies on the sensitivity and spatial resolution of devices with a charge link (CLD) within the X-radiation energy range are described. The areas of the device application are considered

Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus-infected cells to heat and radiation

International Nuclear Information System (INIS)

Wong, G.H.; McHugh, T.; Weber, R.; Goeddel, D.V.

1991-01-01

We report here that infection of the human T-cell line HUT-78 with human immunodeficiency virus (HIV) increases its sensitivity to heat and radiation toxicity. A possible explanation for this result may be the reduced expression of manganous superoxide dismutase (MnSOD) in HIV-infected cells compared to uninfected cells. Tumor necrosis factor alpha (TNF-alpha) further sensitizes HIV-infected cells but not uninfected cells to heat and radiation. This is consistent with the ability of TNF-alpha to induce the expression of MnSOD in uninfected but not in HIV-infected cells. HIV-infected HUT-78 cell lines engineered to overexpress MnSOD are more resistant to heat and radiation than HIV-infected cells that do not overexpress MnSOD. However, treatment with TNF-alpha still sensitizes these cells to heat and radiation

A case of severe rectal hemorrhage possibly caused by radiation recall after administration of gemcitabine

International Nuclear Information System (INIS)

Nishimoto, Koshiro; Akise, Yushi; Uchida, Atsushi; Miyazawa, Masaharu; Kutsuki, Shoji; Hashimoto, Subaru

2016-01-01

Radiation recall is an acute inflammatory reaction that can be triggered when systemic agents are administered long time after radiotherapy. Because radiotherapy is now indicated for many types of cancer, care should be taken regarding possible toxic events relating to radiotherapy in combination with radio-sensitizing agents. Gemcitabine, one such anti-cancer agent, is widely used, especially for urologic cancers. We report an intriguing case of possible radiation recall in the rectum caused by gemcitabine administration 37 years after radiation therapy. From a review of the literature, it appears that there have been no reported cases of radiation recall in the rectum with such a long interval between radiation therapy and chemotherapy. Here, we describe the case and provide a literature review. (author)

Sea urchin coelomocytes are resistant to a variety of DNA damaging agents

Energy Technology Data Exchange (ETDEWEB)

Loram, Jeannette; Raudonis, Renee; Chapman, Jecar; Lortie, Mae [Bermuda Institute of Ocean Sciences, St. George' s, Bermuda, GE 01 (Bermuda); Bodnar, Andrea, E-mail: andrea.bodnar@bios.edu [Bermuda Institute of Ocean Sciences, St. George' s, Bermuda, GE 01 (Bermuda)

2012-11-15

Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H{sub 2}O{sub 2}), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD{sub 50} values determined for coelomocytes after 24 h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H{sub 2}O{sub 2}, MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.

Radiation-induced mutagenicity and lethality in Ames tester strains of Salmonella

International Nuclear Information System (INIS)

Isildar, M.; Bakale, G.

1984-01-01

Mutation and killing induced by X radiation and 60 Co γ radiation were studied in six different histidine-requiring auxotrophs of Salmonella typhimurium. Strain TA100, which is sensitive to base-pair substitutions, and strains TA2637 and TA98, which are sensitive to frameshifts, carry the pKM101 plasmid and exhibit significantly higher radiation-induced mutations compared to their plasmidless parent strains TA1535, TA1537, and TA1538, respectively. Among the plasmid-containing strains, TA98 and TA2637 are much more sensitive to the mutagenic action of radiation than is TA100 based on a comparison with their respective spontaneous mutation rates; however, no uniformity was observed in the responses of the strains to the lethal action of ionizing radiation. The following conclusions are consistent with these observations: (1) the standard Ames Salmonella assay correctly identifies ionizing radiation as a mutagenic agent; (2) frameshift-sensitive parent strains are more sensitive to the mutagenic effects of ionizing radiation than is the only strain studied that is sensitive to base-pair substitutions; and (3) enhancement of mutagenesis and survival is related to plasmid-mediated repair of DNA damage induced by ionizing radiation and does not involve damage induced by Cerenkov-generated uv radiation which is negligible for our irradiation conditions

Relationship of radiation sensitivity and aberrant DNA synthesis in repair deficient CHO cells

International Nuclear Information System (INIS)

Newman, C.N.; Hagler, H.; Miller, J.H.

1986-11-01

Comparison of alkaline sucrose gradient profiles of pulse-labeled DNA from a normal CHO cell line and its radiation-sensitive mutant, xrs-5, reveals significant differences in the replicon elongation/maturation process in these two cells. During a one hr period of growth subsequent to labeling, the molecular weight of pulse-labeled DNA from the mutant cell increases considerably more rapidly than that of the parent cell. For xrs-5, the presence of 2 mM deoxycytidine (CdR) in the culture medium reduces the replication rate to one approaching that of the parent cell growing in the standard medium. Corresponding uv resistance of the mutant likewise increases to nearly that of the parent cell line. These results suggest that the locus conferring radiation sensitivity to xrs-5 affects the DNA replisome complex and that replicative activity and radiation sensitivity are jointly modulated by CdR. 19 refs., 4 figs

Sensitivity of an autoradiographic film to ionizing radiation of different types and energies

International Nuclear Information System (INIS)

Kras, A.B.; Lutzke-Birk, A.; Kalicki, A.

1984-01-01

The ORWO-AF3 autoradiographic film has been studied with regard to its sensitivity to beta radiation (E/sub max/ = 0.155 and 0.306 MeV, resp.), gamma radiation of more than 1 MeV and K/sub α/ and K/sub β/ radiation of about 5.9 KeV. The obtained data can be used for the correction of depth distribution profiles if elements are labelled with radioisotopes emitting mixed radiation, e.g., beta and gamma radiation

DNA and cancer biology: role in radiation and drug sensitivity, carcinogenesis and mutations

International Nuclear Information System (INIS)

Yielding, K.L.

1974-01-01

The DNA excision repair mechanism is an important factor in the resistance exhibited by tumor cells toward both x rays and alkylating agents as demonstrated by the fact that the chemical alterations to cellular DNA caused by these agents are substrates for the repair enzymes. Furthermore, experiments performed in our laboratory demonstrate that: (a) tumor sensitivity to alkylating agents and x-ray can be increased by inhibition of the repair process, and (b) there is a suggestion that this sensitization can be achieved with some degree of selectivity, thereby improving the balance of sensitivites between tumor and normal tissue. Other work from this laboratory has shown that cocarcinogens probably act by preventing repair of carcinogenic damage to the DNA genome. The possibility has also been raised that mistakes made during repair synthesis might be responsible for some genetic diversity and for the mutations which arise in resting cells. (U.S.)

UV- and gamma-radiation sensitive mutants of Arabidopsis thaliana

International Nuclear Information System (INIS)

Jiang, C.Z.; Yen, C.N.; Cronin, K.; Mitchell, D.; Britt, A.B.

1997-01-01

Arabidopsis seedlings repair UV-induced DNA damage via light-dependent and -independent pathways. The mechanism of the ''dark repair'' pathway is still unknown. To determine the number of genes required for dark repair and to investigate the substrate-specificity of this process we isolated mutants with enhanced sensitivity to UV radiation in the absence of photoreactivating light. Seven independently derived UV sensitive mutants were isolated from an EMS-mutagenized population. These fell into six complementation groups, two of which (UVR1 and UVH1) have previously been defined. Four of these mutants are defective in the dark repair of UV-induced pyrimidine [6-4] pyrimidinone dimers. These four mutant lines are sensitive to the growth-inhibitory effects of gamma radiation, suggesting that this repair pathway is also involved in the repair of some type of gamma-induced DNA damage product. The requirement for the coordinate action of several different gene products for effective repair of pyrimidine dimers, as well as the nonspecific nature of the repair activity, is consistent with nucleotide excision repair mechanisms previously described in Saccharomyces cerevisiae and nonplant higher eukaryotes and inconsistent with substrate-specific base excision repair mechanisms found in some bacteria, bacteriophage, and fungi. (author)

Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2

Science.gov (United States)

Fedier, A; Ruefenacht, U B; Schwarz, V A; Haller, U; Fink, D

2002-01-01

A large fraction of human tumours carries mutations in the p53 gene. p53 plays a central role in controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack of p53 function impairs these cellular processes, and this may be the basis of resistance to chemotherapeutic regimens. By virtue of the involvement of DNA mismatch repair in modulating cytotoxic pathways in response to DNA damaging agents, we investigated the effects of loss of Pms2 on the sensitivity to a panel of widely used anticancer agents in E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient in Pms2. We report that lack of the Pms2 gene is associated with an increased sensitivity, ranging from 2–6-fold, to some types of anticancer agents including the topoisomerase II poisons doxorubicin, etoposide and mitoxantrone, the platinum compounds cisplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, and the antimetabolite gemcitabine. In contrast, no change in sensitivity was found after treatment with 5-fluorouracil. Cell cycle analysis revealed that both, Pms2-deficient and -proficient cells, retain the ability to arrest at the G2/M upon cisplatin treatment. The data indicate that the concomitant loss of Pms2 function chemosensitises p53-deficient cells to some types of anticancer agents, that Pms2 positively modulates cell survival by mechanisms independent of p53, and that increased cytotoxicity is paralleled by increased apoptosis. Tumour-targeted functional inhibition of Pms2 may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers. British Journal of Cancer (2002) 87, 1027–1033. doi:10.1038/sj.bjc.6600599 www.bjcancer.com © 2002 Cancer Research UK PMID:12434296

Radiation sensitive area detection device and method

Science.gov (United States)

Carter, Daniel C. (Inventor); Hecht, Diana L. (Inventor); Witherow, William K. (Inventor)

1991-01-01

A radiation sensitive area detection device for use in conjunction with an X ray, ultraviolet or other radiation source is provided which comprises a phosphor containing film which releases a stored diffraction pattern image in response to incoming light or other electromagnetic wave. A light source such as a helium-neon laser, an optical fiber capable of directing light from the laser source onto the phosphor film and also capable of channelling the fluoresced light from the phosphor film to an integrating sphere which directs the light to a signal processing means including a light receiving means such as a photomultiplier tube. The signal processing means allows translation of the fluoresced light in order to detect the original pattern caused by the diffraction of the radiation by the original sample. The optical fiber is retained directly in front of the phosphor screen by a thin metal holder which moves up and down across the phosphor screen and which features a replaceable pinhole which allows easy adjustment of the resolution of the light projected onto the phosphor film. The device produces near real time images with high spatial resolution and without the distortion that accompanies prior art devices employing photomultiplier tubes. A method is also provided for carrying out radiation area detection using the device of the invention.

Radiation sensitive polymers of oxygen-substituted maleimides and elements containing same

International Nuclear Information System (INIS)

Wilson, J.C.

1977-01-01

Radiation sensitive polymers comprising from about 1 to 100 mole % of a polymerized maleimide monomer consisting of a hydrocarbon group having from 2 to 20 carbon atoms, preferably a bridged hydrocarbon group having from 6 to 10 carbon atoms and from 0 to about 99 mole % of at least one additional polymerized ethylenically unsaturated monomer are described. The polymers are soluble in organic solvents, possess desirably high glass transition temperatures and are capable of undergoing a photochemical reaction to yield polymers having isocyanate and oxy-substituted cyclopropane moieties which are capable of crosslinking in the presence of active hydrogen-containing compounds. The polymers are useful in radiation sensitive compositions and elements containing same

Biodegradable, pH-sensitive chitosan beads obtained under microwave radiation for advanced cell culture.

Science.gov (United States)

Piątkowski, Marek; Janus, Łukasz; Radwan-Pragłowska, Julia; Bogdał, Dariusz; Matysek, Dalibor

2018-04-01

A new type of promising chitosan beads with advanced properties were obtained under microwave radiation according to Green Chemistry principles. Biomaterials were prepared using chitosan as raw material and glutamic acid/1,5-pentanodiol mixture as crosslinking agents. Additionally beads were modified with Tilia platyphyllos extract to enhance their antioxidant properties. Beads were investigated over their chemical structure by FT-IR analysis. Also their morphology has been investigated by SEM method. Additionally swelling capacity of the obtained hydrogels was determined. Lack of cytotoxicity has been confirmed by MTT assay. Proliferation studies were carried out on L929 mouse fibroblasts. Advanced properties of the obtained beads were investigated by studying pH sensitivity and antioxidant properties by DPPH method. Also susceptibility to degradation and biodegradation by Sturm Test method was evaluated. Results shows that proposed chitosan beads and their eco-friendly synthesis method can be applied in cell therapy and tissue engineering. Copyright © 2018 Elsevier B.V. All rights reserved.

Radiobiological aspects of application of interleucine as agents for the first aid under strong radiation action

International Nuclear Information System (INIS)

Rozhdestvensij, L.M.

1997-01-01

The paper substantiates the application of the interleucine-1 beta (IL-1) as an emergency medical care agent in case of the acute emergency exposure of a human being. During simulation experiments a human recombinant IL-1 was added to suspension of the affected bony marrow-cells extracted a few minutes following the total 5 Gy exposure of Fi male-mice (CBAxC57B1). Recombinant mouse IL-3 and GM-CSF agents (produced by Bering company, Germany) were used for comparison purpose (agent concentration constituted 100-10000 unit/ml). The incubated bony marrow cells were tested for trunk potencies in mice-recipients irradiated by 8.5 Gy dose during 24 h. Following nine days the colonies in their spleen and bony marrow cellular texture were estimated. IL-1 was shown to have the protective effect both on separated trunk type hemopoietic cells and on the whole body irradiated hemopoietic system. IL-1 turned to be similar to radiation-protective agents of polysaccharide nature and to radiation-protective EIR procedure. It is pointed out that IL-1 has no whole body toxic or any other by effects [ru

Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents.

Science.gov (United States)

Wang, Pu; Wu, Jing; Ma, Shenghong; Zhang, Lei; Yao, Jun; Hoadley, Katherine A; Wilkerson, Matthew D; Perou, Charles M; Guan, Kun-Liang; Ye, Dan; Xiong, Yue

2015-12-22

Chemotherapy of a combination of DNA alkylating agents, procarbazine and lomustine (CCNU), and a microtubule poison, vincristine, offers a significant benefit to a subset of glioma patients. The benefit of this regimen, known as PCV, was recently linked to IDH mutation that occurs frequently in glioma and produces D-2-hydroxyglutarate (D-2-HG), a competitive inhibitor of α-ketoglutarate (α-KG). We report here that D-2-HG inhibits the α-KG-dependent alkB homolog (ALKBH) DNA repair enzymes. Cells expressing mutant IDH display reduced repair kinetics, accumulate more DNA damages, and are sensitized to alkylating agents. The observed sensitization to alkylating agents requires the catalytic activity of mutant IDH to produce D-2-HG and can be reversed by the deletion of mutant IDH allele or overexpression of ALKBH2 or AKLBH3. Our results suggest that impairment of DNA repair may contribute to tumorigenesis driven by IDH mutations and that alkylating agents may merit exploration for treating IDH-mutated cancer patients. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

{sup 166}Ho-chitosan as a radiation synovectomy agent - biocompatibility study of {sup 166}Ho-chitosan in rabbits

Energy Technology Data Exchange (ETDEWEB)

Kim, Sug Jun; Lee, Soo Yong; Jeon, Dae Geun; Seok, Lee Jong [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1997-01-01

Radiation synovectomy is a noninvasive therapy that has been investigated as an alternative to surgical synovectomy. It is been successfully employed in the treatment of synovitis in rheumatoid arthrits and other inflammatory arthropathies. We developed the {sup 166}Ho-chitosan complex for possible use as a radiation synovectomy agent. Holmium is the more practical isotope based on its higher radioactivity and logner half-life. And isotope based on its higher radioactivity and logner half-life. And chitosan is ideal and suitable particles based on its soluble and biodegradable characteristics. So we investigated the biocompatibility of the {sup 166}Ho-chitosan complex to evaluated the suitability as a radiation synovectomy agent. In this study, we performed in vivo and in vitro stability test and biodistribution test. Our results indicate that {sup 166}Ho-chitosan may be an effective radiopharmaceutical for radiation synovectomy. (author). 30 refs., 7 tabs.

The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

Science.gov (United States)

Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

2000-05-25

DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

A new sensitive technique for study of radiation effects in amino acids

International Nuclear Information System (INIS)

Thwaites, D.I.; Buchan, G.; Ettinger, K.V.; Mallard, J.R.; Takavar, A.

1976-01-01

A new technique for the study of radiation induced free radicals in amino acids based on their reactions when untrapped by dissolution in water is reported. The light emission or lyoluminescence response of various amino acids to gamma radiation ( 60 Co) measured 4 hr after irradiation are shown. The sensitivities vary over three orders of magnitude, but there is little or no correlation between the lyoluminescent response and the structural type of amino acid. Dose-reponse curves indicate that the useful range extends from a few krad to a few hundred krad. Methods of extending the lower limits are discussed. Storage of irradiated material over a period of 4 months at 20 0 C showed changes of the order of 10%. Exposure to daylight has no effect on the light yield of amino acids. It is stated that the lyoluminescence technique is more sensitive than ESR in detecting radiation effects in amino acids. Lyoluminescence of irradiated proteins, RNA and DNA, has been observed. It appears that the new method may be particularly useful in providing information on the nature and magnitude of direct radiation damage in biologically important compounds and find applications in radiation dosimetry. (U.K.)

Research on Paramecium aurelia sensitivity factors to natural ionizing radiations

International Nuclear Information System (INIS)

Croute, F.; Soleilhavoup, J.P.; Gros, N.; Planel, H.

1976-01-01

Previous results have demonstrated that the proliferative activity of Paramecium aurelia is linked to the level of natural ionizing radiations since this activity is decreased under radiation protection (lead cell) and increased under chronic exposure to very low dose of 60 Co gamma rays. The results of this investigation indicate that cell sensitivity in spite of variations in natural irradiation levels can be isolated; they are called 'radioresistant' in opposition to 'radiosensitive' cells which present the other response. These characters are being retained for 9 months after the strains have been isolated. On the other hand, in the case of radiosensitive strains, it has been demonstrated that autogamy affected the cell response to background irradiation; no response at all occured on the very day when autogamy took place, but it reached a maximum level 8 days approximately after autogamy. Moreover, it has been proved that the catalase activity of Paramecium aurelia is higher than those already studied in other cell varieties. This great amount of catalase, which seems to vary with the age of cultures after autogamy, could act on Paramecium sensitivity to very low radiation doses [fr

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

International Nuclear Information System (INIS)

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

1982-01-01

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

MicroRNA-203 Modulates the Radiation Sensitivity of Human Malignant Glioma Cells

International Nuclear Information System (INIS)

Chang, Ji Hyun; Hwang, Yeo Hyun; Lee, David J.; Kim, Dan Hyo; Park, Ji Min; Wu, Hong-Gyun; Kim, In Ah

2016-01-01

Purpose: We investigated whether miR-203 could modulate the radiation sensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved. Methods and Materials: Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR-203. Real-time PCR (RT-PCR), clonogenic assays, immunofluorescence, and invasion/migration assays were performed. To predict the target(s), bioinformatics analyses using microRNA target databases were performed. Results: Overexpression of miR-203 increased the radiation sensitivity of all 3 human MG cell lines and prolonged radiation-induced γ-H2AX foci formation. Bioinformatics analyses suggested that miR-203 could be involved in post-transcriptional control of DNA repair, PI3K/AKT, SRC, and JAK/STAT3 and the vascular signaling pathway. Western blot analysis validated the fact that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1α, and MMP2. Overexpression of miR-203 inhibited invasion and migration potentials, downregulated SLUG and Vimentin, and upregulated Claudin-1 and ZO1. Conclusions: These data demonstrate that miR-203 potentially controls DNA damage repair via the PI3K/AKT and JAK/STAT3 pathways and may collectively contribute to the modulation of radiation sensitivity in MG cells by inhibiting DNA damage repair, prosurvival signaling, and epithelium-mesenchyme transition. Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radiation resistance of GBM.

MicroRNA-203 Modulates the Radiation Sensitivity of Human Malignant Glioma Cells

Energy Technology Data Exchange (ETDEWEB)

Chang, Ji Hyun [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Hwang, Yeo Hyun; Lee, David J.; Kim, Dan Hyo; Park, Ji Min [Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, In Ah, E-mail: inah228@snu.ac.kr [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

2016-02-01

Purpose: We investigated whether miR-203 could modulate the radiation sensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved. Methods and Materials: Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR-203. Real-time PCR (RT-PCR), clonogenic assays, immunofluorescence, and invasion/migration assays were performed. To predict the target(s), bioinformatics analyses using microRNA target databases were performed. Results: Overexpression of miR-203 increased the radiation sensitivity of all 3 human MG cell lines and prolonged radiation-induced γ-H2AX foci formation. Bioinformatics analyses suggested that miR-203 could be involved in post-transcriptional control of DNA repair, PI3K/AKT, SRC, and JAK/STAT3 and the vascular signaling pathway. Western blot analysis validated the fact that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1α, and MMP2. Overexpression of miR-203 inhibited invasion and migration potentials, downregulated SLUG and Vimentin, and upregulated Claudin-1 and ZO1. Conclusions: These data demonstrate that miR-203 potentially controls DNA damage repair via the PI3K/AKT and JAK/STAT3 pathways and may collectively contribute to the modulation of radiation sensitivity in MG cells by inhibiting DNA damage repair, prosurvival signaling, and epithelium-mesenchyme transition. Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radiation resistance of GBM.

Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

Science.gov (United States)

He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

2014-02-01

Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy

International Nuclear Information System (INIS)

Vaughan, W.P.; Karp, J.E.; Burke, P.J.

1983-01-01

Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have ''secondary'' acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of ''primary'' acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively

Toxic agent and radiation control: progress toward objectives for the nation for the year 1990

International Nuclear Information System (INIS)

Rall, D.P.

1988-01-01

In 1980, the Department of Health and Human Services set national prevention objectives for 1990 in 15 health priority areas, 1 of which is the control of toxic agents and radiation. Ten objectives related to this area are priorities for the national control effort. Progress is reviewed on those priorities within the responsibilities of the Public Health Service. Six key program elements, or types of support activities, are deemed essential to preventing, identifying, and controlling toxic agent and radiation threats. Significant progress has been made toward achieving objectives for which all key program elements have been successfully implemented to provide the requisite know-how, manpower, and tools. Important advances have been made in reducing the blood lead levels of the population, reducing unnecessary exposure to medical X-rays, evaluating the toxicities of chemicals in toxic waste dumps, and improving the scientific and technical information base and its availability for prevention and control efforts. The most important priority for the forseeable future will be to expand our knowledge of potential health risks posed by toxic agents and radiation. Expanded surveillance systems and data bases are essential to determining the extent of the problems in terms of human health effects and for measuring the impact of prevention programs. Emphasis on the activities embodied in the key elements will encourage the expansion of the knowledge base and its effective application to prevention and control problems

Modification of radiation sensitivity by edaravone

International Nuclear Information System (INIS)

Sasano, Nakashi; Enomoto, Atsushi; Miyagawa, Kiyoshi; Hosoi, Yoshio; Nakagawa, Keiichi

2009-01-01

Studied was the effect of edaravone (E), a clinical therapeutic drug for brain infarction possessing properties of free radical scavenger, on apoptosis in vitro. Human T-cell leukemic MOLT-4 cells and p53-knockdown MOLT-4 cells which overexpressing short hairpin type p53 by siRNA treatment were X-irradiated by Shimadzu Pantak HF 350 machine at 135-140 cGy/min for 2-5 Gy in total, in the presence of E. Cell death was estimated by dye-exclusion, apoptosis by EPICS flow cytometry, cellular reactive oxygen species by chloromethyl-2',7'-dichlorodihydrofluoresein diacetate (CM-H 2 -DCFDA) fluorometry, and p53-related protein expression by Western blotting. E was found to have a radio-protective effect on cells at high concentrations (e.g., 2.7 and 3 mg/mL, 2Gy) and radio-sensitizing action at low concentrations (e.g., 0.15-1.5 mg/mL). Clinical plasma levels of E have been reportedly far lower than the concentrations in this experiment: ideally, E can sensitize tumor cells to radiation and protect normal cells from. (K.T.)

High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Wolfe, Adam R. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Rachel L. [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Debeb, Bisrat G.; Larson, Richard; Li, Li [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Masuda, Hiroko; Brewer, Takae [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Bradley J. [Department of Clinical Pharmacy Services, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brewster, Abeena [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ueno, Naoto T. [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-04-01

Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

International Nuclear Information System (INIS)

Wolfe, Adam R.; Atkinson, Rachel L.; Reddy, Jay P.; Debeb, Bisrat G.; Larson, Richard; Li, Li; Masuda, Hiroko; Brewer, Takae; Atkinson, Bradley J.; Brewster, Abeena; Ueno, Naoto T.; Woodward, Wendy A.

2015-01-01

Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

Radiation induced variations in photoperiod-sensitivity, thermo-sensitivity and the number of days to heading in rice

International Nuclear Information System (INIS)

Hsieh, S.C.

1975-01-01

Radiation induced semi-dwarf mutants derived from five japonica type varieties of rice were studied with regard to their photoperiod-sensitivity, thermo-sensitivity and the number of days to heading. The experiment was carried out under the natural conditions at Taipei. The coefficient of photoperiod-sensitivity and thermo-sensitivity as developed by Oka (1954) were estimated for the mutants in comparison with their original varieties. It was observed that these various physiological characters could be altered easily by mutations. Mutants showed wider ranges in both positive and negative directions than their original varieties in all physiological characters studied. Even though heading date depends on both photoperiod-sensitivity and thermo-sensitivity, it was estimated which of the two contributed more to the induced earliness in each mutant. This offers a basis for selecting early maturing lines of rice

Effect of oxygen pressure on sensitivity of CR-39 used for astronauts radiation dosimetry

International Nuclear Information System (INIS)

Murai, T.; Yabe, S.; Nagamatsu, A.; Tawara, H.; Kumagai, H.; Miyazawa, Y.; Kitajo, K.; Kodaira, S.; Yasuda, N.

2006-01-01

The personal radiation dosimeters for astronauts are exposed to low-pressure oxygen gas (0.29 atmospheres) during extra-vehicle activities. CR-39 plastic track detectors are one of the typical passive dosimeters for space radiation monitoring. We investigated change in track formation sensitivity of the antioxidant-doped CR-39 plastic with which oxygen gas comes in contact at different pressures up to 2 atmospheres for 1h to 10 days. The oxygen effect on sensitivity was measured for the C, Si and Fe ions (10-200 keV/μm) from the HIMAC heavy ion accelerator. The sensitivity is obviously sensitive to oxygen pressure at heavy-ion exposures, but not sensitive to the experience of oxygen atmosphere before and after the ion exposures. The maximum sensitivity is obtained at 0.29 atmospheres. The present experimental data suggested that the effect depends on LET of incident particles. (author)

Radiation sensitive polymer gel dosimeters

International Nuclear Information System (INIS)

Lepage, M.; Back, S.A.J.; Baldock, C.; Whittaker, A.K.; Rintoul, L.

2000-01-01

Full text: Radiation sensitive gels are studied for their potential to retain a permanent 3D dose distribution for applications in radiotherapy. Co-monomers dissolved in a tissue-equivalent hydrogel undergo a polymerization reaction upon absorption of ionizing radiation. The polymer formed influences the local spin-spin relaxation time (T 2 ) of the dosimeter that can be determined using magnetic resonance imaging (MRI). The relationship between T2 and the absorbed dose was studied for different initial chemical compositions. The aim was to find a model linking the changes in T 2 with absorbed dose to the initial composition of the dosimeter. It is believed this will help designing new gel dosimeters having desired properties to minimize the uncertainty in the determination of the dose distribution. 1 H, 13 C nuclear magnetic resonance spectroscopy and FT-Raman spectroscopy were used to quantify the amount of monomers still remaining after the absorption of a given dose of radiation. This data is used to model the changes of T2 as a function of the absorbed dose. A model of fast exchange of magnetization between three proton pools was used, where the fraction of protons (f x H ) in the x th pool is obtained from the chemical composition of the dosimeter and the apparent T2 of each pool is determined for a given composition. Initially, the protons are contained in two pools; a mobile (mob), which contains the water protons and the monomers protons, and a gelatin (gela) proton pool. The mobile pool is partially depleted as polymer is formed, the protons are transferred into the polymer (pol) pool. In the figure, the experimental data along with the calculated values are plotted for three different monomer concentrations, with the gelatin concentration fixed. The model is seen to provide a good fit to the experimental data

Effect of radiation and other cytotoxic agents on the growth of cells cultured from normal and tumor tissues from the female genital tract

International Nuclear Information System (INIS)

Mothersill, C.; Seymour, C.B.; Bonnar, J.

1990-01-01

A technique is presented which allows the response of human gynecological tissue to radiation and cytotoxic drugs to be assessed using a tissue culture explant system. The technique is simple to use and gives results in line with those obtained for human tissues by more complex culture methods. Data are presented showing how the explant technique developed by the group for other tissues can be adapted to yield acceptable results for normal tissue response to radiation. The potential of the technique for use in predictive testing of individual tumor response is then assessed in five cases of gynecological malignancy. It is clear that variations in sensitivity to different radio- and chemotherapy agents and combinations can be detected. The results obtained require clinical validation and it is hoped that this will come over the next few years from evaluation of patient response to treatment using individually optimized, rather than empirical therapy

Radiation sensitivity and gene expression in Enchytraeus japonensis, a species of earth worm

International Nuclear Information System (INIS)

Kubota, Yoshihisa

2011-01-01

The importance of radiological protection of the environment based on scientific principles is gaining international recognition as environment issues garner more attention. Earthworm (annelids) is a ubiquitous soil invertebrate known to play an important role in the maintenance of the soil ecosystem and thus selected as one of 12 kinds of reference animals and plants by the ICRP. In the present study, radiation sensitivity and gene expression in a recently described terrestrial oligochaete, Enchytraeus japonensis (E. japonensis) were studied. E. japonensis worms were acutely irradiated at increasing doses of gamma radiation, and the number of worms after 30 days of radiation was examined. The dose effectively inhibiting 50% of proliferation was approximately 22 Gy, which was comparable to the dose required to elicit growth inhibition in other earthworm species. In order to seek other biological endpoints for more sensitive and/or quicker assessment of radiation effects, gene expression profiling in E. japonensis was also performed, and poly (ADP-ribose) polymerase I (PARP I) was identified as a radiation-responsive gene. PARP I transcript level increased dose-dependently. (author)

The combination of novel targeted molecular agents and radiation in the treatment of pediatric gliomas

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Tina eDasgupta

2013-05-01

Full Text Available Brain tumors are the most common solid pediatric malignancy. For high-grade, recurrent or refractory pediatric brain tumors, radiation therapy (XRT is an integral treatment modality. In the era of personalized cancer therapy, molecularly targeted agents have been designed to inhibit pathways critical to tumorigenesis. Our evolving knowledge of genetic aberrations in low-grade gliomas is being exploited with targeted inhibitors. These agents are also being combined with XRT to increase their efficacy. In this review, we discuss novel agents targeting three different pathways in low-grade gliomas, and their potential combination with XRT. B-Raf is a kinase in the Ras/Raf/MAPK kinase pathway, which is integral to cellular division, survival and metabolism. In low-grade pediatric gliomas, point mutations in BRAF (BRAF V600E or a BRAF fusion mutation (KIAA1549:BRAF causes overactivation of the MEK/MAPK pathway. Pre-clinical data shows cooperation between XRT and tagrgeted inhibitors of BRAF V600E, and MEK and mTOR inhibitors in the gliomas with the BRAF fusion. A second important signaling cascade in pediatric glioma pathogenesis is the PI3 kinase (PI3K/mTOR pathway. Dual PI3K/mTOR inhibitors are poised to enter studies of pediatric tumors. Finally, many brain tumors express potent stimulators of angiogenesis. Several inhibitors of immunomodulators are currently being evaluated in in clinical trials for the treatment of recurrent or refractory pediatric central nervous system (CNS tumors. In summary, combinations of these targeted inhibitors with radiation are currently under investigation in both translational bench research and early clinical trials. We summarize the molecular rationale for, and the pre-clinical data supporting the combinations of these targeted agents with other anti-cancer agents and XRT in pediatric gliomas. Parallels are drawn to adult gliomas, and the molecular mechanisms underlying the efficacy of these agents is discussed

Derivation of Continuum Models from An Agent-based Cancer Model: Optimization and Sensitivity Analysis.

Science.gov (United States)

Voulgarelis, Dimitrios; Velayudhan, Ajoy; Smith, Frank

2017-01-01

Agent-based models provide a formidable tool for exploring complex and emergent behaviour of biological systems as well as accurate results but with the drawback of needing a lot of computational power and time for subsequent analysis. On the other hand, equation-based models can more easily be used for complex analysis in a much shorter timescale. This paper formulates an ordinary differential equations and stochastic differential equations model to capture the behaviour of an existing agent-based model of tumour cell reprogramming and applies it to optimization of possible treatment as well as dosage sensitivity analysis. For certain values of the parameter space a close match between the equation-based and agent-based models is achieved. The need for division of labour between the two approaches is explored. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ecological effects of ionizing radiation and other toxic agents on the aquatic microcosm

International Nuclear Information System (INIS)

Fuma, Shoichi; Ishii, Nobuyoshi; Tanaka, Nobuyuki; Takeda, Hiroshi; Miyamoto, Kiriko; Yanagisawa, Kei; Kawabata, Zen'ichiro

2004-01-01

The purpose of this study was comparative evaluation of effects of ionizing radiation and other various toxic agents on aquatic microbial communities. For this purpose, the authors investigated effects of γ-rays, ultraviolet (UV) radiation, acidification, aluminum, manganese, nickel, copper and gadolinium on the microcosm, i.e., the experimental model ecosystem consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Eseherichia coli as a decomposer. Effects of toxic agents in the microcosm were not only direct effects but also community-level effects due to interactions among the constituting species or between organisms and toxic agents. In general, the degrees of effects observed in the microcosm could be categorized as follows: no effects; recognizable effects, i.e., decrease or increase in the cell densities of at least one species; severe effects, i.e., extinction of one or two species; and destructive effects, i.e., extinction of all species. These results were analyzed by the ecological effect index (EEI), in which differences in the cell densities between exposed and control microcosm were represented by the Euclidean distance function. A 50% effect doses for the microcosm (ED M50 ), at which the EEI became 50%, were evaluated to be 530 Gy for γ-rays, 2100 J m -2 for UV, 4100 μM for manganese, 45 μM for nickel, 110 μM for copper and 250 μM for gadolinium. (author)

A ΔdinB mutation that sensitizes Escherichia coli to the lethal effects of UV- and X-radiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Mei-Chong W.; Franco, Magdalena; Vargas, Doris M. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Hudman, Deborah A. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States); White, Steven J. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Fowler, Robert G., E-mail: rfowler@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Sargentini, Neil J. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States)

2014-05-15

Highlights: • We describe Δ(dinB-yafN)883(::kan), a novel dinB allele, referred to as ΔdinB883, a deletion that sensitizes E. coli cells to UV irradiation. • This UV radiation sensitivity is most acute in the early logarithmic phase of culture growth. • This UV radiation sensitivity is completely dependent upon a functional umuDC operon. • Sequencing reveals ΔdinB883 retains the proximal 161 nucleotides, i.e., 54 amino acids, of the wild-type sequence. • The ΔdinB883 mutant is hypothesized to produce a peptide of 83 amino acids, DinB883, that compromises UmuDC function. - Abstract: The DinB (PolIV) protein of Escherichia coli participates in several cellular functions. We investigated a dinB mutation, Δ(dinB-yafN)883(::kan) [referred to as ΔdinB883], which strongly sensitized E. coli cells to both UV- and X-radiation killing. Earlier reports indicated dinB mutations had no obvious effect on UV radiation sensitivity which we confirmed by showing that normal UV radiation sensitivity is conferred by the ΔdinB749 allele. Compared to a wild-type strain, the ΔdinB883 mutant was most sensitive (160-fold) in early to mid-logarithmic growth phase and much less sensitive (twofold) in late log or stationary phases, thus showing a growth phase-dependence for UV radiation sensitivity. This sensitizing effect of ΔdinB883 is assumed to be completely dependent upon the presence of UmuDC protein; since the ΔdinB883 mutation did not sensitize the ΔumuDC strain to UV radiation killing throughout log phase and early stationary phase growth. The DNA damage checkpoint activity of UmuDC was clearly affected by ΔdinB883 as shown by testing a umuC104 ΔdinB883 double-mutant. The sensitivities of the ΔumuDC strain and the ΔdinB883 ΔumuDC double-mutant strain were significantly greater than for the ΔdinB883 strain, suggesting that the ΔdinB883 allele only partially suppresses UmuDC activity. The ΔdinB883 mutation partially sensitized (fivefold) uvrA and uvr

Effect of ethanol of the radiation sensitivity of human hemoglobin

International Nuclear Information System (INIS)

Szweda-Lewandowska, Z.; Puchala, M.

1981-01-01

Radiation sensitivity of oxy-, deoxy-, and methemoglobin (HbOs, Hbbj, and MetHb) in water solutions containing 0.2 M ethanol and in ethanol-free solutions was compared. Radiation sensitivity was estimated on the basis of changes in absorbance at the Soret band (a = 430 nm for deoxyhemoglobin), changes in the absorbance ration Avqv/Avwt determined after conversion of irradiated preparations to methemoglobin, and changes in the value of parameters describing the reaction of hemoglobin oxygenation. The protection coefficient p of hemoglobin by ethanol (ratio of a change in the absence of ethanol to that in its presence) calculated from changes in absorbance at the Soret band equaled about 1.5 at a 4-Mrad dose in all bases except MetHb irradiated in air for which p was much higher (about 3.2). The protection coefficient p' calculated from Dtx values for changes in Avchemically bondv/Avwt equaled 2.2 for HbOs, and 2.8 for MetHb for preparations irradiated in air; p' = 1.7 for Hbbj and 1.8 for MetHb for preparations irradiated under argon. On the basis of these results, the role of /sup ./OH radicals and oxygen in the radiation damage of hemoglobin is discussed

Effect of radiation and alkylating agents on chromatin degradation in normal and malignant lymphoid cells

International Nuclear Information System (INIS)

Ryabchenko, N.I.; Yurashkova, V.; Ivannik, B.P.; Konov, A.V.; Drashil, V.

1991-01-01

Regularities of chromatin degradation in thymocytes and LS/BL tumor cells have been investigated. It has been shown that the rate of DNA degradation by Ca/Mg-dependent endonuclease in LS/BL tumor cells is 25 times lower than that in thymocytes, and radiation does not induce chormatin degradation. The alkylating agent TS 160 causes chromatin degradation in both LS/Bl cells and thymocytes. In contrast to radiation TS 160 inhibits the endogenous chromatin degradation by Ca/Mg-dependent endonuclease in thymocytes

Production and characterization of radiation-sensitive meiotic mutants of Coprinus cinereus

International Nuclear Information System (INIS)

Zolan, M.E.; Tremel, C.J.; Pukkila, P.J.

1988-01-01

We have isolated four gamma-sensitive mutants of the basidiomycete Coprinus cinereus. When homozygous, two of these (rad 3-1 and rad 9-1) produce fruiting bodies with very few viable basidiospores, the products of meiosis in this organism. A less radiation-sensitive allele of RAD 3, rad 3-2, causes no apparent meiotic defect in homozygous strains. Quantitative measurements of oidial survival of rad 3-1;rad 9-1 double mutants compared to the single mutants indicated that rad 3-1 and rad 9-1 mutants are defective in the same DNA repair pathway. In the pew viable basidiospores that are produced by these two strains, essentially normal levels of meiotic recombination can be detected. None of the mutants exhibits increased sensitivity to UV radiation. Cytological examination of meiotic chromosomes from mutant and wild-type fruiting bodies showed that rad 3-1 homozygous strains fail to condense and pair homologous chromosomes during prophase I. Although rad 9-1 strains are successful at chromosome pairing, meiosis is usually not completed in these mutants

Methylation of the ATM promoter in glioma cells alters ionizing radiation sensitivity

International Nuclear Information System (INIS)

Roy, Kanaklata; Wang, Lilin; Makrigiorgos, G. Mike; Price, Brendan D.

2006-01-01

Glioblastomas are among the malignancies most resistant to radiation therapy. In contrast, cells lacking the ATM protein are highly sensitive to ionizing radiation. The relationship between ATM protein expression and radiosensitivity in 3 glioma cell lines was examined. T98G cells exhibited normal levels of ATM protein, whereas U118 and U87 cells had significantly lower levels of ATM and increased (>2-fold) sensitivity to ionizing radiation compared to T98G cells. The ATM promoter was methylated in U87 cells. Demethylation by azacytidine treatment increased ATM protein levels in the U87 cells and decreased their radiosensitivity. In contrast, the ATM promoter in U118 cells was not methylated. Further, expression of exogenous ATM did not significantly alter the radiosensitivity of U118 cells. ATM expression is therefore heterogeneous in the glioma cells examined. In conclusion, methylation of the ATM promoter may account for the variable radiosensitivity and heterogeneous ATM expression in a fraction of glioma cells

Hydroxyurea as a radiation sensitizer in malignancies of the head and neck

International Nuclear Information System (INIS)

Mohanta, P.K.; Singhal, R.M.; Jindel, R.; Sharma, R.L.; Julka, P.K.

1992-01-01

A prospective randomized trail was undertaken to assess the efficacy of hydroxyurea as a radiation sensitizer. Disease control rates achieved significance (p<0.01) values only at 2 and 3 months post-radiation. At the end of 2 years of follow-up there was no significant difference in the disease control rate between the control and the experimental group. The toxicity in the experimental group was acceptable. One patient had severe vomiting; 13% showed severe mucositis, 4.5% had erythema of the treatment area and 40% showed dry desquamation. There seems to be no added advantage of hydroxyurea and radiation over radiation alone. (author). 12 refs., 2 tabs

Residual injury to the hemopoietic microenvironment following sequential radiation and alkylating agents

International Nuclear Information System (INIS)

Wathen, L.M.K.

1981-01-01

To assess the hemopoietic impact following combined therapy, mice received intraperitoneal doses of cyclophosphamide one week after 1500 rad leg irradiation. This treatment inhibited repopulation of endogenous nucleated cells to less than 60% of normal. Leg irradiation alone repressed the repopulation to about 75% of normal and cyclophosphamide alone suppressed to 80% of normal. Differential marrow counts revealed that marrow stromal cells were suppressed to less than 30% normal for 3 months following combined modality treatment. Studies were initiated to determine whether busulfan, an alkylating agent known to produce aplastic anemia, would cause microenvironmental damage similar to that seen following cyclophosphamide. The mice received intraperitoneal doses of busulfan one week after 1500 rad leg irradation. In general, the pattern of hemopoietic suppression was similar to that following sequential radiation and cyclophosphamide. However, at 4 and 6 months post-irradiation, the busulfan treated mice had a more severe suppression of CFU-S, CFU-C, and marrow stromal cells than mice treated with cyclophosphamide alone. In addition, an excessive number of myeloid blast cells and a severe erythroid depletion suggested that the BU-treated mice were preleukemic. Vascular patency was studied by injecting 51 Cr labeled autologous red blood cells into mice treated with the radiation and busulfan regimen. Combined modality therapy inhibited the ingress of 51 Cr labeled erythrocytes into the irradiated femur but either modality alone did not cause inhibition. It was concluded that a portion of the microenvironmental defect seen in the combined radiation and alkylating agent studies was the result of microvascular damage and that a portion was due to marrow stromal cell insufficiency

Modification of radiation sensitivity by edaravone

Energy Technology Data Exchange (ETDEWEB)

Sasano, Nakashi; Enomoto, Atsushi; Miyagawa, Kiyoshi [Tokyo Univ., Graduate School of Medicine, Tokyo (Japan); Hosoi, Yoshio [Niigata Univ., School of Health Sciences, Niigata, Niigata (Japan); Nakagawa, Keiichi [Tokyo Univ., Hospital, Tokyo (Japan)

2009-03-15

Studied was the effect of edaravone (E), a clinical therapeutic drug for brain infarction possessing properties of free radical scavenger, on apoptosis in vitro. Human T-cell leukemic MOLT-4 cells and p53-knockdown MOLT-4 cells which overexpressing short hairpin type p53 by siRNA treatment were X-irradiated by Shimadzu Pantak HF 350 machine at 135-140 cGy/min for 2-5 Gy in total, in the presence of E. Cell death was estimated by dye-exclusion, apoptosis by EPICS flow cytometry, cellular reactive oxygen species by chloromethyl-2',7'-dichlorodihydrofluoresein diacetate (CM-H{sub 2}-DCFDA) fluorometry, and p53-related protein expression by Western blotting. E was found to have a radio-protective effect on cells at high concentrations (e.g., 2.7 and 3 mg/mL, 2Gy) and radio-sensitizing action at low concentrations (e.g., 0.15-1.5 mg/mL). Clinical plasma levels of E have been reportedly far lower than the concentrations in this experiment: ideally, E can sensitize tumor cells to radiation and protect normal cells from. (K.T.)

Investigation of some parameters influencing the sensitivity of human tooth enamel to gamma radiation using electron paramagnetic resonance

International Nuclear Information System (INIS)

El-Faramawy, N.

2008-01-01

Electron paramagnetic resonance (EPR) has been successfully used as a physical technique for gamma radiation dose reconstruction using calcified tissues. To minimize potential discrepancies between EPR readings in future studies, the effects of cavity response factor, tooth position and donor gender on the estimated gamma radiation dose were studied. It was found that the EPR response per sample mass used for assessment of doses in teeth outside of the 70-100 mg range should be corrected by a factor which is a function of the sample mass. In the EPR measurements, the difference in sensitivity of different tooth positions to γ-radiation was taken into consideration. It was determined that among all the premolars and molars tooth positions, the relative standard deviation of sensitivity was 6.5%, with the wisdom teeth and the first molars having the highest and lowest sensitivity to γ-radiation, respectively. The current results reveal no effect of the donor gender on the sensitivity to γ-radiation. (author)

Sensitivity to low-dose radiation in radiosensitive ''wasted'' mice

International Nuclear Information System (INIS)

Paunesku, T.; Protic, M.; Woloschak, G. E.

1999-01-01

Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T-cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T-lymphocytes and motor neuron cells afflicted by the 3-bp deletion in the PCNA promoter. The model is as follows: Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis; this absence of expression is mediated by a positive transactor that can bind to the wild-type but not the wasted mutant PCNA promoter; the bound protein induces late expression of PCNA in T-lymphocytes and prevents onset of radiation sensitivity in the cells

Control of radiation sensitivity of mammalian cells. Regulation of expression of DNA repair genes

International Nuclear Information System (INIS)

Yoshida, Kayo; Morita, Takashi

2003-01-01

This review describes authors' investigations concerning regulation of expression of DNA repair genes for the purpose of control of radiosensitivity of mammalian cells for cancer radiotherapy. One of their experiments concerns the enhancement of sensitivity to radiation and anti-tumor agents by suppressing the expression of mammalian Rad51 gene which playing a central role in recombination repair against DNA double-strand break, by RNA interference (RNAi). Described are the mode of action of RNAi, mechanism of suppression of Rad51 gene expression by it, enhancing effect in radiosensitivity, stable suppression and enhancement by hairpin RNA and its possible usefulness in cancer therapy. The other concerns the histone H2AX gene, which delivering the repair signal post phosphorylation in chromatin against the double-strand break. Experimental results of suppression of the histone H2AX gene by tet-off system, enhancement of radiosensitivity by the suppression and functional recovery by the gene transfer are described, and the radiosensitivity can be thus artificially controlled by tetracycline in authors' F9 2AX (tet/tet) cells. (N.I.)

Characterization of image heterogeneity using 2D Minkowski functionals increases the sensitivity of detection of a targeted MRI contrast agent.

Science.gov (United States)

Canuto, Holly C; McLachlan, Charles; Kettunen, Mikko I; Velic, Marko; Krishnan, Anant S; Neves, Andre' A; de Backer, Maaike; Hu, D-E; Hobson, Michael P; Brindle, Kevin M

2009-05-01

A targeted Gd(3+)-based contrast agent has been developed that detects tumor cell death by binding to the phosphatidylserine (PS) exposed on the plasma membrane of dying cells. Although this agent has been used to detect tumor cell death in vivo, the differences in signal intensity between treated and untreated tumors was relatively small. As cell death is often spatially heterogeneous within tumors, we investigated whether an image analysis technique that parameterizes heterogeneity could be used to increase the sensitivity of detection of this targeted contrast agent. Two-dimensional (2D) Minkowski functionals (MFs) provided an automated and reliable method for parameterization of image heterogeneity, which does not require prior assumptions about the number of regions or features in the image, and were shown to increase the sensitivity of detection of the contrast agent as compared to simple signal intensity analysis. (c) 2009 Wiley-Liss, Inc.

Rapid-mixing studies on the time-scale of radiation damage in cells

International Nuclear Information System (INIS)

Adams, G.E.; Michael, B.D.; Asquith, J.C.; Shenoy, M.A.; Watts, M.E.; Whillans, D.W.

1975-01-01

Rapid mixing studies were performed to determine the time scale of radiation damage in cells. There is evidence that the sensitizing effects of oxygen and other chemical dose-modifying agents on the response of cells to ionizing radiation involve fast free-radical processes. Fast response technique studies in bacterial systems have shown that extremely fast processes occur when the bacteria are exposed to oxygen or other dose-modifying agents during irradiation. The time scales observed were consistent with the involvement of fast free-radical reactions in the expression of these effects

Specificity and sensitivity of NMR based urinary metabolic biomarker for radiation injury

International Nuclear Information System (INIS)

Tyagi, Ritu; Watve, Apurva; Khushu, Subash; Rana, Poonam

2016-01-01

Increasing burden of natural background radiation and terrestrial radionuclides is a big threat of radiation exposure to the population at large. It is necessary to develop biomarker of ionizing radiation exposure that can be used for mass screening in the event of a radiological mass casualty incident. Metabolomics has already been proven as an excellent developing prospect for capturing diseases specific metabolic signatures as possible biomarkers. The aim of the present study is to evaluate the sensitivity and specificity of the urinary metabolites after whole body radiation exposure which can further be used as early predictive marker. The PLS-DA based ROC curve depicted taurine as a biomarker of early radiation injury. This study along with other 'omics' technique will be useful to help design strategies for non-invasive radiation biodosimetry through metabolomics in human populations

Sensitivity of APSIM/ORYZA model due to estimation errors in solar radiation

Directory of Open Access Journals (Sweden)

Alexandre Bryan Heinemann

2012-01-01

Full Text Available Crop models are ideally suited to quantify existing climatic risks. However, they require historic climate data as input. While daily temperature and rainfall data are often available, the lack of observed solar radiation (Rs data severely limits site-specific crop modelling. The objective of this study was to estimate Rs based on air temperature solar radiation models and to quantify the propagation of errors in simulated radiation on several APSIM/ORYZA crop model seasonal outputs, yield, biomass, leaf area (LAI and total accumulated solar radiation (SRA during the crop cycle. The accuracy of the 5 models for estimated daily solar radiation was similar, and it was not substantially different among sites. For water limited environments (no irrigation, crop model outputs yield, biomass and LAI was not sensitive for the uncertainties in radiation models studied here.

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)

Sensitization of human cells by inhibitors of DNA synthesis following the action of DNA-damaging agents

Energy Technology Data Exchange (ETDEWEB)

Filatov, M.V.; Noskin, L.A. (Leningrad Inst. of Nuclear Physics, Gatchina (USSR))

1983-08-01

Inhibitors of DNA synthesis 1-..beta..-arabinofuranosylcytosine (Ac) and hydroxyurea (Hu) taken together drastically sensitized human cells to the killing effect of DNA-damaging agents. For UV-irradiation this sensitization depended on the cells' ability for excision repair. By using viscoelastometric methods of measurement of double-strand breaks (DSB) in the genome, it was established that the first DSB were generated after incubation of the damaged cells in the mixture of inhibitors at about the same dose when sensitization appeared. A scheme is proposed to describe molecular events associated with the phenomenon studied. 35 refs.

The role of the HCR system in the repair of lethal lesions of Bacillus subtilis phages and their transfecting DNA damaged by radiation and alkylating agents

International Nuclear Information System (INIS)

Vizdalova, M.; Janovska, E.; Zhestyanikov, V.D.

1980-01-01

The role of the HCR system in the repair of prelethal lesions induced by UV light, γ radiation and alkylating agents was studied in the Bacillus subtilis SPP1 phage, its heat sensitive mutants (N3, N73 nad ts 1 ) and corresponding infectious DNA. The survival of phages and their transfecting DNA after treatment with UV light is substantially higher in hcr + cells than in hcr cells, the differences being more striking in intact phages than in their transfecting DNA's. Repair inhibitors reduce survival in hcr + cells: caffeine lowers the survival of UV-irradiated phage SPP1 in exponentially growing hcr + cells but has no effect on its survival in competent hcr + cells; acriflavin and ethidium bromide decrease the survival of the UV-irradiated SPP1 phage in both exponentially growing and competent hcr + cells to the level of survival observed in hcr cells; moreover, ethidium bromide lowers the number of infective centres in hcr + cells of the UV-irradiated DNA of the SPP1 phage. Repair inhibitors do not lower the survival of the UV-irradiated phages or their DNA in hcr cells. The repair mechanism under study also effectively repairs lesions induced by polyfunctional alkylating agents in the transfecting DNA's of B. subtilis phages but is not functional with lesions induced by these agents in free phages and lesions caused in the phages and their DNA by ethyl methanesulphonate or γ radiation. (author)

The study of the radiation protection effects of TMG to the fetus on the organogenesis stage in ICR mice

International Nuclear Information System (INIS)

Gu, Yeunhwa; Santokuya, Takumi; Suzuki, Ikukatsu; Hasegawa, Takeo; Yamamoto, Youichi; Bamen, K.; Yanagisawa, Takaharu; Iwasa, Toshihiro

2000-01-01

Experimental studies on mice have made it clear that embryos are more sensitive to radiation during Organogenesis than other prenatal periods. However, the radiation protection of TMG at Organogenesis in mice has yet to be described. The Organogenesis stage is the most important from the viewpoint of ionizing protection. Many physical and chemical agents in the environment can affect an embryo. Fetal deaths were classified as Preimplantation, Embryonic and Fetal. The sensitivity of the fetus is high in comparison with the maturates and the child to the various environmental agent. It is the individium, which should pay attention to it specially when a fetus' safety is thought about. Because it isn't noticed, the fetus of the organogenesis can't avoid fetus' existence regardless of the individium of which sensibility is high in the intention target. Therefore, protection resource and others must be studied after the fetus' effects of the organogenesis are studied fully. It paid attention to radiation in the environmental agent, and it was examined about the radiation protection effect of TMG to fetus' teratogenesis by this study. We studied an excuse as a radioprotective agent of the high malformation of the sensitivity most by using TMG to the radiation. This study aimed at obtaining the information to provide it for the fetus' protection to the various environmental radiations. As for Preimplantation death, there was a statistical difference the 2.0 Gy Group in comparison with the control group (p<0.05). Embryonic death, a statistical difference was recognized as in all the treatment groups (p<0.001). But, as for the TMG+radiation group, Embryonic death decreased to 1/4. As for Malformation rate, a statistical difference was recognized as in all treatment group (p<0.001). But, as for the TMG+radiation group, Malformation rate decreased to 1/2. As for Fetal body weight, a statistical difference was recognized in radiation group, the radiation+TMG infusion group

Comparison of the oncogenic potential of several chemotherapeutic agents

International Nuclear Information System (INIS)

Miller, R.C.; Hall, E.J.; Osmak, R.S.

1981-01-01

Several chemotherapeutic drugs that have been routinely used in cancer treatment were tested for their carcinogenic potential. Two antitumor antibiotics (adriamycin and vincristine), an alkalating agent (melphalan), 5-azacytidine and the bifunctional agent cis-platinum that mimics alkylating agents and/or binds Oxygen-6 or Nitrogen-7 atoms of quanine were tested. Cell killing and cancer induction was assessed using in vitro transformation system. C3H/10T 1/2 cells, while normally exhibiting contact inhibition, can undergo transformation from normal contact inhibited cells to tumorgenic cells when exposed to chemical carcinogens. These cells have been used in the past by this laboratory to study oncogenic transformation of cells exposed to ionizing radiation and electron affinic compounds that sensitize hypoxic cells to x-rays. The endpoints of cell killing and oncogenic transformation presented here give an estimate of the carcinogenic potential of these agents

Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

Energy Technology Data Exchange (ETDEWEB)

Sekhar, Konjeti R. [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Benamar, Mouadh [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Venkateswaran, Amudhan; Sasi, Soumya [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Penthala, Narsimha R.; Crooks, Peter A. [Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hann, Stephen R. [Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Geng, Ling [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Balusu, Ramesh [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas (United States); Abbas, Tarek [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Freeman, Michael L., E-mail: michael.freeman@vanderbilt.edu [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States)

2014-08-01

Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity.

Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

International Nuclear Information System (INIS)

Sekhar, Konjeti R.; Benamar, Mouadh; Venkateswaran, Amudhan; Sasi, Soumya; Penthala, Narsimha R.; Crooks, Peter A.; Hann, Stephen R.; Geng, Ling; Balusu, Ramesh; Abbas, Tarek; Freeman, Michael L.

2014-01-01

Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity

[Fitness of workers with particular sensitivity to non-ionizing radiation].

Science.gov (United States)

Moccaldi, R; Grandi, C

2011-01-01

Chapter IV and V of Title VIII of D.Lgs 81/2008, implementing the Directives 2004/40/EC respectively (protection of workers exposed to electromagnetic fields) and 2006/25/EC (protection of workers exposed to artificial optical radiation), make frequent reference to the workers as "at particular risk" namely those workers who, by their biological or pathological characteristics, lifestyles, multiple exposure to other risk factors, may be more susceptible to the effects of electromagnetic fields or optical radiation. The identification of workers with particular sensitivity is essential for health surveillance, in particular regarding the determination of fitness. The operational guidance on Title VIII of D.Lgs 81/2008 drafted by the Italian Technical Coordination for Safety in the workplace of Regions and Autonomous Provinces (Document No. 1-2009), in collaboration with ISPESL and ISS, includes a preliminary identification of the categories of workers considered most susceptible to the risk from exposure to electromagnetic fields and optical radiation. On the basis of this information the authors identified more focused and structured classes of workers to be considered as "particularly sensitive to risk", it is not only related to a specific wavelength, but based on a comprehensive risk assessment in individual exposure situation, with regard to the exposure levels, any multiple exposures, the possibility of adequate personal protection.

SENSITIVITY TO ANTIBACTERIAL DRUGS IN AGENTS OF COMMUNITY-ACQUIRED INFECTIONS

Directory of Open Access Journals (Sweden)

Osolodchenko T.,

2015-04-01

Full Text Available Introduction The widespread and uncontrolled use of antibiotics leads to selection of resistant strains and rise to atypical forms of most infectious agents. Constantly progressive resistance of microorganisms is currently the most important negative phenomenon of antibiotic therapy. The aim of the work was to optimize antibiotic therapy in community-acquired infections. The objective of study was to determine the range and degree of resistance in clinical isolates of microorganisms of different taxonomic groups, obtained from patients in outpatient care. Material and methods 213 clinical isolates of microorganisms obtained from patients in outpatient care were studied: 34,7 % strains were obtained from patients with inflammatory processes in upper respiratory tract, 11,7 % – with ear inflammation, 36,6 % – with inflammatory diseases of urinary and genital tracts, 11,3 % – with of skin and soft tissues inflammation, 4,2 % – eye inflammation and 1,4 % – with postoperative infectious complications. The collection of clinical material was performed accordingly before the start of antibacterial therapy. Microorganisms’ isolation and identification were carried out with the help of microbiological methods according to the regulatory documents. The study of resistance of bacterial strains to the antibacterial drugs was performed with the help of disc diffusion method on the Muller-Hinton nutritional medium and of fungal strains – on Saburo medium with the use of standard commercial discs. Results and discussion The array and level of resistance to antibacterial drugs in clinical isolates of microorganisms of different taxonomic groups obtained from patients in outpatient care was established. The research has established that 43,3 % Staphylococcus spp. isolates possessed polyantibiotic resistance and 3,8 % – extensive resistance, only sensitivity to aminoglycosides and glycopeptides was preserved. The majority of beta

Incoming longwave radiation to melting snow: observations, sensitivity and estimation in Northern environments

Science.gov (United States)

Sicart, J. E.; Pomeroy, J. W.; Essery, R. L. H.; Bewley, D.

2006-11-01

At high latitudes, longwave radiation can provide similar, or higher, amounts of energy to snow than shortwave radiation due to the low solar elevation (cosine effect and increased scattering due to long atmospheric path lengths). This effect is magnified in mountains due to shading and longwave emissions from the complex topography. This study examines longwave irradiance at the snow surface in the Wolf Creek Research Basin, Yukon Territory, Canada (60° 36N, 134° 57W) during the springs of 2002 and 2004. Incoming longwave radiation was estimated from standard meteorological measurements by segregating radiation sources into clear sky, clouds and surrounding terrain. A sensitivity study was conducted to detect the atmospheric and topographic conditions under which emission from adjacent terrain significantly increases the longwave irradiance. The total incoming longwave radiation is more sensitive to sky view factor than to the temperature of the emitting terrain surfaces. Brutsaert's equation correctly simulates the clear-sky irradiance for hourly time steps using temperature and humidity. Longwave emissions from clouds, which raised longwave radiation above that from clear skies by 16% on average, were best estimated using daily atmospheric shortwave transmissivity and hourly relative humidity. An independent test of the estimation procedure for a prairie site near Saskatoon, Saskatchewan, Canada, indicated that the calculations are robust in late winter and spring conditions. Copyright

Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Luzhna, Lidia [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada); Kovalchuk, Olga, E-mail: olga.kovalchuk@uleth.ca [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada)

2010-02-05

Chemoresistant tumors often fail to respond to other cytotoxic treatments such as radiation therapy. The mechanisms of chemo- and radiotherapy cross resistance are not fully understood and are believed to be epigenetic in nature. We hypothesize that MCF-7 cells and their doxorubicin-resistant variant MCF-7/DOX cells may exhibit different responses to ionizing radiation due to their dissimilar epigenetic status. Similar to previous studies, we found that MCF-7/DOX cells harbor much lower levels of global DNA methylation than MCF-7 cells. Furthermore, we found that MCF-7/DOX cells had lower background apoptosis levels and were less responsive to radiation than MCF-7 cells. Decreased radiation responsiveness correlated to significant global DNA hypomethylation in MCF-7/DOX cells. Here, for the first time, we show that the radiation resistance of MCF-7/DOX cells can be reversed by an epigenetic treatment - the application of methyl-donor SAM. SAM-mediated reversal of DNA methylation led to elevated radiation sensitivity in MCF-7/DOX cells. Contrarily, application of SAM on the radiation sensitive and higher methylated MCF-7 cells resulted in a decrease in their radiation responsiveness. This data suggests that a fine balance of DNA methylation is needed to insure proper radiation and drug responsiveness.

Comparison of two different techniques on the human lymphocytes morphology and sensitivity to gamma radiation

International Nuclear Information System (INIS)

Kol, R.

1985-02-01

The lymphocytes in the peripheral blood are divided into two main subclasses: T cells and B cells. These differ from each other in function and in their sensitivity to radiation. The effort to study which group is more sensitive to radiation has resulted in many contradictory results. In the present study we examined whether the methods that are used to separate the lymphocytes from the whole blood, before their separation into subclasses, have an effect on the cells and whether this might contribute to the contradictory results. Blood samples were taken from several normal donors and each sample was devided into two fractions. Lymphocytes in each fraction were separated by one of the two following methods: a) sedimentation of erythrocytes by gravitation; b) separation on Ficoll-Paque density gradient. For cells obtained by these two methods, the ultrastructure was examined by electron microscopy and their ability to incorporate radioactive thymidine was measured. Samples separated on Ficoll-Paque showed a subpopulation with morphological changes similar to those occuring in lymphocytes undergoing stimulation. Unstimulated cells separated on Ficoll-Paque showed greater sensitivity to radiation. The effect of gamma radiation on the capability of lymphocytes to undergo transformation in response to three mitogens; PHA, PWM and Con A was examined. Different mitogens stimulate different lymphocytes subpopulations. There was no difference between the two separation methods regarding the sensitivity to gamma radiation of stimulation by PAH and PWM. The transformation by Con A of lymphocytes separated on Ficoll-Paque was more radiosensitive. This could indicate that the separation by Ficoll-Paque density gradient causes a selective depletion of T lymphocytes that react with Con A and are considered more radioresistant. The use of different methods for separating lymphocytes from whole blood- each has a different influence on the cells- can contribute to contradictory

Oyster radiation sensitivity; Sensibilidade de ostras a radiacao

Energy Technology Data Exchange (ETDEWEB)

Marchese, Sandra R.M. [Centro Tecnologico da Marinha em Sao Paulo (CTMSP), SP (Brazil); Mastro, Nelida L. del [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

1996-07-01

Various food products like oysters, crabs and shrimps have been described as possible Vibrio spp. transmitting agents. Seafood irradiation is been presented as an alternative among the different public health intervention measures to control food borne diseases. The objective of this work was to establish, firstly, the radioresistance of Crassostrea brasiliana oysters. The oysters were irradiated with Co-60 radiation with doses of 0, 1.5,3 and 6 kGy. Survival curves a function of time showed that 100% of samples irradiated with 3 kGy survived at least 6 days; among those irradiated with 6 kGy, 100% survived 3 days. These results are encouraging since a dose of 2 kGy is already effective in diminishing oyster bioburden. (author)

Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Gaikwad, Pallavi S. [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India); Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Panicker, Lata [Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Mohole, Madhura; Sawant, Sangeeta [Bioinformatics Center, Savitribai Phule Pune University, Pune, 411007 (India); Mukhopadhyaya, Rita [Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Nath, Bimalendu B., E-mail: bbnath@gmail.com [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India)

2016-08-05

Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.

Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

International Nuclear Information System (INIS)

Gaikwad, Pallavi S.; Panicker, Lata; Mohole, Madhura; Sawant, Sangeeta; Mukhopadhyaya, Rita; Nath, Bimalendu B.

2016-01-01

Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.

Age dependent radiation sensitivity of eggs of Dysdercus koenigii Fabricius

International Nuclear Information System (INIS)

Harwalkar, M.R.

1992-01-01

Eggs of Dysdercus koenigii Fabricius aged 0 to 2, 24, 48 and 72 hr were irradiated with X-ray doses ranging between 3 to 15 Gy to determine radiation sensitivity. It was observed that age of the eggs greatly influenced their response to radiation treatment. A dose of 6 Gy was required to prevent hatching of 0 to 2 hr old eggs but older eggs (24 and 48 hr) required 9 and 15 Gy, respectively, to bring about the same effect. At all the doses hatchability of 72 hr old irradiated eggs was much higher than those irradiated at younger age. Survival of nymphs emerging from 72 hr irradiated eggs at different dose levels was found to be dose dependent. Percentage of nymphs metamorphosing into adults decreased with increasing radiation dose received at the embryonic stage. (author). 21 refs., 2 figs

Metal-containing radiation-sensitive polymers

International Nuclear Information System (INIS)

Lee, A.Y.

1986-01-01

The copolymers of methyl methacrylate with alkali metal salts (Na, K, and Cs) of methacrylic acid have been prepared by saponification K, and Cs) of methylacrylic acid have been prepared by saponification of the homopolymer poly(methyl methacrylate), PMMA. Low degrees of hydrolysis have been achieved by a heterogeneous system, and from the infrared spectra it has been confirmed that the ester groups of the methyl methacrylates are directly converted to the metal salts of methacrylic acid. These ionomers exhibit pseudo high molecular weights in gel permeation chromatogram, but no appreciable increase in intrinsic viscosities is observed in comparison to PMMA. The coordinated inorganic polymers poly[(dithio-2,2'-diacetato)bis(dimethylsulfoxide)dioxouranium(VI)] and poly[{methylenebis(thio)-2,2'-bis(acetato)}bis(dimethylsulfoxide)dioxouranium(VI)]have been synthesized in dimethyl sulfoxide solution with about 90% yield. The degree of polymerization and the number of average molecular weights of these polymers have been assessed by high resolution nuclear magnetic resonance, with which the acetato end group to the bridging ligand group ratios have been determined. The polymers bridging ligand group ratios have been determined. The polymers have been characterized by employing various techniques: infrared spectra, thermal gravimetric analysis, 13 C solid state nuclear magnetic resonance, and gel permeation chromatography. The prepared polymer samples have been subjected to various doses of 137 Cs gamma radiation under which the polymers predominantly undergo chain scission. The radiation sensitivities of the polymers are assessed by G values which are obtained from gel permeation chromatograms. These uranyl polymers exhibit unusually high G values

Sensitivity of Escherichia coli acrA Mutants to Psoralen plus Near-Ultraviolet Radiation

DEFF Research Database (Denmark)

Hansen, M. Trier

1982-01-01

The sensitivity to psoralen plus near-ultraviolet radiation (PUVA) was compared in a pair of E. coli strains differing at the acrA locus. Survival was determined for both bacteria and phage λ. AcrA mutant cells were 40 times more sensitive than wild type to the lethal effect of PUVA. Free λ phage...

The potential sensitivity of tropical plants to increased ultraviolet-B radiation

International Nuclear Information System (INIS)

Ziska, L.H.

1996-01-01

Little is known concerning the impact of stratospheric ozone depletion and increasing ultraviolet (UV)-B radiation on the phenology and growth of tropical plants. This is because, ostensibly, tropical plants are already exposed to relatively high levels of UV-B radiation (relative to a temperate environment) and should, therefore, possess a greater degree of tolerance to increased UV-B radiation. In this brief review I hope to show that, potentially, direct and indirect effects on photosynthesis, assimilate partitioning, phenology and biomass could occur in both tropical crops (e.g. cassava, rice) and native species (e.g. Cecropia obtusifolia (Bertol. Fl)., Tetramolopium humile (Gray), Nana sandwicensis L.). However, it should be noted that differences in sensitivity to UV-B radiation can be related to experimental conditions, and care should be taken to ensure that the quantity and quality of background solar radiation remains at near ambient conditions. Nevertheless, by integrating current and past studies on the impact of UV-B radiation on tropical species, I hope to be able to demonstrate that photosynthesis, morphology and growth in tropical plants could be directly affected by UV-B radiation and that UV-B radiation may be a factor in species and community dynamics in natural plant populations in the tropics

166Ho-chitosan as a radiation synovectomy agent - antigen-induced arthritis in rabbits

International Nuclear Information System (INIS)

Kim, Sug Jun; Lee, Soo Yong; Jeon, Dae Geun; Lee, Jong Seok

1998-01-01

Radiation synovectomy is a noninvasive therapy that has been investigated as an alternative to surgical synovectomy. It has been successfully employed in the treatment of synovitis in rheumatoid arthritis and other inflammatory arthropathies. In this study, we developed experimental animal model for radiation synovectomy. A model system in which a single injection of ovalbumin into the knee joints of previously sensitized rabbits consistently produced a chronic arthritis which was histologically similiar to human rheumatoid arthritis. (author). 8 refs., 8 figs

Potentially three distinct roles for hypoxic cell sensitizers in the clinic

International Nuclear Information System (INIS)

Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

1979-01-01

Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

[Genetic differences in mice in the sensitivity to the immunodepressive action of alkylating agents].

Science.gov (United States)

Kim, N I; Telegin, L Iu; Pevnitskiĭ, L A

1983-04-01

The immunodepressant action of cyclophosphamide, thiophosphamide and sarcolysine was examined in experimental primary immune response in mice of different lines immunized with sheep red blood cells. DBA/2 and C3H/Sn mice were marked by the highest sensitivity to the immunodepressant action of the alkylating agents. BALB/c mice were relatively resistant to the immunodepressant action. Possible reasons for the interspecific differences found are discussed.

Combined effect of environmental radiation and other agents: Is there a synergism trap?

International Nuclear Information System (INIS)

Hornhardt, S.; Jung, T.; Burkart, W.

2002-01-01

Most assessments of possible deleterious outcomes from environmental and occupational exposures concentrate on single agents and neglect the potential for combined effects, i.e. synergisms or antagonisms. Biomechanistic considerations based on multistep processes such as carcinogenesis indicate the potential for highly detrimental interactions, if two or more consecutive rate limiting steps are specifically effected by different agents. However, low specificity towards molecular structure or DNA-sequence - and therefore exchangeability - of many genotoxic agents indicate little functional specificity and therefore little vulnerability towards synergism at most occupational and environmental exposure situations. The low potential for significant combined effects for those common low exposure situations where non-genotoxic agents with highly non-linear dose effect relationships and apparent thresholds are involved, is also evident. Nevertheless, a quantitative assessment of the contribution of synergistic interactions to the total detriment from natural and man-made toxicants based on experimental data is far away. The existing database on combined effects is rudimentary, mainly descriptive and rarely covers exposure ranges large enough to make direct inferences to present day low dose exposure situations. In view of the multitude of possible interactions between the large number of potentially harmful agents in the human environment, descriptive approaches will have to be supplemented by the use of mechanistic models for critical health endpoints such as cancer. Finally an important question considering the shape of dose effect relationships for ionizing radiation arises from the unresolved question whether real or apparent thresholds may be used for any genotoxic agent separately or only one time for an exposed genome. (author)

X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

Energy Technology Data Exchange (ETDEWEB)

Game, John C.; Williamson, Marsha S.; Baccari, Clelia

2004-01-07

The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

Energy Technology Data Exchange (ETDEWEB)

Gross, N.J.; Holloway, N.O.; Narine, K.R. (Medical Radiology Service, Hines VA Hospital, Maywood, IL (United States))

1991-09-01

Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.

Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

International Nuclear Information System (INIS)

Gross, N.J.; Holloway, N.O.; Narine, K.R.

1991-01-01

Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis

Distinctions in sensitivity and repair of cells of children with some hereditary diseases

International Nuclear Information System (INIS)

Zasukhina, G.D.; Barashnev, Yu.I.; Vasil'eva, I.M.; Sdirkova, N.I.; Semyachkina, A.N.

1982-01-01

A study was made of blood cell sensitivity of children, with some hereditary diseases, to ν-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes

In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation.

Science.gov (United States)

Barazzuol, Lara; Jeggo, Penny A

2016-08-01

The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Abnormal sensitivity of skin fibroblasts from familial polyposis patients to DNA alkylating agents

International Nuclear Information System (INIS)

Barfknecht, T.R.; Little, J.B.

1982-01-01

Fibroblast cell strains derived from different patients all afflicted with genetic predisposing to the development of intestinal polyposis and cancer were tested for their sensitivity to the lethal effects of the DNA alkylating agents methylmethanesulfonate (MMS), ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and 4-nitroquinoline 1-oxide. The genetic syndromes studied were: (a) adenomatosis of the colon and rectum only, an autosomal dominant trait; (b) Turcot's syndrome, a rare autosomal recessive polyposis syndrome also characterized by central nervous system tumors; and (c) Gardner's syndrome, an autosomal dominant syndrome which, in addition to intestinal polyposis, is also clinically characterized by osteomas and soft tissue tumors. Fibroblasts from a patient with Turcot's syndrome were hypersensitive to MMS, having a D0 value of 0.24 mM (p less than 0.01) versus the normal average D0 of 0.36 mM and a D10 value of 0.95 mM (p less than 0.01) compared with the normal average value of 1.3 mM. Fibroblasts from the Gardner's syndrome proband were moderately sensitive to MMS, ethyl methanesulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine due to significant differences of D10 values of 0.60 mM (p less than 0.01), 15 mM (p less than 0.01), and 4.8 microM (p less than 0.025), respectively, versus the normal average values of 1.3 mM, 28 mM, and 9.4 microM. Fibroblasts from the clinically affected Gardner's syndrome daughter of the proband were significantly more sensitive to MMS treatment, D0 of 0.22 mM (p less than 0.01) versus the normal average D0 of 0.36 mM and a D10 of 0.97 mM (p less than 0.01) versus the normal average. This differential sensitivity to the several DNA alkylating agents suggests that different mechanisms of hypersensitivity to these chemicals may be associated with fibroblasts from the various forms of familial polyposis

Enhanced tumor responses through therapies combining CCNU, MISO and radiation

International Nuclear Information System (INIS)

Siemann, D.W.; Hill, S.A.

1984-01-01

Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

Combined effect of gamma radiation and some fungal control agents on the greasy cut- worm

International Nuclear Information System (INIS)

Abd EL- Wahed, A. G.

2011-01-01

The greasy cut worm, Agrotis ipsilon (Lepidoptera- Noctuidae) is widely distributed all over the world, particularly in moderate and subtropical countries of the northern and southern hemispheres (Kononenko ,2003). The greasy cut worm causes damage to vegetables, cucurbitaceous and industrial crops. The greatest damage is caused to cotton, essential-oil cultures, maize, tobacco, sunflower, tomatoes, sugar beet and potato. The pest can strongly harm vegetables, and also damage seedlings of tree species (pine, maple, and nut). This pest has solitary habits. They commonly feed on seedlings at ground level, cutting off the stem and sometimes dragging the plants into their burrows. The continuous use of chemical pesticides against pests, resistance to the action of pesticides had dramatically evolved. Also, the extensive use of these chemicals has given rise to problems such as residual toxicity (pollution) and harmful effects on beneficial insects, which are natural enemies of target or nontarget pest species. Such problems have become a cause of search for safety pesticides including microbial agents as fungi, bacteria and viruses (Rashed, 1993). The use of radiation to induce dominate lethal mutations in the sterile insect technique (SIT) is now as the major component of many large and successful programs for pest suppression and eradication. Adult insects, and their different developmental stages, differ in their sensitivity to the induction of dominate lethal mutation. Care has to be taken to identify the appropriate dose of radiation that produces the required level of sterility without impairing the overall fitness of the released insects.(Sawires, 2005). This technique would be successful control device for suppressing and combating many lepidopteraus insect pests, including A. Ipsilon has been studied (EL- kady et al., 1983, EL-Naggar et al., 1984, Abd El -Hamid 2004 and Gabarty, 2008). Entomopathogenic fungi that infect insects have received considerable

Improved Intratumoral Oxygenation Through Vascular Normalization Increases Glioma Sensitivity to Ionizing Radiation

International Nuclear Information System (INIS)

McGee, Mackenzie C.; Hamner, J. Blair; Williams, Regan F.; Rosati, Shannon F.; Sims, Thomas L.; Ng, Catherine Y.; Gaber, M. Waleed; Calabrese, Christopher; Wu Jianrong; Nathwani, Amit C.; Duntsch, Christopher; Merchant, Thomas E.; Davidoff, Andrew M.

2010-01-01

Purpose: Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, thus, the antiglioma efficacy of ionizing radiation. Methods and Materials: Orthotopic U87 xenografts were treated with either continuous interferon-β (IFN-β) or bevacizumab, alone, or combined with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; the tumor vasculature using immunohistochemical staining, and tumor oxygenation using hypoxyprobe staining. Results: Both IFN-β and bevaziumab profoundly affected the tumor vasculature, albeit with different cellular phenotypes. IFN-β caused a doubling in the percentage of area of perivascular cell staining, and bevacizumab caused a rapid decrease in the percentage of area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab, the effect was transient, being lost by 5 days. Administration of IFN-β or bevacizumab before RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-β or bevacizumab or 5 days after bevacizumab. Conclusion: Bevacizumab and continuous delivery of IFN-β each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the antitumor activity of ionizing radiation. Additional investigation into the use and timing of these and other agents that modify the vascular phenotype, combined with RT, is warranted to optimize cytotoxic activity.

Radiation exposure and contrast agent use related to radial versus femoral arterial access during percutaneous coronary intervention (PCI)—Results of the FERARI study

Energy Technology Data Exchange (ETDEWEB)

Becher, Tobias, E-mail: Tobias.Becher@umm.de [First Department of Medicine, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Behnes, Michael; Ünsal, Melike; Baumann, Stefan; El-Battrawy, Ibrahim; Fastner, Christian; Kuschyk, Jürgen; Papavassiliu, Theano; Hoffmann, Ursula [First Department of Medicine, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Mashayekhi, Kambis [Division of Cardiology and Angiology II, University Heart Center Freiburg Bad Krozingen, Bad Krozingen (Germany); Borggrefe, Martin; Akin, Ibrahim [First Department of Medicine, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany)

2016-12-15

Summary: Background: Data regarding radiation exposure related to radial versus femoral arterial access in patients undergoing percutaneous coronary intervention (PCI) remain controversial. This study aims to evaluate patients enrolled in the FERARI study regarding radiation exposure, fluoroscopy time and contrast agent use. Methods: The Femoral Closure versus Radial Compression Devices Related to Percutaneous Coronary Interventions (FERARI) study evaluated prospectively 400 patients between February 2014 and May 2015 undergoing PCI either using the radial or femoral access. In these 400 patients, baseline characteristics, procedural data such as procedural duration, fluoroscopy time, dose–area product (DAP) as well as the amount of contrast agent used were documented and analyzed. Results: Median fluoroscopy time was not significantly different in patients undergoing radial versus femoral access (12.2 vs. 9.8 min, p = 0.507). Furthermore, median DAP (54.5 vs. 52.0 Gycm2, p = 0.826), procedural duration (46.0 vs. 45.0 min, p = 0.363) and contrast agent use (185.5 vs. 199.5 ml, p = 0.742) were also similar in radial and femoral PCI. Conclusion: There was no difference regarding median fluoroscopy time, procedural duration, radiation dose or contrast agent use between radial versus femoral arterial access in PCI. - Highlights: • Data comparing radiation exposure in radial versus femoral PCI remain controversial. • 400 enrolled in the FERARI study were prospectively evaluated. • There was no difference regarding radiation exposure in radial versus femoral access. • Furthermore, there was no significant difference regarding contrast agent use.

Radiation exposure and contrast agent use related to radial versus femoral arterial access during percutaneous coronary intervention (PCI)—Results of the FERARI study

International Nuclear Information System (INIS)

Becher, Tobias; Behnes, Michael; Ünsal, Melike; Baumann, Stefan; El-Battrawy, Ibrahim; Fastner, Christian; Kuschyk, Jürgen; Papavassiliu, Theano; Hoffmann, Ursula; Mashayekhi, Kambis; Borggrefe, Martin; Akin, Ibrahim

2016-01-01

Summary: Background: Data regarding radiation exposure related to radial versus femoral arterial access in patients undergoing percutaneous coronary intervention (PCI) remain controversial. This study aims to evaluate patients enrolled in the FERARI study regarding radiation exposure, fluoroscopy time and contrast agent use. Methods: The Femoral Closure versus Radial Compression Devices Related to Percutaneous Coronary Interventions (FERARI) study evaluated prospectively 400 patients between February 2014 and May 2015 undergoing PCI either using the radial or femoral access. In these 400 patients, baseline characteristics, procedural data such as procedural duration, fluoroscopy time, dose–area product (DAP) as well as the amount of contrast agent used were documented and analyzed. Results: Median fluoroscopy time was not significantly different in patients undergoing radial versus femoral access (12.2 vs. 9.8 min, p = 0.507). Furthermore, median DAP (54.5 vs. 52.0 Gycm2, p = 0.826), procedural duration (46.0 vs. 45.0 min, p = 0.363) and contrast agent use (185.5 vs. 199.5 ml, p = 0.742) were also similar in radial and femoral PCI. Conclusion: There was no difference regarding median fluoroscopy time, procedural duration, radiation dose or contrast agent use between radial versus femoral arterial access in PCI. - Highlights: • Data comparing radiation exposure in radial versus femoral PCI remain controversial. • 400 enrolled in the FERARI study were prospectively evaluated. • There was no difference regarding radiation exposure in radial versus femoral access. • Furthermore, there was no significant difference regarding contrast agent use

Estimations of climate sensitivity based on top-of-atmosphere radiation imbalance

Directory of Open Access Journals (Sweden)

B. Lin

2010-02-01

Full Text Available Large climate feedback uncertainties limit the accuracy in predicting the response of the Earth's climate to the increase of CO₂ concentration within the atmosphere. This study explores a potential to reduce uncertainties in climate sensitivity estimations using energy balance analysis, especially top-of-atmosphere (TOA radiation imbalance. The time-scales studied generally cover from decade to century, that is, middle-range climate sensitivity is considered, which is directly related to the climate issue caused by atmospheric CO₂ change. The significant difference between current analysis and previous energy balance models is that the current study targets at the boundary condition problem instead of solving the initial condition problem. Additionally, climate system memory and deep ocean heat transport are considered. The climate feedbacks are obtained based on the constraints of the TOA radiation imbalance and surface temperature measurements of the present climate. In this study, the TOA imbalance value of 0.85 W/m² is used. Note that this imbalance value has large uncertainties. Based on this value, a positive climate feedback with a feedback coefficient ranging from −1.3 to −1.0 W/m²/K is found. The range of feedback coefficient is determined by climate system memory. The longer the memory, the stronger the positive feedback. The estimated time constant of the climate is large (70~120 years mainly owing to the deep ocean heat transport, implying that the system may be not in an equilibrium state under the external forcing during the industrial era. For the doubled-CO₂ climate (or 3.7 W/m² forcing, the estimated global warming would be 3.1 K if the current estimate of 0.85 W/m² TOA net radiative heating could be confirmed. With accurate long-term measurements of TOA radiation, the analysis method suggested by this study provides a great potential in the

Bacterial agents and sensitivity pattern of neonatal conjuctivitis in ...

African Journals Online (AJOL)

Introduction: In Africa alone, between 1000 – 4000 children are blinded annually by conjunctivitis. In view of the changing aetiological agents documented in other parts of the world and evolving resistance of infective agents to therapeutic agents, the present study was designed to define the bacterial agents, their antibiotic ...

Radiation Recall Reaction: Two Case Studies Illustrating an Uncommon Phenomenon Secondary to Anti-Cancer Agents

International Nuclear Information System (INIS)

Zhu, Su-yu; Yuan, Yuan; Xi, Zhen

2012-01-01

Radiation recall phenomenon is a tissue reaction that develops throughout a previously irradiated area, precipitated by the administration of certain drugs. Radiation recall is uncommon and easily neglected by physicians; hence, this phenomenon is underreported in literature. This manuscript reports two cases of radiation recall. First, a 44-year-old man with nasopharyngeal carcinoma was treated with radiotherapy in 2010 and subsequently developed multi-site bone metastases. A few days after the docetaxel-based chemotherapy, erythema and papules manifested dermatitis, as well as swallowing pain due to pharyngeal mucositis, developed on the head and neck that strictly corresponded to the previously irradiated areas. Second, a 19-year-old man with recurrent nasal NK/T cell lymphoma initially underwent radiotherapy followed by chemotherapy after five weeks. Erythema and edema appeared only at the irradiated skin. Both cases were considered chemotherapeutic agents that incurred radiation recall reactions. Clinicians should be knowledgeable of and pay attention to such rare phenomenon

Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

NARCIS (Netherlands)

van Bree, Chris; Castro Kreder, Natasja; Loves, Willem J. P.; Franken, Nicolaas A. P.; Peters, Godefridus J.; Haveman, Jaap

2002-01-01

Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel,

The proliferative status of intestinal epithelial clonogenic cells: sensitivity to S phase specific cytotoxic agents.

Science.gov (United States)

Boarder, T A; Blackett, N M

1976-11-01

High concentrations of tritiated thymidine and cytosine arabinoside (Ara-C) have been used to selectively kill cells in the crypts of Lieberkuhn that are synthesizing DNA. The effect of these agents on the number of regenerating microcolonies seen 3 1/2 days after a range of radiation doses indicates that a majority of the clonogenic cells are proliferating rapidly and that the slowly proliferating cells at the base of the crypt do not represent the whole clonogenic population.

Effect of gamma radiation dose and sensitizer on the physical properties of irradiated natural rubber latex

International Nuclear Information System (INIS)

Komgrit, R.; Thawat, C.; B, Tripob; Wirach, T.

2009-07-01

Full text: The vulcanization of natural rubber latex can be induced by gamma radiation, which enhances cross-linking within the rubber matrix. The purpose of this research is to investigate the effect of gamma radiation dose and sensitizers on the physical properties of irradiated natural rubber. Three sensitizers n-butyl acrylate (n-B A), tetrachloroethylene (C 2 Cl 4 ) and trichloromethane (CHCl 3 ) were mixed with natural rubber latex before irradiation with gamma ray dose varied from 14 to 22 kGy. Results showed that the mixture of three sensitizers with specific ratios effectively induced the cross-linking of natural rubber latex. The cross-linking ratio and improved physical properties increased with increasing gamma dose. Therefore, the mixture ratios of n-B A, C 2 Cl 4 and CHCl 3 have shown to be a critical parameter in the vulcanization of natural rubber latex by gamma radiation

Bacterial agents and antibiotic sensitivity in children with urinary infection in two hospitals of Popayan, Colombia

Directory of Open Access Journals (Sweden)

Carolina Álvarez-Czeczotta

2012-06-01

Full Text Available Introduction: Urinary Tract Infection (UTI is a common condition in children. Isolation of bacteria and early management is a priority in order to contribute to the reduction of morbidity and avoid bacterial resistance. Objectives: To identify bacterial etiologic agents and antibiotic sensitivity in children (1 month to 5 years of age with UTI in two hospitals of Popayán, Colombia. Materials and methods: We conducted a cross-sectional study in children aged 1 month to 5 years of age who consulted the emergency services of two hospitals with clinical suspicion of UTI. The sample was 123 children. Using an instrument collected demographic variables, signs and symptoms, results of urinalysis, urine culture, sensitivity testing, treatment, and UTI classification. We determined the frequency and proportions of sociodemographic and clinical variables, bacterial agents and antibiotic resistance. Data was analyzed using SPSS 11.5 program. Results: We included 129 children diagnosed with UTI with positive urine culture, bladder catheter taken with 97.7% of cases. 74.8% of patients were female. Escherichia coli was the seed that was isolated more frequently (95.4%, then Sp Proteus (2.4%, and Klebsiella pneumoniae (1.6%. The antibiotics to which the bacteria showed adequate sensitivity were: ceftriaxone, amikacin, gentamicin, ciprofloxacin, nitrofurantoin, cefuroxime and cephalexin. Showed low sensitivity: ampicillin and trimethoprim sulfa. Conclusions: Escherichia coli was the bacteria that cause of UTI in our study population. For initial empiric treatment of hospitalized patients would recommend parenteral drug third generation cephalosporins (ceftriaxone and aminoglycosides (amikacin, gentamicin. For outpatient management, oral antibiotics showed greater sensitivity were nalidixic acid, cefuroxime and cephalexin.

Distinctions in sensitivity and repair of cells of children with some hereditary diseases

Energy Technology Data Exchange (ETDEWEB)

Zasukhina, G.D.; Barashnev, Yu.I.; Vasil' eva, I.M.; Sdirkova, N.I.; Semyachkina, A.N. (AN SSSR, Moscow. Inst. Obshchej Genetiki)

A study was made of blood cell sensitivity of children with some hereditary diseases, to ..gamma..-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes.

Resveratrol sensitization of DU145 prostate cancer cells to ionizing radiation is associated to ceramide increase.

Science.gov (United States)

Scarlatti, Francesca; Sala, Giusy; Ricci, Clara; Maioli, Claudio; Milani, Franco; Minella, Marco; Botturi, Marco; Ghidoni, Riccardo

2007-08-08

Radiotherapy is an established therapeutic modality for prostate cancer. Since it is well known that radiotherapy is limited due to its severe toxicity towards normal cells at high dose and minimal effect at low dose, the search for biological compounds that increase the sensitivity of tumors cells to radiation may improve the efficacy of therapy. Resveratrol, a natural antioxidant, was shown to inhibit carcinogenesis in animal models, and to block the process of tumor initiation and progression. The purpose of this study was to examine whether or not resveratrol can sensitize DU145, an androgen-independent human prostate cancer cell line, to ionizing radiation. We report here that DU145 cells are resistant to ionizing radiation-induced cell death, but pretreatment with resveratrol significantly enhances cell death. Resveratrol acts synergistically with ionizing radiation to inhibit cell survival in vitro. Resveratrol also potentiates ionizing radiation-induced ceramide accumulation, by promoting its de novo biosynthesis. This confirms ceramide as an effective mediator of the anticancer potential induced by resveratrol.

The study of the radiation protection effects of TMG to the fetus on the organogenesis stage in ICR mice

Energy Technology Data Exchange (ETDEWEB)

Gu, Yeunhwa; Santokuya, Takumi; Suzuki, Ikukatsu; Hasegawa, Takeo; Yamamoto, Youichi [Suzuka Univ. of Medical Science, Mie (Japan); Bamen, K.; Yanagisawa, Takaharu; Iwasa, Toshihiro

2000-05-01

Experimental studies on mice have made it clear that embryos are more sensitive to radiation during Organogenesis than other prenatal periods. However, the radiation protection of TMG at Organogenesis in mice has yet to be described. The Organogenesis stage is the most important from the viewpoint of ionizing protection. Many physical and chemical agents in the environment can affect an embryo. Fetal deaths were classified as Preimplantation, Embryonic and Fetal. The sensitivity of the fetus is high in comparison with the maturates and the child to the various environmental agent. It is the individium, which should pay attention to it specially when a fetus' safety is thought about. Because it isn't noticed, the fetus of the organogenesis can't avoid fetus' existence regardless of the individium of which sensibility is high in the intention target. Therefore, protection resource and others must be studied after the fetus' effects of the organogenesis are studied fully. It paid attention to radiation in the environmental agent, and it was examined about the radiation protection effect of TMG to fetus' teratogenesis by this study. We studied an excuse as a radioprotective agent of the high malformation of the sensitivity most by using TMG to the radiation. This study aimed at obtaining the information to provide it for the fetus' protection to the various environmental radiations. As for Preimplantation death, there was a statistical difference the 2.0 Gy Group in comparison with the control group (p<0.05). Embryonic death, a statistical difference was recognized as in all the treatment groups (p<0.001). But, as for the TMG+radiation group, Embryonic death decreased to 1/4. As for Malformation rate, a statistical difference was recognized as in all treatment group (p<0.001). But, as for the TMG+radiation group, Malformation rate decreased to 1/2. As for Fetal body weight, a statistical difference was recognized in radiation group

Preliminary Study of Position-Sensitive Large-Area Radiation Portal Monitor

Energy Technology Data Exchange (ETDEWEB)

Lim, Chang Hwy; Kim, Hyunok; Moon, Myung Kook [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Jongyul [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Park, Jong Won; Lim, Yong Kon [Korea Institute of Ocean Science and Technology, Daejeon (Korea, Republic of)

2013-10-15

An RPM, which is a passive inspection method, is a system for monitoring the movement of radioactive materials at an airport, seaport, border, etc. To detect a γ-ray, an RPM using the plastic scintillator is generally used. The method of γ-ray detection using an RPM with a plastic scintillator is to measure lights generated by an incident γ-ray in the scintillator. Generally, a large-area RPM uses one or two photomultiplier tubes (PMT) for light collection. However, in this study, we developed a 4-ch RPM that can measure the radiation signal using 4 PMTs. The reason for using 4 PMTs is to calculate the position of the radiation source. In addition, we developed an electric device for acquisition of a 4-ch output signal at the same time. To estimate the performance of the developed RPM, we performed an RPM test using a {sup 60}Co γ-ray check source. In this study, we performed the development of a 4-ch RPM. The major function of the typical RPM is to measure the radiation. However, we developed a position-sensitive 4-ch RPM, which can be used to measure the location of the radiation source, as well as the radiation measurement, at the same time. In the future, we plan to develop an algorithm for a position detection of the radiation. In addition, an algorithm will be applied to an RPM.

Methods and tools for the evaluation of the sensitivity to natural radiations of advanced integrated circuits

International Nuclear Information System (INIS)

Peronnard, P.

2009-10-01

Atmospheric neutrons, whose fluxes and energies dependent on the altitude, the sun activity and the geographic coordinates, have been identified as being capable to provoke SEE (Single Event Effects), by indirect ionisation, in integrated devices issued from advanced manufacturing processes (nano-metric devices). This concerns not only avionics but also applications operating at ground level. The evaluation of the sensitivity to SEE provoked by natural radiation becomes thus a mandatory step during the selection of devices devoted to be included in applications requiring high reliability. The sensitivity to SEE can be mitigated by different approaches at different levels from manufacturing level (use of particular process technologies such as SOI - Silicon On Isolator -) to the system level (hardware/software redundancy). Independently of the adopted hardening approach, the so-called radiation ground testing are mandatory to evaluate the error rates of a device or a system. During such tests, the DUT (Device Under Test) is exposed to a flux of particles while it performs a given activity. For SEU (Single Event Upsets) radiation ground testing, two main strategies exist: static test: the circuit areas which are supposed to be sensitive to SEUs (registers, memories,...) are initialized with a reference pattern. The content of the sensitive area is periodically compared to the reference pattern to identify potential SEU. Dynamic test: the DUT performs an activity representative of the one it will execute during the final application. Static test: strategies are frequently adopted as they provide the intrinsic sensitivity, in terms of the average number of particles needed to provoke an SEU, of different sensitive areas of the device. From such a strategy can thus be obtained a 'worst case estimation' of the device sensitivity. This thesis aims at giving a description and validating the methodologies required to estimate the sensitivity to radiations of two types of

Radiation therapy for gastric cancer

International Nuclear Information System (INIS)

Dobelbower, R.R.; Bagne, F.; Ajlouni, M.I.; Milligan, A.J.

1988-01-01

Adenocarcinoma of the stomach is a moderately radioresponsive neoplasm. Attempts to treat patients with unresectable disease with external beam radiation therapy alone have generally failed because of problems with tumor localization and adequate dose delivery as well as the inherent radioresponsiveness of the gastric mucosa and the organs intimately related to the stomach. Combining external beam therapy and chemotherapy (acting as a systemic agent and as a radiosensitizer) seems to be of some (albeit limited) benefit in the management of unresectable adenocarcinoma of the stomach. Optimum combinations of radiation therapy, chemotherapy, and radiation sensitizers in this situation remain to be determined. The authors discuss strides which have been made in the treatment of gastric cancer. They also address the unanswered clinical questions which remain regarding the use of radiation therapy in the treatment of this highly lethal disease

Thermal radiosensitization in heat- and radiation-sensitive mutants of CHO cells

International Nuclear Information System (INIS)

Kampinga, H.H.; Kanon, B.; Konings, A.W.T.; Stackhouse, M.A.; Bedford, J.S.

1993-01-01

In the current study, the extent of hyperthermic radiosensitization in a new γ-radiation-sensitive cell line, irs-20, recently isolated by Stackhouse and Bedford (1991) and a heat-sensitive mutant hs-36 (Harvey and Bedford 1988) was compared with the radiosensitization of their mutual parent CHO 10B12 cell line. The irs-20 and CHO 10B12 cells have comparable heat (43.5 o C) sensitivities, whereas hs-36 and CHO 10B12 show a similar sensitivity to γ- and X-rays. Radiosensitization due to pre-exposure to 43.5 o C heating of plateau phase cultures was found for all three cell lines, even after relatively mild heat treatment killing <20% of cells. Experiments using CHEF electrophoresis confirmed the dsb repair deficiency of the irs-20 cells (Stackhouse and Bedford 1992) and showed that heat inhibited dsb repair in all three cell lines. (Author)

The SOS Chromotest applied for screening plant antigenotoxic agents against ultraviolet radiation.

Science.gov (United States)

Fuentes, J L; García Forero, A; Quintero Ruiz, N; Prada Medina, C A; Rey Castellanos, N; Franco Niño, D A; Contreras García, D A; Córdoba Campo, Y; Stashenko, E E

2017-09-13

In this work, we investigated the usefulness of the SOS Chromotest for screening plant antigenotoxic agents against ultraviolet radiation (UV). Fifty Colombian plant extracts obtained by supercritical fluid (CO 2 ) extraction, twelve plant extract constituents (apigenin, carvacrol, β-caryophyllene, 1,8-cineole, citral, p-cymene, geraniol, naringenin, pinocembrin, quercetin, squalene, and thymol) and five standard antioxidant and/or photoprotective agents (curcumin, epigallocatechin gallate, resveratrol, α-tocopherol, and Trolox®) were evaluated for their genotoxicity and antigenotoxicity against UV using the SOS Chromotest. None of the plant extracts, constituents or agents were genotoxic in the SOS Chromotest at tested concentrations. Based on the minimal extract concentration that significantly inhibited UV-genotoxicity (CIG), five plant extracts were antigenotoxic against UV as follows: Baccharis nítida (16 μg mL -1 ) = Solanum crotonifolium (16 μg mL -1 ) > Hyptis suaveolens (31 μg mL -1 ) = Persea caerulea (31 μg mL -1 ) > Lippia origanoides (62 μg mL -1 ). Based on CIG values, the flavonoid compounds showed the highest antigenotoxic potential as follows: apigenin (7 μM) > pinocembrin (15 μM) > quercetin (26 μM) > naringenin (38 μM) > epigallocatechin gallate (108 μM) > resveratrol (642 μM). UV-genotoxicity inhibition with epigallocatechin gallate, naringenin and resveratrol was related to its capability for inhibiting protein synthesis. A correlation analysis between compound antigenotoxicity estimates and antioxidant activity evaluated by the oxygen radical absorbance capacity (ORAC) assay showed that these activities were not related. The usefulness of the SOS Chromotest for bioprospecting of plant antigenotoxic agents against UV was discussed.

[Sensitivity of the splenic immunocompetent cells of mice with different genotypes to the action of alkylating agents].

Science.gov (United States)

Pevnitskiĭ, L A; Telegin, L Iu; Ir, K N

1985-08-01

It has been established in experiments in vitro that splenocytes of DBA/2GSto mice are more sensitive to the immunosuppressant action of the alkylating agents (cyclophosphamide, sarcolysine and thiophosphamide) than splenocytes of BALB/cGLacSto mice. Splenocytes of C3H/SnRap mice exhibit and intermediate type of sensitivity. T-lymphocytes of the spleen of BALB/cGLacSto and DBA/2GSto mice are more sensitive in vitro to the action of active metabolites of cyclophosphamide as compared to B-lymphocytes, with both types of the cells of DBA/2GSto mice being affected to a greater extent than the cells of BALB/cGLacSto mice.

{sup 166}Ho-chitosan as a radiation synovectomy agent - antigen-induced arthritis in rabbits

Energy Technology Data Exchange (ETDEWEB)

Kim, Sug Jun; Lee, Soo Yong; Jeon, Dae Geun; Lee, Jong Seok [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1998-01-01

Radiation synovectomy is a noninvasive therapy that has been investigated as an alternative to surgical synovectomy. It has been successfully employed in the treatment of synovitis in rheumatoid arthritis and other inflammatory arthropathies. In this study, we developed experimental animal model for radiation synovectomy. A model system in which a single injection of ovalbumin into the knee joints of previously sensitized rabbits consistently produced a chronic arthritis which was histologically similiar to human rheumatoid arthritis. (author). 8 refs., 8 figs

Evaluation of image quality and radiation dose using gold nanoparticles and other clinical contrast agents in dual-energy Computed Tomography (CT): CT abdomen phantom

Science.gov (United States)

Zukhi, J.; Yusob, D.; Tajuddin, A. A.; Vuanghao, L.; Zainon, R.

2017-05-01

The aim of this study was to evaluate the image quality and radiation dose using commercial gold nanoparticles and clinical contrast agents in dual-energy Computed Tomography (CT). Five polymethyl methacrylate (PMMA) tubes were used in this study, where four tubes were filled with different contrast agents (barium, iodine, gadolinium, and gold nanoparticles). The fifth tube was filled with water. Two optically stimulated luminescence dosimeters (OSLD) were placed in each tube to measure the radiation dose. The tubes were placed in a fabricated adult abdominal phantom of 32 cm in diameter using PMMA. The phantom was scanned using a DECT at low energy (80 kV) and high energy (140 kV) with different pitches (0.6 mm and 1.0 mm) and different slice thickness (3.0 mm and 5.0 mm). The tube current was applied automatically using automatic exposure control (AEC) and tube current modulation recommended by the manufacturer (CARE Dose 4D, Siemens, Germany). The contrast-to-noise ratio (CNR) of each contrast agent was analyzed using Weasis software. Gold nanoparticles has highest atomic number (Z = 79) than barium (Z = 56), iodine (Z = 53) and gadolinium (Z = 64). The CNR value of each contrast agent increases when the slice thickness increases. The radiation dose obtained from this study decreases when the pitch increases. The optimal imaging parameters for gold nanoparticles and other clinical contrast agents is obtained at pitch value of 1.0 mm and slice thickness of 5.0 mm. Low noise and low radiation dose obtained at these imaging parameters. The optimal imaging parameters obtained in this study can be applied in multiple contrast agents imaging.

Evaluation of image quality and radiation dose using gold nanoparticles and other clinical contrast agents in dual-energy Computed Tomography (CT): CT abdomen phantom

International Nuclear Information System (INIS)

Zukhi, J; Yusob, D; Vuanghao, L; Zainon, R; Tajuddin, A A

2017-01-01

The aim of this study was to evaluate the image quality and radiation dose using commercial gold nanoparticles and clinical contrast agents in dual-energy Computed Tomography (CT). Five polymethyl methacrylate (PMMA) tubes were used in this study, where four tubes were filled with different contrast agents (barium, iodine, gadolinium, and gold nanoparticles). The fifth tube was filled with water. Two optically stimulated luminescence dosimeters (OSLD) were placed in each tube to measure the radiation dose. The tubes were placed in a fabricated adult abdominal phantom of 32 cm in diameter using PMMA. The phantom was scanned using a DECT at low energy (80 kV) and high energy (140 kV) with different pitches (0.6 mm and 1.0 mm) and different slice thickness (3.0 mm and 5.0 mm). The tube current was applied automatically using automatic exposure control (AEC) and tube current modulation recommended by the manufacturer (CARE Dose 4D, Siemens, Germany). The contrast-to-noise ratio (CNR) of each contrast agent was analyzed using Weasis software. Gold nanoparticles has highest atomic number (Z = 79) than barium (Z = 56), iodine (Z = 53) and gadolinium (Z = 64). The CNR value of each contrast agent increases when the slice thickness increases. The radiation dose obtained from this study decreases when the pitch increases. The optimal imaging parameters for gold nanoparticles and other clinical contrast agents is obtained at pitch value of 1.0 mm and slice thickness of 5.0 mm. Low noise and low radiation dose obtained at these imaging parameters. The optimal imaging parameters obtained in this study can be applied in multiple contrast agents imaging. (paper)

Effects of ionizing radiation on bacteria

Energy Technology Data Exchange (ETDEWEB)

Suhadi, F [National Atomic Energy Agency, Jakarta (Indonesia). Pasar Djumat Research Centre

1976-10-01

The differences of radiosensitivities among bacteria in addition to the dependence upon the species or strains also depends on the environmental condition during irradiation (temperature, medium, the presence of protective or sensitizing agents, the gas phase or atmosphere, and water activity, or degree of hydration) and on the effects of the environmental condition before and after irradiation treatment (temperature of incubation, age of culture and growth medium). In general, spores are more resistant to radiation than vegetatic bacteria, with the exception that a few cocci are the most radiation resistant bacteria (Micrococcus and Streptococcus). The application of ionizing radiation in the fields of microbiology supports the radiation sterilization of medical and pharmaceutical products. In addition, microbiological aspects of food preservation, especially radurization, radicidation, and immunization studies by using irradiated microorganisms, are also important.

Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Prakash, L.; Prakash, S.

1977-01-01

We have isolated mutants sensitive to methyl methanesulfonate (MMS) in Saccharomyces cerevisiae. Alleles of rad1, rad4, rad6, rad52, rad55 and rad57 were found among these mms mutants. Twenty-nine of the mms mutants which complement the existing radiation-sensitive (rad and rev) mutants belong to 22 new complementation groups. Mutants from five complementation groups are sensitive only to MMS. Mutants of 11 complementation groups are sensitive to uv or x rays in addition to MMS, mutants of six complementation groups are sensitive to all three agents. The cross-sensitivities of these mms mutants to uv and x rays are discussed in terms of their possible involvement in DNA repair. Sporulation is reduced or absent in homozygous diploids of mms mutants from nine complementation groups

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

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster (Crassostrea gigas) and culture broth under different conditions

Energy Technology Data Exchange (ETDEWEB)

Jung, Pil-Mun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Park, Jae Seok [Korea Food and Drug Administration, Seoul 122-704 (Korea, Republic of); Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Baek, Min [Atomic Energy Policy Division, Ministry of Education, Science and Technology, Gwacheon 427-715 (Korea, Republic of); Chung, Young-Jin [Department of Food and Nutrition, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Ju-Woon [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

2009-07-15

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster (Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D{sub 10} value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster (Crassostrea gigas) and culture broth under different conditions

International Nuclear Information System (INIS)

Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

2009-01-01

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster (Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D 10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster ( Crassostrea gigas) and culture broth under different conditions

Science.gov (United States)

Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

2009-07-01

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster ( Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

Gene targeting associated with the radiation sensitivity in squamous cell carcinoma by using microarray analysis

International Nuclear Information System (INIS)

Nimura, Yoshinori; Kumagai, Ken; Kouzu, Yoshinao; Higo, Morihiro; Kato, Yoshikuni; Seki, Naohiko; Yamada, Shigeru

2005-01-01

In order to identify a set of genes related to radiation sensitivity of squamous cell carcinoma (SCC) and establish a predictive method, we compared expression profiles of radio-sensitive/radio-resistant SCC cell lines, using the in-house cDNA microarray consisting of 2,201 human genes derived from full-length enriched SCC cDNA libraries and the Human oligo chip 30 K (Hitachi Software Engineering). Surviving fractions (SF) after irradiation of heavy iron were calculated by colony formation assay. Three pairs (TE2-TE13, YES5-YES6, and HSC3-HSC2), sensitive (SF1 0.6), were selected for the microarray analysis. The results of cDNA microarray analysis showed that 20 genes in resistant cell lines and 5 genes in sensitive cell lines were up regulated more than 1.5-fold compared with sensitive and resistant cell lines respectively. Fourteen out of 25 genes were confirmed the gene expression profiles by real-time polymerase chain reaction (PCR). Twenty-seven genes identified by Human oligo chip 30 K are candidate for the markers to distinguish radio-sensitive from radio-resistant. These results suggest that the isolated 27 genes are the candidates that might be used as specific molecular markers to predict radiation sensitivity. (author)

Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming

KAUST Repository

Xiao, Xi; de Bettignies, Thibaut; Olsen, Ylva S.; Agusti, Susana; Duarte, Carlos M.; Wernberg, Thomas

2015-01-01

Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia–Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16–30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius’ model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming

KAUST Repository

Xiao, Xi

2015-12-02

Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia–Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16–30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius’ model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

Temporal correlations between sensitivity to radiation-induced mitotic delay and the S phase of the sea urchin egg

International Nuclear Information System (INIS)

Rustad, R.C.; Viswanathan, G.; Antonellis, B.C.

1979-01-01

Separate samples of eggs from the sea urchin Arbacia punctulata were gamma irradiated (4kR) at different times after fertilisation and division delay measured. The results demonstrated a characteristic post-fertilisation pattern of a rise in sensitivity to radiation-induced mitotic delay, followed by a biphasic decrease in sensitivity to a refractory period. Measurements of the cumulative incorporation of 3 H-TdR showed that the first period of decreasing radiation sensitivity was closely associated with the bulk synthesis of DNA (S phase). (U.K.)

An Escherichia coli strain deficient for both exonuclease 5 and deoxycytidine triphosphate deaminase shows enhanced sensitivity to ionizing radiation

International Nuclear Information System (INIS)

Estevenon, A.M.; Kooistra, J.; Sicard, N.

1995-01-01

An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores the wild type level of UV and gamma ray resistance to this mutant has been cloned in the multicopy vector pBR322. Comparison of its restriction map with the physical map of the E. coli chromosome revealed complete identity to the recBD genes. ior affects ATP-dependent exonuclease activity, suggesting that it is an allele of recB. This mutation alone does not confer sensitivity to UV and gamma radiation, indicating that lack of Dcd activity is also required for expression of radiation sensitivity

Radiation Sensitivity of some Food Borne Bacterial Pathogens in Animal Foods and Minced Meat

International Nuclear Information System (INIS)

Mohammed, W.S.; Ali, A.R.; Alexan, A.F.

2010-01-01

Bacteriological examination of 100 samples of animal food stuffs (fish meal and bone and meat meal; as models of dry food materials) and 50 samples of minced meat (as a model of moist food materials) revealed the isolation of different bacterial pathogens; Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Proteus spp., Staph. aureus and Salmonella species, in a decreasing order of occurrence. In the experiment; the dry food stuffs were sterilized in autoclave and the minced meat was sterilized by gamma irradiation at 10 kGy. The efficacy of gamma irradiation against the inoculated bacterial isolates (E coli 0157: H7, Salmonella enteritidis and Staph. aureus) in animal food stuffs and minced meat was investigated. Irradiated samples were stored at room temperature (25 degree C) for 2 weeks. The food borne pathogens used in this study showed a difference in radiation sensitivity. E. coli 0157: H7, Staphylococcus aureus and Salmonella enteritidis were eradicated at 1, 2 and 3 kGy, respectively. Also, inoculated pathogens in minced meat were more sensitive to ionizing radiation than dry animal food stuffs. It could be concluded that low doses of gamma irradiation are effective means of inactivating pathogenic bacteria. This radiation sensitivity is related to the bacterial isolates and the evaluated growth

Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins

International Nuclear Information System (INIS)

Joseph, J.A.; Kandasamy, S.B.; Hunt, W.A.; Dalton, T.K.; Stevens, S.

1988-01-01

The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin

Limit values for exposure to physical agents

International Nuclear Information System (INIS)

Anon.

1983-01-01

The limit values for exposure to thermal environments adopted by the French AFNOR and by the ISO Working Group (AFNOR Standard X 35-201 and ISO Standard 7243, and AFNOR Standard X 35-204). The limit values for exposure to other physical agents established by the American ACGIH for 1982. The following agents are covered: - laser radiation (ocular and skin exposure); - ultraviolet radiation; - visible and near-infrared radiation (retinal thermal and photochemical injury); - airborne and upper sonic and ultrasonic acoustic radiation; - radiofrequency radiation [fr

In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation

International Nuclear Information System (INIS)

Barazzuol, Lara; Jeggo, Penny A.

2016-01-01

The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5–14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4 Y288C ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4 Y288C embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4 Y288C mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis

Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents

DEFF Research Database (Denmark)

Birkbak, Nicolai J.; Wang, Zhigang C.; Kim, Ji-Young

2012-01-01

with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of NtAI forecast a better initial response. We found an inverse relationship between BRCA1 expression and NtAI in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation...... of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (NtAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients...... also benefit from these agents. NtAI, a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair. Cancer Discov; 2(4); 366–75. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 288...

Cooperative biological effects between ionizing radiation and other physical and chemical agents.

Science.gov (United States)

Manti, Lorenzo; D'Arco, Annalisa

2010-01-01

Exposure to ionizing radiation (IR), at environmentally and therapeutically relevant doses or as a result of diagnostics or accidents, causes cyto- and genotoxic damage. However, exposure to IR alone is a rare event as it occurs in spatial and temporal combination with several physico-chemical agents. Some of these are of known noxiousness, as is the case with chemical compounds at high dose, hence additive/synergistic effects can be expected or have been demonstrated. Conversely, the cellular toxicity of other agents, such as non-ionizing electromagnetic fields (EMFs), is only presumed and their short- and long-term cooperation on IR-induced damage remains undetermined. In this review, we shall examine evidence in support of the interplay between spatially and/or temporally related environmentally relevant stressors. In vitro or animal-based studies as well as epidemiological surveys have generally examined the combined action of no more than a couple of known or potentially DNA-damaging agents. Moreover, most existing research mainly focused on short-term effects of combined exposures. Hence, it is important that quantitative research addresses the issue of the possible cooperation between chronic exposure to environmental trace contaminants and exposure to EMFs, examining not only the modulation of damage acutely induced by IR but also long-term genome stability. 2010 Elsevier B.V. All rights reserved.

Variation in radiation sensitivity and repair kinetics in different parts of the spinal cord

International Nuclear Information System (INIS)

Adamus-Gorka, Magdalena; Brahme, Anders; Mavroidis, Panayiotis; Lind, Bengt K.

2008-01-01

Background. The spinal cord, known for its strongly serial character and high sensitivity to radiation even when a small segment is irradiated, is one of the most critical organs at risk to be spared during radiation therapy. To compare the sensitivity of different parts of the spinal cord, data for radiation myelopathy have been used. Material and methods. In the present study, the relative seriality model was fitted to two different datasets of clinical radiation myelitis concerning cervical spinal cord after treating 248 patients for head and neck cancer and thoracic spinal cord after treating 43 patients with lung carcinoma. The maximum likelihood method was applied to fit the clinical data. The model parameters and their 68% confidence intervals were calculated for each dataset. The α/β ratio for the thoracic cord was also was also found to be 0.9 (0-3.0) Gy. Results. The dose-response curve for the more sensitive cervical myelopathy is well described by the parameters D 50 =55.9 (54.8-57.1) Gy, γ=6.9 (5.0-9.2), s=0.13 (0.07-0.24), whereas the thoracic myelopathy is described by the parameters D 50 =75.5 (70.5-80.8) Gy, γ=1.1 (0.6-1.6), s=36 (3.3-8). Discussion and conclusions. Large differences in radiation response between the cervical and thoracic region of spinal cord are thus observed: cervical myelopathy seems to be characterized by medium seriality, while thoracic spinal cord is characterized by a highly serial dose-response. The much steeper dose-response curve for cervical spinal cord myelopathy can be interpreted as a higher number of functional subunits consistent with a higher amount of white matter close to the brain

Delay-Line Three-Dimensional Position Sensitive Radiation Detection

Science.gov (United States)

Jeong, Manhee

High-resistivity silicon(Si) in large volumes and with good charge carrier transport properties has been produced and achieved success as a radiation detector material over the past few years due to its relatively low cost as well as the availability of well-established processing technologies. One application of that technology is in the fabrication of various position-sensing topologies from which the incident radiation's direction can be determined. We have succeeded in developing the modeling tools for investigating different position-sensing schemes and used those tools to examine both amplitude-based and time-based methods, an assessment that indicates that fine position-sensing can be achieved with simpler readout designs than are conventionally deployed. This realization can make ubiquitous and inexpensive deployment of special nuclear materials (SNM) detecting technology becomes more feasible because if one can deploy position-sensitive semiconductor detectors with only one or two contacts per side. For this purpose, we have described the delay-line radiation detector and its optimized fabrication. The semiconductor physics were simulated, the results from which guided the fabrication of the guard ring structure and the detector electrode, both of which included metal-field-plates. The measured improvement in the leakage current was confirmed with the fabricated devices, and the structures successfully suppressed soft-breakdown. We also demonstrated that fabricating an asymmetric strip-line structure successfully minimizing the pulse shaping and increases the distance through which one can propagate the information of the deposited charge distribution. With fabricated delay-line detectors we can acquire alpha spectra (Am-241) and gamma spectra (Ba-133, Co-57 and Cd-109). The delay-line detectors can therefore be used to extract the charge information from both ion and gamma-ray interactions. Furthermore, standard charge-sensitive circuits yield high SNR

Combination of vascular targeting agents with thermal or radiation therapy

International Nuclear Information System (INIS)

Horsman, Michael R.; Murata, Rumi

2002-01-01

Purpose: The most likely clinical application of vascular targeting agents (VTAs) is in combination with more conventional therapies. In this study, we report on preclinical studies in which VTAs were combined with hyperthermia and/or radiation. Methods and Materials: A C3H mammary carcinoma grown in the right rear foot of female CDF1 mice was treated when at 200 mm 3 in size. The VTAs were combretastatin A-4 disodium phosphate (CA4DP, 25 mg/kg), flavone acetic acid (FAA, 150 mg/kg), and 5,6-dimethylxanthenone-4-acetic acid (DMXAA, 20 mg/kg), and were all injected i.p. Hyperthermia and radiation were locally administered to tumors of restrained, nonanesthetized mice, and response was assessed using either a tumor growth or tumor control assay. Results: Heating tumors at 41.5 degree sign C gave rise to a linear relationship between the heating time and tumor growth with a slope of 0.02. This slope was increased to 0.06, 0.09, and 0.08, respectively, by injecting the VTAs either 30 min (CA4DP), 3 h (FAA), or 6 h (DMXAA) before heating. The radiation dose (±95% confidence interval) that controls 50% of treated tumors (the TCD 50 value) was estimated to be 53 Gy (51-55 Gy) for radiation alone. This was decreased to 48 Gy (46-51 Gy), 45 Gy (41-49 Gy), and 42 Gy (39-45 Gy), respectively, by injecting CA4DP, DMXAA, or FAA 30-60 min after irradiating. These values were further decreased to around 28-33 Gy if the tumors of VTA-treated mice were also heated to 41.5 degree sign C for 1 h, starting 4 h after irradiation, and this effect was much larger than the enhancement seen with either 41.5 degree sign C or even 43 degree sign C alone. Conclusions: Our preclinical studies and those of others clearly demonstrate that VTAs can enhance tumor response to hyperthermia and/or radiation and support the concept that such combination studies should be undertaken clinically for the full potential of VTAs to be realized

Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

DEFF Research Database (Denmark)

Horsman, Michael R

2017-01-01

INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

Biological effects of radiation in combination with other physical, chemical or biological agents. Annex L

International Nuclear Information System (INIS)

1982-01-01

This Annex considers the combined action of radiation with potentially important environmental conditions. Since there is a scarcity of systematic data on which an analysis of combined effects can be based, this Annex will be more hypothetical and will attempt to suggest definitions, to identify suitable methods of analysis, to select from a large amount of diffuse information the conditions and the data of importance for further consideration and to provide suggestions for future research. For humans in environmental circumstances the UNSCEAR Committee has been unable to document any clear case of synergistic interaction between radiation and other agents, which could lead to substantial modifications of the risk estimates for significant sections of the population.

Sensitive and Rapid Identification of Biological Threat Agents

Science.gov (United States)

1999-12-01

plague, and Bruceila abortis , the etiologic agent of brucellosis, indicate that the Qiagen procedures will also be effective in preparing these agents for...procedure for two bacteria, Yersinia pestis and Bruceila abortis , and found that DNA isolated with this method yielded PCR detection limits at least

Investigation of the modifying effects of vitamin A and hypoxic cell sensitizers in radiation carcinogenesis in mice

International Nuclear Information System (INIS)

Mian, T.A.

1982-01-01

The effect of vitamin A (retinyl acetate) and three hypoxic cell sensitizers (metronidazole, misonidazole and desmethylmisonidazole) on lung tumor development in strain A mice exposed to radiation was assessed. In experiments involving vitamin A, two groups of mice were fed a low vitamin A diet (< 100 IU/100g diet) while the two other groups were fed a high vitamin A diet (800 IU/100 g diet). After two weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. Mice were killed, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post irradiation as compared to the irradiated group maintained on a low vitamin A diet. In the other experiment two dose levels of the hypoxic cell sensitizers, 0.2 mg/g and 0.6 mg/g, were used either alone or in combination with 900 rad of gamma radiation in a fractionated dose schedule of twice a week for three weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased in the higher dose group (0.6 mg/g) of misonidazole but was not significantly different from the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with the control group

Designing novel cellulase systems through agent-based modeling and global sensitivity analysis

Science.gov (United States)

Apte, Advait A; Senger, Ryan S; Fong, Stephen S

2014-01-01

Experimental techniques allow engineering of biological systems to modify functionality; however, there still remains a need to develop tools to prioritize targets for modification. In this study, agent-based modeling (ABM) was used to build stochastic models of complexed and non-complexed cellulose hydrolysis, including enzymatic mechanisms for endoglucanase, exoglucanase, and β-glucosidase activity. Modeling results were consistent with experimental observations of higher efficiency in complexed systems than non-complexed systems and established relationships between specific cellulolytic mechanisms and overall efficiency. Global sensitivity analysis (GSA) of model results identified key parameters for improving overall cellulose hydrolysis efficiency including: (1) the cellulase half-life, (2) the exoglucanase activity, and (3) the cellulase composition. Overall, the following parameters were found to significantly influence cellulose consumption in a consolidated bioprocess (CBP): (1) the glucose uptake rate of the culture, (2) the bacterial cell concentration, and (3) the nature of the cellulase enzyme system (complexed or non-complexed). Broadly, these results demonstrate the utility of combining modeling and sensitivity analysis to identify key parameters and/or targets for experimental improvement. PMID:24830736

Designing novel cellulase systems through agent-based modeling and global sensitivity analysis.

Science.gov (United States)

Apte, Advait A; Senger, Ryan S; Fong, Stephen S

2014-01-01

Experimental techniques allow engineering of biological systems to modify functionality; however, there still remains a need to develop tools to prioritize targets for modification. In this study, agent-based modeling (ABM) was used to build stochastic models of complexed and non-complexed cellulose hydrolysis, including enzymatic mechanisms for endoglucanase, exoglucanase, and β-glucosidase activity. Modeling results were consistent with experimental observations of higher efficiency in complexed systems than non-complexed systems and established relationships between specific cellulolytic mechanisms and overall efficiency. Global sensitivity analysis (GSA) of model results identified key parameters for improving overall cellulose hydrolysis efficiency including: (1) the cellulase half-life, (2) the exoglucanase activity, and (3) the cellulase composition. Overall, the following parameters were found to significantly influence cellulose consumption in a consolidated bioprocess (CBP): (1) the glucose uptake rate of the culture, (2) the bacterial cell concentration, and (3) the nature of the cellulase enzyme system (complexed or non-complexed). Broadly, these results demonstrate the utility of combining modeling and sensitivity analysis to identify key parameters and/or targets for experimental improvement.

Sensitive Detection of Thirteen Bacterial Vaginosis-Associated Agents Using Multiplex Polymerase Chain Reaction

Directory of Open Access Journals (Sweden)

Natália Malaguti

2015-01-01

Full Text Available Bacterial vaginosis (BV is characterized by a polymicrobial proliferation of anaerobic bacteria and depletion of lactobacilli, which are components of natural vaginal microbiota. Currently, there are limited conventional methods for BV diagnosis, and these methods are time-consuming, expensive, and rarely allow for the detection of more than one agent simultaneously. Therefore, we conceived and validated a multiplex polymerase chain reaction (M-PCR assay for the simultaneous screening of thirteen bacterial vaginosis-associated agents (BV-AAs related to symptomatic BV: Gardnerella vaginalis, Mobiluncus curtisii, Mobiluncus mulieris, Bacteroides fragilis, Mycoplasma hominis, Atopobium vaginae, Ureaplasma urealyticum, Megasphaera type I, Clostridia-like bacteria vaginosis-associated bacteria (BVABs 1, 2, and 3, Sneathia sanguinegens, and Mycoplasma genitalium. The overall validation parameters of M-PCR compared to single PCR (sPCR were extremely high, including agreement of 99.1% and sensitivity, specificity, and positive predictive values of 100.0%, negative predictive value of 97.0%, accuracy of 99.3%, and agreement with Nugent results of 100.0%. The prevalence of BV-AAs was very high (72.6%, and simultaneous agents were detected in 53.0%, which demonstrates the effectiveness of the M-PCR assay. Therefore, the M-PCR assay has great potential to impact BV diagnostic methods in vaginal samples and diminish associated complications in the near future.

Optical fiber radiation sensors: first in vivo measurements during orbital irradiation

International Nuclear Information System (INIS)

Gripp, S.; Bannach, B.; Muskalla, K.; Haesing, F.; Bueker, H.; Schmitt, G.

1995-01-01

Purpose: To investigate the applicability of doped optical fiber radiation sensors in clinical dosimetry. Methods: Ionizing radiation causes a dose depending discoloring in silica. When proper impurities (doping agents) are added, the radiation sensitivity may be increased to a range suited for clinical dosimetry. We performed in-vivo-measurements using a lead doped silica fiber (d TM ) in comparison to thermoluminescence detectors (TLDs). Results: The scattered radiation is easily detected with this sensor fiber. In contrast to TLDs the dose and doserate values are obtained immediately and setup errors can be recognized before irradiation is completed. The SD clearly depends on setup modifications due to the extent of disease. Other doping agents (GeP) provide better tissue equivalence and less energy dependence. Conclusions: Optical fibers are suitable for in vivo dosimetry purposes. Fiber sensors provide real time dose values, and the readout procedure is much easier compared to TLDs. These features may gain significance in quality assurance, conformal therapy, and intraoperative radiotherapy (IORT)

Study of radiation sensitization of artesunate on human HeLa cells of cervical cancer

International Nuclear Information System (INIS)

Ji Rong; Cao Jianping; Chen Xialin; Zhu Wei; Jiang Qing; Pan Chunyan; Zhou Yuanyuan; Feng Yang; Peng Xiaomei; Liu Yang; Fan Saijun

2010-01-01

Objective: To investigate the radiosensitizing effects of artesunate on human HeLa cells of cervical cancer in vitro. Methods: Hela cells irradiated with 60 Co γ-rays. The dose rate was 0.635 Gy/min and the radiation dose was 0, 1, 2, 4, 6 Gy, respectively. The anti-proliferation activities of artesunate on HeLa cells were evaluated with MTT assay, to determine the most appropriate drug concentration. The effect of radiosensitivity was observed by using clonogenic assay. The single-hit multi-target model was used to plot the HeLa cell's dose-survival curve, to calculate mean lethal dose, quasi-threshold dose and sensitization enhancement rate, and to evaluate its radiosensitization effect. The apoptosis was analyzed with flow cytometry (FCM) to further test the radiation sensitization of artesunate on HeLa cells. Results: The inhibition of artesunate on HeLa cells increased with concentration. In radiation group, the cell cloning efficiency were 91.67%, 82.02%, 58.06%, 25.01%, respectively, and in artesunate (2.0 μmol/L) + radiation group, the cell cloning efficiency were 74.93%, 60.53%, 22.38%, 5.05%. In radiation group and artesunate (2.0 μmol/L) + radiation group, the mean lethal dose (D 0 ) was 2.95 and 2.07 Gy, respectively, while the qusai-threshold dose (D q ) were 2.01 and 1.24 Gy, respectively, and SER was 1.43. Compared with 2 and 6 Gy radiation group, the apoptosis rate of drug + radiation group increased from 12.26%, 40.08% to 22.71%, 59.92. Conclusions: The inhibiting effect of artesunate on HeLa cells is concentration-dependent. Artesunate has radiosensitizing effect on HeLa cells in vitro. (authors)

Age and radiation sensitivity of rat mammary clonogenic cells

International Nuclear Information System (INIS)

Shimada, Yoshiya; Yasukawa-Barnes, J.; Kim, R.Y.; Gould, M.N.; Clifton, K.H.

1994-01-01

The relative risk of breast cancer is very high among women who were exposed to ionizing radiation during or before puberty. In the current studies, the surviving fractions of clonogenic mammary cells of groups of virgin rats were estimated after single exposures to 137 Cs γ rays at intervals from 1 to 12 weeks after birth. The radiosensitivity of clonogens from prepubertal rats was high and changed with the onset of puberty at between 4 and 6 weeks of age. By this time, the increase in the size of the clonogenic cell subpopulation was slowing and differentiation of terminal mammary end buds and alveolar structures was occurring. Analysis of the relationship of clonogen survival and radiation dose according to the α/β model showed that the exponential αD term predominated at the second and fourth weeks of age. By the eighth week of age, the βD 2 term had come to predominate and the survival curve had a pronounced initial convex shoulder. Further experiments are required to determine whether there is an association between the high sensitivity of the prepubertal and pubertal mammary clonogens to radiation killing and a high susceptibility to radiogenic initiation of cancer. 24 refs., 4 figs., 1 tab

Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy – case report and review of literature

International Nuclear Information System (INIS)

Putnik, Kurt; Stadler, Peter; Schäfer, Christof; Koelbl, Oliver

2006-01-01

Modern radiotherapy (RT) reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a 'recall phenomenon' imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of 'radiation recall dermatitis' (RRD) one year after RT as a result of taking hypericin (St. John's wort). A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially for complementary or alternative

Studies on the Mechanism of Radiation Resistance in Micrococcus Radiodurans and its Sensitization

Energy Technology Data Exchange (ETDEWEB)

Kitayama, S.; Matsuyama, A. [Radiobiology Laboratory, Institute of Physical and Chemical Research, Wako-shi, Saitama-ken (Japan)

1978-06-15

Efficient and accurate repair of radiation-induced lesions in M. radiodurans was investigated as to the cause of its extreme radioresistance. The cells were made permeable to deoxyribonucleoside triphosphate by treatment with non-ionic detergent, Triton X-100. After irradiation with 2 krad gamma rays more than 80% of the single-strand scissions were rejoined in the permeable cells within 10 min at 37 Degree-Sign C. This fast repair process requires the presence of deoxyribonucleoside triphosphates and NAD. However, rejoining of DNA strand scission was incomplete after prolonged incubation in the permeable cells. This suggests that alternate repair reaction(s) is necessary for complete recovery. The other type of radiation lesion was found by postirradiation incubation at non-permissive temperature, which markedly sensitizes this bacterium to radiation. Postincubation at this temperature also sensitizes the cells to chemicals that damage DNA. The extreme radioresistance of this bacterium was also lost by mutation and an isolated radiosensitive mutant showed almost the same radiosensitivity as E. coli K12 or B/r. These results are discussed in connection with the extreme radioresistance of M. radiodurans. (author)

Studies on the mechanism of radiation resistance in Micrococcus radiodurans and its sensitization

International Nuclear Information System (INIS)

Kitayama, S.; Matsuyama, A.

1978-01-01

Efficient and accurate repair of radiation-induced lesions in M. radiodurans was investigated as to the cause of its extreme radioresistance. The cells were made permeable to deoxyribonucleoside triphosphate by treatment with non-ionic detergent, Triton X-100. After irradiation with 2 krad gamma rays more than 80% of the single-strand scissions were rejoined in the permeable cells within 10 min at 37 0 C. This fast repair process requires the presence of deoxyribonucleoside triphosphates and NAD. However, rejoining of DNA strand scission was incomplete after prolonged incubation in the permeable cells. This suggests that alternate repair reaction(s) is necessary for complete recovery. The other type of radiation lesion was found by post-irradiation incubation at non-permissive temperature, which markedly sensitizes this bacterium to radiation. Postincubation at this temperature also sensitizes the cells to chemicals that damage DNA. The extreme radioresistance of this bacterium was also lost by mutation and an isolated radiosensitive mutant showed almost the same radiosensitivity as E. coli K12 or B/r. These results are discussed in connection with the extreme radioresistance of M. radiodurans. (author)

Radiation exposure and contrast agent use related to radial versus femoral arterial access during percutaneous coronary intervention (PCI)-Results of the FERARI study.

Science.gov (United States)

Becher, Tobias; Behnes, Michael; Ünsal, Melike; Baumann, Stefan; El-Battrawy, Ibrahim; Fastner, Christian; Kuschyk, Jürgen; Papavassiliu, Theano; Hoffmann, Ursula; Mashayekhi, Kambis; Borggrefe, Martin; Akin, Ibrahim

2016-12-01

Data regarding radiation exposure related to radial versus femoral arterial access in patients undergoing percutaneous coronary intervention (PCI) remain controversial. This study aims to evaluate patients enrolled in the FERARI study regarding radiation exposure, fluoroscopy time and contrast agent use. The Femoral Closure versus Radial Compression Devices Related to Percutaneous Coronary Interventions (FERARI) study evaluated prospectively 400 patients between February 2014 and May 2015 undergoing PCI either using the radial or femoral access. In these 400 patients, baseline characteristics, procedural data such as procedural duration, fluoroscopy time, dose-area product (DAP) as well as the amount of contrast agent used were documented and analyzed. Median fluoroscopy time was not significantly different in patients undergoing radial versus femoral access (12.2 vs. 9.8min, p=0.507). Furthermore, median DAP (54.5 vs. 52.0 Gycm2, p=0.826), procedural duration (46.0 vs. 45.0min, p=0.363) and contrast agent use (185.5 vs. 199.5ml, p=0.742) were also similar in radial and femoral PCI. There was no difference regarding median fluoroscopy time, procedural duration, radiation dose or contrast agent use between radial versus femoral arterial access in PCI. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiation sensitivity of foodborne pathogens in meat byproducts with different packaging

International Nuclear Information System (INIS)

Yong, Hae In; Kim, Hyun-Joo; Nam, Ki Chang; Kwon, Joong Ho; Jo, Cheorun

2015-01-01

The aim of this study was to determine radiation sensitivity of Escherichia coli O157:H7 and Listeria monocytogenes in edible meat byproducts. Seven beef byproducts (heart, liver, lung, lumen, omasum, large intestine, and small intestine) and four pork byproducts (heart, large intestine, liver, and small intestine) were used. Electron beam irradiation significantly reduced the numbers of pathogenic microorganisms in meat byproducts and no viable cells were detected in both aerobically- and vacuum-packaged samples irradiated at 4 kGy. Meat byproducts packed under vacuum had higher D 10 value than the ones packed aerobically. No significant difference was observed between the D 10 values of E. coli O157:H7 and L. monocytogenes inoculated in either aerobically or vacuum packaged samples. These results suggest that low-dose electron beam irradiation can significantly decrease microbial numbers and reduce the risk of meat byproduct contamination by the foodborne pathogens. - Highlights: • Radiation sensitivities of pathogens in meat byproduct were tested. • Electron beam irradiation of 3 or 4 kGy reduced pathogens by> 9 log • The D 10 values were lower in the aerobic-packaging than under vacuum condition

Three-dimensional, position-sensitive radiation detection

Science.gov (United States)

He, Zhong; Zhang, Feng

2010-04-06

Disclosed herein is a method of determining a characteristic of radiation detected by a radiation detector via a multiple-pixel event having a plurality of radiation interactions. The method includes determining a cathode-to-anode signal ratio for a selected interaction of the plurality of radiation interactions based on electron drift time data for the selected interaction, and determining the radiation characteristic for the multiple-pixel event based on both the cathode-to-anode signal ratio and the electron drift time data. In some embodiments, the method further includes determining a correction factor for the radiation characteristic based on an interaction depth of the plurality of radiation interactions, a lateral distance between the selected interaction and a further interaction of the plurality of radiation interactions, and the lateral positioning of the plurality of radiation interactions.

Complex control of ATM in response to radiation damage to DNA

International Nuclear Information System (INIS)

Lavin, M.F.; Beamish, H.; Chen, P.; Keating, K.; Scott, S.; Spring, K.; Kozlov, S.; Walters, D.

2000-01-01

Full text: The human genetic disorder ataxia-telangiectasia is characterized by neurodegeneration, immunodeficiency, extreme sensitivity to ionizing radiation, abnormalities in cell cycle checkpoints and a predisposition to develop leukemias and lymphomas. It appears likely that the basis of the hypersensitivity to ionizing radiation is due to defective sensing of double strand breaks in DNA and as a consequence a failure to repair all of these breaks. After exposure of cells to radiation the kinase activity of pre-existing ATM protein is rapidly activated leading to the radiation-induced phosphoylation of a number of important substrates including p53, c-Abl, BRCA1, NBS1 and chk2. Defective phosphorylation of BRCA1 and NBS1 is associated with increased sensitivity to ionizing radiation. We have also demonstrated that a reduction in the amount of ATM protein using antisense ATM cDNA transfection prior to exposure to radiation also sensitizes cells. This was further confirmed by treating human lymphoblastoid cells with EGF prior to radiation exposure. Furthermore radiation reverses the downregulation of ATM by EGF over a 3 hour period. Under these conditions cells are still sensitized to radiation since the restoration of ATM kinase activity is slower than that arising from activation of existing protein. Alterations in the amount of ATM protein are also observed in response to mitogenic agents. Thus it is evident that ATM protein and kinase activity are regulated in a complex fashion and this appears to vary in different tissues. The implications for altering ATM for therapeutic benefit will be discussed

Contrast agent choice for intravenous coronary angiography

International Nuclear Information System (INIS)

Zeman, H.D.; Siddons, D.P.

1990-01-01

The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. (orig./HSI)

Radiation dosimetry of iodine-123 HEAT, an alpha-1 receptor imaging agent

International Nuclear Information System (INIS)

Thomas, K.D.; Greer, D.M.; Couch, M.W.; Williams, C.M.

1987-01-01

Biologic distribution data in the rat were obtained for the alpha-1 adrenoceptor imaging agent (+/-) 2-[beta-(iodo-4-hydroxyphenyl)ethylaminomethyl]tetralone (HEAT) labeled with [ 123 I]. The major excretory routes were through the liver (67%) and the kidney (33%). Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads, and red bone marrow were calculated for the human using the physical decay data for [ 123 I]. The critical organ was found to be the lower large intestine, receiving 1.1 rad per mCi of [ 123 I]HEAT administered. The total-body dose was found to be 58 mrad per mCi

Economic Value of Narrowing the Uncertainty in Climate Sensitivity: Decadal Change in Shortwave Cloud Radiative Forcing and Low Cloud Feedback

Science.gov (United States)

Wielicki, B. A.; Cooke, R. M.; Golub, A. A.; Mlynczak, M. G.; Young, D. F.; Baize, R. R.

2016-12-01

Several previous studies have been published on the economic value of narrowing the uncertainty in climate sensitivity (Cooke et al. 2015, Cooke et al. 2016, Hope, 2015). All three of these studies estimated roughly 10 Trillion U.S. dollars for the Net Present Value and Real Option Value at a discount rate of 3%. This discount rate is the nominal discount rate used in the U.S. Social Cost of Carbon Memo (2010). The Cooke et al studies approached this problem by examining advances in accuracy of global temperature measurements, while the Hope 2015 study did not address the type of observations required. While temperature change is related to climate sensitivity, large uncertainties of a factor of 3 in current anthropogenic radiative forcing (IPCC, 2013) would need to be solved for advanced decadal temperature change observations to assist the challenge of narrowing climate sensitivity. The present study takes a new approach by extending the Cooke et al. 2015,2016 papers to replace observations of temperature change to observations of decadal change in the effects of changing clouds on the Earths radiative energy balance, a measurement known as Cloud Radiative Forcing, or Cloud Radiative Effect. Decadal change in this observation is direclty related to the largest uncertainty in climate sensitivity which is cloud feedback from changing amount of low clouds, primarily low clouds over the world's oceans. As a result, decadal changes in shortwave cloud radiative forcing are more directly related to cloud feedback uncertainty which is the dominant uncertainty in climate sensitivity. This paper will show results for the new approach, and allow an examination of the sensitivity of economic value results to different observations used as a constraint on uncertainty in climate sensitivity. The analysis suggests roughly a doubling of economic value to 20 Trillion Net Present Value or Real Option Value at 3% discount rate. The higher economic value results from two changes: a

Effects of food diets on insect development and its sensitivity to gamma radiation

International Nuclear Information System (INIS)

Khattak, S.U.; Azhar, A.; Shahid, M.

2004-01-01

Taking red flour beetle, Tribolium castaneum (Herbst), as a study case, studies on the effect of different food diets on insect development and losses and its sensitivity to gamma radiation, were conducted under controlled laboratory conditions. The results revealed that all the three major parameters (development, losses and sensitivity) varied significantly (P< 0.05) with respect to fed diet. Developmental period was highest (43.5 days) in wheat starch and lowest (22 days) in wheat flour + 5% yeast (Standard diet). A significantly highest progeny (948) was produced in barley and lowest (105.3) in wheat starch. Maximum adult weight (37.35 mg/20 adults) was recorded in sorghum and minimum (33.4) in starch. Percent weight loss was highest (21.25) in barley and lowest (8.0) in starch. Barley flour was found as the most preferred diet. Radiosensitivity in relation to diet indicated that adults reared on wheat starch were most sensitive. Comparing the dose response, insect mortality was dose, diet and post irradiation duration dependent. However, 2.5kGy proved quite lethal. No significant effect of radiation was observed on moisture and protein contents of the diets, except reducing sugars. (author)

On the sensitivity of a helicopter combustor wall temperature to convective and radiative thermal loads

International Nuclear Information System (INIS)

Berger, S.; Richard, S.; Duchaine, F.; Staffelbach, G.; Gicquel, L.Y.M.

2016-01-01

Highlights: • Coupling of LES, DOM and conduction is applied to an industrial combustor. • Thermal sensitivity of the combustor to convection and radiation is investigated. • CHT based on LES is feasible in an industrial context with acceptable CPU costs. • Radiation heat fluxes are of the same order of magnitude that the convective ones. • CHT with radiation are globally in good agreement with thermocolor test. - Abstract: The design of aeronautical engines is subject to many constraints that cover performance gain as well as increasingly sensitive environmental issues. These often contradicting objectives are currently being answered through an increase in the local and global temperature in the hot stages of the engine. As a result, hot spots could appear causing a premature aging of the combustion chamber. Today, the characterization of wall temperatures is performed experimentally by complex thermocolor tests in advanced phases of the design process. To limit such expensive experiments and integrate the knowledge of the thermal environment earlier in the design process, efforts are currently performed to provide high fidelity numerical tools able to predict the combustion chamber wall temperature including the main physical phenomena: combustion, convection and mixing of hot products and cold flows, radiative transfers as well as conduction in the solid parts. In this paper, partitioned coupling approaches based on a Large Eddy Simulation (LES) solver, a Discrete Ordinate Method radiation solver and an unsteady conduction code are used to investigate the sensitivity of an industrial combustor thermal environment to convection and radiation. Four computations including a reference adiabatic fluid only simulation, Conjugate Heat Transfer, Radiation-Fluid Thermal Interaction and fully coupled simulations are performed and compared with thermocolor experimental data. From the authors knowledge, such comparative study with LES has never been published. It

Can climate sensitivity be estimated from short-term relationships of top-of-atmosphere net radiation and surface temperature?

International Nuclear Information System (INIS)

Lin Bing; Min Qilong; Sun Wenbo; Hu Yongxiang; Fan, Tai-Fang

2011-01-01

Increasing the knowledge in climate radiative feedbacks is critical for current climate studies. This work focuses on short-term relationships between global mean surface temperature and top-of-atmosphere (TOA) net radiation. The relationships may be used to characterize the climate feedback as suggested by some recent studies. As those recent studies, an energy balance model with ocean mixed layer and both radiative and non-radiative heat sources is used here. The significant improvement of current model is that climate system memories are considered. Based on model simulations, short-term relationship between global mean surface temperature and TOA net radiation (or the linear striation feature as suggested by previous studies) might represent climate feedbacks when the system had no memories. However, climate systems with the same short-term feedbacks but different memories would have a similar linear striation feature. This linear striation feature reflects only fast components of climate feedbacks and may not represent the total climate feedback even when the memory length of climate systems is minimal. The potential errors in the use of short-term relationships in estimations of climate sensitivity could be big. In short time scales, fast climate processes may overwhelm long-term climate feedbacks. Thus, the climate radiative feedback parameter obtained from short-term data may not provide a reliable estimate of climate sensitivity. This result also suggests that long-term observations of global surface temperature and TOA radiation are critical in the understanding of climate feedbacks and sensitivities.

The influence of radiolytic sensitizers in natural rubber latex vulcanization induced by ionizing radiation

International Nuclear Information System (INIS)

Guedes, S.M.L.; Souza, A. de

1991-01-01

This work made on radiation vulcanization of natural rubber latex process by gamma rays from 60 Co source and electron beam of 1.5 MeV, 25 m A by Dynamitron, instead of classic process using sulfur. The experiment was carried out to study the influence of sensitizers (C Cl 4 and n-butyl acrylate) and was reported the vulcanization dose for each sensitizers, related to maximum tensile strength. The results show the possibility to introduce the volatile sensitizer (n-butyl acrylate) instead of C Cl 4 (toxic) in industry applications. (author)

A position-sensitive scintillation detector for two-dimensional angular correlation of annihilation radiation using metal-package position-sensitive photomultiplier tubes

International Nuclear Information System (INIS)

Inoue, Koji; Nagai, Yasuyoshi; Saito, Haruo; Nagashima, Yasuyuki; Hyodo, Toshio; Muramatsu, Shinichi; Nagai, Shota

1999-01-01

We have constructed and tested a prototype of a new position sensitive γ-ray detector which consists of an array of 2.6x2.6x18 mm 3 BGO scintillator blocks, a light guide, and four metal-package position-sensitive photomultiplier tubes (R5900-00-C8) recently developed by Hamamatsu Photonics Co. Ltd. Scalability of the detector of this type makes it possible to construct a larger detector using many PS-PMTs, which will be useful for the two-dimensional angular correlation of annihilation radiation apparatus

Combinatorial effect of maytansinol and radiation in Drosophila and human cancer cells

Directory of Open Access Journals (Sweden)

Anthony Edwards

2011-07-01

Combination therapy, in which two or more agents are applied, is more effective than single therapies for combating cancer. For this reason, combinations of chemotherapy with radiation are being explored in clinical trials, albeit with an empirical approach. We developed a screen to identify, from the onset, molecules that act in vivo in conjunction with radiation, using Drosophila as a model. Screens through two small molecule libraries from the NCI Developmental Therapeutics Program yielded microtubule poisons; this class of agents is known to enhance the effect of radiation in mammalian cancer models. Here we report an analysis of one microtubule depolymerizing agent, maytansinol isobutyrate (NSC292222; maytansinol, in Drosophila and in human cancer cells. We find that the effect of maytansinol is p53 dependent in Drosophila cells and human cancer cells, that maytansinol enhances the effect of radiation in both systems, and that the combinatorial effect of drug and radiation is additive. We also uncover a differential sensitivity to maytansinol between Drosophila cells and Drosophila larvae, which illustrates the value of studying cell behavior in the context of a whole organism. On the basis of these results, we propose that Drosophila might be a useful model for unbiased screens through new molecule libraries to find cancer drugs for combination therapy.

Health effects of ionizing radiation

International Nuclear Information System (INIS)

Pathak, B.

1989-12-01

Ionizing radiation is energy that travels through space as electromagnetic waves or a stream of fast moving particles. In the workplace, the sources of ionizing radiation are radioactive substances, nuclear power plants, x-ray machines and nuclear devices used in medicine, research and industry. Commonly encountered types of radiation are alpha particles, beta particles and gamma rays. Alpha particles have very little penetrating power and pose a risk only when the radioactive substance is deposited inside the body. Beta particles are more penetrating than alpha particles and can penetrate the outer body tissues causing damage to the skin and the eyes. Gamma rays are highly penetrating and can cause radiation damage to the whole body. The probability of radiation-induced disease depends on the accumulated amount of radiation dose. The main health effects of ionizing radiation are cancers in exposed persons and genetic disorders in the children, grandchildren and subsequent generations of the exposed parents. The fetus is highly sensitive to radiation-induced abnormalities. At high doses, radiation can cause cataracts in the eyes. There is no firm evidence that ionizing radiation causes premature aging. Radiation-induced sterility is highly unlikely for occupational doses. The data on the combined effect of ionizing radiation and other cancer-causing physical and chemical agents are inconclusive

Contrast agent choice for intravenous coronary angiography

International Nuclear Information System (INIS)

Zeman, H.D.; Siddons, D.P.

1989-01-01

The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth

The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.

Science.gov (United States)

Lorusso, Domenica; Fontanella, Caterina; Maltese, Giuseppa; Lepori, Stefano; Tripodi, Elisa; Bogani, Giorgio; Raspagliesi, Francesco

2017-06-01

Recurrence is a common event in endothelial ovarian cancer (EOC) patients, and the choice of the most appropriate treatment is driven by the platinum-free interval, molecular characteristics of the disease such as BRCA mutational status, previous treatments and toxicity. Areas covered: This review focuses on the main hematologic and non-hematologic toxicities correlated with the use of licensed antiangiogenic agents and PARP inhibitors in recurrent platinum-sensitive EOC, providing recommendations for their management. Expert opinion: The clinical research over the next years will be focused on a more precise characterization of molecular pathways underlying tumorigenesis of the five ovarian tumors, to improve the decision-making process in these rare diseases. For this purpose, new study designs and international collaborations will become mandatory. Immunotherapy, antiangiogenic agents and PARP inhibitors will be combined to build a treatment strategy algorithm which will allow patients to receive all the available treatment option, in the more appropriate sequence.

Biological Research for Radiation Protection

International Nuclear Information System (INIS)

Kim, In Gyu; Kim, Kug Chan; Jung, Il Lae; Choi, Yong Ho; Kim, Jin Sik; Moon, Myung Sook; Byun, Hee Sun; Phyo, Ki Heon; Kim, Sung Keun

2005-04-01

The work scope of 'Biological Research for the Radiation Protection' had contained the research about ornithine decarboxylase and its controlling proteins, thioredoxin, peroxiredoxin, S-adenosymethionine decarboxylase, and glutamate decarboxylase 67KD effect on the cell death triggered ionizing radiation and H 2 O 2 (toxic agents). In this study, to elucidate the role of these proteins in the ionizing radiation (or H 2 O 2 )-induced apoptotic cell death, we utilized sensesed (or antisensed) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation and H 2 O 2 (or paraquat). We also investigated whether genisteine(or thiamine) may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation (may enhance the preventing effect radiation or paraquat-induced damage) because such compounds are able to potentiate the cell-killing or cell protecting effects. Based on the above result, we suggest that the express regulation of theses genes have potentially importance for sensitizing the efficiency of radiation therapy of cancer or for protecting the radiation-induced damage of normal cells

Individual radiation sensitivity (gender, age, genetic disposition). Consequences for radiation protection

International Nuclear Information System (INIS)

Streffer, C.

2013-01-01

The effects of ionising radiation on human health is influenced by a number of physiological and molecular biological factors. This is also valid for the causation of stochastic radiation effects especially the causation of cancer. Several epidemiological studies have resulted with respect to the total rate of solid cancers that women are more sensitive than men by a factor of 1.6 to 2.0. For leukaemia this is not the case. The largest studies come from the investigations on the survivors of the atomic bombs in Hiroshima and Nagasaki. But also studies on the population of the Techa River (Southeast Urals) yield such data. The analyses of single cancer localizations come to different results with respect to the dependence on the sex. Secondary cancers after radiotherapy for cancer treatment show also higher rates in women than in men. A similar situation is observed with respect to the dependence of cancer rate on age. The total rate of solid cancers is highest with children and decreases with increasing age. The effects are very different again with single cancer localizations. An especially strong age dependence was observed for thyroid cancer. Increasingly individuals have been found who are especially radiosensitive on the basis of their genetic disposition also with respect to the causation of cancer. Mechanisms and possibilities to trace these individuals are discussed. It is also discussed whether and to which extent these data should have consequences for the practical radiological protection. (orig.)

Position sensitive regions in a generic radiation sensor based on single event upsets in dynamic RAMs

International Nuclear Information System (INIS)

Darambara, D.G.; Spyrou, N.M.

1997-01-01

Modern integrated circuits are highly complex systems and, as such, are susceptible to occasional failures. Semiconductor memory devices, particularly dynamic random access memories (dRAMs), are subject to random, transient single event upsets (SEUs) created by energetic ionizing radiation. These radiation-induced soft failures in the stored data of silicon based memory chips provide the foundation for a new, highly efficient, low cost generic radiation sensor. The susceptibility and the detection efficiency of a given dRAM device to SEUs is a complicated function of the circuit design and geometry, the operating conditions and the physics of the charge collection mechanisms involved. Typically, soft error rates measure the cumulative response of all sensitive regions of the memory by broad area chip exposure in ionizing radiation environments. However, this study shows that many regions of a dynamic memory are competing charge collection centres having different upset thresholds. The contribution to soft fails from discrete regions or individual circuit elements of the memory device is unambiguously separated. Hence the use of the dRAM as a position sensitive radiation detector, with high spatial resolution, is assessed and demonstrated. (orig.)

Modification of the cellular heat sensitivity of cucumber by growth under supplemental ultraviolet-B radiation

International Nuclear Information System (INIS)

Caldwell, C.R.

1994-01-01

The effect of ultraviolet B (UV-B) radiation on the thermal sensitivity of cucumber (Cucumis sativus L.) was studied using UV-B-sensitive cv Poinsett 76 and UV-B-resistant cv Ashley grown under control and elevated (300 mW m -2 ) UV-B radiation levels. Using both cotyledon and leaf discs, the ability of the tissue to reduce triphenyl tetrazolium chloride (TTC) was determined after treatment at 50 degrees C for various times. Semilogarithmic plots of TTC reduction as a function of time at 50 degrees were curvilinear. They were monophasic for the control cucumber and biphasic for cucumber grown in the presence of elevated UV-B. Treatment of cucumber plants at 37 degrees C for 24 h or of tissue discs at acute UV-B levels for 1 h further modified their response to elevated temperature. These results suggest that growth of cucumber under enhanced UV-B radiation levels increased its ability to withstand elevated temperatures. 19 refs., 2 figs., 2 tabs

New therapeutic agent for radiation synovectomy - preparation of 166Ho-EDTMP-HA particle

International Nuclear Information System (INIS)

Bai, H.; Jin, X.; Du, J.; Wang, F.; Chen, D.; Fan, H.; Cheng, Z.; Zhang, J.

1997-01-01

In order to prepare new therapeutical agent for radiation synovectomy, Hydroxyapatite (HA) was labelled with 166 Ho by EDTMP that had high affinity to HA particles. Radiolabelling of HA particles was divided into two steps, 166 Ho-EDTMP was prepared first; then mixed with HA particles completely and vibrated for 15 minutes on the micromixer at room temperature, washed 3 times with deionized water. Radiolabelling particle was separated from free 166 Ho via centrifugation to determine its radiolabelling efficiency. 166 Ho-EDTMP-HA and 166 Ho-EDTMP were injected into knee joint of normal rabbits respectively, every group was killed at different time postinjection, took out major organ and collected urine and blood, then weighted and determined their radio counts. HA particles, as a natural component of bone was known to have good compatibility with soft tissue and biodegrade into calcium and phosphate in vivo. It was readily prepared from common chemical and formed into particles of desired size range in a controlled process, it had high stability in vitro and vivo. Radiolabelling of HA particle with 166 Ho by EDTMP was simple to perform and provides an excellent labelling yield that was more than 95% under the optimal labelling condition. The optimal labelling condition at room temperature was pH 6.0-8.0 and vibration time 15 minutes. The absorbed capacity of HA particle was 5 mg Ho/g HA particle and size of radiolabelling particle was at range of 2-5,μm that is suitable for therapy of radiation synovectomy. 166 Ho-EDTMP-HA particle demonstrated high in vitro stability in either normal saline or 1% BSA solution, but instability under extremely acidic condition (pH 1-2). The control studies performed with 166 Ho-EDTMP not bound to HA particle provided information on the distribution of radioactivity that would occur upon leakage of the radiochemical compound from joint. Its short half-life, its extremely low leakage from the joint and its even distribution throughout

Comparison of alkylating agent and radiation carcinogenesis: some aspects of the possible involvement of effects on DNA

International Nuclear Information System (INIS)

Lawley, P.D.

1976-01-01

A series of alkylating agents was classified in terms of increasing relative ability to react at O-atom sites in DNA, MMS 6 -alkylguanines are directly miscoding bases. This series of agents was also used in a study of comparative carcinogenicity with respect to induction of thymic lymphoma in mice, a system in which x-irradiation yields tumors. A positive correlation between ability of agents to alkylate O-6 of guanine in DNA of thymus and carcinogenic potency was found. Although MMS was not active in this system, it was noted that it can induce tumors in other systems. The relationship between repair of alkylation and radiation induced damage in DNA was briefly discussed. The methylating agents induce single-strand breaks in DNA, and the principal repair system appears to fall into the category of short repair as denoted by Regan and Setlow (1974). These single-strand breaks may result from spontaneous hydrolytic depurinations of 3- and 7-methylpurines, or from enzymatic depurinations, e.g., of 3-alkyladenine and O 6 -alkylguanine. Aralkylating agents, which are also carcinogens, can evoke an alternative repair response of the uvr type

Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents.

Directory of Open Access Journals (Sweden)

Ryan J Mailloux

2010-10-01

Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.

Radiation sterilization of pharmaceuticals and polymers

International Nuclear Information System (INIS)

Gopal, N.G.S.

1978-01-01

Radiation, in the form of high energy electrons as well as gamma radiation, has featured in the last 15 yr as a promising sterilization agent for many heat sensitive and ethylene oxide incompatible pharmaceuticals and polymers of medical usage. This article deals with (i) a comparison of the various methods of sterilization and their shortcomings, (ii) modes of interaction of radiation with matter, (iii) the types of radiation sources in common use, (iv) dosimetry, (v) dose rate effect, (vi) a literature survey of the radiation effect on pharmaceuticals in solid form as well as in aqueous solution and on polymers in the form of plastic medical products and (vii) the evaluation of the irradiated products. The effect of dose rate on the stability of these materials is emphasized. Either very little work has been done on the dose rate effect or the published information is scanty. The literature survey covers the recent period of 5 to 6 years. (author)

Studies on radiation-sensitive nonsilver halide materials, (1)

International Nuclear Information System (INIS)

Komizu, Hideo; Honda, Koichi; Yabe, Akira; Kawasaki, Masami; Fujii, Etsuo

1978-01-01

In order to discover new radiation-sensitive nonsilver halide materials, the coloration based on the formation of Stenhouse salts was studied in the following three systems: (a) furfural-amine/HCl aq/methanol solution, (b) furfural-amine/polyhalogenide/PMMA matrix, (c) furfural-amine/PVC matrix. Firstly, forty-five aromatic amines were surveyed to find out the amines suitable for the color precursors (reactant from furfural and amine) in the system (a). As a result, the five amines, which gave the precursors in good yields by the reaction with furfural, were selected: m-nitroaniline, N-methylaniline, m-methyl-N-methylaniline, aniline, and o-methoxyaniline. Secondly, the coloration induced by electron beam bombardment was studied in the systems (b) and (c) containing the color precursors (the reactants from these amines and furfural). Although the PMMA films containing the color precursors and polyhalogenides were sensitive to electron beam, they were not stable when standing under daylight at room temperature. The PVC films containing the color precursors were very stable and colored to reddish yellow (lambda sub(max) 498 - 545 nm) by electron beam bombardment. The PVC film containing N-methylaniline-furfural was the most sensitive and the increase in absorbance at 498 nm was 0.78 by electron beam bombardment of 60 kV - 7.5 x 10 -7 C/cm 2 . A good linear relationship existed between the degree of coloration and the amounts of electron beam bombardment in the range from 0 to 10 -6 C/cm 2 . (author)

The combined effects of radiation and ultrasound on ICR mouse embryos

International Nuclear Information System (INIS)

Hong, A.I.C.; Kusama, T.; Gu, Y.; Aoki, Y.

1993-01-01

We have investigated the combined effects of radiation and ultrasound on the embryos of ICR mice. The pregnant ICR mice on day 8 of gestation were irradiated with 1.0 W ultrasound after exposure to 1.5 Gy radiation immediately or irradiated with time interval of one hour. The incidences of external malformations synergistically increased in the group irradiated with both agents. Especially in the group treated with time interval of one hour, the incidences of external malformations reached to the maximum. The histological examination showed that the frequencies of pyknotic cells in the neutral folds of embryos on day 8 of gestation increased synergistically while the frequencies of mitotic cells decreased steeply in the group treated with both agents. We concluded that the combined effects of radiation and ultrasound on external malformations and the histological changes in mouse embryos were synergistic-sensitization effects. (6 figs.)

Enhanced killing of mammalian cells by radiation combined with m-AMSA

International Nuclear Information System (INIS)

Roberts, P.B.; Millar, B.C.

1980-01-01

m-AMSA is an intercalating agent at present on Phase II trial as a chemotherapeutic drug. A 30min exposure of Chinese hamster (Line V79-753B) cells to submicromolar concentrations of m-AMSA killed 50% of the cells. The survivors had an enhanced sensitivity to radiation-induced cell killing. Depending upon the conditions, m-AMSA enhanced the radiation effect by either a decrease in the survival-curve shoulder or by an increase in slope. m-AMSA may act partly by suppressing the accumulation of sublethal damage but, if so, recovery from damage as measured in split-dose experiments with cells pretreated with the drug is not affected. m-AMSA increased radiation lethality throughout the cell cycle, but a contribution to its radiation effect from selective toxicity to cells in a radioresistant phase of the cell cycle cannot be excluded. Radiation and the drug interacted to give increased cell killing, even when the exposures to each agent were separated in time. It is concluded that m-ASMA may behave like actinomycin D and adriamycin, and enhance clinical radiation responses. In vivo testing to determine the effect of m-AMSA on the therapeutic index is recommended. (author)

Enhanced killing of mammalian cells by radiation combined with m-AMSA

Energy Technology Data Exchange (ETDEWEB)

Roberts, P B; Millar, B C [Institute of Cancer Research, Sutton (UK). Surrey Branch

1980-11-01

m-AMSA is an intercalating agent at present on Phase II trial as a chemotherapeutic drug. A 30 min exposure of Chinese hamster (Line V79-753B) cells to submicromolar concentrations of m-AMSA killed 50% of the cells. The survivors had an enhanced sensitivity to radiation-induced cell killing. Depending upon the conditions, m-AMSA enhanced the radiation effect by either a decrease in the survival-curve shoulder or by an increase in slope. m-AMSA may act partly by suppressing the accumulation of sublethal damage but, if so, recovery from damage as measured in split-dose experiments with cells pretreated with the drug is not affected. m-AMSA increased radiation lethality throughout the cell cycle, but a contribution to its radiation effect from selective toxicity to cells in a radioresistant phase of the cell cycle cannot be excluded. Radiation and the drug interacted to give increased cell killing, even when the exposures to each agent were separated in time. It is concluded that m-ASMA may behave like actinomycin D and adriamycin, and enhance clinical radiation responses. In vivo testing to determine the effect of m-AMSA on the therapeutic index is recommended.

Protective roles of bacterioruberin and intracellular KCl in the resistance of Halobacterium salinarium against DNA-damaging agents

International Nuclear Information System (INIS)

Shahmohammadi, H.R.; Asgarani, E.; Terato, Hiroaki; Saito, Takeshi; Ohyama, Yoshihiko; Gekko, Kunihiko; Yamamoto, Osamu; Ide, Hiroshi

1998-01-01

Halobacterium salinarium, a member of the extremely halophilic archaebacteria, contains a C 50 -carotenoid namely bacterioruberin. We have previously reported the high resistance of this organism against the lethal actions of DNA-damaging agents including ionizing radiation and ultraviolet light (UV). In this study, we have examined whether bacterioruberin and the highly concentrated salts in this bacterium play protective roles against the lethal actions of ionizing radiation, UV, hydrogen peroxide, and mitomycin-C (MMC). The colourless mutant of H. salinarium deficient in bacterioruberin was more sensitive than the red-pigmented wild-type to all tested DNA-damaging agents except MMC. Circular dichroism (CD) spectra of H. salinarium chromosomal DNA at various concentrations of KCl (0-3.5 M) were similar to that of B-DNA, indicating that no conformational changes occurred as a result of high salt concentrations. However, DNA strand-breaks induced by ionizing radiation were significantly reduced by the presence of either bacterioruberin or concentrated KCl, presumably due to scavenging of free radicals. These results suggest that bacterioruberin and intracellular KCl of H. salinarium protect this organism against the lethal effects of oxidative DNA-damaging agents. (author)

Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

2014-11-21

Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

International Nuclear Information System (INIS)

Kim, In-Gyu; Lee, Jae-Ha; Kim, Seo-Yoen; Kim, Jeong-Yul; Cho, Eun-Wie

2014-01-01

Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

Status of multigroup sensitivity profiles and covariance matrices available from the radiation shielding information center

International Nuclear Information System (INIS)

Roussin, R.W.; Drischler, J.D.; Marable, J.H.

1980-01-01

In recent years multigroup sensitivity profiles and covariance matrices have been added to the Radiation Shielding Information Center's Data Library Collection (DLC). Sensitivity profiles are available in a single package. DLC-45/SENPRO, and covariance matrices are found in two packages, DLC-44/COVERX and DLC-77/COVERV. The contents of these packages are described and their availability is discussed

Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Walden, Jr, T L; Holahan, Jr, E V; Catravas, G N

1986-01-01

Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

Radiation sensitivity of Merkel cell carcinoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Leonard, J.H.; Ramsay, J.R.; Birrell, G.W. [Queensland Institute of Medical Research (Australia)] [and others

1995-07-30

Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

Radiation sensitivity of Merkell cell carcinoma cell lines

International Nuclear Information System (INIS)

Leonard, J. Helen; Ramsay, Jonathan R.; Kearsley, John H.; Birrell, Geoff W.

1995-01-01

Purpose: Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Methods and Materials: Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after γ irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. Results: We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to γ irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Conclusion: Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution

Low-power millimeter wave radiations do not alter stress-sensitive gene expression of chaperone proteins.

Science.gov (United States)

Zhadobov, M; Sauleau, R; Le Coq, L; Debure, L; Thouroude, D; Michel, D; Le Dréan, Y

2007-04-01

This article reports experimental results on the influence of low-power millimeter wave (MMW) radiation at 60 GHz on a set of stress-sensitive gene expression of molecular chaperones, namely clusterin (CLU) and HSP70, in a human brain cell line. Selection of the exposure frequency is determined by its near-future applications for the new broadband civil wireless communication systems including wireless local area networks (WLAN) for domestic and professional uses. Frequencies around 60 GHz are strongly attenuated in the earth's atmosphere and such radiations represent a new environmental factor. An exposure system operating in V-band (50-75 GHz) was developed for cell exposure. U-251 MG glial cell line was sham-exposed or exposed to MMW radiation for different durations (1-33 h) and two different power densities (5.4 microW/cm(2) or 0.54 mW/cm(2)). As gene expression is a multiple-step process, we analyzed chaperone proteins induction at different levels. First, using luciferase reporter gene, we investigated potential effect of MMWs on the activation of transcription factors (TFs) and gene promoter activity. Next, using RT-PCR and Western blot assays, we verified whether MMW exposure could alter RNA accumulation, translation, or protein stability. Experimental data demonstrated the absence of significant modifications in gene transcription, mRNA, and protein amount for the considered stress-sensitive genes for the exposure durations and power densities investigated. The main results of this study suggest that low-power 60 GHz radiation does not modify stress-sensitive gene expression of chaperone proteins. (c) 2006 Wiley-Liss, Inc.

Position sensitive detection of neutrons in high radiation background field.

Science.gov (United States)

Vavrik, D; Jakubek, J; Pospisil, S; Vacik, J

2014-01-01

We present the development of a high-resolution position sensitive device for detection of slow neutrons in the environment of extremely high γ and e(-) radiation background. We make use of a planar silicon pixelated (pixel size: 55 × 55 μm(2)) spectroscopic Timepix detector adapted for neutron detection utilizing very thin (10)B converter placed onto detector surface. We demonstrate that electromagnetic radiation background can be discriminated from the neutron signal utilizing the fact that each particle type produces characteristic ionization tracks in the pixelated detector. Particular tracks can be distinguished by their 2D shape (in the detector plane) and spectroscopic response using single event analysis. A Cd sheet served as thermal neutron stopper as well as intensive source of gamma rays and energetic electrons. Highly efficient discrimination was successful even at very low neutron to electromagnetic background ratio about 10(-4).

SENSITIVITY OF THE CUMIN SEEDS ASSOCIATED FUNGI TO GAMMA RADIATION

International Nuclear Information System (INIS)

BOTROS, H.W.; HELAL, I.M.; EL TOBGY, K.M.K.

2008-01-01

The present study was carried out to investigate the sensitivity of fungi associated to cumin seeds for gamma radiation. In this regard, the isolated seed associated fungi from the cumin seeds were fifteen fungal species belonging to five genera. The fungal species concerning, Aspergillus ochraceus, Fusarium oxysporium and Aspergillus flavus were the predominant fungi in percentages of 17.8, 15.83 and 12.78 %, respectively. Aspergillus ochraceus was the most effective prevalent fungi on the seed germination causing highest percentage of seed invasion followed by Fusarium oxysporium and Aspergillus flavus. The amylolytic, proteolytic and lipolytic activity and mycotoxin production of the three predominant fungi were negatively influenced by gamma radiation when exposed to doses of 1.0 , 1.5 , 2.5 , 3.5 , 5.0 and 7.5 kGy a behaviour which was parallel to the inhibition in the amount of growth by gamma irradiation

A survey of cross-section sensitivity analysis as applied to radiation shielding

International Nuclear Information System (INIS)

Goldstein, H.

1977-01-01

Cross section sensitivity studies revolve around finding the change in the value of an integral quantity, e.g. transmitted dose, for a given change in one of the cross sections. A review is given of the principal methodologies for obtaining the sensitivity profiles-principally direct calculations with altered cross sections, and linear perturbation theory. Some of the varied applications of cross section sensitivity analysis are described, including the practice, of questionable value, of adjusting input cross section data sets so as to provide agreement with integral experiments. Finally, a plea is made for using cross section sensitivity analysis as a powerful tool for analysing the transport mechanisms of particles in radiation shields and for constructing models of how cross section phenomena affect the transport. Cross section sensitivities in the shielding area have proved to be highly problem-dependent. Without the understanding afforded by such models, it is impossible to extrapolate the conclusions of cross section sensitivity analysis beyond the narrow limits of the specific situations examined in detail. Some of the elements that might be of use in developing the qualitative models are presented. (orig.) [de

FDTD solutions for the distribution of radiation from dipoles embedded in dielectric particles

Energy Technology Data Exchange (ETDEWEB)

Li Changhui [Department of Physics, Texas A and M University, College Station, TX (United States)]. E-mail: cli@biomed.wustl.edu; Kattawar, George W. [Department of Physics, Texas A and M University, College Station, TX (United States); You, Yu [Department of Physics, Texas A and M University, College Station, TX (United States); Zhai Pengwang [Department of Physics, Texas A and M University, College Station, TX (United States); Yang Ping [Department of Atmospheric Sciences, Texas A and M University, College Station, TX (United States)

2007-07-15

The finite-difference time-domain (FDTD) method is used to simulate the electromagnetic radiation emitted by an infinitesimal electric dipole embedded in a small particle with an arbitrary shape and internal composition. The far-field pattern of the radiation pertaining to dipoles embedded in a host particle is highly sensitive to the particle shape. Thus, it is possible to discriminate host particles according to their radiation patterns. The method reported here is also applicable to the study of induced Raman scattering and fluorescence phenomena and the detection of biological agents.

Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin

International Nuclear Information System (INIS)

Greene, M.H.; Goedert, J.J.; Bech-Hansen, N.T.; McGuire, D.; Paterson, M.C.; Fraumeni, J.F. Jr.

1983-01-01

A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis

Role of p53 status in radiation sensitivity and cell cycle progression

International Nuclear Information System (INIS)

Zellars, Richard C.; Loney, Tania; Schott, Ann F.; Davis, Mary A.; Maybaum, Jonathan; Clarke, Michael F.; Lawrence, Theodore S.

1995-01-01

Purpose: Although p53 function plays a major role in G1 arrest after radiation, the influence of p53 status on progress through other phases of the cell cycle and on radiation sensitivity of human tumors is less clear. We investigated these issues using cells with a conditional expression system for wild type p53. Methods: A temperature sensitive murine wild type p53 plasmid was used (Ginsberg D, et al: Mol. Cell.Biol . 11:582, 1991). At the permissive temperature (32 deg. C), this plasmid produces a protein which assumes a conformation that exhibits wild type p53 function. However, when cells are cultured at 38 deg. C, this protein assumes an inactive conformation. HT29 human colon cancer cells (which are p53 mutant) were transduced with this plasmid (designated PEP A and PEP G cells) or a control vector (designated CCH1 cells) using electroporation and Geneticin selection. The presence of murine p53 transcript in the PEP cells was confirmed by Northern analysis. Results: Cells were cultured under 3 conditions: 1) 38 deg. C at all times; 2) 32 deg. C for 24 hours prior to irradiation and 3) 32 deg. C for 24 hours after irradiation. We found that culturing under permissive temperatures produced a small decrease in surviving fraction in the PEP clones (0.61 ± 0.10 and 0.64 ± 0.07, for PEP A and G, respectively) but not the CCH1 controls (1.14 ± 0.15). PEP cells tended to be more radiosensitive than CCH1 cells (even under non-permissive conditions) and demonstrated a trend towards increased radiosensitivity under both Conditions 2 and 3. In addition, flow cytometry revealed that a 24 hour exposure to permissive conditions increased the fraction of cells in G1 slightly and in G2/M substantially. S phase was almost absent. Conclusion: Restoration of p53 function in HT29 human colon cancer cells using this temperature sensitive system produced increased cytotoxicity and radiation sensitivity as well as cell cycle redistribution. It will be important to assess the

Sensitivity to UV radiation in early life stages of the Mediterranean sea urchin Sphaerechinus granularis (Lamarck)

International Nuclear Information System (INIS)

Nahon, Sarah; Castro Porras, Viviana A.; Pruski, Audrey M.; Charles, Francois

2009-01-01

The sea urchin Sphaerechinus granularis was used to investigate the impact of relevant levels of UV-B radiation on the early life stages of a common Mediterranean free spawning benthic species. Sperm, eggs and embryos were exposed to a range of UV radiation doses. The resulting endpoints were evaluated in terms of fertilisation success, development and survival rates. Above a weighted UV radiation dose of 0.0029 kJ m -2 , fertilisation capability of irradiated sperm decreased rapidly. The exposure of the eggs to 0.0175 kJ m -2 and more led to delayed and inhibited development with ensuing embryonic morphological abnormalities. One-day old larvae remained strongly sensitive to UV radiation as shown by the 50% decrease of the larval survival rate for a dose of 0.025 kJ m -2 UVR. The elevated sensitivity of embryos to experimental UVR went along with a lack of significant amount of sunscreen compounds (e.g., mycosporine-like amino acids) in the eggs. The present results demonstrated that gamete viability and embryonic development may be significantly impaired by solar UV radiation in S. granularis, compromising in this way the reproduction of the species. Unless adaptive behavioural reproductive strategies exist, the influence of ambient UV radiation appears as a selective force for population dynamics of broadcast spawners in the shallow benthic Mediterranean environment

Sensitivity to UV radiation in early life stages of the Mediterranean sea urchin Sphaerechinus granularis (Lamarck)

Energy Technology Data Exchange (ETDEWEB)

Nahon, Sarah [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Castro Porras, Viviana A. [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Pruski, Audrey M. [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Charles, Francois [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France)], E-mail: charles@obs-banyuls.fr

2009-03-01

The sea urchin Sphaerechinus granularis was used to investigate the impact of relevant levels of UV-B radiation on the early life stages of a common Mediterranean free spawning benthic species. Sperm, eggs and embryos were exposed to a range of UV radiation doses. The resulting endpoints were evaluated in terms of fertilisation success, development and survival rates. Above a weighted UV radiation dose of 0.0029 kJ m{sup -2}, fertilisation capability of irradiated sperm decreased rapidly. The exposure of the eggs to 0.0175 kJ m{sup -2} and more led to delayed and inhibited development with ensuing embryonic morphological abnormalities. One-day old larvae remained strongly sensitive to UV radiation as shown by the 50% decrease of the larval survival rate for a dose of 0.025 kJ m{sup -2} UVR. The elevated sensitivity of embryos to experimental UVR went along with a lack of significant amount of sunscreen compounds (e.g., mycosporine-like amino acids) in the eggs. The present results demonstrated that gamete viability and embryonic development may be significantly impaired by solar UV radiation in S. granularis, compromising in this way the reproduction of the species. Unless adaptive behavioural reproductive strategies exist, the influence of ambient UV radiation appears as a selective force for population dynamics of broadcast spawners in the shallow benthic Mediterranean environment.

Sodium butyrate affects the cytotoxic and mutagenic response of V79 Chinese hamster cells to the genotoxic agents, daunorubicin and U.V. radiation

International Nuclear Information System (INIS)

Pani, B.; Babudri, N.; Giancotti, V.; Russo, E.

1984-01-01

It has been suggested that conditions which lead to modifications in the chromatin structure could be responsible for an increased accessibility of DNA to genotoxic agents in eukaryotic cells. With this in mind, the cytotoxic and mutagenic activity of the anthracycline antibiotic, daunorubicin, and of UV radiation was assayed on V79 Chinese hamster cells pretreated or not with 5 mM sodium butyrate, an agent known to induce modifications in the chromatin structure: this treatment in fact proved to induce the hyperacetylation of the core histones, and moreover to enhance the cytotoxic response of the cells to both daunorubicin and UV radiation and the mutagenic response to daunorubicin. (orig.)

Effect of nitric oxide and hydrogen sulfide on radiation sensitivity of spores of Bacillus megaterium in suspension

Energy Technology Data Exchange (ETDEWEB)

Russell, C

1966-01-01

The effect of nitric oxide on the sensitivity to radiation of spores of B. megaterium in water suspension is similar to that seen in vegetative cells of E. coli. The spores are less sensitive in the presence of hydrogen sulfide. 11 references, 1 figure.

The sensitivity of human mesenchymal stem cells to ionizing radiation

International Nuclear Information System (INIS)

Chen, M.-F.; Lin, C.-T.; Chen, W.-C.; Yang, C.-T.; Chen, C.-C.; Liao, S.-K.; Liu, J.M.; Lu, C.-H.; Lee, K.-D.

2006-01-01

Purpose: Recent studies have shown that mesenchymal stem cells (MSCs) obtained from bone marrow transplantation patients originate from the host. This clinical observation suggests that MSCs in their niches could be resistant to irradiation. However, the biologic responses of bone marrow MSCs to irradiation have rarely been described in the literature. Methods and Materials: In this study, human bone marrow-derived, clonally expanded MSCs were used to investigate their sensitivity to irradiation in vitro, and the cellular mechanisms that may facilitate resistance to irradiation. The human lung cancer cell line A549 and the breast cancer cell line HCC1937 were used as controls for radiosensitivity; the former line has been shown to be radioresistant and the latter radiosensitive. We then examined their in vitro biologic changes and sensitivities to radiation therapy. Results: Our results suggest that MSCs are characterized as resistant to irradiation. Several cellular mechanisms were demonstrated that may facilitate resistance to irradiation: ATM protein phosphorylation, activation of cell-cycle checkpoints, double-strand break repair by homologous recombination and nonhomologous end joining (NHEJ), and the antioxidant capacity for scavenging reactive oxygen species. Conclusions: As demonstrated, MSCs possess a better antioxidant reactive oxygen species-scavenging capacity and active double-strand break repair to facilitate their radioresistance. These findings provide a better understanding of radiation-induced biologic responses in MSCs and may lead to the development of better strategies for stem cell treatment and cancer therapy

Differential sensitivity to natural ultraviolet radiation among phytoplankton species in Arctic lakes (Spitsbergen, Norway)

NARCIS (Netherlands)

Donk, van E.; Faafeng, B.A.; Lange, de H.J.

2001-01-01

Incubation experiments demonstrated a differential sensitivity to natural UV-radiation among the dominant phytoplankton species from three Arctic lakes, situated near Ny-Ålesund, Spitsbergen (79° N). The growth of small chlorophytes, diatoms and picocyanobacteria from two oligotrophic lakes was

A novel high sensitivity HPLC assay for topiramate, using 4-chloro-7-nitrobenzofurazan as pre-column fluorescence derivatizing agent.

Science.gov (United States)

Bahrami, Gholamreza; Mohammadi, Bahareh

2007-05-01

A new, sensitive and simple high-performance liquid chromatographic method for analysis of topiramate, an antiepileptic agent, using 4-chloro-7-nitrobenzofurazan as pre-column derivatization agent is described. Following liquid-liquid extraction of topiramate and an internal standard (amlodipine) from human serum, derivatization of the drugs was performed by the labeling agent in the presence of dichloromethane, methanol, acetonitrile and borate buffer (0.05 M; pH 10.6). A mixture of sodium phosphate buffer (0.05 M; pH 2.4): methanol (35:65 v/v) was eluted as mobile phase and chromatographic separation was achieved using a Shimpack CLC-C18 (150 x 4.6 mm) column. In this method the limit of quantification of 0.01 microg/mL was obtained and the procedure was validated over the concentration range of 0.01 to 12.8 microg/mL. No interferences were found from commonly co-administrated antiepileptic drugs including phenytoin, phenobarbital carbamazepine, lamotrigine, zonisamide, primidone, gabapentin, vigabatrin, and ethosuximide. The analysis performance was carried-out in terms of specificity, sensitivity, linearity, precision, accuracy and stability and the method was shown to be accurate, with intra-day and inter-day accuracy from -3.4 to 10% and precise, with intra-day and inter-day precision from 1.1 to 18%.

Mutagenic interactions between near-ultraviolet (365 nm) radiation and alkylating agents in Escherichia coli

International Nuclear Information System (INIS)

Moraes, E.C. de; Tyrell, R.M.

1981-01-01

The mutagenic interaction between near-ultrviolet (365 nm) radiation and the alkylting agents ehtyl methanesulponate (EMS) and methyl methanesulphonate (MMS) was studied in a repair-component and an excision-deficient stram of Escherichia coli. Near-UV raditation modified the metabolic response of of exposure to these chemicals and either reduced or increased their mutagenic efficiency. Based on these results, an experimental model was formulated to explain the mutagenic interactions that occur between near-UV and various agents that induce prototrophic reverants cia error-prone repair of DNA. According to this model, low doses of near-UV provoke conditions for mutation frequency decline (MFI) and lead to a mutagenic antagonism. With increasing near-Uv doses, damage to constitutive error-free repairs system increases, favouring the error-prone system and inhibiting the MFD. Under these conditions there will be a progressive decrease in antagonism until at high doses an enhancement of mutation frequency (positive interaction) will occur. (orig.)

Sensitivity of strains of Escherichia coli differing in repair capability to far UV, near UV and visible radiations

International Nuclear Information System (INIS)

Webb, R.B.; Brown, M.S.

1976-01-01

In stationary phase, strains of Escherichia coli deficient in excision (B/r Hcr) or recombination repair (K12 AB2463) were more sensitive than a repair proficient strain (B/r) to monochromatic near-ultraviolet (365nm) and visible (460 nm) radiations. The relative increase in sensitivity of mutants deficient in excision or recombination repair in comparison to the wildtype, was less at 365 nm than at 254 nm. However, a strain deficient in both excision and recombination repair (K12 AB2480) showed a large, almost equal, increase in sensitivity over mutants deficient in either excision or recombination repair at 365 nm and 254 nm. All strains tested were highly resistant to 650 nm radiation. Action spectra for lethality of strains B/r and B/r Hcr in stationary phase reveal small peaks or shoulders in the 330 to 340, 400 to 410 and 490 to 510 nm wavelength ranges. The presence of 5 micro g/ml acriflavine (an inhibitor of repair) in the plating medium greatly increased the sensitivity of strain B/r to radiation at 254, 365 and 460 nm, while strains E.coli B/r Hcr and K12 AB2463 were sensitized by small amounts. At each of the wavelengths tested, acriflavine in the plating medium had at most a small effect on E.coli K12 AB2480. Acriflavine failed to sensitize any strain tested at 650 nm. Evidence supports the interpretation that lesions induced in DNA by 365 nm and 460 nm radiations play the major role in the inactivation of E.coli by these wavelengths. Single-strand breaks (or alkali-labile bonds), but not pyrimidine dimers are candidates for the lethal DNA lesions in uvrA and repair proficient strains. At high fluences lethality may be enhanced by damage to the excision and recombination repair systems. (author)

Sensitivity of strains of Escherichia coli differing in repair capability to far uv, near uv and visible radiations

Energy Technology Data Exchange (ETDEWEB)

Webb, R B; Brown, M S [Argonne National Lab., Ill. (USA)

1976-11-01

In stationary phase, strains of Escherichia coli deficient in excision (B/r Hcr) or recombination repair (K12 AB2463) were more sensitive than a repair proficient strain (B/r) to monochromatic near-ultraviolet (365nm) and visible (460 nm) radiations. The relative increase in sensitivity of mutants deficient in excision or recombination repair in comparison to the wildtype, was less at 365 nm than at 254 nm. However, a strain deficient in both excision and recombination repair (K12 AB2480) showed a large, almost equal, increase in sensitivity over mutants deficient in either excision or recombination repair at 365 nm and 254 nm. All strains tested were highly resistant to 650 nm radiation. Action spectra for lethality of strains B/r and B/r Hcr in stationary phase reveal small peaks or shoulders in the 330 to 340, 400 to 410 and 490 to 510 nm wavelength ranges. The presence of 5 micro g/ml acriflavine (an inhibitor of repair) in the plating medium greatly increased the sensitivity of strain B/r to radiation at 254, 365 and 460 nm, while strains E.coli B/r Hcr and K12 AB2463 were sensitized by small amounts. At each of the wavelengths tested, acriflavine in the plating medium had at most a small effect on E.coli K12 AB2480. Acriflavine failed to sensitize any strain tested at 650 nm. Evidence supports the interpretation that lesions induced in DNA by 365 nm and 460 nm radiations play the major role in the inactivation of E.coli by these wavelengths. Single-strand breaks (or alkali-labile bonds), but not pyrimidine dimers are candidates for the lethal DNA lesions in uvrA and repair proficient strains. At high fluences lethality may be enhanced by damage to the excision and recombination repair systems.

Comparison of radiation dosimetry for several potential myocardial imaging agents

International Nuclear Information System (INIS)

Watson, E.E.; Stabin, M.G; Goodman, M.M.; Knapp, F.F. Jr.; Srivastava, P.C.

1986-01-01

Although myocardial imaging is currently dominated by Tl-201, several alternative agents with improved physiologic or radionuclidic properties have been proposed. Based on human and animal studies in the literature, the metabolism of several of these compounds was studied for the purpose of generating radiation dose estimates. Dose estimates are listed for several I-123-labeled free fatty acids, an I-123-labeled phosphonium compound, Rb-82, Cu-64, F-18 FDG (all compounds which are taken up by the normal myocardium), and for Tc-99m pyrophosphate (PYP) (which localizes in myocardial infarcts). Dose estimates could not be generated for C-11 palmitate, but his compound was included in a comparison of myocardial retention times. For the I-123-labeled compounds, I-124 was included as a contaminant in generating the dose estimates. Radiation doses were lowest for Rb-82 (gonads 0.3-0.4 Gy/MBq, kidneys 8.6 Gy/MBq). Doses for the I-123-labeled fatty acids were similar to one another, with IPPA being the lowest (gonads 15 Gy/MBq, heart wall 18 Gy/MBq). Doses for Tc-99m PYP were also low (gonads 4-7 Gy/MBq, heart wall 4 Gy/MBq, skeleton 15 Gy/MBq). The desirability of these compounds is discussed briefly, considering half-life, imaging mode and energy, and dosimetry, including a comparison of the effective whole body dose equivalents. 37 references, 11 tables

The SOS chromotest: bacterial cells to detect and characterize genotoxic products and radiations

International Nuclear Information System (INIS)

Quillardet, P.; Hofnung, M.

1994-01-01

The advanced knowledge we have on the bacterium Escherichia coli has facilitated the development of the colorimetric and fast assay, the SOS chromotest, which involves a single tester strain and gives a qualitative and a quantitative assay of the action of a genotoxic agent. We discuss a number of possibilities opened by this test in order to make a genetic diagnosis of the chemical nature of the damages caused in the genetic material by means of a battery of strains which have been genetically modified for that purpose. In order to give an idea of the accuracy of the bacterial responses and of the way they can be used to characterize the DNA damage by a genetic approach, the case of alkylating agents is described in a relatively detailed fashion, and the case of oxidative agents is rapidly mentioned. The sensitivity to ionizing radiation is such that the test is able to detect doses of the order of 1 Gy. We discuss briefly how it could be possible to increase this sensitivity by genetically inactivating repair systems which process the injuries caused by these agents, and how the use of a battery of tester strains could also give information on the nature of injuries caused by various types of ionizing radiation. (authors). 39 refs. 4 figs. 1 tab

Mutation induction by 365-nm radiation and far-ultraviolet light in Escherichia coli differing in near- and far-ultraviolet light sensitivity

International Nuclear Information System (INIS)

Leonardo, J.M.; Reynolds, P.R.; Tuveson, R.W.

1984-01-01

The his-4 locus derived from Escherichia coli strain AB1157 has been transduced into 4 E. coli strains that exhibit all 4 possible combinations of genes controlling sensitivity to near-ultraviolet light (nur versus nur + ) and far-ultraviolet light (uvrA6 versus uvrA + ). The 4 strains exhibited the predicted sensitivity to 254-nm radiation based on the sensitivity of the parent strains from which they were derived and the frequency of his + mutations predicted from experiments with AB1157 from which the his-4 locus was derived. When the 4 strains were treated with 365-nm radiation, they exhibited the predicted sensitivity based on the near-ultraviolet light sensitivity of the strains from which they were derived while his + mutations were undetectable with the 4 strains as well as with strain AB1157. When treated with 365-nm radiation, cells of a WP2sub(s) strain (a derivative of B/r transduced to his-4) plated on semi-enriched medium prepared with casamino acids did not yield induced mutations, whereas plating on semi-enriched medium prepared with nutrient broth did yield mutants at both the his-4 and trp loci at frequencies at least an order of magnitude lower than that observed with far-ultraviolet light. The induction of nutritionally independent mutants by 365-nm radiation is strongly dependent on the supplement used for semi-enrichment. When compared at equivalent survival levels, mutant frequencies are significantly less following 365-nm radiation when compared with far-ultraviolet radiation. (Auth.)

The radiation protection effects of TMG to the embryonic effects on the organogenesis stage in ICR mice

International Nuclear Information System (INIS)

Santokuya, Takumi; Gu, Yeunhwa; Suzuki, Ikukatsu; Hasegawa, Takeo; Yamamoto, Youichi; Iwasa, Toshihiro; Yanagisawa, Takaharu

1999-01-01

The Organogenesis stage is the most important from the viewpoint of ionizing protection. Many physical and chemical agents in the environment can effect an embryo. Fetal deaths were classified as Preimplantation, Embryonic and Fetal. We studied an excuse as a radio protective agent of the high malformation of the sensitivity most by using TMG to the radiation. This study aimed at obtaining the information to provide it for the fetus' protection to the various environmental radiations. As for Preimplantation death, there was a statistical difference the 2.0Gy Group in comparison with the control group (p<0.05). Embryonic death, a statistical difference was recognized as in all the treatment groups (p<0.001). But, as for the TMG+radiation group, Malformation rate decreased to 1/2. As for Fetal body weight, a statistical difference was recognized in radiation group, the radiation+TMG infusion group chisels for medical use (p<0.05). Therefore, TMG protecting effect to the radiation was made clear by this research

Glow discharge, its sensitivity to infra-red radiation. Observations made during the testing of multiwire proportional chambers

International Nuclear Information System (INIS)

Marsh, J.B.; Souten, K.H.; O'Hagan, B.

1979-05-01

It has been shown that under glow discharge conditions, multiwire proportional chambers are sensitive to infra-red radiation. Discharge current measurements and light change measurements have been made and the effect of the input window on the output signal and the importance of the finish of the anode and HT wires have been investigated. From these observations it would appear that a glow discharge in the form detailed in this report is sensitive to infra-red radiation though work is still required to optimise the parameters of such a device for IR detection or solar cell technology. (UK)

Effect of ionizing radiation on mechanical and thermal properties of low-density polyethylene containing pro-degradant agents

International Nuclear Information System (INIS)

Bardi, Marcelo A.G.; Kodama, Yasko; Machado, Luci D.B.; Giovedi, Claudia; Rosa, Derval S.

2009-01-01

The wide use of plastics on packages of short-lifetime products has presented harmful consequences for the environment due to their low degradation rate. By this way, improved results to the bio-assimilation of polyolefins have been achieved by the incorporation of pro-oxidant components. The aim of this work is to evaluate the mechanical and thermal behavior of low-density polyethylene (LDPE) modified by those agents and submitted to ionizing radiation by gamma rays. LDPE was modified using a masterbatch containing calcium stearate (CaSt), or magnesium stearate (MgSt) or Clariant R commercial metallic complex. The final amount of stearate in modified LDPE was 0.2%. The films were obtained by compression molding. Samples were gamma irradiated at absorbed doses of 15 kGy and 100 kGy. Differential scanning calorimetry (DSC) and thermogravimetry (TG) were performed on samples, as well as mechanical analysis by universal testing machine. Thermal properties of samples presenting pro-degradant agents were affected by the ionizing radiation in the dose range studied, and some of the mechanical properties were clearly modified by reducing their values of tensile strength at break and elongation at break. (author)

Effect of ionizing radiation on mechanical and thermal properties of low-density polyethylene containing pro-degradant agents

Energy Technology Data Exchange (ETDEWEB)

Bardi, Marcelo A.G.; Kodama, Yasko; Machado, Luci D.B., E-mail: magbardi@ipen.b, E-mail: ykodama@ipen.b, E-mail: lmachado@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Giovedi, Claudia, E-mail: giovedi@ctmsp.mar.mil.b [Centro Tecnologico da Marinha em Sao Paulo (CTMSP), Sao Paulo, SP (Brazil); Rosa, Derval S., E-mail: derval.rosa@ufabc.edu.b [Universidade Federal do ABC (UFABC), Santo Andre, SP (Brazil)

2009-07-01

The wide use of plastics on packages of short-lifetime products has presented harmful consequences for the environment due to their low degradation rate. By this way, improved results to the bio-assimilation of polyolefins have been achieved by the incorporation of pro-oxidant components. The aim of this work is to evaluate the mechanical and thermal behavior of low-density polyethylene (LDPE) modified by those agents and submitted to ionizing radiation by gamma rays. LDPE was modified using a masterbatch containing calcium stearate (CaSt), or magnesium stearate (MgSt) or Clariant{sup R} commercial metallic complex. The final amount of stearate in modified LDPE was 0.2%. The films were obtained by compression molding. Samples were gamma irradiated at absorbed doses of 15 kGy and 100 kGy. Differential scanning calorimetry (DSC) and thermogravimetry (TG) were performed on samples, as well as mechanical analysis by universal testing machine. Thermal properties of samples presenting pro-degradant agents were affected by the ionizing radiation in the dose range studied, and some of the mechanical properties were clearly modified by reducing their values of tensile strength at break and elongation at break. (author)

Sensitive fluorescence on-off probes for the fast detection of a chemical warfare agent mimic.

Science.gov (United States)

Khan, Muhammad Shar Jhahan; Wang, Ya-Wen; Senge, Mathias O; Peng, Yu

2018-01-15

Two highly sensitive probes bearing a nucleophilic imine moiety have been utilized for the selective detection of chemical warfare agent (CWA) mimics. Diethyl chlorophosphate (DCP) was used as mimic CWAs. Both iminocoumarin-benzothiazole-based probes not only demonstrated a remarkable fluorescence ON-OFF response and good recognition, but also exhibited fast response times (10s) along with color changes upon addition of DCP. Limits of detection for the two sensors 1 and 2 were calculated as 0.065μM and 0.21μM, respectively, which are much lower than most other reported probes. These two probes not only show high sensitivity and selectivity in solution, but can also be applied for the recognition of DCP in the gas state, with significant color changes easily observed by the naked eye. Copyright © 2017 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

Prakash, L.

1976-01-01

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

Population sensitivities of animals to chronic ionizing radiation-model predictions from mice to elephant.

Science.gov (United States)

Sazykina, Tatiana G

2018-02-01

Model predictions of population response to chronic ionizing radiation (endpoint 'morbidity') were made for 11 species of warm-blooded animals, differing in body mass and lifespan - from mice to elephant. Predictions were made also for 3 bird species (duck, pigeon, and house sparrow). Calculations were based on analytical solutions of the mathematical model, simulating a population response to low-LET ionizing radiation in an ecosystem with a limiting resource (Sazykina, Kryshev, 2016). Model parameters for different species were taken from biological and radioecological databases; allometric relationships were employed for estimating some parameter values. As a threshold of decreased health status in exposed populations ('health threshold'), a 10% reduction in self-repairing capacity of organisms was suggested, associated with a decline in ability to sustain environmental stresses. Results of the modeling demonstrate a general increase of population vulnerability to ionizing radiation in animal species of larger size and longevity. Populations of small widespread species (mice, house sparrow; body mass 20-50 g), which are characterized by intensive metabolism and short lifespan, have calculated 'health thresholds' at dose rates about 6.5-7.5 mGy day -1 . Widespread animals with body mass 200-500 g (rat, common pigeon) - demonstrate 'health threshold' values at 4-5 mGy day -1 . For populations of animals with body mass 2-5 kg (rabbit, fox, raccoon), the indicators of 10% health decrease are in the range 2-3.4 mGy day -1 . For animals with body mass 40-100 kg (wolf, sheep, wild boar), thresholds are within 0.5-0.8 mGy day -1 ; for herbivorous animals with body mass 200-300 kg (deer, horse) - 0.5-0.6 mGy day -1 . The lowest health threshold was estimated for elephant (body mass around 5000 kg) - 0.1 mGy day -1 . According to the model results, the differences in population sensitivities of warm-blooded animal species to ionizing radiation are generally

Effect of free radicals and cultivation media on radiation sensitivities of escherichia coli and related bacteria

International Nuclear Information System (INIS)

Ito, Hitoshi

2000-01-01

Effects of gamma-irradiation on some strains of Escherichia coli, Salmonella enteritidis and Staphylococcus aureus were investigated in the presence of N 2 , N 2 O and O 2 and with the hydroxyl radical (OH) scavengers glycerol, polyethylene glycerol and formate. Injured cell membrane of bacteria was detected using with MacConkey agar for E. coli and S. enteritidis and 7% NaCl Triptic soy agar for St. aureus instead of Tryptic soy agar for recovery medium. From this study, addition of glycerol significantly reduced the sensitivity in all of strains, and cell membrane was not injured significantly except in radiation sensitive strain E. coli A4-1. When superoxide radicals (O 2 ) were generated during irradiation in the presence of formate, injured cell membrane increased significantly in all of strains. However, molecular oxygen (O 2 ) and OH radicals also had some effects on the damage of cell membrane. These results suggest that most radiation induced cell lethality was responsible to the cooperative effects of intracellular OH radicals and O 2 on DNA with lessor effect of damage on cell membrane by O 2 radicals, O 2 and OH radicals. On the radiation sensitive strain of E. coli, cell lethality occurred significantly by the injury of cell membrane compared with other strains. (author)

Repair of gamma radiation damage in wild type and a radiation sensitive mutant of Deinococcus radiodurans

International Nuclear Information System (INIS)

Mizuma, Nagayo

1989-01-01

In an effort to examine production and repair of radiation-induced single and double strand breaks in the DNA, a repair-deficient wild type and a repair-deficient mutant, UV17, of Deinococcus radiodurans were subjected to Co-60 gamma irradiation at a dose rate of 6.3 kGy/hr for wild type and 3.9 kGy/hr for UV17 mutant. The shoulder of the curve of UV17 mutant was narrow but existed with the intercept of 0.7 kGy and the corresponding value of the wild type was 4.2 kGy. Mutant cells exhibited about 6 fold increases in sensitivity for the shoulder relative to the wild type. The D 37 doses in the wild type and the mutant were 0.57 kGy and 0.25 kGy, respectively. From the survival curves, difference in the sensitivity between two strains was mainly due to difference of repair capacity than the number of radiation sensitive target. Sedimentation rate of the main component in the irradiated cells of UV17 mutant increased almost to the level of unirradiated control by the postincubation at 30deg C for 3 hrs. The results indicated that this sensitive mutant also exhibited an ability to restore single strand breaks after exposure to a sublethal dose of 0.6 kGy. When restitution of double strand breaks was analyzed by sedimentation in a neutral sucrose gradient, the wild type showed restitution to DNA-membrane complex from large part of the breaks. For UV17 mutant, the apparent increase in DNA-membrane complex formation was seen after 3 hours incubation. Large part of the decrease in the activities of peak 2 was recovered in the peak 1 for the wild type. For the mutant, there was little restitution to peak 1. Almost free DNA component in UV17 mutant, therefore, was merely degraded into shorter pieces. Restoration of DNA-membrane complex from free DNA derived from gamma-ray induced double strand scission involved closely in the repair of gamma-induced damage and survival. (N.K.)