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Sample records for cell specific radiation

  1. Specification of fast neutron radiation quality from cell transformation data

    International Nuclear Information System (INIS)

    Coppola, M.

    1992-01-01

    Experimental data on the neoplastic transformation of C3H 10T1/2 cells measured at Casaccia after neutron and X-ray irradiation were used to determine neutron RBE values for the RSV-Tapiro fast reactor energy spectrum and for monoenergetic neutrons of 0.5, 1, and 6 MeV. In parallel, micro-dosimetric measurements provided the actual lineal energy distributions and related mean parameters for the reactor radiation. From these experiments, values of the neutron quality factor were derived for the reactor neutron energy spectrum and, in turn, for the other neutron energies tested. A mathematical expression giving a smooth dependence on neutron energy was also determined for the effective quality factor in the entire energy range examined. The results were compared with other proposals

  2. Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope

    International Nuclear Information System (INIS)

    Ciernik, Ilja F.; Romero, Pedro; Berzofsky, Jay A.; Carbone, David P.

    1999-01-01

    Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines

  3. Hypoxia- and radiation-inducible, breast cell-specific targeting of retroviral vectors

    International Nuclear Information System (INIS)

    Lipnik, Karoline; Greco, Olga; Scott, Simon; Knapp, Elzbieta; Mayrhofer, Elisabeth; Rosenfellner, Doris; Guenzburg, Walter H.; Salmons, Brian; Hohenadl, Christine

    2006-01-01

    To facilitate a more efficient radiation and chemotherapy of mammary tumours, synthetic enhancer elements responsive to hypoxia and ionizing radiation were coupled to the mammary-specific minimal promoter of the murine whey acidic protein (WAP) encoding gene. The modified WAP promoter was introduced into a retroviral promoter conversion (ProCon) vector. Expression of a transduced reporter gene in response to hypoxia and radiation was analysed in stably infected mammary cancer cell lines and an up to 9-fold increase in gene expression demonstrated in comparison to the respective basic vector. Expression analyses in vitro, moreover, demonstrated a widely preserved mammary cell-specific promoter activity. For in vivo analyses, xenograft tumours consisting of infected human mammary adenocarcinoma cells were established in SCID/beige mice. Immunohistochemical analyses demonstrated a hypoxia-specific, markedly increased WAP promoter-driven expression in these tumours. Thus, this retroviral vector will facilitate a targeted gene therapeutic approach exploiting the unique environmental condition in solid tumours

  4. Specific locus mutagenesis of human mammary epithelial cells by ultraviolet radiation

    International Nuclear Information System (INIS)

    Eldridge, S.R.; Gould, M.N.

    1991-01-01

    Tissue and locus specificity of mutation induction was studied in human mammary epithelial cells (HMEC). Primary HMEC from normal tissue, and immortalized HMEC (184B5) derived from normal HMEC, were cultured under identical conditions and exposed to 10J/m 2 ultraviolet (UV) radiation (254 nm peak wavelength), which produced approximately 50% mean survival in all cell strains and lines tested. UV radiation was found to induce mutations at the Na + -K + ATPase locus as determined by ouabain-resistance in both normal and immortalized HMEC. Mutation frequencies measured in these cells following UV exposure were similar to those reported for human diploid fibroblasts. Mutation induction was investigated at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus in normal and immortalized HMEC. Induced mutations at the HPRT locus as determined by 6-thioguanine resistance in normal primary HMEC were not observed following UV radiation. Mutation induction was observed at this locus UV-exposed immortalized HMEC. (author)

  5. Ionizing radiation affects generation of MART-1-specific cytotoxic T cell responses by dendritic cells

    International Nuclear Information System (INIS)

    Liao, Y.P.; Wang, C.-C.; McBride, W.H.

    2003-01-01

    Full text: The human MART-1/Melan-A (MART-1) melanoma tumor antigen is known to be recognized by cytotoxic T lymphocytes (CTLs) and several groups are using this target for clinical immunotherapy. Most approaches use dendritic cells (DCs) that are potent antigen presentation cells for initiating CTL responses. In order for CTL recognition to occur, DCs must display 9-residue antigenic peptides on MHC class I molecules. These peptides are generated by proteasome degradation and then transported through the endoplasmic reticulum to the cell surface where they stabilize MHC class I expression. Our previous data showed that irradiation inhibits proteasome function and, therefore, we hypothesized that irradiation may inhibit antigen processing and CTL activation, as has been shown for proteasome inhibitors. To study the importance of irradiation effects on DCs, we studied the generation MART-1-specific CTL responses. Preliminary data showed that irradiation of murine bone marrow derived DCs did not affect expression of MHC class I, II, CD80, or CD86, as assessed by flow cytometric analyses 24-hour after irradiation. The effect of irradiation on MART-1 antigen processing by DCs was evaluated using DC transduced with adenovirus MART-1 (AdVMART1). C57BL/6 mice were immunized with AdVMART1 transduced DCs, with and without prior irradiation. IFN-γ production was measured by ELISPOT assays after 10-14 days of immunization. Prior radiation treatment resulted in a significant decrease in MART-1-specific T cell responses. The ability of irradiated and non-irradiated AdVMART1/DC vaccines to protect mice against growth of murine B16 tumors, which endogenously express murine MART-1, was also examined. AdVMART1/DC vaccination protected C57BL/6 mice against challenge with viable B16 melanoma cells while DCs irradiated (10 Gy) prior to AdVMART1 transduction abrogated protection. These results suggest that proteasome inhibition in DCs by irradiation may be a possible pathway in

  6. Effects of concomitant temozolomide and radiation therapies on WT1-specific T-cells in malignant glioma

    International Nuclear Information System (INIS)

    Chiba, Yasuyoshi; Hashimoto, Naoya; Tsuboi, Akihiro

    2010-01-01

    Immunotherapy targeting the Wilms' tumour 1 gene product has been proven safe and effective for treating malignant glioma in a phase II clinical study. Currently, radiation/temozolomide therapy is the standard treatment with only modest benefit. Whether combining radiation/temozolomide therapy with WT1 immunotherapy will have a negating effect on immunotherapy is still controversial because of the significant lymphocytopaenia induced by the former therapy. To address this issue, we investigated the changes in frequency and number of WT1-specific T-cells in patients with malignant gliomas. Twenty-two patients with newly diagnosed malignant glioma who received standard radiation/temozolomide therapy were recruited for the study. Blood samples were collected before treatment and on the sixth week of therapy. The frequencies and numbers of lymphocytes, CD8 + T-cells, WT1-specific T-cells, regulatory T-cells, natural killer cells and natural killer T-cells were measured and analysed using T-tests. Analysis of the frequency of T lymphocytes and its subpopulation showed an increase in regulatory T-cells, but no significant change was noted in the populations of T-cells, WT1-specific T-cells, natural killer (NK) cells and natural killer T (NKT) cells. Reductions in the total numbers of T-cells, WT1-specific T-cells, NK cells and NKT cells were mainly a consequence of the decrease in the total lymphocyte count. Radiation/temozolomide therapy did not significantly affect the frequency of WT1-specific T-cells, suggesting that the combination with WT1 immunotherapy may be possible, although further assessment in the clinical setting is warranted. (author)

  7. Study on the specificity of yeast cell damage by high-intensity UV radiation (266nm)

    International Nuclear Information System (INIS)

    Burchuladze, T.G.; Frajkin, G.Ya.; Rubin, L.B.

    1981-01-01

    Peculiarities of photoreactivation and photoprotection of the Candida guilliermondii and Candida utilis yeast cells, irradiated with far and near ultraviolet radiation, are considered. New results on the study of the dependence of the cells inactivation degree on the intensity of ultraviolet radiation are presented. The impulse rate density at 266 nm reached 10 10 Ix m -2 xs -1 at the impulse duration of 10 -8 s. Survival curves of the yeast cells during their irradiation with ultraviolet radiation of 266 nm and 254 nm are given. It is shown that with the increase of the irradiation intensity of 266 nm the rates and final levels of photoreactivation decrease. Under the effect of ultraviolet irradiation of high intensity contribution of pyrimidine dimers to the cell inactivation decreases [ru

  8. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kleinhenz, M.E.; Ellner, J.J.

    1985-07-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the (/sup 3/H)thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced (/sup 3/H)thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% (SD)) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition.

  9. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

    International Nuclear Information System (INIS)

    Kleinhenz, M.E.; Ellner, J.J.

    1985-01-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the [ 3 H]thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced [ 3 H]thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% [SD]) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition

  10. Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [CEA, DSV/DRR/SEGG/LDRG, Laboratory of Differentiation and Radiobiology of the Gonads, Unit of Gametogenesis and Genotoxicity, F-92265 Fontenay aux Roses (France); Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [Univ. Paris 7-Denis Diderot, UFR of Biology, UMR-S 566, F-92265 Fontenay aux Roses (France); Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [INSERM, U566, F-92265 Fontenay aux Roses (France); Bakalska, M. [Institute of Experimental Morphology and Anthropology, Bulgarian Academy of Sciences, Sofia (Bulgaria); Frydman, R. [Univ Paris-Sud, Clamart F-92140 (France); Frydman, R. [AP-HP, Service de Gynecologie-Obstetrique et Medecine de la Reproduction, Hopital Antoine Beclere, Clamart F-92141 (France); Frydman, R. [INSERM, U782, Clamart F-92140 (France)

    2009-07-01

    Background: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin {alpha}, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells. Methods and results: Both male and female fetal germ cells displayed a similar number of {gamma}H2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin {alpha} did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout. Conclusions: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress-irradiation with oogonia being less sensitive and undergoing p53-independent apoptosis. (authors)

  11. Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation

    International Nuclear Information System (INIS)

    Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Bakalska, M.; Frydman, R.; Frydman, R.; Frydman, R.

    2009-01-01

    Background: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin α, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells. Methods and results: Both male and female fetal germ cells displayed a similar number of γH2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin α did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout. Conclusions: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress-irradiation with oogonia being less sensitive and undergoing p53-independent apoptosis. (authors)

  12. Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

    International Nuclear Information System (INIS)

    Bernal-Estévez, David; Sánchez, Ramiro; Tejada, Rafael E.; Parra-López, Carlos

    2016-01-01

    Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells. T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy. We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy. Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in

  13. Lack of specificity of chromosome breaks resulting from radiation-induced genomic instability in Chinese hamster cells

    International Nuclear Information System (INIS)

    Trott, K.-R.; Teibe, A.

    1998-01-01

    In V79 Chinese hamster cells, radiation-induced genomic instability results in a persistently increased frequency of micronuclei, dicentric chromosomes and apoptosis and in decreased colony-forming ability. These manifestations of radiation-induced genomic instability may be attributed to an increased rate of chromosome breakage events many generations after irradiation. This chromosomal instability does not seem to be a property which has been inflicted on individual chromosomes at the time of irradiation. Rather, it appears to be secondary to an increased level of non-specific clastogenic factors in the progeny of most if not all irradiated cells. This conclusion is drawn from the observations presented here, that all the chromosomes in surviving V79 cells are involved in the formation of dicentric chromosome aberrations 1 or 2 weeks after irradiation with about equal probability if corrections are made for chromosome length. (orig.)

  14. Radiation effects on the species-specific cell sorting-out of the cellular slime molds

    International Nuclear Information System (INIS)

    Satow, Takashi

    1976-01-01

    The effects of gamma-rays irradiation on the development and the species-specific cell sorting-out of the cellular slime mold, Dictyostelium discoideum, were investigated. The interphase amoebae of the organism showed extremely resistant to 60 Co gamma-rays. The percentage of non-stained cells estimated by dye staining method was more than 90% at the dose of 270 kR. The amoebae irradiated at 270 kR performed the development similar in the most respects to that of the un-irradiated amoebae except that a little portion of the fruiting bodies were abnormal and that the appearance of aggregates and slugs delayed 3 hrs. The ability of the species-specific cell sorting-out was not affected by gamma-rays irradiation at 270 kR. (auth.)

  15. Modulation of differentiation and self-renewal of tissue specific stem cells for effective mitigation of radiation injury

    International Nuclear Information System (INIS)

    Bandekar, Mayuri; Patwardhan, R.S.; Maurya, Dharmendra K.; Bhilwade, Hari N.; Sharma, Deepak; Sandur, Santosh Kumar

    2017-01-01

    The use of stem cells in regenerative medicine for the treatment of various human diseases is one of the active research areas. The aim of regenerative medicine is to restore normal tissue functions by replenishing injured tissues using either cell-based therapy or by inducing certain factors that can aid endogenous repair and regeneration. The approach for inducing endogenous repair and regeneration requires in vivo modulation of tissue-specific stem cells by therapeutic agents and enhance their abundance through activation, proliferation, differentiation, or reprogramming. Here we describe three different approaches to enhance the abundance of hematopoietic stem cells in vivo for mitigation of radiation induced toxicity. Baicalein, a flavonoid derived from Chinese and Indian medicinal plants like Scutellaria baicalensis and Terminalia ariuna enhanced the abundance of hematopoietic stem cells through activation of Nrf-2 in the lineage negative cells. Another anti-oxidant, chlorophyllin derived from green plant pigment, chlorophyll also enhanced the abundance of hematopoietic stem cells through modulation of cell cycle in cells of the bone marrow. Treatment of mice with Cobaltus chloride (CoCl_2), a well-known activator of hypoxia inducible factor-1α (HIP-1α), also led to increase in the number of hematopoietic stem cells in the bone marrow. Whereas chlorophyllin offered up to 100 % protection against whole body irradiation (WBI, 8 Gy) induced mortality in mice, baicalein offered up to70%protection. Cobaltus chloride treatment offered 40% protection against 8 Gy of WBI. These studies indicate potential use of stem cell modulating agents as effective mitigators of radiation induced toxicity in vivo. (author)

  16. Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.

    Science.gov (United States)

    Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

    2016-04-01

    To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Splenocytes and IM-9 cells were uniformly irradiated with various doses of a (137)Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

    International Nuclear Information System (INIS)

    Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

    2016-01-01

    Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a "1"3"7Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

  18. Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Seong-Jun; Kang, Hana [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Kim, Min Young [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan (Korea, Republic of); Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Pyo, Suhkneung [College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do (Korea, Republic of); Yang, Kwang Hee, E-mail: kwangheey@khnp.co.kr [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of)

    2016-04-01

    Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a {sup 137}Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

  19. Temperature-specific inhibition of human red cell (Na/sup +//K/sup +/) ATPase by 2450-MHz microwave radiation

    Energy Technology Data Exchange (ETDEWEB)

    Allis, J.W.; Sinha-Robinson, B.L.

    1987-01-01

    The ATPase activity in human red blood cell membranes was investigated in vitro as a function of temperature and exposure to 2450-MHz (CW) microwave radiation. Assays were conducted spectrophotometrically during microwave exposure with a custom-made spectrophotometer-waveguide apparatus. Temperature profiles of total ATPase and Ca+2 ATPase (ouabain-inhibited) activity between 17 and 31 C were graphed as an Arrhenius plot. Each data set was fitted to two straight lines which intersected between 23 and 24 C. The difference between the total and Ca+2 ATPase activities, which represented the Na+/K+ ATPase activity, was also plotted and treated similarly to yield an intersection near 25 C. Exposure of membrane suspensions to a 6 W/kg dose rate at 1 C intervals between 23 and 27 C, resulted in an activity change only for the Na+/K+ ATPase at 25 C. The activity decreased by approximately 35% compared to sham-irradiated samples. An hypothesis based on the interaction of microwave radiation with enzyme structure during a conformational rearrangement is proposed as an explanation for the effect.

  20. Temperature-specific inhibition of human red cell Na+/K+ ATPase by 2450-MHz microwave radiation

    Energy Technology Data Exchange (ETDEWEB)

    Allis, J.W.; Sinha-Robinson, B.L.

    1987-01-01

    The ATPase activity in human red blood cell membranes was investigated in vitro as a function of temperature and exposure to 2450-MHz continuous wave microwave radiation to confirm and extend a report of Na+ transport inhibition under certain conditions of temperature and exposure. Assays were conducted spectrophotometrically during microwave exposure with a custom-made spectrophotometer-waveguide apparatus. Temperature profiles of total ATPase and Ca+2 ATPase (ouabain-inhibited) activity between 17 and 31 degrees C were graphed as an Arrhenius plot. Each data set was fitted to two straight lines which intersect between 23 and 24 degrees C. The difference between the total and Ca+2 ATPase activities, which represented the Na+/K+ ATPase activity, was also plotted and treated similarly to yield an intersection near 25 degrees C. Exposure of membrane suspensions to electromagnetic radiation, at a dose rate of 6 W/kg and at five temperatures between 23 and 27 degrees C, resulted in an activity change only for the Na+/K+ ATPase at 25 degrees C. The activity decreased by approximately 35% compared to sham-irradiated samples. A possible explanation for the unusual temperature/microwave interaction is proposed.

  1. Protecting effects specifically from low doses of ionizing radiation to mammalian cells challenge the concept of linearity

    International Nuclear Information System (INIS)

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

    1998-01-01

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced changes in intracellular signaling that induce mechanisms of DNA damage control different from those operating at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. The aim of this paper is to demonstrate that by use of microdosimetric concepts, the energy deposited in cell mass can be related to the occurrence of cellular responses, both damaging and defensive

  2. Protecting effects specifically from low doses of ionizing radiation to mammalian cells challenge the concept of linearity

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced changes in intracellular signaling that induce mechanisms of DNA damage control different from those operating at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. The aim of this paper is to demonstrate that by use of microdosimetric concepts, the energy deposited in cell mass can be related to the occurrence of cellular responses, both damaging and defensive.

  3. Solar cell radiation handbook

    Science.gov (United States)

    Tada, H. Y.; Carter, J. R., Jr.; Anspaugh, B. E.; Downing, R. G.

    1982-01-01

    The handbook to predict the degradation of solar cell electrical performance in any given space radiation environment is presented. Solar cell theory, cell manufacturing and how they are modeled mathematically are described. The interaction of energetic charged particles radiation with solar cells is discussed and the concept of 1 MeV equivalent electron fluence is introduced. The space radiation environment is described and methods of calculating equivalent fluences for the space environment are developed. A computer program was written to perform the equivalent fluence calculations and a FORTRAN listing of the program is included. Data detailing the degradation of solar cell electrical parameters as a function of 1 MeV electron fluence are presented.

  4. Specification for symbol for ionizing radiation

    International Nuclear Information System (INIS)

    1974-01-01

    This Malaysia Standard specification specifies a symbol recommended for use only to signify the actual or potential presence of ionizing radiation (#betta#, α, #betta# only) and to identify objects, devices, materials or combinations of materials which emit such radiation. (author)

  5. Mesenchymal stem cells with high telomerase expression do not actively restore their chromosome arm specific telomere length pattern after exposure to ionizing radiation

    DEFF Research Database (Denmark)

    Graakjaer, Jesper; Christensen, Rikke; Kolvraa, Steen

    2007-01-01

    were measured using Fluorescence In Situ Hybridization (Q-FISH). RESULTS: A telomere length pattern was found to exist in primary hMSC's as well as in hMSC-telo1. This pattern is similar to what was previously found in lymphocytes and fibroblasts. The cells were then exposed to a high dose of ionizing...... radiation. Irradiation caused profound changes in chromosome specific telomere lengths, effectively destroying the telomere length pattern. Following long term culturing after irradiation, a telomere length pattern was found to re-emerge. However, the new telomere length pattern did not resemble...

  6. Donor-specific cell-based assays in studying sensitivity to low-dose radiation: a population-based perspective

    Directory of Open Access Journals (Sweden)

    Dora eIl'yasova

    2014-11-01

    Full Text Available Currently, a linear no-threshold model is used to estimate health risks associated with exposure to low-dose radiation, a prevalent exposure in the general population, because the direct estimation from epidemiological studies suffers from uncertainty. This model has been criticized based on unique biology of low-dose radiation. Whether the departure from linearity is toward increased or decreased risk is intensely debated. We present an approach based on individual radiosensitivity testing and discuss how individual radiosensitivity can be assessed with the goal to develop a quantifiable measure of cellular response that can be conducted via high-throughput population testing.

  7. Specificity of antigens on UV radiation-induced antigenic tumor cell variants measured in vitro and in vivo

    International Nuclear Information System (INIS)

    Hostetler, L.W.; Romerdahl, C.A.; Kripke, M.L.

    1989-01-01

    The purpose of this study was to determine whether antigenic variants cross-react immunologically with the parental tumor and whether the UVR-associated antigen unique to UVR-induced tumors is also present on the variants. Antigenic (regressor) variants and nonimmunogenic (progressor) clones derived from UV-irradiated cultures of the C3H K1735 melanoma and SF19 spontaneous fibrosarcoma cell lines were used to address these questions. In an in vivo immunization and challenge assay, the antigenic variants did not induce cross-protection among themselves, but each induced immunity against the immunizing variant, the parent tumor cells, and nonimmunogenic clones derived from UV-irradiated parent cultures. Therefore, the variants can be used to induce in mice a protective immunity that prevents the growth of the parent tumor and nonimmunogenic clones, but not other antigenic variants. In contrast, immunization with cells of the parental tumor or the nonimmunogenic clones induced no protective immunity against challenge with any of the cell lines. Utilizing the K1735 melanoma-derived cell lines in vitro, T-helper (Th) cells isolated from tumor-immunized mice were tested for cross-reactivity by their ability to collaborate with trinitrophenyl-primed B-cells in the presence of trinitrophenyl-conjugated tumor cells. Also, the cross-reactivity of cytotoxic T-lymphocytes from tumor-immunized mice was assessed by a 4-h 51Cr-release assay. Antigenic variants induced cytotoxic T-lymphocytes and Th activity that was higher than that induced by the parent tumor and nonimmunogenic clones from the UVR-exposed parent tumor and cross-reacted with the parental tumor cells and nonimmunogenic clones, but not with other antigenic variants

  8. CCL22-specific T Cells

    DEFF Research Database (Denmark)

    Martinenaite, Evelina; Munir Ahmad, Shamaila; Hansen, Morten

    2016-01-01

    Tumor cells and tumor-infiltrating macrophages produce the chemokine CCL22, which attracts regulatory T cells (Tregs) into the tumor microenvironment, decreasing anticancer immunity. Here, we investigated the possibility of targeting CCL22-expressing cells by activating specific T cells. We...... analyzed the CCL22 protein signal sequence, identifying a human leukocyte antigen A2- (HLA-A2-) restricted peptide epitope, which we then used to stimulate peripheral blood mononuclear cells (PMBCs) to expand populations of CCL22-specific T cells in vitro. T cells recognizing an epitope derived from...... the signal-peptide of CCL22 will recognize CCL22-expressing cells even though CCL22 is secreted out of the cell. CCL22-specific T cells recognized and killed CCL22-expressing cancer cells. Furthermore, CCL22-specific T cells lysed acute monocytic leukemia cells in a CCL22 expression-dependent manner. Using...

  9. Radiation effects on tumor-specific DTH response, 2

    International Nuclear Information System (INIS)

    Nobusawa, Hiroshi; Hachisu, Reiko.

    1991-01-01

    Tumor-specific immunity was induced in C3H mice by immunizing with syngeneic MH134 hepatoma cells. Radiation sensitivity of anti-tumor activity of immunized spleen cells were examined and compared with the radiation sensitivity of the delayed-type hypersensitivity (DTH)-response. The spleen cells were irradiated in vitro, then mixed with the tumor cells. DTH-response intensity was determined from the footpad increment twenty-four hours after inoculation of tumor cells with immunized spleen cells. Anti-tumor activity of the spleen cells, based on growth inhibition of tumor cells, was measured by a cytostatic test in vivo with diffusion chambers. Tumor-specific DTH response was suppressed dose-dependently in the range of 12-24 Gy irradiation. No suppression was observed below 12 Gy. Without irradiation, growth of tumor cells was inhibited by immunized spleen cells more effectively than by normal spleen cells. Anti-tumor activity of immunized and normal spleen cells was diminished by irradiation doses of 20 Gy and 10 Gy, respectively. Comparing our report with others that analyzed the type of anti-tumor effector cells induced in this experimental system, we concluded that tumor-specific anti-tumor activity (tumor growth inhibition in vivo) that was radiosensitive at 10-20 Gy depended on a DTH-response. (author)

  10. 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

  11. Repair of radiation damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  12. Repair of radiation damage in mammalian cells

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

  13. Specific-locus mutation frequencies in mouse stem-cell spermatogonia at very low radiation dose rates, and their use in the estimation of genetic hazards of radiation in man

    International Nuclear Information System (INIS)

    Russell, W.L.; Kelly, E.M.

    1982-01-01

    Experiments were undertaken to augment the information on the lowest radiation dose rates feasible for scoring transmitted induced mutations detected by the specific-locus method in the mouse. This is the type of information most suitable for estimating genetic hazards of radiation in man. The results also aid in resolving conflicting possibilities about the relationship between mutation frequency and radiation dose at low dose rates

  14. Radiation injuries of plasmatic membrane and lethal action of radiation on cells

    Energy Technology Data Exchange (ETDEWEB)

    Fomenko, B S; Akoev, I G [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

    1984-01-01

    Data on modification of procaryotes and eukaryotes cell injuries using preparations not penetrating into cells and also membrane-specific drugs localized in cells in a lipid phase are generalized. A conclusion is drawn that radiation injuries of plasmatic membrane of prokaryotes and eukaryotes contribute considerably to lethal action of radiation on cells.

  15. Radiation injuries of plasmatic membrane and lethal action of radiation on cells

    International Nuclear Information System (INIS)

    Fomenko, B.S.; Akoev, I.G.

    1984-01-01

    Data on modification of procaryotes and eukaryotes cell injuries using preparations not penetrating into cells and also membrane-specific drugs localized in cells in a lipid phase are generalized. A conclusion is drawn that radiation injuries of plasmatic membrane of prokaryotes and eukaryotes contribute considerably to lethal action of radiation on cells

  16. Radiation effects on cell membranes

    International Nuclear Information System (INIS)

    Koeteles, G.J.

    1982-01-01

    Experimental data are presented concerning the effects of relatively low doses of x radiation and low concentration of tritiated water (HTO) on various receptor functions - concanavalin A, cationized ferritin, poliovirus of plasma membranes of animal and human cells which point to early and temporary disturbances of the composite structures and functions of membranes. References are given to the manifold influence of radiation-induced membrane phenomenon on the development and regeneration of radiation injuries. (author)

  17. Radiation hard solar cell and array

    International Nuclear Information System (INIS)

    Russell, R.L.

    1975-01-01

    A power generating solar cell for a spacecraft solar array is hardened against transient response to nuclear radiation while permitting normal operation of the cell in a solar radiation environment by shunting the cell with a second solar cell whose contacts are reversed relative to the power cell to form a cell module, exposing the power cell only to the solar radiation in a solar radiation environment to produce an electrical output at the module terminals, and exposing both cells to the nuclear radiation in a nuclear radiation environment so that the radiation induced currents generated by the cells suppress one another

  18. Cell membranes in radiation injury

    International Nuclear Information System (INIS)

    Koeteles, G.J.

    1986-01-01

    Cell membrane-related phenomena caused by low linear energy transfer radiation with doses lower than those producing cell killing are outlined. Micromorphological alterations as well as functional activities appearing with the receptors and in binding sites render it possible to reveal early and temporary changes. The cell injuries are suggested to transfer damaging conditions to surviving cells and to contribute to further development of non-stochastic effects in tissues

  19. Tumour-specific radiosensitizers for radiation therapy

    International Nuclear Information System (INIS)

    Denekamp, J.

    1977-01-01

    Recently Adams and coworkers at the Gray Laboratory have developed a new class of radiosensitizers which act specifically on hypoxic cells by abolishing the protection afforded by low oxygen concentrations. Since most experimental tumours contain a high proportion of oxygen-deprived cells, and most normal tissues are well oxygenated, these drugs are tumour specific radiosensitizers. Based on the hypothesis that sensitization increases with increasing electron affinity, the two nitroimidazoles, metronidazole (Flagyl) and Ro-07/0582 were identified as potent radiosensitizers with low toxicity. These drugs are effective only in the absence of oxygen, and only if the drug is present at the time of irradiation. The degree of sensitization increases with drug concentration rapidly over the range 0.1 to 1.0mg/g body weight for Ro-07-0582, and more gradually for Flagyl. Tumour studies have been performed on at least 12 different experimental tumours, using a variety of end points. Significant sensitization has been observed in every tumour studied, often corresponding to a dose reduction factor of 2.0 for high but non-toxic drug doses. Fractionated studies have also been performed on a few tumour lines. In most cases a useful therapeutic advantage was observed, although the sensitization was smaller. Ro-07-0582 used with X-rays gives a therapeutic gain comparable with that from cyclotron-produced fast neutrons. Neutrons used together with Ro-07-0582 are even more effective. In addition to the radiosensitization there is a specific cytotoxicity to hypoxic cells after prolonged exposure to Ro-07-0582. This cytotoxicity can be greatly enhanced in vitro by moderate hyperthermia. Flagyl and Ro-07-0582 have been used clinically as radiosensitizers, with promising early results. The clinical application is limited to certain dose fractionation patterns because of neurotoxicity. (author)

  20. Cell Phone RF Radiation

    Science.gov (United States)

    Abdul-Razzaq, Wathiq

    2015-01-01

    In a recent article in "Physics Today," Meredith and Redish emphasized the need to make introductory physics courses beneficial for life sciences majors. In this study, a lab activity is proposed to measure the intensity of electromagnetic waves emitted by cell phones and connect these measurements to various standards, biological…

  1. Cell fusion by ionizing radiation

    International Nuclear Information System (INIS)

    Khair, M.B.

    1993-08-01

    The relevance and importance of cell fusion are illustrated by the notion that current interest in this phenomenon is shared by scientists in quite varied disciplines. The diversity of cellular membrane fusion phenomena could provoke one to think that there must be a multitude of mechanisms that can account for such diversity. But, in general, the mechanism for the fusion reaction itself could be very similar in many, or even all, cases. Cell fusion can be induced by several factors such as virus Sendai, polyethylene glycol, electric current and ionizing radiation. This article provides the reader with short view of recent progress in research on cell fusion and gives some explanations about fusion mechanisms. This study shows for the first time, the results of the cell fusion induced by ionizing radiations that we have obtained in our researches and the work performed by other groups. (author). 44 refs

  2. Toxic properties of specific radiation determinant molecules, derived from radiated species

    Science.gov (United States)

    Popov, Dmitri; Maliev, Vecheslav; Kedar, Prasad; Casey, Rachael; Jones, Jeffrey

    Introduction: High doses of radiation induce the formation of radiation toxins in the organs of irradiated mammals. After whole body irradiation, cellular macromolecules and cell walls are damaged as a result of long-lived radiation-induced free radicals, reactive oxygen species, and fast, charged particles of radiation. High doses of radiation induce breaks in the chemical bonds of macromolecules and cross-linking reactions via chemically active processes. These processes result in the creation of novel modified macromolecules that possess specific toxic and antigenic properties defined by the type and dose of irradiation by which they are generated. Radiation toxins isolated from the lymph of irradiated animals are classified as hematotoxic, neurotoxic, and enteric non-bacterial (GI) radiation toxins, and they play an important role in the development of hematopoietic, cerebrovascular, and gastrointestinal acute radiation syndromes (ARS). Seven distinct toxins derived from post-irradiated animals have been designated as Specific Radiation Determinants (SRD): SRD-1 (neurotoxic radiation toxin generated by the cerebrovascular form of ARS), SRD-3 (enteric non-bacterial radiation toxins generated by the gastrointestinal form of ARS), and SRD-4 (hematotoxic radiation toxins generated by the hematological, bone marrow form of ARS). SRD-4 is further subdivided into four groups depending on the severity of the ARS induced: SRD-4/1, mild ARS; SRD-4/2, moderate ARS; SRD-4/3, severe ARS; and SRD-4/4, extremely severe ARS. The seventh SRD, SRD-2 is a toxic extract derived from animals suffering from a fourth form of ARS, as described in European literature and produces toxicity primarily in the autonimic nervous system. These radiation toxins have been shown to be responsible for the induction of important pathophysiological, immunological, and biochemical reactions in ARS. Materials and Methods: These studies incorporated the use of statistically significant numbers of a

  3. Radiation effects on cell membranes

    International Nuclear Information System (INIS)

    Koeteles, G.J.

    1982-01-01

    The recent developments in the field of membrane biology of eukaryotic cells result in revival of relevant radiobiological studies. The spatial relations and chemical nature of membrane components provide rather sensitive targets. Experimental data are presented concerning the effects of relatively low doses of X-irradiation and low concentration of tritiated water (HTO) on various receptor functions - concanavalin A, cationized ferritin, poliovirus - of plasma membranes of animal and human cells which point to early and temporary disturbances of the composite structures and functions of membranes. References are given to the multifold roles of radiationinduced membrane phenomena on the development and regeneration of radiation injuries. (orig.)

  4. Radiation effects on cell membranes

    Energy Technology Data Exchange (ETDEWEB)

    Koeteles, G.J.

    1982-11-01

    The recent developments in the field of membrane biology of eukaryotic cells result in revival of relevant radiobiological studies. The spatial relations and chemical nature of membrane components provide rather sensitive targets. Experimental data are presented concerning the effects of relatively low doses of X-irradiation and low concentration of tritiated water (HTO) on various receptor functions - concanavalin A, cationized ferritin, poliovirus - of plasma membranes of animal and human cells which point to early and temporary disturbances of the composite structures and functions of membranes. References are given to the multifold roles of radiationinduced membrane phenomena on the development and regeneration of radiation injuries.

  5. H-2 restriction specificity of T cells from H-2 incompatible radiation bone marrow chimeras: further evidence for the absence of crucial influence of the host/thymus environment on the generation of H-2 restricted TNP-specific T lymphocyte precursors

    International Nuclear Information System (INIS)

    Aizawa, S.; Sado, T.; Kubo, E.

    1984-01-01

    Experiments were conducted to answer the questions related to (a) the role played by the antigen-presenting cells (APCs) present within the thymus and (b) the effect of radiation dose to the recipients on the H-2 restriction profile of TNP-specific cytotoxic T lymphocyte precursors (CTLP) recovered from spleens and/or thymuses of H-2 incompatible radiation bone marrow chimeras (BMC). The H-2 restriction profile of intrathymically differentiating TNP-specific CTLPs was also analyzed in order to test an argument that donor-H-2 restricted CTLP detected in spleens of H-2 incompatible BMC were due to the extrathymically differentiated T cells under the influence of donor-derived lymphoreticular cells. The results indicated the following: (i) splenic T cells from B10(H-2b) leads to (B10(H-2b) leads to B10.BR(H-2k)) chimeras, which were constructed by irradiating primary B10 leads to B10.BR chimeras with 1100 R and reconstituting them with donor-type (B10) bone marrow cells as long as 8 months after their construction, manifested restriction specificities for both donor- and host-type H-2, (ii) splenic T cells from two types of (B10 X B10.BR)F1 leads to B10 chimeras which were reconstituted after exposure of the recipients with either 900 or 1100 R with donor-type bone marrow cells generated both donor- and host-H-2 restricted TNP-specific cytotoxic T cells, and (iii) the TNP-specific CTLPs present in the regenerating thymuses of B10.BR leads to B10 and (B10 X B10.BR)F1 leads to B10 chimeras 4 weeks after their construction were also shown to manifest both donor- and host-H-2 restriction specificities. The significance of these findings on the H-2 restriction profile of CTLP generated in BMCs is discussed

  6. Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during ionization radiation induced DNA damage response in human cells

    International Nuclear Information System (INIS)

    Sharma, Ajit K.; Bhattacharya, Saikat; Khan, Shafqat A.; Khade, Bharat; Gupta, Sanjay

    2015-01-01

    Highlights: • Loss of H3S10P in response to DNA damage is a universal phenomenon from G1 cells. • The loss happens predominantly from histone H3.3, a transcription activation mark. • Compaction of chromatin occurs during repair stage of DDR. • The alteration of H3S10P shows an inverse correlation with γH2AX. - Abstract: Chromatin acts as a natural barrier in DNA-damage recognition and repair. Histones undergo differential post-translational modification(s) to facilitate DNA damage response (DDR). Importance of modifications like phosphorylation of histone variant H2A.X in DNA repair is very well understood, however, ambiguous results exist in literature regarding the levels of certain histone modifications and their possible role in repair. In the present study, we have investigated in depth the alteration in the level of the highly dynamic histone mark H3S10P as it plays a dual role in different phases of the cell cycle. We show here that H3S10P decreases specifically from irradiated G1-enriched cells irrespective of the damaging agent or the cell line used in the study. Interestingly, the loss occurs predominantly from H3.3 variant which is a transcription activation mark like H3S10P itself, suggesting that the alteration might be implicated in transcription repression. The decrease in other transcription marks like H3K9Ac, H3K14Ac, H3K56Ac and H3S28P along with the occurrence of chromatin condensation in response to DNA damage in G1 phase strengthens the hypothesis. In addition, the alteration in the level of H3S10P shows an inverse correlation with that of γH2AX in a dose-dependent manner and probably occurs from the same mononucleosome. We propose that the drop in the levels of histone H3S10 phosphorylation is a universal phenomenon in response to DNA damage and is a trigger to induce transcription repressive state to facilitate repair

  7. Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during ionization radiation induced DNA damage response in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Ajit K.; Bhattacharya, Saikat; Khan, Shafqat A.; Khade, Bharat; Gupta, Sanjay, E-mail: sgupta@actrec.gov.in

    2015-03-15

    Highlights: • Loss of H3S10P in response to DNA damage is a universal phenomenon from G1 cells. • The loss happens predominantly from histone H3.3, a transcription activation mark. • Compaction of chromatin occurs during repair stage of DDR. • The alteration of H3S10P shows an inverse correlation with γH2AX. - Abstract: Chromatin acts as a natural barrier in DNA-damage recognition and repair. Histones undergo differential post-translational modification(s) to facilitate DNA damage response (DDR). Importance of modifications like phosphorylation of histone variant H2A.X in DNA repair is very well understood, however, ambiguous results exist in literature regarding the levels of certain histone modifications and their possible role in repair. In the present study, we have investigated in depth the alteration in the level of the highly dynamic histone mark H3S10P as it plays a dual role in different phases of the cell cycle. We show here that H3S10P decreases specifically from irradiated G1-enriched cells irrespective of the damaging agent or the cell line used in the study. Interestingly, the loss occurs predominantly from H3.3 variant which is a transcription activation mark like H3S10P itself, suggesting that the alteration might be implicated in transcription repression. The decrease in other transcription marks like H3K9Ac, H3K14Ac, H3K56Ac and H3S28P along with the occurrence of chromatin condensation in response to DNA damage in G1 phase strengthens the hypothesis. In addition, the alteration in the level of H3S10P shows an inverse correlation with that of γH2AX in a dose-dependent manner and probably occurs from the same mononucleosome. We propose that the drop in the levels of histone H3S10 phosphorylation is a universal phenomenon in response to DNA damage and is a trigger to induce transcription repressive state to facilitate repair.

  8. Predicted solar cell edge radiation effects

    International Nuclear Information System (INIS)

    Gates, M.T.

    1993-01-01

    The Advanced Solar Cell Orbital Test (ASCOT) will test six types of solar cells in a high energy proton environment. During the design of the experiment a question was raised about the effects of proton radiation incident on the edge of the solar cells and whether edge radiation shielding was required. Historical geosynchronous data indicated that edge radiation damage is not detectable over the normal end of life solar cell degradation; however because the ASCOT radiation environment has a much higher and more energetic fluence of protons, considerably more edge damage is expected. A computer analysis of the problem was made by modeling the expected radiation damage at the cell edge and using a network model of small interconnected solar cells to predict degradation in the cell's electrical output. The model indicated that the deepest penetration of edge radiation was at the top of the cell near the junction where the protons have access to the cell through the low density cell/cover adhesive layer. The network model indicated that the cells could tolerate high fluences at their edge as long as there was high electrical resistance between the edge radiated region and the contact system on top of the cell. The predicted edge radiation related loss was less than 2% of maximum power for GaAs/Ge solar cells. As a result, no edge radiation protection was used for ASCOT

  9. Ionizing radiation-induced cell death

    International Nuclear Information System (INIS)

    Szumiel, I.

    1994-01-01

    Selected aspects of radiation-induced cell death, connected with signal transduction pathways are reviewed. Cell death is defined as insufficiency of the cellular signal transducing system to maintain the cell's physiological functions. The insufficiency may be due to impaired signal reception and/or transduction, lack or erroneous transcription activation, and eventual cellular ''misexpression'' of the signal. The molecular basis of this insufficiency would be damage to genomic (but also other cellular) structures and closing of specific signalling pathways or opening of others (like those leading to apoptosis). I describe experimental data that suggest an important role of RAS/NFI and p53/p105 Rb proteins in cell cycle control-coupled responses to DNA damage. (Author)

  10. PD-L1-specific T cells

    DEFF Research Database (Denmark)

    Ahmad, Shamaila Munir; Borch, Troels Holz; Hansen, Morten

    2016-01-01

    -specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy...... for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses...

  11. Intrinsic radiation resistance in human chondrosarcoma cells

    International Nuclear Information System (INIS)

    Moussavi-Harami, Farid; Mollano, Anthony; Martin, James A.; Ayoob, Andrew; Domann, Frederick E.; Gitelis, Steven; Buckwalter, Joseph A.

    2006-01-01

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16 ink4a , one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16 ink4a contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16 ink4a expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16 ink4a expression on chondrosarcoma cell resistance to low-dose γ-irradiation (1-5 Gy). p16 ink4a expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16 ink4a transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16 ink4a plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas

  12. Radiation-induced bystander effects in vivo are sex specific

    International Nuclear Information System (INIS)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-01-01

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes

  13. Radiation-induced bystander effects in vivo are sex specific

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  14. Radiation-induced bystander effects in vivo are sex specific.

    Science.gov (United States)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naïve cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  15. The convergence of radiation and immunogenic cell death signaling pathways

    International Nuclear Information System (INIS)

    Golden, Encouse B.; Pellicciotta, Ilenia; Demaria, Sandra; Barcellos-Hoff, Mary H.; Formenti, Silvia C.

    2012-01-01

    Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill. As a result, traditional measurements of radiation-induced tumor cell death, in vitro, fail to represent the extent of clinically observed responses, including reductions in loco-regional failure rates and improvements in metastases free and overall survival. Hence, understanding the immunological responses to the type of radiation-induced cell death is critical. In this review, the mechanisms of radiation-induced tumor cell death are described, with particular focus on immunogenic cell death (ICD). Strategies combining radiotherapy with specific chemotherapies or immunotherapies capable of inducing a repertoire of cancer specific immunogens might potentiate tumor control not only by enhancing cell kill but also through the induction of a successful anti-tumor vaccination that improves patient survival.

  16. Radiation hard memory cell and array thereof

    International Nuclear Information System (INIS)

    Gunckel, T.L. II; Rovell, A.; Nielsen, R.L.

    1978-01-01

    A memory cell configuration that is implemented to be relatively hard to the adverse effects of a nuclear event is discussed. The presently disclosed memory cell can be interconnected with other like memory cells to form a high speed radiation hard register file. Information is selectively written into and read out of a memory cell comprising the register file, which memory cell preserves previously stored data without alteration in the event of exposure to high levels of nuclear radiation

  17. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  18. Cell-cycle phase specificity of chloroethylnitrosoureas

    International Nuclear Information System (INIS)

    Linfoot, P.A.

    1986-01-01

    Although the cancer chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is considered a non-cell cycle phase specific drug, it has been shown to produce differential cell killing in G 1 , S, and G 2 /M phase cells, with S phase cells appearing relatively resistant. Studies of cell cycle phase specific cell killing produced by nitrosoureas with different chemical reactivities, clearly indicated that the ability of compounds to cross-link DNA was important in determining their phase specificity. Cells that lacked guanine O 6 -alkytransferase activity showed similar patterns of BCNU phase specificity regardless of their intrinsic sensitivity to BCNU. DNA inter-strand cross-linking, as measured by alkaline elution, was similar in cells exposed to BCNU in G 1 or S phase. 3 H [1-chloroethyl-1nitrosourea] binding to DNA was the same in G 1 , S and G 2 /M phase cells indicating that phase-specific differences in drug uptake and intracellular drug dose were not responsible for phase specific cell kill. These studies suggest that cross-link lesions, other than DNA inter-strand cross-links, and/or effects on DNA repair, other than guanine O 6 -alkyltransferase, are additional important determinants of BCNU phase specific cell killing

  19. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

  20. Radiation-induced cell death in embryogenic cells of coniferous plants

    International Nuclear Information System (INIS)

    Watanabe, Yoshito; Homma-Takeda, Shino; Yukawa, Masae; Nishimura, Yoshikazu; Sasamoto, Hamako; Takahagi, Masahiko

    2004-01-01

    Reproductive processes are particularly radiosensitive in plant development, which was clearly illustrated in reduction of seed formation in native coniferous plants around Chernobyl after the nuclear accident. For the purpose to investigate the effects of ionizing radiation on embryonic formation in coniferous plants, we used an embryo-derived embryogenic cell culture of a Japanese native coniferous plant, Japanese cedar (Cryplomeria japonica). The embryogenic cells were so radiosensitive that most of the cells died by X-ray irradiation of 5 Gy. This indicated that the embryogenic cells are as radiosensitive as some mammalian cells including lymphocytes. We considered that this type of radiosensitive cell death in the embryogenic cells should be responsible for reproductive damages of coniferous plants by low dose of ionizing radiation. The cell death of the embryogenic cells was characteristic of nuclear DNA fragmentation, which is typically observed in radiation-induced programmed cell death, i.e. apoptosis, in mammalian cells. On the other hand, cell death with nuclear DNA fragmentation did not develop by X-ray irradiation in vegetative cells including meristematic cells of Japanese cedar. This suggests that an apoptosis-like programmed cell death should develop cell-specifically in embryogenic cells by ionizing radiation. The abortion of embryogenic cells may work to prevent transmission of radiation-induced genetic damages to the descendants. (author)

  1. Molecular mechanism of cell damage and protection against ionizing radiation. Communication 3. Correlation between the protective effect and development of a non-specific reaction

    International Nuclear Information System (INIS)

    Veksler, A.M.; Ermekova, V.M.; Kozlovich, L.I.

    1975-01-01

    The dynamics of reversible unspecific reaction (UR) of chinese hamster fibroblast cell culture to hypothermia and cysteamine addition has been studied. A correlation between UR development and radioresistance has been established. The post-irradiation protection has been shown to grow undulatorilly o cysteamine addition at different times after irradiation. This is explained by superimposition of two processes: realization of latent lesions which is delayed by UR development, and repair of these lesions by the enzymatic system the activity of which changes periodicallY, also as a result of UR development

  2. Intestinal endocrine cells in radiation enteritis

    NARCIS (Netherlands)

    Pietroletti, R.; Blaauwgeers, J. L.; Taat, C. W.; Simi, M.; Brummelkamp, W. H.; Becker, A. E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were

  3. Induction of specific suppressor T cells in vitro

    International Nuclear Information System (INIS)

    Eardley, D.D.; Gershon, R.K.

    1976-01-01

    We describe conditions for generating sheep red blood cell-specific suppressor T cells in Mishell-Dutton cultures. The production of specific suppressor cells is favored by increasing antigen dose in the initial culture but can be produced by transferring more cells when lower doses of antigen are used. Transfer of small numbers of cells cultured with low doses of antigen leads to a specific helper effect. Transfer of large numbers of educated cells leads to nonspecific suppression. Suppression can be effected by the effluent cells from nylon wool columns which do not make detectable PFC. A fraction of these cells become resistant to treatment with anti-T cell sera and complement after culture. The suppressor cells are radiation sensitive and must be able to synthesize protein to suppress. They take 2 to 3 days of education to reach maximum suppressive efficiency and will not suppress cultures if added 2 to 3 days after culture initiation. Their production is favored by the absence of mercaptoethanol, suggesting that the observed suppression is not ''too much help.'' The ability to generate specific suppressor cells in vitro should be of great benefit in determining the factors that regulate their appearance in vivo

  4. Radiation effects on cultured human lymphoid cells

    International Nuclear Information System (INIS)

    Johansson, L.; Nilsson, K.; Carlsson, J.; Larsson, B.; Jakobsson, P.

    1981-01-01

    The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed non-neoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. (Auth.)

  5. Haemopoietic cell renewal in radiation fields

    Science.gov (United States)

    Fliedner, T. M.; Nothdurft, W.; Tibken, B.; Hofer, E.; Weiss, M.; Kindler, H.

    1994-10-01

    Space flight activities are inevitably associated with a chronic exposure of astronauts to a complex mixture of ionising radiation. Although no acute radiation consequences are to be expected as a rule, the possibility of Solar Particle Events (SPE) associated with relatively high doses of radiation (1 or more Gray) cannot be excluded. It is the responsibility of physicians in charge of the health of astronauts to evaluate before, during and after space flight activities the functional status of haemopoietic cell renewal. Chronic low level exposure of dogs indicate that daily gamma-exposure doses below about 2 cGy are tolerated for several years as far as blood cell concentrations are concerned. However, the stem cell pool may be severely affected. The maintenance of sufficient blood cell counts is possible only through increased cell production to compensate for the radiation inflicted excess cell loss. This behaviour of haemopoietic cell renewal during chronic low level exposure can be simulated by bioengineering models of granulocytopoiesis. It is possible to define a ``turbulence region'' for cell loss rates, below which an prolonged adaptation to increased radiation fields can be expected to be tolerated. On the basis of these experimental results, it is recommended to develop new biological indicators to monitor haemopoietic cell renewal at the level of the stem cell pool using blood stem cells in addition to the determination of cytokine concentrations in the serum (and other novel approaches). To prepare for unexpected haemopoietic effects during prolonged space missions, research should be increased to modify the radiation sensitivity of haemopoietic stem cells (for instance by the application of certain regulatory molecules). In addition, a ``blood stem cell bank'' might be established for the autologous storage of stem cells and for use in space activities keeping them in a radiation protected container.

  6. Epidermal stem cells response to radiative genotoxic stress

    International Nuclear Information System (INIS)

    Marie, Melanie

    2013-01-01

    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  7. Radiation hardened high efficiency silicon space solar cell

    International Nuclear Information System (INIS)

    Garboushian, V.; Yoon, S.; Turner, J.

    1993-01-01

    A silicon solar cell with AMO 19% Beginning of Life (BOL) efficiency is reported. The cell has demonstrated equal or better radiation resistance when compared to conventional silicon space solar cells. Conventional silicon space solar cell performance is generally ∼ 14% at BOL. The Radiation Hardened High Efficiency Silicon (RHHES) cell is thinned for high specific power (watts/kilogram). The RHHES space cell provides compatibility with automatic surface mounting technology. The cells can be easily combined to provide desired power levels and voltages. The RHHES space cell is more resistant to mechanical damage due to micrometeorites. Micro-meteorites which impinge upon conventional cells can crack the cell which, in turn, may cause string failure. The RHHES, operating in the same environment, can continue to function with a similar crack. The RHHES cell allows for very efficient thermal management which is essential for space cells generating higher specific power levels. The cell eliminates the need for electrical insulation layers which would otherwise increase the thermal resistance for conventional space panels. The RHHES cell can be applied to a space concentrator panel system without abandoning any of the attributes discussed. The power handling capability of the RHHES cell is approximately five times more than conventional space concentrator solar cells

  8. Specific inhibition of Wee1 kinase and Rad51 recombinase: A strategy to enhance the sensitivity of leukemic T-cells to ionizing radiation-induced DNA double-strand breaks

    International Nuclear Information System (INIS)

    Havelek, Radim; Cmielova, Jana; Kralovec, Karel; Bruckova, Lenka; Bilkova, Zuzana; Fousova, Ivana; Sinkorova, Zuzana; Vavrova, Jirina; Rezacova, Martina

    2014-01-01

    Highlights: • Pre-treatment with the inhibitors increased the sensitivity of Jurkat cells to irradiation. • Combining both inhibitors together resulted in a G2 cell cycle arrest abrogation in Jurkat. • Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. • Pre-treatment with Rad51 RI-1 had no effect on apoptosis induction in MOLT-4 cells. • When dosed together, the combination decreased MOLT-4 cell survival. - Abstract: Present-day oncology sees at least two-thirds of cancer patients receiving radiation therapy as a part of their anticancer treatment. The objectives of the current study were to investigate the effects of the small molecule inhibitors of Wee1 kinase II (681641) and Rad51 (RI-1) on cell cycle progression, DNA double-strand breaks repair and apoptosis following ionizing radiation exposure in human leukemic T-cells Jurkat and MOLT-4. Pre-treatment with the Wee1 681641 or Rad51 RI-1 inhibitor alone increased the sensitivity of Jurkat cells to irradiation, however combining both inhibitors together resulted in a further enhancement of apoptosis. Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. MOLT-4 cells were less affected by inhibitors application prior to ionizing radiation exposure. Pre-treatment with Rad51 RI-1 had no effect on apoptosis induction; however Wee1 681641 increased ionizing radiation-induced cell death in MOLT-4 cells

  9. Basal cell carcinoma after radiation therapy

    International Nuclear Information System (INIS)

    Shimbo, Keisuke; Terashi, Hiroto; Ishida, Yasuhisa; Tahara, Shinya; Osaki, Takeo; Nomura, Tadashi; Ejiri, Hirotaka

    2008-01-01

    We reported two cases of basal cell carcinoma (BCC) that developed after radiation therapy. A 50-year-old woman, who had received an unknown amount of radiation therapy for the treatment of intracranial germinoma at the age of 22, presented with several tumors around the radiation ulcer. All tumors showed BCC. A 33-year-old woman, who had received an unknown amount of radiation therapy on the head for the treatment of leukemia at the age of 2, presented with a black nodule within the area of irradiation. The tumor showed BCC. We discuss the occurrence of BCC after radiation therapy. (author)

  10. At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology.

    Science.gov (United States)

    Gerweck, Leo E; Wakimoto, Hiroaki

    2016-03-01

    Reports that a small subset of tumor cells initiate and sustain tumor growth, are resistant to radiation and drugs, and bear specific markers have led to an explosion of cancer stem cell research. These reports imply that the evaluation of therapeutic response by changes in tumor volume is misleading, as volume changes reflect the response of the sensitive rather than the resistant tumorigenic cell population. The reports further suggest that the marker-based selection of the tumor cell population will facilitate the development of radiation treatment schedules, sensitizers, and drugs that specifically target the resistant tumorigenic cells that give rise to treatment failure. This review presents evidence that contests the observations that cancer stem cell markers reliably identify the subset of tumor cells that sustain tumor growth and that the marker-identified population is radioresistant relative to the marker-negative cells. Experimental studies show that cells and tumors that survive large radiation doses are not more radioresistant than unirradiated cells and tumors, and also show that the intrinsic radiosensitivity of unsorted colony-forming tumor cells, in combination with the fraction of unsorted tumor cells that are tumor initiating, predicts tumor radiocurability. ©2016 American Association for Cancer Research.

  11. Radiation Enhances Regulatory T Cell Representation

    Energy Technology Data Exchange (ETDEWEB)

    Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei; DeMarco, John J.; Agazaryan, Nzhde [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Economou, James S. [Department of Surgical Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); McBride, William H. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States)

    2011-11-15

    Purpose: Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. Methods and Materials: Treg cells were identified as a CD4{sup +}CD25{sup hi}Foxp3{sup +} lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4{sup +}CD25{sup hi}Foxp3{sup +} Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. Conclusions: We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.

  12. Radiation Enhances Regulatory T Cell Representation

    International Nuclear Information System (INIS)

    Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei; DeMarco, John J.; Agazaryan, Nzhde; Economou, James S.; McBride, William H.; Schaue, Dörthe

    2011-01-01

    Purpose: Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. Methods and Materials: Treg cells were identified as a CD4 + CD25 hi Foxp3 + lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4 + CD25 hi Foxp3 + Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. Conclusions: We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.

  13. Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.

  14. Cells, targets, and molecules in radiation biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    Cellular damage and repair are discussed with regard to inactivation models, dose-effect curves and cancer research, repair relative to damage accumulation, potentially lethal damage, repair of potentially lethal vs. sublethal damage, cell killing and DNA damage due to nonionizing radiation, and anisotonicity vs. lethality due to nonionizing radiation. Other topics discussed are DNA damage and repair in cells exposed to ionizing radiation, kinetics of repair of single-strand DNA breaks, effects of actinomycin D on x-ray survival curve of hamster cells, misrepair and lethality, and perspective and prospects

  15. Cell cycle arrest induced by radiation

    International Nuclear Information System (INIS)

    Okaichi, Yasuo; Matsumoto, Hideki; Ohnishi, Takeo

    1994-01-01

    It is known that various chemical reactions, such as cell cycle arrest, DNA repair and cell killing, can occur within the cells when exposed to ionizing radiation and ultraviolet radiation. Thus protein dynamics involved in such chemical reactions has received considerable attention. In this article, cell cycle regulation is first discussed in terms of the G2/M-phase and the G1/S-phase. Then, radiation-induced cell cycle arrest is reviewed. Cell cycle regulation mechanism involved in the G2 arrest, which is well known to occur when exposed to radiation, has recently been investigated using yeasts. In addition, recent study has yielded a noticeable finding that the G1 arrest can occur with intracellular accumulation of p53 product following ionization radiation. p53 is also shown to play an extremely important role in both DNA repair and cell killing due to DNA damage. Studies on the role of genes in protein groups induced by radiation will hold promise for the elucidation of cell cycle mechanism. (N.K.) 57 refs

  16. Radiation resistant passivation of silicon solar cells

    International Nuclear Information System (INIS)

    Swanson, R.M.; Gan, J.Y.; Gruenbaum, P.E.

    1991-01-01

    This patent describes a silicon solar cell having improved stability when exposed to concentrated solar radiation. It comprises a body of silicon material having a major surface for receiving radiation, a plurality of p and n conductivity regions in the body for collecting electrons and holes created by impinging radiation, and a passivation layer on the major surface including a first layer of silicon oxide in contact with the body and a polycrystalline silicon layer on the first layer of silicon oxide

  17. Radiation effects in C cells

    International Nuclear Information System (INIS)

    Alcaraz Banos, M.; Garcia Ayala, A.; Meseguer Penalver, J.; Genoves Garcia, J.L.

    1994-01-01

    The para follicular cell (C cell) ultrastructure of euthyroid, propyl thiouracil-treated (PTU) and protyrreline-treated (TRH) irradiated rabbit thyroid gland was studied. The ultrastructural features of C cells in the non-irradiated thyroid glands were similar to those described in other mammals. We have not observed the disappearance of the C cells in irradiated thyroid glands. Clusters of C cells were occasionally observed in the irradiated glands. The irradiated C cells showed intranuclear, filamentous bundles and a dense body together with a well-developed endoplasmic reticulum and numerous secretory vesicles. C cells follicles could be observed in irradiated and TRH-treated animals. (Author)

  18. High Radiation Resistance IMM Solar Cell

    Science.gov (United States)

    Pan, Noren

    2015-01-01

    Due to high launch costs, weight reduction is a key driver for the development of new solar cell technologies suitable for space applications. This project is developing a unique triple-junction inverted metamorphic multijunction (IMM) technology that enables the manufacture of very lightweight, low-cost InGaAsP-based multijunction solar cells. This IMM technology consists of indium (In) and phosphorous (P) solar cell active materials, which are designed to improve the radiation-resistant properties of the triple-junction solar cell while maintaining high efficiency. The intrinsic radiation hardness of InP materials makes them of great interest for building solar cells suitable for deployment in harsh radiation environments, such as medium Earth orbit and missions to the outer planets. NASA Glenn's recently developed epitaxial lift-off (ELO) process also will be applied to this new structure, which will enable the fabrication of the IMM structure without the substrate.

  19. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  20. Biomarkers specific to densely-ionising (high LET) radiations

    International Nuclear Information System (INIS)

    Brenner, D.J.; Okladnikova, N.; Hande, P.; Burak, L.; Geard, C.R.; Azizova, T.

    2001-01-01

    There have been several suggestions of biomarkers that are specific to high LET radiation. Such a biomarker could significantly increase the power of epidemiological studies of individuals exposed to densely-ionising radiations such as alpha particles (e.g. radon, plutonium workers, individuals exposed to depleted uranium) or neutrons (e.g. radiation workers, airline personnel). We discuss here a potentially powerful high LET biomarker (the H value) which is the ratio of induced inter-chromosomal aberrations to intra-arm aberrations. Both theoretical and experimental studies have suggested that this ratio should differ by a factor of about three between high LET radiation and any other likely clastogen, and will yield more discrimination than the previously suggested F value (ratio of inter-chromosomal aberrations to intra-chromosomal inter-arm aberrations). Evidence of the long-term stability of such chromosomal biomarkers has also been generated. Because these stable intra-arm and inter-chromosomal aberrations are (1) frequent and (2) measurable at long times after exposure, this H value appears to be a practical biomarker of high LET exposure, and several in vitro studies have confirmed the approach for unstable aberrations. The approach is currently being tested in a population of Russian radiation workers exposed several decades ago to high- or low LET radiation. (author)

  1. Cell-specific targeting by heterobivalent ligands.

    Science.gov (United States)

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  2. Albendazole sensitizes cancer cells to ionizing radiation

    International Nuclear Information System (INIS)

    Patel, Kirtesh; Doudican, Nicole A; Schiff, Peter B; Orlow, Seth J

    2011-01-01

    Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted

  3. Albendazole sensitizes cancer cells to ionizing radiation

    Science.gov (United States)

    2011-01-01

    Background Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Methods Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. Results ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Conclusions Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted. PMID:22094106

  4. Changing T cell specificity by retroviral T cell receptor display

    NARCIS (Netherlands)

    Kessels, H. W.; van den Boom, M. D.; Spits, H.; Hooijberg, E.; Schumacher, T. N.

    2000-01-01

    The diversity of the T cell receptor (TCR) repertoire is limited, because of the processes of positive and negative T cell selection. To obtain T cells with specificities beyond the immune system's capacity, we have developed a strategy for retroviral TCR display. In this approach, a library of T

  5. Radiation-induced genetic effects in germ cells of mammals

    International Nuclear Information System (INIS)

    Van der Schans, G.P.

    1993-01-01

    The objectives of the project are a better understanding of the fundamental principles that determine the radiation sensitivity in humans, with specific attention for the role of DNA repair in germ cells. The induction and repair of damage in DNA of germ cells of the Syrian golden hamster exposed to ionizing radiation is studied at biologically relevant doses. It has also been investigated which aspects of DNA sequence or chromosomal organisation are important with respect to their influence on the repairability of DNA damage. (R.P.) 10 refs

  6. Origin of specific chromosome aberration in radiation-induced leukemia

    International Nuclear Information System (INIS)

    Ban, Nobuhiko; Kai, Michiaki; Masuno, Yoko

    2005-01-01

    The theme in the title is discussed from the four aspects of specific chromosome aberration (sAb) patterns in radiation-induced leukemia (RIL), possibility for radiation to induce the sAb in RIL, any evidence for participation of delayed aberration to form sAb and the proportion of such healthy humans as having the specifically rearranged genome. Data of sAb observed in leukemia of 25 A-bomb survivors and of 38 patients post radiotherapy of cancers give a rather common pattern. However, many inconsistent results are obtained for sAb in patients post radiotherapy, A-bomb survivors, residents living in radio-contaminated houses in Taipei, in vitro exposure, and Chernobyl residents. At present, any clear evidence is available neither for sAb derived from the delayed aberration nor for estimating the proportion with the specifically rearranged gene. As above, it is unlikely that radiation induces such a translocation abnormality as BCR-ABL specifically seen in leukemia, and this aspect will be important for studies on the genesis of RIL and its risk assessment. (S.I.)

  7. Learning LM Specificity for Ganglion Cells

    Science.gov (United States)

    Ahumada, Albert J.

    2015-01-01

    Unsupervised learning models have been proposed based on experience (Ahumada and Mulligan, 1990;Wachtler, Doi, Lee and Sejnowski, 2007) that allow the cortex to develop units with LM specific color opponent receptive fields like the blob cells reported by Hubel and Wiesel on the basis of visual experience. These models used ganglion cells with LM indiscriminate wiring as inputs to the learning mechanism, which was presumed to occur at the cortical level.

  8. Changes in T-cell subsets after radiation therapy

    International Nuclear Information System (INIS)

    Yang, S.J.; Rafla, S.; Youssef, E.; Selim, H.; Salloum, N.; Chuang, J.Y.

    1988-01-01

    The T-cell subsets of 129 patients with cancer were counted before and after radiation therapy. The cells were labeled with monoclonal antibodies that were specific for each type of T cell. Significant changes after therapy were decreases in the proportion of T-helper/inducer cells, pan-T cells, and in the ratio of T-helper/inducer to T-suppressor/cytotoxic cells. There was an increase in the percentage of T-suppressor/cytotoxic cells. When the site of the primary cancer was considered, genitourinary cancer and cancer of the head and neck both showed a decreased percentage of T-helper/inducer cells and a reduced ratio of T-helper/inducer to T-suppressor/cytotoxic cells. The percentage of pan-T cells in head and neck cancer and the ratio of T-helper/inducer to T-suppressor/cytotoxic cells in breast cancer were decreased. The percentage of T-helper cells was particularly decreased by radiation therapy in advanced stages of cancer, in higher grade tumors, and in larger tumors. The absolute numbers of various T-cell subsets were decreased in all groups

  9. The Effect of 5-FU and Radiation on A549 Cells In Vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Za [Hanyang University College of Medicine, Seoul (Korea, Republic of); Chun, Ha Chong [Medical College of Virgina, Richmond (United States); Lee, Won Young [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1989-06-15

    Effects of ionizing radiation alone and combined with chemotherapy on tumor growth and it clonal specificity Monitored by changes in distribution of chromosome number were studies in A549 cell line originated from human adenocarcinoma of the lung. Radiation (300 rad, 600 rad and 900 rad) were delivered with or without 5-FU. Forty eight hours later, 57.5% of growth inhibition of cell was Seen in cells treated with 5-FU concentration of 0.47g/ml for 24 hr exposure. Cell survival carves after radiation with and without 5-FU were made. Chromosomal analysis of cells in metaphase in control, and in cells treated with 300 rad of radiation, or 0.47g/ml of 5-FU treatment, and combined treatment of cloth were 77ne to examine the changes in ploidy and number of chromosome. Radiation combined with 5-FU enhanced growth inhibition of A549 cells. However, no evidence of synergetic effects in growth inhibition was observed in the cells treated with the combination therapy. Pattern of chromosomal distribution of survived cells were shifted from hyperploidy to hypoploidy by single dose of radiation(300 rad). As radiation dose increased a large number of hypoploidy cells were observed. Following treatment of cells with 5-FU, chomosomal distribution of survived cells were also shifted to hypodiploidy, which were seen in cells treated with radiation. The cell treated with 5-FU and followed by radiation within 24 hrs had cell with increased number of hypodiploidy cells. Almost same type of chromosomal changes were reproduced in cells treated with combined treatment with radiation and 5-FU. Minor differences were that cells with fewer number of chromosome were more frequent in cells treated with combined therapy. Further increase in cells of hypoploidy(93%) having 1-10 chromosome were induced by additional radiation. Therefore, the enhanced therapeutic effect of 5-FU combined with radiation of A549 cells appeared to be additive rather than synergistic.

  10. Protocol of specific health monitoring: ionizing radiation, 11 years later

    International Nuclear Information System (INIS)

    Castillejo Puertas, F. M.

    2016-01-01

    Since the approval on November 11 t h 2003 of the Protocol of Specific Health Monitoring for Workers Exposed to Ionizing Radiation a study has been carried out to discover its effectiveness. These areas were examined: the daily practice od accupational medicine and, in particular, its specific task in the application of the different clinical/labour criteria for workers exposed to ionizing radiation or at risk of radioactive contamination; the degree of its uses as well as the updates and improvements. For that purpose, a descriptive bibliographic revision has been used for the last 11 years. The results revealed the lack of updates of the Protocol as well as the few usable objective criteria, when the clinical/labour aptitudes are reflected upon. (Author)

  11. Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

    Science.gov (United States)

    Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

    1989-01-01

    Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

  12. The radiation hypersensitivity of cells at mitosis.

    Science.gov (United States)

    Stobbe, C C; Park, S J; Chapman, J D

    2002-12-01

    Mitotic cells are hypersensitive to ionizing radiation, exhibiting single-hit inactivation coefficients near to those of repair deficient cell lines and lymphocytes. To elucidate possible mechanisms for this hypersensitivity, the kinetics of oxygen radiosensitization, the proportion of indirect effect by OH radicals and the kinetics of radiation-induced DNA strand breakage in the chromatin of mitotic cells were investigated. Synchronized populations of >90% mitotic HT-29 cells were obtained by the mitotic shake-off method. Cells were irradiated at indirect effect of OH radicals was investigated with the radical scavenger, DMSO. DNA strand breakage was measured by the comet assay. Mitotic HT-29 cell inactivation is well described by a single-hit inactivation coefficient (alpha) of 1.14 +/- 0.06 Gy(-1). The oxygen enhancement ratio of mitotic cells (at 10% survival) was found to be approximately 2.0, significantly lower than the value of 2.8 measured for interphase (asynchronous) cells. More than 60% of mitotic cell killing was eliminated when the media contained 2 M DMSO, indicating that indirect effect is as important in the killing of mitotic cells as it is for interphase cells. The chromatin in mitotic cells was found to be ~2.8 times more sensitive to radiation-induced DNA single-strand breakage than the chromatin of interphase cells. The alpha-inactivation coefficient of mitotic HT-29 cells was ~30 times larger than that of interphase cells. Mitotic cell chromatin appears to contain intrinsic DNA breaks that are not lethal. In addition, chromatin in mitotic cells was found to be more susceptible to radiation-induced DNA strand-breakage than the dispersed chromatin of interphase cells. How the enhanced production of these simple DNA lesions (that are usually reparable) translates into the lethal (non-reparable) events associated with alpha-inactivation is not known. The compaction/dispersion status of DNA throughout the cell cycle appears to be an important

  13. The radiation effects on the living cell

    International Nuclear Information System (INIS)

    Sage, E.; Dutrillaux, B.; Soussi, Th.; Boiteux, S.; Lopez, B.; Feunteun, J.

    1999-06-01

    This publication is a presentation of particular points discussed during the colloquium of the 15-18 june 1999, for which scientific researches are performed at the CEA/CNRS. They deal with the radiobiology, for the radiation effects on living matter; with the DNA, for the knowledge and repair mechanisms on cells submitted to ionizing radiations; with the exposition to UV in correlation with neoplasms; with the P53 gene which is a tumour suppressor. (A.L.B.)

  14. Average radiation weighting factors for specific distributed neutron spectra

    International Nuclear Information System (INIS)

    Ninkovic, M.M.; Raicevic, J.J.

    1993-01-01

    Spectrum averaged radiation weighting factors for 6 specific neutron fields in the environment of 3 categories of the neutron sources (fission, spontaneous fission and (α,n)) are determined in this paper. Obtained values of these factors are greater 1.5 to 2 times than the corresponding quality factors used for the same purpose until a few years ago. This fact is very important to have in mind in the conversion of the neutron fluence into the neutron dose equivalent. (author)

  15. Promotion of initiated cells by radiation-induced cell inactivation.

    Science.gov (United States)

    Heidenreich, W F; Paretzke, H G

    2008-11-01

    Cells on the way to carcinogenesis can have a growth advantage relative to normal cells. It has been hypothesized that a radiation-induced growth advantage of these initiated cells might be induced by an increased cell replacement probability of initiated cells after inactivation of neighboring cells by radiation. Here Monte Carlo simulations extend this hypothesis for larger clones: The effective clonal expansion rate decreases with clone size. This effect is stronger for the two-dimensional than for the three-dimensional situation. The clones are irregular, far from a circular shape. An exposure-rate dependence of the effective clonal expansion rate could come in part from a minimal recovery time of the initiated cells for symmetric cell division.

  16. TEA HF laser with a high specific radiation energy

    Science.gov (United States)

    Puchikin, A. V.; Andreev, M. V.; Losev, V. F.; Panchenko, Yu. N.

    2017-01-01

    Results of experimental studies of the chemical HF laser with a non-chain reaction are presented. The possibility of the total laser efficiency of 5 % is shown when a traditional C-to-C pumping circuit with the charging voltage of 20-24 kV is used. It is experimentally shown that the specific radiation output energy of 21 J/l is reached at the specific pump energy of 350 J/l in SF6/H2 = 14/1 mixture at the total pressure of 0.27 bar.

  17. Atypical radiation response of SCID cells

    Science.gov (United States)

    Chawapun, Nisa

    Murine SCID (severe combined immune deficiency) cells are well known for their defect in DNA double-strand break repair and in variable(diversity)joining [V(D)J] recombination due to a mutation in a catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). As a consequence, scid cells are hypersensitive to ionizing radiation. The present study showed that asynchronous populations of scid cells were about two-fold more sensitive than Balb/c with respect to cell killing and the defect in scid cells was corrected by complementation with human chromosome 8. Analysis of the survival of synchronized populations as a function of the cell cycle revealed that while scid cells were hypersensitive in all cell cycle phases compared to wild-type cells, this hypersensitivity is even more pronounced in G1 phase. The hypersensitivity reduced as the cells progressed into S phase suggested that homologous recombination repair plays a role. The results imply that there are at least two pathways for the repair of DSB DNA, consistent with a model previously proposed by others. The scid cells were also more sensitive to UVC light (254 nm) killing as compared to wild type cells by clonogenic survival. Using a host cell reactivation (HCR) assay to study the nucleotide excision repair (NER) which is the major repair pathway for UV-photoproducts, the results showed that NER in scid cells was not as efficient as CB- 17. This suggests that DNA-PK is involved in NER as well as non-homologous end-joining (NHEJ) DSB repair which is responsible for ionizing radiation sensitivity in scid cells. Repair in scid cells was not totally absent as shown by low dose rate sparing of cell killing after exposure to 137Cs γ-rays at dose rate of 0.6 cGy/h, 1.36 cGy/h, 6 cGy/h as compared to high dose rate at 171 cGy/min, although this phenomenon could be explained partly by proliferation. However, for radiation induced transformation, no significant dose rate effect was seen. A plot of transformation

  18. Radiation induced processes in moss cells

    International Nuclear Information System (INIS)

    Doehren, R. v.

    1975-01-01

    The moss F.h. shows apical growth in the protonema cells which spread radially from the spor. Every apical daughter cell during the state of 'Caulonema' and just before in the state of 'Caulonema Primanen' initiates cell division as soon as more than twice the length of the mother cell is reached. All this allows to follow radiation effects in single cells conveniently. UV irradiation on the range of 254 nm and 280 nm delivered at different parts of the cell area delays cell division markedly may suppress it, and is able to stop the process of growing in relation to the delivered dose and to the irradiated area as well. In case of irradiation of the area next to where the membrane is just being formed - that is to say next to the phragmoplast - the new membrane will be wrongly oriented. In particular giant cells are occurring in the case of nucleus irradiation during early prophase. (orig./GSE) [de

  19. Cell-Specific Aptamers as Emerging Therapeutics

    Directory of Open Access Journals (Sweden)

    Cindy Meyer

    2011-01-01

    Full Text Available Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands by exponential enrichment. Since then, numerous aptamers with specificities for a variety of targets from small molecules to proteins or even whole cells have been selected. Their applications range from biosensing and diagnostics to therapy and target-oriented drug delivery. More recently, selections using complex targets such as live cells have become feasible. This paper summarizes progress in cell-SELEX techniques and highlights recent developments, particularly in the field of medically relevant aptamers with a focus on therapeutic and drug-delivery applications.

  20. Comparison of GSM Modulated and CW Radiofrequency Radiation on Cells

    International Nuclear Information System (INIS)

    Pavicic, I.; Marjanovic, A.M.; Trosic, I.

    2011-01-01

    The aim of our study was to evaluate and compare effect of global system of mobile (GSM) modulation and continuous wave (CW) radiofrequency radiation (RF) on proliferation ability and viability of V79 Chinese hamster lung cells. Previously prepared samples of cells in culture were exposed for 1, 2 and 3 hours both to 915 MHz GSM modulated and to 935 MHz CW RF field in gigahertz transversal electromagnetic mode cell (GTEM-cell). Electric field strength for cells exposed to GSM modulation was set at 10 V/m and for CW exposed cells was 8.2 V/m. Average specific absorption rate (SAR) was calculated to be for GSM 0.23 W/kg and for CW 0.12 W/kg. V79 samples were plated in concentration of 1x10 4 cells/mL. Cell proliferation was determined by cell counts for each hour of exposure during five post-exposure days. Trypan blue exclusion test was used to determine cell viability. In comparison to control cell samples, proliferation of GSM irradiated cells showed significant decrease after 3 hours of exposure on the second and third post-exposure day. CW exposed cell samples showed significant decrease after 3 hours of exposure on the third post-exposure day. Viability of GSM and CW exposed cells did not significantly differ from matched control cell samples. Both applied RF fields have shown similar effect on cell culture growth, and cell viability of V79 cell line. In addition, applied GSM modulated RF radiation demonstrate bigger influence on proliferation of cells. (author)

  1. IRID: specifications for the Ionising Radiations Incident Database

    International Nuclear Information System (INIS)

    Thomas, G.O.; Croft, J.R.; Williams, M.K.; McHugh, J.O.

    1996-01-01

    Technologies that make use of ionising radiations are widespread. They provide many benefits but, as with other technologies, the use of ionising radiations carries with it the potential for incidents and accidents. Their severity can vary from the trivial to the fatal and may involve substantial economic penalties. In order to minimise the number of incidents and their consequences it is important that there is a mechanism to learn the lessons from those that do occur. To help pursue this objective the National Radiological Protection Board, the Health and Safety Executive and the Environment Agency have established a national Ionising Radiations Incident Database (IRID) to cover radiation incidents in industry, medicine, research and teaching. This publication details the specifications for IRID and its methods of operation. All information in the database will be unattributable and names of persons or organisations will not be included. It is a personal computer based system with 24 fields to categorise an incident, including a text field that will provide a description of the incident giving the causes, consequences, follow-up actions and lessons to be learned. These descriptions will be used in subsequent publications to provide feedback to the users. (UK)

  2. Radiation-induced cell damage

    International Nuclear Information System (INIS)

    Felix, W.D.; Schneiderman, M.H.

    1976-01-01

    The addition of irradiated crystals of galactose to Chinese hamster ovary cells resulted in mitotic delay, whereas exposure to nonirradiated crystals resulted in no detectable delay. The inference from this preliminary data is that free radicals or other transient irradiation products have reacted with external cellular components

  3. The hypoxic tumour cell in radiation therapy

    International Nuclear Information System (INIS)

    Trott, K.R.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Neuherberg/Muenchen

    1976-01-01

    In most tumours there is a disproportion between the tumour cells and vascular connective tissue. A lack of oxygen depending on extent and duration, leads to changes of the metabolism and of the proliferative properties of the cells, to an increase of radiation resistance and to a reduction of the ability to recover from radiation injuries. Finally with longer duration, hypoxy leads to cell killing. As a result of irradiation, a reoxygenation of a part of the previous hypoxic tumour cell occurs more or less quickly. The time and topographic changes of these factors are involved in a complex manner in the radiotherapy of malignant tumours and essentially share the responsibility regarding the curative success of radiotherapy. (orig./LH) [de

  4. Radiation Therapy of Suprasellar Germ Cell Tumors

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Choi, Doo Ho; Choi, Eun Kyung; Kim, Il Han; Ha, Sung Whan; Park, Charn Il

    1988-01-01

    A retrospective study was performed on 15 patients with suprasellar germ cell tumors treated by megavoltage external beam irradiation between Feb. 1979 and Dec. 1985. Follow-up period of survivors was 30 to 91 months. Histologic diagnosis was obtained before radiation therapy in 10 patients (9 germinomas and 1 mixed). Five patients were treated without histologic verification. In 9 patients with biopsy-proven germinomas radiation therapy was delivered to the craniospinal axis in 6, to the whole brain in 3. In 5 patients with mixed germ cell tumor or elevated tumor marker, irradiation was delivered to the craniospinal axis in 2, to the whole brain in 2, and to the primary site only in 1. Total doses ranged from 5,000 to 5,500 cGy to the primary site, 3,000 to 4,400 cGy to the whole brain, and 1,300 to 3,000 cGy to the spine. In these 14, local tumor was controlled and primary or spinal failure was not observed. One patient without elevated tumor marker was treated to the whole brain, The tumor was not controlled and he had spinal recurrence. It is proven that radiation therapy is an effective treatment for suprasellar germ cell tumors. The neuroendocrinologic presentation, tumor marker status, early response to radiation measured on CT seem to be useful means for selecting patients for radiation therapy when tissue diagnosis is not available

  5. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    Tease, C.

    1989-01-01

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

  6. Radiation Changes the Metabolic Profiling of Melanoma Cell Line B16.

    Directory of Open Access Journals (Sweden)

    Lige Wu

    Full Text Available Radiation therapy can be an effective way to kill cancer cells using ionizing radiation, but some tumors are resistant to radiation therapy and the underlying mechanism still remains elusive. It is therefore necessary to establish an appropriate working model to study and monitor radiation-mediated cancer therapy. In response to cellular stress, the metabolome is the integrated profiling of changes in all metabolites in cells, which can be used to investigate radiation tolerance mechanisms and identify targets for cancer radiation sensibilization. In this study, using 1H nuclear magnetic resonance for untargeted metabolic profiling in radiation-tolerant mouse melanoma cell line B16, we comprehensively investigated changes in metabolites and metabolic network in B16 cells in response to radiation. Principal component analysis and partial least squares discriminant analysis indicated the difference in cellular metabolites between the untreated cells and X-ray radiated cells. In radiated cells, the content of alanine, glutamate, glycine and choline was increased, while the content of leucine, lactate, creatine and creatine phosphate was decreased. Enrichment analysis of metabolic pathway showed that the changes in metabolites were related to multiple metabolic pathways including the metabolism of glycine, arginine, taurine, glycolysis, and gluconeogenesis. Taken together, with cellular metabolome study followed by bioinformatic analysis to profile specific metabolic pathways in response to radiation, we deepened our understanding of radiation-resistant mechanisms and radiation sensibilization in cancer, which may further provide a theoretical and practical basis for personalized cancer therapy.

  7. Radiation effects in mammalian cells in vitro

    International Nuclear Information System (INIS)

    Hill, C.K.; Han, A.; Elkind, M.M.; Wells, R.L.; Buess, E.M.; Lin, C.M.

    1985-01-01

    The purpose of this research effort is to elucidate the mechanisms for the radiation-induced changes in mammalian cells that lead to cell death, mutation, neoplastic transformation, DNA damage, and chromosomal alterations. Of particular interest are the effects of low-dose-rate and fractionated irradiation on these end points with respect to the mechanisms whereby these effects are influenced by cellular repair processes, inhibitors, and promoters that act at the genetic or biochemical level. 17 refs

  8. Microdosimetric constraints on specific adaptation mechanisms to reduce DNA damage caused by ionising radiation

    International Nuclear Information System (INIS)

    Burkart, W.; Heusser, P.; Vijayalaxmi

    1990-01-01

    The protective effect of pre-exposure of lymphocytes to ionising radiation indicates the presence of 'adaptive repair' in mammalian cells. Microdosimetric considerations, however, raise some doubts on the advantage of such a cellular mechanism for specifically reducing the radiation damage caused by environmental exposures. Contrary to most chemicals which endanger the integrity of the mammalian genome, the local dose and dose rate from ionising radiation at the cellular level remain quite high, even at lowest exposures. A single electron or alpha particle passing through a cell nucleus already yields nuclear doses of up to about 3 mGy and 400 mGy, respectively. Macroscopic doses below these nuclear doses from a single event will only reduce the fraction of cell nuclei encountering the passage of a particle but not the dose or dose rate in the affected volume. At environmental doses in the range of 1 to 5 mGy per annum, the time between two consecutive hits in a specific cell nucleus is in the range of months to years. Very low concentrations of bleomycin, a drug with high affinity to DNA, also triggers an adaptive response. This points to a more general stress response mechanism which may benefit the cell even at environmental levels of radioactivity, e.g. by protecting the integrity of DNA from attacks by chemicals, by endogenous radicals, by acids from anoxia, etc. (author)

  9. Cell cycle kinetics and radiation therapy

    International Nuclear Information System (INIS)

    Mendelsohn, M.L.

    1975-01-01

    Radiation therapy as currently practiced involves the subtle largely empirical art of balancing the recurrence of cancer due to undertreatment against severe damage to local tissues due to overtreatment. Therapeutic results too often fall short of desired success rates; yet, the therapist is continually tantalized to the likelihood that a slight shift of therapeutic ratio favoring normal tissue over cancer would have a profoundly beneficial effect. The application of cell cycle kinetics to radiation therapy is one hope for improving the therapeutic ratio; but, as I will try to show, kinetic approaches are complex, poorly understood, and presently too elusive to elicit confidence or to be used clinically. Their promise lies in their diversity and in the magnitude of our ignorance about how they work and how they should be used. Potentially useful kinetic approaches to therapy can be grouped into three classes. The first class takes advantage of intracyclic differential sensitivity, an effect involving the metabolism and biology of the cell cycle; its strategies are based on synchronization of cells over intervals of hours to days. The second class involves the distinction between cycling and noncycling cells; its strategies are based on the resistance of noncycling cells to cycle-linked radiation sensitizers and chemotherapeutic agents. The third class uses cell repopulation between fractions; its strategies are based on the relative growth rates of tumor and relevant normal tissue before and after perturbation

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  11. Cell fusion induced by ionizing radiation in various cell lines

    International Nuclear Information System (INIS)

    Khair, M.B.

    1994-07-01

    Cell fusion induced by ionizing radiation has been studied in rat's hepatocytes in vivo and in different cell lines in vitro. These cell lines were: Hela cells, V-79 fibroblasts, human and rat lymphocytes. For irradiation, 0.85 MeV fission neutrons and 14 MeV fast neutrons were used. Cell analyses were performed by fluorescent dyes using immunofluorescent microscope and flow cytometre. Our results in vivo showed that, regardless the dose-rate, a dose of 1 Gy approximately was enough to induce a significant level of cell fusion depending on neutron energy and the age of rats. The level of cell fusion was also significant in Hela cells at a dose of 0.5 Gy. Similar effect, but to a lesser extent, was observed in V-79 cells. Whereas, in lymphocytes insignificant cell fusion was noticed. The varying levels of cell-fusion in different cell lines could be attributed to the type of cells and mutual contact between cells. Furthermore irradiation did not show any influence on cell division ability in both hepatocytes and Hela cells and that fused cells were also able to divide forming a new generation of cells. (author). 36 refs., 8 figs., 10 tabs

  12. The Effects of Ionizing Radiation on Mammalian Cells.

    Science.gov (United States)

    Biaglow, John E.

    1981-01-01

    Discusses the effects of radiation on dividing cells and factors influencing these effects; also briefly reviews the radical mechanism for radiation damage. Emphasizes the importance of oxygen in radiation effects. (CS)

  13. Radiation Protection: The Specific Case of Cabin Crew

    International Nuclear Information System (INIS)

    Lecouturier, B.

    1999-01-01

    Exposure to cosmic radiation is one important element of the in-flight working environment. The new requirements of the Council Directive 96/29 Euratom set out basic safety standards in radiation protection which are particularly important to cabin crew. There are two major reasons why they relate specifically to this category of crew member. One is the great diversity of or in some cases the lack of, medical requirements and surveillance. The situation in this area notably differs from that relating to the cockpit crew, who have an aeronautical licence with detailed and rigid medical requirements. The other major reason is the very high percentage of women among the cabin crew (from 65% to 100% depending on the airline concerned), which emphasises the question of protection during pregnancy. The issue of radiation protection of aircrew therefore differs not only according to country and airline, but also according to the crew members concerned. The need is stressed for a harmonised application of the new requirements of the Council Directive 96/29 Euratom and, hopefully in the future, for equivalent protective provisions to be applied worldwide. (author)

  14. Pattern specification in the insect embryo. [uv radiation, Smittia

    Energy Technology Data Exchange (ETDEWEB)

    Sander, K

    1975-01-01

    Specification of developmental pathways by specific determining substances prelocalized in the egg cytoplasm is discussed using the so-called germ cell determinants as an example. Some theoretical considerations speak against the assumption that in insects the various elements of the basic body plan are specified by a prelocalized mosaic of specific determinants. Experimental evidence also points towards a largely epigenetic mode of pattern specification. The process of axial pattern specification can be altered drastically by experiment: in some insects, tail ends may be formed in place of head parts and identical sequences of body segments may be specified two or even three times along the longitudinal egg axis. The experimental results indicate that polarity and regional character of pattern elements formed are specified by one and the same influence, and that this influence can be shifted to or simulated in various other egg regions by transposition or elimination of egg components, or by uv irradiation. Evidence obtained from several types of experiment in the chironomid midge Smittia points towards a key role for local metabolism or energy charge in determination of cell polarity and in pattern spcification. A model for embryonic pattern specification involving differential reaction of cells to a system of longitudinal gradients, which was proposed in 1960, can in principle formally account for all results described. Some striking coincidences of model and experimental results with Wolpert's concept of positional information are noted. Finally it is pointed out that universality of mechanisms for pattern specification is much more likely with respect to formal principles than at the level of their physiological realization.

  15. Radiation protection measures for hot cell sanitation

    International Nuclear Information System (INIS)

    Berger, H.U.; Burck, W.; Dilger, H.

    1983-01-01

    The cell 5 of the Hot Cell Facility of the Kernforschungszentrum Karlsruhe GmbH (KfK) was to be restored and reequipped after 12 years of operation. The decontamination work was first done remotely controlled and afterwards by 38 persons entering the cell, which took about 2 months. The radiation protection methods and personal dosimetry systems are described. At the beginning of the work the γ-dose rate amounted up to 900 mSv/h. After completion of the remotely controlled decontamination work the γ-dose rate decreased to 1.5 mSv/h. At that time the (α+β-contamination was 10 5 Bq/cm 2 . Till the end of the work the removable activity dropped to 10 2 - 10 3 Bq/cm 2 for β-radiation, to 0.3 - 30 Bq/cm 2 for α-radiation and the local dose rate to about 0.03 mSv/h. During the work the accumulated collective doses were listed for breast, hand, head, gonads and foot. In the figure the development with the time of the doses for breast and hand is shown. During restoration work of the cell the accumulated collective whole-body dose amounted to 30 mSv. (orig.) [de

  16. Solar cell radiation handbook. Addendum 1: 1982-1988

    International Nuclear Information System (INIS)

    Anspaugh, B.E.

    1989-02-01

    The Solar Cell Radiation Handbook (JPL Publication 82-69) is updated. In order to maintain currency of solar cell radiation data, recent solar cell designs have been acquired, irradiated with 1 MeV electrons, and measured. The results of these radiation experiments are reported

  17. Radiation hybrids from human chromosome 3: A basis for the construction of region and specific sublibraries

    International Nuclear Information System (INIS)

    Atchison, L.; Cosmis, R.L.; Atchison, M.L.

    1990-01-01

    The authors are interested in identifying genes on human chromosome involved in disease processes. To date at least 20 different loci on this chromosome are implicated with various disease states. DNA libraries containing clones derived from a small chromosomal subregion implicated in a particular disease would greatly assist these studies. They have utilized the radiation hybrid (RH) technique to generate a series of somatic cell hybrids that contain small segments of human chromosome 3 as the only human genetic material. A Chinese hamster-human cell hybrid (Q314-2) containing only human chromosome 3 was used to prepare radiation hybrids. Cells were lethally X-irradiated with 6,000 rads and fused to Urd(??) Chinese hamster cells by PEG 1000 treatment. The majority of hybrids (>72%) analyzed retained portions of chromosome 3. The amount of chromosome 3 in each hybrid ranged from nearly all of the chromosome to very little. Currently these hybrids are being further characterized with single copy probes of known map location in order to isolate regions of chromosome 3 that contain specific disease locus. These reduced hybrids can then be used for the construction of region specific libraries and for the generation of new DNA probes from the specific region of interest

  18. [Technological innovations in radiation oncology require specific quality controls].

    Science.gov (United States)

    Lenaerts, E; Mathot, M

    2014-01-01

    During the last decade, the field of radiotherapy has benefited from major technological innovations and continuously improving treatment efficacy, comfort and safety of patients. This mainly concerns the imaging techniques that allow 4D CT scan recording the respiratory phases, on-board imaging on linear accelerators that ensure perfect positioning of the patient for treatment and irradiation techniques that reduce very significantly the duration of treatment sessions without compromising quality of the treatment plan, including IMRT (Intensity Modulated Radiation Therapy) and VMAT (Volumetric Modulated Arc therapy). In this context of rapid technological change, it is the responsibility of medical physicists to regularly and precisely monitor the perfect functioning of new techniques to ensure patient safety. This requires the use of specific quality control equipment best suited to these new techniques. We will briefly describe the measurement system Delta4 used to control individualized treatment plan for each patient treated with VMAT technology.

  19. Radiation-induced bystander effects in cultured human stem cells.

    Directory of Open Access Journals (Sweden)

    Mykyta V Sokolov

    2010-12-01

    Full Text Available The radiation-induced "bystander effect" (RIBE was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR. RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed.Human bone-marrow mesenchymal stem cells (hMSC and embryonic stem cells (hESC were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05. A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05.These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.

  20. NMR imaging of cell phone radiation absorption in brain tissue

    Science.gov (United States)

    Gultekin, David H.; Moeller, Lothar

    2013-01-01

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

  1. Distributed solar radiation fast dynamic measurement for PV cells

    Science.gov (United States)

    Wan, Xuefen; Yang, Yi; Cui, Jian; Du, Xingjing; Zheng, Tao; Sardar, Muhammad Sohail

    2017-10-01

    To study the operating characteristics about PV cells, attention must be given to the dynamic behavior of the solar radiation. The dynamic behaviors of annual, monthly, daily and hourly averages of solar radiation have been studied in detail. But faster dynamic behaviors of solar radiation need more researches. The solar radiation random fluctuations in minute-long or second-long range, which lead to alternating radiation and cool down/warm up PV cell frequently, decrease conversion efficiency. Fast dynamic processes of solar radiation are mainly relevant to stochastic moving of clouds. Even in clear sky condition, the solar irradiations show a certain degree of fast variation. To evaluate operating characteristics of PV cells under fast dynamic irradiation, a solar radiation measuring array (SRMA) based on large active area photodiode, LoRa spread spectrum communication and nanoWatt MCU is proposed. This cross photodiodes structure tracks fast stochastic moving of clouds. To compensate response time of pyranometer and reduce system cost, the terminal nodes with low-cost fast-responded large active area photodiode are placed besides positions of tested PV cells. A central node, consists with pyranometer, large active area photodiode, wind detector and host computer, is placed in the center of the central topologies coordinate to scale temporal envelope of solar irradiation and get calibration information between pyranometer and large active area photodiodes. In our SRMA system, the terminal nodes are designed based on Microchip's nanoWatt XLP PIC16F1947. FDS-100 is adopted for large active area photodiode in terminal nodes and host computer. The output current and voltage of each PV cell are monitored by I/V measurement. AS62-T27/SX1278 LoRa communication modules are used for communicating between terminal nodes and host computer. Because the LoRa LPWAN (Low Power Wide Area Network) specification provides seamless interoperability among Smart Things without the

  2. Task-specific monitoring of nuclear medicine technologists' radiation exposure

    International Nuclear Information System (INIS)

    Smart, R.

    2004-01-01

    Many studies have demonstrated that the exposure of nuclear medicine technologists arises primarily from radioactive patients rather than from preparation of radiopharmaceuticals. However, in order to devise strategies to reduce staff exposure, it is necessary to identify the specific tasks within each procedure that result in the highest radiation doses. An ESM Eberline FH41B-10 radiation dosemeter, which records the ambient dose equivalent rate, was used to monitor the radiation exposure of a technologist and to record the dose rate in μSv per hour every 32 s throughout a working day. The technologist recorded the procedures that were being performed so that the procedures that resulted in higher doses could be identified clearly. The measured doses clearly showed that the major contributions to the technologist's dose were the following: (1) transferring incapacitated patients from the imaging table to a hospital trolley; (2) difficult injections without syringe shields; and (3) setting up patients for gated myocardial scans. The average dose to the technologist from transferring patients after a bone scan was 0.54 μSv, 40% of the total dose of 1.3 μSv for the complete bone scan procedure. The average dose received injecting 900 MBq of 99 Tc m -HDP using a tungsten syringe shield was 0.57 μSv, but the highest dose was 1.6 μSv, in a patient in whom the injection was difficult. A 0.5 mm lead apron was found to reduce the dose when setting up a patient for a gated stress 99 Tc m -sestamibi myocardial scan by approximately a factor of 2. The average dose per patient for this task was reduced from 1.1 to 0.6 μSv. It is recommended that staff waiting for assistance with patient transfers stand away from the patient, that tungsten syringe shields be used for all radiopharmaceutical injections and that a 0.5 mm lead apron be worn when attending patients containing high activities of 99 Tc m radiopharmaceuticals, such as those having myocardial imaging. (authors)

  3. Radiation damage to integrated injection logic cells

    International Nuclear Information System (INIS)

    Pease, R.L.; Galloway, K.F.; Stehlin, R.A.

    1975-01-01

    The effects of neutron and total dose gamma irradiations on the electrical characteristics of an integrated injection logic (l 2 L) cell and an l 2 L multiple inverter circuit were investigated. These units were designed and fabricated to obtain circuit development information and did not have radiation hardness as a goal. The following parameters of the test structures were measured as a function of total dose and neutron fluence: the dc common-base current gain of the lateral pnp transistor; the dc common-emitter current gain of the vertical npn transistor; the forward current-voltage characteristics of the injector-substrate junction, and the propagation delay versus power dissipation per gate for the multiple inverter circuit. The limitations of the present test structures in a radiation environment and possible hardening techniques are discussed

  4. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Horsman, Michael Robert; Kassem, Moustapha

    2012-01-01

    Background. Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Material and methods....... Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under...... the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin....

  5. Virus-Specific T Cells: Broadening Applicability.

    Science.gov (United States)

    Barrett, A John; Prockop, Susan; Bollard, Catherine M

    2018-01-01

    Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody therapy may help prevent or treat viral disease, these drugs are expensive, toxic, and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (eg, adenovirus, BK virus), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplantation without causing graft-versus-host disease. This review will explore how the VST field has improved outcomes for many patients with life-threatening viral infections after HSCT, and how to broaden applicability beyond the "patient-specific" products, as well as extending to other viral diseases even outside the context of HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved.

  6. Investigation of solar cell radiation damage

    International Nuclear Information System (INIS)

    Bernard, J.; Reulet, R.; Arndt, R.A.

    1974-01-01

    Development of communications satellites has led to the requirement for a greater and longer lived solar cell power source. Accordingly, studies have been undertaken with the aim of determining which solar cell array provides the greatest power at end of life and the amount of degradation. Investigation of the damage done to thin silicon and thin film CdS solar cells is being carried out in two steps. First, irradiations were performed singly with 0.15, 1.0 and 2.0MeV electrons and 0.7, 2.5 and 22MeV proton. Solar cells and their cover materials were irradiated separately in order to locate the sites of the damage. Diffusion length and I.V. characteristics of the cells and transmission properties of the cover materials were measured. All neasurements were made in vacuum immediately after irradiation. In the second part it is intended to study the effect of various combinations of proton, electron and photon irradiation both with and without an electrical load. The results of this part show whether synergism is involved in solar cell damage and the relative importance of each of three radiation sources if synergism is found [fr

  7. Exposing exposure: automated anatomy-specific CT radiation exposure extraction for quality assurance and radiation monitoring.

    Science.gov (United States)

    Sodickson, Aaron; Warden, Graham I; Farkas, Cameron E; Ikuta, Ichiro; Prevedello, Luciano M; Andriole, Katherine P; Khorasani, Ramin

    2012-08-01

    To develop and validate an informatics toolkit that extracts anatomy-specific computed tomography (CT) radiation exposure metrics (volume CT dose index and dose-length product) from existing digital image archives through optical character recognition of CT dose report screen captures (dose screens) combined with Digital Imaging and Communications in Medicine attributes. This institutional review board-approved HIPAA-compliant study was performed in a large urban health care delivery network. Data were drawn from a random sample of CT encounters that occurred between 2000 and 2010; images from these encounters were contained within the enterprise image archive, which encompassed images obtained at an adult academic tertiary referral hospital and its affiliated sites, including a cancer center, a community hospital, and outpatient imaging centers, as well as images imported from other facilities. Software was validated by using 150 randomly selected encounters for each major CT scanner manufacturer, with outcome measures of dose screen retrieval rate (proportion of correctly located dose screens) and anatomic assignment precision (proportion of extracted exposure data with correctly assigned anatomic region, such as head, chest, or abdomen and pelvis). The 95% binomial confidence intervals (CIs) were calculated for discrete proportions, and CIs were derived from the standard error of the mean for continuous variables. After validation, the informatics toolkit was used to populate an exposure repository from a cohort of 54 549 CT encounters; of which 29 948 had available dose screens. Validation yielded a dose screen retrieval rate of 99% (597 of 605 CT encounters; 95% CI: 98%, 100%) and an anatomic assignment precision of 94% (summed DLP fraction correct 563 in 600 CT encounters; 95% CI: 92%, 96%). Patient safety applications of the resulting data repository include benchmarking between institutions, CT protocol quality control and optimization, and cumulative

  8. Case report 600: Post-radiation dermatitis with radiation-induced squamous cell carcinoma (well differentiated) of right third finger

    International Nuclear Information System (INIS)

    Nelson, M.C.; Stull, M.A.; Lack, E.E.; Bogumill, G.P.

    1990-01-01

    A complication of radiation injury - chronic dermatitis with secondary squamous cell carcinoma - is presented. The patient, a radiology technologist, endured years of direct hand exposure that led to precancerous changes and eventually to malignant change, one of the known deleterious effects of radiation. MR imaging, while not diagnostically specific, provided preoperative data. The tumor was totally excised. Six months postoperatively no evidence of recurrent tumor is identified. (orig.)

  9. Cell kinetic studies on radiation induced leukemogenesis

    International Nuclear Information System (INIS)

    Nakao, Isamu; Suzuki, Gen; Imai, Yasufumi; Kawase, Yoshiko; Nose, Masako; Hirashima, Kunitake; Bessho, Masami

    1989-01-01

    The purpose of this study was threefold: (1) to determine the clonal origin of radiation-induced thymic lymphoma in mice with cellular mosaicism for phosphoglycerate kinase; (2) to determine the incidence and latent period of myeloid leukemia and thymic lymphoma induced by whole-body exposure to median doses (3.0 Gy or less) in RFM/MsNrs-2 mice; and (3) to examine the influence of human recombinant interleukin-2 (hrIL-2). Thymic lymphoma was of a single cell origin. The incidence of radiation-induced myeloid leukemia and thymic lymphoma in RFM mice increased in a dose dependent fashion. Mean latent periods of both myeloid leukemia and thymic lymphoma after irradiation became shorter in proportion to radiation doses. When hrIL-2 was injected to RFM mice receiving 3.0 Gy, mean survivals were shorter in thymoma-bearing mice than the control mice. This suggested that hrIL-2 shortens the promotion step of thymoma. Administration of hrIL-2 failed to alter the incidence of myeloid leukemia or the mean survival of mice having myeloid leukemia, indicating that the protocol of hrIL-2 administration was not so sufficient as to alter the myeloid leukemogenesis. (Namekawa, K)

  10. General specifications for silicon semiconductors for use in radiation dosimetry

    International Nuclear Information System (INIS)

    Rikner, G.; Grusell, E.

    1987-01-01

    Silicon semiconductor detectors used in radiation dosimetry have different properties, just as e.g. ionisation chambers, affecting the interaction of radiation with matter in the vicinity of the sensitive volume of the detector, e.g. wall materials, and also the collection of the charges liberated in the detector by the radiation. The charge collection depends on impurities, lattice imperfections and other properties of the semiconductor crystal. In this paper the relevant parameters of a silicon semiconductor detector intended for dosimetry are reviewed. The influence of doping material, doping level, various effects of radiation damage, mechanical construction, detector size, statistical noise and connection to the electrometer are discussed. (author)

  11. Radiolabeled blood cells: radiation dosimetry and significance

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1986-01-01

    Over the past few years blood cells labeled with In-111 have become increasingly useful in clinical diagnosis and biomedical research. Indium-111 by the virtue of its physical characteristics and ability to bind to cell cytoplasmic components, provides an excellent cell tracer and thereby, allows investigators to monitor in vivo cell distribution by external imaging and help determine a course of regimen in treating life threatening diseases. Due to natural phenomena such as margination, blood pool, and reticuloendothelial cell activity, in the normal state, depending upon the cell type and the quality of cell preparations, 30%-50% of the administered radioactivity is immediately distributed in the liver, spleen and bone marrow. Over a period of time the radioactivity in these organs slightly increases and decays with a physical half-life of In-111. The resulting radiation dose to these organs ranges between 1-25 rads/mCi In-111 administered. The authors have developed a new In-111 labeling technique which preserves platelet ultrastructure and shown that human lymphocytes labeled with In-111 in mixed leukocytes preparations a) are only 0.003% of the total -body lymphocytes population and b) are killed. The consequence if any may be considered insignificant, particularly because 5.6% metaphases from normal men and 6.5% metaphases from normal women in the US have at least one chromosome aberration. Calculations have shown that the risk of fatal hematological malignancy, over a 30 year period, in recipients of 100 million lymphocytes labeled with 100 μCi In-111 is 1/million patients studied. This risk is less than 0.025% of the 1981 spontaneous cancer patient rate in the country. 32 references, 10 tables

  12. Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation

    International Nuclear Information System (INIS)

    Planel, H.; Soleilhavoup, J.P.; Tixador, R.; Richoilley, G.; Conter, A.; Croute, F.; Caratero, C.; Gaubin, Y.

    1987-01-01

    Investigations carried out on the protozoan Paramecium tetraurelia and the cyanobacteria Synechococcus lividus, which were shielded against background radiation or exposed to very low doses of gamma radiation, demonstrated that radiation can stimulate the proliferation of these two single-cell organisms. Radiation hormesis depends on internal factors (age of starting cells) and external factors (lighting conditions). The stimulatory effect occurred only in a limited range of doses and disappeared for dose rates higher than 50 mGy/y

  13. The Radiation Effect on Peripheral Blood Cell

    International Nuclear Information System (INIS)

    Lee, Tae June; Kwon, Hyoung Cheol; Kim, Jung Soo; Im, Sun Kyun; Choi, Ki Chul

    1988-01-01

    To evaluate radiation effect on the hematopoietic system, we analyzed 44 patients who were treated with conventionally fractionated radiation therapy (RT) at Chonbuk National University Hospital. According to the treatment sites, we classified them into three groups: group I as head and neck, group II as thorax, and group III as pelvis. White blood cell, lymphocyte, platelet and hemoglobin were checked before and during RT The results were as follow; 1. White blood cell (WBC) and lymphocyte count were declined from the first week of RT to the third week, and then slightly recovered after the third or fourth week. There was prominent decrease in lymphocyte counts than WBC. 2. Platelet counts were declined until the second week of the RT, showed slight recovery at fourth week in all groups. Hemoglobin values were slightly decreased in the first week and then recovered the level of pretreatment value, gradually. 3. Lymphocyte count were declined significantly on group III(p<0.01), WBC and platelet counts were decreased on group II but statistically not significant

  14. Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions.

    Science.gov (United States)

    Maria, Ola M; Maria, Ahmed M; Ybarra, Norma; Jeyaseelan, Krishinima; Lee, Sangkyu; Perez, Jessica; Shalaby, Mostafa Y; Lehnert, Shirley; Faria, Sergio; Serban, Monica; Seuntjens, Jan; El Naqa, Issam

    2016-04-01

    Lung tissue exposure to ionizing irradiation can invariably occur during the treatment of a variety of cancers leading to increased risk of radiation-induced lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to differentiate into epithelial cells. However, cell culture methods of primary type II pneumocytes are slow and cannot provide a sufficient number of cells to regenerate damaged lungs. Moreover, effects of ablative radiation doses on the ability of MSCs to differentiate in vitro into lung cells have not been investigated yet. Therefore, an in vitro coculture system was used, where MSCs were physically separated from dissociated lung tissue obtained from either healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats. Around 10±5% and 20±3% of cocultured MSCs demonstrated a change into lung-specific Clara and type II pneumocyte cells when MSCs were cocultured with healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies, the percentage of MSCs changed into Clara and type II pneumocytes cells increased to 40±7% and 50±6% at 16 Gy irradiation dose and 30±5% and 40±8% at 20 Gy irradiation dose, respectively. These data suggest that MSCs to lung cell differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole thorax irradiation doses that can cause varying levels of RILD, induced different percentages of MSCs to adopt lung cell phenotype compared with healthy lung tissue, providing encouraging outlook for RILD therapeutic intervention for ablative radiotherapy prescriptions.

  15. Cell oxidation-reduction imbalance after modulated radiofrequency radiation.

    Science.gov (United States)

    Marjanovic, Ana Marija; Pavicic, Ivan; Trosic, Ivancica

    2015-01-01

    Aim of this study was to evaluate an influence of modulated radiofrequency field (RF) of 1800 MHz, strength of 30 V/m on oxidation-reduction processes within the cell. The assigned RF field was generated within Gigahertz Transversal Electromagnetic Mode cell equipped by signal generator, modulator, and amplifier. Cell line V79, was irradiated for 10, 30, and 60 min, specific absorption rate was calculated to be 1.6 W/kg. Cell metabolic activity and viability was determined by MTT assay. In order to define total protein content, colorimetric method was used. Concentration of oxidised proteins was evaluated by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) marked with fluorescent probe 2',7'-dichlorofluorescin diacetate were measured by means of plate reader device. In comparison with control cell samples, metabolic activity and total protein content in exposed cells did not differ significantly. Concentrations of carbonyl derivates, a product of protein oxidation, insignificantly but continuously increase with duration of exposure. In exposed samples, ROS level significantly (p < 0.05) increased after 10 min of exposure. Decrease in ROS level was observed after 30-min treatment indicating antioxidant defence mechanism activation. In conclusion, under the given laboratory conditions, modulated RF radiation might cause impairment in cell oxidation-reduction equilibrium within the growing cells.

  16. Ionizing radiation induces heritable disruption of epithelial cell interactions

    Science.gov (United States)

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

    2003-01-01

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

  17. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Science.gov (United States)

    Gruel, Gaëtan; Villagrasa, Carmen; Voisin, Pascale; Clairand, Isabelle; Benderitter, Marc; Bottollier-Depois, Jean-François; Barquinero, Joan Francesc

    2016-01-01

    Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to

  18. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Directory of Open Access Journals (Sweden)

    Gaëtan Gruel

    Full Text Available Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This

  19. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Effect of radiation on microtubule structure in cancer cells

    International Nuclear Information System (INIS)

    Tripath, Shambhoo Sharan; Panda, Dulal; Jayakumar, S.; Maikho, Thoh; Sandur, Santosh Kumar

    2017-01-01

    Microtubules (MT) are dynamic structural cellular components. In proliferating cells, they are essential components in cell division through the formation of the mitotic spindle. Radiotherapy is an integral part of cancer treatment for most of the solid cancers. Scanty data exists in the literature related to how ionizing radiation affects microtubule reorganization in tumor cells. In the present study, breast cancer cell line (MCF-7 cells) was exposed to different doses of radiation (2-10Gy). Cells were cultured for 24 h, fixed and stained with antitubulin antibody and subjected to immunofluorescence microscopy. In another experiment, cells were subjected to cold treatment for 5 min or 30 min for studying the disassembly of microtubules after 24 h of irradiation. Further, these cells were incubated at 37°C for 20 min for studying the reassembly of microtubules. Acetylation of microtubule was also examined after exposure of cells to radiation. Experiments were also performed by combining radiation with low concentration of CXI-Benzo 84 (MT destabilizing agent 1 and 2.5 uM). Exposure of MCF-7 cells to radiation lead to destabilization of microtubules. Interestingly, destabilization of microtubule was faster upon cold treatment in irradiated group as compared to control group. These cells failed to re-stabilize at 37°C. Radiation also reduced the acetylation level of microtubule. Combination treatment of CXI-Benzo 84 with radiation exhibited additive effect in terms of depolymerization of MT. Our results suggest that ionizing radiation indeed modulates microtubule dynamics. (author)

  1. Mobile phone radiation alters proliferation of hepatocarcinoma cells.

    Science.gov (United States)

    Ozgur, Elcin; Guler, Goknur; Kismali, Gorkem; Seyhan, Nesrin

    2014-11-01

    This study investigated the effects of intermittent exposure (15 min on, 15 min off for 1, 2, 3, or 4 h, at a specific absorption rate of 2 W/kg) to enhanced data rates for global system for mobile communication evolution-modulated radiofrequency radiation (RFR) at 900- and 1,800-MHz frequencies on the viability of the Hepatocarcinoma cells (Hep G2). Hep G2 cell proliferation was measured by a colorimetric assay based on the cleavage of the tetrazolium salt WST-1 by mitochondrial dehydrogenases in viable cells. Cell injury was evaluated by analyzing the levels of lactate dehydrogenase (LDH) and glucose released from lysed cells into the culture medium. Morphological observation of the nuclei was carried out by 4',6-diamidino-2-phenylindole (DAPI) staining using fluorescence microscopy. In addition, TUNEL assay was performed to confirm apoptotic cell death. It was observed that cell viability, correlated with the LDH and glucose levels, changed according to the frequency and duration of RFR exposure. Four-hour exposure produced more pronounced effects than the other exposure durations. 1,800-MHz RFR had a larger impact on cell viability and Hep G2 injury than the RFR at 900 MHz. Morphological observations also supported the biochemical results indicating that most of the cells showed irregular nuclei pattern determined by using the DAPI staining, as well as TUNEL assay which shows DNA damage especially in the cells after 4 h of exposure to 1,800-MHz RFR. Our results indicate that the applications of 900- and 1,800-MHz (2 W/kg) RFR cause to decrease in the proliferation of the Hep G2 cells after 4 h of exposure. Further studies will be conducted on other frequency bands of RFR and longer duration of exposure.

  2. Mechanisms of radiation-induced neoplastic cell transformation

    International Nuclear Information System (INIS)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

  3. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  4. Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Chang, Joe Y.; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

    2006-01-01

    Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival

  5. 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.

  6. 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

  7. Virus-Specific T Cells for the Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Amy Houghtelin

    2017-10-01

    Full Text Available While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST, which are not only effective but also confer protection in 70–90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo.

  8. Virus-Specific T Cells for the Immunocompromised Patient.

    Science.gov (United States)

    Houghtelin, Amy; Bollard, Catherine M

    2017-01-01

    While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but also confer protection in 70-90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo .

  9. The advancement of stem cells in radiation medicine

    International Nuclear Information System (INIS)

    Guo Li; Fan Hongxue

    2003-01-01

    It may result in acute radiation syndrome after body is exposed to ionizing radiation. The one of long-term effects of irradiation injury is leukemia. The bone marrow cells (BMC) transplantation including stem cells is the only effective therapy for acute radiation syndrome patients. Recently, with the advancement of stem cell research that the stem cells have multipotential and can convert each other, it may supply the new stem source for the irradiation injury patients. At the same time with the further research of radioprotective reagents, the hematopoietic stem cells proliferation after irradiation injury is promoted

  10. Cell immobilization by radiation polymerization-a comparative study

    International Nuclear Information System (INIS)

    Dahlan bin Hj Mohd; Abu Bakar bin Salleh; Che Nyonya binti Abd Razak; Meheran binti Hamenudin; Kamaruzaman bin Ampon; Wan Md Zin bin Wan Yunus; Mahiran binti Basri

    1991-01-01

    An extracellular lipase producing fungus, Rhizopus rhizopodi formis was immobilised using radiation-induced polyHEMA, alginate and k-carrageenan. Immobilizations were done on spores since they showed better resistance against gamma radiation. The simultaneous radiation immobilization technique was found to be unsuitable because of contamination. Post-radiation immobilization using polyHEMA yielded 2-3 times more enzyme than the free cells. The value, however was slightly lower than the ones given by the cells immobilised using alginate or k-carrageenan, but the radiation-induced polymer was stronger and less likely to disintegrate

  11. Radiosensitivity of yeast cells as a function of radiation LET

    International Nuclear Information System (INIS)

    Lobachevskij, P.N.; Krasavin, E.A.

    1988-01-01

    A model is proposed for interpreting the radiosensitivity of yeast cells as a function of linear energy transfer (LET) of ionizing radiation. The model takes into account the role of repair processes in sensitivity of yeast cells to ionizing radiation of different LET. Two types of repair are discussed: (1) a nonspecific repair (characteristic of both haploid and diploid cells), and (2) a diploid - soecific repair (characteristic of diploid cells only)

  12. Prototype Operational Advances for Atmospheric Radiation Dose Rate Specification

    Science.gov (United States)

    Tobiska, W. K.; Bouwer, D.; Bailey, J. J.; Didkovsky, L. V.; Judge, K.; Garrett, H. B.; Atwell, W.; Gersey, B.; Wilkins, R.; Rice, D.; Schunk, R. W.; Bell, D.; Mertens, C. J.; Xu, X.; Crowley, G.; Reynolds, A.; Azeem, I.; Wiltberger, M. J.; Wiley, S.; Bacon, S.; Teets, E.; Sim, A.; Dominik, L.

    2014-12-01

    Space weather's effects upon the near-Earth environment are due to dynamic changes in the energy transfer processes from the Sun's photons, particles, and fields. The coupling between the solar and galactic high-energy particles, the magnetosphere, and atmospheric regions can significantly affect humans and our technology as a result of radiation exposure. Space Environment Technologies (SET) has developed innovative, new space weather observations that will become part of the toolset that is transitioned into operational use. One prototype operational system for providing timely information about the effects of space weather is SET's Automated Radiation Measurements for Aerospace Safety (ARMAS) system. ARMAS will provide the "weather" of the radiation environment to improve aircraft crew and passenger safety. Through several dozen flights the ARMAS project has successfully demonstrated the operation of a micro dosimeter on commercial aviation altitude aircraft that captures the real-time radiation environment resulting from Galactic Cosmic Rays and Solar Energetic Particles. The real-time radiation exposure is computed as an effective dose rate (body-averaged over the radiative-sensitive organs and tissues in units of microsieverts per hour); total ionizing dose is captured on the aircraft, downlinked in real-time via Iridium satellites, processed on the ground into effective dose rates, compared with NASA's Langley Research Center (LaRC) most recent Nowcast of Atmospheric Ionizing Radiation System (NAIRAS) global radiation climatology model runs, and then made available to end users via the web and smart phone apps. We are extending the dose measurement domain above commercial aviation altitudes into the stratosphere with a collaborative project organized by NASA's Armstrong Flight Research Center (AFRC) called Upper-atmospheric Space and Earth Weather eXperiment (USEWX). In USEWX we will be flying on the ER-2 high altitude aircraft a micro dosimeter for

  13. Radiation damage and repair in cells and cell components. Part 2. Physical radiations and biological significance. Final report

    International Nuclear Information System (INIS)

    Fluke, D.J.

    1984-08-01

    The report comprises a teaching text, encompassing all physical radiations likely to be of biological interest, and the relevant biological effects and their significance. Topics include human radiobiology, delayed effects, radiation absorption in organisms, aqueous radiation chemistry, cell radiobiology, mutagenesis, and photobiology

  14. Epigenetic cell response to an influence of ionizing radiation

    International Nuclear Information System (INIS)

    Mikheev, A.N.; Gushcha, N.I.; Malinovskij, Yu.Yu.

    1999-01-01

    Importance of radiation modification of epigenetic activity in the general mechanism of radiobiological reactions is proved. Inheritable epigenetic changes induced by irradiation are one of the basic reasons of formation of the remote radiation pathology. It is noted that epigenetic inheritable changes of cells have the determined character distinguishing them mutation changes, being individual and not directed. It is underlined the ability of ionizing radiation to modify level of spontaneous genetic instability inherited in a number of cell generations on epigenetic mechanism [ru

  15. Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

    2006-01-01

    Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

  16. Immobilization of microbial cell and yeast cell and its application to biomass conversion using radiation techniques

    International Nuclear Information System (INIS)

    Kaetsu, Isao; Kumakura, Minoru; Fujimura, Takashi; Kasai, Noboru; Tamada, Masao

    1987-01-01

    The recent results of immobilization of cellulase-producing cells and ethanol-fermentation yeast by radiation were reported. The enzyme of cellulase produced by immobilized cells was used for saccharification of lignocellulosic wastes and immobilized yeast cells were used for fermentation reaction from glucose to ethanol. The wastes such as chaff and bagasse were treated by γ-ray or electron-beam irradiation in the presence of alkali and subsequent mechanical crushing, to form a fine powder less than 50 μm in diameter. On the other hand, Trichoderma reesei as a cellulase-producing microbial cell was immobilized on a fibrous carrier having a specific porous structure and cultured to produce cellulase. The enzymatic saccharification of the pretreated waste was carried out using the produced cellulase. The enhanced fermentation process to produce ethanol from glucose with the immobilized yeast by radiation was also studied. The ethanol productivity of immobilized growing yeast cells thus obtained was thirteen times that of free yeast cells in a 1:1 volume of liquid medium to immobilized yeast cells. (author)

  17. Immobilization of microbial cell and yeast cell and its application to biomass conversion using radiation techniques

    Science.gov (United States)

    Kaetsu, Isao; Kumakura, Minoru; Fujimura, Takashi; Kasai, Noboru; Tamada, Masao

    The recent results of immobilization of cellulase-producing cells and ethanol-fermentation yeast by radiation were reported. The enzyme of cellulase produced by immobilized cells was used for saccharification of lignocellulosic wastes and immobilized yeast cells were used for fermentation reaction from glucose to ethanol. The wastes such as chaff and bagasse were treated by γ-ray or electron-beam irradiation in the presence of alkali and subsequent mechanical crushing, to form a fine powder less than 50 μm in diameter. On the other hand, Trichoderma reesei as a cellulase-producing microbial cell was immobilized on a fibrous carrier having a specific porous structure and cultured to produce cellulase. The enzymatic saccharification of the pretreated waste was carried out using the produced cellulase. The enhanced fermentation process to produce ethanol from glucose with the immobilized yeast by radiation was also studied. The ethanol productivity of immobilized growing yeast cells thus obtained was thirteen times that of free yeast cells in a 1:1 volume of liquid medium to immobilized yeast cells.

  18. Altruistic cell suicide in relation to radiation hormesis

    International Nuclear Information System (INIS)

    Kondo, Sohei

    1988-01-01

    The high radiosensitivity to killing of undifferentiated primordial cells (Bergonie and Tribondeau 1906) can be described as a manifestation of the suicide of injured cells for the benefit of an organism as a whole if their suicide stimulates proliferation of healthy cells to replace them, resulting in complete elimination of injury. This process is called cell-replacement repair, to distinguish it from DNA repair which is rarely complete. 'Cell suicide', 'programmed death' and 'apoptosis' are terms used for the same type of active cell death. Cell suicide is not always altruistic. Altruistic suicide in Drosophila, mice, humans, plants, and E. coli is reviewed in this paper to illustrate its widely different facets. The hypothesis that in animals, radiation hormesis results from altruistic cell suicide is proposed. This hypothesis can explain the hormetic effect of low doses of radiation on the immune system in mice. In contrast, in plants, radiation hormesis seems to be mainly due to non-altruistic cell death. (author)

  19. Brain-specific enhancers for cell-based therapy

    Science.gov (United States)

    Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun; Pennacchio, Len A.; Vogt, Daniel; Nicholas, Cory; Kriegstein, Arnold

    2018-04-24

    Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

  20. Increased radiation resistance in lithium-counterdoped silicon solar cells

    Science.gov (United States)

    Weinberg, I.; Swartz, C. K.; Mehta, S.

    1984-01-01

    Lithium-counterdoped n(+)p silicon solar cells are found to exhibit significantly increased radiation resistance to 1-MeV electron irradiation when compared to boron-doped n(+)p silicon solar cells. In addition to improved radiation resistance, considerable damage recovery by annealing is observed in the counterdoped cells at T less than or equal to 100 C. Deep level transient spectroscopy measurements are used to identify the defect whose removal results in the low-temperature aneal. It is suggested that the increased radiation resistance of the counterdoped cells is primarily due to interaction of the lithium with interstitial oxygen.

  1. 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)

  2. Radiation Safety in Industrial Radiography. Specific Safety Guide (Spanish Edition)

    International Nuclear Information System (INIS)

    2013-01-01

    This Safety Guide provides recommendations for ensuring radiation safety in industrial radiography used in non-destructive testing. This includes industrial radiography work that utilizes X ray and gamma sources, both in shielded facilities that have effective engineering controls and in outside shielded facilities using mobile sources. Contents: 1. Introduction; 2. Duties and responsibilities; 3. Safety assessment; 4. Radiation protection programme; 5. Training and qualification; 6. Individual monitoring of workers; 7. Workplace monitoring; 8. Control of radioactive sources; 9. Safety of industrial radiography sources and exposure devices; 10. Radiography in shielded enclosures; 11. Site radiography; 12. Transport of radioactive sources; 13. Emergency preparedness and response; Appendix: IAEA categorization of radioactive sources; Annex I: Example safety assessment; Annex II: Overview of industrial radiography sources and equipment; Annex III: Examples of accidents in industrial radiography

  3. Radiation Safety in Industrial Radiography. Specific Safety Guide

    International Nuclear Information System (INIS)

    2011-01-01

    This Safety Guide provides recommendations for ensuring radiation safety in industrial radiography used in non-destructive testing. This includes industrial radiography work that utilizes X ray and gamma sources, both in shielded facilities that have effective engineering controls and in outside shielded facilities using mobile sources. Contents: 1. Introduction; 2. Duties and responsibilities; 3. Safety assessment; 4. Radiation protection programme; 5. Training and qualification; 6. Individual monitoring of workers; 7. Workplace monitoring; 8. Control of radioactive sources; 9. Safety of industrial radiography sources and exposure devices; 10. Radiography in shielded enclosures; 11. Site radiography; 12. Transport of radioactive sources; 13. Emergency preparedness and response; Appendix: IAEA categorization of radioactive sources; Annex I: Example safety assessment; Annex II: Overview of industrial radiography sources and equipment; Annex III: Examples of accidents in industrial radiography.

  4. Radiation Safety in Industrial Radiography. Specific Safety Guide (French Edition)

    International Nuclear Information System (INIS)

    2013-01-01

    This Safety Guide provides recommendations for ensuring radiation safety in industrial radiography used in non-destructive testing. This includes industrial radiography work that utilizes X ray and gamma sources, both in … shielded facilities that have effective engineering controls and in outside shielded facilities using mobile sources. Contents: 1. Introduction; 2. Duties and responsibilities; 3. Safety assessment; 4. Radiation protection programme; 5. Training and qualification; 6. Individual monitoring of workers; 7. Workplace monitoring; 8. Control of radioactive sources; 9. Safety of industrial radiography sources and exposure devices; 10. Radiography in shielded enclosures; 11. Site radiography; 12. Transport of radioactive sources; 13. Emergency preparedness and response; Appendix: IAEA categorization of radioactive sources; Annex I: Example safety assessment; Annex II: Overview of industrial radiography sources and equipment; Annex III: Examples of accidents in industrial radiography

  5. Radiation Safety in Industrial Radiography. Specific Safety Guide (Arabic Edition)

    International Nuclear Information System (INIS)

    2012-01-01

    This Safety Guide provides recommendations for ensuring radiation safety in industrial radiography used in non-destructive testing. This includes industrial radiography work that utilizes X ray and gamma sources, both in shielded facilities that have effective engineering controls and outside shielded facilities using mobile sources. Contents: 1. Introduction; 2. Duties and responsibilities; 3. Safety assessment; 4. Radiation protection programme; 5. Training and qualification; 6. Individual monitoring of workers; 7. Workplace monitoring; 8. Control of radioactive sources; 9. Safety of industrial radiography sources and exposure devices; 10. Radiography in shielded enclosures; 11. Site radiography; 12. Transport of radioactive sources; 13. Emergency preparedness and response; Appendix: IAEA categorization of radioactive sources; Annex I: Example safety assessment; Annex II: Overview of industrial radiography sources and equipment; Annex III: Examples of accidents in industrial radiography.

  6. Radiation-induced malignant tumours: a specific cytogenetic profile?

    International Nuclear Information System (INIS)

    Chauveinc, L.; Gaboriaux, G.; Dutrillaux, A. M.; Dutrillaux, B.; Chauveinc, L.; Ricoul, M.; Sabatier, L.; Dutrillaux, B.

    1997-01-01

    To date, there is no criterion enabling to determine the spontaneous or radio-induced origin of malignant tumour occurring in a previously irradiated patient. Biological studies are rare. The cytogenetic data which could be found in the literature for eleven radio-induced tumours suggest that aneuploidies and polyclonality are frequent events. We studied, by R-Banding cytogenetic technique, five patients with short-term cultures (3 cases), short and long-term cultures (1 case) and xeno-grafting on nude pattern a high rate of balanced translocations, numerous random break points and a polyclonal evolution (10 clones). All other tumours, including the xeno-grafting sarcoma, had a monoclonal profile with complex karyotypes, hypo-diploid formulas and many deletions. These results show that the mechanism of radiation-induced tumours frequently involves chromosomes losses and deletions. The most likely explanation is that these alterations unmask radiation induced recessive mutations of tumour suppressor genes. (authors)

  7. 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.

  8. Effects of radiation and chemical substances on cells and organism

    International Nuclear Information System (INIS)

    Fremuth, F.

    1981-01-01

    The book treats the radiation chemistry part of biophysics and applied biophysics in the sphere of ionizing radiation. Discussed are the concepts of radiation units and radioactivity units and the relative biological efficiency. The effects of ionizing and UV radiations are analyzed at the level of macromolecular changes. Chapters dealing with genetic radiation effects discuss the effects at the cellular level with respect to cell proliferation. All these problems are used to illustrate the effect on the organism as a whole. The chapters on applied biophysics deal with the indications of radiation and chemical damage, sensitivity of cells and the organism, and the study and influencing of growth at the cellular level. The concluding chapter is devoted to the environmental impact of radiation. (J.P.)

  9. Stem cell-based therapies for acute radiation syndrome

    International Nuclear Information System (INIS)

    Guha, Chandan

    2014-01-01

    Exposure to high doses of ionizing radiation in the event of accidental or intentional incident such as nuclear/radiological terrorism can lead to debilitating injuries to multiple organs resulting in death within days depending on the amount of radiation dose and the quality of radiation. Unfortunately, there is not a single FDA-licensed drug approved against acute radiation injury. The RadStem Center for Medical Countermeasures against Radiation (RadStem CMGR) program at Einstein is developing stem cell-based therapies to treat acute radiation syndrome (ARS). We have demonstrated that intravenous transplantation of bone marrow-derived and adipose-derived stromal cells, consisting of a mixture of mesenchymal, endothelial and myeloid progenitors can mitigate mice exposed to whole body irradiation of 12 Gy or whole abdominal irradiation of up to 20 Gy. We identified a variety of growth and differentiation factors that individually is unable to improve survival of animals exposed to lethal irradiation, but when administered sequentially mitigates radiation injury and improves survival. We termed this phenomenon as synthetic survival and describe a new paradigm whereby the 'synthetic survival' of irradiated tissues can be promoted by systemic administration of growth factors to amplify residual stem cell clonogens post-radiation exposure, followed by a differentiation factor that favors tissue stem cell differentiation. Synthetic survival can be applied to mitigate lethal radiation injury in multiple organs following radiation-induced hematopoeitic, gastrointestinal and pulmonary syndromes. (author)

  10. Biological response of cancer cells to radiation treatment

    Directory of Open Access Journals (Sweden)

    Rajamanickam eBaskar

    2014-11-01

    Full Text Available Cancer is a class of diseases characterized by uncontrolled cell growth and has the ability to spread or metastasize throughout the body. In recent years, remarkable progress has been made towards the understanding of proposed hallmarks of cancer development, care and treatment modalities. Radiation therapy or radiotherapy is an important and integral component of cancer management, mostly conferring a survival benefit. Radiation therapy destroys cancer by depositing high-energy radiation on the cancer tissues. Over the years, radiation therapy has been driven by constant technological advances and approximately 50% of all patients with localized malignant tumors are treated with radiation at some point in the course of their disease. In radiation oncology, research and development in the last three decades has led to considerable improvement in our understanding of the differential responses of normal and cancer cells. The biological effectiveness of radiation depends on the linear energy transfer (LET, total dose, number of fractions and radiosensitivity of the targeted cells or tissues. Radiation can either directly or indirectly (by producing free radicals damages the genome of the cell. This has been challenged in recent years by a newly identified phenomenon known as radiation induced bystander effect (RIBE. In RIBE, the non-irradiated cells adjacent to or located far from the irradiated cells/tissues demonstrate similar responses to that of the directly irradiated cells. Understanding the cancer cell responses during the fractions or after the course of irradiation will lead to improvements in therapeutic efficacy and potentially, benefitting a significant proportion of cancer patients. In this review, the clinical implications of radiation induced direct and bystander effects on the cancer cell are discussed.

  11. Definitive radiation therapy for squamous cell carcinoma of the vagina

    International Nuclear Information System (INIS)

    Frank, Steven J.; Jhingran, Anuja; Levenback, Charles; Eifel, Patricia J.

    2005-01-01

    Purpose: To evaluate outcome and describe clinical treatment guidelines for patients with primary squamous cell carcinoma of the vagina treated with definitive radiation therapy. Methods and Materials: Between 1970 and 2000, a total of 193 patients were treated with definitive radiation therapy for squamous cell carcinoma of the vagina at The University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed to obtain information about patient, tumor, and treatment characteristics, as well as outcome and patterns of recurrence. Surviving patients were followed for a median of 137 months. Survival rates were calculated using the Kaplan-Meier method, with differences assessed using log-rank tests. Results: Disease-specific survival (DSS) and pelvic disease control rates correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor size. At 5 years, DSS rates were 85% for the 50 patients with Stage I, 78% for the 97 patients with Stage II, and 58% for the 46 patients with Stage III-IVA disease (p = 0.0013). Five-year DSS rates were 82% and 60% for patients with tumors ≤4 cm or >4 cm, respectively (p = 0.0001). At 5 years, pelvic disease control rates were 86% for Stage I, 84% for Stage II, and 71% for Stage III-IVA (p = 0.027). The predominant mode of relapse after definitive radiation therapy was local-regional (68% and 83%, respectively, for patients with stages I-II or III-IVA disease). The incidence of major complications was correlated with FIGO stage; at 5 years, the rates of major complications were 4% for Stage I, 9% for Stage II, and 21% for Stage III-IVA (p < 0.01). Conclusions: Excellent outcomes can be achieved with definitive radiation therapy for invasive squamous cell carcinoma of the vagina. However, to achieve these results, treatment must be individualized according to the site and size of the tumor at presentation and the response to initial external-beam radiation therapy. Brachytherapy

  12. SU-F-T-683: Cancer Stem Cell Hypothesis and Radiation Treatments

    International Nuclear Information System (INIS)

    Fourkal, E

    2016-01-01

    Purpose: The tumor control probability in radiation therapy allows comparing different radiation treatments to each other by means of calculating the probability that a prescribed dose of radiation eradicates or controls the tumor. In the conventional approach, all cancer cells can divide unlimited number of times and the tumor control often means eradicating every malignant cell by the radiation. In recent years however, there is a mounting consensus that in a given tumor volume there is a sub-population of cells, known as cancer stem cells (CSCs) that are responsible for tumor initiation and growth. Other or progenitor cancer cells can only divide limited number of times. This entails that only cancer stem cells may nned to be eliminated in order to control the tumor. Thus one may define TCP as the probability of eliminating CSCs for the given dose of radiation. Methods: Using stochastic methods, specifically the birth-and-death Markov processes, an infinite system of equations is set for probabilities of having m cancer stem cells at time t after the start of radiation. The TCP is calculated as the probability of no cancer stem cells surviving the radiation. Two scenarios are studied. In the first situation, the TCP is calculated for a unidirectional case when CSC gives birth to another CSC or a progenitor cell. In the second scenario, a bidirectional model is studied where the progenitor cell gives rise to CSC. Results: The proposed calculations show that the calculated TCP for CSC depends on whether one adopts unidirectional or bidirectional conversion models. The bidirectional model shows significantly lower TCP values for the given dose delivered to the tumor. Conclusion: Incorporating CSC hypothesis into the TCP modeling may notably influence the dose prescription as well as the concept of the expected TCP after the radiation treatments.

  13. SU-F-T-683: Cancer Stem Cell Hypothesis and Radiation Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Fourkal, E [Pinnacle Health Cancer Center, Harrisburg, PA (United States)

    2016-06-15

    Purpose: The tumor control probability in radiation therapy allows comparing different radiation treatments to each other by means of calculating the probability that a prescribed dose of radiation eradicates or controls the tumor. In the conventional approach, all cancer cells can divide unlimited number of times and the tumor control often means eradicating every malignant cell by the radiation. In recent years however, there is a mounting consensus that in a given tumor volume there is a sub-population of cells, known as cancer stem cells (CSCs) that are responsible for tumor initiation and growth. Other or progenitor cancer cells can only divide limited number of times. This entails that only cancer stem cells may nned to be eliminated in order to control the tumor. Thus one may define TCP as the probability of eliminating CSCs for the given dose of radiation. Methods: Using stochastic methods, specifically the birth-and-death Markov processes, an infinite system of equations is set for probabilities of having m cancer stem cells at time t after the start of radiation. The TCP is calculated as the probability of no cancer stem cells surviving the radiation. Two scenarios are studied. In the first situation, the TCP is calculated for a unidirectional case when CSC gives birth to another CSC or a progenitor cell. In the second scenario, a bidirectional model is studied where the progenitor cell gives rise to CSC. Results: The proposed calculations show that the calculated TCP for CSC depends on whether one adopts unidirectional or bidirectional conversion models. The bidirectional model shows significantly lower TCP values for the given dose delivered to the tumor. Conclusion: Incorporating CSC hypothesis into the TCP modeling may notably influence the dose prescription as well as the concept of the expected TCP after the radiation treatments.

  14. A mathematical correlation between variations in solar radiation parameters. 2. Global radiation, air temperature and specific humidity

    International Nuclear Information System (INIS)

    Njau, E.C.

    1988-06-01

    We derive from first principles, an equation which expresses global radiation as a function of specific humidity and air temperature at screen height. The practical validity of this equation is tested by using humidity, air temperature and global radiation data from Tanzania. It is shown that global radiation values calculated on the basis of the derived equation agree with measured radiation values to within ± 8% as long as the prevalent (horizontal) winds are either calm or light. It is noted that the equation is equally valid at times of strong horizontal winds provided that the temperature and humidity measuring site is sufficiently shielded from the winds. This implies that meteorological stations that are (for some unavoidable reasons) unable to stock pyranometers can still procure reasonable estimates of local global radiation as long as they can, at least, stock the relatively cheaper barometers and wet- and dry-bulb psychrometers. (author). 12 refs, 1 fig., 4 tabs

  15. 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)

  16. Radiation-induced cell death by chromatin loss

    International Nuclear Information System (INIS)

    Campbell, I.R.; Warenius, H.M.

    1989-01-01

    A model is proposed which relates reproductive death of cells caused by radiation to loss of chromatin at cell division. This loss of chromatin can occur through chromosomal deletions or through the formation of asymmetrical chromosomal exchanges. It is proposed that smaller doses of radiation produce fewer chromatin breaks, which are more likely to be accurately repaired, compared with larger doses. Consequently, smaller doses of radiation are less efficient in causing cell death, leading to a shoulder on the cell survival curve. Experimental evidence supports this model, and the fit between the derived formula and experimental cell survival curves is good. The derived formula approximates to the linear-quadratic equation at low doses of radiation. (author)

  17. 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

  18. Radiation Grafted Polymer Membranes for Fuel Cell Applications

    International Nuclear Information System (INIS)

    Scherer, G.G.; Wallasch, F.; Ben Youcef, H.; Gubler, L.

    2012-01-01

    Partially fluorinated proton exchange membranes prepared via radiation induced graft copolymerization ('radiation grafting') offer the prospect of cost-effective and tailor made membrane electrolytes for the polymer electrolyte fuel cell (PEFC). The composition and structure of radiation grafted membranes can be adjusted in a broad range to balance the different requirements of proton transport and mechanical robustness. Based on the earlier work on Styrene grafting, the novel monomer combination α-methyl-styrene/methacrylonitrile (AMS/MAN) is introduced for improved stability in the prevailing fuel cell environment. Successful fuel cell experiments proved the concept. (author)

  19. Radiation Grafted Polymer Membranes for Fuel Cell Applications

    Energy Technology Data Exchange (ETDEWEB)

    Scherer, G G; Wallasch, F; Ben Youcef, H; Gubler, L [Electrochemistry Laboratory, Paul Scherrer Institut, CH-5232 Villigen (Switzerland)

    2012-09-15

    Partially fluorinated proton exchange membranes prepared via radiation induced graft copolymerization ('radiation grafting') offer the prospect of cost-effective and tailor made membrane electrolytes for the polymer electrolyte fuel cell (PEFC). The composition and structure of radiation grafted membranes can be adjusted in a broad range to balance the different requirements of proton transport and mechanical robustness. Based on the earlier work on Styrene grafting, the novel monomer combination {alpha}-methyl-styrene/methacrylonitrile (AMS/MAN) is introduced for improved stability in the prevailing fuel cell environment. Successful fuel cell experiments proved the concept. (author)

  20. Primary radiation damage and disturbance in cell divisions

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Lee, Yun-Jong; Kim, Jae-Hun; Petin, Vladislav G.; Nili, Mohammad

    2008-01-01

    Survived cells from a homogeneous population exposed to ionizing radiation form various colonies of different sizes and morphology on a solid nutrient medium, which appear at different time intervals after irradiation. Such a phenomenon agrees well with the modern theory of microdosimetry and classical hit-and-target models of radiobiology. According to the hit-principle, individual cells exposed to the same dose of radiation are damaged in different manners. It means that the survived cells can differ in the content of sublethal damage (hits) produced by the energy absorbed into the cell and which is not enough to give rise to effective radiation damage which is responsible for cell killing or inactivation. In diploid yeast cells, the growth rate of cells from 250 colonies of various sizes appeared at different time intervals after irradiation with 600 Gy of gamma radiation from a 60 Co isotopic source was analyzed. The survival rate after irradiation was 20%. Based on the analyses results, it was possible to categorize the clones grown from irradiated cells according to the number of sub-lesions from 1 to 4. The clones with various numbers of sub-lesions were shown to be different in their viability, radiosensitivity, sensitivity to environmental conditions, and the frequency of recombination and respiratory deficient mutations. Cells from unstable clones exhibited an enhanced radiosensitivity, and an increased portion of morphologically changed cells, nonviable cells and respiration mutants, as well. The degree of expression of the foregoing effects was higher if the number of primary sublethal lesions was greater in the originally irradiated cell. Disturbance in cell division can be characterized by cell inactivation or incorrect distribution of mitochondria between daughter cells. Thus, the suggested methodology of identification of cells with a definite number of primary sublethal lesions will promote further elucidation of the nature of primary radiation

  1. 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.

  2. Mucorales-Specific T Cells in Patients with Hematologic Malignancies

    OpenAIRE

    Potenza, L; Vallerini, D; Barozzi, P; Riva, G; Gilioli, A; Forghieri, F; Candoni, A; Cesaro, S; Quadrelli, C; Maertens, J; Rossi, G; Morselli, M; Codeluppi, M; Mussini, C; Colaci, E

    2016-01-01

    Background Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. Method...

  3. Cell Type-Specific Contributions to the TSC Neuropathology

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0415 TITLE: Cell Type-Specific Contributions to the TSC Neuropathology PRINCIPAL INVESTIGATOR: Gabriella D’Arcangelo...AND SUBTITLE Cell Type-Specific Contributions to the TSC Neuropathology 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0415 5c. PROGRAM...how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells , in vivo

  4. 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

  5. Air pollution radiative forcing from specific emissions sectors at 2030

    Science.gov (United States)

    Unger, Nadine; Shindell, Drew T.; Koch, Dorothy M.; Streets, David G.

    2008-01-01

    Reduction of short-lived air pollutants can contribute to mitigate global warming in the near-term with ancillary benefits to human health. However, the radiative forcings of short-lived air pollutants depend on the location and source type of the precursor emissions. We apply the Goddard Institute for Space Studies atmospheric composition-climate model to quantify near-future (2030 A1B) global annual mean radiative forcing by ozone (O3) and sulfate from six emissions sectors in seven geographic regions. At 2030 the net forcings from O3, sulfate, black and organic carbon, and indirect CH4 effects for each emission sector are (in mWm-2) biomass burning, +95; domestic, +68; transportation, +67; industry, -131; and power, -224. Biomass burning emissions in East Asia and central and southern Africa, domestic biofuel emissions in East Asia, south Asia, and central and southern Africa, and transportation emissions in Europe and North America have large net positive forcings and are therefore attractive targets to counter global warming. Power and industry emissions from East Asia, south Asia, and north Africa and the Middle East have large net negative forcings. Therefore air quality control measures that affect these regional sectors require offsetting climate measures to avoid a warming impact. Linear relationships exist between O3 forcing and biomass burning and domestic biofuel CO precursor emissions independent of region with sensitivity of +0.2 mWm-2/TgCO. Similarly, linear relationships exist between sulfate forcing and SO2 precursor emissions that depend upon region but are independent of sector with sensitivities ranging from -3 to -12 mWm-2/TgS.

  6. Immobilization of Trichoderma reesei cells by radiation polymerization

    International Nuclear Information System (INIS)

    Kumakura, M.; Kaetsu, I.

    1983-01-01

    Trichoderma reesei cells were immobilized by radiation polymerization 2-hydroxyethyl acrylate monomer at low temperature. Cellulase production resulting from the growth of the cells in the porous polymer matrix of immobilized cell composites was confirmed by measuring the cellulase activity and pH during the culture. (orig.)

  7. 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.)

  8. Tumourigenicity and radiation resistance of mesenchymal stem cells.

    Science.gov (United States)

    D'Andrea, Filippo P; Horsman, Michael R; Kassem, Moustapha; Overgaard, Jens; Safwat, Akmal

    2012-05-01

    Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under nontreated and irradiated conditions, were assessed with microarrays (Affymetrix Human Exon 1.0 ST array). The cellular functions affected by the altered gene expressions were assessed through gene pathway mapping (Ingenuity Pathway Analysis). Based on the clonogenic assay the nontumourigenic cell line was found to be more sensitive to radiation than the tumourigenic cell line. Using the exon chips, 297 genes were found altered between untreated samples of the cell lines whereas only 16 genes responded to radiation treatment. Among the genes with altered expression between the untreated samples were PLAU, PLAUR, TIMP3, MMP1 and LOX. The pathway analysis based on the alteration between the untreated samples indicated cancer and connective tissue disorders. This study has shown possible common genetic events linking tumourigenicity and radiation response. The PLAU and PLAUR genes are involved in apoptosis evasion while the genes TIMP3, MMP1 and LOX are involved in regulation of the surrounding matrix. The first group may contribute to the difference in radiation resistance observed and the latter could be a major contributor to the tumourigenic capabilities by degrading the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin.

  9. DNA from radiation resistant human tumor cells transfers resistance to NIH/3T3 cells with varying degrees of penetrance

    International Nuclear Information System (INIS)

    Kasid, U.; Dritschilo, A.; Weichselbaum, R.

    1987-01-01

    Experimental evidence suggests that clinical radiation resistance may correlate with in vitro radiation survival parameters. Specifically, they isolated several cell lines from radioresistant head and neck carcinomas with D/sub 0/ values greater than 2 Gy. The authors co-transfected DNA from cell line SQ2OB (D/sub 0/ = 2.4 Gy) with the rhoSVNeO plasmid into NIH/3T3 cells (D/sub 0/ = 1.7 Gy). Antibiotic G418 resistant, transformed clones were isolated and confirmed by Southern blotting to contain human alu, as well as rhoSVNeO sequences. Screening for radiation resistance with 8Gy (Cs-137) revealed that 3 of 4 tested hybrid clones show a radiation survival intermediate between NIH/3T3 and SQ2OB. This suggests that radiation resistance is a dominant, transfectable phenotype of mammalian cells and can be expressed in more sensitive cells. Karyotyping of resistant hybrid clones shows the presence of double minute chromosomes. Secondary transfection results and experiments to clone the genetic factors responsible for radiation resistance are in progress and results will be reported

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

    International Nuclear Information System (INIS)

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

    1997-01-01

    For REC:myc(ch1), Rat1 and Rat1:myc b cells, we determined the events in the development of radiation-induced apoptosis to be in the following order: cell division followed by chromatin condensation, membrane blebbing, loss of adhesion and the uptake of vital dye. Experimental data which were obtained using 4 He ions of well defined energies and which compared the dependence of apoptosis and clonogenic survival on 4 He range strongly suggested that in our cells both apoptosis and loss of clonogenic survival resulted from radiation damage to the cell nucleus. Corroboratory evidence was that BrdU incorporation sensitized these cells to radiation-induced apoptosis. Comparing the dose response for apoptosis and the clonogenic survival curves for Rat1 and Rat1:myc b cells, we concluded that radiation-induced cell inactivation as assayed by clonogenic survival, and that a modified linear-quadratic model, proposed previously, modeled such a contribution effectively. In the same context, the selective increase in radiation-induced apoptosis. Comparing the dose response for apoptosis and the clonogenic survival curves for Rat1 and Rat1:myc b cells, we concluded that radiation-induced apoptosis contributed to the overall radiation-induced cell inactivation as assayed by clonogenic survival, and that a modified linear-quadratic model, proposed previously, modeled such a contribution effectively. In the same context, the selective increase in radiation-induced apoptosis during late S and G 2 phases reduced the relative radioresistance observed for clonogenic survival during late S and G 2 phases. 30 refs., 8 figs

  11. Tissue specific heterogeneity in effector immune cell response

    Directory of Open Access Journals (Sweden)

    Saba eTufail

    2013-08-01

    Full Text Available Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct ‘homing codes’ (adhesion molecules and chemokine receptors during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A and sunlight (vitamin D3 prime dendritic cells, imprinting them to play centrestage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues alongwith giving an overview of tissue tropism in B cells.

  12. Mucorales-Specific T Cells in Patients with Hematologic Malignancies.

    Science.gov (United States)

    Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Gilioli, Andrea; Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Lewis, Russell E; Luppi, Mario

    2016-01-01

    Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

  13. Mucorales-Specific T Cells in Patients with Hematologic Malignancies.

    Directory of Open Access Journals (Sweden)

    Leonardo Potenza

    Full Text Available Invasive mucormycosis (IM is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients.By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3% of 204 patients, accounting for 32 (5.3% of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD, showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD: 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD.Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

  14. In vitro assays for predicting tumor cell response to radiation by apoptotic pathways

    International Nuclear Information System (INIS)

    Algan, Oe.; Hanks, G.E.; Biade, S.; Chapman, J.D.

    1995-01-01

    were detected by gel electrophoresis procedures but this technique is laborious and difficult to quantify. Centrifugation procedures of irradiation cells which had been pre-labeled with 3 H-thymidine showed ∼18% of total cellular DNA to be fragmented within 12 hr, after which time the extent of DNA fragmentation plateaued. The labeling of 3'-OH ends in cellular DNA by the immunofluorescence reagent, ApopTag[reg], showed ∼15% of cells to undergo apoptotic degradation. Staining of irradiated cells with LIVE/DEAD[reg] EUKOLIGHT TM and trypan blue showed 20-25% cell death. Although the vital stain assays are not specific for apoptosis, the proportion of rapid cell death (within 24-48 hr) which they measure is close to that obtained with the apoptotic-specific assays. These studies indicate that 24 hr after irradiation with 10 Gy, approximately 20% of DU-145 cells undergo death by apoptosis. Survival curves constructed with different radiation doses indicate that this rapid mechanism of cell death follows single-hit kinetics and constitutes between 10-30% of the total α coefficient measured by clonogenic assays with this cell line. Conclusion: Two phases of cell death are observed after ionizing radiation of the DU-145 prostate cancer cell line. Rapid cell death occurs within ∼24 hr and appears to correlate with apoptotic cell death. The vital stains, LIVE/DEAD[reg] EUKOLIGHT TM and trypan blue, yield quantitatively similar estimates of rapid cell killing to the apoptosis-specific assays. We are currently extending these studies to other human prostate tumor cell lines and to tumor cells released from human prostate biopsies. Such assays may provide additional prognostic information for predicting radiotherapy outcome of patients receiving radiotherapy

  15. RNAi screen reveals host cell kinases specifically involved in Listeria monocytogenes spread from cell to cell.

    Directory of Open Access Journals (Sweden)

    Ryan Chong

    Full Text Available Intracellular bacterial pathogens, such as Listeria monocytogenes and Rickettsia conorii display actin-based motility in the cytosol of infected cells and spread from cell to cell through the formation of membrane protrusions at the cell cortex. Whereas the mechanisms supporting cytosolic actin-based motility are fairly well understood, it is unclear whether specific host factors may be required for supporting the formation and resolution of membrane protrusions. To address this gap in knowledge, we have developed high-throughput fluorescence microscopy and computer-assisted image analysis procedures to quantify pathogen spread in human epithelial cells. We used the approach to screen a siRNA library covering the human kinome and identified 7 candidate kinases whose depletion led to severe spreading defects in cells infected with L. monocytogenes. We conducted systematic validation procedures with redundant silencing reagents and confirmed the involvement of the serine/threonine kinases, CSNK1A1 and CSNK2B. We conducted secondary assays showing that, in contrast with the situation observed in CSNK2B-depleted cells, L. monocytogenes formed wild-type cytosolic tails and displayed wild-type actin-based motility in the cytosol of CSNK1A1-depleted cells. Furthermore, we developed a protrusion formation assay and showed that the spreading defect observed in CSNK1A1-depleted cells correlated with the formation of protrusion that did not resolve into double-membrane vacuoles. Moreover, we developed sending and receiving cell-specific RNAi procedures and showed that CSNK1A was required in the sending cells, but was dispensable in the receiving cells, for protrusion resolution. Finally, we showed that the observed defects were specific to Listeria monocytogenes, as Rickettsia conorii displayed wild-type cell-to-cell spread in CSNK1A1- and CSNK2B-depleted cells. We conclude that, in addition to the specific host factors supporting cytosolic actin

  16. Ionizing radiation sensitivity of DNA polymerase lambda-deficient cells.

    NARCIS (Netherlands)

    Vermeulen, C.; Bertocci, B.; Begg, A.C.; Vens, C.

    2007-01-01

    Ionizing radiation induces a diverse spectrum of DNA lesions, including strand breaks and oxidized bases. In mammalian cells, ionizing radiation-induced lesions are targets of non-homologous end joining, homologous recombination, and base excision repair. In vitro assays show a potential involvement

  17. Membrane phospholipids and radiation-induced death of mammalian cells

    International Nuclear Information System (INIS)

    Wolters, H.

    1987-01-01

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

  18. Open cell conducting foams for high synchrotron radiation accelerators

    Directory of Open Access Journals (Sweden)

    S. Petracca

    2014-08-01

    Full Text Available The possible use of open cell conductive foams in high synchrotron radiation particle accelerators is considered. Available materials and modeling tools are reviewed, potential pros and cons are discussed, and preliminary conclusions are drawn.

  19. Engineering hot-cell windows for radiation protection

    International Nuclear Information System (INIS)

    Ferguson, K.R.; Courtney, J.C.

    1983-01-01

    Radiation protection considerations in the design and construction of hot-cell windows are discussed. The importance of evaluating the potential gamma spectra and neutron source terms is stressed. 11 references

  20. Single-hit mechanism of tumour cell killing by radiation.

    Science.gov (United States)

    Chapman, J D

    2003-02-01

    To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells

  1. Low dose ionizing radiation responses and knockdown of ATM kinase activity in glioma stem cells

    International Nuclear Information System (INIS)

    Lim, Y.C.; Roberts, T.; Day, B.; Kozlov, S.; Walker, D.; Lavin, M.; Harding, A.

    2009-01-01

    Genesis of new cells in the mammalian brain has previously been regarded as a negligible event; an assumption that long limited our understanding in the development of neoplasias. The recent discovery of perpetual lineages derived from neural stem cells has resulted in a new approach to studying the cellular behaviour of potential cancer stem cells in the brain. Glioblastoma multiforme (GBM), the most aggressive and lethal brain tumour is derived from a group of cancerous stem cells known as glioma stem cells. GBM cells are impervious to conventional therapies such as surgical resection and ionizing radiation because of their pluripotent and radioresistant properties. Thus in our study, we aim to investigate whether a combination of chemo- and radio- therapies is an effective treatment for glioma stem cells. The study utilizes a specific kinase inhibitor (ATMi) of the ATM (Ataxia-telangiectasia mutated) protein which is an essential protein in DNA-damage responses. In the presence of both low dose radiation and ATMi, glioma stem cells have rapid onset of cell death and reduction in growth. Since DNA damage can be inherited through cell division, accumulated DNA breaks in later generations may also lead to cell death. The limitation of conventional radiation therapy is that administration of fractionated (low) doses to reduce any potential harm to the surrounding healthy cells in the brain outweighs the benefits of high radiation doses to induce actual arrest in the propagation of malignant cells. Our study demonstrates a benefit in using low dose radiation combined with chemotherapy resulting in a reduction in malignancy of glioma stem cells. (author)

  2. Effects of long-term low dose radiation. Epstein-Barr virus-specific antibodies in radiological technologists

    Energy Technology Data Exchange (ETDEWEB)

    Kumagai, Etsuko; Higashida, Yoshiharu; Onomichi, Mitsukazu; Nakamura, Ikuo; Tanoue, Shozo; Tanaka, Ryuji; Kumagai, Takashi; Katsuki, Takato; Sawada, Shozo.

    1988-09-01

    To clarify the long-term effects of occupational exposure to low doses of radiation, Epstein-Barr virus (EBV)-specific antibody titers in sera from 104 radiological technologists (R.T.) and 118 controls in Kumamoto prefecture were measured by the immunofluorescence method. Antibody titers to viral capsid antigen (VCA)-IgG increased with the years of experience as R.T., and the prevalence of abnormal antibody titers to both VCA-IgG and early antigen (EA)-IgG were significantly higher in R.T. with over 15 years of experience or 30 rads of cumulative radiation dose than in the controls. However, there was no correlation between exposure and the frequency of abnormal EBV-associated nuclear antigen (EBNA) antibody titers. The EBV-specific antibody titers of 24 Hiroshima atomic-bomb survivors were also measured. They were similar to those of the R.T. with over 30 years of experience. The EBV-specific antibody titers of R.T. suggest that there may be an impairment of immunologic competence after continuous long-term exposure to low doses of radiation. Also, the correlation of EBV-specific antibody titers and frequency of cells with chromosome aberrations in 53 R.T. was studied. Some correlations were found between the antibody titers to both of the VCA-IgG and EBNA and the frequency of cells with chromosome aberrations.

  3. Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis

    International Nuclear Information System (INIS)

    Marini, Patrizia; Schmid, Angelika; Jendrossek, Verena; Faltin, Heidrun; Daniel, Peter T; Budach, Wilfried; Belka, Claus

    2005-01-01

    TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. Tumour cell systems derived from breast- (MDA MB231), lung- (NCI H460) colorectal- (Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor

  4. Angiocrine functions of organ-specific endothelial cells

    Science.gov (United States)

    Rafii, Shahin; Butler, Jason M; Ding, Bi-Sen

    2016-01-01

    Preface Endothelial cells lining blood vessel capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establish specialized vascular niches that deploy specific sets of growth factors, known as angiocrine factors, which actively participate in inducing, specifying, patterning, and guiding organ regeneration and maintaining homeostasis and metabolism. Angiocrine factors upregulated in response to injury orchestrates self-renewal and differentiation of tissue-specific repopulating resident stem and progenitor cells into functional organs. Uncovering the precise mechanisms whereby physiological-levels of angiocrine factors are spatially and temporally produced, and distributed by organotypic endothelium to repopulating cells, will lay the foundation for driving organ repair without scarring. PMID:26791722

  5. A system of radiation monitoring, and methods and equipment for measuring water of low specific activity

    International Nuclear Information System (INIS)

    Sivintsev, Yu.V.

    1975-01-01

    The author considers criteria for the radiation protection of the population and the environment. He describes the role of procedures for monitoring waters of low specific activity in the framework of a system for ensuring the radiation safety of the population living near a nuclear power station. The main technical characteristics (background, efficiency, sensitivity) of the laboratory equipment for gamma spectrometric analysis of water samples of low specific activity are discussed. (author)

  6. Final report of the specific research. Investigations on the analysis of bio-protective factors against radiation. 1998-2000 FY (Research Group of NIRS)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-03-01

    This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and published original articles are also given. (N.I.)

  7. Final report of the specific research. Investigations on the analysis of bio-protective factors against radiation. 1998-2000 FY (Research Group of NIRS)

    International Nuclear Information System (INIS)

    2002-03-01

    This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK cs ), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and published original articles are also given. (N.I.)

  8. Immobilization of yeast cells by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Fujimura, T.; Kaetsu, I.

    1982-01-01

    Radiation-induced polymerization method was applied to the immobilization of yeast cells. The effects of irradiation, cooling and monomer, which are neccessary for polymerization, were recovered completely by subsequent aerobical incubation of yeast cells. The ethanol productive in immobilized yeast cells increased with the increase of aerobical incubation period. The growth of yeast cells in immobilized yeast cells was indicated. The maximum ethanol productivity in immobilized yeast cell system was around three times as much as that in free yeast cell system. (orig.)

  9. Effects of combined radiofrequency radiation exposure on levels of reactive oxygen species in neuronal cells

    International Nuclear Information System (INIS)

    Kang, Kyoung Ah; Lee, Hyung Chul; Lee, Je-Jung

    2014-01-01

    The objective of this study was to investigate the effects of the combined RF radiation (837 MHz CDMA plus 1950 MHz WCDMA) signal on levels of intracellular reactive oxygen species (ROS) in neuronal cells. Exposure of the combined RF signal was conducted at specific absorption rate values of 2 W/kg of CDMA plus 2 W/kg of WCDMA for 2 h. Co-exposure to combined RF radiation with either H 2 O 2 or menadione was also performed. The experimental exposure groups were incubator control, sham-exposed, combined RF radiation-exposed with or without either H 2 O 2 or menadione groups. The intracellular ROS level was measured by flow cytometry using the fluorescent probe dichlorofluorescein diacetate. Intracellular ROS levels were not consistently affected by combined RF radiation exposure alone in a time-dependent manner in U87, PC12 or SH-SY5Y cells. In neuronal cells exposed to combined RF radiation with either H 2 O 2 or menadione, intracellular ROS levels showed no statically significant alteration compared with exposure to menadione or H 2 O 2 alone. These findings indicate that neither combined RF radiation alone nor combined RF radiation with menadione or H 2 O 2 influences the intracellular ROS level in neuronal cells such as U87, PC12 or SH-SY5Y. (author)

  10. Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells

    International Nuclear Information System (INIS)

    Murakami, Sho; Yoshino, Hironori; Ishikawa, Junya; Yamaguchi, Masaru; Tsujiguchi, Takakiyo; Nishiyama, Ayaka; Yokoyama, Kouki; Kashiwakura, Ikuo

    2015-01-01

    Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E–mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell–related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E–mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells. (author)

  11. 1950MHz Radio Frequency Electromagnetic Radiation Inhibits Testosterone Secretion of Mouse Leydig Cells.

    Science.gov (United States)

    Lin, Yan-Yun; Wu, Tao; Liu, Jun-Ye; Gao, Peng; Li, Kang-Chu; Guo, Qi-Yan; Yuan, Meng; Lang, Hai-Yang; Zeng, Li-Hua; Guo, Guo-Zhen

    2017-12-23

    More studies that are focused on the bioeffects of radio-frequency (RF) electromagnetic radiation that is generated from the communication devices, but there were few reports with confirmed results about the bioeffects of RF radiation on reproductive cells. To explore the effects of 1950 MHz RF electromagnetic radiation (EMR) on mouse Leydig (TM3) cells. TM3 cells were irradiated or sham-irradiated continuously for 24 h by the specific absorption rate (SAR) 3 W/kg radiation. At 0, 1, 2, 3, 4, and 5 days after irradiation, cell proliferation was detected by cell counting kit-8 (CCK-8) method, cell cycle distribution, percentage of apoptosis, and cellular reactive oxygen species (ROS) were examined by flow cytometry, Testosterone level was measured using enzyme-linked immunosorbent assay (ELISA) assay, messenger ribonucleic acid (mRNA) expression level of steroidogenic acute regulatory protein (StAR) and P450scc in TM3 cells was detected by real-time polymerase chain reaction (PCR). After being irradiated for 24 h, cell proliferation obviously decreased and cell cycle distribution, secretion capacity of Testosterone, and P450scc mRNA level were reduced. While cell apoptosis, ROS, and StAR mRNA level did not change significantly. The current results indicated that 24 h of exposure at 1950 MHz 3 W/kg radiation could cause some adverse effects on TM3 cells proliferation and Testosterone secretion, further studies about the biological effects in the reproductive system that are induced by RF radiation are also needed.

  12. Cybernetical investigations on the radiation effects on tumour cells

    International Nuclear Information System (INIS)

    Iliakis, G.

    1978-01-01

    The goal of this work was to find suitable conditions for the in-vitro investigations with these E.A.T. cells so that basic experiments carried out with yeast cells will also be possible. Systematic investigations on cell multiplication led to reliable and definite test conditions for these cells. For the evaluation of the data which had been measured with several sorts of radiation the cybernetic model was applied. (orig./MG) [de

  13. Squamous cell carcinoma following radiation therapy for the infiltrative thymoma

    International Nuclear Information System (INIS)

    Ozawa, Shinji; Kitao, Takeshi

    1992-01-01

    This report represents one case of infiltrative thymoma followed by squamous cell carcinoma of the lungs. A 69-year-old man suffered from infiltrative thymoma which reduced by the radiation therapy. Seven years later its replase and the onset of squamous cell carcinoma were found simultaneously. Infiltrative thymoma metastasized not only to the mediastinum but also to the liver and bronchus. Squamous cell carcinoma developed in the right upper lobe. In spite of chemotherapy against them, the patient died. There are many cases in which infiltrative thymoma is accompanied by squamous cell carcinoma of the lung simultaneously; however, secondary onset of squamous cell carcinoma after the radiation therapy of infiltrative thymoma is rare. Secondary carcinogenesis of this case was considered to be closely related with immunological abnormalities caused by thymoma, effects of radiation, smoking and so on. (author)

  14. 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.

  15. Models relevant to radiation effects on stem cell pools

    Energy Technology Data Exchange (ETDEWEB)

    Lajtha, L G

    1971-04-01

    regeneration of haemopoiesis. There is no information available to indicate what regulates the differentiation of the primitive CFU into the ERC or other similar precursor populations. There is also no clear or unequivocal evidence which could indicate whether the ERC and the potential GRC are different or related to each other. There is no information available on a committed precursor population for the thrombocytic series of cells. There is, however, evidence in the small rodent that the potential focus-forming cells detected by immunological methods may represent a precursor population, specific for future antibody-producing cells. The mechanisms involved in the 'second step' differentiation, e.g. that of the ERC into the erythron, are beginning to be understood and it is clear that humoral factors, e.g. erythropoietin, are involved. There is also increasing evidence for the existence of a humoral thrombopoietic factor, although no clear evidence is yet available regarding the existence of a 'granulopoietin'. The outstanding problem at the moment is to understand the mechanisms regulating the differentiation of the CFU into the precursor populations and the nature of the control of the population size of the CFU population itself. Understanding and eventual manipulation of these two phenomena would greatly enhance our capacity in modifying radiation damage to haemopoietic tissues.

  16. Ionizing radiation induces PI3K-dependent JNK activation for amplifying mitochondrial dysfunction in human cervical cancer cells

    International Nuclear Information System (INIS)

    Kim, Min Jung; Choi, Soon Young; Bae, Sang Woo; Kang, Chang Mo; Lee, Yun Sil; Lee, Su Jae

    2005-01-01

    Ionizing radiation is one of the most commonly used treatments for a wide variety of tumors. Exposure of cells to ionizing radiation results in the simultaneous activation or down regulation of multiple signaling pathways, which play critical role in controlling cell death and cell survival after irradiation in a cell type specific manner. The molecular mechanism by which apoptotic cell death occurs in response to ionizing radiation has been widely explored but not precisely deciphered. Therefore an improved understanding of the mechanisms involved in radiation-induced apoptosis may ultimately provide novel strategies of intervention in specific signal transduction pathways to favorably alter the therapeutic ratio in the treatment of human malignancies. The aim of our investigation was to elucidate molecular mechanisms of the mitochondrial dysfunction mediated apoptotic cell death triggered by ionizing radiation in human cervical cancer cells. We demonstrated that ionizing radiation utilizes PI3K-JNK signaling pathway for amplifying mitochondrial dysfunction and susequent apoptotic cell death: We showed that PI3K-dependent JNK activation leads to transcriptional upregulation of Fas and the phosphorylation/inactivation of Bcl-2, resulting in mitochondrial dysfunction-mediated apoptotic cell death in response to ionizing radiation

  17. Surface-modified gold nanorods for specific cell targeting

    Science.gov (United States)

    Wang, Chan-Ung; Arai, Yoshie; Kim, Insun; Jang, Wonhee; Lee, Seonghyun; Hafner, Jason H.; Jeoung, Eunhee; Jung, Deokho; Kwon, Youngeun

    2012-05-01

    Gold nanoparticles (GNPs) have unique properties that make them highly attractive materials for developing functional reagents for various biomedical applications including photothermal therapy, targeted drug delivery, and molecular imaging. For in vivo applications, GNPs need to be prepared with very little or negligible cytotoxicitiy. Most GNPs are, however, prepared using growth-directing surfactants such as cetyl trimethylammonium bromide (CTAB), which are known to have considerable cytotoxicity. In this paper, we describe an approach to remove CTAB to a non-toxic concentration. We optimized the conditions for surface modification with methoxypolyethylene glycol thiol (mPEG), which replaced CTAB and formed a protective layer on the surface of gold nanorods (GNRs). The cytotoxicities of pristine and surface-modified GNRs were measured in primary human umbilical vein endothelial cells and human cell lines derived from hepatic carcinoma cells, embryonic kidney cells, and thyroid papillary carcinoma cells. Cytotoxicity assays revealed that treating cells with GNRs did not significantly affect cell viability except for thyroid papillary carcinoma cells. Thyroid cancer cells were more susceptible to residual CTAB, so CTAB had to be further removed by dialysis in order to use GNRs for thyroid cell targeting. PEGylated GNRs are further modified to present monoclonal antibodies that recognize a specific surface marker, Na-I symporter, for thyroid cells. Antibody-conjugated GNRs specifically targeted human thyroid cells in vitro.

  18. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke

    2011-01-01

    of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system....

  19. Osteocalcin and bone-specific alkaline phosphatase in Sickle cell ...

    African Journals Online (AJOL)

    specific alkaline phosphatase (b-AP) total protein levels were evaluated as indicators of bone turnover in twenty patients with sickle cell haemoglobinopathies and in twenty normal healthy individuals. The serum bonespecific alkaline phosphatase ...

  20. Target-specific delivery of doxorubicin to human glioblastoma cell ...

    Indian Academy of Sciences (India)

    Abdullah Tahir Bayraç

    2018-01-29

    Jan 29, 2018 ... was previously selected for specific recognition of glioblastoma and represented many advantageous ... antigens, receptors or any 3-D structure on the target cells ..... both PSMA (?) and PSMA (-) prostate cancers.

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  2. Birthdating studies reshape models for pituitary gland cell specification.

    Science.gov (United States)

    Davis, Shannon W; Mortensen, Amanda H; Camper, Sally A

    2011-04-15

    The intermediate and anterior lobes of the pituitary gland are derived from an invagination of oral ectoderm that forms Rathke's pouch. During gestation proliferating cells are enriched around the pouch lumen, and they appear to delaminate as they exit the cell cycle and differentiate. During late mouse gestation and the postnatal period, anterior lobe progenitors re-enter the cell cycle and expand the populations of specialized, hormone-producing cells. At birth, all cell types are present, and their localization appears stratified based on cell type. We conducted a birth dating study of Rathke's pouch derivatives to determine whether the location of specialized cells at birth is correlated with the timing of cell cycle exit. We find that all of the anterior lobe cell types initiate differentiation concurrently with a peak between e11.5 and e13.5. Differentiation of intermediate lobe melanotropes is delayed relative to anterior lobe cell types. We discovered that specialized cell types are not grouped together based on birth date and are dispersed throughout the anterior lobe. Thus, the apparent stratification of specialized cells at birth is not correlated with cell cycle exit. Thus, the currently popular model of cell specification, dependent upon timing of extrinsic, directional gradients of signaling molecules, needs revision. We propose that signals intrinsic to Rathke's pouch are necessary for cell specification between e11.5 and e13.5 and that cell-cell communication likely plays an important role in regulating this process. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Radiation effect on oligodendroglial lineage cells of brain

    International Nuclear Information System (INIS)

    Yu Dahai; Tianye

    2009-01-01

    Radiotherapy is a important treatment method for primary and metastatic cancers in the brain. How-ever, a high dose of radiation always leads to the brain injury. A representative pathological manifest of the radiation-induced brain impairment is demyelination. Therefore oligodendrocytes, the myelin-forming cells in the central nervous system, have been focused more attention recently. Oligodendrocytes originate from the migratory, mitotic progenitors and mature progressively into postmitotic myelinating cells. Recent years, a series of studies have been initiated to address the role of oligodendrocyte lineage cells in radiation-induced neurotoxic processes. This article pays attention to these studies, aiming to explore mechanisms of the radiation-induced brain impairment. (authors)

  4. Dissection of T-cell antigen specificity in human melanoma

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Albæk Thrue, Charlotte; Junker, Niels

    2012-01-01

    Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-as...... from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined....

  5. [Specification of cell destiny in early Caenorhabditis elegans embryo].

    Science.gov (United States)

    Schierenberg, E

    1997-02-01

    Embryogenesis of the nematode Caenorhabditis elegans has been described completely on a cell-by-cell basis and found to be essentially invariant. With this knowledge in hands, micromanipulated embryos and mutants have been analyzed for cell lineage defects and the distribution of specific gene products. The results challenge the classical view of cell-autonomous development in nematodes and indicate that the early embryo of C. elegans is a highly dynamic system. A network of inductive events between neighboring cells is being revealed, which is necessary to assign different developmental programs to blastomeres. In those cases where molecules involved in these cell-cell interactions have been identified, homologies to cell surface receptors, ligands and transcription factors found in other systems have become obvious.

  6. Ionizing radiation induces senescence and differentiation of human dental pulp stem cells.

    Science.gov (United States)

    Havelek, R; Soukup, T; Ćmielová, J; Seifrtová, M; Suchánek, J; Vávrová, J; Mokrý, J; Muthná, D; Řezáčová, M

    2013-01-01

    Head and neck cancer is one of the most common cancers in Europe. Many current anti-cancer treatments, including ionizing radiation, induce apoptosis via DNA damage. Unfortunately, such treatments are non-selective to cancer cells and produce similar toxicity in normal cells, including adult stem cells. One of the fundamental properties of an adult stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. However, under certain stimuli, unspecialized adult stem cells can give rise to specialized cells to generate replacements for cells that are lost during one's life or due to injury or disease. Nevertheless, specialization of stem cells must be controlled by specific milieu and also initiated at the proper time, making the entire process beneficial for tissue recovery and maintaining it for a long time. In this paper we assess whether irradiated dental pulp stem cells have maintained open their options to mature into specialized cells, or whether they have lost their unspecialized (immature) state following irradiation. Our findings showed radiation-induced premature differentiation of dental pulp stem cells towards odonto-/osteoblast lineages in vitro. Matrix calcification was visualized from Day 6 or Day 9 following irradiation of cells expressing low or high levels of CD146, respectively.

  7. Remarks on the radiation chemistry of radiation damage in cells

    International Nuclear Information System (INIS)

    Powers, E.L.

    1975-01-01

    Several models of the actions of compounds that sensitize cells to x-irradiation are reviewed and commented on. The electron sequestration model is described in detail and typical experimental results upon which it is based are reviewed. The varieties of responses induced by a number of sensitizers and their antagonists are stressed; there is no single, simple chemical explanation that can account for all the results. However, the importance of the e - /sub aq/ -- .OH relation is evident in all the experimental results with the compounds tested to date

  8. Radiation sensitization studies by silymarin on HCT-15 cells

    International Nuclear Information System (INIS)

    Lal, Mitu; Gupta, Damodar; Arora, R.

    2014-01-01

    Radiotherapy has been widely used for treatment of human cancers. However, cancer cells develop radioresistant phenotypes following multiple exposures to the treatment agent that decrease the efficacy of radiotherapy. Here it was investigated that the radiation sensitization effects of silymarin found in colon cancer. The aim of this study was to investigate mechanisms involved in radiation sensitization growth inhibitory effect of silymarin in combination with radiation, in Human colon carcinoma (HCT-15). The human colon carcinoma was utilized and SRB-assay was performed to study anti-proliferative effect of silymarin in combination with gamma radiation (2 Gy) appropriate radiation dose was optimized and confirmed by clonogenic assay. Microscopic analysis was done by staining with Hoechst-33342, DAPI, Propidium iodide to confirm the presence of apoptosis. Nitric oxide production, changes in lipid peroxidation, Cell cycle analysis were carried out and mitochondrial membrane potential was measured by uptake of cationic dye JC-1 by using flow cytometer. Silymarin in combination with radiation (2 Gy) inhibited 70% ± 5% population growth of HCT-15 cells in time and dose dependent manner. Pre treatment of cells with silymarin for 30 min before radiation was found to be most effective for radiation sensitization. There was 25% increase in levels of nitric oxide as compare to control, whereas 2.5 fold change in lipid peroxidation with respect to control. IR-induced apoptosis in HCT-15 cell line was significantly enhanced by silymarin, as reflected by viability, DNA fragmentation, and mitochondrial dysfunction. Additionally, silymarin in combination with IR is found to be effective in sensitization of HCT-15 cells. In vivo studies on development of tumor and sensitization aspects needs to done in future. (author)

  9. Determining T-cell specificity to understand and treat disease

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker; Newell, Evan W.

    2017-01-01

    Adaptive immune responses and immunopathogeneses are based on the ability of T cells to respond to specific antigens. Consequently, understanding T-cell recognition patterns in health and disease involves studying the complexity and genetic heterogeneity of the antigen recognition pathway, which...

  10. Radiation related basic cancer research : research for radiation induced tumor cell killing

    International Nuclear Information System (INIS)

    Lee, Seung Hoon; Hong, Seok Il; Cho, Kyung Ja; Kim, Byung Gi; Lee, Kee Ho; Nam, Myung Jin

    1999-04-01

    The radioresistant clones was established from human U251 glioblastoma cell line through intermittently exposed to 3 Gy gamma-radiation for six months. Treatment of SNU-16 cells with various doses of radiation, TNF alpha and PMA resulted in a decrease in cell viability. The results prove that cell death of SNU16 is a apoptosis mediated by caspase-3. We have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia (CIN) to determine the role of coexpression of bcl-3 and c-myc during progression into cervical cancer. The frequent alterations in FHIT expression in many cervical carcinomas and their cell lines suggest that FHIT gene alterations are pla a role in cervical tumorigenesis. According to these correlation between the viability and apoptosis of RD cells, the proper range of the dosage for the investigation of differentiation potency in RD cells was assessed as 1 to 3Gy

  11. Radiation related basic cancer research : research for radiation induced tumor cell killing

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hoon; Hong, Seok Il; Cho, Kyung Ja; Kim, Byung Gi; Lee, Kee Ho; Nam, Myung Jin

    1999-04-01

    The radioresistant clones was established from human U251 glioblastoma cell line through intermittently exposed to 3 Gy gamma-radiation for six months. Treatment of SNU-16 cells with various doses of radiation, TNF alpha and PMA resulted in a decrease in cell viability. The results prove that cell death of SNU16 is a apoptosis mediated by caspase-3. We have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia (CIN) to determine the role of coexpression of bcl-3 and c-myc during progression into cervical cancer. The frequent alterations in FHIT expression in many cervical carcinomas and their cell lines suggest that FHIT gene alterations are pla a role in cervical tumorigenesis. According to these correlation between the viability and apoptosis of RD cells, the proper range of the dosage for the investigation of differentiation potency in RD cells was assessed as 1 to 3Gy.

  12. Radiation Interaction with Therapeutic Drugs and Cell Membranes

    International Nuclear Information System (INIS)

    Martin, Diana I.; Manaila, Elena N.; Matei, Constantin I.; Iacob, Nicusor I.; Ighigeanu, Daniel I.; Craciun, Gabriela D.; Moisescu, Mihaela I.; Savopol, Tudor D.; Kovacs, Eugenia A.; Cinca, Sabin A.; Margaritescu, Irina D.

    2007-01-01

    This transient permeabilized state of the cell membrane, named the 'cell electroporation' (CE) can be used to increase cells uptake of drugs that do not readily pass cell membrane, thus enabling their cytotoxicity. The anticancer drugs, such as bleomycin (BL) and cisplatin, are the most candidates for the combined use with ionizing and non-ionizing radiation fields. The methods and installations for the cell electroporation by electron beam (EB) and microwave (MW) irradiation are presented. The viability tests of the human leukocytes under EB and MW exposure with/without the BL in the cell cultures are discussed

  13. Immobilization of Mortierella vinacea cells by radiation polymerization

    International Nuclear Information System (INIS)

    Kumakura, M.; Kaetsu, I.

    1983-01-01

    Immobilization of Mortierella vinacea cells, which contain active α-galactosidase, by radiation polymerization at low temperatures was studied. The durability of the enzymatic activity of the immobilized cells obtained with hydrophilic monomers was affected by the concentrations of the cells and monomer in which optimum conditions were observed. The enzymatic activity of the immobilized cells obtained with hydrophilic monomers was compared to that of hydrophobic monomers. Michaelis constants of the immobilized cells varied with monomer concentration. The effect of addition of porous solid substances on the immobilization of the cells was studied

  14. Liquid holding recovery kinetics in yeast cells with regard to radiation quality

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Lee, Byoung Hun; Petin, Vladislav G.

    2004-01-01

    It is widely accepted that the RBE of ionizing radiation with a high linear energy transfer (LET) is dependent both on the increased probability of primary damage production (physical events) and the reduced ability of a cell for post-irradiation recovery (biological events). A relatively unexpected role of the specific repair pathways in the RBE of high-LET radiation was demonstrated for bacterial, yeast and mammalian cells. It seems to exist a common agreement that high-LET radiations produce more portion of damage that are considered to be irreversible compared with low-LET radiation such as photons. Cellular recovery and repair of radiation-induced DNA double-strand breaks (DSB) could be also dependent upon radiation quality. Studies concerning the rate of the recovery and repair from radiation damage produced with low- and high-LET radiations in cells of various origins on the survival and macromolecular level have also revealed that in general at a high ionization density, these processes may be reduced or even absent. When irradiated yeast cells are held in a liquid non-nutrient media at 30 .deg. C before planting on to a growth medium, their survival increases. This phenomena is known as liquid holding recovery (LHR). A quantitative approach describing the LHR kinetics of the yeast cells was described, which enables the estimation of the probability of the recovery per unit time and the fraction of the irreversible damage. The main goals of this study were (i) to answer the question whether or not high-LET radiation affects the recovery process itself or if it only produces a higher level of severe irreversible damage that cannot be repaired at all; (ii) to elucidate the role of irreversible damage and the probability of recovery in some rad mutants of the yeast Saccharomyces cerevisiae. In this study, the liquid-holing recovery will serve as an indicator of the cellular repair activity

  15. Temporary corneal stem cell dysfunction after radiation therapy

    International Nuclear Information System (INIS)

    Hiroshi, Fujishima; Kazuo, Tsubota

    1996-01-01

    Radiation therapy can cause corneal and conjuctival abnormalities that sometimes require surgical treatment. Corneal stem cell dysfunction is described, which recovered after the cessation of radiation. Methods - A 44-year-old man developed a corneal epithelial abnormality associated with conjuctival and corneal inflammation following radiation therapy for maxillary cancer. Examination of brush cytology samples showed goblet cells in the upper and lower parts of the cornea, which showed increased fluorescein permeability, and intraepithelial lymphocytes. Impression cytology showed goblet cells in the same part of the cornea. Specular microscopy revealed spindle type epithelial cells. Patient follow up included artificial tears and an antibiotic ophthalmic ointment. The corneal abnormalities resolved after 4 months with improved visual acuity without any surgical intervention, but the disappearance of the palisades of Vogt did not recover at 1 year after radiation. Radiation therapy in this patient caused temporary stem cell dysfunction which resulted in conjunctivalisation in a part of the cornea. Although limbal stem cell function did not fully recover, this rare case suggested that medical options should be considered before surgery. (Author)

  16. Cone Penetrometer Load Cell Temperature and Radiation Testing Results

    Energy Technology Data Exchange (ETDEWEB)

    Follett, Jordan R.

    2013-08-28

    This report summarizes testing activities performed at the Pacific Northwest National Laboratory to verify the cone penetrometer load cell can withstand the tank conditions present in 241-AN-101 and 241-AN-106. The tests demonstrated the load cell device will operate under the elevated temperature and radiation levels expected to be encountered during tank farm deployment of the device.

  17. The radiation response of cells recovering after chronic hypoxia

    International Nuclear Information System (INIS)

    Kwok, T.T.; Sutherland, R.M.

    1989-01-01

    Experiments were performed to study the influence of hypoxic pretreatment on the radiation response of A431 human squamous carcinoma cells. Reaeration for 10 min after chronic hypoxia (greater than 2 h) was found to enhance the radiosensitivity of A431 cells, and the maximal effect was seen for those cells reaerated after 12 h of hypoxia. The radiosensitivity enhancement for reaerated cells after 12 h of hypoxia was maximized by 5 min after the return to aerobic conditions and reached the control level by 12 h of reaeration. This enhanced radiosensitive state was characterized by a reduced shoulder region and increased slope of the radiation dose-response curve for cells in both the exponential and plateau phases of growth. There was a slight increase in the number of G1 and decrease in the number of S and G2 + M cells for both exponential- and plateau-phase cultures following 12 h hypoxic treatment. Although growth inhibition induced by 12 h of hypoxia was seen for cells in the exponential phase, there was no cell number change in the plateau-phase culture after hypoxia. Plating efficiency (PE) of cells in both growth phases was reduced by 30% after hypoxia. Furthermore, in the exponential-phase culture, the extent of reduction in PE after hypoxia was similar among cells in different phases of the cell cycle. Although S-phase cells in exponentially growing cultures were relatively more resistant to radiation than G1 and G2 + M cells, the cell age-response pattern was the same whether the cells had been aerobic or hypoxic before reaeration and irradiation. Furthermore, the enhancement ratio associated with reaeration after 12 h of hypoxia for these three subpopulations of cells was 1.3. Our results indicate that the increase in radiosensitivity due to reaeration after chronic hypoxia is unlikely to be related to the changes of cell cycle stage and growth phase during hypoxic treatment

  18. Organelle-specific injury to melanin-containing cells in human skin by pulsed laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G.F.; Shepard, R.S.; Paul, B.S.; Menkes, A.; Anderson, R.R.; Parrish, J.A.

    1983-12-01

    Physical models predict that ultraviolet laser radiation of appropriately brief pulses can selectively alter melanin-containing cellular targets in human skin. Skin of normal human volunteers was exposed to brief (20 nanosecond) 351-nm wave length pulses from a XeF excimer laser, predicting that those cells containing the greatest quantities of melanized melanosomes (lower half of the epidermis) would be selectively damaged. Transmission electron microscopy revealed the earliest cellular alteration to be immediate disruption of melanosomes, both within melanocytes and basal keratinocytes. This disruption was dose dependent and culminated in striking degenerative changes in these cells. Superficial keratinocytes and Langerhans cells were not affected. It was concluded that the XeF excimer laser is capable of organelle-specific injury to melanosomes. These findings may have important clinical implications in the treatment of both benign and malignant pigmented lesions by laser radiations of defined wave lengths and pulse durations.

  19. Award nomination for study of cell death in radiation sickness

    Energy Technology Data Exchange (ETDEWEB)

    Ivanitskiy, G

    1985-01-01

    The author discusses the importance of the work entitled Formulation of Theoretical Bases of the Phenomenon of Cell Death and Their Use in Explaining the Pathogenesis of Radiation Sickness, which has been nominated for the 1985 USSR State Prize. The author notes that the study of the nature and mechanisms of cell death from ionizing radiation consumed the efforts of researchers of various specialties for more than 20 years. The author observes that study of the molecular basis of the high radiosensitivity of lymphocytes became the key to understanding the general biological phenomenon of cell death.

  20. UV radiation hardness of silicon inversion layer solar cells

    International Nuclear Information System (INIS)

    Hezel, R.

    1990-01-01

    For full utilization of the high spectral response of inversion layer solar cells in the very-short-wavelength range of the solar spectrum sufficient ultraviolet-radiation hardness is required. In addition to the charge-induced passivation achieved by cesium incorporation into the silicon nitride AR coating, in this paper the following means for further drastic reduction of UV light-induced effects in inversion layer solar cells without encapsulation are introduced and interpretations are given: increasing the nitride deposition temperature, silicon surface oxidation at low temperatures, and texture etching and using higher substrate resistivities. High UV radiation tolerance and improvement of the cell efficiency could be obtained simultaneously

  1. Biosynthesis of proteins and radiation effects in cells

    International Nuclear Information System (INIS)

    Kolomiets, K.D.

    1982-01-01

    Critical analysis of nowadays literature and own experimental data on importance of biosynthesis of proteins, their modification and functional activity in forming radiation effects in irradiated cells is given. A special place in the development of radiation injury of cellular structures and in reduction processes is allocated to molecular recognition. The data on the role of protein synthesis and molecular recognition in the reduction of main biological cell chromatin system are presented. The dependence of postradiation changes in the cell on structural and functional chromatin state is considered

  2. TU-G-201-00: Imaging Equipment Specification and Selection in Radiation Oncology Departments

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    This session will update therapeutic physicists on technological advancements and radiation oncology features of commercial CT, MRI, and PET/CT imaging systems. Also described are physicists’ roles in every stage of equipment selection, purchasing, and operation, including defining specifications, evaluating vendors, making recommendations, and optimal and safe use of imaging equipment in radiation oncology environment. The first presentation defines important terminology of CT and PET/CT followed by a review of latest innovations, such as metal artifact reduction, statistical iterative reconstruction, radiation dose management, tissue classification by dual energy CT and spectral CT, improvement in spatial resolution and sensitivity in PET, and potentials of PET/MR. We will also discuss important technical specifications and items in CT and PET/CT purchasing quotes and their impacts. The second presentation will focus on key components in the request for proposal for a MRI simulator and how to evaluate vendor proposals. MRI safety issues in radiation Oncology, including MRI scanner Zones (4-zone design), will be discussed. Basic MR terminologies, important functionalities, and advanced features, which are relevant to radiation therapy, will be discussed. In the third presentation, justification of imaging systems for radiation oncology, considerations in room design and construction in a RO department, shared use with diagnostic radiology, staffing needs and training, clinical/research use cases and implementation, will be discussed. The emphasis will be on understanding and bridging the differences between diagnostic and radiation oncology installations, building consensus amongst stakeholders for purchase and use, and integrating imaging technologies into the radiation oncology environment. Learning Objectives: Learn the latest innovations of major imaging systems relevant to radiation therapy Be able to describe important technical specifications of CT, MRI

  3. Low-level radiation effects on immune cells

    International Nuclear Information System (INIS)

    Makinodan, T.

    1995-01-01

    The purpose of this study was to characterize the effects of chronic low-dose ionizing radiation (LDR) on murine immune cells. Previously, it had been reported that LDR enhances the proliferative activity of T cells in vitro and delays the growth of transplantable immunogenic tumors in vivo. This suggests that LDR eliminates immune suppressor cells, which downregulates immune response and/or adoptively upregulates the responsiveness of immune effector cells. It had also been reported that human lymphocytes become refractive to high dose radiation-induced chromosomal aberrations by pretreating mitotically active lymphocytes in vitro with very low doses of ionizing radiation, and the adaptive effect can be abrogated by cycloheximide. This suggests that protein synthesis is required for lymphocytes to respond adoptively to LDR

  4. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Khil, Mark S.; Sang, Hie Kim; Pinto, John T.; Jae, Ho Kim

    1996-01-01

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  5. Roles of ionizing radiation in cell transformation

    International Nuclear Information System (INIS)

    Tobias, C.A.; Albright, N.W.; Yang, T.C.

    1983-07-01

    Earlier the authors described a repair misrepair model (RMR-I) which is applicable for radiations of low LET, e.g., x rays and gamma rays. RMR-II was described later. Here is introduced a mathematical modification of the RMR model, RMR-III, which is intended to describe lethal effects caused by heavily ionizing tracks. 31 references, 4 figures

  6. Mammalian cells exposed to ionizing radiation: structural and biochemical aspects

    International Nuclear Information System (INIS)

    Sabanero, M.; Flores V, L. L.; Azorin V, J. C.; Vallejo, M. A.; Cordova F, T.; Sosa A, M.; Castruita D, J. P.; Barbosa S, G.

    2015-10-01

    Acute or chronic exposure to ionizing radiation is a factor that may be hazardous to health. It has been reported that exposure to low doses of radiation (less than 50 mSv / year) and subsequently exposure to high doses have greater effects in people. However, it is unknown molecular and biochemical level alteration. This study, analyzes the susceptibility of a biological system (HeLa Atcc CCL-2 human cervix cancer cell line) to ionizing radiation (6 and 60 mSv/ 90). Our evaluate multiple variables such as: total protein profile, mitochondrial metabolic activity (XTT assay), cell viability (Trypan blue exclusion assay), cytoskeleton (actin micro filaments), nuclei (D API), genomic DNA. The results indicate, that cells exposed to ionizing radiation structurally show alterations in nuclear phenotype and aneuploidy, further disruption in the tight junctions and consequently on the distribution of actin micro filaments. Similar alterations were observed in cells treated with a genotoxic agent (200μM H 2 O 2 /1 h). In conclusion, this multi-criteria assessment enables precise comparisons of the effects of radiation between any biological systems. However, it is necessary to determine stress markers for integration of the effects of ionizing radiation. (Author)

  7. Mammalian cells exposed to ionizing radiation: structural and biochemical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Sabanero, M.; Flores V, L. L. [Universidad de Guanajuato, Departamento de Biologia, DCNE, Noria Alta s/n, 36250 Guanajuato, Gto. (Mexico); Azorin V, J. C.; Vallejo, M. A.; Cordova F, T.; Sosa A, M. [Universidad de Guanajuato, Departamento de Ingenieria Fisica, DCI, Loma del Bosque 103, Col. Lomas del Campestre, 37150 Leon, Guanajuato (Mexico); Castruita D, J. P. [Universidad de Guadalajara, Departamento de Ecologia, CUCBA, Las Agujas, 45100 Zapopan, Jalisco (Mexico); Barbosa S, G., E-mail: myrna.sabanero@gmail.com [Universidad de Guanajuato, Departamento de Ciencias Medicas, DCS, 20 de Enero No. 929, Col. Obregon, 37000 Leon, Guanajuato (Mexico)

    2015-10-15

    Acute or chronic exposure to ionizing radiation is a factor that may be hazardous to health. It has been reported that exposure to low doses of radiation (less than 50 mSv / year) and subsequently exposure to high doses have greater effects in people. However, it is unknown molecular and biochemical level alteration. This study, analyzes the susceptibility of a biological system (HeLa Atcc CCL-2 human cervix cancer cell line) to ionizing radiation (6 and 60 mSv/ 90). Our evaluate multiple variables such as: total protein profile, mitochondrial metabolic activity (XTT assay), cell viability (Trypan blue exclusion assay), cytoskeleton (actin micro filaments), nuclei (D API), genomic DNA. The results indicate, that cells exposed to ionizing radiation structurally show alterations in nuclear phenotype and aneuploidy, further disruption in the tight junctions and consequently on the distribution of actin micro filaments. Similar alterations were observed in cells treated with a genotoxic agent (200μM H{sub 2}O{sub 2}/1 h). In conclusion, this multi-criteria assessment enables precise comparisons of the effects of radiation between any biological systems. However, it is necessary to determine stress markers for integration of the effects of ionizing radiation. (Author)

  8. Combined effects of hyperthermia and radiation in cultured mammalian cells

    International Nuclear Information System (INIS)

    Ben-Hur, E.; Elkind, M.M.; Riklis, E.

    1977-01-01

    Hyperthermia (temperatures of 39 0 C or higher) enhances the killing of mammalian cells by ionizing radiation (fission-spectrum neutrons and x-rays). The nature and the magnitude of the enhanced radiation killing varies with temperature and for a fixed temperature during irradiation, the enhanced lethality varies inversely with dose rate. For temperatures up to 41 0 C, dose fractionation measurements indicate that hyperthermia inhibits the repair of sublethal damage. At higher temperatures, the expression of potentially lethal damage is enhanced. Since the effect of heat is greatest in cells irradiated during DNA synthesis, the radiation age-response pattern is flattened by hyperthermia. In addition to the enhanced cell killing described above, three other features of the effect of hyperthermia are important in connection with the radiation treatment of cancer. The first is that heat selectively sensitizes S-phase cells to radiation. The second is that it takes radiation survivors 10 to 20 hrs after a modest heat treatment to recover their ability to repair sublethal damage. And the third is that hyperthermia reduces the magnitude of the oxygen enhancement ratio. Thus, heat if applied selectively, could significantly increase the margin of damage between tumors and normal tissues

  9. Adoptive immunotherapy using PRAME-specific T cells in medulloblastoma.

    Science.gov (United States)

    Orlando, Domenico; Miele, Evelina; De Angelis, Biagio; Guercio, Marika; Boffa, Iolanda; Sinibaldi, Matilde; Po, Agnese; Caruana, Ignazio; Abballe, Luana; Carai, Andrea; Caruso, Simona; Camera, Antonio; Moseley, Annemarie; Hagedoorn, Renate S; Heemskerk, Mirjam H M; Giangaspero, Felice; Mastronuzzi, Angela; Ferretti, Elisabetta; Locatelli, Franco; Quintarelli, Concetta

    2018-04-03

    Medulloblastoma is the most frequent malignant childhood brain tumor with a high morbidity. Identification of new therapeutic targets would be instrumental in improving patient outcomes. We evaluated the expression of the tumor-associated antigen PRAME in biopsies from 60 medulloblastoma patients. PRAME expression was detectable in 82% of tissues independent of molecular and histopathologic subgroups. High PRAME expression also correlated with worse overall survival. We next investigated the relevance of PRAME as a target for immunotherapy. Medulloblastoma cells were targeted using genetically modified T cells with a PRAME-specific TCR (SLL TCR T cells). SLL TCR T cells efficiently killed medulloblastoma HLA-A*02+ DAOY cells as well as primary HLA-A*02+ medulloblastoma cells. Moreover, SLL TCR T cells controlled tumor growth in an orthotopic mouse model of medulloblastoma. To prevent unexpected T cell-related toxicity,an inducible caspase 9 (iC9) gene was introduced in frame with the SLL TCR; this safety switch triggered prompt elimination of genetically-modified T cells. Altogether, these data indicate that T cells genetically modified with a high-affinity, PRAME-specific TCR and iC9 may represent a promising innovative approach for treating HLA-A*02+ medulloblastoma patients. Copyright ©2018, American Association for Cancer Research.

  10. Effect of antigen on localization of immunologically specific B cells

    International Nuclear Information System (INIS)

    Ponzio, N.M.; Chapman, J.M.; Thorbecke, G.J.

    1976-01-01

    Studies were conducted to demonstrate homing of memory B cells to sites of antigen localization in lymph nodes, using functional criteria to detect local presence of memory cells at varying intervals after intravenous injection. Cell suspensions were prepared from spleens of donor mice injected with complete Freund's adjuvant. Recipient mice were injected with Escherichia coli endotoxin and immune or normal spleen cells and were gamma-irradiated. Results indicated that passively transferred unilateral B cell memory was established. The development over a period of several days of this difference between left and right lymph nodes suggests that recirculating memory B cells are being progressively selected by antigen in the lymph node, rather than that this difference is due to a specific exit of cells from the circulation towards the antigen

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

    International Nuclear Information System (INIS)

    Averbeck, D.; Boucher, D.

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

  13. Thermal radiation modelling in a tubular solid oxide fuel cell

    International Nuclear Information System (INIS)

    Austin, M.E.; Pharoah, J.G.; Vandersteen, J.D.J.

    2004-01-01

    Solid Oxide Fuel Cells (SOFCs) are becoming the fuel cell of choice among companies and research groups interested in small power generation units. Questions still exist, however, about the operating characteristics of these devices; in particular the temperature distribution in the fuel cell. Using computational fluid dynamics (CFD) a model is proposed that incorporates conduction, convection and radiation. Both surface-to-surface and participating media are considered. It is hoped that a more accurate account of the temperature field in the various flow channels and cell components will be made to assist work on design of fuel cell components and reaction mechanisms. The model, when incorporating radiative heat transfer with participating media, predicts substantially lower operating temperatures and smaller temperature gradients than it does without these equations. It also shows the importance of the cathode air channel in cell cooling. (author)

  14. Radiation-induced apoptosis in F9 teratocarcinoma cells

    International Nuclear Information System (INIS)

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

    1994-01-01

    We have found that F9 murine teratocarcinoma cells undergo morphological changes and internucleosomal DNA fragmentation characteristic of apoptosis after exposure to ionizing radiation. We studied the time course, radiation dose-response, and the effects of protein and RNA synthesis inhibitors on this process. The response is dose dependent in the range 2-12 Gy. Internucleosomal DNA fragmentation can be detected as early as 6 h postirradiation and is maximal by 48 h. Cycloheximide, a protein synthesis inhibitor, and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole, an RNA synthesis inhibitor, both induced internucleosomal DNA fragmentation in the unirradiated cells and enhanced radiation-induced DNA fragmentation. F9 cells can be induced to differentiate into cells resembling endoderm with retinoic acid. After irradiation, differentiated F9 cells exhibit less DNA fragmentation than stem cells. This indicates that ionizing radiation can induce apoptosis in non-lymphoid tumours. We suggest that embryonic tumour cells may be particularly susceptible to agents that induce apoptosis. (Author)

  15. Radiation-induced apoptosis in F9 teratocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-05-01

    We have found that F9 murine teratocarcinoma cells undergo morphological changes and internucleosomal DNA fragmentation characteristic of apoptosis after exposure to ionizing radiation. We studied the time course, radiation dose-response, and the effects of protein and RNA synthesis inhibitors on this process. The response is dose dependent in the range 2-12 Gy. Internucleosomal DNA fragmentation can be detected as early as 6 h postirradiation and is maximal by 48 h. Cycloheximide, a protein synthesis inhibitor, and 5,6-dichloro-1-[beta]-D-ribofuranosylbenzimidazole, an RNA synthesis inhibitor, both induced internucleosomal DNA fragmentation in the unirradiated cells and enhanced radiation-induced DNA fragmentation. F9 cells can be induced to differentiate into cells resembling endoderm with retinoic acid. After irradiation, differentiated F9 cells exhibit less DNA fragmentation than stem cells. This indicates that ionizing radiation can induce apoptosis in non-lymphoid tumours. We suggest that embryonic tumour cells may be particularly susceptible to agents that induce apoptosis. (Author).

  16. Development of materials for fuel cell application by radiation technology

    International Nuclear Information System (INIS)

    Rhee, Chang Kyu; Lee, Min Ku; Park, Junju; Lee, Gyoungja; Lee, Byung Cheol; Shin, Junhwa; Nho, Youngchang; Kang, Philhyun; Sohn, Joon Yong; Rang, Uhm Young

    2012-06-01

    The development of the single cell of SOFC with low operation temperature at and below 650 .deg. C(above 400 mW/cm 2 ) Ο The development of fabrication method for the single cell of solid oxide fuel cell (SOFC) by dip-coating of nanoparticles such as NiO, YSZ, Ag, and Ag/C, etc. Ο The optimization of the preparation and performance of SOFC by using nanoparticles. Ο The preparation of samples for SOFC with large dimension. The development of fluoropolymer-based fuel cell membranes with crosslinked structure by radiation grafting technique Ο The development of fuel cell membranes with low methanol permeability via the introduction of novel monomers (e. g. vinylbenzyl chloride and vinylether chloride) by radiation grafting technique Ο The development of hydrocarbon fuel cell membrane by radiation crosslinking technique Ο The structure analysis and the evaluations of the property, performance, and radiation effect of the prepared membranes Ο The optimization of the preparation and performance of DMFC fuel cell membrane via the structure-property analysis (power: above 130 mW/cm 2 /50 cm 2 at 5M methanol) Ο The preparation of samples for MEA stack assembly

  17. Freedom of expression: cell-type-specific gene profiling.

    Science.gov (United States)

    Otsuki, Leo; Cheetham, Seth W; Brand, Andrea H

    2014-01-01

    Cell fate and behavior are results of differential gene regulation, making techniques to profile gene expression in specific cell types highly desirable. Many methods now enable investigation at the DNA, RNA and protein level. This review introduces the most recent and popular techniques, and discusses key issues influencing the choice between these such as ease, cost and applicability of information gained. Interdisciplinary collaborations will no doubt contribute further advances, including not just in single cell type but single-cell expression profiling. © 2014 Wiley Periodicals, Inc.

  18. Radiation-induced spindle cell sarcoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Khan Mubeen

    2009-01-01

    Full Text Available Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.

  19. Radiation-induced gene amplification in rodent and human cells

    International Nuclear Information System (INIS)

    Luecke-Huhle, C.; Gloss, B.; Herrlich, P.

    1990-01-01

    Ionizing and UV radiations induce amplification of SV40 DNA sequences integrated in the genome of Chinese hamster cells and increase amplification of the dihydrofolate reductase (DHFR) gene during methotrexate selection in human skin fibroblasts of a patient with ataxia telangiectasia. Various types of external (60-Co-γ-rays, 241-Am-α-particles, UV) or internal radiation (caused by the decay of 125 I incorporated into DNA in form of I-UdR) were applied. By cell fusion experiments it could be shown that SV40 gene amplification is mediated by one or several diffusible trans-acting factors induced or activated in a dose dependent manner by all types of radiation. One of these factors binds to a 10 bp sequence within the minimal origin of replication of SV40. In vivo competition with an excess of a synthetic oligonucleotide comprising this sequence blocks radiation-induced amplification. (author) 25 refs.; 8 figs

  20. Applications of Synchrotron Radiation Micro Beams in Cell Micro Biology and Medicine

    CERN Document Server

    Ide-Ektessabi, Ari

    2007-01-01

    This book demonstrates the applications of synchrotron radiation in certain aspects of cell microbiology, specifically non-destructive elemental analyses, chemical-state analyses and imaging (distribution) of the elements within a cell. The basics for understanding and applications of synchrotron radiation are also described to make the contents easier to be understood for a wide group of researchers in medical and biological sciences who might not be familiar with the physics of synchrotron radiation. The two main techniques that are discussed in this book are the x-ray fluorescence spectroscopy (XRF) and the x-ray fine structure analysis (XAFS). Application of these techniques in investigations of several important scientific fields, such as neurodegeneration and other diseases related to cell malfunctioning, are demonstrated in this book.

  1. Low dose ionizing radiation treated lymphoblastoid cells

    Data.gov (United States)

    National Aeronautics and Space Administration — Irradiated cell lines exposed to 1-10 Gy 2 Lymphoblastoid cell lines (GM15510 and GM15036) irradiated 1 2.5 5 7.5 10 Gy RNA is isolated and labeled using a T7...

  2. Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

    Science.gov (United States)

    Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

    2015-01-01

    Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

  3. Handling of Highly Radioactive Radiation Sources in a Hot Cell Using a Mechanically Driven Cell Crane - 13452

    Energy Technology Data Exchange (ETDEWEB)

    Klute, Stefan; Huber, Wolfgang-Bruno [Siempelkamp Nukleartechnik GmbH, Am Taubenfeld 25/1, 69123 Heidelberg (Germany); Meyer, Franz [Nuclear Engineering Seibersdorf GmbH, 2444 Seibersdorf (Austria)

    2013-07-01

    In 2010, Siempelkamp Nukleartechnik GmbH was awarded the contract for design and erection of a Hot Cell for handling and storage of highly radioactive radiation sources. This Hot Cell is part of a new hot cell laboratory, constructed for the NHZ (Neues Handhabungszentrum = New Handling Center) of the Nuclear Engineering Seibersdorf GmbH (NES). All incurring radioactive materials from Austria are collected in the NHZ, where they are safely conditioned and stored temporarily until their final storage. The main tasks of the NES include, apart from the collection, conditioning and storage of radioactive waste, also the reprocessing and the decontamination of facilities and laboratories originating from 45 years of research and development at the Seibersdorf site as well as the operation of the Hot Cell Laboratory [1]. The new Hot Cell Laboratory inside the NHZ consists of the following room areas: - One hot cell, placed in the center, for remote controlled, radiation protected handling of radioactive materials, including an integrated floor storage for the long-term temporary storage of highly radioactive radiation sources; - An anteroom for the loading and unloading of the hot cell; - One control room for the remote controlling of the hot cell equipment; - One floor storage, placed laterally to the hot cell, for burial, interim storage and removal of fissionable radioactive material in leak-proof packed units in 100 l drums. The specific design activity of the hot cell of 1.85 Pbq relating to 1-Me-Radiator including the integrated floor storage influences realization and design of the components used in the cell significantly. (authors)

  4. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon

    2010-01-01

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  5. Case of basal cell epithelioma occurring on chronic radiation dermatitis

    Energy Technology Data Exchange (ETDEWEB)

    Kase, Kayoko; Matsuoka, Yoshitaka; Urushibata, Osamu; Nishiwaki, Soichi (Toho Univ. Ohashi Hosp., Tokyo (Japan))

    1989-05-01

    A 52-year-old woman had been treated with radiation therapy for lymphoid tuberculosis on the right side of the neck 40 years before. Chronic radiation dermatitis occurred on that site. Blackish small mass has appeared 2 years before on the central part of the dermatitis. Histological examination revealed thinning of the epidermis, swelling of the dermal collagen fibers, and follicular clusters composed of basaloid cells from the epidermis to the upper layer of the dermis. (Namekawa, K).

  6. Retinopathy secondary to radiation therapy for squamous cell carcinoma

    International Nuclear Information System (INIS)

    Groomer, A.E.; Gutwein, D.E.

    1989-01-01

    This report discusses a case of radiotherapy-induced retinopathy following treatment of squamous cell carcinoma. Treatment of the carcinoma with external beam radiotherapy to the supraorbital region and base of the skull was followed by the onset of retinopathy. The sensory retina, as well as other central nervous system tissues, is highly resistant to radiation damage; however, the retinal vasculature is extremely sensitive to radiation damage, producing a retinopathy that is characteristic of other vascular occlusive diseases. Management is discussed

  7. Cell-specific monitoring of protein synthesis in vivo.

    Directory of Open Access Journals (Sweden)

    Nikos Kourtis

    Full Text Available Analysis of general and specific protein synthesis provides important information, relevant to cellular physiology and function. However, existing methodologies, involving metabolic labelling by incorporation of radioactive amino acids into nascent polypeptides, cannot be applied to monitor protein synthesis in specific cells or tissues, in live specimens. We have developed a novel approach for monitoring protein synthesis in specific cells or tissues, in vivo. Fluorescent reporter proteins such as GFP are expressed in specific cells and tissues of interest or throughout animals using appropriate promoters. Protein synthesis rates are assessed by following fluorescence recovery after partial photobleaching of the fluorophore at targeted sites. We evaluate the method by examining protein synthesis rates in diverse cell types of live, wild type or mRNA translation-defective Caenorhabditis elegans animals. Because it is non-invasive, our approach allows monitoring of protein synthesis in single cells or tissues with intrinsically different protein synthesis rates. Furthermore, it can be readily implemented in other organisms or cell culture systems.

  8. Materials That Enhance Efficiency and Radiation Resistance of Solar Cells

    Science.gov (United States)

    Sun, Xiadong; Wang, Haorong

    2012-01-01

    A thin layer (approximately 10 microns) of a novel "transparent" fluorescent material is applied to existing solar cells or modules to effectively block and convert UV light, or other lower solar response waveband of solar radiation, to visible or IR light that can be more efficiently used by solar cells for additional photocurrent. Meanwhile, the layer of fluorescent coating material remains fully "transparent" to the visible and IR waveband of solar radiation, resulting in a net gain of solar cell efficiency. This innovation alters the effective solar spectral power distribution to which an existing cell gets exposed, and matches the maximum photovoltaic (PV) response of existing cells. By shifting a low PV response waveband (e.g., UV) of solar radiation to a high PV response waveband (e.g. Vis-Near IR) with novel fluorescent materials that are transparent to other solar-cell sensitive wavebands, electrical output from solar cells will be enhanced. This approach enhances the efficiency of solar cells by converting UV and high-energy particles in space that would otherwise be wasted to visible/IR light. This innovation is a generic technique that can be readily implemented to significantly increase efficiencies of both space and terrestrial solar cells, without incurring much cost, thus bringing a broad base of economical, social, and environmental benefits. The key to this approach is that the "fluorescent" material must be very efficient, and cannot block or attenuate the "desirable" and unconverted" waveband of solar radiation (e.g. Vis-NIR) from reaching the cells. Some nano-phosphors and novel organometallic complex materials have been identified that enhance the energy efficiency on some state-of-the-art commercial silicon and thin-film-based solar cells by over 6%.

  9. Radiation-induced apoptosis and cell cycle checkpoints in human colorectal tumour cell lines

    International Nuclear Information System (INIS)

    Playle, L.C.

    2001-03-01

    The p53 tumour suppressor gene is mutated in 75% of colorectal carcinomas and is critical for DNA damage-induced G1 cell cycle arrest. Data presented in this thesis demonstrate that after treatment with Ionizing Radiation (IR), colorectal tumour cell lines with mutant p53 are unable to arrest at G1 and undergo cell cycle arrest at G2. The staurosporine derivative, UCN-01, was shown to abrogate the IR-induced G2 checkpoint in colorectal tumour cell lines. Furthermore, in some cell lines, abrogation of the G2 checkpoint was associated with radiosensitisation. Data presented in this study demonstrate that 2 out of 5 cell lines with mutant p53 were sensitised to IR by UCN-01. In order to determine whether radiosensitisation correlated with lack of functional p53, transfected derivatives of an adenoma-derived cell line were studied, in which endogenous wild type p53 was disrupted by expression of a dominant negative p53 mutant protein (and with a vector control). In both these cell lines UCN-01 abrogated the G2 arrest however this was not associated with radiosensitisation, indicating that radiosensitisation is a cell type-specific phenomenon. Although 2 colorectal carcinoma cell lines, with mutant p53, were sensitised to IR by UCN-01, the mechanisms of p53-independent IR-induced apoptosis in the colon are essentially unknown. The mitogen-activated protein kinase (MAPK) pathways (that is the JNK, p38 and ERK pathways) have been implicated in apoptosis in a range of cell systems and in IR-induced apoptosis in some cell types. Data presented in this study show that, although the MAPKs can be activated by the known activator anisomycin, there is no evidence of a role for MAPKs in IR-induced apoptosis in colorectal tumour cell lines, regardless of p53 status. In summary, some colorectal tumour cell lines with mutant p53 can be sensitised to IR-induced cell death by G2 checkpoint abrogation and this may be an important treatment strategy, however mechanisms of IR-induced p53

  10. Estramustine: A novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Ryu, S.; Gabel, M.; Khil, M.S.

    1994-01-01

    Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G 2 /M phase of the cell cycle. Since cells in the G 2 /M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S 3 ) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 μM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G 2 /M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity. 29 refs., 4 figs., 1 tab

  11. Cell-type specific four-component hydrogel.

    Directory of Open Access Journals (Sweden)

    Timo Aberle

    Full Text Available In the field of regenerative medicine we aim to develop implant matrices for specific tissue needs. By combining two per se, cell-permissive gel systems with enzymatic crosslinkers (gelatin/transglutaminase and fibrinogen/thrombin to generate a blend (technical term: quattroGel, an unexpected cell-selectivity evolved. QuattroGels were porous and formed cavities in the cell diameter range, possessed gelation kinetics in the minute range, viscoelastic properties and a mechanical strength appropriate for general cell adhesion, and restricted diffusion. Cell proliferation of endothelial cells, chondrocytes and fibroblasts was essentially unaffected. In contrast, on quattroGels neither endothelial cells formed vascular tubes nor did primary neurons extend neurites in significant amounts. Only chondrocytes differentiated properly as judged by collagen isoform expression. The biophysical quattroGel characteristics appeared to leave distinct cell processes such as mitosis unaffected and favored differentiation of sessile cells, but hampered differentiation of migratory cells. This cell-type selectivity is of interest e.g. during articular cartilage or invertebral disc repair, where pathological innervation and angiogenesis represent adverse events in tissue engineering.

  12. Radiation protection technology. Specific course for authorized radiation protection representatives according the qualification guidelines technology for the radiation protection regulations (StrlSchV) and X-ray regulation (RoeV). 2. rev. ed.

    International Nuclear Information System (INIS)

    Rahn, Hans-Joachim

    2012-01-01

    The specific course for authorized radiation protection representatives according the qualification guidelines technology for the radiation protection regulations (StrlSchV) and X-ray regulation (RoeV). Covers the following issues: radiation protection - generally; licenses and notifications; scientific fundamentals; dosimetry, surveillance, control, documentation; technical radiation protection; radiation protection calculations.

  13. Gene expression signatures of radiation response are specific, durable and accurate in mice and humans.

    Directory of Open Access Journals (Sweden)

    Sarah K Meadows

    2008-04-01

    Full Text Available Previous work has demonstrated the potential for peripheral blood (PB gene expression profiling for the detection of disease or environmental exposures.We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy. A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively.We conclude that PB gene expression profiles can be identified in mice and humans that are accurate in predicting medical conditions, are specific to each condition and remain highly accurate over time.

  14. Removal of radiation damage by subpopulations of plateau-phase Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Nelson, J.M.; Metting, N.F.; Braby, L.A.; Roesch, W.C.

    1987-01-01

    Specific cellular radiobiology studies are often required to test aspects of the mathematical models developed in the Radiation Dosimetry program. These studies are designed to determine whether specific mathematical expressions, which characterize the expected effect of biochemical mechanisms on observable biological responses, are consistent with the behavior of selected cell lines. Since these tests place stringent requirements on the cellular system, special techniques and culture conditions are required to minimize biological variability. The use of specialized cell populations is providing data on the extent of repair following low doses, and on the changes in the types of damage that can be repaired as the cell progresses toward mitosis. The stationary-phase Chinese hamster ovary (CHO) cells are composed primarily of G(1)-phase cells (83%), with the remainder comprising both G(2) and S phases. Removal of radiation damage by cells was studied in split-dose experiments. To date, we have observed no significant differences in cellular repair rate. This suggests, therefore, that each of the repair processes found in stationary-phase cells is cell-age independent. However, cellular radiation sensitivity does change rapidly and considerably as the cells progress from one phase to the next through the cell cycle. Since the rate of damage removal appears invariant, the change in survival must reflect the efficiency of producing that damage. The experimental data suggest that production of one or another sort of damage probably dominates during specific phases of the cell cycle, while the capacity for removal of all types of damage remains relatively constant

  15. Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative

    Energy Technology Data Exchange (ETDEWEB)

    Smith, P J; Anderson, C O [Medical Research Council, Cambridge (UK)

    1984-10-01

    A comparison was made of the ability of either X-radiation or a DNA-specific ligand (the vital bis-benzimidazole dye; Hoechst 33342) to induce: cell killing, inhibition of de novo DNA synthesis, DNA strand breakage and the delay of cell division in human colon adenocarcinoma cells in vitro. Unlike radiation-induced cell killing, ligand-induced cytotoxicity appeared to be positively correlated with the extent of inhibition of de novo DNA synthesis-a feature consistent with the persistent binding of ligand molecules to nuclear DNA. Ligand-induced DNA strand-breaks disappeared slowly although ligand-treated cells retained apparently normal capacities to repair discrete radiogenic DNA strand-breaks. Pre-treatment of cells with Hoechst 33342 resulted in a dose-modifying enhancement of radiation resistance not associated with altered dosimetry for strand-break induction. However, radioresistance was accompanied by the protracted retention of cells in the G/sub 2/ phase of the cell cycle. We suggest that the results provide direct evidence that the retention of cells in G/sub 2/ phase is a sparing phenomenon and is triggered by the responses of chromatin domains to the presence of DNA damage.

  16. In vitro cell culture lethal dose submitted to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Carolina S.; Rogero, Sizue O.; Rogero, Jose Roberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: carolina_sm@hotmail.com; Ikeda, Tamiko I.; Cruz, Aurea S. [Instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2009-07-01

    The present study was designed to evaluate the in vitro effect of gamma radiation in cell culture of mouse connective tissue exposed to different doses of gamma radiation and under several conditions. The cell viability was analyzed by neutral red uptake methodology. This assay was developed for establish a methodology to be used in the future in the study of resveratrol radioprotection. Resveratrol (3,4',5- trihydroxystilbene), a phenolic phytoalexin that occurs naturally in some spermatophytes, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is found at high levels and is considered one of the highest antioxidant constituents. The intense antioxidant potential of resveratrol provides many pharmacological activities including cardioprotection, chemoprevention and anti-tumor effects. Our results demonstrated that {sup 60}Co gamma radiation lethal dose (LD50) on NCTC clone 929 cells was about 340Gy. (author)

  17. In vitro cell culture lethal dose submitted to gamma radiation

    International Nuclear Information System (INIS)

    Moreno, Carolina S.; Rogero, Sizue O.; Rogero, Jose Roberto; Ikeda, Tamiko I.; Cruz, Aurea S.

    2009-01-01

    The present study was designed to evaluate the in vitro effect of gamma radiation in cell culture of mouse connective tissue exposed to different doses of gamma radiation and under several conditions. The cell viability was analyzed by neutral red uptake methodology. This assay was developed for establish a methodology to be used in the future in the study of resveratrol radioprotection. Resveratrol (3,4',5- trihydroxystilbene), a phenolic phytoalexin that occurs naturally in some spermatophytes, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is found at high levels and is considered one of the highest antioxidant constituents. The intense antioxidant potential of resveratrol provides many pharmacological activities including cardioprotection, chemoprevention and anti-tumor effects. Our results demonstrated that 60 Co gamma radiation lethal dose (LD50) on NCTC clone 929 cells was about 340Gy. (author)

  18. Suppression of radiation mutagenesis by dactinomycin in Chinese hamster cells

    International Nuclear Information System (INIS)

    Tokita, N.; Capenter, S.G.; Chen, D.J.; MacInnes, M.A.; Raju, M.R.

    1985-01-01

    Dactinomycin (AMD) suppression of radiation mutagenesis was investigated using an in vitro mutation assay (6-thioguanine resistance) in Chinese hamster ovary cells. Cells were exposed to acute single doses of x rays followed by 1 hr-treatment with 0.1 or 1 μg/ml AMD. The cell survival curves plotted as a function of x-ray doses were similar for radiation alone and radiation plus AMD. The results suggest that AMD treatment was only slightly mutagenic, however, when given immediately after irradiation, it suppressed radiatiion mutagenesis at higher x-ray dose regions (below 10% survival levels). Higher AMD concentrations appeared more suppressive than lower concentrations. Dose-response data analyzed based on Poisson distribution models suggest the stochastic dependence of x-ray mutagenesis and AMD cytotoxity

  19. Effect of glucocorticoids and gamma radiation on epidermal Langerhans cells

    International Nuclear Information System (INIS)

    Belsito, D.V.; Baer, R.L.; Thorbecke, G.J.; Gigli, I.

    1984-01-01

    The effect of 750 rads of gamma radiation on the rate of return of epidermal Langerhans cells (LC) following suppressive doses of topical glucorticoids was studied in guinea pigs. Gamma radiation alone had no effect on the LC as assessed by staining for cell membrane ATPase activity and Ia antigen. It did, however, delay the expected return of Ia but not ATPase surface markers on the LC after perturbation with glucocorticoids. The delayed return of surface Ia antigen is possibly related to a radiation-induced defect in the production of a required lymphokine and/or in intracellular Ia transport. Although our data do not rule out a cytolytic effect of steroids on the LC, they do strongly suggest that, at least in part, glucocorticoids act on the LC by altering cell surface characteristics

  20. Radiation pathomorphology of the gastrointestinal endocrine cells

    International Nuclear Information System (INIS)

    Yuzhakov, V.V.; Yakovleva, N.D.; Kvetnoj, I.M.; Ulitina, E.D.

    1994-01-01

    The paper presents the results of histochemical, electronmicroscopic and radioautographic analysis of the effects of a total single gamma irradiation on the functional morphology of cells of the diffuse endocrine system of the gastrointestinal tract of rats and mice. Irradiation in dosses from 5 to 20 Gy results in reduction of the detectability of argyrophilic and argentaffine cells. Changes in these cells counts are related to the irradiation dose. The reaction observed early after the irradiation is related to changes in the endocrine and endoplasmatic reticulum

  1. The process and promotion of radiation-induced cell death

    International Nuclear Information System (INIS)

    Sasaki, Hiroshi

    1998-01-01

    Radiation-induced cell death is divided into reproductive and interphase death, whose process can be revealed by time-lapse observations. Pedigree analyses of progenies derived from a surviving progenitor cell have shown that moribund cells appear in clusters among cells which are apparently undamaged (lethal sectoring). Sister cell fusion, which likely results from chromosome bridge, is the most frequently observed cell abnormality leading to reproductive death. While interphase death does not occur unless the dose exceeds 10 Gy for low LET radiation such as X-rays, high-LET radiation is very effective at inducing interphase death (RBE: ≅3 at 230 keV/μm). Expression or fixation of potentially lethal damage (PLD) is closely associated with cell cycle events and enhanced by inducing premature chromosome condensation (PCC) at a nonpermissive temperature in tsBN2 cells with a ts-defect in RCC1 protein (a regulator of chromatin condensation) which monitors the completion of DNA replication. Furthermore, higher-order structural changes in nuclear matrix such as induced by leptomycin B, an inhibitor of CRM1 (chromosome region maintenance) protein, also play an important role in the fixation of PLD. (author)

  2. Specific Protein Markers for Stem Cell Cross-Talk with Neighboring Cells in the Environment

    OpenAIRE

    Park, Kyung Soo; Shin, Seung Won; Choi, Jeong-Woo; Um, Soong Ho

    2013-01-01

    A stem cell interacts with the neighboring cells in its environment. To maintain a living organism’s metabolism, either cell-cell or cell-environment interactions may be significant. Usually, these cells communicate with each other through biological signaling by interactive behaviors of primary proteins or complementary chemicals. The signaling intermediates offer the stem cell’s functionality on its metabolism. With the rapid advent of omics technologies, various specific markers by which s...

  3. Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

    Directory of Open Access Journals (Sweden)

    Michael C. Gong

    1999-06-01

    Full Text Available The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

  4. Molecular mechanisms of radiation-induced cell proliferation in human carcinoma cells

    International Nuclear Information System (INIS)

    Schmidt-Ullrich, R.K.; Mikkelsen, R.; Valerie, K.; Todd, D.; Kavanagh, B.; Contessa, J.; Rorrer, K.; Chen, P.

    1996-01-01

    Purpose: At therapeutically applied ionizing radiation (IR) doses of 0.5 to 5 Gy, a certain proportion of cells will undergoes radiation-induced death while a varied proportion of cells will survive and be able of furnishing adaptive responses. One of these adaptive responses has been experimentally and clinically described as repopulation. Despite description of this phenomenon more than 20 years ago, the mechanisms of this response have remained relatively unknown until modern experimental techniques have been applied to studies on cellular radiation responses. materials and Methods: Human mammary, MCF-7 and MDA-MB-231, and squamous, A431, carcinoma cells (MCC and SCC), expressing epidermal growth factor-receptor (EGF-R) at widely varied levels, have been exposed under defined culture conditions to single and repeated IR at doses between 0.5 and 5 Gy. Cellular IR responses of activation and expression changes of growth regulatory genes and activation of signal transduction pathways were linked to IR-induced proliferation responses. Specifically, EGF-R activation and expression were assessed by levels of Tyr phosphorylation (Y p ) of the receptor protein and mRNA, respectively. Phospholipase (PL-C) activation was quantified by Y p levels and production of inositol-triphosphate (IP 3 ), elevation of cytoplasmic Ca 2+ by video-intensified florescence microscopy after Fura-2 loading. Mitogen-activated protein (MAP) kinase activation was measured by a MBP receptor assay. The EGF-R and signal transduction activation events were correlated with a proliferation response of irradiated cells as quantified by MTT assay. Results: The cell lines tested showed an about 3-fold stimulation of EGF-R Y p levels within 5 min of IR which was associated with a 2.5-fold upregulation of EGF-R after 24 hr. Repeated daily 2 Gy exposures of MCF-7 and MDA-cells resulted in up to 9-fold increases in EGF-R mRNA. EGF-R downstream signal transduction was evidenced by activation of the

  5. Radiation resistance of solar cells for space application, 1

    International Nuclear Information System (INIS)

    Mitsui, Hiroshi; Tanaka, Ryuichi; Sunaga, Hiromi

    1989-07-01

    A 50-μm thick ultrathin silicon solar cell and a 280-μm thick high performance AlGaAs/GaAs solar cell with high radiation resistance have been recently developed by National Space Development Agency of Japan (NASDA). In order to study the radiation resistance of these cells, a joint research was carried out between Japan Atomic Energy Research Institute (JAERI) and NASDA from 1984 through 1987. In this research, the irradiation method of electron beams, the effects of the irradiation conditions on the deterioration of solar cells by electron beams, and the annealing effects of the radiation damage in solar cells were investigated. This paper is the first one of a series of reports of the joint research. In this paper, the space radiation environment which artificial satellites will encounter, the solar cells used, and the experimental methods are described. In addition to these, the results of the study on the irradiation procedure of electron beams are reported. In the study of the irradiation method of electron beams, three methods, that is, the fixed irradiation method, the moving irradiation method, and the spot irradiation method were examined. In the fixed irradiation method and moving one, stationary solar cells and solar cells moving by conveyer were irradiated by scanning electron beams, respectively. On the other hand, in the spot irradiation method, stationary solar cells were irradiated by non-scanning steady electron beams. It was concluded that the fixed irradiation method was the most proper method. In addition to this, in this study, some pieces of information were obtained with respect to the changes in the electrical characteristics of solar cells caused by the irradiation of electron beams. (author) 52 refs

  6. A 3D Monte Carlo model of radiation affecting cells, and its application to neuronal cells and GCR irradiation

    Science.gov (United States)

    Ponomarev, Artem; Sundaresan, Alamelu; Kim, Angela; Vazquez, Marcelo E.; Guida, Peter; Kim, Myung-Hee; Cucinotta, Francis A.

    A 3D Monte Carlo model of radiation transport in matter is applied to study the effect of heavy ion radiation on human neuronal cells. Central nervous system effects, including cognitive impairment, are suspected from the heavy ion component of galactic cosmic radiation (GCR) during space missions. The model can count, for instance, the number of direct hits from ions, which will have the most affect on the cells. For comparison, the remote hits, which are received through δ-rays from the projectile traversing space outside the volume of the cell, are also simulated and their contribution is estimated. To simulate tissue effects from irradiation, cellular matrices of neuronal cells, which were derived from confocal microscopy, were simulated in our model. To produce this realistic model of the brain tissue, image segmentation was used to identify cells in the images of cells cultures. The segmented cells were inserted pixel by pixel into the modeled physical space, which represents a volume of interacting cells with periodic boundary conditions (PBCs). PBCs were used to extrapolate the model results to the macroscopic tissue structures. Specific spatial patterns for cell apoptosis are expected from GCR, as heavy ions produce concentrated damage along their trajectories. The apoptotic cell patterns were modeled based on the action cross sections for apoptosis, which were estimated from the available experimental data. The cell patterns were characterized with an autocorrelation function, which values are higher for non-random cell patterns, and the values of the autocorrelation function were compared for X rays and Fe ion irradiations. The autocorrelation function indicates the directionality effects present in apoptotic neuronal cells from GCR.

  7. Seven cases of radiation-induced cutaneous squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sugita, Kazunari; Yamamoto, Osamu; Suenaga, Yoshinori

    2000-01-01

    We report 7 cases of radiation-induced skin cancer. The diagnosis was based on the history of radiotherapy for benign skin diseases (5 cases) and of occupational exposures to medical doctors (2 cases). All cases were squamous cell carcinomas which arose from chronic radiodermatitis. The estimated latent period of these tumors ranged from 6 to 64 years, with an average of 29.9 years. After surgical treatments of the lesions, no local recurrences were observed in all cases. Benign skin diseases had sometimes been treated with low-energy radiation before the 1960s. Considering the estimated latent period, the peak time point of developing risk of radiation-induced skin cancer by such treatment has been already passed, however, the danger of it should not be ignored in future. In association with multiplicity of radiation usage, occupational exposure of radiation may develop the risk of occurrence of skin cancer in future. Therefore, we should recognize that radiation-induced skin cancer is not in the past. In the cases of chronic skin diseases showing warty keratotic growth, erosion and ulcer, we should include chronic radio-dermatitis in the differential diagnosis. It is necessary to recall all patients about the history of radiotherapy or radiation exposure. Rapid histopathological examination is mandatory because of the suspicion of radiation-induced skin cancer. (author)

  8. Seven cases of radiation-induced cutaneous squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Kazunari; Yamamoto, Osamu; Suenaga, Yoshinori [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

    2000-09-01

    We report 7 cases of radiation-induced skin cancer. The diagnosis was based on the history of radiotherapy for benign skin diseases (5 cases) and of occupational exposures to medical doctors (2 cases). All cases were squamous cell carcinomas which arose from chronic radiodermatitis. The estimated latent period of these tumors ranged from 6 to 64 years, with an average of 29.9 years. After surgical treatments of the lesions, no local recurrences were observed in all cases. Benign skin diseases had sometimes been treated with low-energy radiation before the 1960s. Considering the estimated latent period, the peak time point of developing risk of radiation-induced skin cancer by such treatment has been already passed, however, the danger of it should not be ignored in future. In association with multiplicity of radiation usage, occupational exposure of radiation may develop the risk of occurrence of skin cancer in future. Therefore, we should recognize that radiation-induced skin cancer is not in the past. In the cases of chronic skin diseases showing warty keratotic growth, erosion and ulcer, we should include chronic radio-dermatitis in the differential diagnosis. It is necessary to recall all patients about the history of radiotherapy or radiation exposure. Rapid histopathological examination is mandatory because of the suspicion of radiation-induced skin cancer. (author)

  9. Radiation response of haematopoietic cell lines of human origin

    International Nuclear Information System (INIS)

    Lehnert, S.; Rybka, W.B.; Suissa, S.; Giambattisto, D.

    1986-01-01

    Six human haematopoietic cell lines, five of leukaemic origin, including cells with myeloid, lymphoid and undifferentiated phenotype have been studied with respect to radiation response. The intrinsic radio-sensitivity of the cells varied widely, the D 0 s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed some capacity to accumulate sublethal damage; in three of these, enhanced survival was demonstrated in split-dose experiments. One cell line (HL-60) was anomalous in that although little accumulation of sublethal damage was demonstrable, survival was enhanced by fractionation of the dose. Five of the six cell lines studied were of leukaemic origin. The results support the belief that, in contrast to the almost constant radiosensitivity of normal haematopoietic cell progenitors, leukaemic cell progenitors may show a wide range of radiosensitivities. (author)

  10. Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

    Science.gov (United States)

    Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

    2011-06-01

    Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

  11. Engineering Specificity and Function of Therapeutic Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Jenny L. McGovern

    2017-11-01

    Full Text Available Adoptive therapy with polyclonal regulatory T cells (Tregs has shown efficacy in suppressing detrimental immune responses in experimental models of autoimmunity and transplantation. The lack of specificity is a potential limitation of Treg therapy, as studies in mice have demonstrated that specificity can enhance the therapeutic potency of Treg. We will discuss that vectors encoding T cell receptors or chimeric antigen receptors provide an efficient gene-transfer platform to reliably produce Tregs of defined antigen specificity, thus overcoming the considerable difficulties of isolating low-frequency, antigen-specific cells that may be present in the natural Treg repertoire. The recent observations that Tregs can polarize into distinct lineages similar to the Th1, Th2, and Th17 subsets described for conventional T helper cells raise the possibility that Th1-, Th2-, and Th17-driven pathology may require matching Treg subsets for optimal therapeutic efficacy. In the future, genetic engineering may serve not only to enforce FoxP3 expression and a stable Treg phenotype but it may also enable the expression of particular transcription factors that drive differentiation into defined Treg subsets. Together, established and recently developed gene transfer and editing tools provide exciting opportunities to produce tailor-made antigen-specific Treg products with defined functional activities.

  12. Treatment of radiation syndrome with emphasis on stem cell implantation

    International Nuclear Information System (INIS)

    Ashry, O.M.

    2010-01-01

    Within few years, the possibility that the human body contains cells that can repair and regenerate damaged and diseased tissue has gone from an unlikely proposition to a virtual certainty. Patients who have received doses of radiation in the potentially low to mid-lethal range (2-6 Gy) will have depression in bone-marrow function with cessation of blood-cell production leading to pancytopenia. Selection of cases for stem cell transplantation is based upon clinical signs and symptoms. Hematopoietic stem cell which produces blood cell progeny provides support for hematopoietic and other cells within the marrow, and has also been a focus for possible tissue repair. Another cell type termed mesenchymal or stromal also exists in the marrow. This cell provides support for hematopoietic and other cells within the marrow, and has also been a focus for possible tissue repair. Stem cells are obtained from bone marrow, peripheral blood, placental and umbilical cord blood, embryonic stem cells and embryonic germ cells. These cells have great potential for clinical research due to their potential to regenerate tissue. As well known, the cryo preservation process can store any cell type, particularly blood cells, for an indeterminate time. (author)

  13. Mechanisms of Enhanced Cell Killing at Low Doses: Implications for Radiation Risk

    International Nuclear Information System (INIS)

    Johnston, Peter J.; Wilson, George D.

    2003-01-01

    We have shown that cell lethality actually measured after exposure to low-doses of low-LET radiation, is markedly enhanced relative to the cell lethality previously expected by extrapolation of the high-dose cell-killing response. Net cancer risk is a balance between cell transformation and cell kill and such enhanced lethality may more than compensate for transformation at low radiation doses over a least the first 10 cGy of low-LET exposure. This would lead to a non-linear, threshold, dose-risk relationship. Therefore our data imply the possibility that the adverse effects of small radiation doses (<10 cGy) could be overestimated in specific cases. It is now important to research the mechanisms underlying the phenomenon of low-dose hypersensitivity to cell killing, in order to determine whether this can be generalized to safely allow an increase in radiation exposure limits. This would have major cost-reduction implications for the whole EM program

  14. Acetylation site specificities of lysine deacetylase inhibitors in human cells

    DEFF Research Database (Denmark)

    Schölz, Christian; Weinert, Brian Tate; Wagner, Sebastian A

    2015-01-01

    Lysine deacetylases inhibitors (KDACIs) are used in basic research, and many are being investigated in clinical trials for treatment of cancer and other diseases. However, their specificities in cells are incompletely characterized. Here we used quantitative mass spectrometry (MS) to obtain acety......1-α, providing a possible mechanistic explanation of its adverse, pro-inflammatory effects. Our results offer a systems view of KDACI specificities, providing a framework for studying function of acetylation and deacetylases....

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

    International Nuclear Information System (INIS)

    Rannou, Emilie

    2015-01-01

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

  16. Combined Effects of Radiation and Mercury on PLHC-1 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Cha, Min Kyoung; Ryu, Tae Ho [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Han, Min [Hankook Samgong Co. Osan (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2011-05-15

    It is inevitable for living objects to expose themselves to multiple factors present in the environment. The combined effect of multi-factors is hard to estimate and predict in advance. Especially factors harmful to organisms can synergistically interact with each other. When the effect of the combined action is greater than expected additivity, it is called synergism or supra-additivity. Ionizing radiation can cause cell death, mainly due to its ability to produce reactive oxygen species in cells. Mercury is one of widespread environmental pollutants which is known to have toxic effects on organisms. There are many reports indicating its genotoxic potential in a variety of aquatic species. Synergistic effects of radiation and mercury on human cells was previously reported. Aerobically growing organisms suffer from exposure to oxidative stress, caused by partially reduced forms of molecular oxygen, known as reactive oxygen species. These are highly reactive and capable of damaging cellular constituents such as DNA, lipids and proteins. Consequently, cells from many different organisms have evolved mechanisms to protect their components against reactive oxygen species. Reactive oxygen species can also be formed by exposure of cells either to ionizing radiation or redox cycling chemicals present in the environment like heavy metals. PLHC-1 hepatoma cell line derived from top minnow (Poeciliopsis lucida) is the most commonly used cell line in toxicology. The PLHC-1 cells are easy to cultivate, and can be used for screening the toxicity of chemicals. The present study was done to evaluate the combined effects of radiation with mercury chloride on the PLHC-1 cells

  17. Autophagy contributes to resistance of tumor cells to ionizing radiation.

    Science.gov (United States)

    Chaachouay, Hassan; Ohneseit, Petra; Toulany, Mahmoud; Kehlbach, Rainer; Multhoff, Gabriele; Rodemann, H Peter

    2011-06-01

    Autophagy signaling is a novel important target to improve anticancer therapy. To study the role of autophagy on resistance of tumor cells to ionizing radiation (IR), breast cancer cell lines differing in their intrinsic radiosensitivity were used. Breast cancer cell lines MDA-MB-231 and HBL-100 were examined with respect to clonogenic cell survival and induction of autophagy after radiation exposure and pharmacological interference of the autophagic process. As marker for autophagy the appearance of LC3-I and LC3-II proteins was analyzed by SDS-PAGE and Western blotting. Formation of autophagic vacuoles was monitored by immunofluorescence staining of LC3. LC3-I and LC3-II formation differs markedly in radioresistant MDA-MB-231 versus radiosensitive HBL-100 cells. Western blot analyses of LC3-II/LC3-I ratio indicated marked induction of autophagy by IR in radioresistant MDA-MB-231 cells, but not in radiosensitive HBL-100 cells. Indirect immunofluorescence analysis of LC3-II positive vacuoles confirmed this differential effect. Pre-treatment with 3-methyladenine (3-MA) antagonized IR-induced autophagy. Likewise, pretreatment of radioresistant MDA-231 cells with autophagy inhibitors 3-MA or chloroquine (CQ) significantly reduced clonogenic survival of irradiated cells. Our data clearly indicate that radioresistant breast tumor cells show a strong post-irradiation induction of autophagy, which thus serves as a protective and pro-survival mechanism in radioresistance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

    Directory of Open Access Journals (Sweden)

    Sebastian Diegeler

    2017-06-01

    Full Text Available Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

  19. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities.

    Science.gov (United States)

    Diegeler, Sebastian; Hellweg, Christine E

    2017-01-01

    Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

  20. Radiation-hard silicon gate bulk CMOS cell family

    International Nuclear Information System (INIS)

    Gibbon, C.F.; Habing, D.H.; Flores, R.S.

    1980-01-01

    A radiation-hardened bulk silicon gate CMOS technology and a topologically simple, high-performance dual-port cell family utilizing this process have been demonstrated. Additional circuits, including a random logic circuit containing 4800 transistors on a 236 x 236 mil die, are presently being designed and processed. Finally, a joint design-process effort is underway to redesign the cell family in reduced design rules; this results in a factor of 2.5 cell size reduction and a factor of 3 decrease in chip interconnect area. Cell performance is correspondingly improved

  1. Response of normal stem cells to ionizing radiation: A balance between homeostasis and genomic stability

    International Nuclear Information System (INIS)

    Harfouche, G.; Martin, M.T.

    2010-01-01

    Stem cells have been described in most adult tissues, where they play a key role in maintaining tissue homeostasis. As they self-renew throughout life, accumulating genetic anomalies can compromise their genomic integrity and potentially give rise to cancer. Stem cells (SCs) may thus be a major target of radiation carcinogenesis. In addition, unrepaired genotoxic damage may cause cell death and stem cell pool depletion, impairing lineage functionality and accelerating aging. Developments in SC biology enabled the characterization of the responses of stem cells to genotoxic stress and their role in tissue damage. We here examine how these cells react to ionizing radiation (IR), and more specifically their radiosensitivity, stress signaling and DNA repair. We first review embryonic SCs, as a paradigm of primitive pluri-potent cells, then three adult tissues, bone marrow, skin and intestine, capable of long-term regeneration and at high risk for acute radiation syndromes and long-term carcinogenesis. We discuss IR disruption of the fine balance between maintenance of tissue homeostasis and genomic stability. We show that stem cell radiosensitivity does not follow a unique model, but differs notably according to the turnover rates of the tissues. (authors)

  2. Specific Cell (Re-)Programming: Approaches and Perspectives.

    Science.gov (United States)

    Hausburg, Frauke; Jung, Julia Jeannine; David, Robert

    2018-01-01

    Many disorders are manifested by dysfunction of key cell types or their disturbed integration in complex organs. Thereby, adult organ systems often bear restricted self-renewal potential and are incapable of achieving functional regeneration. This underlies the need for novel strategies in the field of cell (re-)programming-based regenerative medicine as well as for drug development in vitro. The regenerative field has been hampered by restricted availability of adult stem cells and the potentially hazardous features of pluripotent embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Moreover, ethical concerns and legal restrictions regarding the generation and use of ESCs still exist. The establishment of direct reprogramming protocols for various therapeutically valuable somatic cell types has overcome some of these limitations. Meanwhile, new perspectives for safe and efficient generation of different specified somatic cell types have emerged from numerous approaches relying on exogenous expression of lineage-specific transcription factors, coding and noncoding RNAs, and chemical compounds.It should be of highest priority to develop protocols for the production of mature and physiologically functional cells with properties ideally matching those of their endogenous counterparts. Their availability can bring together basic research, drug screening, safety testing, and ultimately clinical trials. Here, we highlight the remarkable successes in cellular (re-)programming, which have greatly advanced the field of regenerative medicine in recent years. In particular, we review recent progress on the generation of cardiomyocyte subtypes, with a focus on cardiac pacemaker cells. Graphical Abstract.

  3. Exposure of cultured astroglial and microglial brain cells to 900 MHz microwave radiation.

    Science.gov (United States)

    Thorlin, Thorleif; Rouquette, Jean-Michel; Hamnerius, Yngve; Hansson, Elisabeth; Persson, Mikael; Björklund, Ulrika; Rosengren, Lars; Rönnbäck, Lars; Persson, Mikael

    2006-08-01

    The rapid rise in the use of mobile communications has raised concerns about health issues related to low-level microwave radiation. The head and brain are usually the most exposed targets in mobile phone users. In the brain, two types of glial cells, the astroglial and the microglial cells, are interesting in the context of biological effects from microwave exposure. These cells are widely distributed in the brain and are directly involved in the response to brain damage as well as in the development of brain cancer. The aim of the present study was to investigate whether 900 MHz radiation could affect these two different glial cell types in culture by studying markers for damage-related processes in the cells. Primary cultures enriched in astroglial cells were exposed to 900 MHz microwave radiation in a temperature-controlled exposure system at specific absorption rates (SARs) of 3 W/kg GSM modulated wave (mw) for 4, 8 and 24 h or 27 W/kg continuous wave (cw) for 24 h, and the release into the extracellular medium of the two pro-inflammatory cytokines interleukin 6 (Il6) and tumor necrosis factor-alpha (Tnfa) was analyzed. In addition, levels of the astroglial cell-specific reactive marker glial fibrillary acidic protein (Gfap), whose expression dynamics is different from that of cytokines, were measured in astroglial cultures and in astroglial cell-conditioned cell culture medium at SARs of 27 and 54 W/kg (cw) for 4 or 24 h. No significant differences could be detected for any of the parameters studied at any time and for any of the radiation characteristics. Total protein levels remained constant during the experiments. Microglial cell cultures were exposed to 900 MHz radiation at an SAR of 3 W/kg (mw) for 8 h, and I16, Tnfa, total protein and the microglial reactivity marker ED-1 (a macrophage activation antigen) were measured. No significant differences were found. The morphology of the cultured astroglial cells and microglia was studied and appeared to be

  4. The Myth of Cell Phone Radiation

    Indian Academy of Sciences (India)

    IAS Admin

    ous) amount of energy, the light wave could only carry energy which was an integer .... transmission tower, the power levels will be higher than if you just used a cell .... denying residents the joy of wireless connectivity. They should campaign ...

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

    Directory of Open Access Journals (Sweden)

    Miho Kawakatsu

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

  6. Pharmacological inhibition of radiation induced in vitro tumor cell/endothelium cell interactions and in vivo metastasis processes

    International Nuclear Information System (INIS)

    Herzog, Melanie

    2013-01-01

    Exposure of endothelial cells with ionizing radiation (IR) or treatment with inflammatory cytokines (e. g. TNFα) induces a Rho-GTPase and NF-κB dependent activation of the expression of various cell adhesion molecules, including E-selectin. E-selectin mediates the adhesion of tumor cells (TC) to endothelial cells and is probably involved in the extravasation step of circulating tumor cells. HMG-CoA reductase inhibitors (e. g. lovastatin) inhibit the function of Rho-GTPases and thus are anticipated to attenuate Rho-regulated cell-cell-adhesion as well. This study focuses on the influence of IR and TNFα on the expression of endothelial- and/or tumor cell-specific pro-adhesive factors and whether these effects are influenced by lovastatin. To this end, the effect of IR and TNFα on cell-cell-interactions between human colon carcinoma cells (HT29) and human umbilical vein endothelial cells (HUVEC) was investigated using an ELISA-based cell adhesion-assay. Moreover, the influence of pre-treatment with lovastatin and other types of inhibitors on HUVEC-HT29 adhesion was monitored. Additionally, we investigated the effect of lovastatin on mRNA expression level of different cell adhesion molecules, metastatic factors and DNA-repair genes upon radiation exposure by qRT-PCR. To scrutinize the in vivo relevance of the data obtained, we investigated the effect of total body irradiation (TBI) on the mRNA expression of pro-adhesive factors in BALB/c mice. To analyze tumor cell extravasation, tumor cells were injected into the lateral tail vein of immundeficient mice, followed by total body irradiation (TBI, 4 Gy). After four weeks a large increase of lung metastases was monitored, which could be blocked by preatreatment of the mice with lovastatin, the Rac1-specific small-molecule inhibitor NSC23766 as well as the sLe x -mimetic glycyrrhizin. Summarizing, we provide evidence, that irradiation promotes upregulation of different cell adhesion molecules in vitro and stimulates

  7. Coniferyl aldehyde attenuates radiation enteropathy by inhibiting cell death and promoting endothelial cell function.

    Science.gov (United States)

    Jeong, Ye-Ji; Jung, Myung Gu; Son, Yeonghoon; Jang, Jun-Ho; Lee, Yoon-Jin; Kim, Sung-Ho; Ko, Young-Gyo; Lee, Yun-Sil; Lee, Hae-June

    2015-01-01

    Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70 expression. We systemically administered CA to mice with radiation enteropathy following abdominal irradiation (IR) to demonstrate the protective effects of CA against radiation-induced gastrointestinal injury. CA clearly alleviated acute radiation-induced intestinal damage, as reflected by the histopathological data and it also attenuated sub-acute enteritis. CA prevented intestinal crypt cell death and protected the microvasculature in the lamina propria during the acute and sub-acute phases of damage. CA induced HSF1 and HSP70 expression in both intestinal epithelial cells and endothelial cells in vitro. Additionally, CA protected against not only the apoptotic cell death of both endothelial and epithelial cells but also the loss of endothelial cell function following IR, indicating that CA has beneficial effects on the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy due to its ability to promote rapid re-proliferation of the intestinal epithelium by the synergic effects of the inhibition of cell death and the promotion of endothelial cell function.

  8. Non-lethal effects of low- and high-LET radiation on cultured mammalian cells

    International Nuclear Information System (INIS)

    Walker, J.T.

    1982-01-01

    In analyzing post-irradiation growth kinetics of cultured mammalian cells, specifically T1-E human cells, this investigation shows that the shift in post-irradiation clone-size distributions toward small colonies is due to both radiation-induced division delay and increased generation times of the irradiated population. Evidence also indicates that the final shape of the final clone-size distribution is influenced by the age density distribution of the parent cells at the time of plating. From computer-generated delay time distributions it was determined that a large percentage of the parent population was found to be in the plateau phase at early growth times and evidence indicates that these cells may contribute heavily to the total population response to radiation

  9. Radiation enhanced reactivation of irradiated human adenovirus type 2 in human cells

    International Nuclear Information System (INIS)

    Jeeves, W.P.

    1981-04-01

    Radiation-enhanced reactivation (ER) of a radiation-damaged mammalian virus is the term given to the observation that the survival of irradiated virus can be enhanced by irradiation of an appropriate host cell prior to infection. In this work, both UV-enhanced reactivation (UVER) and gamma-ray-enhanced reactivation (γRER) of irradiated human adenovirus type 2 (AD 2) were studied in a variety of normal and DNA repair-deficient human fibroblast host cell strains. In order to examine the lesion specificity of ER in human cells, experiments were performed using UV-irradiated and γ-irradiated virus. The investigation was carried out using a sensitive technique of indirect immunofluorescence, according to which irradiated and unirradiated cell cultures were infected with irradiated or unirradiated AD 2 and were subsequently examined for the presence of viral structural antigens ('V' Ag) at a fixed time after infection

  10. Dying cells protect survivors from radiation-induced cell death in Drosophila.

    Directory of Open Access Journals (Sweden)

    Amber Bilak

    2014-03-01

    Full Text Available We report a phenomenon wherein induction of cell death by a variety of means in wing imaginal discs of Drosophila larvae resulted in the activation of an anti-apoptotic microRNA, bantam. Cells in the vicinity of dying cells also become harder to kill by ionizing radiation (IR-induced apoptosis. Both ban activation and increased protection from IR required receptor tyrosine kinase Tie, which we identified in a genetic screen for modifiers of ban. tie mutants were hypersensitive to radiation, and radiation sensitivity of tie mutants was rescued by increased ban gene dosage. We propose that dying cells activate ban in surviving cells through Tie to make the latter cells harder to kill, thereby preserving tissues and ensuring organism survival. The protective effect we report differs from classical radiation bystander effect in which neighbors of irradiated cells become more prone to death. The protective effect also differs from the previously described effect of dying cells that results in proliferation of nearby cells in Drosophila larval discs. If conserved in mammals, a phenomenon in which dying cells make the rest harder to kill by IR could have implications for treatments that involve the sequential use of cytotoxic agents and radiation therapy.

  11. Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death

    Directory of Open Access Journals (Sweden)

    Naira F. Z. Schneider

    2018-03-01

    Full Text Available Cardiac glycosides (CGs are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities.

  12. Specification of primordial germ cells in medaka (Oryzias latipes

    Directory of Open Access Journals (Sweden)

    Raz Erez

    2007-01-01

    Full Text Available Abstract Background Primordial germ cells (PGCs give rise to gametes that are responsible for the development of a new organism in the next generation. Two modes of germ line specification have been described: the inheritance of asymmetrically-localized maternally provided cytoplasmic determinants and the induction of the PGC fate by other cell types. PGCs specification in zebrafish appears to depend on inheritance of germ plasm in which several RNA molecules such as vasa and nanos reside. Whether the specification mode of PGCs found in zebrafish is general for other fish species was brought into question upon analysis of olvas expression – the vasa homologue in another teleost, medaka (Oryzias latipes. Here, in contrast to the findings in zebrafish, the PGCs are found in a predictable position relative to a somatic structure, the embryonic shield. This finding, coupled with the fact that vasa mRNA, which is localized to the germ plasm of zebrafish but does not label a similar structure in medaka opened the possibility of fundamentally different mechanisms governing PGC specification in these two fish species. Results In this study we addressed the question concerning the mode of PGC specification in medaka using embryological experiments, analysis of RNA stability in the PGCs and electron microscopy observations. Dramatic alterations in the somatic environment, i.e. induction of a secondary axis or mesoderm formation alteration, did not affect the PGC number. Furthermore, the PGCs of medaka are capable of protecting specific RNA molecules from degradation and could therefore exhibit a specific mRNA expression pattern controlled by posttrancriptional mechanisms. Subsequent analysis of 4-cell stage medaka embryos using electron microscopy revealed germ plasm-like structures located at a region corresponding to that of zebrafish germ plasm. Conclusion Taken together, these results are consistent with the idea that in medaka the inheritance of

  13. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  14. Models for cell survival with low LET radiation

    International Nuclear Information System (INIS)

    Payne, M.G.; Garrett, W.R.

    1975-01-01

    A model for cell survival under low LET irradiation was developed in which the cell is considered to have N 0 -independent sensitive sites, each of which can exist in either an undamaged state (state A) or one of two damaged states. Radiation can change the sensitive sites from the undamaged state to either of two damaged states. The first damaged state (state B) can either be repaired or be promoted on the second damaged state (state C), which is irreparable. The promotion from the first damaged state to the second can occur due to any of the following: (1) further radiation damage, (2) an abortive attempt to repair the site, or (3) the arrival at a part of the cell cycle where the damage is ''fixed.'' Subject to the further assumptions that radiation damage can occur either indirectly (i.e., through radiation products) or due to direct interaction, and that repair of the first damaged state is a one-step process, expressions can be derived for P(N/sub A/, N/sub B/,t) = probability that after time t a cell will have N/sub A/ sites in state A and N/sub B/ in state B. The problem of determining P(N/sub A/, N/sub B/, t) is formulated for arbitrary time dependences of the radiation field and of all rate coefficients. A large family of cell-survival models can be described by interpreting the sensitive sites in different ways and by making different choices of rate coefficients and of the combinations of numbers of sites in different states that will lead to cell death. (U.S.)

  15. Radiation-induced genetic effects in germ cells of mammals

    International Nuclear Information System (INIS)

    Van Buul, P.P.W.

    1993-01-01

    The aim of the project is to gain information on the effects of ionizing radiation on germ cells of rodents and primates as measured by induced chromosomal translocations. Different aspects of the very significant interspecies differences between the mouse and the rhesus monkey (Macaca mulatta) for translocation induction in spermatogonial stem cells were studied. In addition, possible mechanisms for the well established reduced transmission of induced mouse translocations were investigated. (R.P.) 6 refs

  16. Destruction of radiation-resistant cell populations by hyperthermia

    International Nuclear Information System (INIS)

    Roettinger, E.M.; Gerweck, L.E.

    1979-01-01

    Animal experiments with local hyperthermia have shown that the radiauion dose necessary for the local control of 50% of the tumours examined was essentially reduced by heating to 42,5 0 C. In-vitro experients indicated selective destruction of relatively radiation-resistent cell populations by the combination of hyperthermie and reduced hydrogen ion concentration. Experiments with glioblastoma cells confirmed these results qualitatively, but showed quantitatively considerably lower sensitivity towards hyperthermia. (orig.) 891 MG/orig. 892 RDG [de

  17. Effect of sunitinib combined with ionizing radiation on endothelial cells

    International Nuclear Information System (INIS)

    Zhang Haiping; Jiao Xiaodong; Li Rui; Wang Jiejun; Takayama, Koichi; Su Bo

    2011-01-01

    The aims of present study were to evaluate the efficacy of combining sunitinib with ionizing radiation (IR) on endothelial cells in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed to IR with or without sunitinib pretreatment. Apoptosis assay and cell cycle distribution were analyzed by flow cytometry. Clonogenic survival assay at 3 Gy dose with or without sunitinib was performed. The activity of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway was detected by Western immunoblot. Lewis lung carcinoma mouse model was built to examine the effect of combination therapy on endothelial cells in vivo. Microvasculature changes were detected by immunohistochemistry using anti-CD31 antibody. Our results showed combination therapy of sunitinib and IR significantly increased apoptosis of endothelial cells and inhibited colony formation compared to sunitinib or radiotherapy alone. It also resulted in cell cycle redistribution (decreasing cells in S phase and increasing cells in G2/M phase). The activity of PI3K/Akt signal pathway was inhibited, which could be the potential mechanisms that account for the enhanced radiation response induced by sunitinib. In vivo analysis showed that combination therapy significantly decreased microvasculature formation. The results demonstrated that combination therapy of sunitinib and IR has the potential to increase the cytotoxic effects on endothelial cells. (author)

  18. Radiation-induced motility alterations in medulloblastoma cells

    International Nuclear Information System (INIS)

    Rieken, Stefan; Rieber, Juliane; Brons, Stephan

    2015-01-01

    Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α 5 . The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α 5 , which lead to increased cell adherence to extracellular matrix proteins. (author)

  19. Radiation activation of transcription factors in mammalian cells

    International Nuclear Information System (INIS)

    Kraemer, M.; Stein, B.; Mai, S.; Kunz, E.; Koenig, H.; Ponta, H.; Herrlich, P.; Rahmsdorf, H.J.; Loferer, H.; Grunicke, H.H.

    1990-01-01

    In mammalian cells radiation induces the enhanced transcription of several genes. The cis acting elements in the control region of inducible genes have been delimited by site directed mutagenesis. Several different elements have been found in different genes. They do not only activate gene transcription in response to radiation but also in response to growth factors and to tumor promoter phorbol esters. The transcription factors binding to these elements are present also in non-irradiated cells, but their DNA binding activity and their transactivating capability is increased upon irradiation. The signal chain linking the primary radiation induced signal (damaged DNA) to the activation of transcription factors involves the action of (a) protein kinase(s). (orig.)

  20. Radiation cell survival and growth delay studies in multicellular spheroids of small-cell lung carcinoma

    International Nuclear Information System (INIS)

    Duchesne, G.M.; Peacock, J.H.

    1987-01-01

    The radiation sensitivity of two small-cell lung carcinoma cell lines growing as multicellular spheroids in static culture was determined using clonogenic cell survival and growth delay as endpoints. Growth delay determination suggested that clonogenic cell kill was less than was obtained by direct assay of cell survival. Recovery from potentially lethal damage was assayed in one line (HC12) but was not demonstrable, and clonogenic cell survival decreased with time in treated spheroids with diameters greater than 300 μm which contained a hypoxic cell population. Microscopic examination of the treated spheroids showed the emergence of an abnormal giant-cell population, and the progressive clonogenic cell loss that occurred after treatment was thought to be due to oxygen and nutrient deprivation of the remaining viable cells by this doomed cell population. Correction of the growth delay measurements for changes in cell size and clonogenic cell population allowed correlation of the growth delay and cell survival data. (author)

  1. Is post-operative radiation for renal cell carcinoma justified?

    International Nuclear Information System (INIS)

    Aref, Ibrahim; Bociek, R. Gregory; Salhani, Douglas

    1997-01-01

    Purpose: To identify the pattern of failure in patients with resected renal cell carcinoma (RCC). Materials and methods: The records of 116 patients with unilateral, non-hematogenous metastatic RCC who were treated with definitive surgery and referred to the Ottawa Regional Cancer Centre between 1977 and 1988 were reviewed. Distribution by stage included T1 (3 patients), T2 (42 patients) and T3 (71 patients). The median follow-up was 44 months, with a range of 4-267 months. Results: Local regional failure (LRF) developed in 8 patients. Nine patients developed local or regional recurrence, plus distant failure. Fifty-eight patients had distant metastases (DM) only. The 7-year actuarial rate for LRF and DM were 12%, and 67%, respectively. The overall 7-year actuarial survival rate was 35%, and cause-specific survival was 42%. Conclusions: LRF alone is rare following nephrectomy. DM is the main pattern of failure. This data does not support the role of adjuvant radiation therapy in this disease

  2. Channels in cell membranes and synchrotron radiation

    International Nuclear Information System (INIS)

    Yan Xiaohui; Tian Liang; Zhang Xinyi

    2004-01-01

    For long time a lot of scientists have devoted to study how matter, such as water molecules and K + , Na + , Ca 2+ , Cl - ions, move through cell membranes and complete the matter exchange between the inside and outside of cells. Peter Agre discovered and characterized the first water channel protein in 1988 and Roderick MacKinnon elucidated the structural and mechanistic basis for ion channel function in 1998. These achievements have made it possible for us to 'see' these exquisitely designed molecular machines in action at the atomic level. The Nobel Prize in Chemistry for 2003 is shared between these two scientists. In determining the high resolution 3D structure of these channels, the synchrotron X-ray diffraction plays an important role

  3. Micro-magnet arrays for specific single bacterial cell positioning

    Energy Technology Data Exchange (ETDEWEB)

    Pivetal, Jérémy, E-mail: jeremy.piv@netcmail.com [Ecole Centrale de Lyon, CNRS UMR 5005, Laboratoire Ampère, F-69134 Écully (France); Royet, David [Ecole Centrale de Lyon, CNRS UMR 5005, Laboratoire Ampère, F-69134 Écully (France); Ciuta, Georgeta [Univ. Grenoble Alpes, Inst NEEL, F-38042 Grenoble (France); CNRS, Inst NEEL, F-38042 Grenoble (France); Frenea-Robin, Marie [Université de Lyon, Université Lyon 1, CNRS UMR 5005, Laboratoire Ampère, F-69622 Villeurbanne (France); Haddour, Naoufel [Ecole Centrale de Lyon, CNRS UMR 5005, Laboratoire Ampère, F-69134 Écully (France); Dempsey, Nora M. [Univ. Grenoble Alpes, Inst NEEL, F-38042 Grenoble (France); CNRS, Inst NEEL, F-38042 Grenoble (France); Dumas-Bouchiat, Frédéric [Univ Limoges, CNRS, SPCTS UMR 7513, 12 Rue Atlantis, F-87068 Limoges (France); Simonet, Pascal [Ecole Centrale de Lyon, CNRS UMR 5005, Laboratoire Ampère, F-69134 Écully (France)

    2015-04-15

    In various contexts such as pathogen detection or analysis of microbial diversity where cellular heterogeneity must be taken into account, there is a growing need for tools and methods that enable microbiologists to analyze bacterial cells individually. One of the main challenges in the development of new platforms for single cell studies is to perform precise cell positioning, but the ability to specifically target cells is also important in many applications. In this work, we report the development of new strategies to selectively trap single bacterial cells upon large arrays, based on the use of micro-magnets. Escherichia coli bacteria were used to demonstrate magnetically driven bacterial cell organization. In order to provide a flexible approach adaptable to several applications in the field of microbiology, cells were magnetically and specifically labeled using two different strategies, namely immunomagnetic labeling and magnetic in situ hybridization. Results show that centimeter-sized arrays of targeted, isolated bacteria can be successfully created upon the surface of a flat magnetically patterned hard magnetic film. Efforts are now being directed towards the integration of a detection tool to provide a complete micro-system device for a variety of microbiological applications. - Highlights: 1.We report a new approach to selectively micropattern bacterial cells individually upon micro-magnet arrays. 2.Permanent micro-magnets of a size approaching that of bacteria could be fabricated using a Thermo-Magnetic Patterning process. 3.Bacterial cells were labeled using two different magnetic labeling strategies providing flexible approach adaptable to several applications in the field of microbiology.

  4. Effect of radiation on bacterial cells pathogenesis

    International Nuclear Information System (INIS)

    Szulc, M.; Tropilo, J.; Zajaczkowska, E.

    1983-01-01

    In order to determine the effect of X rays on the pathogeny of Erysipelothrix rhusiopathiae and Pasteurella multocida 334 mice were infected subcutaneously with the germs exposed to 10 Gy and D 10 . It was found that a single exposition of E. rhusiopathiae and P. multocida to 10 Gy and D 10 did not change pathogenic properties of these cells. P. multocida showed higher sensitivity to X rays: D 10 for that species was 94 Gy and for E. rhusiopathiae - 156 Gy. (author)

  5. Asymmetric cell division requires specific mechanisms for adjusting global transcription.

    Science.gov (United States)

    Mena, Adriana; Medina, Daniel A; García-Martínez, José; Begley, Victoria; Singh, Abhyudai; Chávez, Sebastián; Muñoz-Centeno, Mari C; Pérez-Ortín, José E

    2017-12-01

    Most cells divide symmetrically into two approximately identical cells. There are many examples, however, of asymmetric cell division that can generate sibling cell size differences. Whereas physical asymmetric division mechanisms and cell fate consequences have been investigated, the specific problem caused by asymmetric division at the transcription level has not yet been addressed. In symmetrically dividing cells the nascent transcription rate increases in parallel to cell volume to compensate it by keeping the actual mRNA synthesis rate constant. This cannot apply to the yeast Saccharomyces cerevisiae, where this mechanism would provoke a never-ending increasing mRNA synthesis rate in smaller daughter cells. We show here that, contrarily to other eukaryotes with symmetric division, budding yeast keeps the nascent transcription rates of its RNA polymerases constant and increases mRNA stability. This control on RNA pol II-dependent transcription rate is obtained by controlling the cellular concentration of this enzyme. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Science.gov (United States)

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

    2018-05-01

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

  7. Sequence specific DNA binding by P53 is enhanced by ionizing radiation and is mediated via DNA-PK activity

    International Nuclear Information System (INIS)

    Kachnic, L.A.; Wunsch, H.; Mekeel, K.L.; De Frank, J.S.; Powell, S.N.

    1996-01-01

    Purpose: P53 is known to be involved in the cellular response to DNA damage. It mediates many of its effects by acting as a transcription factor via sequence-specific DNA binding. The half-life of p53 is prolonged following DNA damage, and this results in elevated levels of p53 for a period of 2-8 hours. The increase in p53 is often relatively small, but this produces significant stimulation of a downstream gene such as p21(WAF1/cip1). We investigated post-translational modification of p53 following ionizing radiation damage. Materials and Methods: The response of normal Balb-C mouse fibroblasts (FC) to ionizing radiation (IR, 8 Gy) was measured at 0,3,6,9 and 24 hours, by the levels of p53, p21, flow cytometry and the electrophoretic mobility shift assay (EMSA). EMSA utilized a 26 bp consensus sequence end-labeled oligonucleotide to measure sequence-specific p53 binding. P53 specificity was confirmed by an enhanced mobility shift (retardation) when using p53 antibody. Comparison was made with scid fibroblasts (FS) and FC cells transfected with a plasmid (CX3) containing mutant p53 (alanine-143) or infected with a retrovirus containing the E6 protein of human papilloma virus type 16. Results: The response of p53 to DNA damage shows a 3-fold increase at 3-6 hours, and was not significantly different between FC and FS. FC-CX3 showed detectable basal levels of p53, and a 2-fold further induction of p53 after IR. FC-E6 showed no detectable levels of p53 before or after IR. No induction of p21 or G1/S arrest was seen in FC-CX3 or FC-E6, as has been observed previously. The induction of p21 in FS cells was attenuated and delayed: a 2-3-fold increase seen maximally at 9 hours, compared with a 5-fold increase seen maximally at 3-6 hours in FC cells. The accumulation of cells at the G1/S junction after IR showed the same kinetics as p21 induction: the peak of cells in G1 occurs at 3-6 hours in FC, but not until 9-24 hours in FS. The response is reminiscent of that seen in

  8. Isolation and characterization of human salivary gland cells for stem cell transplantation to reduce radiation-induced hyposalivation

    International Nuclear Information System (INIS)

    Feng Jielin; Zwaag, Marianne van der; Stokman, Monique A.; Os, Ronald van; Coppes, Robert P.

    2009-01-01

    Background: Recently, we showed that transplantation of 100-300 c-Kit + stem cells isolated from cultured salispheres ameliorates radiation-damage in murine salivary glands. The aim of this study is to optimize and translate these findings from mice to man. Methods: Mouse and human non-malignant parotid and submandibular salivary gland tissue was collected and enzymatically digested. The remaining cell suspension was cultured according to our salisphere culture method optimized for murine salispheres. Salisphere cells were tested using 3D matrix culturing for their in vitro stem cell characteristics such as the potential to differentiate into tissue specific cell types. Several potential mouse and human salivary gland stem cells were selected using FACS. Results: In human salivary gland, c-Kit + cells were only detected in excretory ducts as shown previously in mice. From both human parotid and submandibular gland cell suspensions salispheres could be grown, which when placed in 3D culture developed ductal structures and mucin-expressing acinar-like cells. Moreover, cells dispersed from primary salispheres were able to form secondary spheres in matrigel, a procedure that could be repeated for at least seven passages. Approximately 3000 c-Kit + cells could be isolated from primary human salispheres per biopsy. Conclusion: Human salivary glands contain a similar 'putative' stem cell population as rodents, expressing c-kit and capable of in vitro differentiation and self-renewal. In the future, these cells may have the potential to reduce radiotherapy-induced salivary gland dysfunction in patients.

  9. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    International Nuclear Information System (INIS)

    Nicolay, Nils H.; Sommer, Eva; Lopez, Ramon; Wirkner, Ute; Trinh, Thuy; Sisombath, Sonevisay; Debus, Jürgen; Ho, Anthony D.; Saffrich, Rainer; Huber, Peter E.

    2013-01-01

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression

  10. Cell phone radiation effects on cytogenetic abnormalities of oral mucosal cells.

    Science.gov (United States)

    Daroit, Natália Batista; Visioli, Fernanda; Magnusson, Alessandra Selinger; Vieira, Geila Radunz; Rados, Pantelis Varvaki

    2015-01-01

    The aim of this study was to evaluate the effects of exposure to cell phone electromagnetic radiation on the frequency of micronuclei, broken eggs cells, binucleated cells, and karyorrhexis in epithelial cells of the oral mucosa. The sample was composed of 60 cell phone users, who were non-smokers and non-drinkers, and had no clinically visible oral lesions. Cells were obtained from anatomical sites with the highest incidence of oral cancer: lower lip, border of the tongue, and floor of the mouth. The Feulgen reaction was used for quantification of nuclear anomalies in 1,000 cells/slide. A slightly increase in the number of micronucleated cells in the lower lip and in binucleated cells on the floor of the mouth was observed in individuals who used their phones > 60 minutes/week. The analysis also revealed an increased number of broken eggs in the tongue of individuals owning a cell phone for over eight years. Results suggest that exposure to electromagnetic waves emitted by cell phones can increase nuclear abnormalities in individuals who use a cell phone for more than 60 minutes per week and for over eight years. Based on the present findings, we suggest that exposure to electromagnetic radiation emitted by cell phones may interfere with the development of metanuclear anomalies. Therefore, it is demonstrated that, despite a significant increase in these anomalies, the radiation emitted by cell phones among frequent users is within acceptable physiological limits.

  11. Cell phone radiation effects on cytogenetic abnormalities of oral mucosal cells

    Directory of Open Access Journals (Sweden)

    Natália Batista DAROIT

    2015-01-01

    Full Text Available The aim of this study was to evaluate the effects of exposure to cell phone electromagnetic radiation on the frequency of micronuclei, broken eggs cells, binucleated cells, and karyorrhexis in epithelial cells of the oral mucosa. The sample was composed of 60 cell phone users, who were non-smokers and non-drinkers, and had no clinically visible oral lesions. Cells were obtained from anatomical sites with the highest incidence of oral cancer: lower lip, border of the tongue, and floor of the mouth. The Feulgen reaction was used for quantification of nuclear anomalies in 1,000 cells/slide. A slightly increase in the number of micronucleated cells in the lower lip and in binucleated cells on the floor of the mouth was observed in individuals who used their phones > 60 minutes/week. The analysis also revealed an increased number of broken eggs in the tongue of individuals owning a cell phone for over eight years. Results suggest that exposure to electromagnetic waves emitted by cell phones can increase nuclear abnormalities in individuals who use a cell phone for more than 60 minutes per week and for over eight years. Based on the present findings, we suggest that exposure to electromagnetic radiation emitted by cell phones may interfere with the development of metanuclear anomalies. Therefore, it is demonstrated that, despite a significant increase in these anomalies, the radiation emitted by cell phones among frequent users is within acceptable physiological limits.

  12. Radiation induced cell death in cervical squamous cell carcinoma. An immunohistochemical and ultrastructural study

    International Nuclear Information System (INIS)

    Atari, Eio; Toda, Takayoshi; Sadi, A.M.; Egawa, Haruhiko; Moromizato, Hidehiko; Mamadi, T.; Kiyuna, Masaya

    1998-01-01

    To study the process of cell death in cervical squamous cell carcinoma (SCC) after radiation, an ultrastructural and immunohistochemical study was performed. Paraffin-embedded tissue blocks of biopsy samples pre- and post-radiation stage III SCC (n=15) were collected. Irradiation caused varying ultrastructural changes including nuclear and cytoplasmic disorganization suggesting cell necrosis. Immunohistochemically, the pre-radiation specimens showed no positive reaction for tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-receptor (TNF-γ) or Fas. C-fos, p53 and bcl-2 showed positive reactions in only a few non-irradiated specimens. All of the irradiated specimens showed a positive reaction for TNF-α, and variable positive reactions were observed for TNF-γ, Fas, p53, c-fos and bcl-2. These results suggest that TNF-α, TNF-γ, and c-fos are responsible for radiation induced cell death in cervical SCC. (author)

  13. Electron microbeam specifications for use in cell irradiation experiments

    International Nuclear Information System (INIS)

    Kim, E.-H.; Choi, M.-C.; Lee, D.-H.; Chang, M.; Kang, C.-S.

    2003-01-01

    The microbeam irradiation system was devised originally to identify the hit and unhit cells by confining the beam within the target cell. The major achievement through the microbeam experiment studies has turned out to be the discovery of the 'bystander effect'. Microbeam experiments have been performed with alpha and proton beams in major and with soft x-rays in minor. The study with electron microbeam has been deferred mainly due to the difficulty in confining the electron tracks within a single target cell. In this paper, the electron microbeam irradiation system under development in Korea is introduced in terms of the beam specifications. The KIRAMS electron microbeam irradiation system consists of an electron gun, a vacuum chamber for beam collimation into 5 μm in diameter and a biology stage. The beam characteristics in terms of current and energy spectrum of the electrons entering a target cell and its neighbor cells were investigated by Monte Carlo simulation for the electron source energies of 25, 50, 75 and 100 keV. Energy depositions in the target cell and the neighbor cells were also calculated. The beam attenuation in current and energy occurs while electrons pass through the 2 μm-thick Mylar vacuum window, 100 μm-thick air gap and the 2 μm-thick Mylar bottom of cell dish. With 25 keV electron source, 80 % of decrease in current and 30 % of decrease in average energy were estimated before entering the target cell. With 75 keV electron source, on the other hand, 55 % of decrease in current and less than 1 % of decrease in average energy were estimated. Average dose per single collimated electron emission was 0.067 cGy to the target cell nucleus of 5 μm in diameter and 0.030 cGy to the cytoplasm of 2.5 μm in thickness with 25 keV electron source while they were 0.15 cGy and 0.019 cGy, respectively, with 75 keV electron source. The multiple scattering of electrons resulted in energy deposition in the neighbor cells as well. Dose to the first

  14. Repair mechanisms in radiation-induced cell transformation

    International Nuclear Information System (INIS)

    Elkind, M.M.; Han, A.; Hill, C.K.; Buonaguro, F.

    1983-01-01

    Our data with both low- and high-LET radiations are qualitatively similar to results obtained in vivo. This is evident, for example, in the reductions in cell transformation for protracted exposures of γ-rays. The consistencies between our results with cells and the data of others with animals lend support to Gray's hypothesis that tumorigenesis is the net effect of a low probability inductive process, and a high probability killing process. An important prediction can be made when spontaneous frequency is appreciable (e.g., 43% in the case of reticulum cell sarcoma in RFM mice). For small doses, tumorigenesis would drop provided that: (a) the cells responsible for the spontaneous incidence are present at the time of exposure; and (b) the progenitor cells of the tumor are not resistant to cell killing

  15. Flow cytometric quantification of radiation responses of murine peritoneal cells

    International Nuclear Information System (INIS)

    Tokita, N.; Raju, M.R.

    1982-01-01

    Methods have been developed to distinguish subpopulations of murine peritoneal cells, and these were applied to the measurement of early changes in peritoneal cells after irradiation. The ratio of the two major subpopulations in the peritoneal fluid, lymphocytes and macrophages, was measured rapidly by means of cell volume distribution analysis as well as by hypotonic propidium iodide (PI) staining. After irradiation, dose and time dependent changes were noted in the cell volume distributions: a rapid loss of peritoneal lymphocytes, and an increase in the mean cell volume of macrophages. The hypotonic PI staining characteristics of the peritoneal cells showed two or three distinctive G 1 peaks. The ratio of the areas of these peaks was also found to be dependent of the radiation dose and the time after irradiation. These results demonstrate that these two parameters may be used to monitor changes induced by irradiation (biological dosimetry), and to sort different peritoneal subpopulations

  16. Action spectra in mammalian cells exposed to ultraviolet radiation

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    A review is given of the literature published since 1977 on action spectra in mammalian cells exposed to ultraviolet radiation in the wavelength region above 220 nm. Action spectra for lethal events are discussed for cell inactivation in normal cells, growth arrested cells and photosensitive cells. Action spectra for non-lethal events are also discussed in relation to pyrimidine dimer formation, photoreactivation and the use of photosensitisers. It was concluded from these studies that damage to the DNA, and the extent of the repair of this damage, seems to determine a cell's response to such parameters as inactivation, mutation, transformation, latent viral activation, cellular viral capacity and ultraviolet enhanced viral reactivation. In addition to the direct effects of UV on DNA, photosensitization of cellular responses with chemicals such as 8-MOP extend the wavelength range at which damage can be demonstrated. (U.K.)

  17. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun [Division of heavy ion clinical research, Korea University, Seoul (Korea, Republic of); Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2012-11-15

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy.

  18. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    International Nuclear Information System (INIS)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun; Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook

    2012-01-01

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy

  19. Radiation damage in flash memory cells

    International Nuclear Information System (INIS)

    Claeys, C.; Ohyama, H.; Simoen, E.; Nakabayashi, M.; Kobayashi, K.

    2002-01-01

    Results are presented of a study on the effects of total ionization dose and displacement damage, induced by high-energy electrons, protons and alphas, on the performance degradation of flash memory cells integrated in a microcomputer. A conventional stacked-gate n-channel flash memory cell using a 0.8 μm n-polysilicon gate technology is employed. Irradiations by 1-MeV electrons and 20-MeV protons and alpha particles were done at room temperature. The impact of the fluence on the input characteristics, threshold voltage shift and drain and gate leakage was investigated. The threshold voltage change for proton and alpha irradiations is about three orders of magnitude larger than that for electrons. The performance degradation is mainly caused by the total ionization dose (TID) damage in the tunnel oxide and in the interpoly dielectric layer and by the creation of interface traps at the Si-SiO 2 interface. The impact of the irradiation temperature on the device degradation was studied for electrons and gammas, pointing out that irradiation at room temperature is mostly the worst case. Finally, attention is given to the impact of isochronal and isothermal annealing on the recovery of the degradation introduced after room temperature proton and electron irradiation

  20. Generation of Transplantable Beta Cells for Patient-Specific Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2012-01-01

    Full Text Available Islet cell transplantation offers a potential cure for type 1 diabetes, but it is challenged by insufficient donor tissue and side effects of current immunosuppressive drugs. Therefore, alternative sources of insulin-producing cells and isletfriendly immunosuppression are required to increase the efficiency and safety of this procedure. Beta cells can be transdifferentiated from precursors or another heterologous (non-beta-cell source. Recent advances in beta cell regeneration from somatic cells such as fibroblasts could circumvent the usage of immunosuppressive drugs. Therefore, generation of patient-specific beta cells provides the potential of an evolutionary treatment for patients with diabetes.

  1. Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.

    Science.gov (United States)

    Kim, J H; Hyun, S J; Yoon, M Y; Ji, Y H; Cho, C K; Yoo, S Y

    1997-06-01

    Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

  2. Biological effects of space radiation on human cells. History, advances and outcomes

    International Nuclear Information System (INIS)

    Maalouf, M.; Foray, N.; Durante, M.

    2011-01-01

    Exposure to radiation is one of the main concerns for space exploration by humans. By focusing deliberately on the works performed on human cells, we endeavored to review, decade by decade, the technological developments and conceptual advances of space radiation biology. Despite considerable efforts, the cancer and the toxicity risks remain to be quantified: the nature and the frequency of secondary heavy ions need to be better characterized in order to estimate their contribution to the dose and to the final biological response; the diversity of radiation history of each astronaut and the impact of individual susceptibility make very difficult any epidemiological analysis for estimating hazards specifically due to space radiation exposure. Cytogenetic data undoubtedly revealed that space radiation exposure produce significant damage in cells. However, our knowledge of the basic mechanisms specific to low-dose, to repeated doses and to adaptive response is still poor. The application of new radiobiological techniques, like immunofluorescence, and the use of human tissue models different from blood, like skin fibroblasts, may help in clarifying all the above items. (author)

  3. Specific insulin binding in bovine chromaffin cells; demonstration of preferential binding to adrenalin-storing cells

    International Nuclear Information System (INIS)

    Serck-Hanssen, G.; Soevik, O.

    1987-01-01

    Insulin binding was studied in subpopulations of bovine chromaffin cells enriched in adrenalin-producing cells (A-cells) or noradrenalin-producing cells (NA-cells). Binding of 125 I-insulin was carried out at 15 0 C for 3 hrs in the absence or presence of excess unlabeled hormone. Four fractions of cells were obtained by centrifugation on a stepwise bovine serum albumin gradient. The four fractions were all shown to bind insulin in a specific manner and the highest binding was measured in the cell layers of higher densities, containing mainly A-cells. The difference in binding of insulin to the four subpopulations of chromaffin cells seemed to be related to differences in numbers of receptors as opposed to receptor affinities. The authors conclude that bovine chromaffin cells possess high affinity binding sites for insulin and that these binding sites are mainly confined to A-cells. 24 references, 2 figures, 1 table

  4. Photoluminescence in large fluence radiation irradiated space silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Hisamatsu, Tadashi; Kawasaki, Osamu; Matsuda, Sumio [National Space Development Agency of Japan, Tsukuba, Ibaraki (Japan). Tsukuba Space Center; Tsukamoto, Kazuyoshi

    1997-03-01

    Photoluminescence spectroscopy measurements were carried out for silicon 50{mu}m BSFR space solar cells irradiated with 1MeV electrons with a fluence exceeding 1 x 10{sup 16} e/cm{sup 2} and 10MeV protons with a fluence exceeding 1 x 10{sup 13} p/cm{sup 2}. The results were compared with the previous result performed in a relative low fluence region, and the radiation-induced defects which cause anomalous degradation of the cell performance in such large fluence regions were discussed. As far as we know, this is the first report which presents the PL measurement results at 4.2K of the large fluence radiation irradiated silicon solar cells. (author)

  5. Radiation resistance of amorphous silicon alloy solar cells

    International Nuclear Information System (INIS)

    Hanak, J.J.; Chen, E.; Myatt, A.; Woodyard, J.R.

    1987-01-01

    The radiation resistance of a-Si alloy solar cells when bombarded by high energy particles is reviewed. The results of investigations of high energy proton radiation resistance of a-Si alloy thin film photovoltaic cells are reported. Irradiations were carried out with 200 keV and 1.00 MeV protons with fluences ranging betweeen 1E11 and 1E15 cm-2. Defect generation and passivation mechanisms were studied using the AM1 conversion efficiency and isochronal anneals. It is concluded that the primary defect generation mechanism results from the knock-on of Si and Ge in the intrinsic layer of the cells. The defect passivation proceeds by the complex annealing of Si and Ge defects and not by the simple migration of hydrogen

  6. Secondary immunization generates clonally related antigen-specific plasma cells and memory B cells.

    Science.gov (United States)

    Frölich, Daniela; Giesecke, Claudia; Mei, Henrik E; Reiter, Karin; Daridon, Capucine; Lipsky, Peter E; Dörner, Thomas

    2010-09-01

    Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their V(H) genes.

  7. Identifying States along the Hematopoietic Stem Cell Differentiation Hierarchy with Single Cell Specificity via Raman Spectroscopy.

    Science.gov (United States)

    Ilin, Yelena; Choi, Ji Sun; Harley, Brendan A C; Kraft, Mary L

    2015-11-17

    A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely related short-term repopulating HSCs (ST-HSCs) and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four subpopulations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that

  8. Radiation doses and cause-specific mortality among workers at a nuclear materials fabrication plant

    International Nuclear Information System (INIS)

    Checkoway, H.; Pearce, N.; Crawford-Brown, D.J.; Cragle, D.L.

    1988-01-01

    A historical cohort mortality study was conducted among 6781 white male employees from a nuclear weapons materials fabrication plant for the years 1947-1979. Exposures of greatest concern are alpha and gamma radiation emanating primarily from insoluble uranium compounds. Among monitored workers, the mean cumulative alpha radiation dose to the lung was 8.21 rem, and the mean cumulative external whole body penetrating dose from gamma radiation was 0.96 rem. Relative to US white males, the cohort experienced mortality deficits from all causes combined, cardiovascular diseases, and from most site-specific cancers. Mortality excesses of lung and brain and central nervous system cancers were seen from comparisons with national and state rates. Dose-response trends were detected for lung cancer mortality with respect to cumulative alpha and gamma radiation, with the most pronounced trend occurring for gamma radiation among workers who received greater than or equal to 5 rem of alpha radiation. These trends diminished in magnitude when a 10-year latency assumption was applied. Under a zero-year latency assumption, the rate ratio for lung cancer mortality associated with joint exposure of greater than or equal to 5 versus less than 1 rem of both types of radiation is 4.60 (95% confidence limits (CL) 0.91, 23.35), while the corresponding result, assuming a 10-year latency, is 3.05 (95% CL 0.37, 24.83). While these rate ratios, which are based on three and one death, respectively, lack statistical precision, the observed dose-response trends indicate potential carcinogenic effects to the lung of relatively low-dose radiation. There are no dose-response trends for mortality from brain and central nervous system cancers

  9. Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Chen, Xiangyun; Wu, Jingjing; Chen, Yitian; Ye, Dongxia; Lei, Hu; Xu, Hanzhang; Yang, Li; Wu, Yingli; Gu, Wenli

    2016-10-01

    Ubiquitin-specific protease 14, a deubiquitinating enzyme, has been implicated in the tumorigenesis and progression of several cancers, but its role in oral squamous cell carcinoma remains to be elucidated. The aim of this study was to explore the expression pattern and roles of Ubiquitin-specific protease 14 in the occurrence and development of oral squamous cell carcinoma. Interestingly, Ubiquitin-specific protease 14 was overexpressed in oral cancer tissues and cell lines at both mRNA and protein levels. b-AP15, a specific inhibitor of Ubiquitin-specific protease 14, significantly inhibited the growth of cancer cells and increased cell apoptosis in a dose-dependent manner. Moreover, knockdown of Ubiquitin-specific protease 14 by shRNA significantly inhibited the proliferation and migration of cancer cells in vitro. Finally, using a xenograft mouse model of oral squamous cell carcinoma, knockdown of Ubiquitin-specific protease 14 markedly inhibited tumor growth and triggered the cancer cell apoptosis in vivo, supporting previous results. In conclusion, for the first time we have demonstrated the expression pattern of Ubiquitin-specific protease 14 in oral squamous cell carcinoma and verified a relationship with tumor growth and metastasis. These results may highlight new therapeutic strategies for tumor treatment, application of Ubiquitin-specific protease 14 selective inhibitor, such as b-AP15, or knockdown by shRNA. Collectively, Ubiquitin-specific protease 14 could be a potential therapeutic target for oral squamous cell carcinoma patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Simulation of TGF-Beta Activation by Low-Dose HZE Radiation in a Cell Culture

    Science.gov (United States)

    Plante, Ianik; Cucinotta, Francis A.

    2009-01-01

    High charge (Z) and energy (E) (HZE) nuclei comprised in the galactic cosmic rays are main contributors to space radiation risk. They induce many lesions in living matter such as non-specific oxidative damage and the double-strand breaks (DSBs), which are considered key precursors of early and late effects of radiation. There is increasing evidence that cells respond collectively rather than individually to radiation, suggesting the importance of cell signaling1. The transforming growth factor (TGF ) is a signaling peptide that is expressed in nearly all cell type and regulates a large array of cellular processes2. TGF have been shown to mediate cellular response to DNA damage3 and to induce apoptosis in non-irradiated cells cocultured with irradiated cells4. TFG molecules are secreted by cells in an inactive complex known as the latency-associated peptide (LAP). TGF is released from the LAP by a conformational change triggered by proteases, thrombospondin-1, integrins, acidic conditions and .OH radical5. TGF then binds to cells receptors and activates a cascade of events mediated by Smad proteins6, which might interfere with the repair of DNA. Meanwhile, increasingly sophisticated Brownian Dynamics (BD) algorithms have appeared recently in the literature7 and can be applied to study the interaction of molecules with receptors. These BD computer models have contributed to the elucidation of signal transduction, ligand accumulation and autocrine loops in the epidermal growth factor (EGF) and its receptor (EFGR) system8. To investigate the possible roles of TGF in an irradiated cell culture, our Monte-Carlo simulation codes of the radiation track structure9 will be used to calculate the activation of TFG triggered by .OH produced by low doses of HZE ions. The TGF molecules will then be followed by a BD algorithm in a medium representative of a cell culture to estimate the number of activated receptors.

  11. Biochemical and biological responses in V79 cells grown in different background radiation environment

    International Nuclear Information System (INIS)

    Amicarelli, F.; Colafarina, S.; Ara, C.; Antonelli, F.; Balata, M.; Belli, M.; Simone, G.; Satta, L.

    2003-01-01

    Full text: In order to investigate the influence of a low background radiation environment on the biochemical and biological responses of mammalian cells cultured in vitro, a cell culture laboratory has been set up at the Gran Sasso National Laboratory (LNGS) of the Istituto Nazionale di Fisica Nucleare (INFN), located under the Gran Sasso d'Italia mountain, where cosmic rays are reduced by a factor of 10 6 and neutrons by a factor of 10 3 respect to the outside environment. Chinese hamster V79 cells were grown in parallel for up to nine months at LNGS and at the Istituto Superiore di Sanita (ISS). At the LNGS the exposure due to radon was reduced by a factor of about 25 with respect to the ISS. The biological end points addressed concerned cells proliferation, the expression of enzymes specific for the reduction of superoxydes, mutation induction by gamma-rays at the hprt locus and apoptotic sensitivity. After 9 months of culture, the cells grown at the LNGS, compared to the cells grown at the ISS, exhibit: i) a significant increase of the cell density at confluence; ii) a significantly higher capacity to scavenge organic and inorganic hydroperoxydes but a reduced scavenging capacity towards superoxide anions; iii) an increase in both the basal hprt mutation frequency and the sensitivity to the mutagenic effect of gamma-rays. The cells grown at the LNGS also show greater apoptotic sensitivity at the third month of culture that is no longer detected after nine months. Overall, these data suggest that cell response to ionizing radiation may be more complex than that predicted by a linear relationship with the dose and are consistent with the occurrence of an adaptive response related to the background radiation. However, other possibilities cannot be excluded such as the selection, in the two cultures, of clones having different characteristics, independently of the different radiation background. Work is in progress to better elucidate this point

  12. Cell-cycle distributions and radiation responses of Chinese hamster cells cultured continuously under hypoxic conditions

    International Nuclear Information System (INIS)

    Tokita, N.; Carpenter, S.G.; Raju, M.R.

    1984-01-01

    Cell-cycle distributions were measured by flow cytometry for Chinese hamster (CHO) cells cultured continuously under hypoxic conditions. DNA histograms showed an accumulation of cells in the early S phase followed by a traverse delay through the S phase, and a G 2 block. During hypoxic culturing, cell viability decreased rapidly to less than 0.1% at 120 h. Radiation responses for cells cultured under these conditions showed an extreme radioresistance at 72 h. Results suggest that hypoxia induces a condition similar to cell synchrony which itself changes the radioresistance of hypoxic cells. (author)

  13. Radiation response characteristics of human cell in vitro

    International Nuclear Information System (INIS)

    Hall, E.J.

    1987-01-01

    Improvements in tissue culture techniques and growth media have made it possible to culture a range of cells of human origin, both normal and malignant. The most recent addition to the list are endothelial cells. Interesting results have been obtained, some of which may have implications in Radiation Therapy. (i) Repair of Potentially Lethal Damage (PLDR) has been observed in all cell lines investigated; cells of normal origin repair PLD at least as well as malignant cells, which makes clinical trials of PLDR inhibitors of doubtful usefulness. (ii) PLD in fibroblasts of human origin appears to have a component that is repaired rapidly, in a matter of minutes, as well as a slower component that takes hours to repair. (iii) Sublethal damage repair, manifest by a dose-rate effect, has also been observed in all human cell lines tested. Cells of normal tissue origin, including fibroblasts and endothelial cells, exhibit a dose-rate effect that is intermediate between that for cells from traditionally resistant tumors (melanoma and osteosarcoma) and cells from more sensitive tumors (neuroblastoma and breast). (iv) Fibroblasts from patients with Ataxia Telangectasia (AT) are much more sensitive to x-rays, with a D/sub o/ about half that for normal human fibroblasts. Nevertheless repair of both PLD and SLD can be demonstrated in these cells

  14. Radiation adaptive response for the growth of cultured glial cells

    International Nuclear Information System (INIS)

    Suzuki, S.; Miura, Y.; Kano, M.; Toda, T.; Urano, S.

    2003-01-01

    Full text: To examine the molecular mechanism of radiation adaptive response (RAR) for the growth of cultured glial cells and to investigate the influence of aging on the response, glial cells were cultured from young and aged rats (1 month and 24 months old). RAR for the growth of glial cells conditioned with a low dose of X-rays and subsequently exposed to a high dose of X-rays was examined for cell number and BrdU incorporation. Involvement of the subcellular signaling pathway factors in RAR was investigated using their inhibitors, activators and mutated glial cells. RAR was observed in cells cultured from young rats, but was not in cells from aged rats. The inhibitors of protein kinase C (PKC) and DNA-dependent protein kinase (DNA-PK) or phosphatidylinositol 3-kinase (PI3K) suppressed RAR. The activators of PKC instead of low dose irradiation also caused RAR. Moreover, glial cells cultured from severe combined immunodeficiency (scid) mice (CB-17 scid) and ataxia-telangiectasia (AT) cells from AT patients showed no RAR. These results indicated that PKC, ATM, DNAPK and/or PI3K were involved in RAR for growth and BrdU incorporation of cultured glial cells and RAR decreased with aging. Proteomics data of glial cells exposed to severe stress of H 2 O 2 or X-rays also will be presented in the conference since little or no difference has not been observed with slight stress yet

  15. CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

    Directory of Open Access Journals (Sweden)

    Mariam El-Ashmawy

    Full Text Available Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs. In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF = 1.3, and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

  16. Promoting effects of adipose-derived stem cells on breast cancer cells are reversed by radiation therapy.

    Science.gov (United States)

    Baaße, Annemarie; Juerß, Dajana; Reape, Elaine; Manda, Katrin; Hildebrandt, Guido

    2018-04-01

    Partial breast irradiation of early breast cancer patients after lumpectomy and the use of endogenous adipose tissue (AT) for breast reconstruction are promising applications to reduce the side effects of breast cancer therapy. This study tries to investigate the possible risks associated with these therapeutic approaches. It also examines the influence of adipose derived stem cells (ADSCs) as part of the breast cancer microenvironment, and endogenous AT on breast cancer cells following radiation therapy. ADSCs, isolated from human reduction mammoplasties of healthy female donors, exhibited multilineage capacity and specific surface markers. The promoting effects of ADSCs on the growth and survival fraction of breast cancer cells were reversed by treatment with high (8 Gy) or medium (2 Gy) radiation doses. In addition, a suppressing influence on breast cancer growth could be detected by co-culturing with irradiated ADSCs (8 Gy). Furthermore the clonogenic survival of unirradiated tumor cells was reduced by medium of irradiated ADSCs. In conclusion, radiation therapy changed the interactions of ADSCs and breast cancer cells. On the basis of our work, the importance of further studies to exclude potential risks of ADSCs in regenerative applications and radiotherapy has been emphasized.

  17. Site-Specific Genome Engineering in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Merkert, Sylvia; Martin, Ulrich

    2016-06-24

    The possibility to generate patient-specific induced pluripotent stem cells (iPSCs) offers an unprecedented potential of applications in clinical therapy and medical research. Human iPSCs and their differentiated derivatives are tools for diseases modelling, drug discovery, safety pharmacology, and toxicology. Moreover, they allow for the engineering of bioartificial tissue and are promising candidates for cellular therapies. For many of these applications, the ability to genetically modify pluripotent stem cells (PSCs) is indispensable, but efficient site-specific and safe technologies for genetic engineering of PSCs were developed only recently. By now, customized engineered nucleases provide excellent tools for targeted genome editing, opening new perspectives for biomedical research and cellular therapies.

  18. Rapid assay for cell age response to radiation by electronic volume flow cell sorting

    International Nuclear Information System (INIS)

    Freyer, J.P.; Wilder, M.E.; Raju, M.R.

    1987-01-01

    A new technique is described for measuring cell survival as a function of cell cycle position using flow cytometric cell sorting on the basis of electronic volume signals. Sorting of cells into different cell age compartments is demonstrated for three different cell lines commonly used in radiobiological research. Using flow cytometric DNA content analysis and [ 3 H]thymidine autoradiography of the sorted cell populations, it is demonstrated that resolution of the age compartment separation is as good as or better than that reported for other cell synchronizing techniques. Variation in cell survival as a function of position in the cell cycle after a single dose of radiation as measured by volume cell sorting is similar to that determined by other cell synchrony techniques. Advantages of this method include: (1) no treatment of the cells is required, thus, this method is noncytotoxic; (2) no cell cycle progression is needed to obtain different cell age compartments; (3) the cell population can be held in complete growth medium at any desired temperature during sorting; (4) a complete radiation age - response assay can be plated in 2 h. Applications of this method are discussed, along with some technical limitations. (author)

  19. Radiation and biophysical studies on cells and viruses. Progress report, February 29, 1974--March 31, 1975

    International Nuclear Information System (INIS)

    Cole, A.

    Progress is reported on the following research projects: sedimentation analysis of chromosome components from interphase and mitotic chromosomes; electron microscopy of mitotic chromosomes; radiosensitive site analysis using short range particle beams; studies on nucleoproteins and DNA; RBE and OER for double strand breaks and single strand breaks of DNA irradiated with 241 Am alpha particles; use of 241 Am alpha particle track-ends to study the location of radiosensitive sites; gamma irradiation of nucleoprotein model systems; assembly of new equipment for the analysis of DNA size distributions; cell rejoining of DNA breaks induced by various radiations; studies on cell transformation induced by gamma radiation; localization of cellular sites for DNA breakage using labeled specific antibodies; and semiconductor properties of melanins related to preferential killing of melanoma cells. (U.S.)

  20. Radiation effects in heteroepitaxial InP solar cells

    Science.gov (United States)

    Weinberg, I.; Curtis, H. B.; Swartz, C. K.; Brinker, D. J.; Vargas-Aburto, C.

    1993-01-01

    Heteroepitaxial InP solar cells, with GaAs substrates, were irradiated by 0.5 and 3 MeV protons and their performance, temperature dependency, and carrier removal rates determined as a function of fluence. The radiation resistance of the present cells was significantly greater than that of non-heteroepitaxial InP cells at both proton energies. A clear difference in the temperature dependency of V(sub oc), was observed between heteroepitaxial and homoepitaxial InP cells. The analytically predicted dependence of dV(sub oc)/dT on Voc was confirmed by the fluence dependence of these quantities. Carrier removal was observed to increase with decreasing proton energy. The results obtained for performance and temperature dependency were attributed to the high dislocation densities present in the heteroepitaxial cells while the energy dependence of carrier removal was attributed to the energy dependence of proton range.

  1. Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model

    Directory of Open Access Journals (Sweden)

    Osman Nadia

    2004-09-01

    Full Text Available Abstract Background Leucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy. Method A midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion were then analysed in ileal venules 2 – 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO and cell histology were analysed. Results The highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation. Conclusion This study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological

  2. Mutagenesis in mammalian cells can be modulated by radiation-induced voltage-dependent potassium channels

    International Nuclear Information System (INIS)

    Saad, A.H.; Zhou, L.Y.; Lambe, E.K.; Hahn, G.M.

    1994-01-01

    In mammalian cells, little is known about the initial events whose ultimate consequence is mutagenesis or DNA repair. The role the plasma membrane may play as an initiator of such a pathway is not understood. We show, for the first time, that membrane voltage-dependent potassium (K + ) currents, activated by ionizing radiation play a significant role in radiation mutagenesis. Specifically, we show that the frequency of mutation at the HGPRT locus is increased as expected to 37.6±4.0 mutations per 100,000 survivors by 800 cGy of ionizing radiation from a spontaneous frequency of 1.5±1.5. This increase, however, is abolished if either K + channel blocker, CsCl or BaCl 2 , is present for 2h following irradiation of the cells. RbCl, chemically similar to CsCl but known not to block K + channels, is ineffective in reducing the mutation frequency. Treatment of cells with CsCl or BaCl 2 had no effect on radiation-induced cell killing

  3. Radiation therapy in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Fietkau, R.; Grabenbauer, G.G.; Sauer, R.

    1994-01-01

    The records of 52 patients with inoperable but localized squamous cell carcinomas of the esophagus were reviewed to determine the influence of different treatment modalities on survival, dysphagia and sites of recurrence. 22 patients were treated by concurrent radio-chemotherapy with cis-platin/5-FU or carboplatin/5-FU; 19 patients by radiotherapy alone; six patients by chemotherapy followed by irradiation and five patients by concurrent radio-chemotherapy with various drugs. External beam radiotherapy consisted of treating the primary lesion (mean dose 53 Gy) and the lymphatic areas (mean dose 31±26 Gy) at the rate of 2 Gy/day for five days/week. Additional intraluminal high-dose-rate radiotherapy was performed in 13 patients with single fractions of 6 Gy as a boost. Minimum follow-up was twelve months, median follow-up 4.3 years. For the whole population a remission rate of 65% (34/52 patients) was achieved (complete remission 18/52 patients=35%; partial remission 16/52 patients=31%). Relief of dysphagia accompanied tumor regression. Median survival was eleven months; three-year survival rate 23%; five-year survival rate 7.6%. The analysis of recurrence revealed a high rate of local failures (26/52 patients=50%) and distant metastases (9/52 patients=18%). Comparing the different modalities the best results were achieved by concurrent radio-chemotherapy with cis-platin/5-FU or carboplatin/5-FU: Complete remission could be determined in 46% and median survival was 14.9 months. Additional intracavitary radiotherapy resulted in a slightly better local control rate (54% vs. 46%) and three-year-survival rate (30% vs. 20%) compared to external beam irradiation alone. (orig./MG) [de

  4. Comparison of gamma radiation - induced effects in two human prostate cancer cells

    International Nuclear Information System (INIS)

    Vucic, V.; Adzic, M.; Ruzdijic, S.; Radojcic, M.B. . E-mail address of corresponding author: vesnav@vin.bg.ac.yu; Vucic, V.)

    2005-01-01

    In this study, the effects of gamma radiation on two hormone refractory human prostate cancer cell lines, DU 145 and PC-3, were followed. It was shown that gamma radiation induced significant inhibition of cell proliferation and viability in dose dependent manner. Antiproliferative effects of radiation were similar in both cell lines, and more pronounced than cytotoxic effects. In addition to that, PC-3 cell line was more resistant to radiation -induced cytotoxicity. (author)

  5. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  6. Peroxiredoxin IV Protects Cells From Radiation-Induced Apoptosis in Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Park, Jung Je; Chang, Hyo Won; Jeong, Eun-Jeong; Roh, Jong-Lyel; Choi, Seung-Ho; Jeon, Sea-Yuong; Ko, Gyung Hyuck; Kim, Sang Yoon

    2009-01-01

    Purpose: Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and -II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). Methods and Materials: To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. Results: Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. Conclusion: The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma

  7. DNA Damage by Radiation in Tradescantia Leaf Cells

    International Nuclear Information System (INIS)

    Han, Min; Hyun, Kyung Man; Ryu, Tae Ho; Kim, Jin Kyu; Nili, Mohammad

    2010-01-01

    The comet assay is currently used in different areas of biological sciences to detect DNA damage. The comet assay, due to its simplicity, sensitivity and need of a few cells, is ideal as a short-term genotoxicity test. The comet assay can theoretically be applied to every type of eukaryotic cell, including plant cells. Plants are very useful as monitors of genetic effects caused by pollution in the atmosphere, water and soil. Tradescantia tests are very useful tools for screening the mutagenic potential in the environment. Experiments were conducted to study the genotoxic effects of ionizing radiations on the genome integrity, particularly of Tradescantia. The increasingly frequent use of Tradescantia as a sensitive environmental bioindicator of genotoxic effects. This study was designed to assess the genotoxicity of ionizing radiation using Tradescnatia-comet assay. The development of comet assay has enabled investigators to detect DNA damage at the levels of cells. To adapt this assay to plant cells, nuclei were directly obtained from Tradescantia leaf samples. A significant dose-dependent increase in the average tail moment values over the negative control was observed. Recently the adaptation of this technique to plant cells opens new possibilities for studies in variety area. The future applications of the comet assay could impact some other important areas, certainly, one of the limiting factors to its utility is the imagination of the investigator.

  8. DNA Damage by Radiation in Tradescantia Leaf Cells

    Energy Technology Data Exchange (ETDEWEB)

    Han, Min; Hyun, Kyung Man; Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2010-04-15

    The comet assay is currently used in different areas of biological sciences to detect DNA damage. The comet assay, due to its simplicity, sensitivity and need of a few cells, is ideal as a short-term genotoxicity test. The comet assay can theoretically be applied to every type of eukaryotic cell, including plant cells. Plants are very useful as monitors of genetic effects caused by pollution in the atmosphere, water and soil. Tradescantia tests are very useful tools for screening the mutagenic potential in the environment. Experiments were conducted to study the genotoxic effects of ionizing radiations on the genome integrity, particularly of Tradescantia. The increasingly frequent use of Tradescantia as a sensitive environmental bioindicator of genotoxic effects. This study was designed to assess the genotoxicity of ionizing radiation using Tradescnatia-comet assay. The development of comet assay has enabled investigators to detect DNA damage at the levels of cells. To adapt this assay to plant cells, nuclei were directly obtained from Tradescantia leaf samples. A significant dose-dependent increase in the average tail moment values over the negative control was observed. Recently the adaptation of this technique to plant cells opens new possibilities for studies in variety area. The future applications of the comet assay could impact some other important areas, certainly, one of the limiting factors to its utility is the imagination of the investigator.

  9. Radiation effects in silicon and gallium arsenide solar cells using isotropic and normally incident radiation

    Science.gov (United States)

    Anspaugh, B. E.; Downing, R. G.

    1984-01-01

    Several types of silicon and gallium arsenide solar cells were irradiated with protons with energies between 50 keV and 10 MeV at both normal and isotropic incidence. Damage coefficients for maximum power relative to 10 MeV were derived for these cells for both cases of omni-directional and normal incidence. The damage coefficients for the silicon cells were found to be somewhat lower than those quoted in the Solar Cell Radiation Handbook. These values were used to compute omni-directional damage coefficients suitable for solar cells protected by coverglasses of practical thickness, which in turn were used to compute solar cell degradation in two proton-dominated orbits. In spite of the difference in the low energy proton damage coefficients, the difference between the handbook prediction and the prediction using the newly derived values was negligible. Damage coefficients for GaAs solar cells for short circuit current, open circuit voltage, and maximum power were also computed relative to 10 MeV protons. They were used to predict cell degradation in the same two orbits and in a 5600 nmi orbit. Results show the performance of the GaAs solar cells in these orbits to be superior to that of the Si cells.

  10. Comparison of 864 and 935 MHz microwave radiation effects on cell culture

    International Nuclear Information System (INIS)

    Pavicic, I.; Trosic, I.; Sarolic, A.

    2005-01-01

    The aim of our study was to evaluate and compare the effect of 864 and 935 MHz microwave radiation on proliferation, colony forming and viability of Chinese hamster lung cells, cell line V79. Cell cultures were exposed both to the 864 MHz microwave field in transversal electromagnetic mode cell (TEM-cell) and to the 935 MHz field in Gigahertz transversal electromagnetic mode cell (GTEM-cell) for 1, 2 and 3 hours. Philips PM 5508 generator connected with a signal amplifier generated the frequency of 864 MHz, whereas Hewlett Packard HP8657A signal generator was used to generate the frequency of 935 MHz. The average specific absorption rate (SAR) was 0.08 W/kg for 864 MHz and 0.12 W/kg for 935 MHz. To determine the cell growth, V79 cells were plated in the concentration of 1x10 4 cells per milliliter of nutrient medium. Cells were cultured in a humidified atmosphere at 37 degrees of C in 5% CO 2 . Cell proliferation was determined by cell counts for each hour of exposure during the five post-exposure days. To identify colony-forming ability, cells were cultivated in the concentration of 40 cells/mL of medium and incubated as described above. Colony-forming ability was assessed for each exposure time by colony count on post-exposure day 7. Trypan blue exclusion test was used to determine cell viability. On post-exposure day 3, the growth curve of 864 MHz irradiated cells showed a significant decrease (p less than 0.05) after 2 and 3 hours of exposure in comparison with control cells. Cells exposed to 935 MHz radiation showed a significant decrease (p less than 0.05) after 3 hours of exposure on post-exposure day 3. Both the colony-forming ability and viability of 864 MHz and 935 MHz exposed cells did not significantly differ from matched control cells. In conclusion, both applied RF/MW fields have shown similar effects on cell culture growth, colony forming and cell viability of the V79 cell line.(author)

  11. EORTC radiation proctitis-specific quality of life module - Pretesting in four European countries

    International Nuclear Information System (INIS)

    Halkett, Georgia; Aoun, Samar; Hayne, Dickon; Lund, Jo-Asmund; Gruen, Arne; Villa, Julie; Livi, Lorenzo; Arcangeli, Stefano; Velikova, Galina; Spry, Nigel

    2010-01-01

    Background and purpose: Radiation proctitis is a side effect which can occur after pelvic radiation therapy. Currently available questionnaires do not comprehensively assess the range of problems, nor impact on quality of life associated with proctitis. This article reports on the cultural testing phase of an EORTC module (QLQ-PRT21) developed to assess radiation proctitis specific issues and designed to be used in conjunction with the EORTC core quality of life questionnaire (QLQ-C30). Methods: The previously developed 21-item module, pre-tested in Australia, was translated into Norwegian, German, French and Italian. Patients completed the EORTC QLQ-C30 and module questionnaires towards the end of their radical pelvic radiation treatment to target acute side effects. Patients experiencing chronic proctitis were also surveyed. Patients also participated in structured interviews to determine issues of comprehensibility, coverage and relevance. Results were compared with Australian data. Results: Questionnaires were completed by 64 European patients. The module was found to be relevant and culturally acceptable to participants. Feedback has led to minor translation modifications and the inclusion of two additional questions. Conclusion: This module is ready for Phase IV testing which will consist of large scale field testing with the aim to perform psychometric analysis and finalise a module that will be suitable in the assessment of radiation induced proctitis.

  12. Stem cell, cytokine and plastic surgical management for radiation injuries

    International Nuclear Information System (INIS)

    Akita, Sadanori; Hirano, Akiyoshi; Akino, Kozo

    2008-01-01

    Increasing concern on systemic and local radiation injuries caused by nuclear power plant accident, therapeutic irradiation or nuclear terrorism should be treated and prevented properly for life-saving and improved wound management. We therefore reviewed our therapeutic regimens and for local radiation injuries and propose surgical methods reflecting the importance of the systemic and general conditions. For local radiation injuries, after careful and complete debridement, sequential surgeries with local flap, arterialized or perforator flap and to free flap are used when the patients' general conditions allow. Occasionally, undetermined wound margins in acute emergency radiation injuries and the regenerative surgical modalities should be attempted with temporal artificial dermis impregnated and sprayed with angiogenic factor such as basic fibroblast growth factor (bFGF) and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Human mesenchymal stem cells (hMSCs) and adipose-derived stem cells (ADSCs), together with angiogenic and mitogenic factor of basic fibroblast growth factor (bFGF) and an artificial dermis were applied over the excised irradiated skin defect are tested for differentiation and local stimulation effects in the radiation-exposed wounds. The perforator flap and artificial dermal template with growth factor were successful for reconstruction in patients who are suffering from complex underlying disease. Patients were uneventfully treated with minimal morbidities. The hMSCs are strongly proliferative even after 20 Gy irradiation in vitro. Immediate artificial dermis application impregnated with hMSCs and bFGF over the 20 Gy irradiated skin and soft tissues demonstrated the significantly improved fat angio genesis, architected dermal reconstitution and less inflammatory epidermal recovery. Even though emergent cases are more often experienced, detailed understanding of underlying diseases and rational

  13. Stem cell, cytokine and plastic surgical management for radiation injuries

    Energy Technology Data Exchange (ETDEWEB)

    Akita, Sadanori; Hirano, Akiyoshi [Dept. of Plastic and Reconstructive Surgery, Nagasaki (Japan); Akino, Kozo [Nagasaki Univ. (Japan). Graduate School of Biomedical Sciences, Dept. of Neuroanatomy; Ohtsuru, Akira [Nagasaki Univ. Hospital (Japan). Takashi Nagai Memorial, International Hibakusha Medical Center; Yamashita, Shunichi [Nagasaki Univ. School of Medicine (Japan). Atomic Bomb Disease Institute; World Health Organization (WHO), Nagasaki (Japan)

    2008-07-01

    Increasing concern on systemic and local radiation injuries caused by nuclear power plant accident, therapeutic irradiation or nuclear terrorism should be treated and prevented properly for life-saving and improved wound management. We therefore reviewed our therapeutic regimens and for local radiation injuries and propose surgical methods reflecting the importance of the systemic and general conditions. For local radiation injuries, after careful and complete debridement, sequential surgeries with local flap, arterialized or perforator flap and to free flap are used when the patients' general conditions allow. Occasionally, undetermined wound margins in acute emergency radiation injuries and the regenerative surgical modalities should be attempted with temporal artificial dermis impregnated and sprayed with angiogenic factor such as basic fibroblast growth factor (bFGF) and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Human mesenchymal stem cells (hMSCs) and adipose-derived stem cells (ADSCs), together with angiogenic and mitogenic factor of basic fibroblast growth factor (bFGF) and an artificial dermis were applied over the excised irradiated skin defect are tested for differentiation and local stimulation effects in the radiation-exposed wounds. The perforator flap and artificial dermal template with growth factor were successful for reconstruction in patients who are suffering from complex underlying disease. Patients were uneventfully treated with minimal morbidities. The hMSCs are strongly proliferative even after 20 Gy irradiation in vitro. Immediate artificial dermis application impregnated with hMSCs and bFGF over the 20 Gy irradiated skin and soft tissues demonstrated the significantly improved fat angio genesis, architected dermal reconstitution and less inflammatory epidermal recovery. Even though emergent cases are more often experienced, detailed understanding of underlying diseases and rational

  14. Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zwicker, F.; Roeder, F.; Debus, J.; Huber, P.E. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology; Kirsner, A.; Weber, K.J. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Peschke, P. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology

    2013-08-15

    Background: Inhibition of pyruvate dehydrogenase kinase (PDK) by dichloroacetate (DCA) can shift tumor cell metabolism from anaerobic glycolysis to glucose oxidation, with activation of mitochondrial activity and chemotherapy-dependent apoptosis. In radiotherapy, DCA could thus potentially enhance the frequently moderate apoptotic response of cancer cells that results from their mitochondrial dysfunction. The aim of this study was to investigate tumor-specific radiosensitization by DCA in vitro and in a human tumor xenograft mouse model in vivo. Materials and methods: The interaction of DCA with photon beam radiation was investigated in the human tumor cell lines WIDR (colorectal) and LN18 (glioma), as well as in the human normal tissue cell lines HUVEC (endothelial), MRC5 (lung fibroblasts) and TK6 (lymphoblastoid). Apoptosis induction in vitro was assessed by DAPI staining and sub-G1 flow cytometry; cell survival was quantified by clonogenic assay. The effect of DCA in vivo was investigated in WIDR xenograft tumors growing subcutaneously on BALB/c-nu/nu mice, with and without fractionated irradiation. Histological examination included TUNEL and Ki67 staining for apoptosis and proliferation, respectively, as well as pinomidazole labeling for hypoxia. Results: DCA treatment led to decreased clonogenic survival and increased specific apoptosis rates in tumor cell lines (LN18, WIDR) but not in normal tissue cells (HUVEC, MRC5, TK6). However, this significant tumor-specific radiosensitization by DCA in vitro was not reflected by the situation in vivo: The growth suppression of WIDR xenograft tumors after irradiation was reduced upon additional DCA treatment (reflected by Ki67 expression levels), although early tumor cell apoptosis rates were significantly increased by DCA. This apparently paradoxical effect was accompanied by a marked DCA-dependent induction of hypoxia in tumor-tissue. Conclusion: DCA induced tumor-specific radiosensitization in vitro but not in vivo

  15. Technical specifications manual for the MARK-1 pulsed ionizing radiation detection system

    International Nuclear Information System (INIS)

    Lawrence, R.S.; Harker, Y.D.; Jones, J.L.; Hoggan, J.M.

    1993-03-01

    The MARK-1 detection system was developed by the Idaho National Engineering Laboratory for the US Department of Energy Office of Arms Control and Nonproliferation. The completely portable system was designed for the detection and analysis of intense photon emissions from pulsed ionizing radiation sources. This manual presents the technical design specifications for the MARK-1 detection system and was written primarily to assist the support or service technician in the service, calibration, and repair of the system. The manual presents the general detection system theory, the MARK-1 component design specifications, the acquisition and control software, the data processing sequence, and the system calibration procedure. A second manual entitled: Volume 2: Operations Manual for the MARK-1 Pulsed Ionizing Radiation Detection System (USDOE Report WINCO-1108, September 1992) provides a general operational description of the MARK-1 detection system. The Operations Manual was written primarily to assist the field operator in system operations and analysis of the data

  16. Technical specifications manual for the MARK-1 pulsed ionizing radiation detection system. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, R.S.; Harker, Y.D.; Jones, J.L.; Hoggan, J.M.

    1993-03-01

    The MARK-1 detection system was developed by the Idaho National Engineering Laboratory for the US Department of Energy Office of Arms Control and Nonproliferation. The completely portable system was designed for the detection and analysis of intense photon emissions from pulsed ionizing radiation sources. This manual presents the technical design specifications for the MARK-1 detection system and was written primarily to assist the support or service technician in the service, calibration, and repair of the system. The manual presents the general detection system theory, the MARK-1 component design specifications, the acquisition and control software, the data processing sequence, and the system calibration procedure. A second manual entitled: Volume 2: Operations Manual for the MARK-1 Pulsed Ionizing Radiation Detection System (USDOE Report WINCO-1108, September 1992) provides a general operational description of the MARK-1 detection system. The Operations Manual was written primarily to assist the field operator in system operations and analysis of the data.

  17. Detection and specifity of class specific antibodies to whole bacteria cells using a solid phase radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Czerkinsky, C.; Rees, A.S.; Bergimeier, L.A.; Challacombe, S.J. (Guy' s Hospital Medical and Dental Schools, London (UK))

    1983-07-01

    A solid phase radioimmunoassay has been developed which can be used for the detection of isotype specific antibodies to whole bacteria and other particulate antigens, and is applicable to a variety of species. Bacteria are bound to the solid phase by the use either of antibodies, or of methyl glyoxal. Both methods result in a sensitive and reproducible assay, and bacteria do not appear to desorb from the solid phase. The specificity of antibodies to whole bacteria was examined by absorption of antisera with various species of bacteria and retesting, or by determining the binding of antisera to various bacteria bound to the solid phase. Both methods revealed specificity for the bacteria examined. Inhibition studies showed that antibodies to Streptococcus mutans whole cells could be inhibited by purified cell surface antigens glucosyltransferase and antigen I/II, but only minimally by lipoteichoic acid, c polysaccharide or dextran. In murine antisera antibodies of the IgG, IgM, and IgA classes could be detected at amounts of less than 1 ng/ml.

  18. The effect of MLS laser radiation on cell lipid membrane.

    Science.gov (United States)

    Pasternak, Kamila; Wróbel, Dominika; Nowacka, Olga; Pieszyński, Ireneusz; Bryszewska, Maria; Kujawa, Jolanta

    2018-03-14

    Authors of numerous publications have proved the therapeutic effect of laser irradiation on biological material, but the mechanisms at cellular and subcellular level are not yet well understood. The aim of this study was to assess the effect of laser radiation emitted by the MLS M1 system (Multiwave Locked System) at two wavelengths (808 nm continuous and 905 nm pulsed) on the stability and fluidity of liposomes with a lipid composition similar to that of human erythrocyte membrane or made of phosphatidylocholine. Liposomes were exposed to low-energy laser radiation at surface densities 195 mW/cm2 (frequency 1,000 Hz) and 230 mW/cm2 (frequency 2,000 Hz). Different doses of radiation energy in the range 0-15 J were applied. The surface energy density was within the range 0.46 - 4.9 J/cm 2. The fluidity and stability of liposomes subjected to such irradiation changed depending on the parameters of radiation used. Since MLS M1 laser radiation, depending on the parameters used, affects fluidity and stability of liposomes with the lipid content similar to erythrocyte membrane, it may also cause structural and functional changes in cell membranes.

  19. Specific spheres of application of ionising radiation effects, some realized results and comparative advantages

    International Nuclear Information System (INIS)

    Benderac, R.

    2007-01-01

    The papers discusses some results of ionizing radiation effects in realization of non-destructive methods, achieved progress from the aspect of innovation, comparative results with previously used methods, etc. A review is given of methods based on alpha-radiography, auto-alpha radiography, beta-radiography, X-ray-fluorescent analysis, X- and gamma radiography, and photos of specific samples of neutron radiography [sr

  20. Methodological principles of radiation influence upon specific function of female organism and gynecological diseases

    International Nuclear Information System (INIS)

    Tsvelev, Yu.V.; Kira, E.F.

    1994-01-01

    1025 women permanently residing at the territory subjected to radioactive contamination due to the Chernobyl NPP accident underwent dispensary examination in 1991-1992. Study of ionizing radiation influence on specific functions (menstrual, reproductive, secretory and gynecological) of female organism is carried out. It is found that the highest percentage in the structure of gynecological diseases is accounted for inflammatory diseases of uterine appendages and neck of the uterus. 1 tab

  1. The effect of patient-specific factors on radiation-induced regional lung injury

    International Nuclear Information System (INIS)

    Garipagaoglu, Melahat; Munley, Michael T.; Hollis, Donna; Poulson, Jean M.; Bentel, Gunilla C.; Sibley, Gregory; Anscher, Mitchell S.; Fan Ming; Jaszczak, Ronald J.; Coleman, R. Edward; Marks, Lawrence B.

    1999-01-01

    Purpose: To assess the impact of patient-specific factors on radiation (RT)-induced reductions in regional lung perfusion. Methods: Fifty patients (32 lung carcinoma, 7 Hodgkin's disease, 9 breast carcinoma and 2 other thoracic tumors) had pre-RT and ≥24-week post-RT single photon emission computed tomography (SPECT) perfusion images to assess the dose dependence of RT-induced reductions in regional lung perfusion. The SPECT data were analyzed using a normalized and non-normalized approach. Furthermore, two different mathematical methods were used to assess the impact of patient-specific factors on the dose-response curve (DRC). First, DRCs for different patient subgroups were generated and compared. Second, in a more formal statistical approach, individual DRCs for regional lung injury for each patient were fit to a linear-quadratic model (reduction = coefficient 1 x dose + coefficient 2 x dose 2 ). Multiple patient-specific factors including tobacco history, pre-RT diffusion capacity to carbon monoxide (DLCO), transforming growth factor-beta (TGF-β), chemotherapy exposure, disease type, and mean lung dose were explored in a multivariate analysis to assess their impact on the coefficients. Results: None of the variables tested had a consistent impact on the radiation sensitivity of regional lung (i.e., the slope of the DRC). In the formal statistical analysis, there was a suggestion of a slight increase in radiation sensitivity in the dose range >40 Gy for nonsmokers (vs. smokers) and in those receiving chemotherapy (vs. no chemotherapy). However, this finding was very dependent on the specific statistical and normalization method used. Conclusion: Patient-specific factors do not have a dramatic effect on RT-induced reduction in regional lung perfusion. Additional studies are underway to better clarify this issue. We continue to postulate that patient-specific factors will impact on how the summation of regional injury translates into whole organ injury

  2. Lethals induced by γ-radiation in drosophila somatic cells

    International Nuclear Information System (INIS)

    Ivanov, A.I.

    1989-01-01

    Exposure of 3-hour drosophila male embryos to γ-radiation during the topographic segregation of the germ anlage nuclei caused recessive sex-linked lethals in somatic cells only. The selectivity of the screening was determined by the ratio of mutation frequencies induced in embryos and adult males. Analysis of lethal mutations shows that a minimal rate of the divergence between germinal and somatic patterns of the cell development is observed in the embryogenesis, the 3d instar larva and prepupa, and maximal in the 1st and 2nd larva and pupa

  3. A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Seonmi Park

    2017-04-01

    Full Text Available Summary: Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes, and fetal hemoglobin (HbF levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS mutation. : In this resource article, Mostoslavsky, Murphy, and colleagues of the NextGen consortium describe a diverse, comprehensive, and characterized library of sickle cell disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes and fetal hemoglobin (HbF levels. This bank is readily available and accessible to all investigators. Keywords: induced pluripotent stem cells, iPSCs, sickle cell disease, disease modeling, directed differentiation, gene correction

  4. CELLISA: reporter cell-based immunization and screening of hybridomas specific for cell surface antigens.

    Science.gov (United States)

    Chen, Peter; Mesci, Aruz; Carlyle, James R

    2011-01-01

    Monoclonal antibodies (mAbs) specific for cell surface antigens are an invaluable tool to study immune receptor expression and function. Here, we outline a generalized reporter cell-based approach to the generation and high-throughput screening of mAbs specific for cell surface antigens. Termed CELLISA, this technology hinges upon the capture of hybridoma supernatants in mAb arrays that facilitate ligation of an antigen of interest displayed on BWZ reporter cells in the form of a CD3ζ-fusion chimeric antigen receptor (zCAR); in turn, specific mAb-mediated cross-linking of zCAR on BWZ cells results in the production of β-galactosidase enzyme (β-gal), which can be assayed colorimetrically. Importantly, the BWZ reporter cells bearing the zCAR of interest may be used for immunization as well as screening. In addition, serial immunizations employing additional zCAR- or native antigen-bearing cell lines can be used to increase the frequency of the desired antigen-specific hybridomas. Finally, the use of a cohort of epitope-tagged zCAR (e.g., zCAR(FLAG)) variants allows visualization of the cell surface antigen prior to immunization, and coimmunization using these variants can be used to enhance the immunogenicity of the target antigen. Employing the CELLISA strategy, we herein describe the generation of mAb directed against an uncharacterized natural killer cell receptor protein.

  5. Intestinal cell proliferation following hyperthermia-radiation combinations

    International Nuclear Information System (INIS)

    Burholt, D.R.; Wilkinson, D.A.; Shrivastava, P.N.

    1987-01-01

    The present work is an investigation of the extent to which hyperthermia enhances x-ray induced inhibition of intestinal epithelial cell proliferation in mice. Hyperthermia was achieved by whole body immersion of anesthetized ice in a temperature controlled water bath (+-0.1 0 C). Post-treatment proliferative activity was monitored by determining the incorporation of /sup 3/H-TdR into intestinal crypt cells and by the counting of epithelial cell mitotic figures. Initial levels of cell kill were assessed by the microcolony crypt survival technique. All heat treatments were 41.5 0 C for 0.5h. Heat alone reduced the /sup 3/H-TdR incorporation to 50% of the control value by 2h post-treatment. This was followed by a return to control value by 10h and a slight hyperplasia at 24h. Heat either immediately before or after 2Gy abdominal field x-irradiation produced a prolonged period of depressed cell proliferation: /sup 3/H-TdR incorporation remained below control value for the first 24h. As the heat and radiation were separated in time from each other (up to 4h) the interaction between the two decreased. The development of thermotolerance was observed following the second and third treatment during either a heat-only or a heat-radiation multifraction treatments schedule with the treatment spaced 24h apart

  6. 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

  7. Radiation effect on partially synchronized Yoshida sarcoma cells

    International Nuclear Information System (INIS)

    Bippus, P.H.; Heitz, J.; Ruehl, U.; Averdunk, R.

    1982-01-01

    Yoshida sarcoma cells, which have the same growth characteristics as ascites cells in the mouse and in cell suspension, were partially synchronized in vitro by means of excess thymidine (0.1 mM thymidine for 18 h). The growth of non-synchronized cultures was inhibited by irradiation, the degree depending on the dose of radiation. At the same time, a 50% inhibition in vivo (380 rad) and in vitro (480 rad) was determined. The incorporation of 3 H-thymidine into the DNA is inhibited by 10-32%, depending on the radiation dose. The mitotic index decreases 2 h after irradiation by a dose-dependent amount. A mitotic maximum develops later; the delay is dose-dependent. Partially synchronized cells were irradiated in the G 1 /S-, S-, G 2 -, and G 1 -phase. As compared to the 3 H-thymidine incorporation and the mitotic index there were no significant differences between the cultures which were irradiated in the individual phases of the non-synchronized control cultures. The cultures which were irradiated in the G 2 -phase, however, showed a significantly reduced growth in vivo after 48 h. If the cells were cultured for more than 72 h after irradiation, the differences between the cultures irradiated in the G 2 -phase and the other phases were reduced. (orig.)

  8. Partial reconstitution of virus-specific memory CD8+ T cells following whole body γ-irradiation

    International Nuclear Information System (INIS)

    Grayson, Jason M.; Laniewski, Nathan G.; Holbrook, Beth C.

    2006-01-01

    CD8 + memory T cells are critical in providing immunity to viral infection. Previous studies documented that antigen-specific CD8 + memory T cells are more resistant to radiation-induced apoptosis than naive T cells. Here, we determined the number and in vivo function of memory CD8 + T cells as immune reconstitution progressed following irradiation. Immediately following irradiation, the number of memory CD8 + T cells declined 80%. As reconstitution progressed, the number of memory cells reached a zenith at 33% of pre-irradiation levels, and was maintained for 120 days post-irradiation. In vitro, memory CD8 + T cells were able to produce cytokines at all times post-irradiation, but when adoptively transferred, they were not able to expand upon rechallenge immediately following irradiation, but regained this ability as reconstitution progressed. When proliferation was examined in vitro, irradiated memory CD8 + T cells were able to respond to mitogenic growth but were unable to divide

  9. 8-aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells

    International Nuclear Information System (INIS)

    Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu; Eitaki, Masato; Inanami, Osamu; Matsuda, Akira

    2011-01-01

    The combination of a chemotherapeutic agent and radiation is widely applied to enhance cell death in solid tumor cells in cancer treatment. The purine analogue 8-aminoadenosine (8-NH 2 -Ado) is known to be a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. In this report, to examine whether 8-NH 2 -Ado had the ability to enhance the radiation-induced cell killing in solid tumor cells, human lung adenocarcinoma A549 cells were irradiated in the presence and absence of 8-NH 2 -Ado. 8-NH 2 -Ado significantly increased reproductive cell death and apoptosis in A549 cells exposed to X-rays. When peptide inhibitors against caspase-3, -8, and -9 were utilized to evaluate the involvement of caspases, all inhibitors suppressed the enhancement of radiation-induced apoptosis, suggesting that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated pathways were involved in this enhancement of apoptosis. In addition, in the cells exposed to the treatment combining X-irradiation and 8-NH 2 -Ado, reduction of the intracellular ATP concentration was essential for survival, and down-regulation of the expression of antiapoptotic proteins such as survivin and X-linked inhibitor of apoptosis protein (XIAP) was observed. These results indicate that 8-NH 2 -Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors. (author)

  10. Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

    Science.gov (United States)

    Hannemann, Sebastian; Galán, Jorge E

    2017-07-01

    Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

  11. Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

    Directory of Open Access Journals (Sweden)

    Sebastian Hannemann

    2017-07-01

    Full Text Available Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

  12. Gene-specific cell labeling using MiMIC transposons.

    Science.gov (United States)

    Gnerer, Joshua P; Venken, Koen J T; Dierick, Herman A

    2015-04-30

    Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Mitigation of radiation induced hematopoietic injury via regulation of Nrf-2 and increasing hematopoietic stem cells

    International Nuclear Information System (INIS)

    Patwardhan, R.S.; Sharma, Deepak; Checker, Rahul; Santosh Kumar, S.

    2014-01-01

    Therapeutic doses of ionizing radiation (IR) that can be delivered to tumors are restricted due to radiation induced damage to surrounding normal tissues thereby limiting the effectiveness of radiotherapy. Strategies to develop agents that selectively protect normal cells yielded limited success in the past. There is pressing need to develop safe, syndrome specific and effective radiation countermeasures to prevent or mitigate the harmful consequences of radiation exposure. Survival of bone marrow stem cells (HSCs) play a key role in protecting against IR induced hematopoietic injury. Many studies have shown manipulation of HSC frequency and/or survival as principal mechanism of radioprotection. It is known that, Nrf-2 plays crucial role in HSC survival and maintenance under oxidative stress conditions. In the present study, we have investigated the radioprotective ability of a flavonoid baicalein (5,6,7-trihydroxyflavone), extracted from the root of Scutellaria baicalensis Georgi, a medicinal plant traditionally used in Oriental medicine. There are numerous reports showing anti-inflammatory, anti-apoptotic, anti-oxidant, anti-cancer, anti-microbial, anti-mutagenic and neuroprotective properties of baicalein. Based on these reports, we have investigated the ability of baicalein to protect against radiation induced hematopoietic injury. Baicalein administration to mice protected against WBI induced mortality. Interestingly, the stem cell frequency increased in bone marrow cells obtained from baicalein administered mice as compared to vehicle treated mice. Baicalein treatment led to increased phospho-Nrf-2 levels in lineage negative BM-MNC. Administration of mice with Nrf-2 inhibitor prior to baicalein treatment led to significant abrogation of radioprotective ability of baicalein. This result suggests that, Nrf-2 may be playing a key role in baicalein mediated radioprotection. Here, we have shown that baicalein administration augments stem cell frequency, induces

  14. Natural killer cells facilitate PRAME-specific T-cell reactivity against neuroblastoma

    Science.gov (United States)

    Spel, Lotte; Boelens, Jaap-Jan; van der Steen, Dirk M.; Blokland, Nina J.G.; van Noesel, Max M.; Molenaar, Jan J.; Heemskerk, Mirjam H.M.

    2015-01-01

    Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20–40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for neuroblastoma treatment, these immune escape mechanisms restrain clinical results. Therefore, we aimed to improve neuroblastoma immunogenicity to further the development of antigen-specific immunotherapy against neuroblastoma. We found that neuroblastoma cells significantly increase surface expression of MHC I upon exposure to active NK cells which thereby readily sensitize neuroblastoma cells for recognition by CTLs. We show that oncoprotein PRAME serves as an immunodominant antigen for neuroblastoma as NK-modulated neuroblastoma cells are recognized by PRAMESLLQHLIGL/A2-specific CTL clones. Furthermore, NK cells induce MHC I upregulation in neuroblastoma through contact-dependent secretion of IFNγ. Our results demonstrate remarkable plasticity in the peptide/MHC I surface expression of neuroblastoma cells, which is reversed when neuroblastoma cells experience innate immune attack by sensitized NK cells. These findings support the exploration of NK cells as adjuvant therapy to enforce neuroblastoma-specific CTL responses. PMID:26452036

  15. Study of cell cycle and apoptosis after radiation with electron linear accelerator injury

    International Nuclear Information System (INIS)

    Xu Lan; Zhou Yinghui; Shi Ning; Peng Miao; Wu Shiliang

    2002-01-01

    Purpose: To determine the cell cycle and apoptosis of the injured cells after radiation with the electron linear accelerator. Methods: NIH 3T3 cells were irradiated by the radiation with the electron linear accelerator. In the experiment the condition of the cell cycle and apoptosis of the injured cells were measured. The expression of p53 was also tested. Results: After exposure to radiation, the number of apoptotic cells as well as the expression of p53 increased. Conclusion: The electron linear accelerator radiation injury can induce cell apoptosis

  16. Radiation response of spermatogonial stem cells in the mouse

    International Nuclear Information System (INIS)

    Bootsma, A.L.

    1978-01-01

    Spermatogonial stem cells are able to repopulate the testis by forming clones that elongate along the walls of the seminiferous tubules depleted of spermatogenetic cells as a result of an irradiation. The surviving number of stem cells after irradiation was estimated by determining the fraction of repopulated tubules in cross-sections of the testis 11 weeks after irradiation. This fraction, called the 'repopulation index', is assumed to be directly proportional to the number of surviving stem cells. The response of spermatogonial stem cells in the CBA mouse to 1-MeV fission neutrons was investigated. Radioresistant, colony forming stem cells in the mouse testis move into a much more radiosensitive phase of their cell cycle shortly after irradiation. This is demonstrated in publication II in experiments in which total doses of 300 rad of neutrons and 1200 rad of X-rays were split into two equal fractions. The radiation response of spermatogonial stem cells in the mouse which survived various doses of fission neutrons 24 hours before was studied in publication III. Twenty four hours after a dose of 150 rad of fission neutrons all first-dose survivors have moved from a radioresistant (D 0 89+-4 rad in this study) towards a radiosensitive phase of their cell cycle. Spermatogonial stem cells which survive a neutron dose of 150 rad all belong to a radioresistant stem cell population in the seminiferous epithelium. The data in publication IV show that during the first 26 days after a dose of 150 rad of neutrons the stem cell population first increases and then slowly decreases its radiosensitivity, to stay fixed at a relatively high level. (Auth.)

  17. Biochemical changes to fibroblast cells subjected to ionizing radiation.

    Science.gov (United States)

    Jones, Pamala; Benghuzzi, Hamed; Tucci, Michelle; Richards, Latoya; Harrison, George; Patel, Ramesh

    2008-01-01

    High energy X-rays are capable of interacting with biological membranes to cause both functional and structural modifications. The goal of the present study was to investigate the effects human fibroblast cells exposed multiple times to 10 Gy over time. Following exposures of 2, 3, or 4 times to 10 Gy/10min the cells were evaluated for cell number changes, membrane damage, and intracellular glutathione content after 24, 48 and 72 hours. Twenty-four hours following exposure the cell numbers were reduced and increased levels of cellular membrane damage was evident. This trend was observed for the duration of the study. Interestingly, there was not an exposure dependent increase in cell damage or cell loss with time. Intracellular antioxidant systems were activated as indicated by anincrease in total cellular glutathione content. Additional studies are needed to determine if the cellular reduction is caused by a direct effect of the X-rays targeting the DNA or an indirect effect of the X-ray targeting the cellular membrane, which then generates radicals that target cell cycle checkpoints or DNA damage. In conclusion, fibroblast cells can be used to determine early and late events of cellular function following exposure to harmful levels of radiation exposure and results of exposure can be seen within twenty four hours.

  18. Ionizing radiation induces apoptosis in hematopoietic stem and progenitor cells

    International Nuclear Information System (INIS)

    Meng, A.; Zhou, D.; Geiger, H.; Zant, G.V.

    2003-01-01

    The aims of this study was to determine if ionizing radiation (IR) induces apoptosis in hematopoietic stem (HSC) and progenitor cells. Lin-cells were isolated from mouse bone marrow (BM) and pretreated with vehicle or 100 μM z-VAD 1 h prior to exposure to 4 Gy IR. The apoptotic and/or necrotic responses of these cells to IR were analyzed by measuring the annexin V and/or 7-AAD staining in HSC and progenitor populations using flow cytometry, and hematopoietic function of these cells was determined by CAFC assay. Exposure of Lin-cells to IR selectively decreased the numbers of HSC and progenitors in association with an increase in apoptosis in a time-dependent manner. Pretreatment of Lin- cells with z-VAD significantly inhibited IR-induced apoptosis and the decrease in the numbers of HSC and progenitors. However, IR alone or in combination with z-VAD did not lead to a significant increase in necrotic cell death in either HSC or progenitors. In addition, pretreatment of BM cells with z-VAD significantly attenuated IR-induced reduction in the frequencies of day-7, -28 and -35 CAFC. Exposure of HSC and progenitors to IR induces apoptosis. The induction of HSC and progenitor apoptosis contributes to IR-induced suppression of their hematopoietic function

  19. Bimodal cell death induced by high radiation doses in the radioresistant sf9 insect cell line

    International Nuclear Information System (INIS)

    Chandna, S.

    2003-01-01

    Full text: This study was conducted to investigate the mode(s) of cell death induced by high radiation doses in the highly radioresistant Sf9 insect ovarian cell line. Methods: Cells were exposed to γ-radiation doses 200Gy and 500Gy, harvested at various time intervals (6h-72h) following irradiation, and subjected to cell morphology assay, DNA agarose gel electrophoresis, single cell gel electrophoresis (SCGE; comet assay) and Annexin-V labeling for the detection of membrane phosphatidylserine externalization. Cell morphology was assessed in cells entrapped and fixed in agarose gel directly from the cell suspension, thus preventing the possible loss of fragments/ apoptotic bodies. Surviving fraction of Sf9 cells was 0.01 at 200Gy and 98%) undergoing extensive DNA fragmentation at 500Gy, whereas the frequency of cells with DNA fragmentation was considerably less (∼12%) at 200Gy. Conclusions: While the mode of cell death at 200Gy seems to be different from typical apoptosis, a dose of 500Gy induced bimodal cell death, with typical apoptotic as well as the atypical cell death observed at 200Gy

  20. Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

    International Nuclear Information System (INIS)

    Garbe, Yvette; Klier, Ulrike; Linnebacher, Michael

    2011-01-01

    Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells. Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells. We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays. The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4 + , activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed. Cellular fusions of MSI + carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and

  1. Practice specific model regulations: Radiation safety of non-medical irradiation facilities. Interim report for comment

    International Nuclear Information System (INIS)

    2003-08-01

    the infrastructure aimed at achieving its maximum efficiency, and extensively covers performance regulations. The BSS cover the application of ionizing radiation for all practices and interventions and are, therefore, basic and general in nature. Users must apply these basic requirements to their own particular practices. In this context, the preamble of the BSS states that: 'The Regulatory Authority may need to provide guidance on how certain regulatory requirements are to be fulfilled for various practices, for example in regulatory guideline documents.' There are certain requirements that, when applied to specific practices, can be fulfilled through virtually only one practical solution. In these cases, the regulatory authority would use a 'shall' statement for this solution. To meet other requirements, there may be more than one option. In these cases the regulatory authority would usually indicate the recommended option with a 'should' statement, which implies that licensees may choose another alternative provided that the level of safety is equivalent. This distinction has been maintained in this 'model regulations' for irradiation facilities in order to facilitate the decision of regulatory authorities on the degree of obligation

  2. Synthetic radiation diagnostics in PIConGPU. Integrating spectral detectors into particle-in-cell codes

    Energy Technology Data Exchange (ETDEWEB)

    Pausch, Richard; Burau, Heiko; Huebl, Axel; Steiniger, Klaus [Helmholtz-Zentrum Dresden-Rossendorf (Germany); Technische Universitaet Dresden (Germany); Debus, Alexander; Widera, Rene; Bussmann, Michael [Helmholtz-Zentrum Dresden-Rossendorf (Germany)

    2016-07-01

    We present the in-situ far field radiation diagnostics in the particle-in-cell code PIConGPU. It was developed to close the gap between simulated plasma dynamics and radiation observed in laser plasma experiments. Its predictive capabilities, both qualitative and quantitative, have been tested against analytical models. Now, we apply this synthetic spectral diagnostics to investigate plasma dynamics in laser wakefield acceleration, laser foil irradiation and plasma instabilities. Our method is based on the far field approximation of the Lienard-Wiechert potential and allows predicting both coherent and incoherent radiation spectrally from infrared to X-rays. Its capability to resolve the radiation polarization and to determine the temporal and spatial origin of the radiation enables us to correlate specific spectral signatures with characteristic dynamics in the plasma. Furthermore, its direct integration into the highly-scalable GPU framework of PIConGPU allows computing radiation spectra for thousands of frequencies, hundreds of detector positions and billions of particles efficiently. In this talk we will demonstrate these capabilities on resent simulations of laser wakefield acceleration (LWFA) and high harmonics generation during target normal sheath acceleration (TNSA).

  3. Tract specific analysis in patients with sickle cell disease

    Science.gov (United States)

    Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

    2015-12-01

    Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

  4. Non-specific chemical inhibition of the Fanconi anemia pathway sensitizes cancer cells to cisplatin

    Directory of Open Access Journals (Sweden)

    Jacquemont Céline

    2012-04-01

    Full Text Available Abstract Background Platinum compounds such as cisplatin and carboplatin are DNA crosslinking agents widely used for cancer chemotherapy. However, the effectiveness of platinum compounds is often tempered by the acquisition of cellular drug resistance. Until now, no pharmacological approach has successfully overcome cisplatin resistance in cancer treatment. Since the Fanconi anemia (FA pathway is a DNA damage response pathway required for cellular resistance to DNA interstrand crosslinking agents, identification of small molecules that inhibit the FA pathway may reveal classes of chemicals that sensitize cancer cells to cisplatin. Results Through a cell-based screening assay of over 16,000 chemicals, we identified 26 small molecules that inhibit ionizing radiation and cisplatin-induced FANCD2 foci formation, a marker of FA pathway activity, in multiple human cell lines. Most of these small molecules also compromised ionizing radiation-induced RAD51 foci formation and homologous recombination repair, indicating that they are not selective toward the regulation of FANCD2. These compounds include known inhibitors of the proteasome, cathepsin B, lysosome, CHK1, HSP90, CDK and PKC, and several uncharacterized chemicals including a novel proteasome inhibitor (Chembridge compound 5929407. Isobologram analyses demonstrated that half of the identified molecules sensitized ovarian cancer cells to cisplatin. Among them, 9 demonstrated increased efficiency toward FA pathway-proficient, cisplatin-resistant ovarian cancer cells. Six small molecules, including bortezomib (proteasome inhibitor, CA-074-Me (cathepsin B inhibitor and 17-AAG (HSP90 inhibitor, synergized with cisplatin specifically in FA-proficient ovarian cancer cells (2008 + FANCF, but not in FA-deficient isogenic cells (2008. In addition, geldanamycin (HSP90 inhibitor and two CHK1 inhibitors (UCN-01 and SB218078 exhibited a significantly stronger synergism with cisplatin in FA

  5. Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs

    International Nuclear Information System (INIS)

    Kurayoshi, Kenta; Ozono, Eiko; Iwanaga, Ritsuko; Bradford, Andrew P.; Komori, Hideyuki; Ohtani, Kiyoshi

    2014-01-01

    Highlights: • ARF promoter showed higher responsiveness to deregulated E2F activity than the E2F1 promoter. • ARF promoter showed higher cancer cell-specificity than E2F1 promoter to drive gene expression. • HSV-TK driven by ARF promoter showed higher cancer cell-specific cytotoxicity than that driven by E2F1 promoter. - Abstract: In current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicide gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF promoter

  6. Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs

    Energy Technology Data Exchange (ETDEWEB)

    Kurayoshi, Kenta [Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan); Ozono, Eiko [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ (United Kingdom); Iwanaga, Ritsuko; Bradford, Andrew P. [Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045 (United States); Komori, Hideyuki [Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 (United States); Ohtani, Kiyoshi, E-mail: btm88939@kwansei.ac.jp [Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan)

    2014-07-18

    Highlights: • ARF promoter showed higher responsiveness to deregulated E2F activity than the E2F1 promoter. • ARF promoter showed higher cancer cell-specificity than E2F1 promoter to drive gene expression. • HSV-TK driven by ARF promoter showed higher cancer cell-specific cytotoxicity than that driven by E2F1 promoter. - Abstract: In current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicide gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF promoter

  7. Specific chemical and structural damage to proteins produced by synchrotron radiation.

    Science.gov (United States)

    Weik, M; Ravelli, R B; Kryger, G; McSweeney, S; Raves, M L; Harel, M; Gros, P; Silman, I; Kroon, J; Sussman, J L

    2000-01-18

    Radiation damage is an inherent problem in x-ray crystallography. It usually is presumed to be nonspecific and manifested as a gradual decay in the overall quality of data obtained for a given crystal as data collection proceeds. Based on third-generation synchrotron x-ray data, collected at cryogenic temperatures, we show for the enzymes Torpedo californica acetylcholinesterase and hen egg white lysozyme that synchrotron radiation also can cause highly specific damage. Disulfide bridges break, and carboxyl groups of acidic residues lose their definition. Highly exposed carboxyls, and those in the active site of both enzymes, appear particularly susceptible. The catalytic triad residue, His-440, in acetylcholinesterase, also appears to be much more sensitive to radiation damage than other histidine residues. Our findings have direct practical implications for routine x-ray data collection at high-energy synchrotron sources. Furthermore, they provide a direct approach for studying the radiation chemistry of proteins and nucleic acids at a detailed, structural level and also may yield information concerning putative "weak links" in a given biological macromolecule, which may be of structural and functional significance.

  8. Reprint of: Virus-Specific T Cells: Broadening Applicability.

    Science.gov (United States)

    Barrett, A John; Prockop, Susan; Bollard, Catherine M

    2018-03-01

    Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody therapy may help prevent or treat viral disease, these drugs are expensive, toxic, and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (eg, adenovirus, BK virus), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplantation without causing graft-versus-host disease. This review will explore how the VST field has improved outcomes for many patients with life-threatening viral infections after HSCT, and how to broaden applicability beyond the "patient-specific" products, as well as extending to other viral diseases even outside the context of HSCT. Copyright © 2018. Published by Elsevier Inc.

  9. Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival

    Directory of Open Access Journals (Sweden)

    Kushchayev SV

    2012-09-01

    Full Text Available Sergiy V Kushchayev,1 Tejas Sankar,1 Laura L Eggink,5,6 Yevgeniya S Kushchayeva,5 Philip C Wiener,1,5 J Kenneth Hoober,5,6 Jennifer Eschbacher,3 Ruolan Liu,2 Fu-Dong Shi,2 Mohammed G Abdelwahab,4 Adrienne C Scheck,4 Mark C Preul11Neurosurgery Research Laboratory, 2Neuroimmunology Laboratory, 3Department of Pathology, 4Neurooncology Research, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, 5School of Life Sciences, Arizona State University, Tempe, 6Susavion Biosciences, Inc, Tempe, AZ, USABackground: A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated.Methods: C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven. Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay.Results: GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001 and tumor size was smaller (P < 0.02 in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005 and contralateral tumor-free hemisphere (P< 0.01 was

  10. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

    OpenAIRE

    Diegeler, Sebastian; Hellweg, Christine E.

    2017-01-01

    Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an e...

  11. The influence of the cellular phone radiation on the growth of mark145 cell

    International Nuclear Information System (INIS)

    Li Ruifang; Sun Jie; Yang Lili

    2007-01-01

    Objective: To explore the effects of radiation of cellular phone on the growth of cells. Methods: A radiation cycle was designed as working 25 minutes and then resting for 5 minutes for cellular phone. The Mark145 cell bottles were divided into six groups. The first two groups were radiated for two cycles, and the second two groups for four cycles, and the third two groups for five cycles. Each two groups were put 10cm far away from cellular phone and attach to it separately. Results: After culturing for 3 days there are many dead cells in the bottles. After culturing for 6 days, there is few living cells. Conclusions: cellular phone radiation is fatal to Mark145 cells, and the quantity of the dead cells change with the radiation time and the distance to radiation. That is to say, with the prolonging of radiation time and the shortening of the distance, the quantity of the dead cells is increasing. (authors)

  12. Effect of ionizing radiation on human skeletal muscle precursor cells

    International Nuclear Information System (INIS)

    Jurdana, Mihaela; Cemazar, Maja; Pegan, Katarina; Mars, Tomaz

    2013-01-01

    Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures. Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin – 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death. Compared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70). Our results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions

  13. Time-specific measurements of energy deposition from radiation fields in simulated sub-micron tissue volumes

    International Nuclear Information System (INIS)

    Famiano, M.A.

    1997-01-01

    A tissue-equivalent spherical proportional counter is used with a modified amplifier system to measure specific energy deposited from a uniform radiation field for short periods of time (∼1 micros to seconds) in order to extrapolate to dose in sub-micron tissue volumes. The energy deposited during these time intervals is compared to biological repair processes occurring within the same intervals after the initial energy deposition. The signal is integrated over a variable collection time which is adjusted with a square-wave pulse. Charge from particle passages is collected on the anode during the period in which the integrator is triggered, and the signal decays quickly to zero after the integrator feedback switch resets; the process repeats for every triggering pulse. Measurements of energy deposited from x rays, 137 Cs gamma rays, and electrons from a 90 Sr/ 90 Y source for various time intervals are taken. Spectral characteristics as a function of charge collection time are observed and frequency plots of specific energy and collection time-interval are presented. In addition, a threshold energy flux is selected for each radiation type at which the formation of radicals (based on current measurements) in mammalian cells equals the rate at which radicals are repaired

  14. Radiation Dose Effects into LCO in Technical Specification by Iodine in Hanul units 1,2

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hye Min; Lee, Seung Chan [KHNP Central Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    This study estimates the impact of the 1-th coolant system in NPP to the LCO (Limiting Condition of Operation) limits which is in the site boundary. Dose limit is merged into the effective dose from whole body and thyroid dose limits, that is possible to combine the two LCOs to a unified LCO. To estimate the limits, the radiation dose of one of the designed accidents should be chosen to check the radiation dose response. The selected accident is based on Seung Chan Lee's study at KHNP in 2011. Using the selected accident, Iodine dose effect is reviewed depending on the LCO limiting responsibility and the specific behavior. In order to evaluate the radiation dose effect in Technical Specification of Hanul 1,2, SGTR is selected for some sensitivity analysis. From the results, in Hanul site, the case of LOOP plus ADV plus GIS is the most severe case and the dose limit margin is about 110% in LCO.

  15. Acquired Tumor Cell Radiation Resistance at the Treatment Site Is Mediated Through Radiation-Orchestrated Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Aravindan, Natarajan, E-mail: naravind@ouhsc.edu [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Aravindan, Sheeja; Pandian, Vijayabaskar; Khan, Faizan H.; Ramraj, Satish Kumar; Natt, Praveen [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Natarajan, Mohan [Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)

    2014-03-01

    Purpose: Radiation resistance induced in cancer cells that survive after radiation therapy (RT) could be associated with increased radiation protection, limiting the therapeutic benefit of radiation. Herein we investigated the sequential mechanistic molecular orchestration involved in radiation-induced radiation protection in tumor cells. Results: Radiation, both in the low-dose irradiation (LDIR) range (10, 50, or 100 cGy) or at a higher, challenge dose IR (CDIR), 4 Gy, induced dose-dependent and sustained NFκB-DNA binding activity. However, a robust and consistent increase was seen in CDIR-induced NFκB activity, decreased DNA fragmentation, apoptosis, and cytotoxicity and attenuation of CDIR-inhibited clonal expansion when the cells were primed with LDIR prior to challenge dose. Furthermore, NFκB manipulation studies with small interfering RNA (siRNA) silencing or p50/p65 overexpression unveiled the influence of LDIR-activated NFκB in regulating CDIR-induced DNA fragmentation and apoptosis. LDIR significantly increased the transactivation/translation of the radiation-responsive factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), cMYC, and SOD2. Coculture experiments exhibit LDIR-influenced radiation protection and increases in cellular expression, secretion, and activation of radiation-responsive molecules in bystander cells. Individual gene-silencing approach with siRNAs coupled with coculture studies showed the influence of LDIR-modulated TNF-α, IL-1α, cMYC, and SOD2 in induced radiation protection in bystander cells. NFκB inhibition/overexpression studies coupled with coculture experiments demonstrated that TNF-α, IL-1α, cMYC, and SOD2 are selectively regulated by LDIR-induced NFκB. Conclusions: Together, these data strongly suggest that scattered LDIR-induced NFκB-dependent TNF-α, IL-1α, cMYC, and SOD2 mediate radiation protection to the subsequent challenge dose in tumor cells.

  16. Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Xiaodi Qiu

    Full Text Available The development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic expression of defined transcription factors was a transformational event in the field of regenerative medicine. The development of this technique also impacted ophthalmology, as patient-specific induced pluripotent stemcells (iPSCs may be useful resources for some ophthalmological diseases. The lens is a key refractive element in the eye that focuses images of the visual world onto the retina. To establish a new model for drug screening to treat lens diseases and investigating lens aging and development, we examined whether human lens epithelial cells (HLECs could be induced into iPSCs and if lens-specific differentiation of these cells could be achieved under defined chemical conditions. We first efficiently reprogrammed HLECs from age-related cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLEC-derived iPS (HLE-iPS colonies were indistinguishable from human ES cells with respect to morphology, gene expression, pluripotent marker expression and their ability to generate all embryonic germ-cell layers. Next, we performed a 3-step induction procedure: HLE-iPS cells were differentiated into large numbers of lens progenitor-like cells with defined factors (Noggin, BMP and FGF2, and we determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3, CRYAB, CRYAA, BFSP1, and MIP. In addition, HLE-iPS-derived lens cells exhibited reduced expression of epithelial mesenchymal transition (EMT markers compared with human embryonic stem cells (hESCs and fibroblast-derived iPSCs. Our study describes a highly efficient procedure for generating lens progenitor cells from cataract patient HLEC-derived iPSCs. These patient-derived pluripotent cells provide a valuable model for studying the developmental and molecular biological mechanisms that underlie cell determination in lens development and cataract

  17. Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

    Science.gov (United States)

    Reagan-Shaw, Shannon; Mukhtar, Hasan; Ahmad, Nihal

    2008-01-01

    Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

  18. Effects of combined X-radiation and UV-radiation on HeLa cells

    International Nuclear Information System (INIS)

    Luible, M.

    1982-01-01

    A combined X-ray-UV irradiation was performed in nonsynchronized HeLa-cells. A pre-irradiation with UV-light, that reduced the survival rate to 42% and the following X-ray radiation yielded a similar dose-effect characteristic as with ordinary X-ray irradiation, only its shoulder was smaller. An additive radiation interaction with the cellular molecular structure was observed. A pre-irradiation with X-rays followed by step-wise UV-irradiation yielded a function similar to the UV-action curve but also with a narrower shoulder. A additive effect could be observed. One can conclude from this that in combined irradiation two interacting processes cause the death of the cells. The gene mutations caused by UV-light lead to cell death. X-rays however cause chromosome breaks, that in an unfavourable combination also lead to cell death. The DNA distorsion caused by the UV-light increases the possibility of misrepair. (orig.) [de

  19. 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

  20. Cytotoxic effects of radiation and docetaxel in human tumour cells

    International Nuclear Information System (INIS)

    Dunne, A.L.

    2000-12-01

    Data from both single institutions and from randomised multicentre trials have demonstrated that the combination of chemotherapy with radiotherapy can increase the survival of cancer patients. Treatment regimens consisting of taxanes (paclitaxel and docetaxel), a potent class of new chemotherapeutic agents, combined with radiotherapy have recently undergone preclincal investigation. Overall, these studies show that taxanes can enhance the radiation sensitivity of tumour cells. However, data on docetaxel is very limited and the mechanism of radiosensitisation by docetaxel remains largely unknown. The chief purpose of this thesis was to investigate the ability of docetaxel to radiosensitise human tumour cells and investigate potential mechanisms for radiosensitisation. The results reported here for docetaxel indicate that for the cell fines examined this drug does have a synergistic effect and is thus a radiosensitising agent. The degree of radiosensitisation seen seems to be largely dependent on drug concentration. A mechanism involving docetaxel potentiation of radiation-induced apoptosis is also suggested. The second purpose of this thesis is to investigate the potential usefulness of an apoptosis assay and the comet assay as biological indicators for cellular radiosensitivity. Many scientists and clinicans have highlighted the need for development of new rapid, predictive assays of radiation responses. If the radiosensitivity of tumours could be predicted, it may eventually allow the individualisation of patient treatment by radiotherapy. In summary, initial DNA damage measured using the comet assay was successful in predicting the radiosensitivity of colorectal tumour cells. The results suggest that the comet assay appears more suitable than the detection of apoptosis for the prediction of radiosensitivity. We conclude that the results obtained from this thesis will contribute to the current attempts to improve the radiotherapeutic management of cancer. (author)

  1. Cell-type-specific gene delivery into neuronal cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Parveen, Zahida; Mukhtar, Muhammad; Rafi, Mohammed; Wenger, David A.; Siddiqui, Khwaja M.; Siler, Catherine A.; Dietzschold, Bernhard; Pomerantz, Roger J.; Schnell, Matthias J.; Dornburg, Ralph

    2003-01-01

    The avian retroviruses reticuloendotheliosis virus strain A (REV-A) and spleen necrosis virus (SNV) are not naturally infectious in human cells. However, REV-A-derived viral vectors efficiently infect human cells when they are pseudotyped with envelope proteins displaying targeting ligands specific for human cell-surface receptors. Here we report that vectors containing the gag region of REV-A and pol of SNV can be pseudotyped with the envelope protein of vesicular stomatitis virus (VSV) and the glycoproteins of different rabies virus (RV) strains. Vectors pseudotyped with the envelope protein of the highly neurotropic RV strain CVS-N2c facilitated cell type-specific gene delivery into mouse and human neurons, but did not infect other human cell types. Moreover, when such vector particles were injected into the brain of newborn mice, only neuronal cells were infected in vivo. Cell-type-specific gene delivery into neurons may present quite specific gene therapy approaches for many degenerative diseases of the brain

  2. Alterations induced in Escherichia Coli cells by gamma radiation

    International Nuclear Information System (INIS)

    Kappke, J.; Schelin, H.R.; Paschuk, S.A.; Denyak, V.; Silva, E.R. da; Jesus, E.F.O. de; Lopes, R.T.; Carlin, N.; Toledo, E.S.

    2007-01-01

    Modifications occurred in Escherichia coli cells exposed to gamma radiation ( 60 Co source) were investigated. The irradiations were done at the LIN-COPPE laboratory of the UFRJ and the analysis at the Biology Department of the UTFPR. The E. coli cells were irradiated with 30, 60, 90, 120, 150, 180, 210, 240, 300, 480, 600 e 750 Gy doses. The samples were analyzed with Gram-stain, biochemical tests in EPM, MIO and Lysine Broth, Simmons Cytrate Medium and Rhamnose Broth, antibiogram and isolation of auxotrophic mutants. It was observed that for the received doses the E. coli did not show morphological alterations in the tests. Some E. Coli cells showed to be able to deaminade the L-tryptophan or they changed their sensibility for amoxillin and cephaloonine after the irradiation. The existence of aauxotrophic mutants after irradiation was also verified. (author)

  3. Sensitivity of mitochondria of the mouse liver cells to radiation

    International Nuclear Information System (INIS)

    Shima, Akihiro

    1974-01-01

    In order to study the sensitivity of mitochondria (Mt) of the liver cells to radiation, 0.4 mg of riboflavine (RF) was intraperitoneally injected into mice which had been fed RF deficient food for 13 weeks. Three hours later 400 R of X-ray (190 KVP, 25 mA, 0.5 mmCu, 0.5 mmAl filter, FSD 61.5 cm, and HVL 0.80 mmCu) were irradiated to the whole body, and giant Mt of the liver cells were observed. When the liver cells were observed 24 hours after injection, neither giant Mt nor mitotic findings of Mt were found. All Mt observed were small (1.2 μ), although mice received 400 R of X-ray. (Serizawa, K.)

  4. Sensitization of ultraviolet radiation damage in bacteria and mammalian cells

    International Nuclear Information System (INIS)

    Fisher, G.J.; Watts, M.E.; Patel, K.B.; Adams, G.E.

    1978-01-01

    Bacteria (Serratia marcescens) and mammalian cells (Chinese hamsters V79-379A) were irradiated in monolayers with ultraviolet light at 254 nm or 365 nm in the presence or absence of radiosensitizing drugs. At 254 nm, killing is very efficient (Dsub(37) approximately equal 1 J m -2 exposure, or approximately equal 6 x 10 4 photons absorbed by DNA per bacterium), and sensitizers have no effect. At 365 nm, cells are not killed in buffer, but are inactivated in the presence of nifurpipone or misonidazole. Lethal exposures (approximately equal 5 x 10 3 J m -2 at 10 nM misonidazole) correspond to about 10 7 photons absorbed by sensitizer molecules per bacterium. Toxicity of stable photoproducts of the drugs is not involved, nor is oxygen required. Hence the transient species formed by photo-excitation of radiosensitizer molecules are capable of killing cells in the absence of other types of radiation damage. (author)

  5. Sensitivity of mitochondria of the mouse liver cells to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shima, A [Tokyo Univ. (Japan). Faculty of Science

    1974-06-01

    In order to study the sensitivity of mitochondria (Mt) of the liver cells to radiation, 0.4 mg of riboflavine (RF) was intraperitoneally injected into mice which had been fed RF deficient food for 13 weeks. Three hours later 400 R of X-ray (190 KVP, 25 mA, 0.5 mmCu, 0.5 mmAl filter, FSD 61.5 cm, and HVL 0.80 mmCu) were irradiated to the whole body, and giant Mt of the liver cells were observed. When the liver cells were observed 24 hours after injection, neither giant Mt nor mitotic findings of Mt were found. All Mt observed were small (1.2 ..mu..), although mice received 400 R of X-ray.

  6. Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Scott G Kitchen

    Full Text Available There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR. Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.

  7. Dose-rate dependent stochastic effects in radiation cell-survival models

    International Nuclear Information System (INIS)

    Sachs, R.K.; Hlatky, L.R.

    1990-01-01

    When cells are subjected to ionizing radiation the specific energy rate (microscopic analog of dose-rate) varies from cell to cell. Within one cell, this rate fluctuates during the course of time; a crossing of a sensitive cellular site by a high energy charged particle produces many ionizations almost simultaneously, but during the interval between events no ionizations occur. In any cell-survival model one can incorporate the effect of such fluctuations without changing the basic biological assumptions. Using stochastic differential equations and Monte Carlo methods to take into account stochastic effects we calculated the dose-survival rfelationships in a number of current cell survival models. Some of the models assume quadratic misrepair; others assume saturable repair enzyme systems. It was found that a significant effect of random fluctuations is to decrease the theoretically predicted amount of dose-rate sparing. In the limit of low dose-rates neglecting the stochastic nature of specific energy rates often leads to qualitatively misleading results by overestimating the surviving fraction drastically. In the opposite limit of acute irradiation, analyzing the fluctuations in rates merely amounts to analyzing fluctuations in total specific energy via the usual microdosimetric specific energy distribution function, and neglecting fluctuations usually underestimates the surviving fraction. The Monte Carlo methods interpolate systematically between the low dose-rate and high dose-rate limits. As in other approaches, the slope of the survival curve at low dose-rates is virtually independent of dose and equals the initial slope of the survival curve for acute radiation. (orig.)

  8. Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

    Directory of Open Access Journals (Sweden)

    Marcin Szczot

    2017-12-01

    Full Text Available Summary: Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, whereas non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell type specific. Biophysical characterization revealed substantial differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together, our results describe, at the molecular level, a potential mechanism by which transduction is tuned, permitting the detection of a variety of mechanosensory stimuli. : Szczot et al. find that the mechanoreceptor Piezo2 is extensively alternatively spliced, generating multiple distinct isoforms. Their findings indicate that these splice products have specific tissue and cell type expression patterns and exhibit differences in receptor properties. Keywords: Piezo, touch, sensation, ion-channel, splicing

  9. Radiation induced formation of giant cells (Saccharomyces uvarum). Pt. 1

    Energy Technology Data Exchange (ETDEWEB)

    Baumstark-Khan, C; Schnitzler, L; Rink, H

    1984-02-01

    X-irradiated yeast cells (Saccharomyces uvarum) grown in liquid media stop mitosis and form giant cells. Chitin ring formation, being a prerequisite for cell separation, was studied by fluorescence microscopy using Calcofluor White, a chitin specific dye. Experiments with inhibitors of DNA synthesis (hydroxyurea) and chitin synthesis (polyoxin D) demonstrate chitin ring formation to be dependent on DNA synthesis, whereas bud formation is independent of DNA synthesis and chitin ring formation respectively. Basing on these results the formation of X-ray induced giant cells implies one DNA replication which in turn induces the formation of only one chitin ring between mother cell and giant bud. Obviously no septum can be formed. Thus cell separation does not occur, but the bud already formed, produces another bud demonstrating that bud formation itself is independent of DNA synthesis.

  10. Radiation induced formation of giant cells (Saccharomyces uvarum). Pt. 1

    International Nuclear Information System (INIS)

    Baumstark-Khan, C.; Schnitzler, L.; Rink, H.

    1984-01-01

    X-irradiated yeast cells (Saccharomyces uvarum) grown in liquid media stop mitosis and form giant cells. Chitin ring formation, being a prerequisite for cell separation, was studied by fluorescence microscopy using Calcofluor White, a chitin specific dye. Experiments with inhibitors of DNA synthesis (hydroxyurea) and chitin synthesis (polyoxin D) demonstrate chitin ring formation to be dependent on DNA synthesis, whereas bud formation is independent of DNA synthesis and chitin ring formation respectively. Basing on these results the formation of X-ray induced giant cells implies one DNA replication which in turn induces the formation of only one chitin ring between mother cell and giant bud. Obviously no septum can be formed. Thus cell separation does not occur, but the bud already formed, produces another bud demonstrating that bud formation itself is independent of DNA synthesis. (orig.)

  11. Effect of radiation combined with hyperthermia on human prostatic carcinoma cell lines in culture

    International Nuclear Information System (INIS)

    Kaver, I.; Ware, J.L.; Wilson, J.D.; Koontz, W.W. Jr.

    1991-01-01

    The effect of radiation combined with heat on three human prostatic carcinoma cell lines growing in vitro was investigated. Cells were exposed to different radiation doses followed by heat treatment at 43 degrees C for one hour. Heat treatment, given ten minutes after radiation, significantly enhanced the radiation response of all the cell lines studied. The combined effect of radiation and heat produced greater cytotoxicity than predicted from the additive effects of the two individual treatment modalities alone. These results indicate that a combined treatment regimen of radiation plus hyperthermia (43 degrees, 1 hr) might be an important tool in maintaining a better local control of prostatic cancer

  12. Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II

    Directory of Open Access Journals (Sweden)

    Diaz AJG

    2013-10-01

    Full Text Available Anthony Joseph Gomez Diaz,1 Daniel Tamae,2 Yun Yen,3 JianJian Li,4 Tieli Wang1 1Department of Chemistry and Biochemistry, California State University at Dominguez Hills, Carson, CA, 2Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 3Department of Clinical and Molecular Pharmacology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA, 4Department of Radiation Oncology, University of California Davis, Sacramento, CA, USA Abstract: In our previous study, we identified that a protein target, peroxiredoxin II (PrxII, is overexpressed in radioresistant MCF+FIR3 breast-cancer cells and found that its expression and function is associated with breast-cancer radiation sensitivity or resistance. Small interference RNA (siRNA targeting PrxII gene expression was able to sensitize MCF+FIR3 radioresistant breast-cancer cells to ionizing radiation. The major focus of this work was to investigate how the radiation response of MCF+FIR3 radioresistant cells was affected by the siRNA that inhibits PrxII gene expression. Our results, presented here, show that silencing PrxII gene expression increased cellular toxicity by altering cellular thiol status, inhibiting Ca2+ efflux from the cells, and perturbing the intracellular Ca2+ homeostasis. By combining radiotherapy and siRNA technology, we hope to develop new therapeutic strategies that may have potential to enhance the efficacy of chemotherapeutic agents due to this technology's property of targeting to specific cancer-related genes. Keywords: siRNA, PrxII, radiation resistance, Ca2+, MCF+FIR3

  13. Light scattering on PHA granules protects bacterial cells against the harmful effects of UV radiation.

    Science.gov (United States)

    Slaninova, Eva; Sedlacek, Petr; Mravec, Filip; Mullerova, Lucie; Samek, Ota; Koller, Martin; Hesko, Ondrej; Kucera, Dan; Marova, Ivana; Obruca, Stanislav

    2018-02-01

    Numerous prokaryotes accumulate polyhydroxyalkanoates (PHA) in the form of intracellular granules. The primary function of PHA is the storage of carbon and energy. Nevertheless, there are numerous reports that the presence of PHA granules in microbial cells enhances their stress resistance and fitness when exposed to various stress factors. In this work, we studied the protective mechanism of PHA granules against UV irradiation employing Cupriavidus necator as a model bacterial strain. The PHA-accumulating wild type strain showed substantially higher UV radiation resistance than the PHA non-accumulating mutant. Furthermore, the differences in UV-Vis radiation interactions with both cell types were studied using various spectroscopic approaches (turbidimetry, absorption spectroscopy, and nephelometry). Our results clearly demonstrate that intracellular PHA granules efficiently scatter UV radiation, which provides a substantial UV-protective effect for bacterial cells and, moreover, decreases the intracellular level of reactive oxygen species in UV-challenged cells. The protective properties of the PHA granules are enhanced by the fact that granules specifically bind to DNA, which in turn provides shield-like protection of DNA as the most UV-sensitive molecule. To conclude, the UV-protective action of PHA granules adds considerable value to their primary storage function, which can be beneficial in numerous environments.

  14. Mesenchymal stem cell therapy for cutaneous radiation syndrome.

    Science.gov (United States)

    Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

    2010-06-01

    Systemic and local radiation injuries caused by nuclear power reactor accidents, therapeutic irradiation, or nuclear terrorism should be prevented or properly treated in order to improve wound management and save lives. Currently, regenerative surgical modalities should be attempted with temporal artificial dermis impregnated and sprayed with a local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Human mesenchymal stem cells and adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and were tested for differentiation and local stimulation effects in the radiation-exposed wounds. The perforator flap and artificial dermal template with growth factor were successful for reconstruction in patients who were suffering from complex underlying disease. Patients were uneventfully treated with minimal morbidities. In the experiments, the hMSCs are strongly proliferative even after 20 Gy irradiation in vitro. In vivo, 4 Gy rat whole body irradiation demonstrated that sustained marrow stromal (mesenchymal stem) cells survived in the bone marrow. Immediate artificial dermis application impregnated with cells and the cytokine over the 20 Gy irradiated skin and soft tissues demonstrated the significantly improved fat angiogenesis, architected dermal reconstitution, and less inflammatory epidermal recovery. Detailed understanding of underlying diseases and rational reconstructive procedures brings about good outcomes for difficult irradiated wound healing. Adipose-derived stem cells are also implicated in the limited local injuries for short cell harvesting and processing time in the same subject.

  15. Priming anticancer active specific immunotherapy with dendritic cells.

    Science.gov (United States)

    Mocellin, Simone

    2005-06-01

    Dendritic cells (DCs) probably represent the most powerful naturally occurring immunological adjuvant for anticancer vaccines. However, the initial enthusiasm for DC-based vaccines is being tempered by clinical results not meeting expectations. The partial failure of current vaccine formulations is explained by the extraordinary complexity of the immune system, which makes the task of exploiting the potential of such a biotherapeutic approach highly challenging. Clinical findings obtained in humans so far indicate that the immune system can be actively polarized against malignant cells by means of DC-based active specific immunotherapy, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally 'dormant' immune effectors can actually be employed as endogenous weapons against malignant cells. Only the thorough understanding of DC biology and tumor-host immune system interactions will allow researchers to reproduce, in a larger set of patients, the cellular/molecular conditions leading to an effective immune-mediated eradication of cancer.

  16. Rare earth fluorescent nanoparticles for specific cancer cell targeting

    International Nuclear Information System (INIS)

    Stefanakis, Dimitrios; Ghanotakis, Demetrios F.

    2016-01-01

    Terbium layered hydroxide nanoparticles (Tb_2(OH)_5NO_3) were synthesized by a one-pot coprecipitation method. The characterization of this preparation revealed highly oriented fluorescent nanoparticles. An attempt to improve the properties of Tb_2(OH)_5NO_3 resulted in the preparation of two optimized nanoparticles. In particular, Tb_2(OH)_5NO_3:Eu and Tb_2(OH)_5NO_3-FA were prepared when Tb_2(OH)_5NO_3 was doped with Europium and when the surface was modified with folic acid (FA), respectively. The size of the above nanoparticles was below 100 nm, and thus they have the potential to be used for biomedical applications. The interaction of nanoparticles with human cells was studied using confocal microscopy. This study revealed that only the nanoparticles modified with folic acid have the ability to be targeted to HeLa cells. This specific identification of cancer cells, in combination with the fluorescent properties of Tb_2(OH)_5NO_3, could render these nanoparticles appropriate for biomedical applications.

  17. Rare earth fluorescent nanoparticles for specific cancer cell targeting

    Energy Technology Data Exchange (ETDEWEB)

    Stefanakis, Dimitrios; Ghanotakis, Demetrios F., E-mail: ghanotakis@uoc.gr [University of Crete, Department of Chemistry (Greece)

    2016-07-15

    Terbium layered hydroxide nanoparticles (Tb{sub 2}(OH){sub 5}NO{sub 3}) were synthesized by a one-pot coprecipitation method. The characterization of this preparation revealed highly oriented fluorescent nanoparticles. An attempt to improve the properties of Tb{sub 2}(OH){sub 5}NO{sub 3} resulted in the preparation of two optimized nanoparticles. In particular, Tb{sub 2}(OH){sub 5}NO{sub 3}:Eu and Tb{sub 2}(OH){sub 5}NO{sub 3}-FA were prepared when Tb{sub 2}(OH){sub 5}NO{sub 3} was doped with Europium and when the surface was modified with folic acid (FA), respectively. The size of the above nanoparticles was below 100 nm, and thus they have the potential to be used for biomedical applications. The interaction of nanoparticles with human cells was studied using confocal microscopy. This study revealed that only the nanoparticles modified with folic acid have the ability to be targeted to HeLa cells. This specific identification of cancer cells, in combination with the fluorescent properties of Tb{sub 2}(OH){sub 5}NO{sub 3}, could render these nanoparticles appropriate for biomedical applications.

  18. Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Kirstin B. Langer

    2018-04-01

    Full Text Available Summary: Retinal ganglion cells (RGCs are the projection neurons of the retina and transmit visual information to postsynaptic targets in the brain. While this function is shared among nearly all RGCs, this class of cell is remarkably diverse, comprised of multiple subtypes. Previous efforts have identified numerous RGC subtypes in animal models, but less attention has been paid to human RGCs. Thus, efforts of this study examined the diversity of RGCs differentiated from human pluripotent stem cells (hPSCs and characterized defined subtypes through the expression of subtype-specific markers. Further investigation of these subtypes was achieved using single-cell transcriptomics, confirming the combinatorial expression of molecular markers associated with these subtypes, and also provided insight into more subtype-specific markers. Thus, the results of this study describe the derivation of RGC subtypes from hPSCs and will support the future exploration of phenotypic and functional diversity within human RGCs. : In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes. Keywords: iPSC, retina, retinal ganglion cell, RGC subtype, stem cell, ipRGC, alpha RGC, direction selective RGC, RNA-seq

  19. Influence of chemical inhibitors on cell recovery after exposure to different LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Evstratova, Ekaterina S.; Petin, Vladislav G. [Medical Radiological Research Center, Obninsk (Russian Federation); Kim, Jin Kyu; KIm, Jin Hong [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2016-12-15

    Chemical radiosensitizers are often used to increase cell radiosensitivity. It is known that the ability of chemical drugs to increase cell radiosensitivity is related with inhibition of cell recovery from damage induced by ionizing radiation. However, there are little comparative investigations of cell sensitivity modification after exposure to radiation with high linear energy transfer (LET). Therefore, we studied the anticancer drugs cisplatin and endoxan and their impact on the ability of yeast cells to recover after cell exposure to radiations with different LET. The ability of cell recovery from radiation damage was less effective after exposure to high-LET radiation, when cells were irradiated without drug, with the increase in cisplatin concentration resulting in the disappearance of this difference. The increase of cisplatin concentration results in progressive increase in the fraction of irreversible damage independently of radiation quality.

  20. Influence of chemical inhibitors on cell recovery after exposure to different LET radiation

    International Nuclear Information System (INIS)

    Evstratova, Ekaterina S.; Petin, Vladislav G.; Kim, Jin Kyu; KIm, Jin Hong

    2016-01-01

    Chemical radiosensitizers are often used to increase cell radiosensitivity. It is known that the ability of chemical drugs to increase cell radiosensitivity is related with inhibition of cell recovery from damage induced by ionizing radiation. However, there are little comparative investigations of cell sensitivity modification after exposure to radiation with high linear energy transfer (LET). Therefore, we studied the anticancer drugs cisplatin and endoxan and their impact on the ability of yeast cells to recover after cell exposure to radiations with different LET. The ability of cell recovery from radiation damage was less effective after exposure to high-LET radiation, when cells were irradiated without drug, with the increase in cisplatin concentration resulting in the disappearance of this difference. The increase of cisplatin concentration results in progressive increase in the fraction of irreversible damage independently of radiation quality.

  1. Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell–Mediated Killing

    Energy Technology Data Exchange (ETDEWEB)

    Gameiro, Sofia R.; Malamas, Anthony S. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bernstein, Michael B. [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Tsang, Kwong Y. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Vassantachart, April; Sahoo, Narayan; Tailor, Ramesh; Pidikiti, Rajesh [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Guha, Chandan P. [Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York (United States); Hahn, Stephen M.; Krishnan, Sunil [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Hodge, James W., E-mail: jh241d@nih.gov [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2016-05-01

    Purpose: To provide the foundation for combining immunotherapy to induce tumor antigen–specificcells with proton radiation therapy to exploit the activity of those T cells. Methods and Materials: Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences. Results: These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibility leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells. Conclusions: These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.

  2. Identification of cellular responses to low-dose radiation by antibody array in human B-lymphoblasts IM-9 cells

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Kim, Ji Young; Nam, Seon Young [Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro and Nuclear Power Co. LTD., Seoul (Korea, Republic of)

    2017-04-15

    The low-dose radiation (LDR)-induced various responses can reduce genetic mutation, enhance cell survival, and increase infection resistance (1). The antibody array for global analysis of phosphorylated proteins might be very useful to study signaling networks of LDR-induced cellular responses (2). Therefore, global analysis of phospho- proteins in cells exposed to radiation is important to understand the signaling mechanisms induced by changes of protein phosphorylation which lead to various biological effects by radiation. The aim is to explore the possibility of LDR-specific signaling for various beneficial effects and elucidate the potential signaling pathways representing LDR responses. Our results suggest that LDR did not affect cell death and that the increased proteins phosphorylation by LDR might be involved in various cellular responses for cell homeostasis. These results might be useful to further studies aimed at investigating potential regulatory markers that represent responses to LDR.

  3. Identification of cellular responses to low-dose radiation by antibody array in human B-lymphoblasts IM-9 cells

    International Nuclear Information System (INIS)

    Eom, Hyeon Soo; Kim, Ji Young; Nam, Seon Young

    2017-01-01

    The low-dose radiation (LDR)-induced various responses can reduce genetic mutation, enhance cell survival, and increase infection resistance (1). The antibody array for global analysis of phosphorylated proteins might be very useful to study signaling networks of LDR-induced cellular responses (2). Therefore, global analysis of phospho- proteins in cells exposed to radiation is important to understand the signaling mechanisms induced by changes of protein phosphorylation which lead to various biological effects by radiation. The aim is to explore the possibility of LDR-specific signaling for various beneficial effects and elucidate the potential signaling pathways representing LDR responses. Our results suggest that LDR did not affect cell death and that the increased proteins phosphorylation by LDR might be involved in various cellular responses for cell homeostasis. These results might be useful to further studies aimed at investigating potential regulatory markers that represent responses to LDR

  4. Effect of bFGF on radiation-induced apoptosis of vascular endothelial cells

    International Nuclear Information System (INIS)

    Gu Qingyang; Wang Dewen; Li Yuejuan; Peng Ruiyun; Dong Bo; Wang Zhaohai; Liu Jie; Deng Hua; Jiang Tao

    2003-01-01

    Objective: To study the effect of bFGF on radiation-induced apoptosis vascular endothelial cells. Methods: A cell line PAE (porcine aortic endothelial cells) and primary cultured HUVEC (human umbilical vein endothelial cells) were irradiated with 60 Co γ-rays to establish cell apoptosis models. Flow cytometry with annexin-V-FITC + PI labeling was used to evaluate cell apoptosis. Different amounts of bFGF were used to study their effects on radiation-induced endothelial cell apoptosis. Results and Conclusions: It is found that bFGF could inhibit radiation-induced endothelial cell apoptosis in a considerable degree

  5. Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Sharrow, S.O.; Mathieson, B.J.; Singer, A.

    1981-01-01

    The phenotypic appearance of cell surface antigens on murine thymocytes from long-term radiation bone marrow chimeras was analyzed using indirect immunofluorescence and flow microfluorometry. Cells maturing in the thymi of these mice were typed for MHC (Kk, I-Ak, H-2b, Kb, and Ib) and non-MHC (Lty 1, Ly 9, and TL) determinants. All cells were of donor origin as determined by non-MHC (Ly) phenotype in P1 leads to P2, P1 x P2 leads to P1, and P1 leads to P2 radiation chimeras. In contrast, the MHC phenotypes of these thymocytes were markedly affected by the host environment. Specifically, H-2 and I-A determinants of both parental phenotypes were detected on thymocytes from P1 leads to P1 x P2 chimeras; I-A determinants of host phenotype were present, whereas I-A determinants of donor phenotype were reduced on thymocytes from P1 x P2 leads to P1 chimeras; and thymocytes from P1 leads to P2 chimeras possessed H-2 and I-A determinants of host phenotype but showed reduction of donor I-A phenotype determinants. The appearance of host cell surface H-2 and I-A determinants on thymocytes from chimeras closely parallels the functional recognition of MHC determinants by T cells from chimeric mice and thus may be significantly related to the development of the self-recognition repertoire by maturing T cells

  6. A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells

    DEFF Research Database (Denmark)

    Andersen, P S; Stryhn, A; Hansen, B E

    1996-01-01

    Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might ...

  7. A study on immobilized ethanol yeast cells by radiation technique

    International Nuclear Information System (INIS)

    Li Zhengkui; Zhang Bosen

    1994-01-01

    Hydrophilic monomer 2-hydroxyethyl acrylate (HEA) and a series of polyethylene glycol dimethacrylate monomers were copolymerized by radiation technique at low temperature (-78 degree C) and hydrophilic hydrogels were obtained. The immobilization of yeast cells with these copolymer carriers led to a higher ethanol productivity than free cells. Of all copolymer carriers, the ethanol yield with poly (HEA-14 G) was the highest, about 2.45 times as high as that of free yeast cells. In addition, the ethanol productivity of 12 batch repeated reactions with poly (HEA-14G) carrier was all higher than that of free yeast cells. The ethanol productivity of immobilized yeast cells was dependent on the proportion of hydrophilic monomer to other monomers in copolymer systems, the chain length of the bifunctional monomer, the degree of hydration of copolymer carriers, the structure of copolymer carriers and porosity in the internal structure of carriers. The ethanol yield of immobilized cells depended on swelling ability and porosity of copolymer carriers

  8. Kinetics of antigen specific and non-specific polyclonal B-cell responses during lethal Plasmodium yoelii malaria

    Directory of Open Access Journals (Sweden)

    Laurence Rolland

    1992-06-01

    Full Text Available In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B-cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17 XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weigth ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection,in parallel to the parasitemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin-containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium-derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin-secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen-induced stimulation of antigen-specific cells rather than a generalized non-specific (mitogen-induced triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation.

  9. Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine.

    Directory of Open Access Journals (Sweden)

    Takahiro Nagatake

    Full Text Available Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4, and are efficiently isolated with the use of an antibody specific for the Cld4 extracellular domain and flow cytometry. Sorted Cld4+ epithelial cells in the small intestine exclusively expressed a chromogranin A gene (Chga and other enteroendocrine cell-related genes (Ffar1, Ffar4, Gpr119, and the population was divided into two subpopulations based on the activity of binding to Ulex europaeus agglutinin-1 (UEA-1. A Cld4+UEA-1- cell population almost exclusively expressed glucose-dependent insulinotropic polypeptide gene (Gip, thus representing K cells, whereas a Cld4+UEA-1+ cell population expressed other gut hormone genes, including glucagon-like peptide 1 (Gcg, pancreatic polypeptide-like peptide with N-terminal tyrosine amide (Pyy, cholecystokinin (Cck, secretin (Sct, and tryptophan hydroxylase 1 (Tph1. In addition, we found that orally administered luminal antigens were taken up by the solitary Cld4+ cells in the small intestinal villi, raising the possibility that enteroendocrine cells might also play a role in initiation of mucosal immunity. Our results provide a useful tool for the cellular and functional characterization of enteroendocrine cells.

  10. Mechanism on radiation degradation of Si space solar cells

    International Nuclear Information System (INIS)

    Yamaguchi, Masafumi; Taylor, S.J.; Hisamatsu, Tadashi; Matsuda, Sumio

    1998-01-01

    Radiation testing of Si n + -p-p + structure space solar cells has revealed an anomalous increase in short-circuit current Isc, followed by an abrupt decrease and cell failure, induced by high fluence electron and proton irradiations. A model to explain these phenomena by expressing the change in carrier concentration p of the base region is proposed in addition to the well-known model where Isc is decreased by minority-carrier lifetime reduction with irradiation. Change in carrier concentration causes broadening the depletion layer to contribute increase in the generated photocurrent and increase in recombination-generation current in the depletion layer, and increase in the resistivity of the base layer to result in the abrupt decrease of Isc and failure of the solar cell. Type conversion from p-type to n-type in base layer has been confirmed by EBIC (electron-beam induced current) and spectral response measurements. Moreover, origins of radiation-induced defects in heavily irradiated Si and generation of deep donor defects have also been examined by using DLTS (deep level transient spectroscopy) analysis. (author)

  11. Structural model of radiation effects in living cells

    International Nuclear Information System (INIS)

    Neyman, J.; Puri, P.S.

    1976-01-01

    The chance mechanism of cell damage and of repair in the course of irradiation involves two details familiar to biologists that thus far seem to have been overlooked in mathematical treatment. One of these details is that, generally, the passage of a single ''primary'' radiation particle generates a ''cluster'' of secondaries which can produce ''hits'' that damage the living cell. With high linear energy transfer, each cluster contains very many secondary particles. With low linear energy transfer, the number of secondaries per cluster is generally small. The second overlooked detail of the chance mechanism is concerned with what may be called the time scales of radiation damage and of the subsequent repair. The generation of a cluster of secondary particles and the possible hits occur so rapidly that, for all practical purposes, they may be considered as occurring instantly. On the other hand, the subsequent changes in the damaged cells appear to require measurable amounts of time. The constructed stochastic model embodies these details, the clustering of secondary particles and the time scale difference. The results explain certain details of observed phenomena

  12. The quantitative description of radiation-unduced cell inactivation. 9. Some remarks on the relative biological effect of ionizing radiation upon reproductive death of diploid and polyploid cells

    International Nuclear Information System (INIS)

    Barsukov, V.S.; Malinovskij, O.V.

    1978-01-01

    A model of repproductive death of cells is suggested and tested on the basis of data on relative biological efficiency (RBE) with provision for microdosimetry approaches. The model considers irradiation of cells with charged particles under conditions of linear energy transfers (LET) to the cell nucleus by a particle. This energy is subject to great fluctuations, and irradiation of a cell should be characterized not by the absorbed dose but rather by its stochastic analogue - specific energy. It appears then that RBE should be determined from the specific energy-response relationshjp rather than from dose-response relationship. The followjng main results were obtained: experimental relationship between the yield of sublesions, one-track and two-track lethals and LET correspond to that expected from the literature data; under the conditions considered, RBE can be determined from absorbed dose-pesponse dependency; RBE for sublesions, one- and two-track lethals taken separatly does not depend on the radiation dose and the relationshjp between the resulting RBE and the response is governed by redistribution of contributions of one- and two-track lethals at different doses. The plausibility of the model suggested is thus confirmed

  13. Intervention of oxygen-control ability to radiation sensitivity, cell aging and cell transformation

    International Nuclear Information System (INIS)

    Yoshii, Hanako; Watanabe, Masami

    2009-01-01

    Oxygen is essential for life, and cells have therefore developed numerous adaptive responses to oxygen change. Here, we examined the difference in oxygen-control functions of human (HE), mouse (ME), and Syrian hamster embryo (SHE) cells cultured under different oxygen conditions (0.5%, 2% and 20%), and also examined whether oxygen tensions contributed to cellular lifespan and transformation. HE cells had their replicative lifespan slightly extended under hypoxic (0.5% and 2% oxygen) conditions, but were not immortalized under any of the oxygen concentrations. On the other hand, although ME cells cultured under 20% oxygen tension decreased their proliferation potency temporarily at early stage, all rodent cells were immortalized and acquired anchorage-independency, regardless of oxygen tension. These results suggest that cellular oxygen control function is related to sensitivities cellular immortalization and transformation. To understand intervention of oxygen control ability on cellular immortalization and transformation, we examined the intracellular oxidative level, mitochondria functions and radiation sensitivity. Intracellular oxidative levels of hypoxically cultured rodent cells were significantly enhanced. Mitochondrial membrane potential was altered depend on oxygen tensions, but the change was not parallel to mitochondria number in rodent cells. ME cells were particularly sensitive to oxygen change, and showed a clear oxygen effect on the X-ray survival. However, there was no difference in frequency of radiation-induced micronuclei between HE and ME cells. These results suggest that the response to oxygen change differs markedly in HE and rodent cells. (author)

  14. Effect of ionizing radiation on the physical biology of head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Baker-Groberg, Sandra M; Bornstein, Sophia; Zilberman-Rudenko, Jevgenia; Schmidt, Mark; Tormoen, Garth W; Kernan, Casey; Thomas, Charles R; Wong, Melissa H; Phillips, Kevin G; McCarty, Owen J T

    2015-09-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Although there are numerous treatment options for HNSCC, such as surgery, cytotoxic chemotherapy, molecularly targeted systemic therapeutics, and radiotherapy, overall survival has not significantly improved in the last 50 years. This sugge