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Sample records for low-dose total-body irradiation

  1. Cyclic, low-dose total body irradiation for metastatic neuroblastoma

    SciTech Connect

    D'Angio, G.J.; Evans, A.E.

    1983-12-01

    Total body irradiation (TBI) can be thought of as a systemic anticancer agent. It therefore might best be given like an adjuvant drug, i.e., in tolerable doses, cyclically. The therapeutic ratio between normal bone marrow stem cells and suitably sensitive cancer cells should be widened by these means. Fourteen children with advanced (Stage IV) neuroblastomas were given 100-150 rad TBI in 50 rad daily fractions along with each three-week cycle of standard triple-agent chemotherapy (vincristine, DTIC, cyclophosphamide). Two patients died of toxicity and one is still undergoing therapy. Four of the remaining 12 survive free of disease for 12+ to 31+ months. The regimen is well tolerated, but prolonged, pronounced bone marrow depression, especially thrombocytopenia, commonly occurs after doses of 300-450 rad.

  2. Serum protein concentration in low-dose total body irradiation of normal and malnourished rats.

    PubMed

    Viana, W C M; Lambertz, D; Borges, E S; Neto, A M O; Lambertz, K M F T; Amaral, A

    2016-12-01

    Among the radiotherapeutics' modalities, total body irradiation (TBI) is used as treatment for certain hematological, oncological and immunological diseases. The aim of this study was to evaluate the long-term effects of low-dose TBI on plasma concentration of total protein and albumin using prematurely and undernourished rats as animal model. For this, four groups with 9 animals each were formed: Normal nourished (N); Malnourished (M); Irradiated Normal nourished (IN); Irradiated Malnourished (IM). At the age of 28 days, rats of the IN and IM groups underwent total body gamma irradiation with a source of cobalt-60. Total protein and Albumin in the blood serum was quantified by colorimetry. This research indicates that procedures involving low-dose total body irradiation in children have repercussions in the reduction in body-mass as well as in the plasma levels of total protein and albumin. Our findings reinforce the periodic monitoring of total serum protein and albumin levels as an important tool in long-term follow-up of pediatric patients in treatments associated to total body irradiation.

  3. Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation

    SciTech Connect

    Barrett, A.; Depledge, M.H.; Powles, R.L.

    1983-07-01

    Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to <0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

  4. Long-term results of low dose total body irradiation for advanced non-Hodgkin lymphoma.

    PubMed

    Lybeert, M L; Meerwaldt, J H; Deneve, W

    1987-08-01

    Sixty-eight patients received fractionated low dose total body irradiation (LTBI) as treatment for non-Hodgkin lymphoma (NHL) at the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) in the period 1973-1979. Ninety percent (61/68) of these patients had advanced disease (Stage III + IV). According to current malignancy grade classifications, 34 patients had low grade NHL, 10 intermediate, and 19 high grade. In 5 cases no exact grading was possible. LTBI was given 3 times a week, midline dose 0.1 Gy, using 6 or 25 MeV photons to a mean total dose of 1.78 Gy. Initial response rate for low, intermediate, and high grade NHL was resp. 84, 42, and 40%. The main prognostic factor for survival and recurrence-free survival (RFS) was malignancy grade. Probability of uncorrected survival at 10 years for low, intermediate, and high grade was resp. 34, 0 and 0%. Probability of RFS at 10 years was resp. 19, 0, and 0%. Neither stage nor sex had any influence on survival. Age was reversely correlated with survival, but was not correlated with RFS. Influence of prior therapy (18 patients) on survival and RFS was separately analyzed. Neither survival nor RFS of unfavorable histologic type NHL (high and intermediate grade) was influenced. On the other hand patients with a favorable histologic type NHL (low grade) had a significantly (p less than 0.05) better RFS if they received LTBI as initial treatment, but survival was not significantly influenced. RFS at 5 and 10 years of patients who received LTBI as first treatment was respectively 32% and 27%. No treatment related complications were noted. Subsequent chemotherapy in case of relapse was not hampered by previous LTBI. The high response rate and extended RFS, without maintenance therapy, makes LTBI a preferable first line treatment for patients with advanced stage low grade NHL.

  5. Low-dose total-body γ irradiation modulates immune response to acute proton radiation.

    PubMed

    Luo-Owen, Xian; Pecaut, Michael J; Rizvi, Asma; Gridley, Daila S

    2012-03-01

    Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate γ rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with ⁵⁷Co (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to γ rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to γ rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+ T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with γ radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate γ rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations.

  6. Hemopoiesis in the Splenectomized-Pregnant Mouse Following Low-Dose Total-Body Irradiation

    DTIC Science & Technology

    1981-05-15

    conditions. Blood was obtained for hematocrit 11).Durig dys 1 to14 o mose peg - (Hct). red blood cell (RBC) count, and white nancy, splenic...BL/6 SPLX C57BL/6 ’I E E S 7 a:0 2 x cc 0 s0 100 150 200 TOTAL BODY IRRADIATION (’ adI Figure 4. Mean ± SEM values for femur mar- 0 SC 10 - - row

  7. Early micro-rheological consequences of single fraction total body low-dose photon irradiation in mice.

    PubMed

    Szluha, Kornelia; Lazanyi, Kornelia; Furka, Andrea; Kiss, Ferenc; Szabo, Imre; Pintye, Eva; Miko, Iren; Nemeth, Norbert

    2014-01-01

    Despite of the studies on widespread biological effects of irradiation, surprisingly only little number of papers can be found dealing with its in vivo hemorheological impact. Furthermore, other studies suggested that low-dose irradiation might differ from high-dose in more than linear ways. On Balb/c Jackson female adult mice hematological and hemorheological impacts of total body irradiation were investigated 1 hour following 0.002, 0.005, 0.01, 0.02, 0.05 and 0.1 Gy dose irradiation. In case of 0.01 Gy further groups were analyzed 30 minutes, 2, 4, 6, 24 and 48 h after irradiation. According to the results, it seems that the dose-dependent changes of blood micro-rheological parameters are not linear. The irradiation dose of 0.01 Gy acted as a point of 'inflexion', because by this dose we found the most expressed changes in hematological parameters, as well as in red blood cell aggregation, deformability and osmoscan data. The time-dependent changes showed progressive decrease in pH, rise in lactate concentration, further decrease in erythrocyte aggregation index and deformability, with moderate shifting of the optimal osmolarity point and modulation in membrane stability. As conclusion, low-dose total body irradiation may cause micro-rheological changes, being non-linearly correlated with the irradiation dose.

  8. Low-dose total body irradiation in non-Hodgkin lymphoma: Short- and long-term toxicity and prognostic factor

    SciTech Connect

    De Neve, W.J.; Lybeert, M.L.; Meerwaldt, J.H. )

    1990-08-01

    The toxicity of low-dose total body irradiation (LTBI), the prognostic factors related to survival and relapse-free survival, and the efficacy of treatment given for relapse after LTBI were analyzed in 68 patients with non-Hodgkin lymphoma (NHL) treated at the Rotterdamsch Radiotherapeutisch Instituut. All patients received LTBI between 1973 and 1979. The patient material was heterogeneous with respect to malignancy grade, stage, age, and therapy given before or after LTBI; the unifying principle was that all patients received LTBI and had symptomatic NHL. Analysis of prognostic variables with Cox's model revealed grade (p less than 0.001) and age (p = 0.004) as predictors for survival and grade (p less than 0.001) and dose of LTBI (p = 0.056) as predictors for relapse-free survival after LTBI. No subjective toxicity was observed during or after LTBI treatment. Hematologic toxicity was dose-limiting and was increased if patients had received cytotoxic treatment before LTBI. LTBI-related hematologic toxicity was lower in patients with low-grade NHL than in those with intermediate or high-grade NHL, was limited in time, and recovered in all patients. Patients relapsing after LTBI received a variety of therapies. Response rates were high, but of short duration, especially in intermediate or high-grade NHL. Duration of response was progressively shorter after multiple relapses.

  9. Low-dose total body irradiation in non-Hodgkin lymphoma: short- and long-term toxicity and prognostic factor.

    PubMed

    De Neve, W J; Lybeert, M L; Meerwaldt, J H

    1990-08-01

    The toxicity of low-dose total body irradiation (LTBI), the prognostic factors related to survival and relapse-free survival, and the efficacy of treatment given for relapse after LTBI were analyzed in 68 patients with non-Hodgkin lymphoma (NHL) treated at the Rotterdamsch Radiotherapeutisch Instituut. All patients received LTBI between 1973 and 1979. The patient material was heterogeneous with respect to malignancy grade, stage, age, and therapy given before or after LTBI; the unifying principle was that all patients received LTBI and had symptomatic NHL. Analysis of prognostic variables with Cox's model revealed grade (p less than 0.001) and age (p = 0.004) as predictors for survival and grade (p less than 0.001) and dose of LTBI (p = 0.056) as predictors for relapse-free survival after LTBI. No subjective toxicity was observed during or after LTBI treatment. Hematologic toxicity was dose-limiting and was increased if patients had received cytotoxic treatment before LTBI. LTBI-related hematologic toxicity was lower in patients with low-grade NHL than in those with intermediate or high-grade NHL, was limited in time, and recovered in all patients. Patients relapsing after LTBI received a variety of therapies. Response rates were high, but of short duration, especially in intermediate or high-grade NHL. Duration of response was progressively shorter after multiple relapses.

  10. Effects of Low-Dose Total-Body Irradiation on Canine Bone Marrow Function and Canine Lymphoma

    DTIC Science & Technology

    1981-11-01

    against distemper , hepati- addiion grnulcytemacophge ol-tis, and rabies. Informed consent was obtained assas in from owners of the lymphomatous dogs...total-body gamma irradiation perpendicularly to parallel-opposed 1’Co sources program paralleling human clinical delivering a midline tissue dose of 9 rad...rad. This schedule is similar to that prescribed imen is marrow suppression, mainl y in many human clinical regimens. thrombocytopenia. Severe

  11. Adoptive transfer of Mammaglobin-A epitope specific CD8 T cells combined with a single low dose of total body irradiation eradicates breast tumors.

    PubMed

    Lerret, Nadine M; Rogozinska, Magdalena; Jaramillo, Andrés; Marzo, Amanda L

    2012-01-01

    Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.

  12. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    SciTech Connect

    Cvetkovic, D; Zhang, P; Wang, B; Chen, L; Ma, C

    2014-06-01

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers.

  13. Treatment of Fanconi anemia patients using fludarabine and low-dose total body irradiation followed by unrelated donor hematopoietic cell transplantation

    PubMed Central

    Thakar, Monica S; Kurre, Peter; Storb, Rainer; Kletzel, Morris; Frangoul, Haydar; Pulsipher, Michael A.; Leisenring, Wendy; Flowers, Mary Evelyn D; Sandmaier, Brenda M; Woolfrey, Ann; Kiem, Hans-Peter

    2010-01-01

    A non-myeloablative conditioning regimen consisting of fludarabine (FLU) and 2 Gy total body irradiation (TBI) has been used with great experience and engraftment success without promoting excessive non-relapse mortality (NRM) in medically infirm patients requiring hematopoietic cell transplantation (HCT). Here, we studied this same low-toxicity regimen as a means to promote engraftment of unrelated donor peripheral blood stem cells (PBSC) in patients with Fanconi Anemia (FA). All patients tolerated the regimen well with no mucositis or other severe toxicity. Of six patients transplanted, five achieved stable mixed or full donor chimerism. Acute and chronic graft-versus-host disease (GVHD) occurred in four and three patients, respectively. Three patients are alive and well a median of 45.9 (range, 20.9–68.1) months after transplant. In summary, this FLU-based regimen facilitates stable engraftment of unrelated PBSC but is associated with significant chronic GVHD. PMID:20581880

  14. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation

    SciTech Connect

    Belkacemi, Yazid . E-mail: y-belkacemi@o-lambret.fr; Labopin, Myriam; Hennequin, Christophe; Hoffstetter, Sylvette; Mungai, Raffaello; Wygoda, Marc; Lundell, Marie; Finke, Jurgen; Aktinson, Chris; Lorchel, Frederic; Durdux, Catherine; Basara, Nadezda

    2007-02-01

    Purpose: The high rate of toxicity is the limitation of myelobalative regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. Methods and Materials: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). Results: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). Conclusions: In this multicenter study, we confirmed high rates of engraftment and chimerism after the reduced intensity regimen. Our results are comparable to those previously reported. Radiation parameters seem to have no impact on outcome. However, the lack of a statistically significant difference in terms of dose rate may have been due, in part, to the small population

  15. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice☆

    PubMed Central

    Uckun, Fatih M.; Myers, Dorothea E.; Cheng, Jianjun; Qazi, Sanjive

    2015-01-01

    This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 (“C61-LNP”). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR–ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone. PMID:26285772

  16. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice.

    PubMed

    Uckun, Fatih M; Myers, Dorothea E; Cheng, Jianjun; Qazi, Sanjive

    2015-06-01

    This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR-ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone.

  17. Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party

    PubMed Central

    Bacigalupo, Andrea; Socie’, Gerard; Lanino, Edoardo; Prete, Arcangelo; Locatelli, Franco; Locasciulli, Anna; Cesaro, Simone; Shimoni, Avichai; Marsh, Judith; Brune, Mats; Van Lint, Maria Teresa; Oneto, Rosi; Passweg, Jacob

    2010-01-01

    Background We analyzed the outcome of 100 patients with acquired severe aplastic anemia undergoing an alternative donor transplant, after immune suppressive therapy had failed. Design and Methods As a conditioning regimen, patients received either a combination of fludarabine, cyclophosphamide, and antithymocyte globulin (n=52, median age 13 years) or this combination with the addition of low dose (2 Gy) total body irradiation (n=48, median age 27 years). Results With a median follow-up of 1665 and 765 days, the actuarial 5-year survival was 73% for the group that received fludarabine, cyclophosphamide, and antithymocyte globulin and 79% for the group given the conditioning regimen including total body irradiation. Acute graft-versus-host disease grade III–IV was seen in 18% and 7% of the groups, respectively. Graft failure was seen in 17 patients with an overall cumulative incidence of 17% in patients receiving conditioning with or without total body irradiation: 9 of these 17 patients survive in the long-term. The most significant predictor of survival was the interval between diagnosis and transplantation, with 5-year survival rates of 87% and 55% for patients grafted within 2 years of diagnosis and more than 2 years after diagnosis, respectively (P=0.0004). Major causes of death were graft failure (n=7), post-transplant-lymphoproliferative-disease (n=4) and graft-versus-host disease (n=4). Conclusions This study confirms positive results of alternative donor transplants in patients with severe aplastic anemia, the best outcomes being achieved in patients grafted within 2 years of diagnosis. Prevention of rejection and Epstein-Barr virus reactivation may further improve these results. PMID:20494932

  18. Fractionated total body irradiation for metastatic neuroblastoma

    SciTech Connect

    Kun, L.E.; Casper, J.T.; Kline, R.W.; Piaskowski, V.D.

    1981-11-01

    Twelve patients over one year old with neuroblastoma (NBL) metastatic to bone and bone marrow entered a study of adjuvant low-dose, fractionated total body irradiation (TBI). Six children who achieved a ''complete clinical response'' following chemotherapy (cyclophosphamide and adriamycin) and surgical resection of the abdominal primary received TBI (10 rad/fraction to totals of 100-120 rad/10-12 fx/12-25 days). Two children received concurrent local irradiation for residual abdominal tumor. The intervals from cessation of chemotherapy to documented progression ranged from 2-16 months, not substatially different from patients receiving similar chemotherapy and surgery without TBI. Three additional children with progressive NBL received similar TBI (80-120 rad/8-12 fx) without objective response.

  19. Total body calcium analysis. [neutron irradiation

    NASA Technical Reports Server (NTRS)

    Lewellen, T. K.; Nelp, W. B.

    1974-01-01

    A technique to quantitate total body calcium in humans is developed. Total body neutron irradiation is utilized to produce argon 37. The radio argon, which diffuses into the blood stream and is excreted through the lungs, is recovered from the exhaled breath and counted inside a proportional detector. Emphasis is placed on: (1) measurement of the rate of excretion of radio argon following total body neutron irradiation; (2) the development of the radio argon collection, purification, and counting systems; and (3) development of a patient irradiation facility using a 14 MeV neutron generator. Results and applications are discussed in detail.

  20. Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure

    PubMed Central

    Camarata, A. S.; Switchenko, J. M.; Demidenko, E.; Flood, A. B.; Swartz, H. M.; Ali, A. N.

    2015-01-01

    Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy/min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures. PMID:26910032

  1. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

    SciTech Connect

    Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

    1994-09-01

    Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig.

  2. Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    PubMed

    Pagel, John M; Gooley, Theodore A; Rajendran, Joseph; Fisher, Darrell R; Wilson, Wendy A; Sandmaier, Brenda M; Matthews, Dana C; Deeg, H Joachim; Gopal, Ajay K; Martin, Paul J; Storb, Rainer F; Press, Oliver W; Appelbaum, Frederick R

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  3. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    SciTech Connect

    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  4. Advanced lymphosarcoma treated by total body irradiation.

    PubMed Central

    Chaffey, J. T.; Rosenthal, D. S.; Pinkus, F.; Hellman, S.

    1975-01-01

    Twenty-five cases of clinical Stage III and Stage IV lymphosarcoma primarily treated by total body irradiation (TBI) are reported. Fifteen cases demonstrated nodular histology and 10 demonstrated diffuse histology by the Rappaport criteria. Treatments were 15 rad given twice weekly, calculated to midpelvis, to a total dose of 150 rad. Toxicity was confined to thrombocytopenia, one-third of patients requiring interruptions in the treatment course to allow platelet count recovery. Five patients had additional local irradiation. Complete responses were seen in 80% of patients and partial responses in 20%. Sixteen patients (64%) have been in continuous, unmaintained remission since treatments for variable periods to 39 months. Of 9 patients with clinically recurrent disease, 3 received further TBI and are in remission, 3 are in remission on chemotherapy, one patient has died, failing on all therapy, and 2 have not been treated. One patient died of pneumonia at 12 months, without clinical evidence of disease. Overall, actuarial survival is 87% at 2 years and compares well with survival in a sequential combination drug treated group of patients matched for age, sex, and histology, though differences are not statistically significant in these small groups. Total body irradiation is an effective systemic agent in the management of advanced lymphosarcoma and should be considered in treating this disease. PMID:810155

  5. Total body irradiation in chronic myeloid leukemia

    SciTech Connect

    Advani, S.H.; Dinshaw, K.A.; Nair, C.N.; Ramakrishnan, G.

    1983-04-01

    Total body irradiation (TBI), given as 10 rad daily for five days a week for a total dose of 150 rad has been used in an attempt to control the chronic phase of chronic myeloid leukemia (CML). Thirteen patients with CML received fractionated TBI leading to rapid and good control of WBC count without any adverse reaction. The chronic phase of CML could also be controlled with TBI, even in three patients who were resistant to busulfan. Following TBI, WBC count remained under control for a period of 32 weeks as compared to 40 weeks following vusulfan alone. Repeat TBI was also well tolerated with good response. It appears that TBI is an effective and safe therapy for controlling the chronic phase of CML.

  6. Radiobiological speculations on therapeutic total body irradiation

    SciTech Connect

    Vriesendorp, H.M. )

    1990-01-01

    Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references.

  7. Aperture modulated, translating bed total body irradiation

    SciTech Connect

    Hussain, Amjad; Villarreal-Barajas, Jose Eduardo; Dunscombe, Peter; Brown, Derek W.

    2011-02-15

    Purpose: Total body irradiation (TBI) techniques aim to deliver a uniform radiation dose to a patient with an irregular body contour and a heterogeneous density distribution to within {+-}10% of the prescribed dose. In the current article, the authors present a novel, aperture modulated, translating bed TBI (AMTBI) technique that produces a high degree of dose uniformity throughout the entire patient. Methods: The radiation beam is dynamically shaped in two dimensions using a multileaf collimator (MLC). The irregular surface compensation algorithm in the Eclipse treatment planning system is used for fluence optimization, which is performed based on penetration depth and internal inhomogeneities. Two optimal fluence maps (AP and PA) are generated and beam apertures are created to deliver these optimal fluences. During treatment, the patient/phantom is translated on a motorized bed close to the floor (source to bed distance: 204.5 cm) under a stationary radiation beam with 0 deg. gantry angle. The bed motion and dynamic beam apertures are synchronized. Results: The AMTBI technique produces a more homogeneous dose distribution than fixed open beam translating bed TBI. In phantom studies, the dose deviation along the midline is reduced from 10% to less than 5% of the prescribed dose in the longitudinal direction. Dose to the lung is reduced by more than 15% compared to the unshielded fixed open beam technique. At the lateral body edges, the dose received from the open beam technique was 20% higher than that prescribed at umbilicus midplane. With AMTBI the dose deviation in this same region is reduced to less than 3% of the prescribed dose. Validation of the technique was performed using thermoluminescent dosimeters in a Rando phantom. Agreement between calculation and measurement was better than 3% in all cases. Conclusions: A novel, translating bed, aperture modulated TBI technique that employs dynamically shaped MLC defined beams is shown to improve dose uniformity

  8. Comparative /sup 60/Co total body irradiation and 25 MV total body irradiation dosimetry. [/sup 60/Co and 25 mv photons

    SciTech Connect

    Glasgow, G.P.; Mill, W.B.; Phillips, G.L. II.; Herzig, G.P.

    1980-09-01

    Adults with acute leukemia and malignant lymphoma in relapse after conventional therapy are treated with cyclophosphamide and total body irradiation (TBI) followed by autologous bone marrow transplants. Phantom dosimetry and dosimetry on patients treated reveals that doses are delivered within 5% accuracy. Patient tolerance of treatment, and some biological considerations of low dose rate therapy are reviewed. Certain dosimetry features of an alternate treatment at 370 cm SAD, using 25 MV photons are also presented.

  9. Health benefits from low-dose irradiation

    SciTech Connect

    Luckey, T.D.

    1996-12-31

    Whole-body exposures of mice and humans show no harm from low doses of ionizing radiation. Forty reports show statistically significant, p < 0.01, beneficial effects when cancer and total mortality rates were examined in mice. In vitro experiments indicate that radiogenic metabolism, adaptive repair mechanisms, such as DNA repair enzymes, and the essential nature of ionizing radiation are responsible for part of this activity. However, overwhelming evidence shows that low-dose irradiation increases immune competence. Such data negate the linear concept, which has no reliable whole-animal data to support it in the low-dose range. Cell culture data are not pertinent; such cells do not have a complete immune system.

  10. Genomic Instability Induced by Low Dose Irradiation

    SciTech Connect

    Evans, Helen H. Sedwick, David W. Veigl, Martina L.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  11. Acute and delayed toxicities of total body irradiation

    SciTech Connect

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

  12. Calculation and prescription of dose for total body irradiation

    SciTech Connect

    Galvin, J.M.

    1983-12-01

    The use of large total body fields creates a unique set of problems that stress the accuracy of techniques routinely used for dose calculation. This paper discusses an approach suggested by the Children's Cancer Study Group (CCSG) for both prescribing the total body irradiation (TBI) dose and calculating the beam-on time or meter set needed to deliver it. It is aimed at guaranteeing the accuracy of the calculation, while at the same time ensuring a high degree of compliance for various CCSG protocols using TBI. Data supporting the various CCSG recommendations are presented.

  13. Systemic lupus erythematosus following total body irradiation for malignant lymphoma.

    PubMed

    Spinozzi, F; Capodicasa, E; Gerli, R; Bertotto, A; Rambotti, P; Grignani, F

    1986-01-01

    A case of a 63-year old man, who developed systemic lupus erythematosus three years after an initial diagnosis of small-cleaved centrofollicular lymphoma is described. The diagnosis of SLE was made on the basis of the accepted "1982 revised criteria for the classification of SLE". The autoimmune disease arose after a cycle of total body irradiation, despite the treatment with combination chemotherapeutic doses such a CVP or COAP or Cyclophosphamide, Vincristine, VM-26 and Prednisone. Genetic, immunological and exogenous environmental factors may co-exist and might equally be implicated in the pathogenesis of SLE and malignant lymphoma. However, the onset of SLE after total body irradiation could have been caused by the inactivation of suppressor T lymphocytes, which are known to be sensitive to radiations in vitro.

  14. On designing room sheilding for total-body irradiation

    SciTech Connect

    Barish, R.J.

    1996-05-01

    When designing shielding for total-body irradiation as an additional modality of treatment in an ordinary radiation therapy room, the extended treatment distance used for these patients greatly increases the workload because of the inverse-square factor. In a seeming contradiction to logic, for a facility with an exterior wall in the path of one lateral primary beam, and a restricted area behind the other primary wall, the overall shielding requirements are lower if the TBI patients are treated with the machine oriented toward the occupied interior. 4 refs.

  15. A variable speed translating couch technique for total body irradiation.

    PubMed

    Chrétien, M; Côté, C; Blais, R; Brouard, L; Roy-Lacroix, L; Larochelle, M; Roy, R; Pouliot, J

    2000-05-01

    We have developed a variable speed translating patient couch system for the delivery of total body irradiation (TBI). For a whole body Rando-type phantom, dose variation at mid-plane relative to the prescription point (navel) can be as high as 15% (neck or legs) with a constant velocity. By taking into account variations in body thickness, the intensity modulation radiation therapy, resulting from variable velocities, effectively delivers a uniform dose distribution at mid plane. The couch control user interface, technical aspects and dose planning optimization procedure for determining velocity distribution are described.

  16. Therapeutic use of fractionated total body and subtotal body irradiation

    SciTech Connect

    Loeffler, R.K.

    1981-05-01

    Ninety-one patients were treated using fractionated subtotal body (STBI) or total body irradiation (TBI). These patients had generalized lymphomas, Hodgkin's disease, leukemias, myelomas, seminomas, or oat-cell carcinomas. Subtotal body irradiation is delivered to the entire body, except for the skull and extremities. It was expected that a significantly higher radiation dose could be administered with STBI than with TBI. STBI was given when there was a reasonable likelihood that malignancy did not involve the shielded volumes. A five- to ten-fold increase in tolerance for STBI was demonstrated. Many of these patients have had long-term (up to 17 year--.permanent) remissions. There is little or no treatment-induced symptomatology, and no sanctuary sites. STBI and TBI are useful therapeutic modalities for many of these malignancies.

  17. Three-Dimensional Dose Calculation for Total Body Irradiation

    NASA Astrophysics Data System (ADS)

    Ito, Akira

    Bone Marrow Transplant (BMT) therapy has been a big success in the treatment of leukemia and other haematopoietic diseases 1 . Prior to BMT, total body irradiation (TBI) is given to the patient for the purpose of (1) killing leukemia cells in bone marrow, as well as in the whole body, and (2) producing immuno-suppressive status in the patient so that the donor's marrow cells will be transplanted without rejection. TBI employs a very large field photon beam to irradiate the whole body of the patient. A uniform dose distribution over the entire body is the treatment goal. To prevent the occurrence of a serious side effect (interstitial pneumonia), the lung dose should not exceed a certain level. This novel technique poses various new radiological physics problems. The accurate assessment of dose and dose distribution in the patient is essential. Physical and dosimetric problems associated with TBI are reviewed elsewhere 2,3 .

  18. Total body irradiation with a sweeping {sup 60}Cobalt beam

    SciTech Connect

    Hussein, S.; El-Khatib, E.

    1995-09-30

    This article describes the physical, technical, and dosimetric aspects of total body irradiation (TBI). The continuous head swivel motion of a standard {sup 60}Cobalt unit has been used to obtain a sweeping beam that encompases the entire length of the patient in TBI. A perspex beam flattener designed to remove the inverse square fall-off in beam intensity along the sweep axis provides a 90% field length of 200 cm in air at a treatment source-to-skin distance of 160 cm. The anterior-posterior parallel pair setup permits accurate placement of customized lead compensators to limit the dose to lungs. Measured beam profiles, dose buildup curves, and percentage depth dose for the technique are presented. With compensators in place, the variation in lung dose is shown to be within {plus_minus}5% of the prescribed tumor dose. 10 refs., 5 figs.

  19. Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

    SciTech Connect

    Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M. )

    1993-03-20

    The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.

  20. Verification of total body photon irradiation dosimetry techniques

    SciTech Connect

    Kirby, T.H.; Hanson, W.F.; Cates, D.A.

    1988-05-01

    A method of verifying the dosimetry of patients undergoing total body irradiation (TBI) with photon beams having energies from cobalt-60 to 25 MV is presented. A simple set of spot checks at the TBI axis has been used to verify data used for TBI dosimetry. Calculations to verify dose delivered to TBI patients are done in the same manner as those irradiated at standard treatment distances. A simple method of effective field size determination for various anatomical locations in a typical adult is presented. Measurements in an Alderson phantom with thermoluminescent dosimeters and an ion chamber at several anatomical locations indicate that this calculational method can predict the dose along the patient axis to within 4% for /sup 60/Co and 18-MV photon beams, provided the dosimetry data are appropriate (as determined by the spot checks). Results of intercomparisons of TBI beam calibration, off-axis and depth-dose data at various institutions visited by the Radiological Physics Center are also presented.

  1. In vivo dosimetry with silicon diodes in total body irradiation

    NASA Astrophysics Data System (ADS)

    Oliveira, F. F.; Amaral, L. L.; Costa, A. M.; Netto, T. G.

    2014-02-01

    The aim of this work is the characterization and application of silicon diode detectors for in vivo dosimetry in total body irradiation (TBI) treatments. It was evaluated the diode response with temperature, dose rate, gantry angulations and field size. A maximum response variation of 2.2% was obtained for temperature dependence. The response variation for dose rate and angular was within 1.2%. For field size dependence, the detector response increased with field until reach a saturation region, where no more primary radiation beam contributes for dose. The calibration was performed in a TBI setup. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings. Subsequent to calibration, in vivo dosimetry measurements were performed. The response difference between diode readings and the prescribed dose for all treatments was below 4%. This difference is in agreement as recommended by the International Commission on Radiation Units and Measurements (ICRU), which is ±5%. The present work to test the applicability of a silicon diode dosimetry system for performing in vivo dose measurements in TBI techniques presented good results. These measurements demonstrated the value of diode dosimetry as a treatment verification method and its applicability as a part of a quality assurance program in TBI treatments.

  2. Renal dysfunction after total body irradiation: Dose-effect relationship

    SciTech Connect

    Kal, Henk B. . E-mail: H.B.Kal@UMCUtrecht.nl; Kempen-Harteveld, M. Loes van

    2006-07-15

    Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated. Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.

  3. Total body irradiation-an attachment free sweeping beam technique.

    PubMed

    Härtl, Petra M; Treutwein, Marius; Hautmann, Matthias G; März, Manuel; Pohl, Fabian; Kölbl, Oliver; Dobler, Barbara

    2016-06-10

    A sweeping beam technique for total body irradiation in standard treatment rooms and for standard linear accelerators (linacs) is introduced, which does not require any accessory attached to the linac. Lung shielding is facilitated to reduce the risk of pulmonary toxicity. Additionally, the applicability of a commercial radiotherapy planning system (RTPS) is examined. The patient is positioned on a low couch on the floor, the longitudinal axis of the body in the rotational plane of the linac. Eight arc fields and five additional fixed beams are applied to the patient in supine and prone position respectively. The dose distributions were measured in a solid water phantom and in an Alderson phantom. Diode detectors were calibrated for in-vivo dosimetry. The RTPS Oncentra was employed for calculations of the dose distribution. For the cranial 120 cm the longitudinal dose profile in a slab phantom measured with ionization chamber varies between 94 and 107 % of the prescription dose. These values were confirmed by film measurements and RTPS calculations. The transmittance of the lung shields has been determined as a function of the thickness of the absorber material. Measurements in an Alderson phantom and in-vivo dosimetry of the first patients match the calculated dose. A treatment technique with clinically good dose distributions has been introduced, which can be applied with each standard linac and in standard treatment rooms. Dose calculations were performed with a commercial RTPS and should enable individual dose optimization.

  4. Low Dose Food Irradiation at Natick

    DTIC Science & Technology

    1977-06-01

    investigated included insect infestation, retention of vitamins (thiamine, riboflavin, pyridoxine and niacin ), chemical characteris- tics (diastase...0.32 0.32 Pyridoxine 0.05 0.04 0.014 0.014 Niacin 0.35 0.39 0.148 0.147 1300 to 500 Gy 2 mg100 gmn Table 11., Effect of irradiation and storage of flour...Thiamine 0.30 0.29 0.148 0.146 Riboflavin 0.22 0.22 0.24 0.214 Pyridoxine 0.014 0.014 0.04 0.04 Niacin 0.27 0.23 0.32 0.31 1 300 to 500 Gy 2mg/l00 gim

  5. Low-dose-rate, low-dose irradiation delays neurodegeneration in a model of retinitis pigmentosa.

    PubMed

    Otani, Atsushi; Kojima, Hiroshi; Guo, Congrong; Oishi, Akio; Yoshimura, Nagahisa

    2012-01-01

    The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (LD) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a condition using 650 mGy irradiation and a 26 mGy/minute dose rate. Multiple rounds of irradiation strengthened this neuroprotective effect. A characteristic up-regulation (563%) of antioxidative gene peroxiredoxin-2 (Prdx2) in the LDR-LD-irradiated retina was observed compared to the sham-treated control retina. Silencing the Prdx2 using small-interfering RNA administration reduced the LDR-LD rescue effect on the photoreceptors. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved.

  6. Patterns of patient specific dosimetry in total body irradiation

    SciTech Connect

    Akino, Yuichi; McMullen, Kevin P.; Das, Indra J.

    2013-04-15

    Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at our institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10

  7. 28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis

    NASA Astrophysics Data System (ADS)

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R.; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2017-05-01

    Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including 28Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of 28Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of 28Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life-threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of 28Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6 J mice were exposed to 0.3, 0.6 and 0.9 Gy 28Si (600 MeV) total body irradiation (TBI). The effects of 28Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to 28Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of 28Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of 28Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to 28Si irradiation leads to acute HSC damage.

  8. (28)Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis.

    PubMed

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2017-05-01

    Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including (28)Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of (28)Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of (28)Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life-threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of (28)Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6J mice were exposed to 0.3, 0.6 and 0.9Gy (28)Si (600MeV) total body irradiation (TBI). The effects of (28)Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to (28)Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of (28)Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of (28)Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to (28)Si irradiation leads to acute HSC damage

  9. Myeloproliferative disorders in patients with rheumatoid arthritis treated with total body irradiation

    SciTech Connect

    Urowitz, M.B.; Rider, W.D.

    1985-01-21

    Four patients with refractory rheumatoid arthritis were treated with total body irradiation administered in two sittings, 300 to 400 rads to each half of the body. All four patients had taken antimetabolites prior to receiving total body irradiation, and two continued to use them after total body irradiation. Two patients had taken alkylating agents before, and one had used them after total body irradiation. All patients showed clinical improvement. However, in two patients myeloproliferative disorders developed: a myelodysplastic preleukemia at 40 months after total body irradiation in one and acute myelogenous leukemia at 25 months in the other. Total body irradiation differs from total nodal irradiation in the total dose of irradiation (300 to 400 rads versus 2,000 to 3,000), and in the duration of the therapy (two sittings versus treatment over several weeks to months). Furthermore, the patients in the total body irradiation study frequently used cytotoxic drugs before and/or after irradiation, whereas in one total nodal irradiation study, azathioprine (2 mg/kg per day or less) was permitted, but no other cytotoxic agents were allowed. Rheumatologists may therefore face a binding decision when deciding to treat a patient with rheumatoid arthritis with either a cytotoxic drug or irradiation.

  10. Responses of astrocytes in culture after low dose laser irradiation

    SciTech Connect

    Yew, D.T.; Zheng, D.R.; Au, C.; Li, W.W. )

    1990-03-01

    The effect of Helium-Neon low dose laser on astrocytes was investigated in cultures of isolated astrocytes from albino neonatal rats. The laser appeared to inhibit the growth of astrocytes as exemplified by the smaller sizes of the cells and the decreased leucine uptake in each cell after treatment. Temporary decrease in the number of mitoses was also observed, but this trend was reversed soon after. Electron microscopic studies revealed an increase in buddings from cell bodies and processes (branches) after irradiation.

  11. Effect of Low-Dose Irradiation on Pregnant Mouse Hemopoiesis

    DTIC Science & Technology

    1980-07-10

    simiLhr for the nonirradiated 200 + ~ 180 *-4 9 IRRADIATED 180 16 ---.U)" IRRADIATED Z 160 --DAY 10.5 ’U~14O 2LU -- 140- - 21 120- 24? 100 -20 z 80 16...3 *%~ 60.~ "" ,,,," 40 V5 1 20 z 0 0 0 • -U 9 IRRADIATED 12 ’-" ’ PIRRADIATED M , DAY 10.S 20 10 4 - -0- 0 0.5 1.0 TOTAL BODY IRRADIATION (Gy) Fit S... plastia dot cultures taininag 50 000 bone marMrw or pe’mse Plier 0. 1 at. Irradiation and Haemopoiesis in Pregnancy 133 in 12 6 0. 8 4 M -2 m 6 0 IO

  12. Evaluation of in vivo low-dose mouse irradiation system

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Kim, H. J.; Kim, H.; Kye, Y.-U.; Kim, J. K.; Son, T. G.; Lee, M. W.; Jeong, D. H.; Yang, K. M.; Nam, S.-H.; Kang, Y.-R.

    2016-03-01

    This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

  13. Inability of donor total body irradiation to prolong survival of vascularized bone allografts: Experimental study in the rat

    SciTech Connect

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J. )

    1990-07-01

    At the present time, the toxic side effects of recipient immunosuppression cannot be justified for human non-vital organ transplantation. Total body irradiation has proven effective in ablating various bone-marrow-derived and endothelial immunocompetent cellular populations, which are responsible for immune rejection against donor tissues. Irradiation at a dose of 10 Gy was given to donor rats six days prior to heterotopic transplantation of vascularized bone allografts to host animals. Another group of recipient rats also received a short-term (sixth to fourteenth day after grafting), low dose of cyclosporine. Total body irradiation was able merely to delay rejection of grafts across a strong histocompatibility barrier for one to two weeks, when compared to nonirradiated allografts. The combination of donor irradiation plus cyclosporine did not delay the immune response, and the rejection score was similar to that observed for control allografts. Consequently, allograft viability was quickly impaired, leading to irreversible bone damage. This study suggest that 10 Gy of donor total body irradiation delivered six days prior to grafting cannot circumvent the immune rejection in a vascularized allograft of bone across a strong histocompatibility barrier.

  14. Response of human fibroblasts to low dose rate gamma irradiation

    SciTech Connect

    Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

    1984-11-01

    Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to ..gamma.. radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D/sub 0/) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury.

  15. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    SciTech Connect

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-06-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.

  16. Transcriptome profiling of mice testes following low dose irradiation

    PubMed Central

    2013-01-01

    Background Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis. Methods Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). Results We identified a subset of transcripts (n = 988) where changes in expression pi can be explained by changes in cellularity. We separated the transcripts into five unique clusters that we associated with spermatogonia, spermatocytes, early spermatids, late spermatids and somatic cells, respectively. Transcripts in the somatic cell cluster showed large changes in expression pi, mainly caused by changes in cellularity. Further investigations revealed that the low dose irradiation seemed to cause Leydig cell hyperplasia, which contributed to the detected expression changes in the somatic cell cluster. Conclusions The five clusters represent gene expression in distinct cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production and inadequate inhibin signalling due to missing germ cells. PMID:23714422

  17. Fractionated sublethal total body irradiation and donor bone marrow infusion for induction of specific allograft tolerance

    SciTech Connect

    Pierce, G.E.; Kimler, B.F.; Thomas, J.H.; Watts, L.M.; Kinnaman, M.L.

    1981-03-01

    Fractionated total lymphoid irradiation (FT-lymphoid-I) plus donor bone marrow (BM) can induce tolerance to skin allografts. In the present study, fractionated total body irradiation (FT-body-I) was studied as an alternative to FT-lymphoid-I. FT-body-I produces less pulmonary and gastrointestinal injury than does single exposure total body irradiation, but because of the decreased capacity of lymphoid tissues to recover from the effects of irradiation between fractions, the effect of FT-body-I on lymphoid cells, when delivered within 24 h, is approximately the same as an equivalent single exposure of total body irradiation. Therefore, FT-body-I, like FT-lymphoid-I, has some selectivity for lymphoid tissues and has the advantage that it can be delivered within the time constraints of ex vivo organ preservation.

  18. Optical fiber sensor for low dose gamma irradiation monitoring

    NASA Astrophysics Data System (ADS)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  19. Radiobiological basis of total body irradiation with different dose rate and fractionation: repair capacity of hemopoietic cells

    SciTech Connect

    Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.

    1981-12-01

    Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (25 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI.

  20. Radiobiological basis of total body irradiation with different dose rate and fractionation: repair capacity of hemopoietic cells

    SciTech Connect

    Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.

    1981-12-01

    Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (26 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI.

  1. Dosimetric aspects of inverse-planned modulated-arc total-body irradiation

    SciTech Connect

    Held, Mareike; Kirby, Neil; Morin, Olivier; Pouliot, Jean

    2012-08-15

    Purpose: To develop optimal beam parameters and to verify the dosimetric aspects of the recently developed modulated-arc total-body irradiation (MATBI) technique, which delivers an inverse-planned dose to the entire body using gantry rotation. Methods: The patient is positioned prone and supine underneath the gantry at about 2 m source-to-surface distance (SSD). Then, up to 28 beams irradiate the patient from different gantry angles. Based on full-body computed-tomography (CT) images of the patient, the weight of each beam is optimized, using inverse planning, to create a uniform body dose. This study investigates how to best simulate patients and the ideal beam setup parameters, such as field size, number of beams, and beam geometry, for treatment time and dose homogeneity. In addition, three anthropomorphic water phantoms were constructed and utilized to verify the accuracy of dose delivery, with both diode array and ion chamber measurements. Furthermore, to improve the accuracy of the new technique, a beam model is created specifically for the extended-SSD positioning for MATBI. Results: Low dose CT scans can be utilized for dose calculations without affecting the accuracy. The largest field size of 40 Multiplication-Sign 40 cm{sup 2} was found to deliver the most uniform dose in the least amount of time. Moreover, a higher number of beams improves dose homogeneity. The average dose discrepancy between ion chamber measurements and extended-SSD beam model calculations was 1.2%, with the largest discrepancy being 3.2%. This average dose discrepancy was 1.4% with the standard beam model for delivery at isocenter. Conclusions: The optimum beam setup parameters, regarding dose uniformity and treatment duration, are laid out for modulated-arc TBI. In addition, the presented dose measurements show that these treatments can be delivered accurately. These measurements also indicated that a new beam model did not significantly improve the accuracy of dose calculations

  2. The effect of melatonin on peripheral blood cells during total body irradiation in rats.

    PubMed

    Koc, Mehmet; Buyukokuroglu, Mehmet Emin; Taysi, Seyithan

    2002-05-01

    Melatonin, has been reported to participate in the regulation of a number of important physiological and pathological process. It has also the ability to protect the genetic material of hematopoietic cells of mice from damaging effects of acute total body irradiation. The objective of this study was to the potential radioprotective effects of pharmacological doses of melatonin in total body irradiated rat's peripheral blood cells. Forty adult rats were divided into 4 equal groups. Group 1 received no melatonin or irradiation (control group), while group 2 received only melatonin (5 mg/kg, i.p.). Group 3 received only total body irradiation (RT) by 5 Gy of gamma irradiation only and group 4 received RT plus melatonin (5 mg/kg, i.p., 30 min before RT). An hour and a half following RT, blood samples were taken. Leukocytes and thrombocytes number and hemoglobin levels were measured in all groups. Five mg/kg dose of melatonin significantly protected leukocytes and as well as thrombocytes number against y irradiation. There were no significant differences between Hb levels. Our results suggest that melatonin administration prior to irradiation prevented radiation damage on peripheral blood cells. Melatonin radioprotection is achieved by its ability as a scavenger for free radicals generated by ionizing radiation and acts probably as a growth factor, especially for granulocytes in bone marrow.

  3. Dosimetry of single fraction high dose total body irradiation as measured by thermoluminescent dosimeters

    SciTech Connect

    Liu, J.C.; Bacza, E.T.; Findley, D.O.; Forell, B.W.

    1983-09-01

    Eighty-five patients with acute myelogenous or acute lymphoblastic leukemia were treated at the Cit of Hope National Medicine Center with chemotherapy, total body irradiation, and bone marrow transplant. The average mid-line dose to these patients was 1002 rad with a uniformity of 8%.

  4. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    NASA Astrophysics Data System (ADS)

    Acheva, A.; Georgieva, R.; Rupova, I.; Boteva, R.; Lyng, F.

    2008-02-01

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy.

  5. Influence of nandrolone decanoate on the repopulation of the thymus after total body irradiation of mice

    SciTech Connect

    Plum, J.; Huys, J.; De Scheerder, Y.; Dhont, E.; De Smedt, M.

    1982-10-01

    It has been reported that nandrolone decanoate is helpful in overcoming the neutropenic phase following irradiation. In the present study the influence of nandrolone decanoate on the thymus' cellularity after total body irradiation was investigated. In comparison with a placebo-treated group, mice receiving nandrolone decanoate showed a similar pattern of thymus repopulation, but a significantly lower number of thymocytes over the whole period of treatment was found. Nonirradiated mice also had a significantly lower number of thymocytes when treated with nandrolone decanoate. In addition, the number of circulating leukocytes was also evaluated over a period of 1 month after total body irradiation. On 11 of the 21 days investigated, a significantly higher number of leukocytes was found in the nandrolone decanoate-treated group. We conclude that the action of nandrolone decanoate was not clearly distinct from that of testosterone regarding either granulopoiesis or thymic involution.

  6. First French experiences of total body irradiations using helical TomoTherapy(®).

    PubMed

    Sun, R; Cuenca, X; Itti, R; Nguyen Quoc, S; Vernant, J-P; Mazeron, J-J; Jenny, C; Chea, M

    2017-08-01

    Dynamic conformal radiotherapy with helical TomoTherapy(®) (HT) offers a more quantitative paradigm for total body irradiation. Treatment planning, delivery, dose verification of the first French experiences of total body irradiation using helical TomoTherapy(®) are presented. Patients planned for total body irradiation at our institution from February 2012 to May 2013 were reported. Total body irradiation consisted in a single fraction of 2Gy. Planning target volume was divided in two due to the limited translation length of the table. Delivery quality assurance was performed with cylindrical phantom, ionization chamber and films. Thermoluminescent dosimeters and radiochromic films were used for in vivo dosimetry and junction region heterogeneity assessment. Six patients were included. One finally did not receive the treatment but dosimetric data were analyzed. Planned V95% was covered by D95% and V2% did not exceed D107% for five of the six patients. The mean relative difference between measured and calculated absolute dose of the Delivery quality assurance was always less than 2.5% (mean value±SD: 1%±0.67%). Gamma index (3%; 3mm) was less than 1 for at least 93% of the points (value±SD: 97.4±1.6% and 96.6±2.5% for upper and lower part of treatment respectively). Difference between in vivo measured and calculated dose was above 5% for only two out of 15 points (maximum: 10.2%, mean: 0.73±4.6%). Junction region heterogeneity was in average 5.8±1%. The total treatment session of total body irradiation lasted 120min, with a mean beam on time of 17.2±0.6 and 11.2±1.6min for upper and lower part of the body respectively. Total body irradiation using helical TomoTherapy(®) guaranteed high dose homogeneity throughout the body and dose verification was achievable, showing small difference between planned and delivered doses. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  7. Metabolic changes in humans following total body irradiation. Report for February 1960-October 1961

    SciTech Connect

    Not Available

    1988-11-29

    These studies are designed to obtain new information about the metabolic effects of total body and partial body irradiation so as to have a better understanding of the acute and subacute effects of irradiation in the human. The initial studies are pointed toward the elucidation of biological indicators of radiation effects in humans. The major parameters being investigated at present are urinary amino aciduria and alterations in immunological patterns. Certain other parameters such as creatine and creatinine excretion and hematological effects are also being followed. The long-term program envisions carrying out the various observations at dose levels of 100 rad and gradually increasing the dose to 150, 200, 250 and 300 rad. Eventually doses up to 600 rad are anticipated. Also comparison of effects of radiomimetic drugs with total body radiation will be studied.

  8. Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation

    SciTech Connect

    Sanders, J.E.; Buckner, C.D.; Leonard, J.M.; Sullivan, K.M.; Witherspoon, R.P.; Deeg, H.J.; Storb, R.; Thomas, E.D.

    1983-09-01

    One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.

  9. Total-Body Irradiation Produces Late Degenerative Joint Damage in Rats

    PubMed Central

    Hutchinson, Ian D.; Olson, John; Lindburg, Carl A.; Payne, Valerie; Collins, Boyce; Smith, Thomas L.; Munley, Michael T.; Wheeler, Kenneth T.; Willey, Jeffrey S.

    2014-01-01

    Purpose Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. Materials and Methods 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV x-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. Results T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. Conclusions Late degenerative changes in articular cartilage and bone were observed after total body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage. PMID:24885745

  10. Cardiac injury following 10 Gy total body irradiation: indirect role of effects on abdominal organs

    PubMed Central

    Lenarczyk, Marek; Lam, Vy; Jensen, Eric; Fish, Brian L; Su, Jidong; Koprowski, Stacy; Komorowski, Richard A; Harmann, Leanne; Migrino, Raymond Q; Li, X Allen; Hopewell, John W; Moulder, John E; Baker, John E

    2014-01-01

    The objective of this study was to determine whether radiation-induced injury to the heart after 10 Gy total body irradiation (TBI) is direct or indirect. Young male WAG/RijCmcr rats received a 10 Gy single dose using TBI, upper hemi-body (UHB) irradiation, lower hemi-body (LHB) irradiation, TBI with the kidneys shielded, or LHB irradiation with the intestines shielded. Age-matched, sham-irradiated rats served as controls. The lipid profile, kidney injury, heart and liver morphology and cardiac function were determined up to 120 days after irradiation. LHB, but not UHB irradiation, increased the risk factors for cardiac disease as well as the occurrence of cardiac and kidney injury in a way that was quantitatively and qualitatively similar to that observed after TBI. Shielding of the kidneys prevented the increases in risk factors for cardiac disease. Shielding of the intestines did not prevent the increases in risk factors for cardiac disease. There was no histological evidence of liver injury 120 days after irradiation. Injury to the heart from irradiation appears to be indirect, supporting the notion that injury to abdominal organs, principally the kidneys, is responsible for the increased risk factors for and the occurrence of cardiac disease after TBI and LHB irradiation. PMID:23919311

  11. Effect of fractionated versus unfractionated total body irradiation on the growth of the BN acute myelocytic leukemia

    SciTech Connect

    Hagenbeek, A.; Martens, A.C.M.

    1981-08-01

    The efficacy of various total body irradiation (TBI) regimens prior to bone marrow transplantation was evaluated in a rat model for acute myelocytic leukemia (Dq = 85.1 cGy gamma ; N = 3.7). Using high dose rate gamma-irradiation (115 cGy/min), fractionated TBI with large total daily doses (400 to 600 cGy), either given as acute doses or as split doses at 8 hr intervals, was most effective. Split doses (2 fractions per day) offered no additional advantage. At the most, a 4 log leukemic cell kill was induced. No lethal toxicity was observed. Nine-hundred cGy flash TBI had a similar anti-tumor effect, but with this regimen almost half of the rats died from radiation-induced toxicity (lungs and gastro-intestinal tract). The results are explained in terms of differences between normal and leukemic cells as regards (a) repair of sublethal damage; and (b) repopulation. Low dose rate continuous gamma-irradiation (0.26 cGy/min) with total doses ranging from 900 to 2000 cGy was also quite effective. Maximally a 4 log cell kill was obtained. With 2000 cGy, 50% of the rats died from the gastro-intestinal tract-syndrome. In addition to the major role played by chemotherapy, TBI is mainly of importance in sterilizing the various sanctuaries in the body which contain leukemic cells anatomically resistant to most cytostatic agents.

  12. Therapeutic use of fractionated total body and subtotal body irradiation. [X-rays

    SciTech Connect

    Loeffler, R.K.

    1981-05-01

    Ninety-one patients were treated using fractionated subtotal body (STBI) or total body irradiation (TBI). These patients had generalized lymphomas, Hodgkin's disease, leukemias, myelomas, seminomas, or oat-cell carcinomas. Subtotal body irradiation is delivered to the entire body, except for the skull and extremities. It was expected that a significantly higher radiation dose could be administered with STBI than with TBI. A five- to ten-fold increase in tolerance for STBI was demonstrated. Many of these patients have had long-term emissions. There is little or no treatment-induced symptomatology, and no sanctuary sites.

  13. The effect of melatonin against oxidative damage during total-body irradiation in rats.

    PubMed

    Koc, Mehmet; Taysi, Seyithan; Emin Buyukokuroglu, M; Bakan, Nuri

    2003-08-01

    Melatonin has been reported to participate in the regulation of a number of important physiological and pathological processes. Melatonin, which is a powerful endogenous antioxidant, may play a role in the prevention of oxidative damage. The aim of this study was to investigate the effect of pretreatment with melatonin (5 mg kg(-1) and 10 mg kg(-1)) on gamma-radiation-induced oxidative damage in plasma and erythrocytes after total-body irradiation with a single dose of 5 Gy. Total-body irradiation resulted in a significant increase in plasma and erythrocyte MDA levels. Melatonin alone increased the levels of SOD and GSH-Px. Erythrocyte and plasma MDA levels in irradiated rats that were pretreated with melatonin (5 or 10 mg kg(-1)) were significantly lower than those in rats that were not pretreated. There was no significant difference between the effects of 5 and 10 mg kg(-1) on plasma MDA activities and CAT activities. However, erythrocyte MDA levels showed a dose-dependent decrease, while GSH-Px activities increased with dose. Our study suggests that melatonin administered prior to irradiation may protect against the damage produced by radiation by the up-regulation of antioxidant enzymes and by scavenging free radicals generated by ionizing radiation.

  14. SU-E-T-522: Investigation of Underdosage of Total Body Irradiation with Bilateral Irradiation Scheme

    SciTech Connect

    Lin, T; Eldib, A; Hossain, M; Price, R; Ma, C

    2015-06-15

    Purpose: Patient in-vivo measurements report lower readings than those predicted from TMR-based treatment planning on TBI patient knees and ankles where rice was placed to fill the gap between patient’s legs. This study is to understand and correct the under dosage of Total Body Irradiation(TBI) with rice tissue equivalent bolus placement at TBI treatment patient setup. Methods: Bilateral TBI scheme was investigated with rice bags bolus placing between patient’s two legs acting as missing tissue. In-house TMR based treatment planning system was commissioned with measurements under TBI condition at 10MV, i.e. source-to-reference distance 383.4cm with 40×40cm field size with 1cm thickness Lucite. Predictions of patient specific dose points are reported at different sites with 200cGy prescription at patient umbilicus point. Solid water and rice bag phantoms are used at TBI conditions for the attenuation factor verification and CT scanned to verify the CT number and electron density. Results: We found that the rice bag bolus overall density is 11% lower than the water; however, the attenuation factor of rice bags could become 15% lower than that of water at TBI condition. This overestimate of rice bag electron density could cause the lack of lateral scatter and the lack of backscatter. This could Result in an overestimate of dose at in-vivo dosimeter measurement points with TMR-based treatment planning systems. Observations of patient specific optically stimulated luminescent dosimeters(OSLDs) were used to confirm this overestimation. Measurements of setups with increasing the rice bag filled patient leg separation were performed to demonstrate eliminating the overdose issue. Conclusion: Rice bolus has a lower electron density than water does(11%) but results in 15% lower in attenuation factor at TBI condition. This effect was observed in patient delivery with OSLD measurements and can be corrected by increasing the filling rice bolus thickness with 15% longer of

  15. Effect of high-dose total body irradiation on ACTH, corticosterone, and catecholamines in the rat.

    PubMed

    Cohen, Eric P; Bruder, Eric D; Cullinan, William E; Ziegler, Dana; Raff, Hershel

    2011-01-01

    Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic-pituitary-adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study assessed HPA axis function in rats undergoing TBI. Using a head-shielded model of TBI, we found an enhanced response to corticotropin-releasing hormone (CRH) in vitro in pituitaries from irradiated compared with nonirradiated rats at both 8 and 70 days after 10-Gy single fraction TBI. At 70, but not 8 days, plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels were increased significantly in irradiated compared with nonirradiated rats. Plasma aldosterone was not affected by TBI at either time point, whereas plasma renin activity was decreased in irradiated rats at 8 days. Basal and stimulated adrenal steroid synthesis in vitro was not affected by TBI. In addition, plasma epinephrine was decreased at 70 days after TBI. The hypothalamic expression of CRH messenger RNA (mRNA) and hippocampal expression of glucocorticoid receptor mRNA were unchanged by irradiation. We conclude that the hypertension of radiation nephropathy is not aldosterone or catecholamine-dependent but that there is an abscopal activation of the HPA axis after 10 Gy TBI. This activation was attributable at least partially to enhanced pituitary ACTH production.

  16. Sudden myelopathy secondary to therapeutic total-body hyperthermia after spinal-cord irradiation

    SciTech Connect

    Douglas, M.A.; Parks, L.C.; Bebin, J.

    1981-03-05

    Hyperthermia is a new method of treatment receiving increasing clinical attention in cancer therapy. Its efficacy has been well demonstrated in animals, but its indications, contraindications, and appropriate place in cancer therapy have yet to be defined. We report three cases of acute myelopathy in patients undergoing hyperthermia after spinal-cord irradiation within the preceding two months. Post-mortem examination in one case revealed findings similar to those seen in myelopathy resulting from long-term irradiation. Several neurologic side effects have been reported previously with total-body hyperthermia - most commonly peripheral neuropathy, but not myelopathy. The mechanism of action of hyperthermia in cancer therapy (with or without prior irradiation) is unknown. The experience reported suggests that in some patients hyperthermia may potentiate radiation-induced damage to the spinal cord or otherwise interact to cause acute spinal-cord necrosis.

  17. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  18. Idiopathic interstitial pneumonia following bone marrow transplantation: the relationship with total body irradiation

    SciTech Connect

    Keane, T.J.; Van Dyk, J.; Rider, W.D.

    1981-10-01

    Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical setting is described.

  19. Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation.

    PubMed

    Shim, Sehwan; Lee, Seung Bum; Lee, Jong-geol; Jang, Won-Suk; Lee, Sun-Joo; Park, Sunhoo; Lee, Seung-Sook

    2013-04-01

    This study evaluated the clinical and pathologic effects of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the recovery from total body irradiation by comparing it with the effects of granulocyte-colony stimulating factor (G-CSF), an efficacious drug in the treatment of acute bone marrow radiation syndrome. BALB/c mice were treated with G-CSF or hUCB-MSCs after they were irradiated with 7 Gy cobalt-60 γ-rays. Circulating blood counts, histopathologic changes in the bone marrow, and plasma level of Flt-3L and transforming growth factor (TGF-β1) were monitored in the postirradiation period. Hematologic analysis revealed that the peripheral leukocyte counts were markedly increased in the hUCB-MSCs-treated group, whereas G-CSF-treated mice did not recover significantly. Moreover, differential counts showed that hUCB-MSC treatment has regenerative effects on white blood cells, lymphocytes, and monocytes compared with the irradiated group. Treatment with hUCB-MSCs or G-CSF significantly increased immunoreactivity of Ki-67 until 3 weeks after total body irradiation. However, at 3 weeks, the number of Ki-67 immunoreactive cells significantly increased in the hUCB-MSCs-treated group compared with the G-CSF-treated group. Furthermore, hUCB-MSC treatment significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGF-β1, whereas G-CSF treatment failed to decrease the plasma Flt-3L levels at 2 weeks after irradiation. Based on the differences in circulating blood cell reconstitution and cell density of bone marrow, the authors suggest that MSC treatment is superior to G-CSF treatment for hematopoietic reconstitution following sublethal dose radiation exposure. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  20. Enhanced charge trapping in bipolar spacer oxides during low-dose-rate irradiation

    SciTech Connect

    Fleetwood, D.M.; Reber, R.A. Jr.; Winokur, P.S.; Kosier, S.L.; Schrimpf, R.D.; Nowlin, R.N.; Pease, R.L.; DeLaus, M.

    1994-03-01

    Thermally-stimulated-current and capacitance-voltage measurements reveal enhanced hole trapping in bipolar spacer-oxide capacitors irradiated at 0 V at low dose rates. Possible mechanisms and implications for bipolar low-rate response are discussed.

  1. Comparison of total body irradiation vs chlorambucil and prednisone for remission induction of active chronic lymphocytic leukemia: an ECOG study. Part I: total body irradiation-response

    SciTech Connect

    Rubin, P.I.; Bennett, J.M.; Begg, C.; Bozdech, M.J.; Silber, R.

    1981-12-01

    Twenty-six evaluable patients were entered into two fractionated total body irradiation (TBI) programs; 11 patients received a course of 150 rad TBI (x 3 if tolerated) and 15 patients received a lower dose course of 50 rad (x 3 if tolerated). Complete remissions (CR) were not produced by either course; however, the higher dose course (Plan I) yielded a partial response (PR) rate of 73%, while the lower dose course yielded a PR of 47%. Although fraction size seemed trivial in both TBI plans, an unexpected high degree of hematologic toxicity was encountered, and was parallel to the response rates: in Plan I 73% of patients experienced severe to life-threatening depression of platelets or granulocytes, whereas in Plan II this rate was 47%. This was of short duration with rapid return of blood counts to normal levels. One death can be attributed to TBI. The chemotherapy arm of the study demonstrated superiority in terms of complete responses. Twenty-three percent of patients treated by cholrambucil and prednisone attained CR, in contrast to 0% of TBI patients. PR for chemotherapy was similar to that obtained with TBI. Chemotherapy also proved superior in terms of overall response rate, number of patients in remission, and in the median duration of response, but not in the median duration of survival. Fractional TBI techniques for active chronic lymphocytic leukemia (CLL) should be interrupted when the platelet count dips below 100,000 and the granulocyte count is lower than 2,000. Future studies should combine TBI radiation therapy and chemotherapy.

  2. THE URINE PROTEOME FOR RADIATION BIODOSIMETRY: EFFECT OF TOTAL BODY VERSUS LOCAL KIDNEY IRRADIATION

    PubMed Central

    Sharma, Mukut; Halligan, Brian D.; Wakim, Bassam T.; Savin, Virginia J.; Cohen, Eric P.; Moulder, John E.

    2009-01-01

    Victims of nuclear accidents or radiological terrorism are likely to receive varying doses of ionizing radiation inhomogeneously distributed over the body. Early biomarkers may be useful in determining organ-specific doses due to total body irradiation (TBI) or partial body irradiation. We used liquid chromatography and mass spectrometry to compare the effect of TBI and local kidney irradiation (LKI) on the rat urine proteome using a single 10 Gy dose of X-rays. Both TBI and LKI altered the urinary protein profile within 24 hours with noticeable differences in Gene Ontology categories. Some proteins including fetuin-B, tissue kallikrein, beta-glucuronidase, vitamin D-dependent calcium binding protein and chondroitin sulfate proteoglycan NG2 were detected only in the TBI group. Some other proteins including major urinary protein-1, RNA binding protein 19, neuron navigator, Dapper homolog 3, WD repeat and FYVE domain containing protein 3, sorting nexin-8, ankycorbin and aquaporin were detected only in the LKI group. Protease inhibitors and kidney proteins were more abundant (fraction of total scans) in the LKI group. Up/Uc ratio and urinary albumin abundance decreased in both TBI and LKI groups. Several markers of acute kidney injury were not detectable in either irradiated group. Present data indicate that abundance and number of proteins may follow opposite trends. These novel findings demonstrate intriguing differences between TBI and LKI, and suggest that urine proteome may be useful in determining organ-specific changes caused by partial body irradiation. PMID:20065682

  3. Survival after total-body irradiation. I. Effects of partial small bowel shielding

    SciTech Connect

    Vigneulle, R.M.; Vriesendorp, H.M.; Taylor, P.; Burns, W.; Pelkey, T. )

    1989-08-01

    The small intestine of the rat was shielded during total-body irradiation (TBI) to evaluate the effects of radiation dose and length of intestine shielded on survival. Sprague-Dawley rats were anesthetized in groups of 10. Using aseptic surgical procedures 80, 40, 20, or 10 cm, or none of the proximal or distal small intestine were temporarily exteriorized and shielded during irradiation with photons from an 18 MeV linear accelerator. Less than 17% of the dose was delivered to the shielded intestines. In unshielded animals deaths occurred from Days 4 to 6 with 13, 15, or 17 Gy and from Days 8 to 30 with 9, 11, and 12 Gy. However, in all animals exposed to 15 Gy with all or part of the small intestine shielded, survival was increased to between 5 and 9 days. Shielding of the distal small intestine was more effective in prolonging survival than shielding of the proximal small intestine. The previously identified target of radiation damage in the small intestine is the crypt stem cell. In this study, the analysis of histological specimens of shielded and irradiated small intestine suggested that humoral factors also influence intestinal histology and survival after irradiation. These humoral factors are thought to originate from the irradiated body tissues, the shielded proximal intestine, and the shielded distal intestine. Further studies are required to identify these factors and to determine their mode of action and their therapeutic potential after radiation damage to the small intestine.

  4. Survival after total-body irradiation. 1. Effects of partial small bowel shielding

    SciTech Connect

    Vigneulle, R.M.; Vriesendorp, H.M.; Taylor, P.; Burns, W.; Pelkey, T.

    1989-01-01

    The small intestine of the rat was shielded during total-body irradiation (TBI) to evaluate the effects of radiation dose and length of intestine shielded on survival. Sprague-Dawley rats were anesthetized in groups of 10. Using aseptic surgical procedures 80, 40, 20, or 10 cm, or none of the proximal or distal small intestine were temporarily exteriorized and shielded during irradiation with photons from an 18-MeV linear accelerator. Less than 17% of the dose was delivered to the shielded intestines. In unshielded animals deaths occurred from Days 4 to 6 with 13, 15, or 17 Gy and from Days 8 to 30 with 9, 11, and 12 Gy. However, in all animals exposed to 15 Gy with all or part of the small intestine shielded, survival was increased to between 5 and 9 days. Shielding of the distal small intestine. The previously identified target of radiation damage in the small intestine is the crypt stem cell. In this study, the analysis of histological specimens of shielded and irradiated small intestine suggested that humoral factors also influence intestinal histology and survival after irradiation. These humoral factors are thought to originate from the irradiated body tissues, the shielded proximal intestine, and the shielded distal intestine. Further studies are required to identify these factors and to determine their mode of action and their therapeutic potential after radiation damage to the small intestine.

  5. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation

    SciTech Connect

    Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.

    1982-04-01

    Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

  6. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation

    SciTech Connect

    Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.

    1982-04-01

    Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given either as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to to 4 X 10/sup 8/ cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single-dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis.In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after in vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

  7. Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity after Lethal Total Body Irradiation

    PubMed Central

    Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S.; Li, Zhiguo; Chao, Nelson J.; Chen, Benny J.

    2012-01-01

    Purpose To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for five consecutive days starting within one hour post exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied using an in vitro culture system. Results IGF-1 protected 8 out of 20 mice (40%) from lethal irradiation while only 2 out of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for five days. Positive effects were noted even when the initiation of treatment was delayed up to six hours post irradiation. Compared with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red cells in peripheral blood, total cell numbers as well as hematopoietic stem cells and progenitors in the bone marrow when measured at day 14 post-irradiation. IGF-1 protected both hematopoietic stem cells and progenitors from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of non-irradiated and irradiated hematopoietic progenitors. Conclusions IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitors. PMID:23021438

  8. Establishment of a mouse model of 70% lethal dose by total-body irradiation

    PubMed Central

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun

    2016-01-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model. PMID:27382380

  9. Establishment of a mouse model of 70% lethal dose by total-body irradiation.

    PubMed

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun; Choi, Yang-Kyu

    2016-06-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.

  10. Irradiation with low-dose gamma ray enhances tolerance to heat stress in Arabidopsis seedlings.

    PubMed

    Zhang, Liang; Zheng, Fengxia; Qi, Wencai; Wang, Tianqi; Ma, Lingyu; Qiu, Zongbo; Li, Jingyuan

    2016-06-01

    Gamma irradiation at low doses can stimulate the tolerance to environmental stress in plants. However, the knowledge regarding the mechanisms underlying the enhanced tolerance induced by low-dose gamma irradiation is far from fully understood. In this study, to investigate the physiological and molecular mechanisms of heat stress alleviated by low-dose gamma irradiation, the Arabidopsis seeds were exposed to a range of doses before subjected to heat treatment. Our results showed that 50-Gy gamma irradiation maximally promoted seedling growth in response to heat stress. The production rate of superoxide radical and contents of hydrogen peroxide and malondialdehyde in the seedlings irradiated with 50-Gy dose under heat stress were significantly lower than those of controls. The activities of antioxidant enzymes, glutathione (GSH) content and proline level in the gamma-irradiated seedlings were significantly increased compared with the controls. Furthermore, transcriptional expression analysis of selected genes revealed that some components related to heat tolerance were stimulated by low-dose gamma irradiation under heat shock. Our results suggest that low-dose gamma irradiation can modulate the physiological responses as well as gene expression related to heat tolerance, thus alleviating the stress damage in Arabidopsis seedlings. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

    SciTech Connect

    Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S.; Li, Zhiguo; Chao, Nelson J.; Chen, Benny J.

    2013-03-15

    Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.

  12. Regenerative effects of tetrachlorodecaoxide in BD IX rats after total-body gamma irradiation

    SciTech Connect

    Ivankovic, S.; Kempf, S.R.

    1988-07-01

    Tetrachlorodecaoxide (TCDO) was tested for its effects in BD IX rats when combined with a single dose nearing LD50 of total-body irradiation (gamma rays, /sup 60/Co). In pilot tests we found that TCDO administrations prior to or immediately after irradiation led to a very high mortality rate (up to 90%), whereas the initiation of TCDO treatment on Day 2, 3, or 4 after irradiation lowered the death rate noticeably, with optimum results when TCDO application was started on Day 4. In our major experiment on 100 BD IX rats, it was demonstrated that the following treatment schedule considerably decreased the death rate (from 44 to 4%): 15.5 mumol TCDO/kg body wt/day on Days 4-6 after irradiation and 7.75 mumol/kg body wt/day on Days 7-11. The animals treated with TCDO showed only mild anemia in the peripheral blood, accompanied by reticulocytosis and low-grade leukocytopenia. Examination of the bone marrow on Day 12 after irradiation revealed X-ray-induced agranulocytosis in the animals that had received only physiological saline solution, whereas in the bone marrow of the animals treated with TCDO there was erythropoiesis as well as myelopoiesis. In addition, the degree of hair loss and depigmentation occurring about 1 month after irradiation was considerably reduced by TCDO. From these results it can be postulated that TCDO has two different effects: as an oxygen donator it causes radiosensitization in the tissue when given before or immediately after irradiation; as an agent stimulating phagocytes and tissue regeneration, it promotes regeneration very effectively when damage is already evident in the tissue.

  13. Survival after total body irradiation: Effects of irradiation of exteriorized small intestine. (Reannouncement with new availability information)

    SciTech Connect

    Vriesendorp, H.M.; Vigneulle, R.M.; Kitto, G.; Pelky, T.; Taylor, P.

    1993-12-31

    Rats receiving lethal irradiation to their exteriorized small intestine with pulsed 18 MVp bremsstrahlung radiation live about 4 days longer than rats receiving a dose of total-body irradiation (TBI) causing intestinal death. The LD50 for intestinal irradiation is approximately 6 Gy higher than the LD50 for intestinal death after TBI. Survival time after exteriorized intestinal irradiation can be decreased, by adding abdominal irradiation. Adding thoracic or pelvic irradiation does not alter survival time. Shielding of large intestine improves survival after irradiation of the rest of the abdomen while the small intestine is also shielded. The kinetics of histological changes in small intestinal tissues implicate the release of humoral factors after irradiation of the abdomen. Radiation injury develops faster in the first (proximal) 40 cm of the small intestine and is expressed predominantly as shortening in villus height. In the last (distal) 40 cm of the small intestine, the most pronounced radiation effect is a decrease in the number of crypts per millimeter. Irradiation (20 Gy) of the proximal small intestine causes 92 % mortality (median survival 10 days). Irradiation (20 Gy) of the distal small intestine causes 27% mortality (median survival > 30 days). In addition to depletion of crypt stem cells in the small intestine, other issues (humoral factors, irradiated subsection of the small intestine and shielding of the large intestine) appear to influence radiation-induced intestinal mortality.

  14. Early Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation In Pediatric Patients With Hematologic Malignancies Following Single Fraction Total Body Irradiation

    PubMed Central

    Druley, Todd E.; Hayashi, Robert; Mansur, David B.; Zhang, Qin (Jean); Barnes, Yvonne; Trinkaus, Kim; Witty, Shannon; Thomas, Tia; Klein, Eric E.; DiPersio, John F.; Adkins, Douglas; Shenoy, Shalini

    2008-01-01

    Fractionated total body irradiation (FTBI) followed by allogeneic hematopoietic stem cell transplantation results in donor engraftment and improves survival in children with high risk hematologic malignancies. However, acute toxicities (skin, lung, mucosa) are common after FTBI. Late complications include cataracts, endocrine dysfunction, sterility and impaired neurodevelopment. In lieu of FTBI, we used low-dose single fraction TBI (550 cGy) with cyclophosphamide as transplant conditioning for pediatric hematologic malignancies. Graft versus host disease prophylaxis included cyclosporine and short course methotrexate; methylprednisolone was added for unrelated donor transplants. Fifty-five children in first (40%) or second remission and beyond (60%) underwent transplantation from bone marrow (65%) or peripheral blood; 62% from unrelated donors; 22% were mismatched. Median follow-up was 18.5 months (1–68). Overall survival and disease-free survival at one year were 60% and 47% respectively. Acute toxicities included grade 3–4 mucositis (18%), invasive infections (11%), multiorgan failure/shock (11%), hemolytic anemia (7%), veno-occlusive disease (4%) and renal failure (4%). Treatment-related mortality was 11% at 100 days. Non-relapse mortality was 6% thereafter. Graft rejection occurred in 2%. Three patients (5%) died of GVHD. The regimen was well tolerated even in heavily pre-treated children and supported donor cell engraftment; long-term follow up is in progress. PMID:19011666

  15. Total-body irradiation and cataract incidence: A randomized comparison of two instantaneous dose rates

    SciTech Connect

    Ozsahin, M.; Belkacemi, Y.; Pene, F.; Dominique, C.; Schwartz, L.H.; Uzal, C.; Lefkopoulos, D.; Gindrey-Vie, B.; Vitu-Loas, L.; Touboul, E. )

    1994-01-15

    To assess the influence of instantaneous total-body irradiation dose rate in hematological malignancies, the authors randomized 157 patients according to different instantaneous dose rates. Patients have undergone a total-body irradiation before bone-marrow transplantation according to two different techniques: Either in one fraction (1000 cGy given to the midplane at the level of L4, and 800 cGy to the lungs) or in six fractions (1200 cGy over 3 consecutive days to the midplane at the level of L4, and 900 cGy to the lungs). Patients were randomized according to two instantaneous dose rates, called LOW and HIGH, in single-dose (6 vs. 15 cGy/min) and fractionated (3 vs. 6 cGy/min) TBI groups; there were 77 cases for the LOW and 80 for the HIGH groups, with 57 patients receiving single-dose (28 LOW, 29 HIGH) and 100 patients receiving fractionated total-body irradiation (49 LOW, 51 HIGH). As of July 1992, 16 of 157 patients developed cataracts after 17 to 46 months, with an estimated incidence of 23% at 5 years. Four of 77 patients in the LOW group, 12 of 80 patients in the HIGH group developed cataracts, with 5-year estimated incidences of 12% and 34%, respectively. Ten of 57 patients in the single-dose group, and 6 of 100 patients in the fractionated group developed cataracts, with 5-year estimated incidences of 39% and 13%, respectively. When the subgroups were considered, in the single-dose group, 3 of 28 LOW patients, and 7 of 29 HIGH patients developed cataracts, with 5-year estimated incidences of 24% and 53%, respectively; in the fractionated group, 1 of 49 LOW patients, and 5 of 51 HIGH patients developed cataracts, with 5-year estimated incidences of 4% and 22%, respectively. There was no statistically significant difference in terms of 5-year estimated cataract incidence between the patients receiving steroids and those not. The instantaneous dose rate was the only independent factor influencing the cataractogenesis. 18 refs., 5 figs., 1 tab.

  16. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    SciTech Connect

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  17. Modification of a standard cobalt-60 unit for total body irradiation at 150 cm SSD

    SciTech Connect

    Peters, V.G.; Herer, A.S.

    1984-06-01

    A cobalt-60 teletherapy unit has been modified to permit total body irradiation (TBI) with a vertical beam in a conventional treatment room. This technique has been implemented at low cost using a few easily made accessories. Removal of the adjustable collimator assembly provides a field 2.3 meters in diameter at 150 cm SSD. A copper flattening filter has been constructed to improve beam uniformity and remove electron contamination. Machine set up time for TBI requires less than 15 minutes and does not affect the routine clinical use of the unit. A dose rate of 32 cGy per minute (midplane) is attainable in a 20 cm thick patient. The dosimetry and technical aspects are presented in this paper.

  18. Total-body irradiation on an isocentric linear accelerator: a radiation output compensation technique.

    PubMed

    Hugtenburg, R P; Turner, J R; Baggarley, S P; Pinchin, D A; Oien, N A; Atkinson, C H; Tremewan, R N

    1994-05-01

    A treatment technique for total-body irradiation (TBI) is proposed that combines arc therapy with dynamic output control to achieve high-grade dose uniformity. The patient lies on a low couch and receives exposure in the prone and supine positions from a modulated arcing beam. The technique has been validated using a personal computer to control the linear accelerator and we demonstrate that only minor alterations to current dynamic therapy systems would be required. We have examined the practical application of this treatment with emphasis on methods of conformal therapy where an optimized dose distribution is prepared from a matrix of caliper measurements taken from the patient. This technique provides a means for regular TBI treatment on a computer-controlled linear accelerator that is easy to set up, requires short exposure times and is comfortable for the patient.

  19. Disturbances in dental development after total body irradiation in bone marrow transplant recipients

    SciTech Connect

    Dahlloef, G.B.; Barr, M.; Bolme, P.; Modeer, T.; Loennqvist, B.R.; Ringden, O.; Heimdahl, A.

    1988-01-01

    The dental status of 16 children who had been treated with bone marrow transplantation (BMT) for serious bone marrow diseases was followed for up to 6 years. Several types of disturbances in dental development were observed in children who had been conditioned with total body irradiation (TBI) at 10 Gy before BMT. Thus, impaired root development that caused short V-shaped roots was found in all patients, a complete failure of root development and premature apical closure were found in five patients, enamel hypoplasia was observed in four patients, and microdontia was observed in three patients conditioned with TBI. Patients younger than 6 years of age at BMT exhibited the most severe and extensive dental aberrations. The TBI at 10 Gy appeared to be the major cause of the disturbances found.

  20. Bone marrow transplantation helps restore the intestinal mucosal barrier after total body irradiation in mice.

    PubMed

    Garg, Sarita; Wang, Wenze; Prabath, Biju G; Boerma, Marjan; Wang, Junru; Zhou, Daohong; Hauer-Jensen, Martin

    2014-03-01

    Bone marrow transplantation (BMT) substantially improves 10-day survival after total body irradiation (TBI), consistent with an effect on intestinal radiation death. Total body irradiation, in addition to injuring the intestinal epithelium, also perturbs the mucosal immune system, the largest immune system in the body. This study focused on how transplanted bone marrow cells (BMCs) help restore mucosal immune cell populations after sublethal TBI (8.0 Gy). We further evaluated whether transplanted BMCs: (a) home to sites of radiation injury using green fluorescent protein labeled bone marrow; and (b) contribute to restoring the mucosal barrier in vivo. As expected, BMT accelerated recovery of peripheral blood (PB) cells. In the intestine, BMT was associated with significant early recovery of mucosal granulocytes (P = 0.005). Bone marrow transplantation did not affect mucosal macrophages or lymphocyte populations at early time points, but enhanced the recovery of these cells from day 14 onward (P = 0.03). Bone marrow transplantation also attenuated radiation-induced increase of intestinal CXCL1 and restored IL-10 levels (P = 0.001). Most importantly, BMT inhibited the post-radiation increase in intestinal permeability after 10 Gy TBI (P = 0.02) and modulated the expression of tight junction proteins (P = 0.01-0.05). Green fluorescent protein-positive leukocytes were observed both in intestinal tissue and in PB. These findings strongly suggest that BMT, in addition to enhancing general hematopoietic and immune system recovery, helps restore the intestinal immune system and enhances intestinal mucosal barrier function. These findings may be important in the development and understanding of strategies to alleviate or treat intestinal radiation toxicity.

  1. Low-dose gamma irradiation of food protein increases its allergenicity in a chronic oral challenge.

    PubMed

    Vaz, A F M; Souza, M P; Medeiros, P L; Melo, A M M A; Silva-Lucca, R A; Santana, L A; Oliva, M L V; Perez, K R; Cuccovia, I M; Correia, M T S

    2013-01-01

    Few chronic food protein models have described the relationship between allergenicity and the molecular structure of food protein after physical processing. The effect of γ-radiation on the structure of food protein was measured by fluorescence, circular dichroism and microcalorimetry. BALB/c mice were intraperitoneally sensitized and then given non-irradiated and irradiated Con-A by daily gavage for 28days. The tendency to form insoluble amorphous aggregates and partially unfolded species was observed after irradiation. The administration of non-irradiated and irradiated samples at low-dose significantly increased weight loss as well as plasma levels of eotaxin in animals repeatedly exposed to Con-A. Significant lymphocytic infiltrate filling completely the stroma of microvilli and tubular glands was observed in the small intestinal of the group given Con-A irradiated at a low dose. This phenotype was not observed in animals treated with Con-A irradiated at a high dose.

  2. Late ophthalmological complications after total body irradiation in non-human primates

    NASA Technical Reports Server (NTRS)

    Niemer-Tucker, M. M.; Sterk, C. C.; de Wolff-Rouendaal, D.; Lee, A. C.; Lett, J. T.; Cox, A.; Emmanouilidis-van der Spek, K.; Davelaar, J.; Lambooy, A. C.; Mooy, C. M.; Broerse, J. J.

    1999-01-01

    PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

  3. Late ophthalmological complications after total body irradiation in non-human primates

    NASA Technical Reports Server (NTRS)

    Niemer-Tucker, M. M.; Sterk, C. C.; de Wolff-Rouendaal, D.; Lee, A. C.; Lett, J. T.; Cox, A.; Emmanouilidis-van der Spek, K.; Davelaar, J.; Lambooy, A. C.; Mooy, C. M.; hide

    1999-01-01

    PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

  4. Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation

    PubMed Central

    Williams, Benjamin B.; Dong, Ruhong; Nicolalde, Roberto J.; Matthews, Thomas P.; Gladstone, David J.; Demidenko, Eugene; Zaki, Bassem I.; Salikhov, Ildar K.; Lesniewski, Piotr N.; Swartz, Harold M.

    2014-01-01

    Purpose The ability to estimate individual exposures to radiation following a large attack or incident has been identified as a necessity for rational and effective emergency medical response. In vivo electron paramagnetic resonance (EPR) spectroscopy of tooth enamel has been developed to meet this need. Materials and methods A novel transportable EPR spectrometer, developed to facilitate tooth dosimetry in an emergency response setting, was used to measure upper incisors in a model system, in unirradiated subjects, and in patients who had received total body doses of 2 Gy. Results A linear dose response was observed in the model system. A statistically significant increase in the intensity of the radiation-induced EPR signal was observed in irradiated versus unirradiated subjects, with an estimated standard error of dose prediction of 0.9 + 0.3 Gy. Conclusions These results demonstrate the current ability of in vivo EPR tooth dosimetry to distinguish between subjects who have not been irradiated and those who have received exposures that place them at risk for acute radiation syndrome. Procedural and technical developments to further increase the precision of dose estimation and ensure reliable operation in the emergency setting are underway. With these developments EPR tooth dosimetry is likely to be a valuable resource for triage following potential radiation exposure of a large population. PMID:21696339

  5. Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation.

    PubMed

    Williams, Benjamin B; Dong, Ruhong; Nicolalde, Roberto J; Matthews, Thomas P; Gladstone, David J; Demidenko, Eugene; Zaki, Bassem I; Salikhov, Ildar K; Lesniewski, Piotr N; Swartz, Harold M

    2011-08-01

    The ability to estimate individual exposures to radiation following a large attack or incident has been identified as a necessity for rational and effective emergency medical response. In vivo electron paramagnetic resonance (EPR) spectroscopy of tooth enamel has been developed to meet this need. A novel transportable EPR spectrometer, developed to facilitate tooth dosimetry in an emergency response setting, was used to measure upper incisors in a model system, in unirradiated subjects, and in patients who had received total body doses of 2 Gy. A linear dose response was observed in the model system. A statistically significant increase in the intensity of the radiation-induced EPR signal was observed in irradiated versus unirradiated subjects, with an estimated standard error of dose prediction of 0.9 ± 0.3 Gy. These results demonstrate the current ability of in vivo EPR tooth dosimetry to distinguish between subjects who have not been irradiated and those who have received exposures that place them at risk for acute radiation syndrome. Procedural and technical developments to further increase the precision of dose estimation and ensure reliable operation in the emergency setting are underway. With these developments EPR tooth dosimetry is likely to be a valuable resource for triage following potential radiation exposure of a large population.

  6. Oral Interleukin 11 as a Countermeasure to Lethal Total-Body Irradiation in a Murine Model

    PubMed Central

    Burnett, Alexander F.; Biju, Prabath G.; Lui, Huanli; Hauer-Jensen, Martin

    2014-01-01

    Countermeasures against radiation are critically needed. Ideally, these measures would be easy to store, easy to administer and have minimal toxicity. We used oral delivery of interleukin 11 (IL11) in mice exposed to lethal doses of total-body irradiation (TBI). Animals were given IL11 by gavage at various daily doses beginning 24 h after TBI, which continued for 5 days. At a TBI of 9.0 Gy, mice treated with IL11 had a 70% survival at 30 days compared with control group survival of 25% (P = 0.035). At 10.0 Gy, treated animals had 50% survival at 30 days compared with no survivors in the control group. Treated animals had significant improvement in intestinal mucosal surface area and crypt survival. In addition bacterial translocation of coliform bacteria was significantly less in the treated animals. Systemic absorption of IL11 was low in treated animals and effects on the hematopoietic cells were not seen. Serum citrulline levels rebounded significantly faster after irradiation in the IL11 treated animals, indicating quicker recovery of small intestine health. These data suggest that IL11 given orally protects the intestinal mucosa from radiation damage and that this compound is beneficial as a mitigating agent even when started 24 h after radiation exposure. PMID:24219324

  7. Long-term results of breast cancer irradiation treatment with low-dose-rate external irradiation

    SciTech Connect

    Pierquin, Bernard; Tubiana, Maurice . E-mail: maurice.tubiana@biomedicale.univ-paris5.fr; Pan, Camille; Lagrange, Jean-Leon; Calitchi, Elie; Otmezguine, Yves

    2007-01-01

    Purpose: The aim of this study was to assess beam therapy with low-dose-rate (LDR) external irradiation in a group of patients with breast cancer. Methods and Materials: This trial compared, from 1986 to 1989, patients with advanced breast cancer treated either by conventional fractionation or low-dose-rate (LDR) external radiotherapy (dose-rate 15 mGy/min, 5 sessions of 9 Gy delivered on 5 consecutive days). Results: A total of 21 patients were included in the fractionated therapy arm. At follow-up 15 years after treatment, 7 local recurrences had occurred, 3 patients had died of cancer, 18 patients were alive, 10 were without evidence of disease, and 6 had evidence of disease. A total of 22 patients had been included in the LDR arm of the study. Of these, 11 had received a dose of 45 Gy; thereafter, in view of severe local reactions, the dose was reduced to 35 Gy. There was no local recurrence in patients who had received 45 Gy, although there were 2 local recurrences among the 11 patients after 35 Gy. The sequelae were severe in patients who received 45 Gy but were comparable to those observed in patients treated by fractionated radiotherapy who received 35 Gy. The higher efficacy of tumor control in patients treated by LDR irradiation as well as the lower tolerance of normal tissue are probably related to the lack of repopulation. Conclusion: Although the patient numbers in this study are limited, based on our study results we conclude that the data for LDR irradiation are encouraging and that further investigation is warranted.

  8. Report on FY16 Low-dose Metal Fuel Irradiation and PIE

    SciTech Connect

    Edmondson, Philip D.

    2016-09-01

    This report gives an overview of the efforts into the low-dose metal fuel irradiation and PIE as part of the Fuel Cycle Research & Development (FCRD) Advanced Fuels Campaign (AFC) milestone M3FT-16OR020303031. The current status of the FCT and FCRP irradiation campaigns are given including a description of the materials that have been irradiated, analysis of the passive temperature monitors, and the initial PIE efforts of the fuel samples.

  9. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model

    PubMed Central

    Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6–14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2–4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies. PMID:27579862

  10. Stimulation of hematopoietic stem cells by interferon inducer in nonhuman primates receiving fractionated total body irradiation

    SciTech Connect

    Lvovsky, E.A.; Levine, P.H.; Bengali, Z.; Leiseca, S.A.; Cicmanec, J.L.; Robinson, J.E.; Bautro, N.; Levy, H.B.; Scott, R.M.

    1982-10-01

    Interferon response and hematopoietic stem cells (spleen colony forming units-CFU-S) were studied in rhesus monkeys subjected to fractionated total body irradiation (FTBI). An interferon inducer, a nuclease resistant complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxmethylcellulose(-poly(ICLC)) was used. Poly(ICLC) at 3.75 mg/m/sup 2/ was given I.V. to 7 monkeys, 5 of which, starting 24 hours later, received 50 rad of 4 MV X rays twice a week for 2.5 weeks (total of 250 rad). Another group of 4 monkeys received FTBI only. Although the initial interferon response was similar in both groups treated with poly(ICLC)-800 international units (IU), the animals receiving FTBI showed reduced interferon levels after 100 rad. These animals, however, did not develop the hyporesponsiveness to subsequent poly(ICLC) injections that was observed in non-irradiated monkeys. Stabile interferon response (30-100 IU) in the FTBI group paralleled the prolonged persistence of the drug in their serum. Bone marrow (BM) aspirates from animals receiving FTBI and poly(ICLC) contained more CFU-S per 10/sup 6/ nucleated cells than those treated with poly(ICLC) alone or FTBI alone. FTBI with and without poly(ICLC) led to thrombocytopenia and leukopenia. Lower white blood cell (WBC) count was found in irradiated animals treated with poly(ICLC). Partial alopecia was observed in animals receiving poly(ICLC). Two animals--one in the poly(ICLC) and FTBI group and the other receiving FTBI alone, died with thrombocytopenia and leukopenia.

  11. Stimulation of hematopoietic stem cells by interferon inducer in nonhuman primates receiving fractionated total body irradiation

    SciTech Connect

    Lvovsky, E.A.; Levine, P.H.; Bengali, Z.; Leiseca, S.A.; Cicmanec, J.L.; Robinson, J.E.; Bautro, N.; Levy, H.B.; Scott, R.M.

    1982-10-01

    Interferon response and hematopoietic stem cells (spleen colony forming units--CFU-S) were studied in rhesus monkeys subjected to fractionated total body irradiation (FTBI). An interferon inducer, a nuclease resistant complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxmethylcellulose(-poly(ICLC)) was used. Poly(ICLC) at 3.75 mg/m/sup 2/ was given I.V. to 7 monkeys, 5 of which, starting 24 hours later, received 50 rad of 4 MV X rays twice a week at 2.5 weeks (total of 250 rad). Another group of 4 monkeys received FTBI only. Although the initial interferon response was similar in both groups treated wih poly(ICLC)--800 international units (IU), the animals that receiving FTBI showed reduced interferon levels after 100 rad. These animals, however, did not develop the hyporesponsiveness to subsequent poly(ICLC) injections that was observed in non-irradiated monkeys. Stabile interferon response (30-100 IU) in the FTBI group paralleled the prolonged persistence of the drug in their serum. Bone marrow (BM) aspirates from animals receiving FTBI and poly(ICLC) contained more CFU-S per 10/sup 6/ nucleated cells than those treated with poly(ICLC) along or FTBI with and without poly(ICLC) lead to thrombocytopenia and leukopenia. Lower white blood cell (WBC) count was found in irradiated animals treated with poly(ICLC). Partial alopecia was observed in animals receiving poly(ICLC). Two animals--one in the poly(ICLC) and FTBI group and the other receiving FTBI along, died with thrombocytopenia and leukopenia.

  12. The effect of irradiation at low doses on human embryos and fetuses

    SciTech Connect

    Romanova, L.K.; Zhorova, E.S.

    1994-05-01

    Data about the biological effect of irradiation at low dose on prenatal human development have been reviewed. The effect of irradiation is observed either immediately after it or in the progeny, as consequences of irradiation affecting the embryo or fetus. Human embryos and fetuses are most sensitive to ionizing irradiation during the peaks of proliferative activity and cell differentiation. The concept has been formulated that any dose of irradiation, however low, can inflict damage to the embryo or fetus. Problems and perspectives of studies in this field are discussed.

  13. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice

    PubMed Central

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with 11C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice. PMID:23908553

  14. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice.

    PubMed

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with (11)C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice.

  15. Low-Dose Irradiation Affects Expression of Inflammatory Markers in the Heart of ApoE -/- Mice

    PubMed Central

    Mathias, Daniel; Mitchel, Ronald E. J.; Barclay, Mirela; Wyatt, Heather; Bugden, Michelle; Priest, Nicholas D.; Scholz, Markus; Hildebrandt, Guido; Kamprad, Manja; Glasow, Annegret

    2015-01-01

    Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025–0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025–2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05–2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and

  16. Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

    PubMed

    Mathias, Daniel; Mitchel, Ronald E J; Barclay, Mirela; Wyatt, Heather; Bugden, Michelle; Priest, Nicholas D; Whitman, Stewart C; Scholz, Markus; Hildebrandt, Guido; Kamprad, Manja; Glasow, Annegret

    2015-01-01

    Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention

  17. A Serum Small Molecule Biosignature of Radiation Exposure from Total Body Irradiated Patients.

    PubMed

    Laiakis, Evagelia C; Pannkuk, Evan L; Chauthe, Siddheshwar Kisan; Wang, Yi-Wen; Lian, Ming; Mak, Tytus D; Barker, Christopher A; Astarita, Giuseppe; Fornace, Albert J

    2017-10-06

    The potential for radiological accidents and nuclear terrorism has increased the need for the development of new rapid biodosimetry methods. In addition, in a clinical setting the issue of an individual's radiosensitivity should be taken into consideration during radiotherapy. We utilized metabolomics and lipidomics to investigate changes of metabolites in serum samples following exposure to total body ionizing radiation in humans. Serum was collected prior to irradiation, at 3-8 h after a single dose of 1.25-2 Gy, and at 24 h with a total delivered dose of 2-3.75 Gy. Metabolomics revealed perturbations in glycerophosphocholine, phenylalanine, ubiquinone Q2, and oxalic acid. Alterations were observed in circulating levels of lipids from monoacylglycerol, triacylglycerol, phosphatidylcholine, and phosphatidylglycerol lipid classes. Polyunsaturated fatty acids were some of the most dysregulated lipids, with increased levels linked to proinflammatory processes. A targeted metabolomics approach for eicosanoids was also employed. The results showed a rapid response for proinflammatory eicosanoids, with a dampening of the signal at the later time point. Sex differences were observed in the markers from the untargeted approach but not the targeted method. The ability to identify and quantify small molecules in blood can therefore be utilized to monitor radiation exposure in human populations.

  18. The fate of cells with chromosome aberrations after total-body irradiation and bone marrow transplantation

    SciTech Connect

    Carbonell, F.; Ganser, A.; Fliedner, T.M.; Arnold, R.; Kubanek, B.

    1983-03-01

    Cytogenetic studies were done on bone marrow cells and peripheral lymphocytes of four patients (three with acute nonlymphocytic leukemia, one with aplastic anemia) at various intervals up to 861 days after total-body X irradiation (TBI) at doses between 4.5 and 10 Gy (450-1000 rad) followed by syngeneic or allogeneic bone marrow transplantation. Whereas no radiation-induced aberrations could be found in the bone marrow, apart from a transient finding in the patient with the lowest radiation dose, aberrant metaphases were seen in the peripheral lymphocytes of three patients in the range from 2.5 to 46% even at 861 days after the exposure. There were no demonstrable aberrations related to TBI in the only patient developing graft-versus-host disease. The dicentric yield as determined in the aberrant metaphases with 46 centromeres ranged between 3.4 +/- 1.3 and 4.9 +/- 0.4. In one patient it was demonstrated by BUdR-labeling that after 10 Gy (1000 rad) TBI the surviving and heavily damaged lymphocytes can go into cell cycle and reach at least the third mitosis. The percentage of aberrant cells diminished by about 25% at each mitotic division.

  19. A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

    SciTech Connect

    Yao Rui; Bernard, Damian; Turian, Julius; Abrams, Ross A.; Sensakovic, William; Fung, Henry C.; Chu, James C. H.

    2012-04-15

    Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lung dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.

  20. Fludarabine Allows Dose Reduction for Total Body Irradiation in Pediatric Hematopoietic Stem Cell Transplantation

    SciTech Connect

    Kornguth, David G. . E-mail: dkorngut@mdanderson.org; Mahajan, Anita; Woo, Shiao; Chan, Ka Wah; Antolak, John; Ha, Chul S.

    2007-07-15

    Purpose: To examine, in the setting of total body irradiation (TBI) for the preparation of pediatric hematopoietic stem cell transplantation (HSCT), whether TBI dose can be reduced without compromising the efficacy of a regimen consisting of fludarabine and radiotherapy; and whether there is any increased risk of pulmonary toxicity due to the radiosensitizing effect of fludarabine. Methods and Materials: A total of 52 pediatric patients with hematologic malignancies received TBI-based conditioning regimens in preparation for allogeneic HSCT. Twenty-three patients received 12 Gy in 4 daily fractions in combination with cyclophosphamide, either alone or with other chemotherapeutic and biologic agents. Twenty-nine patients received 9 Gy in 3 fractions in conjunction with fludarabine and melphalan. Clinical and radiation records were reviewed to determine engraftment, pulmonary toxicity (according to Radiation Therapy Oncology Group criteria), transplant-related mortality, recurrence of primary disease, and overall survival. Results: The two groups of patients had comparable pretransplant clinical characteristics. For the 12-Gy and 9-Gy regimens, the engraftment (89% and 93%; p = 0.82), freedom from life-threatening pulmonary events (65% and 79%; p = 0.33), freedom from relapse (60% and 73%; p = 0.24), and overall survival (26% and 47%; p = 0.09) were not statistically different. Conclusions: The addition of fludarabine and melphalan seems to allow the dose of TBI to be lowered to 9 Gy without loss of engraftment or antitumor efficacy.

  1. [Technic and dosimetry in total body irradiation with 18 MeV photons].

    PubMed

    Ragona, R; Anglesio, S; Urgesi, A; Monetti, U; Rossi, G; Tessa, M

    1987-05-01

    Total body irradiation (TBI) is used in our Institution in the conditioning regimen for bone marrow transplantation. The fractionation pattern consists of two daily fractions of 1.65 Gy repeated for 4 days (total dose 13.20 Gy in 8 fractions). Lung dose is reduced by means of lead custom shaped shields directly strapped to the patient surface. TBI is delivered by a THERAC 20 linear accelerator with two opposing AP-PA photon beams with a maximum energy of 18 MeV. Treatment distance is 340 cm and the patient is treated in a semi-standing position. Dosimetry studies in a homogeneous phantom were performed in the treatment geometry and consisted in the determination of: tissue maximum ratios (TMR) at different depths, absorbed dose along the median axis and the diagonal of the field, variation of the absorbed dose in the prescription point with different volumes of scattering material, and transmission of shielding and compensating material. A semi-empiric formula for the calculation of absorbed dose in a point has been obtained. A subsequent study in a Rando phantom with termoluminescent dosimeters (TLD) has shown a +/- 5% agreement between calculated and measured values and a +/- 7% homogeneity.

  2. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    SciTech Connect

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-11-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  3. Negative Impact of Total Body Irradiation on the Antitumor Activity of Rhenium-(I)-diselenoether.

    PubMed

    Collery, Philippe; Santoni, Francois; Mohsen, Ahmed; Mignard, Caroline; Desmaele, Didier

    2016-11-01

    It has been shown that a rhenium-(I)-diselenoether complex had significant antitumor activity in MDA-MB231 tumor-bearing mice after repeated oral or intraperitoneal administrations for 4 weeks at safe doses of 10 mg/kg/day. It has also been suggested that lower doses could be as effective as this dose. We, thus, tested two doses (5 and 10 mg/kg). The drug was orally administered daily by gavage for 4 weeks and for a further 2 weeks with or without 15 mg/kg paclitaxel treatment (intravenously, once a week). This experiment was performed in MDA-MB 231 tumor-bearing mice, as a model of resistant breast tumor. However, in contrast to previous studies, the mice were pretreated with total body irradiation to increase the tumor growth. These two doses were safe, even in combination with paclitaxel. The expected tumor regression was not observed with the rhenium-(I)-diselenoether complex, and there was even a significant increase of the tumor volume in mice treated with 10 mg/kg versus controls. No synergism was observed with paclitaxel. We comment on the possible negative impact of radiotherapy on the antitumor activity of the drug. Plasma and tumor rhenium and selenium concentrations are also reported. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. The Yiqi and Yangyin Formula ameliorates injury to the hematopoietic system induced by total body irradiation

    PubMed Central

    Zhang, Junling; Li, Hongyu; Lu, Lu; Yan, Lixiang; Yang, Xiangdong; Shi, Zhexin; Li, Deguan

    2017-01-01

    In this study, we examined whether the Yiqi and Yangyin Formula (YYF), used in traditional Chinese medicine, could ameliorate damage to the hematopoietic system induced by total body irradiation (TBI). Treatment with 15 g/kg of YYF increased the survival rate of Institute of Cancer Research (ICR) mice exposed to 7.5 Gy TBI. Furthermore, YYF treatment increased the white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and hematocrit (HCT) counts in ICR mice exposed to 2 Gy or 4 Gy TBI. Treatment with YYF also increased the number of bone marrow cells, hematopoietic progenitor cells (HPCs), hematopoietic stem cells (HSCs) and the colony-forming ability of granulocyte–macrophage cells. YYF alleviated TBI-induced suppression of the differentiation ability of HPCs and HSCs and decreased the reactive oxygen species (ROS) levels in bone marrow mononuclear cells (BMMNCs), HPCs and HSCs from mice exposed to 2 Gy or 4 Gy TBI. Overall, our data suggest that YYF can ameliorate myelosuppression by reducing the intracellular ROS levels in hematopoietic cells after TBI at doses of 2 Gy and 4 Gy. PMID:27422936

  5. Linac-based total body irradiation (TBI) with volumetric modulated arc therapy (VMAT)

    NASA Astrophysics Data System (ADS)

    Tas, B.; Durmus, I. F.; Okumus, A.; Uzel, O. E.

    2017-02-01

    To evaluate dose distribution of Volumetric modulated arc therapy (VMAT) planning tecnique using Versa HD® lineer accelerator to deliver Total Body Irradiation (TBI) on the coach. Eight TBI patient's Treatment Planning System (TPS) were performed with dual arc VMAT for each patient. The VMAT-TBI consisted of three isocentres and three dual overlapping arcs. The prescribed dose was 12 Gy. Mean dose to lung and kidney were restricted less than 10 Gy and max. dose to lens were restricted less than 6 Gy. The plans were verified using 2D array and ion chamber. The comparison between calculation and measurement were made by γ-index analysis and absolute dose. An average total delivery time was determined 923±34 seconds and an average MU was determined 2614±228 MUs for dual arc VMAT. Mean dose to lungs was 9.7±0.2 Gy, mean dose to kidneys was 8.8±0.3 Gy, max. dose to lens was 5.5±0.3 Gy and max. dose was 14.6±0.3 Gy, HI of PTV was 1.13±0.2, mean dose to PTV was 12.6±1.5 Gy and mean γ-index pass rate was %97.1±1.9. The results show that the tecnique for TBI using VMAT on the treatment coach is feasible.

  6. Cataracts after total body irradiation and marrow transplantation: a sparing effect of dose fractionation

    SciTech Connect

    Deeg, H.J.; Flournoy, N.; Sullivan, K.M.; Sheehan, K.; Buckner, C.D.; Sanders, J.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.

    1984-07-01

    Two hundred seventy-seven patients, who have been followed for 1 to 12 years after marrow transplantation, have been examined for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing /sup 60/Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients). To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only, suggesting a significant sparing effect with use of TBI dose fractionation.

  7. Cell survival kinetics in peripheral blood and bone marrow during total body irradiation for marrow transplantation

    SciTech Connect

    Shank, B.; Andreeff, M.; Li, D.

    1983-11-01

    Cell survival kinetics in both peripheral blood and in bone marrow have been studied over the time course of hyperfractionated total body irradiation (TBI) for bone marrow transplantation. Our unique TBI regimen allows the study of the in vivo radiation effect uncomplicated by prior cyclophosphamide, since this agent is given after TBI in our cytoreduction scheme. Peripheral blood cell concentrations were monitored with conventional laboratory cell counts and differentials. Absolute bone marrow cell concentrations were monitored by measuring cell concentrations in an aspirate sample and correcting for dilution with blood by a cell cycle kinetic method using cytofluorometry. For lymphocytes in peripheral blood in patients in remission, the effective D/sub 0/ ranged from 373 rad in 10 children less than or equal to 10 y old, to 536 rad in the four patients between 11 to 17 y old, while n = 1.0 in all groups. There was no trend observed according to age. Granulocytes had a much higher effective D/sub 0/, approximately 1000 rad in vivo. Absolute nucleated cell concentration in marrow dropped slowly initially, due to an increased lymphocyte concentration in marrow during a concurrent drop in lymphocyte concentration in peripheral blood, but eventually fell on the last day of TBI ranging from 7 to 44% of the initial marrow nucleated cell concentration. Marrow myeloid elements, however, dropped continuously throughout the course of TBI.

  8. Monte Carlo optimization of total body irradiation in a phantom and patient geometry

    NASA Astrophysics Data System (ADS)

    Chakarova, R.; Müntzing, K.; Krantz, M.; Hedin, E.; Hertzman, S.

    2013-04-01

    The objective of this work is to apply a Monte Carlo (MC) accelerator model, validated by experimental data at isocentre distances, to a large-field total body irradiation (TBI) technique and to develop a strategy for individual patient treatment on the basis of MC dose distributions. Calculations are carried out using BEAMnrc/DOSXYZnrc code packages for a 15 MV Varian accelerator. Acceptable agreement is obtained between MC data and measurements in a large water phantom behind a spoiler at source-skin distances (SSD) = 460 cm as well as in a CIRS® thorax phantom. Dose distributions in patients are studied when simulating bilateral beam delivery at a distance of 480 cm to the patient central sagittal plane. A procedure for individual improvement of the dose uniformity is suggested including the design of compensators in a conventional treatment planning system (TPS) and a subsequent update of the dose distribution. It is demonstrated that the dose uniformity for the simple TBI technique can be considerably improved. The optimization strategy developed is straightforward and suitable for clinics where the TPS available is deficient to calculate 3D dose distributions at extended SSD.

  9. Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion

    SciTech Connect

    Lichter, A.S.; Tracy, D.; Lam, W.C.; Order, S.E.

    1980-03-01

    Bone marrow transplantation (BMT) after total body irradiation (TBI) and cyclophosphamide is being employed increasingly in the therapy of end stage leukemia. Interstitial pneumonitis (IP) represents a major acute toxicity after allogeneic transplantation. A more rapid reconstitution of lymphoid organs and bone marrow post transplant may result in increased immune competence and hence fewer opportunistic pulmonary infections and IP. By delaying the infusion of marrow to 72 hr after TBI (1250 rad at 7.5 rad/min) instead of the customary 24 hr, we can demonstrate an increase in initial repopulation of thymus, spleen and bone marrow, with syngeneic transplants in Lewis rats. Interstitial pneumonitis may also be caused, in part, by the pulmonary toxicity of large single exposures of TBI. Clinical and laboratory data suggest that fractionated TBI may be less toxic to the lung. When fractionated TBI (625 rad x 2, 7.5 rad/min) is compared to single dose TBI (1250 rad, 7.5 rad/min), and increased initial repopulation of lymphoid organs is observed when fractionated therapy is employed. Delay in marrow infusion and fractionation of TBI exposure may have clinical advantages in patients who receive BMT.

  10. Benefits of online in vivo dosimetry for single-fraction total body irradiation

    SciTech Connect

    Eaton, David J.; Warry, Alison J.; Trimble, Rachel E.; Vilarino-Varela, Maria J.; Collis, Christopher H.

    2014-01-01

    Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.

  11. Anticarcinogenic effect of tetrachlorodecaoxide after total-body gamma irradiation in rats

    SciTech Connect

    Kempf, S.R.; Port, R.E.; Ivankovic, S.

    1994-08-01

    Tetrachlorodecaoxygen (TCDO) therapy of acute radiation syndrome was tested for a possible influence on the development of X-ray-induced malignancies. BD IX rats were exposed to total-body irradiation (TBI, {gamma} rays, 9 or 11 Gy) and received daily intravenous injections of either TCDO or physiological saline solution from days 4 through 11 after TBI. The short-term TCDO therapy reduced the acute death rate markedly, but survival rates after 4 months were similar with and without TCDO. The first malignancy after TBI occurred on day 103, and over the lifetime of the animals the tumor incidence in the group given TBI (11 Gy) without TCDO treatment was 73% vs 20% in animals with short-term TCDO therapy after TBI. In particular, there was a highly significant prevention of radiation-induced leukemia [P (one-sided) < 0.001] by TCDO, and a significantly reduced incidence of malignant epithelial tumors [P (one-sided) < 0.05]. The development of sarcomas was not affected by TCDO. Long-term survival was not enhanced by TCDO due to the occurrence of bronchopneumonial infections about 1 year after TBI. In conclusion, TCDO is not only a potent therapeutic agent in acute radiation syndrome, but it also significantly reduced the carcinogenic risk in rats after exposure to ionizing radiation. 18 refs., 3 figs., 4 tabs.

  12. An anti-apoptotic peptide improves survival in lethal total body irradiation

    SciTech Connect

    McDunn, Jonathan E.; Muenzer, Jared T.; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C.; Davis, Christopher G.; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S.

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 {mu}M) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  13. Benefits of online in vivo dosimetry for single-fraction total body irradiation.

    PubMed

    Eaton, David J; Warry, Alison J; Trimble, Rachel E; Vilarino-Varela, Maria J; Collis, Christopher H

    2014-01-01

    Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.

  14. Beam configuration and physical parameters of clinical high energy photon beam for total body irradiation (TBI).

    PubMed

    Ravichandran, Ramamoorthy; Binukumar, Johnson Pichi; Davis, Chirayathmanjiyil Antony; Sivakumar, Somangali Sathiyamurthy; Krishnamurthy, Kammari; Mandhari, Zahid Al; Rajan, Balakrishnan

    2011-07-01

    To start total body irradiation (TBI) treatments, physical parameters are measured for a magna field irradiation. 6 MV photon beam from Clinac 600 CD linear accelerator (Varian, USA) with fully opened collimator at 45° and gantry at 270° provided a diamond shaped magna field with diagonal dimension 224 cm at 4.0 m source skin distance (SSD). The flatness of the radiation field was measured in the presence of locally designed acrylic beam spoiler and beam flatness filter. Central Axis Depth dose data (CADD), tissue maximum ratios and entrance dose pattern are measured using large phantoms. Methods for clinical dose estimation using semi-conductor diodes and TLD were standardized. PVC beam flattener at the shielding tray position and the presence of acrylic beam spoiler in the radiation field provided a flatness of 100.15% ± 0.44% compared to open beam flatness 101.6 ± 1.5%. A reduction of 2% in percentage depth dose was observed at 10 cm depth in the presence of 15 mm acrylic beam spoiler. However, no changes are observed in the TMRs with presence of beam spoiler. The measured ionization ratios clearly showed change of beam quality with the introduction of beam spoiler. The presence of 15 mm beam spoiler ensured entrance dose 100% at skin and remaining unchanged within 1% upto a depth of 10 mm. Phantom measurements show good agreement between calculated and measured doses. The paper recommends use of modified CADD parameters for treatment planning, if calibration of output is carried out in the presence of beam spoiler. Copyright © 2010. Published by Elsevier Ltd.

  15. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

  16. Attenuator design for organs at risk in total body irradiation using a translation technique

    SciTech Connect

    Lavallee, Marie-Claude; Aubin, Sylviane; Chretien, Mario; Larochelle, Marie; Beaulieu, Luc

    2008-05-15

    Total body irradiation (TBI) is an efficient part of the treatment for malignant hematological diseases. Dynamic TBI techniques provide great advantages (e.g., dose homogeneity, patient comfort) while overcoming treatment room space restrictions. However, with dynamic techniques come additional organs at risk (OAR) protection challenges. In most dynamic TBI techniques, lead attenuators are used to diminish the dose received by the OARs. The purpose of this study was to characterize the dose deposition under various shapes of attenuators in static and dynamic treatments. This characterization allows for the development of a correction method to improve attenuator design in dynamic treatments. The dose deposition under attenuators at different depths in dynamic treatment was compared with the static situation based on two definitions: the coverage areas and the penumbra regions. The coverage area decreases with depth in dynamic treatment while it is stable for the static situation. The penumbra increases with depth in both treatment modes, but the increasing rate is higher in the dynamic situation. Since the attenuator coverage is deficient in the dynamic treatment mode, a correction method was developed to modify the attenuator design in order to improve the OAR protection. The correction method is divided in two steps. The first step is based on the use of elongation charts, which provide appropriate attenuator coverage and acceptable penumbra for a specific depth. The second point is a correction method for the thoracic inclination, which can introduce an orientation problem in both static and dynamic treatments. This two steps correction method is simple to use and personalized to each patient's anatomy. It can easily be adapted to any dynamic TBI techniques.

  17. Development and clinical application of a length-adjustable water phantom for total body irradiation.

    PubMed

    Chen, Zhi-Wei; Yao, Sheng-Yu; Zhang, Tie-Ning; Zhu, Zhen-Hua; Hu, Zhe-Kai; Lu, Xun

    2012-08-01

    A new type of water phantom which would be specialised for the absorbed dose measurement in total body irradiation (TBI) treatment is developed. Ten millimetres of thick Plexiglas plates were arranged to form a square cube with 300 mm of edge length. An appropriate sleeve-type piston was installed on the side wall, and a tabular Plexiglas piston was positioned inside the sleeve. By pushing and pulling the piston, the length of the self-made water phantom could be varied to meet the required patients' physical sizes. To compare the international standard water phantom with the length-adjustable and the Plexiglas phantoms, absorbed dose for 6-MV X ray was measured by an ionisation chamber at different depths in three kinds of phantoms. In 70 cases with TBI, midplane doses were metered using the length-adjustable and the Plexiglas phantoms for simulating human dimensions, and dose validation was synchronously carried out. There were no significant statistical differences, p > 0.05, through statistical processing of data from the international standard water phantom and the self-designed one. There were significant statistical differences, p < 0.05, between the two sets of data from the standard and the Plexiglas one. In addition, the absolute difference had a positive correlation with the varied depth of the detector in the Plexiglas phantom. Comparing the data of clinical treatment, the differences were all <1 % among the prescription doses and the validation data collected from the self-design water phantom. However, the differences collected from the Plexiglas phantom were increasing gradually from +0.77 to +2.30 % along with increasing body width. Obviously, the difference had a positive correlation with the body width. The results proved that the new length-adjustable water phantom is more accurate for simulating human dimensions than Plexiglas phantom.

  18. SU-E-T-275: Dose Build Up and Bolusing Characteristics for Total Body Irradiation Dosimetry

    SciTech Connect

    Butson, M; Pope, D; Whitaker, M

    2015-06-15

    Purpose: Total Body Irradiation (TBI) treatments are mainly used in a preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. Our standard regimen is a 12 Gy / 6 fraction bi-daily technique. To evaluate the delivered dose homogeneity to the patient, EBT3 Gafchromic film is positioned at the head, neck, chest, pelvis and groin for all fractions. This work investigates and quantifies the build-up dose characteristics at TBI distances and requirements for in-vivo dosimetry bolusing. Methods: Percentage dose build up characteristics of photon beams have been investigated at large extended SSD’s using parallel plate ionisations chambers (Attix) and EBT3 Gafchromic film. Measurements were made to open fields at different field sizes as well as large 40cm × 40cm fields with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point. Results: Percentage surface dose measured values for open fields at 300 cm SSD were found to range from 20 % up to 65.5 % for fields of 5 cm × 5 cm to 40 cm × 40 cm. With the introduction of 1cm Perspex scattering plates used in TBI treatments the surface dose values increased up to 83% to 90%, depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 3mm water equivalent bolus / scatter material should be placed over the EBT3 for accurate dose assessment for TBI treatments. Conclusion: Build up dose characteristics exist at long (300cm) SSD’s including treatments using Perspex scattering plates placed at various distances form the patient during TBI treatment. Top accurately assess the applied dose during treatment, in-vivo dosimeters such as Gafchromic EBT3 should have at least 3mm bolus / scatter material placed over them to measure actual applied doses.

  19. Voxel-Based Dose Reconstruction for Total Body Irradiation With Helical TomoTherapy

    SciTech Connect

    Chao Ming; Penagaricano, Jose; Yan Yulong; Moros, Eduardo G.; Corry, Peter; Ratanatharathorn, Vaneerat

    2012-04-01

    Purpose: We have developed a megavoltage CT (MVCT)-based dose reconstruction strategy for total body irradiation (TBI) with helical TomoTherapy (HT) using a deformable registration model to account for the patient's interfraction changes. The proposed technique serves as an efficient tool for delivered dose verification and, potentially, plan adaptation. Methods and Materials: Four patients with acute myelogenous leukemia treated with TBI using HT were selected for this study. The prescription was 12 Gy, 2 Gy/fraction, twice per day, given at least 6 h apart. The original plan achieved coverage of 80% of the clinical target volume (CTV) by the 12 Gy isodose surface. MVCTs were acquired prior to each treatment. Regions of interest were contoured on each MVCT. The dose for each fraction was calculated based on the MVCT using the HT planned adaptive station. B-spline deformable registration was conducted to establish voxel-to-voxel correspondence between the MVCT and the planning CT. The resultant deformation vector was employed to map the reconstructed dose from each fraction to the same point as the plan dose, and a voxel-to-voxel summed dose from all six fractions was obtained. The reconstructed dose distribution and its dosimetric parameters were compared with those of the original treatment plan. Results: While changes in CTV contours occurred in all patients, the reconstructed dose distribution showed that the dose-volume histogram for CTV coverage was close (<1.5%) to that of the original plan. For sensitive structures, the differences between the reconstructed and the planned doses were less than 3.0%. Conclusion: Voxel-based dose reconstruction strategy that takes into account interfraction anatomical changes using MVCTs is a powerful tool for treatment verification of the delivered doses. This proposed technique can also be applied to adaptive TBI therapy using HT.

  20. Evaluation of Field-in-Field Technique for Total Body Irradiation

    SciTech Connect

    Onal, Cem; Sonmez, Aydan; Arslan, Gungor; Sonmez, Serhat; Efe, Esma; Oymak, Ezgi

    2012-08-01

    Purpose: To evaluate the clinical use of a field-in-field (FIF) technique for total body irradiation (TBI) using a treatment-planning system (TPS) and to verify TPS results with in vivo dose measurements using metal-oxide-semiconductor field-effect transistor (MOSFET) detectors. Methods and Materials: Clinical and dosimetric data of 10 patients treated with TBI were assessed. Certain radiation parameters were measured using homogenous and regular phantoms at an extended distance of 380 cm, and the results were compared with data from a conventional standard distance of 100 cm. Additionally, dosimetric validation of TPS doses was performed with a Rando phantom using manual calculations. A three-dimensional computed tomography plan was generated involving 18-MV photon beams with a TPS for both open-field and FIF techniques. The midline doses were measured at the head, neck, lung, umbilicus, and pelvis for both open-field and FIF techniques. Results: All patients received planned TBI using the FIF technique with 18-MV photon energies and 2 Gy b.i.d. on 3 consecutive days. The difference in tissue maximum ratios between the extended and conventional distances was <2%. The mean deviation of manual calculations compared with TPS data was +1.6% (range, 0.1-2.4%). A homogenous dose distribution was obtained with 18-MV photon beams using the FIF technique. The mean lung dose for the FIF technique was 79.2% (9.2 Gy; range, 8.8-9.7 Gy) of the prescribed dose. The MOSFET readings and TPS doses in the body were similar (percentage difference range, -0.5% to 2.5%) and slightly higher in the shoulder and lung (percentage difference range, 4.0-5.5%). Conclusion: The FIF technique used for TBI provides homogenous dose distribution and is feasible, simple, and spares time compared with more-complex techniques. The TPS doses were similar to the midline doses obtained from MOSFET readings.

  1. Development of a Metabolomic Radiation Signature in Urine from Patients Undergoing Total Body Irradiation

    PubMed Central

    Laiakis, Evagelia C.; Mak, Tytus D.; Anizan, Sebastien; Amundson, Sally A.; Barker, Christopher A.; Wolden, Suzanne L.; Brenner, David J.; Fornace, Albert J.

    2014-01-01

    The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4–6 h postirradiation (a single dose of 1.25 Gy) and 24 h (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained through analysis with ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (TOFMS). Prior to further analyses, each sample was normalized to its respective creatinine level. Statistical analysis was conducted by the nonparametric Kolmogorov-Smirnov test and the Fisher’s exact test and markers were validated against pure standards. Seven markers showed distinct differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine and the carnitine conjugates acetylcarnitine, decanoylcarnitine and octanoylcarnitine play an important role in the transportation of fatty acids across mitochondria for subsequent fatty acid β-oxidation. The remaining metabolites, hypoxanthine, xanthine and uric acid are the final products of the purine catabolism pathway, and high levels of excretion have been associated with increased oxidative stress and radiation induced DNA damage. Further analysis revealed sex differences in the patterns of excretion of the markers, demonstrating that generation of a sex-specific metabolomic signature will be informative and can provide a quick and reliable assessment of individuals in a radiological scenario. This is the first radiation metabolomics study in human urine laying the foundation for the use of metabolomics in biodosimetry and providing confidence in biomarker

  2. In vivo dosimetry for total body irradiation: five-year results and technique comparison.

    PubMed

    Patel, Reshma P; Warry, Alison J; Eaton, David J; Collis, Christopher H; Rosenberg, Ivan

    2014-07-08

    The aim of this work is to establish if the new CT-based total body irradiation (TBI) planning techniques used at University College London Hospital (UCLH) and Royal Free Hospital (RFH) are comparable to the previous technique at the Middlesex Hospital (MXH) by analyzing predicted and measured diode results. TBI aims to deliver a homogeneous dose to the entire body, typically using extended SSD fields with beam modulation to limit doses to organs at risk. In vivo dosimetry is used to verify the accuracy of delivered doses. In 2005, when the Middlesex Hospital was decommissioned and merged with UCLH, both UCLH and the RFH introduced updated CT-planned TBI techniques, based on the old MXH technique. More CT slices and in vivo measurement points were used by both; UCLH introduced a beam modulation technique using MLC segments, while RFH updated to a combination of lead compensators and bolus. Semiconductor diodes were used to measure entrance and exit doses in several anatomical locations along the entire body. Diode results from both centers for over five years of treatments were analyzed and compared to the previous MXH technique for accuracy and precision of delivered doses. The most stable location was the field center with standard deviations of 4.1% (MXH), 3.7% (UCLH), and 1.7% (RFH). The least stable position was the ankles. Mean variation with fraction number was within 1.5% for all three techniques. In vivo dosimetry can be used to verify complex modulated CT-planned TBI, and demonstrate improvements and limitations in techniques. The results show that the new UCLH technique is no worse than the previous MXH one and comparable to the current RFH technique.

  3. Build-up material requirements in clinical dosimetry during total body irradiation treatments

    PubMed Central

    Butson, Martin; Pope, Dane; Haque, Mamoon; Chen, Tom; Song, Guangli; Whitaker, May

    2016-01-01

    Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83–90% (93–97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm2. As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications. PMID:27217628

  4. Effects of total body irradiation on fatty acid and total lipid content of rats.

    PubMed

    Chukwuemeka, Nwokocha; Philippe, Mounmbegna; Magdalene, Nwokocha; Onyezuligbo, Onyekachi

    2012-01-01

    We examined time-dependent changes in plasma lipids of rats given total body irradiation (TBI) with X-rays at 3 Gy. for consecutive periods. Animals were exposed to x ray radiations consecutively for 20 days at 5 day interval thereafter five animals were picked at random and sacrificed (5, 10, 15 and 20 days after beginning the exposure). The triacylglycerols and total cholesterol serum levels were significant differences between control and experimental groups after the first exposure (5 days), values for the triacylglcerols were significantly higher with the second (day 10) and third (day 15) radiation exposures but not with the fourth radiation exposures (day 20) (p<0.05). However, the serum cholesterol values were not found to be significant with the second and third exposures but with the fourth exposure (day 20) (p<0.05). The serum HDL-C concentrations were not significantly different between control and experimental groups at any time analyzed. But the LDL cholesterol was found to decrease on days 5 and 20 of the experimental period. Our results indicate that the applied long term exposure to x rays ionization radiations exposure may induce slight but statistically significant alterations in some serum lipids profile of rats, within the physiological range. The mechanisms for the effects of these ionizing radiations on serum lipid profile are not well understand yet, we suggest that the changes could be due to some non-specific stress reactions. The consequences of our observation are not known yet, but could point to some possible clinical intervention.

  5. Attenuator design for organs at risk in total body irradiation using a translation technique.

    PubMed

    Lavallée, Marie-Claude; Aubin, Sylviane; Chrétien, Mario; Larochelle, Marie; Beaulieu, Luc

    2008-05-01

    Total body irradiation (TBI) is an efficient part of the treatment for malignant hematological diseases. Dynamic TBI techniques provide great advantages (e.g., dose homogeneity, patient comfort) while overcoming treatment room space restrictions. However, with dynamic techniques come additional organs at risk (OAR) protection challenges. In most dynamic TBI techniques, lead attenuators are used to diminish the dose received by the OARs. The purpose of this study was to characterize the dose deposition under various shapes of attenuators in static and dynamic treatments. This characterization allows for the development of a correction method to improve attenuator design in dynamic treatments. The dose deposition under attenuators at different depths in dynamic treatment was compared with the static situation based on two definitions: the coverage areas and the penumbra regions. The coverage area decreases with depth in dynamic treatment while it is stable for the static situation. The penumbra increases with depth in both treatment modes, but the increasing rate is higher in the dynamic situation. Since the attenuator coverage is deficient in the dynamic treatment mode, a correction method was developed to modify the attenuator design in order to improve the OAR protection. The correction method is divided in two steps. The first step is based on the use of elongation charts, which provide appropriate attenuator coverage and acceptable penumbra for a specific depth. The second point is a correction method for the thoracic inclination, which can introduce an orientation problem in both static and dynamic treatments. This two steps correction method is simple to use and personalized to each patient's anatomy. It can easily be adapted to any dynamic TBI techniques.

  6. Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation

    SciTech Connect

    Molloy, Janelle A.

    2010-11-15

    Purpose: Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these ''sequential'' techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Methods: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than {+-}10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times

  7. Investigation on using high-energy proton beam for total body irradiation (TBI).

    PubMed

    Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

    2016-09-08

    This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ± 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ± 8.9%, ± 9.0%, ± 9.6%, and ± 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task.

  8. Investigation on using high-energy proton beam for total body irradiation (TBI).

    PubMed

    Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

    2016-09-01

    This work investigated the possibility of using proton beam for total body irradiation (TBI). We hypothesized the broad-slow-rising entrance dose from a monoenergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific compensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ±7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and >40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ±8.9%,±9.0%, ±9.6%, and ±14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In conclusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. PACS number(s): 87.53.Bn, 87.55.K-, 87.55.-x, 87.56.-v. © 2016 The Authors.

  9. Effects of low-dose X-ray irradiation of eggshells on radical production.

    PubMed

    Nakagawa, K

    2014-06-01

    We investigated effects of low-dose X-ray irradiation on eggshells radical production. Eggshells irradiated by low-dose X-ray produced stable radicals. The stable radicals at the central region of the spectrum are the carbonates and CO2(•-) signals. The electron spin resonance (ESR) signals increase with increasing absorbed dose. The estimated radical concentration (spin number) was approximately 3.6 × 10(12) (spins/g) at 10-Gy dose using various known concentrations of TEMPOL (4-hydroxy-2, 2, 6, 6-tretramethylpiperidin-1-oxyl) aqueous solutions. The stable radicals in irradiated eggshells were recognized at the low-level dose (0.10 Gy). In addition, no significant dose rate (0.5-1.5 Gy/min) dependence was found for the radical production.

  10. Chemical-physical characterization of isolated plant cuticles subjected to low-dose γ-irradiation.

    PubMed

    Heredia-Guerrero, José A; de Lara, Rocío; Domínguez, Eva; Heredia, Antonio; Benavente, Juana; Benítez, José J

    2012-12-01

    Isolated tomato fruit cuticles were subjected to low dose (80Gy) γ-irradiation, as a potential methodology to prevent harvested fruit and vegetables spoilage. Both irradiated and non-irradiated samples have been morphologically and chemically characterized by scanning electron (SEM), atomic force (AFM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and X-ray photoelectron (XPS) spectroscopies. Additionally, electrochemical measurements comprising membrane potential and diffusive permeability were carried out to detect modifications in transport properties of the cuticle as the fruit primary protective membrane. It has been found that low dose γ-irradiation causes some textural changes on the surface but no significant chemical modification. Texture modification is found to be due to a partial removal of outermost (epicuticular) waxes which is accompanied by mild changes of electrochemical parameters such as the membrane fixed charge, cation transport number and salt permeability. The modification of such parameters indicates a slight reduction of the barrier properties of the cuticle upon low dose γ-irradiation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    SciTech Connect

    Lapidot, T.; Singer, T.S.; Salomon, O.; Terenzi, A.; Schwartz, E.; Reisner, Y.

    1988-10-15

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.

  12. Low dose irradiation creep of pure nickel. [17 or 15 MeV deuterons

    SciTech Connect

    Henager, C.H. Jr.

    1984-10-01

    A detailed climb-controlled glide model of low dose irradiation creep has been developed to rationalize irradiation creep data of pure nickel irradiated in a light ion irradiation creep apparatus. Experimental irradiation creep data were obtained to study the effects of initial microstructure and stress on low dose irradiation creep in pure nickel. Pure nickel specimens (99.992% Ni), with three different microstructures, were irradiated with 17 or 15 MeV deuterons at 473 K and stresses ranging from 0.35 to 0.9 of the unirradiated yield stress. Transmission electron microscopy revealed that the microstructure following irradiation to 0.05 dpa consisted of a high density of small dislocation loops, some small voids and network dislocations. The creep model predicted creep rates proportional to the mobile dislocation density and a comparison of experimental irradiation creep rates as a function of homologous stress revealed a dependence on initial microstructure of the magnitude predicted by the measured dislocation densities. The three microstructures that were irradiated consisted of 85% and 25% cold-worked Ni specimens and well-annealed Ni specimens. A weak stress dependence of irradiation creep was observed in 85% cold-worked Ni in agreement with experimental determinations of the stress dependence of irradiation creep by others. The weak stress dependence was shown to be a consequence of the stress independence of the dislocation climb velocity and the weak stress dependence of the barrier removal process. The irradiation creep rate was observed to be proportional to the applied stress. This linear stress dependence was suggested to be due to the stress dependence of the mobile dislocation density. 101 references, 27 figures, 11 tables.

  13. Timing of Captopril Administration Determines Radiation Protection or Radiation Sensitization in a Murine Model of Total Body Irradiation

    DTIC Science & Technology

    2010-01-01

    Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation Thomas A...radiation-induced injury to the hemato- poietic system. We investigated the consequences of different regimens of the ACE inhibitor captopril on radiation... Captopril was provided in the water for different time periods relative to irradiation. Results. In untreated mice, the survival rate from 7.5 Gy was

  14. Timing of Captopril Administration Determines Radiation Protection or Radiation Sensitization in a Murine Model of Total Body Irradiation

    DTIC Science & Technology

    2010-04-01

    Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation Thomas A...radiation-induced injury to the hemato- poietic system. We investigated the consequences of different regimens of the ACE inhibitor captopril on radiation... Captopril was provided in the water for different time periods relative to irradiation. Results. In untreated mice, the survival rate from 7.5 Gy was

  15. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue. [Mice

    SciTech Connect

    Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

    1983-04-01

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy.

  16. Radiation-induced apoptosis in SCID mice spleen after low dose irradiation

    NASA Astrophysics Data System (ADS)

    Takahashi, A.; Kondo, N.; Inaba, H.; Uotani, K.; Kiyohara, Y.; Ohnishi, K.; Ohnishi, T.

    To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB-17 Icr +/ + were irradiated with X-ray at 3.0 C3y at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/ + mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.

  17. Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction

    NASA Astrophysics Data System (ADS)

    Bauer, G.

    2011-01-01

    Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.

  18. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  19. Effects of single and fractionated low-dose irradiation on vascular endothelial cells.

    PubMed

    Cervelli, Tiziana; Panetta, Daniele; Navarra, Teresa; Andreassi, Maria Grazia; Basta, Giuseppina; Galli, Alvaro; Salvadori, Piero A; Picano, Eugenio; Del Turco, Serena

    2014-08-01

    An increasing number of epidemiological studies suggest that chronic low-dose irradiation increases the risk of atherosclerosis. We evaluated and compared the in vitro biological effects of both single and fractionated low-doses of X-ray irradiation on endothelial cells. Human umbilical vein endothelial cells (HUVECs) were irradiated with X-rays, with single doses of 0.125, 0.25 and 0.5 Gy or fractionated doses of 2 × 0.125 Gy and 2 × 0.25 Gy, with 24 h interfraction interval. Survival, apoptosis, reactive oxygen species (ROS) production, nuclear factor-κB (NF-κB) activation, intercellular adhesion molecule-1 (ICAM-1) expression, HUVEC adhesiveness and DNA damage were investigated. We did not observe any effect on viability and apoptosis. Both single and fractionated doses induced ROS generation, NF-κB activation, ICAM-1 protein expression and HUVEC adhesiveness, but only fractionated doses increase significantly ICAM-1 mRNA. The effects measured after fractionated dose result always higher than those induced by the single dose. Moreover, we observed that DNA double strand break (DSB), visualized with γ-H2AX foci, is dose-dependent and that the kinetics of γ-H2AX foci is not affected by fractionated doses. We showed that single and fractionated low-dose irradiations with low energy X-rays do not affect cell viability and DNA repair. Interestingly, the greater increase of ICAM-1 surface exposure and endothelial adhesiveness observed after fractionated irradiation, suggests that fractionated low-doses may accelerate chronic vascular inflammation, from which the atherosclerotic process can arise. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Differential effect of L3T4+ cells on recovery from total-body irradiation

    SciTech Connect

    Pantel, K.; Nakeff, A. )

    1990-09-01

    We have examined the importance of L3T4+ (murine equivalent to CD4+) cells for hematopoietic regulation in vivo in unperturbed mice and mice recovering from total-body irradiation (TBI) using a cytotoxic monoclonal antibody (MoAb) raised with the GK 1.5 hybridoma. Ablating L3T4+ cells in normal (unperturbed) B6D2F1 mice substantially decreased the S-phase fraction (determined by in vivo hydroxyurea suicide) of erythroid progenitor cells (erythroid colony-forming units, CFU-E) as compared to the pretreatment level (10% +/- 14.1% (day 3 following depletion) vs 79.8% +/- 15.9%, respectively) with a corresponding decrease in the marrow content of CFU-E at this time to approximately 1% of the pretreatment value. Although the S-phase fraction of CFU-GM was decreased to 2.2% +/- 3.1% 3 days after L3T4+ cell ablation from the 21.3% +/- 8.3% pretreatment value, CFU-GM cellularity showed little change over the 3 days following anti-L3T4 treatment. Anti-L3T4 MoAb treatment had little or no effect on either the S-phase fraction or the marrow content of hematopoietic stem cells (spleen colony-forming units, CFU-S) committed to myeloerythroid differentiation. Ablating L3T4+ cells prior to a single dose of 2 Gy TBI resulted in significantly reduced marrow contents of CFU-S on day 3 and granulocyte-macrophage colony-forming units (CFU-GM) on day 6 following TBI, with little or no effect on the corresponding recovery of CFU-E. The present findings provide the first in vivo evidence that L3T4+ cells are involved in: (1) maintaining the proliferative activity of CFU-E and CFU-GM in unperturbed mice and (2) supporting the restoration of CFU-S and CFU-GM following TBI-induced myelosuppression.

  1. Treosulfan, Fludarabine and 2 Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with MDS and AML

    PubMed Central

    Gyurkocza, Boglarka; Gutman, Jonathan; Nemecek, Eneida R.; Bar, Merav; Milano, Filippo; Ramakrishnan, Aravind; Scott, Bart; Fang, Min; Wood, Brent; Pagel, John M.; Baumgart, Joachim; Delaney, Colleen; Maziarz, Richard T.; Sandmaier, Brenda M.; Estey, Elihu H.; Appelbaum, Frederick R.; Storer, Barry E.; Deeg, H. Joachim

    2014-01-01

    Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial we assessed the efficacy and toxicity of treosulfan, fludarabine and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36; 15 RMCD; 10 RAEB-1; 10 RAEB-2; 1 CMML-1) or AML (n=60; 35 CR1; 18 CR2; 3 advanced CR; 4 refractory relapse) were enrolled; median age was 51 (range: 1–60) years. Twelve patients had undergone a prior HCT with high intensity conditioning. Patients received intravenous (IV) treosulfan, 14 g/m2/day on days −6 to −4, IV fludarabine, 30 mg/m2/day on days −6 to −2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-vs.-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence and non-relapse mortality were 73%, 27% and 8%, respectively. The incidences of grades II–IV (III–IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor risk and good/intermediate risk cytogenetics (69% and 85%, respectively), or between AML patients with unfavorable and favorable/intermediate risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% vs. 18%) and lower OS (41% vs. 79%) at 2 years, when compared to patients without MRD. In conclusion, treosulfan, fludarabine and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML, and resulted in low relapse incidence, regardless

  2. Low dose X-irradiation mitigates diazepam induced depression in rat brain.

    PubMed

    Kaur, Amandeep; Singla, Neha; Dhawan, D K

    2016-10-01

    Depression is considered as one of the most prevalent health ailments. Various anti-depressant drugs have been used to provide succour to this ailment, but with little success and rather have resulted in many side effects. On the other hand, low dose of ionizing radiations are reported to exhibit many beneficial effects on human body by stimulating various biological processes. The present study was conducted to investigate the beneficial effects of low doses of X-rays, if any, during diazepam induced depression in rats. Female Sprague Dawley rats were segregated into four different groups viz: Normal control, Diazepam treated, X-irradiated and Diazepam + X-irradiated. Depression model was created in rats by subjecting them to diazepam treatment at a dosage of 2 mg/kg b.wt./day for 3 weeks. The skulls of animals belonging to X-irradiated and Diazepam + X-irradiated rats were X-irradiated with a single fraction of 0.5 Gy, given twice a day for 3 days, thereby delivered dose of 3 Gy. Diazepam treated animals showed significant alterations in the neurobehavior and neuro-histoarchitecture, which were improved after X-irradiation. Further, diazepam exposure significantly decreased the levels of neurotransmitters and acetylcholinesterase activity, but increased the monoamine oxidase activity in brain. Interestingly, X-rays exposure to diazepam treated rats increased the levels of neurotransmitters, acetylcholinesterase activity and decreased the monoamine oxidase activity. Further, depressed rats also showed increased oxidative stress with altered antioxidant parameters, which were normalized on X-rays exposure. The present study, suggests that low dose of ionizing radiations, shall prove to be an effective intervention and a novel therapy in controlling depression and possibly other brain related disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Fabricating high-density magnetic storage elements by low-dose ion beam irradiation

    SciTech Connect

    Neb, R.; Sebastian, T.; Pirro, P.; Hillebrands, B.; Pofahl, S.; Schaefer, R.; Reuscher, B.

    2012-09-10

    We fabricate magnetic storage elements by irradiating an antiferromagnetically coupled ferromagnetic/nonmagnetic/ferromagnetic trilayer by a low-dose ion beam. The irradiated areas become ferromagnetically coupled and are capable of storing information if their size is small enough. We employ Fe/Cr/Fe trilayers and a 30 keV focused Ga{sup +}-ion beam to demonstrate the working principle for a storage array with a bit density of 7 Gbit/in.{sup 2}. Micromagnetic simulations suggest that bit densities of at least two magnitudes of order larger should be possible.

  4. Reduction in mutation frequency by very low-dose gamma irradiation of Drosophila melanogaster germ cells.

    PubMed

    Ogura, Keiji; Magae, Junji; Kawakami, Yasushi; Koana, Takao

    2009-01-01

    To determine whether the linear no-threshold (LNT) model for stochastic effects of ionizing radiation is applicable to very low-dose radiation at a low dose rate, we irradiated immature male germ cells of the fruit fly, Drosophila melanogaster, with several doses of (60)Co gamma rays at a dose rate of 22.4 mGy/h. Thereafter, we performed the sex-linked recessive lethal mutation assay by mating the irradiated males with nonirradiated females. The mutation frequency in the group irradiated with 500 microGy was found to be significantly lower than that in the control group (P < 0.01), whereas in the group subjected to 10 Gy irradiation, the mutation frequency was significantly higher than that in the control group (P < 0.03). A J-shaped dose-response relationship was evident. Molecular experiments using DNA microarray and quantitative reverse transcription PCR indicated that several genes known to be expressed in response to heat or chemical stress and grim, a positive regulator of apoptosis, were up-regulated immediately after irradiation with 500 microGy. The involvement of an apoptosis function in the non-linear dose-response relationship was suggested.

  5. Regeneration of Murine Hair Follicles is Inhibited by Low-Dose-Rate Gamma Irradiation.

    PubMed

    Sugaya, Kimihiko; Hirobe, Tomohisa; Ishihara, Yoshie; Inoue, Sonoe

    2016-10-01

    To determine whether the effects of low-dose-rate gamma (γ) irradiation are identifiable in the regeneration of murine hair follicles, we irradiated whole bodies of C57BL/10JHir mice in the first telogen phase of the hair cycle with (137)Cs γ-rays. The mice were examined for effects on hair follicles, including number, morphology, and pigmentation in the second anagen phase. Effects of γ-radiation on melanocyte stem cells were also investigated by the indirect immunolabeling of tyrosinase-related protein 2 (TRP2). Irradiated skin showed a decrease in hair follicle density and the induction of curved hair follicles along with the presence of white hairs and hypopigmented hair bulbs. There was a small, but not significant, change in the number of TRP2-positive melanocyte stem cells in the hair bulge region of the irradiated skin. These results suggest that low-dose rate γ-irradiation does not deplete melanocyte stem cells, but can damage stem cells and progenitors for both keratinocytes and melanocytes, thereby affecting the structure and pigmentation of regenerated hair follicles in the 2(nd) anagen phase.

  6. Effect of low dose gamma irradiation on plant and grain nutrition of wheat

    NASA Astrophysics Data System (ADS)

    Singh, Bhupinder; Datta, Partha Sarathi

    2010-08-01

    We recently reported the use of low dose gamma irradiation to improve plant vigor, grain development and yield attributes of wheat ( Singh and Datta, 2010). Further, we report here the results of a field experiment conducted to assess the effect of gamma irradiation at 0, 0.01, 0.03, 0.05, 0.07 and 0.1 kGy on flag leaf area, stomatal conductance, transpiration and photosynthetic rate and plant and grain nutritional quality. Gamma irradiation improved plant nutrition but did not improve the nutritional quality of grains particularly relating to micronutrients. Grain carotene, a precursor for vitamin A, was higher in irradiated grains. Low grain micronutrients seem to be caused by a limitation in the source to sink nutrient translocation rather than in the nutrient uptake capacity of the plant root.

  7. Study on increasing production of natural silk by using low dose irradiation

    SciTech Connect

    Ruiying, Z.; Yinfen, Z.; Dingzhu, C.; Jinxian, R.

    1985-01-01

    Radiation effect on silkworm irradiated by low dose fast neutron and ..gamma..-ray emitted from Ra-Be neutron source are reported. It is shown that increasing production of natural silk can only be obtained by irradiation under specified conditions. It was found that an appropriate fluence employed could lead to increase hatching rate of silkworm eggs, make silkworms' bodies strong, grow fast, possess high disease resistance and reduce the whole stadium by 1/2 to 2 1/2 days. In addition, the irradiated silkworm can be expected to spin bigger cocoons with thick layers and the quality of cocoon silk are remarkable improved. The application of irradiation technique has now been extended to the suburbs of Beijing and welcomed by sericulturist.

  8. Enrichment increases hippocampal neurogenesis independent of blood monocyte-derived microglia presence following high-dose total body irradiation.

    PubMed

    Ruitenberg, Marc J; Wells, Julia; Bartlett, Perry F; Harvey, Alan R; Vukovic, Jana

    2017-06-01

    Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche. This depressive effect of total body irradiation on adult neurogenesis was partially alleviated by exposure to enriched environment but not voluntary exercise, where mice were single-housed with unlimited access to a running wheel. Exposure to voluntary exercise, but not enriched environment, did lead to significant increases in microglia density in the granule cell layer of the hippocampus; our study shows that these changes result from local microglia proliferation rather than recruitment and infiltration of circulating Cx3cr1(+/gfp) blood monocytes that subsequently differentiate into microglia-like cells. In summary, latent neural precursor cells remain present in the neurogenic niche of the adult hippocampus up to 8 weeks following high-dose total body irradiation. Environmental enrichment can partially restore the adult neurogenic process in this part of the brain following high-dose irradiation, and this was found to be independent of blood monocyte-derived microglia presence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  9. Evaluation of low-dose irradiation on microbiological quality of white carrots and string beans

    NASA Astrophysics Data System (ADS)

    Koike, Amanda C. R.; Santillo, Amanda G.; Rodrigues, Flávio T.; Duarte, Renato C.; Villavicencio, Anna Lucia C. H.

    2012-08-01

    The minimally processed food provided the consumer with a product quality, safety and practicality. However, minimal processing of food does not reduce pathogenic population of microorganisms to safe levels. Ionizing radiation used in low doses is effective to maintain the quality of food, reducing the microbiological load but rather compromising the nutritional values and sensory property. The association of minimal processing with irradiation could improve the quality and safety of product. The purpose of this study was to evaluate the effectiveness of low-doses of ionizing radiation on the reduction of microorganisms in minimally processed foods. The results show that the ionizing radiation of minimally processed vegetables could decontaminate them without several changes in its properties.

  10. Low-dose irradiation affects the functional behavior of oral microbiota in the context of mucositis.

    PubMed

    Vanhoecke, Barbara W A; De Ryck, Tine R G; De boel, Kevin; Wiles, Siouxsie; Boterberg, Tom; Van de Wiele, Tom; Swift, Simon

    2016-01-01

    The role of host-microbe interactions in the pathobiology of oral mucositis is still unclear; therefore, this study aimed to unravel the effect of irradiation on behavioral characteristics of oral microbial species in the context of mucositis. Using various experimental in vitro setups, the effects of irradiation on growth and biofilm formation of two Candida spp., Streptococcus salivarius and Klebsiella oxytoca in different culture conditions were evaluated. Irradiation did not affect growth of planktonic cells, but reduced the number of K. oxytoca cells in newly formed biofilms cultured in static conditions. Biofilm formation of K. oxytoca and Candida glabrata was affected by irradiation and depended on the culturing conditions. In the presence of mucins, these effects were lost, indicating the protective nature of mucins. Furthermore, the Galleria melonella model was used to study effects on microbial virulence. Irradiated K. oxytoca microbes were more virulent in G. melonella larvae compared to the nonirradiated ones. Our data indicate that low-dose irradiation can have an impact on functional characteristics of microbial species. Screening for pathogens like K. oxytoca in the context of mucosits could be useful to allow early detection and immediate intervention.

  11. Effect of gamma-ray irradiation at low doses on the performance of PES ultrafiltration membrane

    NASA Astrophysics Data System (ADS)

    Zhang, Xue; Niu, Lixia; Li, Fuzhi; Yu, Suping; Zhao, Xuan; Hu, Hongying

    2016-10-01

    The influence of gamma irradiation on the performance of polyether sulfone (PES) ultrafiltration (UF) membrane was investigated at low absorbed doses (0-75 kGy) using a cobalt source. The performance of the UF membranes was tested using low level radioactive wastewater (LLRW) containing three types of surfactants (anionic, cationic and nonionic surfactants). The physical and chemical properties of membrane surface were analyzed, and relationships between these properties and separation performance and fouling characteristics were determined. At 10-75 kGy irradiation, there were no significant changes observed in the membrane surface roughness or polymer functional groups, however the contact angle decreased sharply from 92° to ca. 70° at irradiation levels as low as 10 kGy. When membranes were exposed to the surfactant-containing LLRW, the flux decreased more sharply for higher dosed irradiated membranes, while flux in virgin membranes increased during the filtration processes. The study highlights that fouling properties of membrane may be changed due to the changes of surface hydrophilicity at low dose irradiation, while other surface properties and retentions remain stable. Therefore, a membrane fouling test with real or simulated wastewater is recommended to fully evaluate the membrane irradiation resistance.

  12. The effects of low dose rate irradiation and thermal aging on reactor structural alloys

    NASA Astrophysics Data System (ADS)

    Allen, T. R.; Trybus, C. L.; Cole, J. I.

    As part of the EBR-II reactor materials surveillance program, test samples of fifteen different alloys were placed into EBR-II in 1965. The surveillance (SURV) program was intended to determine property changes in reactor structural materials caused by irradiation and thermal aging. In this work, the effect of low dose rate (approximately 2 × 10 -8 dpa/s) irradiation at 380-410°C and long term thermal aging at 371°C on the properties of 20% cold worked 304 stainless steel, 420 stainless steel, Inconel X750, 304/308 stainless weld material, and 17-4 PH steel are evaluated. Doses of up to 6.8 dpa and thermal aging to 2994 days did not significantly affect the density of these alloys. The strength of 304 SS, X750, 17-4 PH, and 304/308 weld material increased with irradiation. In contrast, the strength of 420 stainless steel decreased with irradiation. Irradiation decreased the impact energy in both Inconel X750 and 17-4 PH steel. Thermal aging decreased the impact energy in 17-4 PH steel and increased the impact energy in Inconel X750. Tensile property comparisons of 304 SURV samples with 304 samples irradiated in EBR-II at a higher dose rate show that the higher dose rate samples had greater increases in strength and greater losses in ductility.

  13. Low Dose Gamma Irradiation Potentiates Secondary Exposure to Gamma Rays or Protons in Thyroid Tissue Analogs

    SciTech Connect

    Green, Lora M

    2006-05-25

    We have utilized our unique bioreactor model to produce three-dimensional thyroid tissue analogs that we believe better represent the effects of radiation in vivo than two-dimensional cultures. Our thyroid model has been characterized at multiple levels, including: cell-cell exchanges (bystander), signal transduction, functional changes and modulation of gene expression. We have significant preliminary data on structural, functional, signal transduction and gene expression responses from acute exposures at high doses (50-1000 rads) of gamma, protons and iron (Green et al., 2001a; 2001b; 2002a; 2002b; 2005). More recently, we used our DOE funding (ending Feb 06) to characterize the pattern of radiation modulated gene expression in rat thyroid tissue analogs using low-dose/low-dose rate radiation, plus/minus acute challenge exposures. Findings from these studies show that the low-dose/low-dose rate “priming” exposures to radiation invoked changes in gene expression profiles that varied with dose and time. The thyrocytes transitioned to a “primed” state, so that when the tissue analogs were challenged with an acute exposure to radiation they had a muted response (or an increased resistance) to cytopathological changes relative to “un-primed” cells. We measured dramatic differences in the primed tissue analogs, showing that our original hypothesis was correct: that low dose gamma irradiation will potentiate the repair/adaptation response to a secondary exposure. Implications from these findings are that risk assessments based on classical in vitro tissue culture assays will overestimate risk, and that low dose rate priming results in a reduced response in gene expression to a secondary challenge exposure, which implies that a priming dose provides enhanced protection to thyroid cells grown as tissue analogs. If we can determine that the effects of radiation on our tissue analogs more closely resemble the effects of radiation in vivo, then we can better

  14. Excess processing of oxidative damaged bases causes hypersensitivity to oxidative stress and low dose rate irradiation.

    PubMed

    Yoshikawa, Y; Yamasaki, A; Takatori, K; Suzuki, M; Kobayashi, J; Takao, M; Zhang-Akiyama, Q-M

    2015-10-01

    Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in Escherichia coli (E. coli) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the effects and the mechanisms of other radiation, such as low dose rate radiation, heavy-ion beams, or hydrogen peroxide (H2O2), are still poorly understood. In the present study, we constructed a stable HeLaS3 cell line overexpressing human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) protein. We determined the survival of HeLaS3 and HeLaS3/hOGG1 cells exposed to UV, heavy-ion beams, γ-rays, and H2O2. The results showed that HeLaS3 cells overexpressing hOGG1 were more sensitive to γ-rays, OH(•), and H2O2, but not to UV or heavy-ion beams, than control HeLaS3. We further determined the levels of 8-oxoG foci and of chromosomal double-strand breaks (DSBs) by detecting γ-H2AX foci formation in DNA. The results demonstrated that both γ-rays and H2O2 induced 8-oxoguanine (8-oxoG) foci formation in HeLaS3 cells. hOGG1-overexpressing cells had increased amounts of γ-H2AX foci and decreased amounts of 8-oxoG foci compared with HeLaS3 control cells. These results suggest that excess hOGG1 removes the oxidatively damaged 8-oxoG in DNA more efficiently and therefore generates more DSBs. Micronucleus formation also supported this conclusion. Low dose-rate γ-ray effects were also investigated. We first found that overexpression of hOGG1 also caused increased sensitivity to low dose rate γ-ray irradiation. The rate of micronucleus formation supported the notion that low dose rate irradiation increased genome instability.

  15. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect

    Eric Y. Chuang

    2006-08-31

    It has been long recognized that a significant fraction of the radiation-induced genetic damage to cells are caused by secondary oxidative species. Internal cellular defense systems against oxidative stress play significant roles in countering genetic damage induced by ionizing radiation. The role of the detoxifying enzymes may be even more prominent in the case of low-dose, low-LET irradiation, as the majority of genetic damage may be caused by secondary oxidative species. In this study we have attempted to decipher the roles of the superoxide dismutase (SOD) genes, which are responsible for detoxifying the superoxide anions. We used adenovirus vectors to deliver RNA interference (RNAi or siRNA) technology to down-regulate the expression levels of the SOD genes. We have also over-expressed the SOD genes by use of recombinant adenovirus vectors. Cells infected with the vectors were then subjected to low dose γ-irradiation. Total RNA were extracted from the exposed cells and the expression of 9000 genes were profiled by use of cDNA microarrays. The result showed that low dose radiation had clear effects on gene expression in HCT116 cells. Both over-expression and down-regulation of the SOD1 gene can change the expression profiles of sub-groups of genes. Close to 200 of the 9000 genes examined showed over two-fold difference in expression under various conditions. Genes with changed expression pattern belong to many categories that include: early growth response, DNA-repair, ion transport, apoptosis, and cytokine response.

  16. Low-dose irradiation and constrained revision for severe, idiopathic, arthrofibrosis following total knee arthroplasty.

    PubMed

    Farid, Yasser R; Thakral, Rishi; Finn, Henry A

    2013-09-01

    Treatment options for arthrofibrosis following total knee arthroplasty include manipulation under anesthesia, open or arthroscopic arthrolysis, and revision surgery to correct identifiable problems. We propose preoperative low-dose irradiation and Constrained Condylar or Rotating-hinge revision for severe, idiopathic arthrofibrosis. Irradiation may decrease fibro-osseous proliferation while constrained implants allow femoral shortening and release of contracted collateral ligaments. Fourteen patients underwent fifteen procedures for a mean overall motion of 46° and flexion contracture of 30°. One patient had worsening range of motion while thirteen patients had 57° mean gain in range of motion (range 5°-90°). Flexion contractures decreased by a mean of 28°. There were no significant complications at a mean follow up of 34 months (range 24 to 74 months). Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Neonatal low-dose gamma irradiation-induced impaired fertility in mature rats.

    PubMed

    Freud, A; Canfi, A; Sod-Moriah, U A; Chayoth, R

    1990-11-01

    The reproductive capacity of mature rats at the age of 8 days was studied following neonatal exposure to 0.06 Gy dose of gamma-radiation. Decreased litter size and reduced body weight of the pups on weaning day, but not at parturition, were observed in female rats. The reduced litter size was not associated with impaired ovulation, impaired uterine implantation or mortality in utero, but resulted from increased death rate or at near parturition. Of the neonatally irradiated males 29% were found to be sterile and had degenerated or necrotic testes. The testicular damage and the reduced growth rate of the offspring of the irradiated females demonstrate the extreme sensitivity of the immature reproductive system to ionizing radiation, even at very low doses.

  18. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1975-01-01

    A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.

  19. Neurodegeneration and adaptation in response to low-dose photon irradiation

    SciTech Connect

    Limoli, Charles L.

    2014-10-27

    Neural stem and precursor cells (i.e. multipotent neural cells) are concentrated in the neurogenic regions of the brain (hippocampal dentate gyrus, subventricular zones), and considerable evidence suggests that these cells are important in mediating the stress response of the CNS after damage from ionizing radiation. The capability of these cells to proliferate, migrate and differentiate (i.e. to undergo neurogenesis) suggests they can participate in the repair and maintenance of CNS functions by replacing brain cells damaged or depleted due to irradiation. Importantly, we have shown that multipotent neural cells are markedly sensitive to irradiation and oxidative stress, insults that compromise neurogenesis and hasten the onset and progression of degenerative processes that are likely to have an adverse impact on cognition. Our past and current work has demonstrated that relatively low doses of radiation cause a persistent (weeks-months) oxidative stress in multipotent neural cells that can elicit a range of degenerative sequelae in the CNS. Therefore, our project is focused on determining the extent that endogenous and redox sensitive multipotent neural cells represent important radioresponsive targets for low dose radiation effects. We hypothesize that the activation of redox sensitive signaling can trigger radioadaptive changes in these cells that can be either harmful or beneficial to overall cognitive health.

  20. Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.

    PubMed

    Wang, Junru; Shao, Lijian; Hendrickson, Howard P; Liu, Liya; Chang, Jianhui; Luo, Yi; Seng, John; Pouliot, Mylene; Authier, Simon; Zhou, Daohong; Allaben, William; Hauer-Jensen, Martin

    2015-11-01

    The non-human primate has been a useful model for studies of human acute radiation syndrome (ARS). However, to date structural changes in various parts of the intestine after total body irradiation (TBI) have not been systematically studied in this model. Here we report on our current study of TBI-induced intestinal structural injury in the non-human primate after doses typically associated with hematopoietic ARS. Twenty-four non-human primates were divided into three groups: sham-irradiated control group; and total body cobalt-60 (60Co) 6.7 Gy gamma-irradiated group; and total body 60Co 7.4 Gy gamma-irradiated group. After animals were euthanized at day 4, 7 and 12 postirradiation, sections of small intestine (duodenum, proximal jejunum, distal jejunum and ileum) were collected and fixed in 10% formalin. The intestinal mucosal surface length, villus height and crypt depths were assessed by computer-assisted image analysis. Plasma citrulline levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total bone marrow cells were counted and hematopoietic stem/progenitor cells in bone marrow were analyzed by flow cytometer. Histopathologically, all segments exhibited conspicuous disappearance of plicae circulares and prominent atrophy of crypts and villi. Intestinal mucosal surface length was significantly decreased in all intestinal segments on day 4, 7 and 12 after irradiation (P < 0.02-P < 0.001). Villus height was significantly reduced in all segments on day 4 and 7 (P = 0.02-0.005), whereas it had recovered by day 12 (P > 0.05). Crypt depth was also significantly reduced in all segments on day 4, 7 and 12 after irradiation (P < 0.04-P < 0.001). Plasma citrulline levels were dramatically reduced after irradiation, consistent with intestinal mucosal injury. Both 6.7 and 7.4 Gy TBI reduced total number of bone marrow cells. And further analysis showed that the number and function of CD45(+)CD34(+) hematopoietic stem/progenitors in bone

  1. Physiological and molecular characterization of the enhanced salt tolerance induced by low-dose gamma irradiation in Arabidopsis seedlings

    SciTech Connect

    Qi, Wencai; Zhang, Liang; Xu, Hangbo; Wang, Lin; Jiao, Zhen

    2014-07-25

    Highlights: • 50-Gy gamma irradiation markedly promotes the seedling growth under salt stress in Arabidopsis. • The contents of H{sub 2}O{sub 2} and MDA are obviously reduced by low-dose gamma irradiation under salt stress. • Low-dose gamma irradiation stimulates the activities of antioxidant enzymes under salt stress. • Proline accumulation is required for the low-gamma-ray-induced salt tolerance. • Low gamma rays differentially regulate the expression of genes related to salt stress. - Abstract: It has been established that gamma rays at low doses stimulate the tolerance to salt stress in plants. However, our knowledge regarding the molecular mechanism underlying the enhanced salt tolerance remains limited. In this study, we found that 50-Gy gamma irradiation presented maximal beneficial effects on germination index and root length in response to salt stress in Arabidopsis seedlings. The contents of H{sub 2}O{sub 2} and MDA in irradiated seedlings under salt stress were significantly lower than those of controls. The activities of antioxidant enzymes and proline levels in the irradiated seedlings were markedly increased compared with the controls. Furthermore, transcriptional expression analysis of selected genes revealed that some components of salt stress signaling pathways were stimulated by low-dose gamma irradiation under salt stress. Our results suggest that gamma irradiation at low doses alleviates the salt stress probably by modulating the physiological responses as well as stimulating the stress signal transduction in Arabidopsis seedlings.

  2. Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny.

    PubMed

    Lemos, J; Neuparth, T; Trigo, M; Costa, P; Vieira, D; Cunha, L; Ponte, F; Costa, P S; Metello, L F; Carvalho, A P

    2017-02-01

    This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000 mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.

  3. Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides

    SciTech Connect

    Halberg, F.E.; Fu, K.K.; Weaver, K.A.; Zackheim, H.S.; Epstein, E.H. Jr.; Wintroub, B.U.

    1989-08-01

    Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived.

  4. Etoposide in combination with cyclophosphamide and total body irradiation or busulfan as conditioning for marrow transplantation in adults and children

    SciTech Connect

    Spitzer, T.R.; Ortlieb, M.; Tefft, M.C.; Torrisi, J.; Cahill, R.; Deeg, H.J. ); Peters, C.; Gadner, H. ); Urban, C. )

    1994-04-30

    In an attempt to intensify conditioning therapy for bone marrow transplantation of hematologic malignancies, a retrospective three center evaluation of escalating doses of etoposide added to cyclophosphamide and either total body irradiation or busulfan was undertaken. Seventy-six patients who received etoposide (25-65 mg/kg) added to cyclophosphamide (60-120 mg/kg) and either total body irradiation (12.0-13.2 Gy) or busulfan (12-16 mg/kg) were evaluable for toxicity. Fifty-one of the evaluable patients received allogeneic transplants, while twenty-six received autologous transplants. A comparative analysis of toxicities according to conditioning regimen, donor source and etoposide dose was made. Similar toxicities were observed among the treatment groups with the exception of more frequent skin (p = 0.03) and life threatening hepatic toxicities (p = 0.01) in the busulfan treated patients. Life threatening or fatal toxicities were not influenced by donor source, either when analyzed by treatment group or etoposide dose. Etoposide at a dose of 60-65 mg/kg in combination with TBI and cyclophosphamide was associated with a significantly increased incidence of life threatening or fatal toxicities compared with a combination using a dose of 25-50 mg/kg (15 of 24 vs. 5 of 20; p = 0.013). The maximally tolerated dose of etoposide in combination with busulfan and cyclophosphamide cannot be definitively established in this analysis in part due to the heterogeneity of the patient population and treatment schemes. Although toxicities with bone marrow transplant preparative regimens containing etoposide in combination with cyclophosphamide and total body irradiation or busulfan were frequently severe, treatment related mortality risk was believed to be acceptably low. 27 refs., 3 tabs.

  5. The mechanism of recurrence of mouse myeloid leukaemia after total body irradiation and bone marrow transplantation.

    PubMed

    Poljak-Blazi, M; Popović, M; Majić, T

    1994-01-01

    RFM mice were X-irradiated (9.5 Gy) 3, 4, 5, 6 or 7 days after inoculation of a transplantable strain-specific myeloid leukaemia (ML) and were reconstituted or not with syngeneic or allogeneic bone marrow cells. Recurrent leukaemia was observed in mice with either type of the bone marrow transplant, indicating that ML cells survived the dose of 9.5 Gy of X-rays. ML cells exposed in vitro to high doses of X-rays (20, 30, 40, 50, 60 Gy) and injected into lethally irradiated syngeneic recipients were still capable of forming leukaemic colonies on the spleens. Higher doses (70, 80, 90 and 100 Gy) abolished the colony formation completely. Irradiated ML cells were also capable of causing leukaemia (hepatosplenomegaly) if inoculated into lethally irradiated CBA mice reconstituted with bone marrow cells of CBA or RFM mice. That was attributed to the release of a leukaemogenic factor from the ML cells, capable of transforming transplanted normal cells.

  6. Uptake of indium-111-labeled platelets and indium-111 oxine by murine kidneys after total-body irradiation

    SciTech Connect

    Ebbe, S.; Taylor, S.; Maurer, H.; Kullgren, B.

    1996-08-01

    Radiation nephropathy is a well-known late manifestation of renal irradiation in human beings and experimental animals. Its pathogenesis is unclear, but vascular injury may play a role. Endothelial cells have been demonstrated to manifest a variety of abnormalities within hours of exposure to radiation. In the present experiments mice were exposed to lethal doses of whole-body radiation, and the distribution of {sup 111}In-labeled platelets was evaluated during the first week after irradiation. The purpose was to determine if early abnormalities of endothelial cells would be manifested by altered sequestration of platelets in kidneys and other organs. It was found that the indium accumulated in the kidneys of irradiated mice to a greater extent than in nonirradiated mice, but the pattern of accumulation differed from that seen after injection of radiolabeled platelets. Renal hyperemia was not demonstrable with {sup 51}Cr-labeled red cells, renal vascular permeability was not detected with {sup 125}I-labeled albumin, and the pattern of renal uptake of plasma proteins labeled albumin, and the pattern of renal uptake of plasma proteins labeled with {sup 59}Fe {sup 111}In did not coincide with that seen from {sup 111}In administered as labeled platelets or oxine. Renal uptake of {sup 111}In-oxine was not associated with alterations in urinary or fecal excretion or an increase in total-body retention of the radioisotope. The findings are consistent with the notion that renal vascular injury at the time of irradiation results in accumulation of platelets or platelet constituents during the first week after total-body irradiation of mice. 29 refs., 5 figs., 3 tabs.

  7. Overview of Radiosensitivity of Human Tumor Cells to Low-Dose-Rate Irradiation

    SciTech Connect

    Williams, Jerry R. Zhang Yonggang; Zhou Haoming; Gridley, Daila S.; Koch, Cameron J.; Slater, James M.; Little, John B.

    2008-11-01

    Purpose: We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines. Methods and Materials: We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines. Results: Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR radiosensitivity correlates at lower doses ({approx}2 Gy HDR, {approx}6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours. Conclusions: Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications.

  8. SU-E-T-540: Volumetric Modulated Total Body Irradiation Using a Rotational Lazy Susan-Like Immobilization System

    SciTech Connect

    Gu, X; Hrycushko, B; Lee, H; Lamphier, R; Jiang, S; Abdulrahman, R; Timmerman, R

    2014-06-01

    Purpose: Traditional extended SSD total body irradiation (TBI) techniques can be problematic in terms of patient comfort and/or dose uniformity. This work aims to develop a comfortable TBI technique that achieves a uniform dose distribution to the total body while reducing the dose to organs at risk for complications. Methods: To maximize patient comfort, a lazy Susan-like couch top immobilization system which rotates about a pivot point was developed. During CT simulation, a patient is immobilized by a Vac-Lok bag within the body frame. The patient is scanned head-first and then feet-first following 180° rotation of the frame. The two scans are imported into the Pinnacle treatment planning system and concatenated to give a full-body CT dataset. Treatment planning matches multiple isocenter volumetric modulated arc (VMAT) fields of the upper body and multiple isocenter parallel-opposed fields of the lower body. VMAT fields of the torso are optimized to satisfy lung dose constraints while achieving a therapeutic dose to the torso. The multiple isocenter VMAT fields are delivered with an indexed couch, followed by body frame rotation about the pivot point to treat the lower body isocenters. The treatment workflow was simulated with a Rando phantom, and the plan was mapped to a solid water slab phantom for point- and film-dose measurements at multiple locations. Results: The treatment plan of 12Gy over 8 fractions achieved 80.2% coverage of the total body volume within ±10% of the prescription dose. The mean lung dose was 8.1 Gy. All ion chamber measurements were within ±1.7% compared to the calculated point doses. All relative film dosimetry showed at least a 98.0% gamma passing rate using a 3mm/3% passing criteria. Conclusion: The proposed patient comfort-oriented TBI technique provides for a uniform dose distribution within the total body while reducing the dose to the lungs.

  9. In-Utero Low-Dose Irradiation Leads to Persistent Alterations in the Mouse Heart Proteome

    PubMed Central

    Bakshi, Mayur V.; Azimzadeh, Omid; Merl-Pham, Juliane; Verreet, Tine; Hauck, Stefanie M.; Benotmane, Mohammed A.; Atkinson, Michael J.; Tapio, Soile

    2016-01-01

    Prenatal exposure to stress such as increased level of reactive oxygen species or antiviral therapy are known factors leading to adult heart defects. The risks following a radiation exposure during fetal period are unknown, as are the mechanisms of any potential cardiac damage. The aim of this study was to gather evidence for possible damage by investigating long-term changes in the mouse heart proteome after prenatal exposure to low and moderate radiation doses. Pregnant C57Bl/6J mice received on embryonic day 11 (E11) a single total body dose of ionizing radiation that ranged from 0.02 Gy to 1.0 Gy. The offspring were sacrificed at the age of 6 months or 2 years. Quantitative proteomic analysis of heart tissue was performed using Isotope Coded Protein Label technology and tandem mass spectrometry. The proteomics data were analyzed by bioinformatics and key changes were validated by immunoblotting. Persistent changes were observed in the expression of proteins representing mitochondrial respiratory complexes, redox and heat shock response, and the cytoskeleton, even at the low dose of 0.1 Gy. The level of total and active form of the kinase MAP4K4 that is essential for the embryonic development of mouse heart was persistently decreased at the radiation dose of 1.0 Gy. This study provides the first insight into the molecular mechanisms of cardiac impairment induced by ionizing radiation exposure during the prenatal period. PMID:27276052

  10. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    PubMed

    Chang, Jianhui; Luo, Yi; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  11. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice

    PubMed Central

    Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  12. Long-Term Effects of Stem Cells on Total-Body Irradiated Mice

    NASA Astrophysics Data System (ADS)

    Vyalkina, M. V.; Alchinova, I. B.; Yakovenko, E. N.; Medvedeva, Yu S.; Saburina, I. N.; Karganov, M. Yu

    2017-01-01

    C57Bl/6 mice were exposed to γ-radiation in a sublethal dose of 7.5 Gy. In 3 hours injection 106/mouse of bone marrow multipotent mesenchymal stromal cells stem cells intravenously to experimental group was done. Methods used: body weight measurement, open field behavior, subfraction composition of blood serum (laser correlation spectroscopy, LCS), histological examination of the spleen, liver, and pancreas, count of T and B cells, white blood formula. After 1.5 and 3 months the general trend towards intermediate position of the parameters observed in the experimental between those in intact and irradiated controls attests to partial protective/restorative effects of the injected cells.

  13. ROS and ABA signaling are involved in the growth stimulation induced by low-dose gamma irradiation in Arabidopsis seedling.

    PubMed

    Qi, Wencai; Zhang, Liang; Feng, Weisen; Xu, Hangbo; Wang, Lin; Jiao, Zhen

    2015-02-01

    It has been well established that gamma rays at low doses have stimulatory effects on plant growth and development. However, our knowledge regarding the molecular mechanism underlying the growth stimulation remains limited. In this study, we report the role of reactive oxygen species (ROS) and abscisic acid (ABA) in the growth stimulation using irradiated Arabidopsis seeds. The results indicated that 50 Gy gamma irradiation presented maximal beneficial effects on germination index, root length, and fresh weight. The contents of hydrogen peroxide (H2O2) and activities of antioxidant enzymes under gamma irradiation were markedly higher than those of controls. ROS scavenging significantly suppressed the growth of the irradiated plants. Furthermore, endogenous ABA was induced under low-dose gamma irradiation. The growth stimulation and elevated H2O2 level were affected in the irradiated ABA-deficient mutant aba2-1 compared with the mutant control. Transcriptional expression analysis of selected genes revealed that several genes for ABA biosynthesis were upregulated, and the genes for ABA catabolic pathway and transport were differentially regulated in response to low-dose gamma irradiation. Our results suggest that ROS and ABA signaling play an essential role in the stimulatory effects of low-dose gamma irradiation and that ROS, as secondary molecules, mediate ABA signal transduction under irradiation in response to stress factors during plant growth.

  14. Effects of a granulocyte colony stimulating factor, Neulasta, in mini pigs exposed to total body proton irradiation

    PubMed Central

    Sanzari, Jenine K.; Krigsfeld, Gabriel S.; Shuman, Anne L.; Diener, Antonia K.; Lin, Liyong; Mai, Wilfried; Kennedy, Ann R.

    2015-01-01

    Astronauts could be exposed to solar particle event (SPE) radiation, which is comprised mostly of proton radiation. Proton radiation is also a treatment option for certain cancers. Both astronauts and clinical patients exposed to ionizing radiation are at risk for white blood cell (WBC) loss, which are the body’s main defense against infection. In this report, the effect of Neulasta treatment, a granulocyte colony stimulating factor, after proton radiation exposure is discussed. Mini pigs exposed to total body proton irradiation at a dose of 2 Gy received 4 treatments of either Neulasta or saline injections. Peripheral blood cell counts and thromboelastography parameters were recorded up to 30 days post-irradiation. Neulasta significantly improved white blood cell (WBC), specifically neutrophil, loss in irradiated animals by approximately 60% three days after the first injection, compared to the saline treated irradiated animals. Blood cell counts quickly decreased after the last Neulasta injection, suggesting a transient effect on WBC stimulation. Statistically significant changes in hemostasis parameters were observed after proton radiation exposure in both the saline and Neulasta treated irradiated groups, as well internal organ complications such as pulmonary changes. In conclusion, Neulasta treatment temporarily alleviates proton radiation-induced WBC loss, but has no effect on altered hemostatic responses. PMID:25909052

  15. Accelerated marrow recovery following total-body irradiation after treatment with vincristine, lithium or combined vincristine-lithium

    SciTech Connect

    Johnke, R.M.; Abernathy, R.S. )

    1991-01-01

    Accelerated post-irradiation recovery of hematopoietic marrow has been reported following treatment with lithium (Li) or vincristine (VcR). Because these two agents appear to exert their effects on different, albeit overlapping, hematopoietic populations, it was felt that combining them might lead to a wider spectrum of enhanced post-irradiation marrow regeneration. Results demonstrated that an accelerated recovery, which appeared to be additive in nature, was observed in the marrow following combined VcR-Li/4.5 Gy total-body irradiation. The combined schedule significantly enhanced post-irradiation recovery of white blood cells, 12-day spleen colony-forming units, erythroid burst-forming units, and fibroblastic colony-forming units over radiation alone; and recovery of marrow cellularity, multipotential colony-forming units (CFU-gemm) and granulocytic/monocytic colony-forming units (CFU-gm) over both radiation alone and either drug given singly with the 4.5 Gy. In addition, while data on the ability of regenerating stroma to support CFU-gm and CFU-gemm did not suggest that VcR was acting to enhance post-irradiation marrow recovery by increasing stromal production of hematopoietic growth factors, Li did appear to increase production of one or more of these factors, and this may be part of its mechanism of action.

  16. Effects of a granulocyte colony stimulating factor, Neulasta, in mini pigs exposed to total body proton irradiation

    NASA Astrophysics Data System (ADS)

    Sanzari, Jenine K.; Krigsfeld, Gabriel S.; Shuman, Anne L.; Diener, Antonia K.; Lin, Liyong; Mai, Wilfried; Kennedy, Ann R.

    2015-04-01

    Astronauts could be exposed to solar particle event (SPE) radiation, which is comprised mostly of proton radiation. Proton radiation is also a treatment option for certain cancers. Both astronauts and clinical patients exposed to ionizing radiation are at risk for loss of white blood cells (WBCs), which are the body's main defense against infection. In this report, the effect of Neulasta treatment, a granulocyte colony stimulating factor, after proton radiation exposure is discussed. Mini pigs exposed to total body proton irradiation at a dose of 2 Gy received 4 treatments of either Neulasta or saline injections. Peripheral blood cell counts and thromboelastography parameters were recorded up to 30 days post-irradiation. Neulasta significantly improved WBC loss, specifically neutrophils, in irradiated animals by approximately 60% three days after the first injection, compared to the saline treated, irradiated animals. Blood cell counts quickly decreased after the last Neulasta injection, suggesting a transient effect on WBC stimulation. Statistically significant changes in hemostasis parameters were observed after proton radiation exposure in both the saline and Neulasta treated irradiated groups, as well as internal organ complications such as pulmonary changes. In conclusion, Neulasta treatment temporarily alleviates proton radiation-induced WBC loss, but has no effect on altered hemostatic responses.

  17. Defect evolution in single crystalline tungsten following low temperature and low dose neutron irradiation

    SciTech Connect

    Hu, Xunxiang; Koyanagi, Takaaki; Fukuda, Makoto; Katoh, Yutai; Wirth, Brian D; Snead, Lance Lewis

    2016-01-01

    The tungsten plasma-facing components of fusion reactors will experience an extreme environment including high temperature, intense particle fluxes of gas atoms, high-energy neutron irradiation, and significant cyclic stress loading. Irradiation-induced defect accumulation resulting in severe thermo-mechanical property degradation is expected. For this reason, and because of the lack of relevant fusion neutron sources, the fundamentals of tungsten radiation damage must be understood through coordinated mixed-spectrum fission reactor irradiation experiments and modeling. In this study, high-purity (110) single-crystal tungsten was examined by positron annihilation spectroscopy and transmission electron microscopy following low-temperature (~90 °C) and low-dose (0.006 and 0.03 dpa) mixed-spectrum neutron irradiation and subsequent isochronal annealing at 400, 500, 650, 800, 1000, 1150, and 1300 °C. The results provide insights into microstructural and defect evolution, thus identifying the mechanisms of different annealing behavior. Following 1 h annealing, ex situ characterization of vacancy defects using positron lifetime spectroscopy and coincidence Doppler broadening was performed. The vacancy cluster size distributions indicated intense vacancy clustering at 400 °C with significant damage recovery around 1000 °C. Coincidence Doppler broadening measurements confirm the trend of the vacancy defect evolution, and the S–W plots indicate that only a single type of vacancy cluster is present. Furthermore, transmission electron microscopy observations at selected annealing conditions provide supplemental information on dislocation loop populations and visible void formation. This microstructural information is consistent with the measured irradiation-induced hardening at each annealing stage. This provides insight into tungsten hardening and embrittlement due to irradiation-induced matrix defects.

  18. Defect evolution in single crystalline tungsten following low temperature and low dose neutron irradiation

    DOE PAGES

    Hu, Xunxiang; Koyanagi, Takaaki; Fukuda, Makoto; ...

    2016-01-01

    The tungsten plasma-facing components of fusion reactors will experience an extreme environment including high temperature, intense particle fluxes of gas atoms, high-energy neutron irradiation, and significant cyclic stress loading. Irradiation-induced defect accumulation resulting in severe thermo-mechanical property degradation is expected. For this reason, and because of the lack of relevant fusion neutron sources, the fundamentals of tungsten radiation damage must be understood through coordinated mixed-spectrum fission reactor irradiation experiments and modeling. In this study, high-purity (110) single-crystal tungsten was examined by positron annihilation spectroscopy and transmission electron microscopy following low-temperature (~90 °C) and low-dose (0.006 and 0.03 dpa) mixed-spectrum neutronmore » irradiation and subsequent isochronal annealing at 400, 500, 650, 800, 1000, 1150, and 1300 °C. The results provide insights into microstructural and defect evolution, thus identifying the mechanisms of different annealing behavior. Following 1 h annealing, ex situ characterization of vacancy defects using positron lifetime spectroscopy and coincidence Doppler broadening was performed. The vacancy cluster size distributions indicated intense vacancy clustering at 400 °C with significant damage recovery around 1000 °C. Coincidence Doppler broadening measurements confirm the trend of the vacancy defect evolution, and the S–W plots indicate that only a single type of vacancy cluster is present. Furthermore, transmission electron microscopy observations at selected annealing conditions provide supplemental information on dislocation loop populations and visible void formation. This microstructural information is consistent with the measured irradiation-induced hardening at each annealing stage. This provides insight into tungsten hardening and embrittlement due to irradiation-induced matrix defects.« less

  19. Defect evolution in single crystalline tungsten following low temperature and low dose neutron irradiation

    NASA Astrophysics Data System (ADS)

    Hu, Xunxiang; Koyanagi, Takaaki; Fukuda, Makoto; Katoh, Yutai; Snead, Lance L.; Wirth, Brian D.

    2016-03-01

    The tungsten plasma-facing components of fusion reactors will experience an extreme environment including high temperature, intense particle fluxes of gas atoms, high-energy neutron irradiation, and significant cyclic stress loading. Irradiation-induced defect accumulation resulting in severe thermo-mechanical property degradation is expected. For this reason, and because of the lack of relevant fusion neutron sources, the fundamentals of tungsten radiation damage must be understood through coordinated mixed-spectrum fission reactor irradiation experiments and modeling. In this study, high-purity (110) single-crystal tungsten was examined by positron annihilation spectroscopy and transmission electron microscopy following low-temperature (∼90 °C) and low-dose (0.006 and 0.03 dpa) mixed-spectrum neutron irradiation and subsequent isochronal annealing at 400, 500, 650, 800, 1000, 1150, and 1300 °C. The results provide insights into microstructural and defect evolution, thus identifying the mechanisms of different annealing behavior. Following 1 h annealing, ex situ characterization of vacancy defects using positron lifetime spectroscopy and coincidence Doppler broadening was performed. The vacancy cluster size distributions indicated intense vacancy clustering at 400 °C with significant damage recovery around 1000 °C. Coincidence Doppler broadening measurements confirm the trend of the vacancy defect evolution, and the S-W plots indicate that only a single type of vacancy cluster is present. Furthermore, transmission electron microscopy observations at selected annealing conditions provide supplemental information on dislocation loop populations and visible void formation. This microstructural information is consistent with the measured irradiation-induced hardening at each annealing stage, providing insight into tungsten hardening and embrittlement due to irradiation-induced matrix defects.

  20. Cytogenetic characterization of low-dose hyper-radiosensitivity in Cobalt-60 irradiated human lymphoblastoid cells.

    PubMed

    Joshi, Gnanada S; Joiner, Michael C; Tucker, James D

    2014-12-01

    The dose-effect relationships of cells exposed to ionizing radiation are frequently described by linear quadratic (LQ) models over an extended dose range. However, many mammalian cell lines, when acutely irradiated in G2 at doses ≤0.3Gy, show hyper-radiosensitivity (HRS) as measured by reduced clonogenic cell survival, thereby indicating greater cell lethality than is predicted by extrapolation from high-dose responses. We therefore hypothesized that the cytogenetic response in G2 cells to low doses would also be steeper than predicted by LQ extrapolation from high doses. We tested our hypothesis by exposing four normal human lymphoblastoid cell lines to 0-400cGy of Cobalt-60 gamma radiation. The cytokinesis block micronucleus assay was used to determine the frequencies of micronuclei and nucleoplasmic bridges. To characterize the dependence of the cytogenetic damage on dose, univariate and multivariate regression analyses were used to compare the responses in the low- (HRS) and high-dose response regions. Our data indicate that the slope of the response for all four cell lines at ≤20cGy during G2 is greater than predicted by an LQ extrapolation from the high-dose responses for both micronuclei and bridges. These results suggest that the biological consequences of low-dose exposures could be underestimated and may not provide accurate risk assessments following such exposures.

  1. Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells

    SciTech Connect

    Iwata, Masahiro; Kawahara, Ko-ichi; Kawabata, Hisashi; Ito, Takashi; Mera, Kentaro; Biswas, Kamal Krishna; Tancharoen, Salunya; Higashi, Yuko; Kikuchi, Kiyoshi; Hashiguchi, Teruto

    2008-12-12

    Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10 mJ/cm{sup 2}) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and it was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.

  2. Modification of the effects of continuous low dose rate irradiation by concurrent chemotherapy infusion

    SciTech Connect

    Fu, K.K.; Rayner, P.A.; Lam, K.N.

    1984-08-01

    The combined effects of continuous low dose rate irradiation (CLDRI) and concurrent infusion of bleomycin, cyclophosphamide, cis-platinum, 5-fluorouracil, actinomycin D, and mitomycin C were studied in the SCC VII/SF tumor, a squamous cell carcinoma and the jejunal crypt cells in the mouse. For the SCC VII/SF tumor, enhanced cell killing was seen with each of the six drugs when infused concurrently with CLDRI; the greatest enhancement was seen with mitomycin C and cis-platinum. For the jejunal crypt cells, enhanced cell killing was seen primarily with bleomycin. The authors results suggest a therapeutic gain with concurrent CLDRI and chemotherapy infusion for five of the six chemotherapeutic drugs studied with the exception of bleomycin.

  3. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats

    PubMed Central

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-01-01

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage. PMID:26274957

  4. Hydrogen-Rich Water Ameliorates Total Body Irradiation-Induced Hematopoietic Stem Cell Injury by Reducing Hydroxyl Radical

    PubMed Central

    Xue, Xiaolei; Han, Xiaodan; Li, Yuan; Lu, Lu; Li, Deguan

    2017-01-01

    We examined whether consumption of hydrogen-rich water (HW) could ameliorate hematopoietic stem cell (HSC) injury in mice with total body irradiation (TBI). The results indicated that HW alleviated TBI-induced HSC injury with respect to cell number alteration and to the self-renewal and differentiation of HSCs. HW specifically decreased hydroxyl radical (∙OH) levels in the c-kit+ cells of 4 Gy irradiated mice. Proliferative bone marrow cells (BMCs) increased and apoptotic c-kit+ cells decreased in irradiated mice uptaken with HW. In addition, the mean fluorescence intensity (MFI) of γ-H2AX and percentage of 8-oxoguanine positive cells significantly decreased in HW-treated c-kit+ cells, indicating that HW can alleviate TBI-induced DNA damage and oxidative DNA damage in c-kit+ cells. Finally, the cell cycle (P21), cell apoptosis (BCL-XL and BAK), and oxidative stress (NRF2, HO-1, NQO1, SOD, and GPX1) proteins were significantly altered by HW in irradiated mouse c-kit+ cells. Collectively, the present results suggest that HW protects against TBI-induced HSC injury. PMID:28243358

  5. Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation

    SciTech Connect

    Parkman, R.; Rappeport, J.M.; Hellman, S.; Lipton, J.; Smith, B.; Geha, R.; Nathan, D.G.

    1984-10-01

    The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain.

  6. Preliminary analysis of irradiation effects on CLAM after low dose neutron irradiation

    NASA Astrophysics Data System (ADS)

    Peng, Lei; Huang, Qunying; Li, Chunjing; Liu, Shaojun

    2009-04-01

    To investigate the irradiation effects on a new version of reduced activation ferritic/martensitic steels (RAFMs) i.e. China Low Activation Martensitic steel (CLAM), neutron irradiation experiments has been being carried out under wide collaboration in China and overseas. In this paper, the mechanical properties of CLAM heats 0603A, 0408B, and 0408D were investigated before and after neutron irradiation to ˜0.02 dpa at 250 °C. The test results showed that ultimate strength and yield stress of CLAM HEAT 0603A increased about 10-30 MPa and ductile to brittle transition temperature (DBTT) shift was about 5 °C. For CLAM heats 0408B and 0408D, ultimate strength and yield stress increased about 80-150 MPa.

  7. Effect of low dose irradiation on the microbial and sensory characteristics of fresh pork loins. Final report

    SciTech Connect

    Olson, D.G.; Rust, R.E.; Kraft, A.A.; Walker, H.W.

    1986-05-01

    The effects of low dose (100 krad) irradiation on microflora, sensory characteristics, and development of oxidative rancidity of vacuum packed pork loins was investigated after irradiation and during low temperature (4/sup 0/C) storage up to 21 days. Irradiation reduced numbers of mesophiles, psychrotrophs, anaerobic bacteria (P<0.01), and staphylococci (P<0.05), with the effect on mesophiles and psychrotrophic spoilage organisms the greatest. Effect of irradiation on sensory characteristics of pork loin was minimal with no detectable differences between irradiated and nonirradiated pork after 14 days of storage. Irradiation of pork did not affect cooking loss or thiobarbituric acid values. 18 refs., 6 figs., 3 tabs.

  8. Continuous Low-dose-rate Irradiation of Iodine-125 Seeds Inhibiting Perineural Invasion in Pancreatic Cancer

    PubMed Central

    Lu, Zheng; Dong, Teng-Hui; Si, Pei-Ren; Shen, Wei; Bi, Yi-Liang; Min, Min; Chen, Xin; Liu, Yan

    2016-01-01

    Background: Perineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa). The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 (125I) seed implantation. Methods: The in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of 125I seeds CLDR irradiation. The orthotopic models of PNI were established, and 125I seeds were implanted in tumor. The PNI-related molecules were analyzed. In 30 patients with panCa, the pain relief was assessed using a visual analog scale (VAS). Pain intensity was measured before and 1 week, 2 weeks, and 1, 3, and 6 months after 125I seed implantation. Results: The co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites. In co-culture groups, the increased number of DRG neurites and pancreatic cells in radiation group was significantly less. In orthotopic models, the PNI-positive rate in radiation and control group was 3/11 and 7/11; meanwhile, the degrees of PNI between radiation and control groups was significant difference (P < 0.05). At week 2, the mean VAS pain score in patients decreased by 50% and significantly improved than the score at baseline (P < 0.05). The pain scores were lower in all patients, and the pain-relieving effect was retained about 3 months. Conclusions: The CLDR irradiation could inhibit PNI of PanCa with the value of further study. The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain. PMID:27748339

  9. Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation.

    PubMed

    Rajendran, R; Abu, E; Fadl, A; Byrne, C D

    2013-08-01

    Childhood cancer survivors may develop a number of endocrine complications linked to organ failure, such as hypogonadism, diabetes and growth hormone deficiency. However, increasing evidence now suggests that total body irradiation treatment, specifically, is linked with future risk of insulin resistance, hepatic steatosis and dyslipidaemia, possibly because total body irradiation affects adipocyte differentiation and impairs subcutaneous adipose tissue depot expansion during times of positive energy balance. We describe a 20-year-old woman who developed pancreatitis with severe hypertriglyceridaemia (serum triglycerides > 300 mmol/l) that required plasmapheresis. She had received total body irradiation prior to her bone marrow transplant at age 6 years for relapsed acute lymphoblastic leukaemia. She developed ovarian failure at age 12 years. At age 15 years she was noted to have hyperglycaemia, increased blood pressure, hepatic steatosis and mild hypertriglyceridaemia. She presented with severe hypertriglyceridaemia and eruptive xanthoma, and developed pancreatitis 12 h after admission. She was treated with plasmapheresis and intravenous insulin and made an excellent recovery. We implicate and discuss total body irradiation as the major contributing factor to her severe hypertriglyceridaemia, compounded by worsening glycaemic control, oestrogen deficiency and a changing adult lifestyle. Children who have received total body irradiation are at risk of diabetes and an exaggerated form of the metabolic syndrome with hypertriglyceridaemia, which can be life-threatening. We suggest that survivors of total body irradiation treatment require careful lifelong monitoring of their metabolic status. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  10. Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant

    SciTech Connect

    Singh, Anurag K. . E-mail: singan@mail.nih.gov; Karimpour, Shervin E.; Savani, Bipin N.; Guion, Peter M.S.; Hope, Andrew J.; Mansueti, John R.; Ning, Holly; Altemus, Rosemary M. Ph.D.; Wu, Colin O.; Barrett, A. John

    2006-10-01

    Purpose: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. Methods and Materials: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n = 85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n = 35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n = 26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. Results: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV{sub 1}) and a diffusion capacity of carbon dioxide (DLCO) <100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p = 0.042). Conclusion: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival.

  11. Application of thermoluminescence measurements to detect low dose gamma-irradiated table grapes

    NASA Astrophysics Data System (ADS)

    Sillano, O.; Román, A.; Deza, A.; Rubio, T.; Espinoza, J.

    1994-06-01

    A major factor hampering the introduction of ionizing radiation as an alternative quarantine treatment to chemical fumigation for fruit and vegetables is the lack of reliable, simple and inexpensive post-treatment methods to confirm this low dose irradiation treatment. Considering this purpose, thermoluminescence (TL) measurements of the wind blown dust naturally adhered to the surface of table grapes, was surveyed. Two doses, 0.5 and 1.0 kGy, were studied, applied to the main Chilean table grape export varieties: Thompson Seedless and Flame Seedless. TL measurements were carried out over 78 days for Thompson Seedless and 62 days for Flame Seedless varieties, both stored at 1 ± 1°C (usual handling of this fruit). TL response fading of dust samples stored at room temperature was also followed over 125 days. The TL response values obtained from the irradiated samples exceeded at least 3 times the highest ones obtained from the unirradiated counterparts. The treatment, even for the lower γ-radiation dose applied, could be properly detected well above the shipping and marketing time for this Chilean export fruit (2-8 weeks). This method also has the advantage of using relatively inexpensive equipment.

  12. Low-dose thoracoabdominal irradiation for the treatment of refractory chronic graft-versus-host disease.

    PubMed

    Robin, Marie; Guardiola, Philippe; Girinsky, Théodore; Hernandez, Gabriella; Espérou, Hélène; Ribaud, Patricia; Rocha, Vanderson; Garnier, Federico; Socié, Gérard; Gluckman, Eliane; Devergie, Agnès

    2005-09-15

    Half of the patients with chronic graft-versus-host disease (GvHD) do not achieve a complete remission with first-line therapy. No clear recommendations are available regarding second-line treatments. We retrospectively report our single-center experience of low-dose thoracoabdominal irradiation (1-Gy TAI) in 41 patients with refractory extensive chronic GvHD from 1983 to 2000. Median time from extensive chronic GvHD to TAI was one year (median GvHD episodes before TAI, n = 4). Eighty-two percent of the patients achieved a clinical response at a median of 34 days after TAI (range, 15-180). Best response rates were observed in fasciitis (79%), and oral GvHD lesions (73%). A complete clinical response was achieved in 11 patients by 2 years postTAI. Fifty-seven percent of the patients had at least a 50% reduction of their corticosteroid daily dose by 6 months postTAI. Probability of corticosteroid discontinuation was 38% by 2 years postTAI (95% CI, 23-56%). Two-year chronic GvHD relapse incidence was 34%. Ten-year survival from irradiation was 57% (95% CI, 42-78%); patients with fasciitis, lymphocytes >1.0 x 10/L, and platelets >200 x 10/L had a better outcome. TAI is a safe and efficient option in patients with refractory chronic GvHD, leading to a significant tapering of systemic corticosteroid dose in most cases.

  13. The effects of pre-emptive low-dose X-ray irradiation on MIA induced inflammatory pain in rats

    NASA Astrophysics Data System (ADS)

    Hahm, Suk-Chan; Lee, Go-Eun; Kim, Eun-Hye; Kim, Junesun; Lee, Taewoong; Lee, Wonho

    2013-07-01

    This study was performed to determine the effect of pre-emptive low-dose irradiation on the development of inflammatory pain and to characterize the potential mechanisms underlying this effect in osteoarthritis (OA) animal model. Whole-body X-irradiations with 0.1, 0.5, 1 Gy or sham irradiations were performed for 3 days before the induction of ostearthritis with monosodium iodoacetate (MIA) (40 µl, in saline) into the right knee joint in male Sprague Dawley rats. Behavioral tests for arthritic pain including evoked and non-evoked pain were conducted before and after MIA injection and inducible nitric-oxide synthase (iNOS) expression level was measured by western blot. Low-dose radiation significantly prevented the development of mechanical allodynia and thermal hyperalgesia and reduction in weight bearing that is regarded as a behavioral signs of non-evoked pain following MIA injection. Low-dose radiation significantly inhibited the increase in iNOS expression after MIA injection in spinal L3-5 segments in rat. These data suggest that low-dose X-irradiation is able to prevent the development of arthritic pain through modulation of iNOS expression in the spinal cord dorsal horn. Thus, low-dose radiotherapy could be substituted in part for treatment with drugs for patients with chronic inflammatory disease in clinical setting.

  14. Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation

    SciTech Connect

    Clave, E.; Socie, G.; Carosella, E.

    1995-11-01

    Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3{minus}, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation. 20 refs., 3 figs., 1 tab.

  15. CT analysis of lung density changes in patients undergoing total body irradiation prior to bone marrow transplantation

    SciTech Connect

    Lee, J.Y.; Shank, B.; Bonfiglio, P.; Reid, A.

    1984-10-01

    Sequential changes in lung density measured by CT are potentially sensitive and convenient monitors of lung abnormalities following total body irradiation (TBI). Methods have been developed to compare pre- and post-TBI CT of lung. The average local features of a cross-sectional lung slice are extracted from three peripheral regions of interest in the anterior, posterior, and lateral portions of the CT image. Also, density profiles across a specific region may be obtained. These may be compared first for verification of patient position and breathing status and then for changes between pre- and post-TBI. These may also be compared with radiation dose profiles through the lung. A preliminary study on 21 leukemia patients undergoing total body irradiation indicates the following: (a) Density gradients of patients' lungs in the antero-posterior direction show a marked heterogeneity before and after transplantation compared with normal lungs. The patients with departures from normal density gradients pre-TBI correlate with later pulmonary complications. (b) Measurements of average peripheral lung densities have demonstrated that the average lung density in the younger age group is substantially higher: pre-TBI, the average CT number (1,000 scale) is -638 +/- 39 Hounsfield unit (HU) for 0-10 years old and -739 +/- 53 HU for 21-40 years old. (c) Density profiles showed no post-TBI regional changes in lung density corresponding to the dose profile across the lung, so no differentiation of a radiation-specific effect has yet been possible. Computed tomographic density profiles in the antero-posterior direction are successfully used to verify positioning of the CT slice and the breathing level of the lung.

  16. Low doses of prophylactic cranial irradiation effective in limited stage small cell carcinoma of the lung

    SciTech Connect

    Rubenstein, J.H.; Dosoretz, D.E.; Katin, M.J. |

    1995-09-30

    Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses. One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI. Patients receiving PCI exhibited brain failure in 15%, while 38 of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS {ge} 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018). In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials. 44 refs., 4 figs., 2 tabs.

  17. Irradiation effect on deuterium behaviour in low-dose HFIR neutron-irradiated tungsten

    SciTech Connect

    Shimada, Masashi; Cao, G.; Otsuka, T.; Hara, M.; Kobayashi, M.; Oya, Y.; Hatano, Y.

    2014-12-01

    Tungsten samples were irradiated by neutrons in the High Flux Isotope Reactor, Oak Ridge National Laboratory at reactor coolant temperatures of 50-70°C to low displacement damage of 0.025 and 0.3 dpa under the framework of the US-Japan TITAN program (2007-2013). After cooling down, the HFIR neutron-irradiated tungsten samples were exposed to deuterium plasmas in the Tritium Plasma Experiment, Idaho National Laboratory at 100, 200 and 500 °C twice at the ion fluence of 5×10²⁵ m⁻² to reach a total ion fluence of 1×10²⁶ m⁻² in order to investigate the near surface deuterium retention and saturation via nuclear reaction analysis. Final thermal desorption spectroscopy was performed to elucidate irradiation effect on total deuterium retention. Nuclear reaction analysis results showed that the maximum near surface (<5 µm depth) deuterium concentration increased from 0.5 at % D/W in 0.025 dpa samples to 0.8 at. % D/W in 0.3 dpa samples. The large discrepancy between the total retention via thermal desorption spectroscopy and the near surface retention via nuclear reaction analysis indicated the deuterium was migrated and trapped in bulk (at least 50 µm depth for 0.025 dpa and 35 µm depth for 0.025 dpa) at 500 °C case even in the relatively low ion fluence of 10²⁶ m⁻².

  18. Irradiation effect on deuterium behaviour in low-dose HFIR neutron-irradiated tungsten

    DOE PAGES

    Shimada, Masashi; Cao, G.; Otsuka, T.; ...

    2014-12-01

    Tungsten samples were irradiated by neutrons in the High Flux Isotope Reactor, Oak Ridge National Laboratory at reactor coolant temperatures of 50-70°C to low displacement damage of 0.025 and 0.3 dpa under the framework of the US-Japan TITAN program (2007-2013). After cooling down, the HFIR neutron-irradiated tungsten samples were exposed to deuterium plasmas in the Tritium Plasma Experiment, Idaho National Laboratory at 100, 200 and 500 °C twice at the ion fluence of 5×10²⁵ m⁻² to reach a total ion fluence of 1×10²⁶ m⁻² in order to investigate the near surface deuterium retention and saturation via nuclear reaction analysis. Finalmore » thermal desorption spectroscopy was performed to elucidate irradiation effect on total deuterium retention. Nuclear reaction analysis results showed that the maximum near surface (<5 µm depth) deuterium concentration increased from 0.5 at % D/W in 0.025 dpa samples to 0.8 at. % D/W in 0.3 dpa samples. The large discrepancy between the total retention via thermal desorption spectroscopy and the near surface retention via nuclear reaction analysis indicated the deuterium was migrated and trapped in bulk (at least 50 µm depth for 0.025 dpa and 35 µm depth for 0.025 dpa) at 500 °C case even in the relatively low ion fluence of 10²⁶ m⁻².« less

  19. Defect annealing and thermal desorption of deuterium in low dose HFIR neutron-irradiated tungsten

    SciTech Connect

    Masashi Shimada; M. Hara; T. Otsuka; Y. Oya; Y. Hatano

    2014-05-01

    Accurately estimating tritium retention in plasma facing components (PFCs) and minimizing its uncertainty are key safety issues for licensing future fusion power reactors. D-T fusion reactions produce 14.1 MeV neutrons that activate PFCs and create radiation defects throughout the bulk of the material of these components. Recent studies show that tritium migrates and is trapped in bulk (>> 10 µm) tungsten beyond the detection range of nuclear reaction analysis technique [1-2], and thermal desorption spectroscopy (TDS) technique becomes the only established diagnostic that can reveal hydrogen isotope behavior in in bulk (>> 10 µm) tungsten. Radiation damage and its recovery mechanisms in neutron-irradiated tungsten are still poorly understood, and neutron-irradiation data of tungsten is very limited. In this paper, systematic investigations with repeated plasma exposures and thermal desorption are performed to study defect annealing and thermal desorption of deuterium in low dose neutron-irradiated tungsten. Three tungsten samples (99.99 at. % purity from A.L.M.T. Co., Japan) irradiated at High Flux Isotope Reactor at Oak Ridge National Laboratory were exposed to high flux (ion flux of (0.5-1.0)x1022 m-2s-1 and ion fluence of 1x1026 m-2) deuterium plasma at three different temperatures (100, 200, and 500 °C) in Tritium Plasma Experiment at Idaho National Laboratory. Subsequently, thermal desorption spectroscopy (TDS) was performed with a ramp rate of 10 °C/min up to 900 °C, and the samples were annealed at 900 °C for 0.5 hour. These procedures were repeated three (for 100 and 200 °C samples) and four (for 500 °C sample) times to uncover damage recovery mechanisms and its effects on deuterium behavior. The results show that deuterium retention decreases approximately 90, 75, and 66 % for 100, 200, and 500 °C, respectively after each annealing. When subjected to the same TDS recipe, the desorption temperature shifts from 800 °C to 600 °C after 1st annealing

  20. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation

    PubMed Central

    Valente, Marco; Denis, Josiane; Grenier, Nancy; Arvers, Philippe; Foucher, Barbara; Desangles, François; Martigne, Patrick; Chaussard, Hervé; Drouet, Michel; Abend, Michael; Hérodin, Francis

    2015-01-01

    In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI. PMID:26177207

  1. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

    PubMed

    Valente, Marco; Denis, Josiane; Grenier, Nancy; Arvers, Philippe; Foucher, Barbara; Desangles, François; Martigne, Patrick; Chaussard, Hervé; Drouet, Michel; Abend, Michael; Hérodin, Francis

    2015-01-01

    In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

  2. Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation

    PubMed Central

    Davis, Thomas A.; Landauer, Michael R.; Mog, Steven R.; Barshishat-Kupper, Michal; Zins, Stephen R.; Amare, Mihret F.; Day, Regina M.

    2010-01-01

    Objective Angiotensin II (Ang II), a potent vasoconstrictor, affects the growth and development of hematopoietic cells. Mixed findings have been reported for the effects of ACE inhibitors on radiation-induced injury to the hematopoietic system. We investigated the consequences of different regimens of the ACE inhibitor captopril on radiation-induced hematopoietic injury. Methods C57BL/6 mice were either sham irradiated or were exposed to 60Co total body irradiation (0.6 Gy/min). Captopril was provided in the water for different time periods relative to irradiation. Results In untreated mice, the survival rate from 7.5 Gy was 50% at 30 days postirradiation. Captopril treatment for 7 days prior to irradiation resulted in radiosensitization with 100% lethality and a rapid decline of mature blood cells. In contrast, captopril treatment beginning 1 hour postirradiation and continuing for 30 days resulted in 100% survival, with improved recovery of mature blood cells and multilineage hematopoietic progenitors. In nonirradiated control mice captopril biphasically modulated Lin− marrow progenitor cell cycling. After 2 days, captopril suppressed G0-G1 transition and a greater number of cells entered a quiescent state. However, after 7 days of captopril treatment Linprogenitor cell cycling increased compared to untreated control mice. Conclusion These findings suggest that ACE inhibition affects hematopoietic recovery following radiation by modulating the hematopoietic progenitor cell cycle. The timing of captopril treatment relative to radiation exposure differentially affects the viability and repopulation capacity of spared hematopoietic stem cells and therefore can result in either radiation protection or radiation sensitization. PMID:20116413

  3. Total body irradiation with a compensator fabricated using a 3D optical scanner and a 3D printer

    NASA Astrophysics Data System (ADS)

    Park, So-Yeon; Kim, Jung-in; Joo, Yoon Ha; Lee, Jung Chan; Park, Jong Min

    2017-05-01

    We propose bilateral total body irradiation (TBI) utilizing a 3D printer and a 3D optical scanner. We acquired surface information of an anthropomorphic phantom with the 3D scanner and fabricated the 3D compensator with the 3D printer, which could continuously compensate for the lateral missing tissue of an entire body from the beam’s eye view. To test the system’s performance, we measured doses with optically stimulated luminescent dosimeters (OSLDs) as well as EBT3 films with the anthropomorphic phantom during TBI without a compensator, conventional bilateral TBI, and TBI with the 3D compensator (3D TBI). The 3D TBI showed the most uniform dose delivery to the phantom. From the OSLD measurements of the 3D TBI, the deviations between the measured doses and the prescription dose ranged from  -6.7% to 2.4% inside the phantom and from  -2.3% to 0.6% on the phantom’s surface. From the EBT3 film measurements, the prescription dose could be delivered to the entire body of the phantom within  ±10% accuracy, except for the chest region, where tissue heterogeneity is extreme. The 3D TBI doses were much more uniform than those of the other irradiation techniques, especially in the anterior-to-posterior direction. The 3D TBI was advantageous, owing to its uniform dose delivery as well as its efficient treatment procedure.

  4. Total body irradiation with a compensator fabricated using a 3D optical scanner and a 3D printer.

    PubMed

    Park, So-Yeon; Kim, Jung-In; Joo, Yoon Ha; Lee, Jung Chan; Park, Jong Min

    2017-05-07

    We propose bilateral total body irradiation (TBI) utilizing a 3D printer and a 3D optical scanner. We acquired surface information of an anthropomorphic phantom with the 3D scanner and fabricated the 3D compensator with the 3D printer, which could continuously compensate for the lateral missing tissue of an entire body from the beam's eye view. To test the system's performance, we measured doses with optically stimulated luminescent dosimeters (OSLDs) as well as EBT3 films with the anthropomorphic phantom during TBI without a compensator, conventional bilateral TBI, and TBI with the 3D compensator (3D TBI). The 3D TBI showed the most uniform dose delivery to the phantom. From the OSLD measurements of the 3D TBI, the deviations between the measured doses and the prescription dose ranged from  -6.7% to 2.4% inside the phantom and from  -2.3% to 0.6% on the phantom's surface. From the EBT3 film measurements, the prescription dose could be delivered to the entire body of the phantom within  ±10% accuracy, except for the chest region, where tissue heterogeneity is extreme. The 3D TBI doses were much more uniform than those of the other irradiation techniques, especially in the anterior-to-posterior direction. The 3D TBI was advantageous, owing to its uniform dose delivery as well as its efficient treatment procedure.

  5. Pretreatment with low-dose gamma irradiation enhances tolerance to the stress of cadmium and lead in Arabidopsis thaliana seedlings.

    PubMed

    Qi, Wencai; Zhang, Liang; Wang, Lin; Xu, Hangbo; Jin, Qingsheng; Jiao, Zhen

    2015-05-01

    Heavy metals are important environmental pollutants with negative impact on plant growth and development. To investigate the physiological and molecular mechanisms of heavy metal stress mitigated by low-dose gamma irradiation, the dry seeds of Arabidopsis thaliana were exposed to a Cobalt-60 gamma source at doses ranging from 25 to 150Gy before being subjected to 75µM CdCl2 or 500µM Pb(NO3)2. Then, the growth parameters, and physiological and molecular changes were determined in response to gamma irradiation. Our results showed that 50-Gy gamma irradiation gave maximal beneficial effects on the germination index and root length in response to cadmium/lead stress in Arabidopsis seedlings. The hydrogen peroxide and malondialdehyde contents in seedlings irradiated with 50-Gy gamma rays under stress were significantly lower than those of controls. The antioxidant enzyme activities and proline levels in the irradiated seedlings were significantly increased compared with the controls. Furthermore, a transcriptional expression analysis of selected genes revealed that some components of heavy metal detoxification were stimulated by low-dose gamma irradiation under cadmium/lead stress. Our results suggest that low-dose gamma irradiation alleviates heavy metal stress, probably by modulating the physiological responses and gene expression levels related to heavy metal resistance in Arabidopsis seedlings. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

    PubMed

    Cook, S D; Devereux, C; Troiano, R; Wolansky, L; Guarnaccia, J; Haffty, B; Bansil, S; Goldstein, J; Sheffet, A; Zito, G; Jotkowitz, A; Boos, J; Dowling, P; Rohowsky-Kochan, C; Volmer, T

    1997-11-25

    In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

  7. Low-Dose Irradiation Enhances Gene Targeting in Human Pluripotent Stem Cells

    PubMed Central

    Hatada, Seigo; Subramanian, Aparna; Mandefro, Berhan; Ren, Songyang; Kim, Ho Won; Tang, Jie; Funari, Vincent; Baloh, Robert H.; Sareen, Dhruv

    2015-01-01

    Human pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy; however, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. We showed that limited low-dose irradiation (LDI) using either γ-ray or x-ray exposure (0.4 Gy) significantly enhanced HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by more than 30-fold when combined with the targeting tools zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats. Whole-exome sequencing confirmed that the LDI administered to hPSCs did not induce gross genomic alterations or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new, targeted hPSC lines that are crucial to expand the use of disease modeling and to develop novel avenues of cell therapy. Significance The simple and relevant technique described in this report uses a low level of radiation to increase desired gene modifications in human pluripotent stem cells by an order of magnitude. This higher efficiency permits greater throughput with reduced time and cost. The low level of radiation also greatly increased the recombination frequency when combined with developed engineered nucleases. Critically, the radiation did not lead to increases in DNA mutations or to reductions in overall cellular viability. This novel technique enables not only the rapid production of disease models using human stem cells but also the possibility of treating genetically based diseases by correcting patient-derived cells. PMID:26185257

  8. Poster — Thur Eve — 38: Feasibility of a Table-Top Total Body Irradiation Technique using Robotic Couch Motion

    SciTech Connect

    Chin, Erika; Otto, Karl; Hoppe, Richard; Hsu, Annie; Loo, Billy; Million, Lynn; Xing, Lei; Fahimian, Benjamin

    2014-08-15

    Purpose: To develop and test the feasibility of a table-top implementation for total body irradiation (TBI) via robotic couch motion and coordinated monitor unit modulation on a standard C-arm linac geometry. Methods: To allow for collision free delivery and to maximize the effective field size, the couch was rotated to 270° IEC and dropped to 150 cm from the vertical radiation source. The robotic delivery was programmed using the TrueBeam STx Developer Mode using custom XML scripting. To assess the dosimetry of a sliding 30×20 cm{sup 2} field, irradiation on a solid water phantom of varying thickness was analyzed using EDR2 radiographic film and OSLDs. Beam modulation was achieved by dividing the couch path into multiple segments of varying dose rates and couch speeds in order to deliver 120 cGy to the midline. Results: The programmed irradiation in conjunction with coordinated couch motion was successfully delivered on a TrueBeam linac. When no beam modulation was employed, the dose difference between two different phantom sections was 17.0%. With simple beam modulation via changing dose rates and couch speeds, the desired prescription dose can be achieved at the centre of each phantom section within 1.9%. However, dose deviation at the junction was 9.2% due to the nonphysical change in the phantom thickness. Conclusions: The feasibility of robotic table-top TBI on a C-arm linac geometry was experimentally demonstrated. To achieve a more uniform dose distribution, inverse-planning allowing for a combination of dose rate modulation, jaw tracking and MLC motion is under investigation.

  9. TH-C-12A-04: Dosimetric Evaluation of a Modulated Arc Technique for Total Body Irradiation

    SciTech Connect

    Tsiamas, P; Czerminska, M; Makrigiorgos, G; Karen, M; Zygmanski, P

    2014-06-15

    Purpose: A simplified Total Body Irradiation (TBI) was developed to work with minimal requirements in a compact linac room without custom motorized TBI couch. Results were compared to our existing fixed-gantry double 4 MV linac TBI system with prone patient and simultaneous AP/PA irradiation. Methods: Modulated arc irradiates patient positioned in prone/supine positions along the craniocaudal axis. A simplified inverse planning method developed to optimize dose rate as a function of gantry angle for various patient sizes without the need of graphical 3D treatment planning system. This method can be easily adapted and used with minimal resources. Fixed maximum field size (40×40 cm2) is used to decrease radiation delivery time. Dose rate as a function of gantry angle is optimized to result in uniform dose inside rectangular phantoms of various sizes and a custom VMAT DICOM plans were generated using a DICOM editor tool. Monte Carlo simulations, film and ionization chamber dosimetry for various setups were used to derive and test an extended SSD beam model based on PDD/OAR profiles for Varian 6EX/ TX. Measurements were obtained using solid water phantoms. Dose rate modulation function was determined for various size patients (100cm − 200cm). Depending on the size of the patient arc range varied from 100° to 120°. Results: A PDD/OAR based beam model for modulated arc TBI therapy was developed. Lateral dose profiles produced were similar to profiles of our existing TBI facility. Calculated delivery time and full arc depended on the size of the patient (∼8min/ 100° − 10min/ 120°, 100 cGy). Dose heterogeneity varied by about ±5% − ±10% depending on the patient size and distance to the surface (buildup region). Conclusion: TBI using simplified modulated arc along craniocaudal axis of different size patients positioned on the floor can be achieved without graphical / inverse 3D planning.

  10. A phase I study of WR-2721 in combination with total body irradiation (TBI) in patients with refractory lymphoid malignancies

    SciTech Connect

    Coia, L.; Krigel, R.; Hanks, G.; Comis, R.; Algazy, K.; Peters, R.; McCulloch, W.; Schien, P. )

    1992-01-01

    This Phase I study was designed to establish the maximum tolerated dose (MTD) of WR-2721 when given twice weekly with total body irradiation (TBI) in the treatment of patients with advanced refractory lymphoid malignancies and to define the toxicities of this combination and schedule. Patients eligible for this study had advanced recurrent indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Patients had symptomatic or progressive disease, a performance status of 0, 1, or 2, and adequate bone marrow, hepatic, and renal function. Only patients failing one or two regimens of prior chemotherapy were eligible. Patients who had received prior extended field irradiation were ineligible. Patients received TBI twice weekly (Tuesday and Friday) to a total of 10 doses at 15 cGy/fx. WR-2721 was given intravenously over 15 min beginning 30 min before irradiation. The escalation of WR-2721 was Level 1: 740 mg/m2 and Level 2: 910 mg/m2. The MTD of WR-2721 was that dose which produced predictable and reversible toxicity and would not interfere with patient well-being. Seven patients were entered onto the study, three at 740 mg/m2 and four at 910 mg/m2. Five patients had CLL and two patients small lymphocytic NHL. No patient had hypotension or nausea requiring reduction in dose level or even interruption of infusion of WR-2721. At 740 mg/m2 no grade 3 or 4 toxicities related to WR-2721 were observed, but two patients could not complete treatment because of TBI-induced prolonged thrombocytopenia following treatments 5 and 8. One patient completed all 10 treatments. At 910 mg/m2 of WR-2721, two patients requested removal from study because of malaise, one after 5 cycles and one after 7 cycles. One patient completed all 10 treatments.

  11. SU-E-T-600: In Vivo Dosimetry for Total Body and Total Marrow Irradiations with Optically Stimulated Luminescence Dosimeters

    SciTech Connect

    Niedbala, M; Save, C; Cygler, J

    2014-06-01

    Purpose: To evaluate the feasibility of using optically stimulated luminescence dosimeters (OSLDs) for in-vivo dosimetry of patients undergoing Total Body and Total Marrow Irradiations (TBI and TMI). Methods: TBI treatments of 12 Gy were delivered in 6 BID fractions with the patient on a moving couch under a static 10 MV beam (Synergy, Elekta). TMI treatments of 18 Gy in 9 BID fractions were planned and delivered using a 6 MV TomoTherapy unit (Accuray). To provide a uniform dose to the entire patient length, the treatment was split into 2 adjacent fields junctioned in the thigh region. Our standard clinical practice involves in vivo dosimetry with MOSFETs for each TBI fraction and TLDs for at least one fraction of the TMI treatment for dose verification. In this study we also used OSLDs. Individual calibration coefficients were obtained for the OSLDs based on irradiations in a solid water phantom to the dose of 50 cGy from Elekta Synergy 10 MV (TBI) and 6 MV (TMI) beams. Calibration coefficients were calculated based on the OSLDs readings taken 2 hrs post-irradiation. For in vivo dosimetry OSLDs were placed alongside MOSFETs for TBI patients and in approximately the same locations as the TLDs for TMI patients. OSLDs were read 2 hours post treatment and compared to the MOSFET and TLD results. Results: OSLD measured doses agreed within 5% with MOSFET and TLD results, with the exception of the junction region in the TMI patient due to very high dose gradient and difficulty of precise and reproducible detector placement. Conclusion: OSLDs are useful for in vivo dosimetry of TBI and TMI patients. The quick post-treatment readout is an advantage over TLDs, allowing the results to be obtained between BID fractions, while wireless detectors are advantageous over MOSFETs for treatments involving a moving couch.

  12. Inhibitory effects of prior low-dose X-ray irradiation on carbon tetrachloride-induced hepatopathy in acatalasemic mice.

    PubMed

    Yamaoka, Kiyonori; Kataoka, Takahiro; Nomura, Takaharu; Taguchi, Takehito; Wang, Da-Hong; Mori, Shuji; Hanamoto, Katsumi; Kira, Shohei

    2004-03-01

    The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs(b)Cs(b)) mouse of C3H strain are lower than those of the normal (C3H/AnLCs (a)Cs(a)) mouse. We examined the effects of prior low-dose (0.5 Gy) X-ray irradiation, which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in the acatalasemic or normal mice. The acatalasemic mice showed a significantly lower catalase activity and a significantly higher glutathione peroxidase activity compared with those in the normal mice. Moreover, low-dose irradiation increased the catalase activity in the acatalasemic mouse liver to a level similar to that of the normal mouse liver. Pathological examinations and analyses of blood glutamic oxaloacetic and glutamic pyruvic transaminase activity and lipid peroxide levels showed that carbon tetrachloride induced hepatopathy was inhibited by low-dose irradiation. These findings may indicate that the free radical reaction induced by the lack of catalase and the administration of carbon tetrachloride is more properly neutralized by high glutathione peroxidase activity and low-dose irradiation in the acatalasemic mouse liver.

  13. Results of Hematopoietic Stem Cell Transplantation After Treatment With Different High-Dose Total-Body Irradiation Regimens in Five Dutch Centers

    SciTech Connect

    Loes van Kempen-Harteveld, M. Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; Maazen, Richard W. van der; Cornelissen, Jan J.; Eijkenboom, Wil M.H.; Lelie, Johannes P. van der; Oldenburger, Foppe; Barge, Renee M.; Biezen, Anja van; Vossen, Jaak M.J.J.; Noordijk, Evert M.; Struikmans, Henk

    2008-08-01

    Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. Results: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. Conclusions: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced.

  14. Inhibitory effects of prior low-dose x-irradiation on ischemia-reperfusion injury in mouse paw.

    PubMed

    Kataoka, Takahiro; Mizuguchi, Yuko; Yoshimoto, Masaaki; Taguchi, Takehito; Yamaoka, Kiyonori

    2007-11-01

    We have reported that low-dose, unlike high-dose, irradiation enhanced antioxidation function and reduced oxidative damage. On the other hand, ischemia-reperfusion injury is induced by reactive oxygen species. In this study, we examined the inhibitory effects of prior low-dose X-irradiation on ischemia-reperfusion injury in mouse paw. BALB/c mice were irradiated by sham or 0.5 Gy of X-ray. At 4 hrs after irradiation, the left hind leg was bound 10 times with a rubber ring for 0.5, 1, or 2 hrs and the paw thickness was measured. Results show that the paw swelling thickness by ischemia for 0.5 hr was lower than that for 2 hrs. At 1 hr after reperfusion from ischemia for 1 hr, superoxide dismutase activity in serum was increased in those mice which received 0.5 Gy irradiation and in the case of the ischemia for 0.5 or 1 hr, the paw swelling thicknesses were inhibited by 0.5 Gy irradiation. In addition, interstitial edema in those mice which received 0.5 Gy irradiation was less than that in the mice which underwent by sham irradiation. These findings suggest that the ischemia-reperfusion injury is inhibited by the enhancement of antioxidation function by 0.5 Gy irradiation.

  15. Total-body irradiation with high-LET particles: acute and chronic effects on the immune system

    NASA Technical Reports Server (NTRS)

    Gridley, Daila S.; Pecaut, Michael J.; Nelson, Gregory A.

    2002-01-01

    Although the immune system is highly susceptible to radiation-induced damage, consequences of high linear energy transfer (LET) radiation remain unclear. This study evaluated the effects of 0.1 gray (Gy), 0.5 Gy, and 2.0 Gy iron ion (56Fe(26)) radiation on lymphoid cells and organs of C57BL/6 mice on days 4 and 113 after whole body exposure; a group irradiated with 2.0 Gy silicon ions (28Si) was euthanized on day 113. On day 4 after 56Fe irradiation, dose-dependent decreases were noted in spleen and thymus masses and all major leukocyte populations in blood and spleen. The CD19(+) B lymphocytes were most radiosensitive and NK1.1(+) natural killer (NK) cells were most resistant. CD3(+) T cells were moderately radiosensitive and a greater loss of CD3(+)/CD8(+) T(C) cells than CD3(+)/CD4(+) T(H) cells was noted. Basal DNA synthesis was elevated on day 4, but response to mitogens and secretion of interleukin-2 and tumor necrosis factor-alpha were unaffected. Signs of anemia were noted. By day 113, high B cell numbers and low T(C) cell and monocyte percents were found in the 2.0 Gy 56Fe group; the 2.0 Gy 2)Si mice had low NK cells, decreased basal DNA synthesis, and a somewhat increased response to two mitogens. Collectively, the data show that lymphoid cells and tissues are markedly affected by high linear energy transfer (LET) radiation at relatively low doses, that some aberrations persist long after exposure, and that different consequences may be induced by various densely ionizing particles. Thus simultaneous exposure to multiple radiation sources could lead to a broader spectrum of immune dysfunction than currently anticipated.

  16. Total-body irradiation with high-LET particles: acute and chronic effects on the immune system

    NASA Technical Reports Server (NTRS)

    Gridley, Daila S.; Pecaut, Michael J.; Nelson, Gregory A.

    2002-01-01

    Although the immune system is highly susceptible to radiation-induced damage, consequences of high linear energy transfer (LET) radiation remain unclear. This study evaluated the effects of 0.1 gray (Gy), 0.5 Gy, and 2.0 Gy iron ion (56Fe(26)) radiation on lymphoid cells and organs of C57BL/6 mice on days 4 and 113 after whole body exposure; a group irradiated with 2.0 Gy silicon ions (28Si) was euthanized on day 113. On day 4 after 56Fe irradiation, dose-dependent decreases were noted in spleen and thymus masses and all major leukocyte populations in blood and spleen. The CD19(+) B lymphocytes were most radiosensitive and NK1.1(+) natural killer (NK) cells were most resistant. CD3(+) T cells were moderately radiosensitive and a greater loss of CD3(+)/CD8(+) T(C) cells than CD3(+)/CD4(+) T(H) cells was noted. Basal DNA synthesis was elevated on day 4, but response to mitogens and secretion of interleukin-2 and tumor necrosis factor-alpha were unaffected. Signs of anemia were noted. By day 113, high B cell numbers and low T(C) cell and monocyte percents were found in the 2.0 Gy 56Fe group; the 2.0 Gy 2)Si mice had low NK cells, decreased basal DNA synthesis, and a somewhat increased response to two mitogens. Collectively, the data show that lymphoid cells and tissues are markedly affected by high linear energy transfer (LET) radiation at relatively low doses, that some aberrations persist long after exposure, and that different consequences may be induced by various densely ionizing particles. Thus simultaneous exposure to multiple radiation sources could lead to a broader spectrum of immune dysfunction than currently anticipated.

  17. Late tissue-specific toxicity of total body irradiation and busulfan in a murine bone marrow transplant model.

    PubMed

    Down, J D; Berman, A J; Warhol, M; Van Dijken, P J; Ferrara, J L; Yeap, B; Hellman, S; Mauch, P M

    1989-07-01

    Total body irradiation (TBI) and busulfan were compared for late effects in a murine model of bone marrow transplantation (BMT). Male C57BL/6 mice were given fractionated TBI or busulfan given in 4 equal daily doses followed by infusion of 10(7) syngeneic bone marrow cells. Total doses of 16.4 Gy TBI and 3.4 mg busulfan were chosen for their equivalence in inducing near complete engraftment of allogeneic marrow from donor mice of the LP strain. The two treatment groups had a late wave of mortality starting at about 80 weeks after transplantation. Specific tissue damage was manifested in bone marrow stem cells, splenic T-cell precursors, hair greying and cataract formation for both TBI and busulfan but to varying degrees. Severe nephrotoxicity and anemia were observed only after TBI. Although both busulfan and TBI kill early marrow stem cells and are effective preparative agents in bone marrow transplantation, their effects on other stem cell and organ systems are not similar. In addition, many of the injuries seen are late to occur. The delayed expression of injury deserves careful long-term evaluation of BMT recipients before the therapeutic potential of effective preparative regimens can be fully appreciated.

  18. Oocyte donation in women cured of cancer with bone marrow transplantation including total body irradiation in adolescence.

    PubMed

    Larsen, E C; Loft, A; Holm, K; Müller, J; Brocks, V; Andersen, A N

    2000-07-01

    Female survivors of cancer in childhood and adolescence who have been treated with bone marrow transplantation including total body irradiation (TBI) are at high risk of developing ovarian follicular depletion and infertility. The lack of oocytes may be compensated for by oocyte donation but these patients also seem to have a uterine factor. Even though oestrogen replacement therapy is given, the growth of the uterus during adolescence is impaired. To our knowledge there have been no earlier reports of live births after oocyte donation in such patients. We report three cases of oocyte donation in women who, at a young age, were cured of haematological malignancies with bone marrow transplantation including TBI. In adolescence they developed ovarian failure and uterine volumes were assessed by ultrasonography. One woman with a uterus of almost normal size delivered a healthy child in the 37th week of gestation. Another woman with severely diminished uterine volume miscarried in the 17th week of gestation. The third woman has not yet conceived. Pregnancy achieved by oocyte donation is possible despite TBI in adolescence. However, the uterine factor is a concern and complications during pregnancy and preterm birth may be expected in these patients.

  19. Combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation

    SciTech Connect

    Weick, J.K.; Antunez, A.; Kraus, T.A.; Fabian, C.J.; Dixon, D.

    1983-08-01

    The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. Responses were seen in 8/11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3020 x 10/sup 9//..mu..l (range 1.2 to 5.5) and a mean nadir platelet count of 188 x 10/sup 9//..mu..l (range 016 to 270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients.

  20. Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation.

    PubMed

    Moulder, John E; Cohen, Eric P; Fish, Brian L

    2011-01-01

    It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) "Animal Efficacy Rule", we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m(2)/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed.

  1. Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation

    PubMed Central

    Chiang, Yun; Tsai, Cheng-Hong; Kuo, Sung-Hsin; Liu, Chieh-Yu; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Lin, Chien-Ting; Hou, Hsin-An; Chou, Wen-Chien; Liu, Jia-Hau; Lin, Chien-Chin; Wu, Shang-Ju; Hsu, Szu-Chun; Chen, Yao-Chang; Lin, Kai-Hsin; Lin, Dong-Tsamn; Chou, Hsien-Tang; Lu, Meng-Yu; Yang, Yung-Li; Chang, Hsiu-Hao; Liu, Ming-Chih; Liao, Xiu-Wen; Wu, Jian-Kuen; Chou, Sheng-Chieh; Cheng, Chieh-Lung; Chen, Chien-Yuan; Tsay, Woei; Tien, Hwei-Fang; Tang, Jih-Luh; Chen, Yu-Hsuan

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy. PMID:27830767

  2. Total body irradiation for stage II-IV non-Hodgkin's lymphoma: ten-year follow-up

    SciTech Connect

    Mendenhall, N.P.; Noyes, W.D.; Million, R.R.

    1989-01-01

    Between 1972 and 1977, a prospective study was conducted at the University of Florida on the role of total body irradiation (TBI) in the management of stage II-IV non-Hodgkin's lymphoma (NHL). Forty-four consecutive de novo (DN) patients (including ten stage II, 18 stage III, and 16 stage IV), as well as 16 previously treated (PT) patients, were accrued. Twenty of the 44 DN patients were symptomatic at presentation. Complete clinical responses were obtained in 20 of the 27 DN patients with favorable histologies (FH), and six of the 17 with unfavorable histologies (UH). Partial responses were obtained in six patients with FH and 11 patients with UH; only one patient showed no response to TBI. By univariate analysis, PT patients showed a trend for decreased relapse-free survival (P = .066) and decreased survival (P = .093). Multivariate analysis identified the best predictors of response rate to be histology (P = .0146) and marrow involvement (P = .0854); of relapse-free survival, histology (P = .0035), and TBI dose (P = .002); and of absolute survival, age (P = .0012), histology (P = .012), and TBI dose (P = .029). Thirty of the 41 patients who relapsed underwent salvage treatment with either chemotherapy or radiation. Twenty-three of the 30 undergoing salvage therapy obtained a second complete clinical response. There were no treatment-related deaths. The most common complication was thrombocytopenia. The major late complications were myeloproliferative disorders in four patients, which occurred only after cumulative TBI doses in excess of 200 cGy.

  3. Captopril and Losartan for Mitigation of Renal Injury Caused by Single-Dose Total-Body Irradiation

    PubMed Central

    Moulder, John E.; Cohen, Eric P.; Fish, Brian L.

    2011-01-01

    It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) “Animal Efficacy Rule”, we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m2/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed. PMID:21175344

  4. Development and characterization of a novel variable low-dose rate irradiator for in vivo mouse studies

    PubMed Central

    Olipitz, Werner; Hembrador, Sheena; Davidson, Matthew; Yanch, Jacquelyn C.; Engelward, Bevin P.

    2011-01-01

    Radiation exposure of humans generally results in low doses delivered at low dose-rate. Our limited knowledge of the biological effects of low dose radiation is mainly based on data from the atomic bomb long-term survivor study (LSS) cohort. However, the total doses and dose-rates in the LSS cohort are still higher than most environmental and occupational exposures in humans. Importantly, the dose-rate is a critical determinant of health risks stemming from radiation exposure. Understanding the shape of the dose-rate response curve for different biological outcomes is thus crucial for projecting the biological hazard from radiation in different environmental and man-made conditions. A significant barrier to performing low dose-rate studies is the difficulty in creating radiation source configurations compatible with long-term cellular or animal experiments. In this study the design and characterization of a large area, 125I-based irradiator is described. The irradiator allows continuous long-term exposure of mice at variable dose-rates and can be sited in standard animal care facilities. The dose-rate is determined by the level of 125I activity added to a large NaOH filled, rectangular phantom. The desired dose rate is maintained at essentially constant levels by weekly additions of 125I to compensate for decay. Dosimetry results for long-term animal irradiation at targeted dose rates of 0.00021 and 0.0021 cGy min−1 are presented. PMID:20386202

  5. Characterization of the neutron irradiation system for use in the Low-Dose-Rate Irradiation Facility at Sandia National Laboratories.

    SciTech Connect

    Franco, Manuel

    2014-08-01

    The objective of this work was to characterize the neutron irradiation system consisting of americium-241 beryllium (241AmBe) neutron sources placed in a polyethylene shielding for use at Sandia National Laboratories (SNL) Low Dose Rate Irradiation Facility (LDRIF). With a total activity of 0.3 TBq (9 Ci), the source consisted of three recycled 241AmBe sources of different activities that had been combined into a single source. The source in its polyethylene shielding will be used in neutron irradiation testing of components. The characterization of the source-shielding system was necessary to evaluate the radiation environment for future experiments. Characterization of the source was also necessary because the documentation for the three component sources and their relative alignment within the Special Form Capsule (SFC) was inadequate. The system consisting of the source and shielding was modeled using Monte Carlo N-Particle transport code (MCNP). The model was validated by benchmarking it against measurements using multiple techniques. To characterize the radiation fields over the full spatial geometry of the irradiation system, it was necessary to use a number of instruments of varying sensitivities. First, the computed photon radiography assisted in determining orientation of the component sources. With the capsule properly oriented inside the shielding, the neutron spectra were measured using a variety of techniques. A N-probe Microspec and a neutron Bubble Dosimeter Spectrometer (BDS) set were used to characterize the neutron spectra/field in several locations. In the third technique, neutron foil activation was used to ascertain the neutron spectra. A high purity germanium (HPGe) detector was used to characterize the photon spectrum. The experimentally measured spectra and the MCNP results compared well. Once the MCNP model was validated to an adequate level of confidence, parametric analyses was performed on the model to optimize for potential

  6. Mining gene expression data for pollutants (dioxin, toluene, formaldehyde) and low dose of gamma-irradiation.

    PubMed

    Moskalev, Alexey; Shaposhnikov, Mikhail; Snezhkina, Anastasia; Kogan, Valeria; Plyusnina, Ekaterina; Peregudova, Darya; Melnikova, Nataliya; Uroshlev, Leonid; Mylnikov, Sergey; Dmitriev, Alexey; Plusnin, Sergey; Fedichev, Peter; Kudryavtseva, Anna

    2014-01-01

    (dioxin, toluene), low dose of gamma-irradiation and common molecular pathways for different kind of stressors.

  7. Physiological and molecular characterization of the enhanced salt tolerance induced by low-dose gamma irradiation in Arabidopsis seedlings.

    PubMed

    Qi, Wencai; Zhang, Liang; Xu, Hangbo; Wang, Lin; Jiao, Zhen

    2014-07-25

    It has been established that gamma rays at low doses stimulate the tolerance to salt stress in plants. However, our knowledge regarding the molecular mechanism underlying the enhanced salt tolerance remains limited. In this study, we found that 50-Gy gamma irradiation presented maximal beneficial effects on germination index and root length in response to salt stress in Arabidopsis seedlings. The contents of H2O2 and MDA in irradiated seedlings under salt stress were significantly lower than those of controls. The activities of antioxidant enzymes and proline levels in the irradiated seedlings were markedly increased compared with the controls. Furthermore, transcriptional expression analysis of selected genes revealed that some components of salt stress signaling pathways were stimulated by low-dose gamma irradiation under salt stress. Our results suggest that gamma irradiation at low doses alleviates the salt stress probably by modulating the physiological responses as well as stimulating the stress signal transduction in Arabidopsis seedlings. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Modeling Low-Dose-Rate Effects in Irradiated Bipolar-Base Oxides

    SciTech Connect

    Cirba, C.R.; Fleetwood, D.M.; Graves, R.J.; Michez, A.; Milanowski, R.J.; Saigne, F.; Schrimpf, R.D.; Witczak, S.C.

    1998-10-26

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in bipolar junction transistors. Multiple-trapping simulations show that space charge limited transport is partially responsible for low-dose-rate enhancement. At low dose rates, more holes are trapped near the silicon-oxide interface than at high dose rates, resulting in larger midgap voltage shifts at lower dose rates. The additional trapped charge near the interface may cause an exponential increase in excess base current, and a resultant decrease in current gain for some NPN bipolar technologies.

  9. Energy Differential Response of Cancer Cells for Low Dose Irradiation:Impact of Monoenergetic Brachytherapy Sources

    SciTech Connect

    Gueye, Paul; Prilepskiy, Yuriy; Keppel, Cynthia; Britten, R

    2010-06-01

    Purpose: The purpose of this work was to evaluate the energy differential response of cancer cells under identical dose exposure to asses the relevancy of mono-energetic sources for Brachytherapy treatments. Method and Materials: An electron energy spectrum impinging on lived breast cancer cell lines (MDA321) was obtained by placing a 19.65 {micro}Ci {sup 90}Sr/{sup 90}Y radioactive source in front of a non-uniform magnetic field constructed from two 5.08 x 5.0 cm x 2.54 cm neodimium ion permanent dipole magnets with a 1 cm separation gap. The cell lines were placed on the exit pole face of the magnet and were subsequently irradiated with different electron energies ranging from about 0.75 MeV to 1.85 MeV. The energy distribution was accurately measured with a scintillating fiber detector system that provided a 0.5% agreement with ICRU and a 5% energy resolution. The dosimetry was performed using a series of data acquired with a {sup 9}Sr/{sup 90}Y 4.5 mCi SIA-6 eye applicator, 6-21 MeV fixed energies from a Varian 2100 EX linac, EBT Gafchromic and Kodak ERT2 films, and an ion chamber detector. The accuracy of the dose rate obtained at different locations along and away from the magnet inside the cell containers was within 10.7%. Results: The cell lines were irradiated with a 0.5-4 Gy dose range. The data indicate a very strong differential energy response for electrons around 1 MeV (more lethal) compare to those with lesser or greater energy and a survival rate of at most 10% at very low dose (0.5-2 Gy). Conclusion: Mono-energetic Brachytherapy sources may provide a new pathway for radio-therapy treatment optimizations following a dedicated study showing very unusual high lethality in a specific energy window for MDA321 breast cancer cells.

  10. Comparison of total body irradiation vs chlorambucil and prednisone for remission induction of active chronic lymphocytic leukemia: an ECOG study. Part I: total body irradiation-response and toxicity

    SciTech Connect

    Rubin, P.; Bennent, J.M.; Begg, C.; Bozdech, M.J.; Silber, R.

    1981-12-01

    Twenty-six evaluable patients were entered into two fractionated total body irradiation (TBI) programs; 11 patients received a course of 150 rad TBI (x 3 if tolerated) and 15 patients received a lower dose course of 50 rad (x 3 if tolerated). Complete remissions (CR) were not produced by either course; however, the higher dose course (Plan I) yielded a partial response (PR) rate of 73%, while the lower dose course yielded a PR of 47%. Although fraction size seemed trivial in both TBI plans, an unexpected high degree of hematologic toxicity was encountered, and was parallel to the response rates: in Plan I 73% of patients experienced severe to life-threatening depression of platelets, or granulocytes, whereas in Plan II this rate was 47%. This was of short duration with rapid return of blood counts to normal levels. One death can be attributed to TBI. The chemotherapy arm of the study demonstrated superiority in terms of complete responses. Twenty-three percent of patients treated by cholrambucil and prednisone attained CR, in contrast to 0% of TBI patients. PR for chemotherapy was similar to that obtained with TBI. Chemotherapy also proved superior in terms of overall response rate, number of patients in remission, and in the median duration of response, but not in the median duration of survival. Fractional TBI techniques for active chronic lymphocytic leukemia (CLL) should be interrupted when the platelet count dips below 100,000 and the granulocyte count is lower than 2,000. Future studies should continue TBI radiation therapy and chemotherapy.

  11. Effect of low doses beta irradiation on micromechanical properties of surface layer of injection molded polypropylene composite

    NASA Astrophysics Data System (ADS)

    Manas, David; Manas, Miroslav; Gajzlerova, Lenka; Ovsik, Martin; Kratky, Petr; Senkerik, Vojtěch; Skrobak, Adam; Danek, Michal; Manas, Martin

    2015-09-01

    The influence of beta radiation on the changes in the structure and selected properties (mechanical and thermal) was proved. Using low doses of beta radiation for 25% glass fiber filled polypropylene and its influence on the changes of micromechanical properties of surface layer has not been studied in detail so far. The specimens of 25% glass fiber filled PP were made by injection molding technology and irradiated by low doses of beta radiation (0, 15 and 33 kGy). The changes in the microstructure and micromechanical properties of surface layer were evaluated using FTIR, SEM, WAXS and instrumented microhardness test. The results of the measurements showed considerable increase in micromechanical properties (indentation hardness, indentation elastic modulus) when low doses of beta radiation are used.

  12. Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Yaroslav; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kolb, Bryan; Kovalchuk, Olga

    2016-01-01

    Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way. PMID:27375442

  13. Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior.

    PubMed

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Yaroslav; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kolb, Bryan; Kovalchuk, Olga

    2016-01-01

    Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way.

  14. [Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

    PubMed

    Kojima, Shuji

    2006-10-01

    We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

  15. Loss of albumin and megalin binding to renal cubilin in rats results in albuminuria after total body irradiation.

    PubMed

    Yammani, Raghunatha R; Sharma, Mukut; Seetharam, Shakuntla; Moulder, John E; Dahms, Nancy M; Seetharam, Bellur

    2002-08-01

    The role of the renal apical brush-border membrane (BBM) endocytic receptors cubilin and megalin in the onset of albuminuria in rats exposed to a single dose of total body irradiation (TBI) has been investigated. Albuminuria was evident as immunoblot (IB) analysis of the urine samples from TBI rats revealed excretion of large amounts of albumin. IB analysis of the BBM proteins did not reveal any significant changes in cubilin or megalin levels, but (125)I-albumin binding to BBM from TBI rats declined by 80% with a fivefold decrease (from 0.5 to 2.5 microM) in the affinity for albumin. IB analysis of cubilin from the BBM demonstrated a 75% loss when purified using albumin, but not intrinsic factor (IF)-cobalamin (Cbl) ligand affinity chromatography. Immunoprecipitation (IP) of Triton X-100 extract of the BBM with antiserum to cubilin followed by IB of the immune complex with an antiserum to megalin revealed a 75% loss of association between megalin and cubilin. IP studies with antiserum to cubilin or megalin and IB with antiserum to the cation-independent mannose 6-phosphate/insulin-like growth factor II-receptor (CIMPR) revealed that CIMPR interacted with both cubilin and megalin. In addition, TBI did not disrupt the association of CIMPR with either cubilin or megalin in BBM. These results suggest that albuminuria noted in TBI rats is due to selective loss of albumin and megalin, but not CIMPR or IF-Cbl binding by cubilin. Furthermore, these results also suggest that albumin and IF-Cbl binding to cubilin occur at distinct sites and that in the rat renal BBM, CIMPR interacts with both cubilin and megalin.

  16. Cercopithecine Herpesvirus 9 (Simian Varicella Virus) Infection after Total-Body Irradiation in a Rhesus Macaque (Macaca mulatta).

    PubMed

    Gulani, Jatinder; Koch, Amory; Chappell, Mark G; Christensen, Christine L; Facemire, Paul; Singh, Vijay K; Ossetrova, Natalia I; Srinivasan, Venkataraman; Holt, Rebecca K

    2016-04-01

    This case report describes a rhesus macaque (Macaca mulatta; male; age, 5 y; weight, 6.7 kg) with anorexia, dehydration, lethargy, ataxia, and generalized skin rashes that occurred 30 d after total-body irradiation at 6.5 Gy ((60)Co γ-rays). Physical examination revealed pale mucus membranes, a capillary refill time of 4 s, heart rate of 180 bpm. and respirations at 50 breaths per minute. Diffuse multifocal maculopapulovesicular rashes were present on the body, including mucocutaneous junctions. The CBC analysis revealed a Hct of 48%, RBC count of 6.2 × 10(6)/μL, platelet count of 44 × 10(3)/μL, and WBC count of 25 × 10(3)/μL of WBC. The macaque was euthanized in light of a grave prognosis. Gross examination revealed white foci on the liver, multifocal generalized petechiation on serosal and mucosal surfaces of the gastrointestinal tract, hemorrhagic lymph nodes, and hemorrhagic fluid in the thoracic cavity. Microscopic examination revealed cutaneous vesicular lesions with intranuclear eosinophilic viral inclusions within the epithelial cells, consistent with herpesvirus. Immunohistochemistry was positive for herpesvirus. The serum sample was negative for antibodies against Macacine herpesvirus 1 and Cercopithecine herpesvirus 9 (simian varicella virus, SVV). Samples submitted for PCR-based identification of the etiologic agent confirmed the presence of SVV DNA. PCR analysis, immunohistochemistry, and histology confirmed that lesions were attributed to an active SVV infection in this macaque. This case illustrates the importance of screening for SVV in rhesus macaques, especially those used in studies that involve immunosuppressive procedures.

  17. SU-E-T-404: Simple Field-In-Field Technique for Total Body Irradiation in Large Patients

    SciTech Connect

    Chi, P; Pinnix, C; Dabaja, B; Wang, C; Aristophanous, M; Tung, S

    2014-06-01

    Purpose: A simple Field-in-Field technique for Total Body Irradiation (TBI) was developed for traditional AP/PA TBI treatments to improve dosimetric uniformity in patients with large separation. Methods: TBI at our institution currently utilizes an AP/PA technique at an extended source-to-surface distance (SSD) of 380cm with patients in left decubitus position during the AP beam and in right decubitus during the PA beam. Patients who have differences in thickness (separation) between the abdomen and head greater than 10cm undergo CT simulation in both left and right decubitus treatment positions. One plan for each CT is generated to evaluate dose to patient midline with both AP and PA fields, but only corresponding AP fields will be exported for treatment for patient left decubitus position and PA fields for patient right decubitus position. Subfields are added by collimating with the x-ray jaws according to separation changes at 5–7% steps to minimize hot regions to less than 10%. Finally, the monitor units (MUs) for the plans are verified with hand calculation and water phantom measurements. Results: Dose uniformity (+/−10%) is achieved with field-in-field using only asymmetric jaws. It is dosimetrically robust with respect to minor setup/patient variations inevitable due to patient conditions. MUs calculated with Pinnacle were verified in 3 clinical cases and only a 2% difference was found compared to homogeneous calculation. In-vivo dosimeters were also used to verify doses received by each patient with and confirmed dose variations less than 10%. Conclusion: We encountered several cases with separation differences that raised uniformity concerns — based on a 1% dose difference per cm separation difference assumption. This could Resultin an unintended hot spot, often in the head/neck, up to 25%. This method allows dose modulation without adding treatment complexity nor introducing radiobiological variations, providing a reasonable solution for this unique

  18. Impact of total body irradiation on successful neutrophil engraftment in unrelated bone marrow or cord blood transplantation.

    PubMed

    Nakasone, Hideki; Fuji, Shigeo; Yakushijin, Kimikazu; Onizuka, Makoto; Shinohara, Akihito; Ohashi, Kazuteru; Miyamura, Koichi; Uchida, Naoyuki; Takanashi, Minoko; Ichinohe, Tatsuo; Atsuta, Yoshiko; Fukuda, Takahiro; Ogata, Masao

    2017-02-01

    Total body irradiation (TBI) has been thought to promote donor cell engraftment in allogeneic hematopoietic cell transplantation (HCT) from alternative donors. However, recent progress in HCT strategies may affect the clinical significance of TBI on neutrophil engraftment. With the use of a Japanese transplant registry database, we analyzed 3933 adult recipients (>15 y.o.) who underwent HCT between 2006 and 2013 from an 8/8 HLA-matched unrelated bone marrow donor (MUD, n = 1367), an HLA-mismatched unrelated bone marrow donor (MMUD, n = 1102), or unrelated cord blood (CBT, n = 1464). Conditioning regimens were divided into five groups: High-TBI-(>8Gy), Low-TBI- (≤8Gy), and no-TBI-myeloablative conditioning (MAC), and Low-TBI- and no-TBI-reduced-intensity conditioning (RIC). In both MUD and MMUD, neutrophil engraftment rate was >90% in each of the five conditioning groups, and TBI was not associated with prompt neutrophil engraftment in multivariate analyses. Conversely, in CBT, TBI regimens had a higher rate of day-30 neutrophil engraftment than no-TBI-regimens: 78% in High-TBI-MAC, 83% in Low-TBI-MAC, and 76% in Low-TBI-RIC versus 65% in No-TBI-MAC, and 68% in No-TBI-RIC (P < .001). Multivariate analyses in CBT demonstrated that TBI-regimens were significantly associated with a higher rate of neutrophil engraftment. Subsequently focusing on CBT patients alone, TBI-regimens were significantly associated with a higher rate of neutrophil engraftment in patients who received CBT with a 4/6 or less HLA allele-match, or who had anti-HLA antibodies. In summary, TBI-regimens had no impact on neutrophil engraftment in the current practice of unrelated bone marrow transplantation. However, in CBT, TBI is still necessary to enhance engraftment.

  19. The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplant for Patients with Acute Leukemia

    PubMed Central

    Holter-Chakrabarty, Jennifer L.; Pierson, Namali; Zhang, Mei-Jie; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud D.; Artz, Andrew S.; Baron, Frédéric; Bredeson, Christopher N.; Dvorak, Christopher C.; Epstein, Robert B.; Lazarus, Hillard M.; Olsson, Richard F.; Selby, George B.; Williams, Kirsten M.; Cooke, Kenneth R.; Pasquini, Marcelo C.; McCarthy, Philip L.

    2015-01-01

    Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI N=948, TBICy N=821) recipients of related or unrelated hematopoietic cell transplantation (HCT) who received TBI (1200-1500cGY) for acute leukemia from 2003 to 2010. The two cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Ph+ ALL, HLA matched siblings, stem cell source, anti-thymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect TRM (24% vs. 23% at 3y, p=0.67; relative risk [RR] 1.01, p=0.91), leukemia relapse (27% vs. 29% at 3y, p=0.34; RR 0.89, p=0.18), leukemia-free survival (49% vs. 48% at3y, p=0.27; RR 0.93, p=0.29), chronic GVHD (45% vs. 47% at 1y, p=0.39; RR 0.9, p=0.11) or overall survival (53% vs. 52% at 3y, p=0.62; RR 0.96, p=0.57) for CyTBI and TBICy respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (p=0.08). This study demonstrates that the sequence of Cy and TBI does not impact transplant outcomes and complications in patients with acute leukemia undergoing HCT with myeloablative conditioning. PMID:25840335

  20. Relapse after allogeneic bone marrow transplantation for refractory anemia is increased by shielding lungs and liver during total body irradiation.

    PubMed

    Anderson, J E; Appelbaum, F R; Schoch, G; Barnett, T; Chauncey, T R; Flowers, M E; Storb, R

    2001-01-01

    Patients with the refractory anemia (RA) subtype of myelodysplastic syndrome who undergo allogeneic bone marrow transplantation (BMT) have a low risk of relapse, but they have a high risk of nonrelapse mortality when prepared with conventional preparative regimens. To try to reduce nonrelapse mortality, we treated 14 RA patients with a modified approach to total body irradiation (TBI) followed by cyclophosphamide (CY) and HLA-identical sibling BMT. Median patient age was 44 years (range, 28 to 65 years). Patients received TBI with shielding of the right lobe of the liver and both lungs followed by electron beam boosts to shielded ribs. Total radiation exposure in nonshielded areas was 12 Gy (n = 10), 10 Gy (n = 3), or 6 Gy (n = 1). After TBI, patients received CY at 120 mg/kg over 2 days, followed by transplantation of unmanipulated bone marrow. All patients initially achieved engraftment with donor cells, although 2 patients had subsequent reemergence of host hematopoiesis without evidence of disease relapse. Five patients died of transplantation-related causes between 22 and 1262 days post-BMT. Four patients relapsed between 157 and 1096 days post-BMT. These 14 patients were compared with 46 historical controls with RA who received conventional CY/TBI or busulfan/CY preparative regimens. Patients in the experimental group had a similar nonrelapse mortality rate compared with the historical control group (29% versus 37%, respectively; P = .8), but a higher relapse rate (34% versus 2%, P = .0004) and a lower disease-free survival (38% versus 61%, P = .16). We conclude that this modified TBI approach is associated with an unacceptably high risk of relapse for patients with RA undergoing BMT.

  1. Interleukin 1 alpha stimulates hemopoiesis but not tumor cell proliferation and protects mice from lethal total body irradiation

    SciTech Connect

    Constine, L.S.; Harwell, S.; Keng, P.; Lee, F.; Rubin, P.; Siemann, D. )

    1991-03-01

    Interleukin 1 alpha (IL-1) is a polypeptide/glycoprotein growth factor with multiple functions including the modulation of hematopoietic cell proliferation and differentiation. In vivo studies were performed with C57BL/6J mice injected with 0, 0.2, or 2.0 micrograms of IL-1 24 hr before or after lethal total body irradiation (TBI) (9.5 Gy). More mice in the groups administered IL-1 before TBI survived (90% of the 2.0 micrograms group) than those treated 2 or 24 hr after TBI, which was still slightly superior to the uninjected group, which all died within 15 days (p = .0001). Proliferation of bone marrow granulocyte/macrophage colonies following split dose TBI was also greatest for mouse groups treated with IL-1 prior to TBI. These experiments support data from other investigators that IL-1 stimulation of BM is related to IL-1 timing with respect to TBI. Stimulation of hemopoiesis was also assessed in terms of changes in peripheral blood and BM cell numbers and cell cycle kinetics using an electronic particle counter and flow cytometric techniques. Mice injected with 2 micrograms of IL-1 showed an initial decline (at 3-6 hr) and then a selective proliferation (24-48 hr) of early and more committed progenitor cells to 125% and 200% of control values, respectively. Peripheral blood counts rose accordingly. Cells in S and G2/M phases increased over 10 hr and then declined in number. It thus appeared that some synchronization of cell cycling occurred, which might place cells in a more radioresistant phase of the cell cycle. The glutathione (GSH) content and synthesis in BM cells were measured by isocratic paired-ion high performance liquid chromatography and 35S-labelled cysteine incorporation into the GSH tripeptide. An increase in cellular GSH content and synthesis was demonstrated following IL-1 which lasted 24 hr.

  2. Dosimetric Study and Verification of Total Body Irradiation Using Helical Tomotherapy and its Comparison to Extended SSD Technique

    SciTech Connect

    Zhuang, Audrey H.; Liu An; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

    2010-01-01

    The American College of Radiology practice guideline for total body irradiation (TBI) requires a back-up treatment delivery system. This study investigates the development of helical tomotherapy (HT) for delivering TBI and compares it with conventional extended source-to-surface distance (X-SSD) technique. Four patients' head-to-thigh computed tomographic images were used in this study, with the target defined as the body volume without the left and right lungs. HT treatment plans with the standard TBI prescription (1.2 Gy/fx, 10 fractions) were generated and verified on phantoms. To compare HT plans with X-SSD treatment, the dose distribution of X-SSD technique was simulated using the Eclipse software. The average dose received by 90% of the target volume was 12.3 Gy (range, 12.2-12.4 Gy) for HT plans and 10.3 Gy (range, 10.08-10.58 Gy) for X-SSD plans (p < 0.001). The left and right lung median doses were 5.44 Gy and 5.40 Gy, respectively, for HT plans and 8.34 Gy and 8.95 Gy, respectively, for X-SSD treatment. The treatment planning time was comparable between the two methods. The beam delivery time of HT treatment was longer than X-SSD treatment. In conclusion, HT-based TBI plans have better dose coverage to the target and better dose sparing to the lungs compared with X-SSD technique, which applies dose compensators, lung blocks, and electron boosts. This study demonstrates that HT is possible for delivering TBI. Clinical validation of the feasibility of this approach would be of interest in the future.

  3. p38 MAPK Inhibitor Insufficiently Attenuates HSC Senescence Administered Long-Term after 6 Gy Total Body Irradiation in Mice.

    PubMed

    Lu, Lu; Wang, Yue-Ying; Zhang, Jun-Ling; Li, De-Guan; Meng, Ai-Min

    2016-06-08

    Senescent hematopoietic stem cells (HSCs) accumulate with age and exposure to stress, such as total-body irradiation (TBI), which may cause long-term myelosuppression in the clinic. However, the methods available for long-term myelosuppression remain limited. Previous studies have demonstrated that sustained p38 mitogen-activated protein kinases (p38 MAPK) activation in HSCs following exposure to TBI in mice and the administration of its inhibitor twenty-four hours after TBI may partially prevent long-term myelosuppression. However, long-term myelosuppression is latent and identified long after the administration of radiation. In this study, we investigated the effects of SB203580 (a small molecule inhibitor of p38 MAPK) on long-term myelosuppression induced by TBI. Mice with hematopoietic injury were injected intraperitoneally with SB203580 every other day five times beginning 70 days after 6 Gy of (137)Cs γ ray TBI. Our results at 80 days demonstrated that SB203580 did not significantly improve the TBI-induced long-term reduction of peripheral blood cell and bone marrow nucleated cell (BMNC) counts, or defects in hematopoietic progenitor cells (HPCs) and HSC clonogenic function. SB203580 reduced reactive oxygen species (ROS) production and p-p38 expression; however, SB203580 had no effect on p16 expression in the HSCs of mice. In conclusion, these findings suggest that treatment with SB203580 70 days after TBI in mice inhibits the ROS-p38 oxidative stress pathway; however, it has no therapeutic effect on long-term myelosuppression induced by TBI.

  4. Does Total Body Irradiation Conditioning Improve Outcomes of Myeloablative HLA-Identical Sibling Transplants for Chronic Lymphocytic Leukemia?

    PubMed Central

    Sabloff, Mitchell; Sobecks, Ronald M.; Ahn, Kwang Woo; Zhu, Xiaochun; de Lima, Marcos; Brown, Jennifer R.; Inamoto, Yoshihiro; Holland, H. Kent; Aljurf, Mahmoud D.; Laughlin, Mary J.; Kamble, Rammurti T.; Hsu, Jack W.; Wirk, Baldeep M.; Seftel, Matthew; Lewis, Ian D.; Arora, Mukta; Alyea, Edwin P.; Kalaycio, Matt E.; Cortes, Jorge; Maziarz, Richard T.; Gale, Robert Peter; Saber, Wael

    2014-01-01

    An allogeneic hematopoietic cell transplant (HCT) from an HLA-identical donor after high-dose (myeloablative) pre-transplant conditioning, is an effective therapy for some people with chronic lymphocytic leukemia (CLL). Because CLL is a highly radiosensitive cancer, we hypothesized total body irradiation (TBI) conditioning regimens may be associated with better outcomes than those without TBI. To answer this we analyzed data from 180 subjects with CLL receiving myeloablative doses of TBI (N=126) or not (N=54), transplanted from an HLA-identical sibling donor, between 1995 and 2007 and reported to the Center for International Blood & Marrow Transplant Research (CIBMTR). At 5 years, treatment-related mortality was 48% (95% CI, 39–57%) vs. 50% (95% CI, 36–64%); p=NS. Relapse rates were 17% (95% CI, 11–25%) vs. 22% (95% CI, 11–35%); p=NS. Five-year progression-free survival and overall survival was 34% (95% CI, 26–43%) vs. 28% (95% CI, 15–42%); p=NS and 42% (95% CI, 33–51%) vs. 33% (95% CI, 19–48%); p=NS, respectively. The single most common cause of death in both cohorts was recurrent/progressive CLL. No variable tested in the multivariate analysis was found to significantly affect these outcomes including having failed fludarabine. Within the limitations of this study we found no difference in HLA-identical sibling transplant outcomes between myeloablative TBI and chemotherapy pre-transplant conditioning in persons with CLL. PMID:24321745

  5. Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age.

    PubMed

    Davis, N L; Stewart, C E; Moss, A D; Woltersdorf, W W W; Hunt, L P; Elson, R A; Cornish, J M; Stevens, M C G; Crowne, E C

    2015-10-01

    Bone marrow transplantation with total body irradiation (BMT/TBI) has adverse effects on growth, growth hormone status and adiposity. We investigated the GH-IGF-I axis in relation to adiposity. Cross-sectional case control study. BMT/TBI survivors (n = 22) and short stature control participants (n = 19), all GH-naïve or off GH treatment >3 months. Auxology, DEXA scans and GH-IGF-I axis investigation: (i) 12-h overnight GH profiles; (ii) insulin tolerance test (ITT); and (iii) IGF-I generation test. auto-deconvolution of GH profile data and comparison of quantitative parameters using ANOVA. Eighty-two percent of BMT/TBI survivors had growth hormone deficiency (GHD) using ITT. GH profile area-under-the-curve (GH-AUC) was reduced in BMT/TBI survivors vs short stature control participants [geometric mean (range) 209 (21-825) vs 428 (64-1400) mcg/l/12 h, respectively, P = 0·007]. GHD was more marked in those who had additional cranial irradiation (CRT) [ITT peak 1·4 (0·2-3·0) vs TBI only 4·1 (1·1-14·8) mcg/l, P = 0·036]. GHD was more marked at the end of growth in BMT/TBI survivors vs short stature control participants (GH-AUC 551 (64-2474) vs 1369 (192-4197) mcg/l/12 h, respectively, P = 0·011) and more prevalent (9/11 vs 1/9, respectively, P = 0·005). GH profile data were consistent with ITT results in 80% of participants. IGF-I generation tests were normal. BMT/TBI survivors still demonstrated lower GH levels after adjustment for adiposity (fat-adjusted mean difference for GH-AUC 90·9 mcg/l/12 h, P = 0·025). GHD was more prevalent in BMT/TBI survivors than expected for the CRT dose in TBI, worsened with time and persisted into adulthood. GHD could not be explained by adiposity. There was no evidence of GH neurosecretory dysfunction or resistance after BMT/TBI. © 2015 John Wiley & Sons Ltd.

  6. Activation of de novo GSH synthesis pathway in mouse spleen after long term low-dose γ-ray irradiation.

    PubMed

    Lee, E K; Kim, J A; Kim, J S; Park, S J; Heo, K; Yang, K M; Son, T G

    2013-02-01

    Glutathione (GSH) is an important cellular antioxidant and has a critical role in maintaining the balance of cellular redox. In this study, we investigated the GSH biosynthesis genes involved in the elevation of endogenous GSH levels using an irradiation system with an irradiation dose rate of 1.78 mGy/h, which was about 40,000 times less than the dose rates used in other studies. The results showed that GSH levels were significantly increased in the low-dose (0.02 and 0.2 Gy) irradiated group compared to those in the non-irradiated group, but enzymatic antioxidants such as superoxide dismutase and catalase were not induced at any doses tested. The elevation in GSH was accompanied by elevated expression of glutamate-cysteine ligase modifier subunit, but no changes were observed in the expression of glutamate-cysteine ligase catalytic subunit and thioredoxin in de novo GSH synthesis. In the case of genes involved in the GSH regeneration cycle, the expression of glutathione reductase was not changed after irradiation, whereas glutathione peroxidase was only increased in the 0.2 Gy irradiated group. Collectively, our results suggest that the de novo pathway, rather than the regeneration cycle, may be mainly switched on in response to stimulation with long-term low-dose radiation in the spleen.

  7. Effects of low-dose γ-irradiation on the counts of immunocompetent cells in a model experiment on primates.

    PubMed

    Ignatova, I E; Agrba, V Z; Lapin, B A

    2010-12-01

    Cellular immunity was studied by flow cytometry with Becton Dickinson monoclonal antibodies in clinically healthy Macaca mulatta males before and after low-dose exposure to ionizing radiation. It was shown that T and B cells are radiosensitive, B cells being more sensitive, which is seen from a significant drop of their count. Natural killers are radioresistant. The count of immunocompetent cells recovers sooner after single compared to fractionated irradiation in the same summary dose.

  8. Effect of Low Dose Gamma Irradiation together with Lipid A on Human Leukocytes Activities In Vitro

    NASA Astrophysics Data System (ADS)

    Belyakova, E.; Dubnickova, M.; Boreyko, A.

    2010-01-01

    The influence of gamma irradiation and of Lipid A from Escherichia coli on phagocytosis, lyzosyme and peroxidase activities of human leukocytes, in vitro was investigated. Leukocytes samples were irradiated with 1 and 5 Gy, respectively. The number of irradiated leukocytes was decreased in the irradiated samples. Only samples with additive Lipid A were not damaged by irradiation. The Lipid A had positive influence on biological activities of the irradiated leukocytes.

  9. Anti-apoptotic and antioxidant effects of low dose gamma irradiation against diabetes-induced brain injury in rats.

    PubMed

    Rashed, Engy R; El-Daly, Menna A; Abd-Elhalim, Sawsan A; El-Ghazaly, Mona A

    2016-11-01

    The current study aimed to investigate the effect of different low doses of gamma irradiation on hyperglycemia-induced brain injury. The aim was further extended to investigate the sub-chronic effect of low dose radiation on the neuronal damage induced by diabetes. To induce diabetes, male albino rats were injected with dexamethasone (10 mg/kg/day, for 9 successive days, subcutaneously). Different diabetic groups were irradiated with 0.1, 0.25 and 0.5 Gy. The effect of low dose gamma irradiation on the hyperglycemia-induced brain damage based was analyzed at two levels: oxidative stress and apoptosis. The brain contents of glutathione, malondialdhyde and total nitrate/nitrite were measured to assess the oxidative stress. In order to evaluate the extent of the apoptotic changes in brain, tissue caspase-3 expression was detected using immunohistochemistry and the degree of DNA fragmentation was estimated. Moreover, brain tissues were examined using light microscopy to evaluate the histological changes in different groups and serum lactate dehydrogenase activity was determined as an indicator for the brain tissue damage. Results indicated that exposure to 0.5 Gy ameliorated the hyperglycemia and subsequently inhibited oxidative stress and apoptosis. Radiation exposure at this dose level also increased the survival rate of diabetic animals.

  10. Low doses of gamma-irradiation induce an early bystander effect in zebrafish cells which is sufficient to radioprotect cells.

    PubMed

    Pereira, Sandrine; Malard, Véronique; Ravanat, Jean-Luc; Davin, Anne-Hélène; Armengaud, Jean; Foray, Nicolas; Adam-Guillermin, Christelle

    2014-01-01

    The term "bystander effect" is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01-0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of γ-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less γ-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less γ-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors.

  11. Low dose irradiation profoundly affects transcriptome and microRNAme in rat mammary gland tissues

    PubMed Central

    Luzhna, Lidia; Kovalchuk, Olga

    2014-01-01

    Ionizing radiation has been successfully used in medical tests and treatment therapies for a variety of medical conditions. However, patients and health-care workers are greatly concerned about overexposure to medical ionizing radiation and possible cancer induction due to frequent mammographies and/or CT scans. Diagnostic imaging involves the use of low doses of ionizing radiation, and its potential carcinogenic role creates a cancer risk concern for exposed individuals. In this study, the effects of X-ray exposure of different doses on the gene expression patterns and the micro-RNA expression patterns in normal breast tissue were investigated in rats. Our results revealed the activation of immune response pathways upon low dose of radiation exposure. These included natural killer mediated cytotoxicity pathways, antigen processing and presentation pathways, chemokine signaling pathways, and T- and B-cell receptor signaling pathways. Both high and low doses of radiation led to miRNA expression alterations. Increased expression of miR-34a may be linked to cell cycle arrest and apoptosis. Up-regulation of miR-34a was correlated with down-regulation of its target E2F3 and up-regulation of p53. This data suggests that ionizing radiation at specific high and low doses leads to cell cycle arrest and a possible initiation of apoptosis. PMID:25594002

  12. Low-dose gamma irradiation enhances superoxide anion production by nonirradiated cells through TGF-β1-dependent bystander signaling.

    PubMed

    Temme, Jennifer; Bauer, Georg

    2013-04-01

    We show here that low-dose gamma irradiation substantially increase in extracellular superoxide anion production in oncogenically transformed cells and tumor cells but not by nontransformed cells. The transfer of only a few cells from an irradiated culture to nonirradiated control cells was sufficient for the transmission of a signal to induce superoxide anion production in the nonirradiated cells. The number of irradiated cells that was necessary for the successful induction of superoxide anion production in the nonirradiated cells depended on radiation dose. When irradiated cells were allowed to incubate for 1 h before transmission to the nonirradiated cultures, nearly all of the cells from the irradiated cell population were able to communicate the inducing signal to nonirradiated cells. siRNA-dependent knockdown and reconstitution experiments showed that TGF-β1 was sufficient to mediate the bystander effect triggered by low-dose radiation in this experimental system. A kinetic analysis demonstrated that the enhanced superoxide anion production was substantially reduced before the release of the bystander signal by activated TGF-β.

  13. Effect of low-dose irradiation on structural and mechanical properties of hyaline cartilage-like fibrocartilage.

    PubMed

    Öncan, Tevfik; Demirağ, Burak; Ermutlu, Cenk; Yalçinkaya, Ulviye; Özkan, Lütfü

    2013-01-01

    The aim of this study was to analyze the effect of low-dose irradiation on fibrous cartilage and to obtain a hyaline cartilage-like fibrocartilage (HCLF) with similar structural and mechanical properties to hyaline cartilage. An osteochondral defect was created in 40 knees of 20 rabbits. At the 7th postoperative day, a single knee of each rabbit was irradiated with a total dose of 5.0 Gy in 1.0 Gy fractions for 5 days (radiotherapy group), while the other knee was not irradiated (control group). Rabbits were then divided into four groups of 5 rabbits each. The first three groups were sacrificed at the 4th, 8th and the 12th postoperative weeks and cartilage defects were macroscopically and microscopically evaluated. The remaining group of 5 rabbits was sacrificed at the 12th week and biomechanical compression tests were performed on the cartilage defects. There was no significant biomechanical difference between the radiotherapy and the control group (p=0.686). There was no significant macroscopic and microscopic difference between groups (p=0.300). Chondrocyte clustering was observed in the irradiated group. Low-dose irradiation does not affect the mechanical properties of HCLF in vivo. However, structural changes such as chondrocyte clustering were observed.

  14. Low-dose UVB irradiation prevents MMP2-induced skin hyperplasia by inhibiting inflammation and ROS.

    PubMed

    Dang, Lin; Wang, Yan; Xue, Yadong; He, Lei; Li, Yuzhen; Xiong, Jikui

    2015-09-01

    Skin cancer is one of the most common types of malignancy in the world. UV radiation is known as the primary environmental carcinogen responsible for skin cancer development. However, UV radiation is a ubiquitous substance existing in the environment and the physiological effect of UV radiation is consistently ignored. Therefore, in the present study, the physiological effect of UV radiation on inhibition of skin cancer was investigated. Normal mouse skin was processing by no pre-radiation or pre-radiation of low-dose UV before a medium or high dose of UV radiation. We found that the low-dose pre-radiated mouse skin tissue exhibited low skin inflammation, skin ROS production and consequently low skin epithelial hyperplasia after the medium-dose UV radiation compared with the no pre-radiated mouse. However, this inhibition was not indicated in the high-dose UV radiation group after low-dose pre-radiation. Furthermore, western blot analysis and gelatin zymography showed low expression and activation of MMP2 in the skin tissues processed following medium-dose radiation, but not in tissues treated with high-dose radiation after a low-dose pre-radiation. Further investigation of MMP2 inhibitors of TIMP2/TIMP4 showed an upregulated TIMP2 expression, but not TIMP4. Collectively, these data indicate that low-dose pre-radiation attenuates the skin inflammation and ROS production induced by medium-dose UV radiation and also elevates TIMP2 to withstand MMP2, therefore suppressing skin hyperplasia. The present study indicates a novel concept or prophylactic function of moderate UV radiation as a preventative strategy.

  15. SU-E-T-260: Pediatric Total Body Irradiation Calculations and In-Vivo Dosimetry Using Diodes and OSLD's

    SciTech Connect

    Chungbin, S; Fatyga, M

    2014-06-01

    Purpose: To verify that a photon total body irradiation (TBI) calculation method scales properly from adult to pediatric dimensions and to determine TBI in-vivo dosimetry correction factors for diodes and optically stimulated luminescent dosimeters (OSLD's). Methods: TBI technique used is 400 SAD 18 MV opposed laterals with beam spoiler. Water bags are used to supplement narrower lateral dimensions for patient treatments. To verify that dose calculations scale properly with decreasing dimensions, CAX doses were measured and compared to calculations for different rectangular phantom geometries: (L=length(cm), H=height(cm), d=depth(cm)): L(30)xH(30) (d=3-25), L(30)xH(12)(d=2–20), L(13)xH(13) (d=5–13), L(30)x(H=10–40) d=15, L(30–150) x H(10) (d=15). In infant geometry, measured off axis “leg” dose (L(30)xH(2.5–10.6), d=7)) was compared to CAX (“body” L(30)xH(10)(d=7) adjacent to “leg”). Entrance and exit doses were measured with surface diodes, diodes with buildup, OSLD's, as well as ion chambers for comparison. Correction factors ((ion chamber CAX dose)/(in vivo dose)) were calculated for surface diodes, diodes with buildup, OSLD's, and ion chamber. Results: All rectangular phantom measurements agree with calculated within 2.5%. For L(30)xH(30), L(30)xH(12), L(13)xH(13), L(30)x(H=10–40) and L(30–80)xH(10) agreement was within 1%. For the infant geometry, the ratio of leg dose to CAX varies from 0.956 (h=2.5) to 0.995 (h=10.6). The range of in-vivo dosimetry entrance+exit to CAX dose correction factors varied by dosimeter (diode: 0.883–1.015, surface diode: 1.008–1.214, ion chamber: 0.924–1.084, OSLD: 0.920–1.106). Conclusion: TBI calculations scaled properly to pediatric dimensions. In-vivo dosimetry with various detectors demonstrated similar trends with different magnitudes. OSLD measurements agreed well with ion chamber measurements.

  16. Effect of recombinant canine granulocyte-macrophage colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation.

    PubMed

    Nash, R A; Schuening, F G; Seidel, K; Appelbaum, F R; Boone, T; Deeg, H J; Graham, T C; Hackman, R; Sullivan-Pepe, M; Storb, R

    1994-04-01

    Recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF) was studied in normal dogs and in dogs receiving otherwise lethal total body irradiation (TBI) without marrow transplant. Five normal dogs receiving 25 micrograms/kg of rcGM-CSF by subcutaneous (SC) injection twice daily (BID) for 14 days showed increases in peripheral blood neutrophil counts of three to five times the baseline. Platelet counts decreased during administration of rcGM-CSF to a mean nadir of 52,800. Ten dogs received 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow graft. Within 2 hours of TBI, rcGM-CSF was begun at a dose of 50 micrograms/kg SC BID for 5 doses and then continued at 25 micrograms/kg SC BID for 21 days. Only 1 of the 10 dogs receiving rcGM-CSF survived with complete and sustained recovery of hematopoiesis. One of 13 historical control dogs survived after 400 cGy with no hematopoietic growth factor or marrow infusion. Results with rcGM-CSF were compared with previous and concurrent data with G-CSF studied in the same model. Of 10 dogs receiving G-CSF, 8 survived with complete and sustained hematopoietic recovery, a significantly better survival than that seen with rcGM-CSF (P = .006). Neutrophil counts were sustained at higher levels after TBI for the first 18 days in the G-CSF group (P < .016) and the neutrophil nadirs were higher. No differences in neutrophil nadirs were noted between the rcGM-CSF and control groups. Dogs treated with rcGM-CSF experienced a more rapid decline of platelet counts than G-CSF-treated or control dogs over the first 18 days (P < .001). The nadir of the platelet count was higher in the control group than in either the G-CSF or rcGM-CSF group and no significant difference was observed between the G-CSF and rcGM-CSF groups. After otherwise lethal TBI (400 cGy) in dogs, rcGM-CSF was not effective in promoting hematopoietic recovery or improving survival.

  17. SU-E-T-748: Theoretical Investigation On Using High Energy Proton Beam for Total-Body-Irradiation

    SciTech Connect

    Zhang, M; Zou, J; Chen, T; Yue, N

    2015-06-15

    Purpose: The broad-slow-rising entrance dose region proximal to the Bragg peak made by a mono-energetic proton beam could potentially be used for total body irradiation (TBI). Due to the quasi-uniform dose deposition, customized thickness compensation may not be required to deliver a uniform dose to patients with varied thickness. We investigated the possibility, efficacy, and hardware requirement to use such proton beam for TBI. Methods: A wedge shaped water phantom with thickness varying from 2 cm to 40 cm was designed to mimic a patient. Geant4 based Monte Carlo code was used to simulate broad mono-energetic proton beams with energy ranging from 250 MeV to 300 MeV radiating the phantom. A 6 MV photon with 1 cm water equivalent build-up used for conventional TBI was also calculated. A paired-opposing beam arrangement with no thickness compensation was used to generate TBI plans for all beam energies. Dose from all particles were scored on a grid size of 2 mm{sup 3}. Dose uniformity across the phantom was calculated to evaluate the plan. The field size limit and the dose uniformity of Mevion S250 proton system was examined by using radiochromic films placed at extended treatment distance with the open large applicator and 90° gantry angle. Results: To achieve a maximum ± 7.5% dose variation, the largest patient thickness variation allowed for 250 MeV, 275 MeV, and 300 MeV proton beams were 27.0 cm, 34.9 cm and 36.7 cm. The value for 6 MV photon beam was only 8.0 cm to achieve the same dose variation. With open gantry, Mevion S250 system allows 5 m source-to-surface distance producing an expected 70 cm{sup 2} field size. Conclusion: Energetic proton beam can potentially be used to deliver TBI. Treatment planning and delivery would be much simple since no thickness compensation is required to achieve a uniform dose distribution.

  18. Thermal Conductivity Degradation and Microstructural Damage Characterization in Low-Dose Ion Beam-Irradiated 3C-SiC

    NASA Astrophysics Data System (ADS)

    Chauhan, Vinay S.; Riyad, M. Faisal; Du, Xinpeng; Wei, Changdong; Tyburska-Püschel, Beata; Zhao, Ji-Cheng; Khafizov, Marat

    2017-04-01

    This study assesses the impact of low-dose and low-temperature irradiation on the properties of cubic silicon carbide (3C-SiC). 3C-SiC was irradiated with Kr ions to different fluences at 420 K (147 °C). Raman spectroscopy was used to investigate the impact of irradiation-induced defects on vibrational modes and time-domain thermoreflectance (TDTR) was used to measure thermal conductivity. We observe a noticeable reduction in thermal conductivity with increasing fluence. Analysis of Raman spectra reveals the longitudinal optical (LO) and transverse optical (TO) modes with noticeable peak broadening of LO mode with increasing dosage. We also notice a decrease of ratio of peak intensities of LO and TO modes in irradiated samples. We observe a correlation between the thermal conductivity reduction and the decrease in the peak intensity ratio and attribute this to the accumulation of charged vacancy defects.

  19. Low-dose irradiation improves microbial quality and shelf life of fresh mint (Mentha piperita L.) without compromising visual quality.

    PubMed

    Hsu, Wei-Yea; Simonne, Amarat; Jitareerat, Pongphen; Marshall, Maurice R

    2010-05-01

    The effects of low-dose irradiation (0.25 to 2 kGy) and postirradiation storage (at 4 degrees C) on microbial and visual quality, color values (L*, a*, b*, chroma, and hue [ degrees ]), and chlorophyll content (Chl a, Chl b, and total Chl) of fresh mint were evaluated. Samples inoculated with E. coli O157:H7, Salmonella, and MS2 bacteriophage were irradiated and evaluated. E. coli O157:H7 and Salmonella populations were reduced by 2 to 2.4, 3.5, and 5.8 log CFU/g, respectively, 1 d after treatment with 0.25, 0.60, and 1 kGy, respectively, and were completely eliminated at 2 kGy. None of the irradiation doses (P < 0.0001) reduced MS2 bacteriophage populations by more than 0.60 log PFU/g. Irradiation doses did not affect visual quality and samples remained of excellent to good quality (score 7.75 to 9) for up to 9 d of storage. Irradiation at 0.60, 1, and 2 kGy increased (P < 0.0001) Chl a, Chl b, and total Chl. Both total Chl and Chl a decreased significantly after 3 d of storage. Significant decreases in Chl b were not observed until day 12 of storage. Color values (L*, b*, and chroma) were not significantly different until day 6 of storage and hue ( degrees ) remained unchanged (179 degrees ) for the entire storage period of 12 d. Overall, irradiation did not change L*, a*, b*, or chroma. These results demonstrate that irradiation of fresh mint at 2 kGy has the potential to improve its microbial quality and extend its shelf life without compromising its visual quality and color. Mints and other raw fresh herbs are widely used for flavoring as well as garnish in a variety of dishes without further cooking. However, mint is one considered as one of the high-risk herbs when it comes to microbial contamination. We have evaluated the use of gamma irradiation treatment at very low doses ranging from 0 to 2 kGy to eliminate seeded Salmonella spp, E. coli O157:H7, and MS2 bacteriophage, a surrogate of hepatitis A virus. We found that low-dose irradiation (1.0 to 2.0 k

  20. Adjustment function among antioxidant substances in acatalasemic mouse brain and its enhancement by low-dose X-ray irradiation.

    PubMed

    Yamaoka, Kiyonori; Nomura, Takaharu; Wang, Da-Hong; Mori, Shuji; Taguchi, Takehito; Ishikawa, Tetsuya; Hanamoto, Katsumi; Kira, Shohei

    2002-01-01

    The catalase activities in blood and organs of the acatalasemic (C3H/AnLCsbCsb) mouse of the C3H strain are lower than those of the normal (C3H/AnLCsaCsa) mouse. We conducted a study to examine changes in the activities of antioxidant enzymes, such as catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), the total gluathione content, and the lipid peroxide level in the brain, which is more sensitive to oxidative stress than other organs, at 3, 6, or 24 hr following X-ray irradiation at doses of 0.25, 0.5, or 5.0 Gy to the acatalasemic and the normal mice. No significant change in the lipid peroxide level in the acatalasemic mouse brain was seen under non-irradiation conditions. However, the acatalasemic mouse brain was more damaged than the normal mouse brain by excessive oxygen stress, such as a high-dose (5.0 Gy) X-ray. On the other hand, we found that, unlike 5.0 Gy X-ray, a relatively low-dose (0.5 Gy) irradiation specifically increased the activities of both catalase and GPX in the acatalasemic mouse brain making the activities closer to those in the normal mouse brain. These findings may indicate that the free radical reaction induced by the lack of catalase is more properly neutralized by low dose irradiation.

  1. Jeju ground water containing vanadium induced immune activation on splenocytes of low dose γ-rays-irradiated mice.

    PubMed

    Ha, Danbee; Joo, Haejin; Ahn, Ginnae; Kim, Min Ju; Bing, So Jin; An, Subin; Kim, Hyunki; Kang, Kyung-goo; Lim, Yoon-Kyu; Jee, Youngheun

    2012-06-01

    Vanadium, an essential micronutrient, has been implicated in controlling diabetes and carcinogenesis and in impeding reactive oxygen species (ROS) generation. γ-ray irradiation triggers DNA damage by inducing ROS production and causes diminution in radiosensitive immunocytes. In this study, we elucidate the immune activation capacities of Jeju water containing vanadium on immunosuppression caused by γ-ray irradiation, and identify its mechanism using various low doses of NaVO(3). We examined the intracellular ROS generation, DNA damage, cell proliferation, population of splenocytes, and cytokine/antibody profiles in irradiated mice drinking Jeju water for 180 days and in non-irradiated and in irradiated splenocytes both of which were treated with NaVO(3). Both Jeju water and 0.245 μM NaVO(3) attenuated the intracellular ROS generation and DNA damage in splenocytes against γ-ray irradiation. Splenocytes were significantly proliferated by the long-term intake of Jeju water and by 0.245 μM NaVO(3) treatment, and the expansion of B cells accounted for the increased number of splenocytes. Also, 0.245 μM NaVO(3) treatment showed the potency to amplify the production of IFN-γ and total IgG in irradiated splenocytes, which correlated with the expansion of B cells. Collectively, Jeju water containing vanadium possesses the immune activation property against damages caused by γ-irradiation.

  2. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    SciTech Connect

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  3. Low-Dose Gamma Irradiation of Decellularized Heart Valves Results in Tissue Injury in Vitro and in Vivo

    PubMed Central

    Helder, Meghana R. K.; Hennessy, Ryan S.; Spoon, Daniel B.; Tefft, Brandon J.; Witt, Tyra A.; Marler, Ronald J.; Pislaru, Sorin V.; Simari, Robert D.; Stulak, John M.; Lerman, Amir

    2017-01-01

    Background Decellularized heart valves are emerging as a potential alternative to current bioprostheses for valve replacement. While techniques of decellularization have been thoroughly examined, terminal sterilization techniques have not received the same scrutiny. Methods This study evaluated low dose gamma irradiation as a sterilization method for decellularized heart valves. Incubation of valves and transmission electron microscopy evaluation after different doses of gamma irradiation were used to determine the optimal dose of gamma irradiation. Quantitative evaluation of mechanical properties was done by tensile mechanical testing of isolated cusps. Sterilize decellularized heart valves were tested in a sheep model (n=3, 1 1,500 Gy and 2 3,000 Gy) of pulmonary valve replacement. Results Valves sterilized with gamma radiation between 1,000 Gy and 3,000 Gy were found to be optimal with in-vitro testing. However, with in-vivo showed deteriorating valve function within 2 months. On explant the valve with 1,500 Gy gamma irradiation showed signs of endocarditis with neutrophils on hematoxylin and eosin staining, positive gram stain resembling streptococcus infection. The 3,000 Gy valves had no evidence of infection, but the hematoxylin and eosin staining showed evidence of wound remodeling with macrophages and fibroblasts. Tensile strength testing showed decreased strength (0 Gy-2.53±0.98 MPa, 1,500 Gy-2.03±1.23 MPa, 3,000 Gy-1.26±0.90 MPa) with increasing levels of irradiation. Conclusions Low dose gamma irradiation does not maintain the mechanical integrity of valves and the balance between sterilization and damage may not be able to be achieved with gamma irradiation. Other methods of terminal sterilization must be pursued and evaluated. PMID:26453425

  4. Microbial decontamination by low dose gamma irradiation and its impact on the physico-chemical quality of peppermint (Mentha piperita)

    NASA Astrophysics Data System (ADS)

    Machhour, Hasna; El Hadrami, Ismail; Imziln, Boujamaa; Mouhib, Mohamed; Mahrouz, Mostafa

    2011-04-01

    Peppermint was inoculated with Escherichia coli and its decontamination was carried out by gamma irradiation at low irradiation doses (0.5, 1.0 and 2.66 kGy). The efficiency of this decontamination method was evaluated and its impact on the quality parameters of peppermint, such as the color and ash content, as well as the effect on fingerprint components such as phenols and essential oils, was studied. Gas chromatography coupled to mass spectrometry (GC/MS) and High Performance Liquid Chromatography (HPLC) were used to characterize essential oils and phenolic compounds, respectively. The results indicated a complete decontamination of peppermint after the low dose gamma irradiation without a significant loss in quality attributes.

  5. Differential expression of thymic DNA repair genes in low-dose-rate irradiated AKR/J mice

    PubMed Central

    Bong, Jin Jong; Kang, Yu Mi; Shin, Suk Chul; Choi, Seung Jin

    2013-01-01

    We previously determined that AKR/J mice housed in a low-dose-rate (LDR) (137Cs, 0.7 mGy/h, 2.1 Gy) γ-irradiation facility developed less spontaneous thymic lymphoma and survived longer than those receiving sham or high-dose-rate (HDR) (137Cs, 0.8 Gy/min, 4.5 Gy) radiation. Interestingly, histopathological analysis showed a mild lymphomagenesis in the thymus of LDR-irradiated mice. Therefore, in this study, we investigated whether LDR irradiation could trigger the expression of thymic genes involved in the DNA repair process of AKR/J mice. The enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed immune response, nucleosome organization, and the peroxisome proliferator-activated receptors signaling pathway in LDR-irradiated mice. Our microarray analysis and quantitative polymerase chain reaction data demonstrated that mRNA levels of Lig4 and RRM2 were specifically elevated in AKR/J mice at 130 days after the start of LDR irradiation. Furthermore, transcriptional levels of H2AX and ATM, proteins known to recruit DNA repair factors, were also shown to be upregulated. These data suggest that LDR irradiation could trigger specific induction of DNA repair-associated genes in an attempt to repair damaged DNA during tumor progression, which in turn contributed to the decreased incidence of lymphoma and increased survival. Overall, we identified specific DNA repair genes in LDR-irradiated AKR/J mice. PMID:23820165

  6. [Side effects of postoperative irradiation of uterine cancer with high dose rate iridium and low dose rate radium].

    PubMed

    Kucera, H; Unel, N; Weghaupt, K

    1986-02-01

    A report is given about reversible and irreversible complications following postoperative irradiation in cases of endometrial carcinoma. Intravaginal brachytherapy was performed. In advanced cases or in cases with poor prognosis (tumor grading) percutaneous irradiation was added (Co60). In 156 cases low-dose-rate irradiation (Ra226) and in 143 cases high-dose-rate irradiation (Ir192) was applied intravaginally. Reversible complications (cystitis, proctitis) could be observed following Radium in 7%, following Iridium in 14%. Irreversible complications (fistulas, stenoses): 1.9% following Radium and 3.5% following Iridium. When high-dose-rate irradiation was combined with percutaneous Co60 therapy, reversible complications occurred in 22.8%. After changing the Iridium-therapy scheme (reduction of dose from 10 to 7 Gy and irradiation only of the upper two thirds of the vagina) complications only could be observed in the same level as in Radium-therapy. High-dose-rate irradiation does not need hospitalization of the patients.

  7. Low Dose Gamma Irradiation Does Not Affect the Quality or Total Ascorbic Acid Concentration of "Sweetheart" Passionfruit (Passiflora edulis).

    PubMed

    Golding, John B; Blades, Barbara L; Satyan, Shashirekha; Spohr, Lorraine J; Harris, Anne; Jessup, Andrew J; Archer, John R; Davies, Justin B; Banos, Connie

    2015-08-26

    Passionfruit (Passiflora edulis, Sims, cultivar "Sweetheart") were subject to gamma irradiation at levels suitable for phytosanitary purposes (0, 150, 400 and 1000 Gy) then stored at 8 °C and assessed for fruit quality and total ascorbic acid concentration after one and fourteen days. Irradiation at any dose (≤1000 Gy) did not affect passionfruit quality (overall fruit quality, colour, firmness, fruit shrivel, stem condition, weight loss, total soluble solids level (TSS), titratable acidity (TA) level, TSS/TA ratio, juice pH and rot development), nor the total ascorbic acid concentration. The length of time in storage affected some fruit quality parameters and total ascorbic acid concentration, with longer storage periods resulting in lower quality fruit and lower total ascorbic acid concentration, irrespective of irradiation. There was no interaction between irradiation treatment and storage time, indicating that irradiation did not influence the effect of storage on passionfruit quality. The results showed that the application of 150, 400 and 1000 Gy gamma irradiation to "Sweetheart" purple passionfruit did not produce any deleterious effects on fruit quality or total ascorbic acid concentration during cold storage, thus supporting the use of low dose irradiation as a phytosanitary treatment against quarantine pests in purple passionfruit.

  8. Quality changes of the Mediterranean horse mackerel ( Trachurus mediterraneus) during chilled storage: The effect of low-dose gamma irradiation

    NASA Astrophysics Data System (ADS)

    Mbarki, Raouf; Sadok, Saloua; Barkallah, Insaf

    2009-04-01

    Pelagic fishes represent the main Mediterranean fisheries in terms of quantity. However, waste and spoilage of pelagic fish are substantial for a variety of reasons, such as their high perishability and the lack or inadequate supply of ice and freezing facilities. In this work, fresh Mediterranean horse mackerel ( Trachurus mediterraneus) were irradiated at 1 and 2 kGy and stored in ice for 18 days. Quality changes during storage were followed by the determination of microbial counts, trimethylamine (TMA) and volatile basic nitrogen contents. Similarly, lipid composition and sensory analysis were carried out. Irradiation treatment was effective in reducing total bacterial counts throughout storage. Total basic volatile nitrogen content (TVB-N) and TMA levels increased in all lots with storage time, their concentrations being significantly reduced by irradiation, even when the lower level (1 kGy) was used. According to the quality index method, the control lot had a sensory shelf-life of 4 days, whereas those of the irradiated lots were extended by 5 days. Also, low-dose irradiation had no adverse effect on the nutritionally important polyunsaturated fatty acids (PUFA) of Mediterranean horse mackerel. In the same way, thiobarbituric acid-reactive substances values increased with irradiation during the first day, but these values were lower at the end of storage, compared to the control. Results confirm the practical advantages of using γ irradiation as an additional process to chilled storage to enhance the microbiological quality and to extend the shelf-life of small pelagic species.

  9. Low-dose irradiation can be used as a phytosanitary treatment for fresh table grapes.

    PubMed

    Kim, Gina C; Rakovski, Cyril; Caporaso, Fred; Prakash, Anuradha

    2014-01-01

    Grapes (Vitis vinifera var. Sugraone and Vitis labrusca var. Crimson Seedless) were treated with 400, 600, and 800 Gy and the effects on physicochemical factors were measured alongside sensory testing during 3 wk of storage. Significant changes in texture and color with irradiation and age were measured but little visual difference was seen between control and irradiated grapes. However, age had a greater effect on firmness than irradiation for Sugraone grapes. Irradiation did not significantly (P ≤ 0.05) affect the SSC/TA ratio, which increased during storage. The trained panel detected significant changes in the berry texture and rachis color but rated sweetness and flavor significantly higher (P ≤ 0.05) for irradiated Sugraone as compared to the control. Consumers liked both the untreated and 800 Gy treated Sugraone grapes, but liked the untreated grapes more for texture (P ≤ 0.05). However, there was no difference in liking between irradiated (600 Gy or 800 Gy) and control samples of Crimson Seedless for any attribute. The results show that there are varietal differences in response to irradiation but the overall maintenance in quality of irradiated grapes during 3 wk of storage indicates that irradiation can serve as a viable phytosanitary treatment.

  10. Extrapolation of the dna fragment-size distribution after high-dose irradiation to predict effects at low doses

    NASA Technical Reports Server (NTRS)

    Ponomarev, A. L.; Cucinotta, F. A.; Sachs, R. K.; Brenner, D. J.; Peterson, L. E.

    2001-01-01

    The patterns of DSBs induced in the genome are different for sparsely and densely ionizing radiations: In the former case, the patterns are well described by a random-breakage model; in the latter, a more sophisticated tool is needed. We used a Monte Carlo algorithm with a random-walk geometry of chromatin, and a track structure defined by the radial distribution of energy deposition from an incident ion, to fit the PFGE data for fragment-size distribution after high-dose irradiation. These fits determined the unknown parameters of the model, enabling the extrapolation of data for high-dose irradiation to the low doses that are relevant for NASA space radiation research. The randomly-located-clusters formalism was used to speed the simulations. It was shown that only one adjustable parameter, Q, the track efficiency parameter, was necessary to predict DNA fragment sizes for wide ranges of doses. This parameter was determined for a variety of radiations and LETs and was used to predict the DSB patterns at the HPRT locus of the human X chromosome after low-dose irradiation. It was found that high-LET radiation would be more likely than low-LET radiation to induce additional DSBs within the HPRT gene if this gene already contained one DSB.

  11. Extrapolation of the dna fragment-size distribution after high-dose irradiation to predict effects at low doses

    NASA Technical Reports Server (NTRS)

    Ponomarev, A. L.; Cucinotta, F. A.; Sachs, R. K.; Brenner, D. J.; Peterson, L. E.

    2001-01-01

    The patterns of DSBs induced in the genome are different for sparsely and densely ionizing radiations: In the former case, the patterns are well described by a random-breakage model; in the latter, a more sophisticated tool is needed. We used a Monte Carlo algorithm with a random-walk geometry of chromatin, and a track structure defined by the radial distribution of energy deposition from an incident ion, to fit the PFGE data for fragment-size distribution after high-dose irradiation. These fits determined the unknown parameters of the model, enabling the extrapolation of data for high-dose irradiation to the low doses that are relevant for NASA space radiation research. The randomly-located-clusters formalism was used to speed the simulations. It was shown that only one adjustable parameter, Q, the track efficiency parameter, was necessary to predict DNA fragment sizes for wide ranges of doses. This parameter was determined for a variety of radiations and LETs and was used to predict the DSB patterns at the HPRT locus of the human X chromosome after low-dose irradiation. It was found that high-LET radiation would be more likely than low-LET radiation to induce additional DSBs within the HPRT gene if this gene already contained one DSB.

  12. p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation.

    PubMed

    Höfig, Ines; Ingawale, Yashodhara; Atkinson, Michael J; Hertlein, Heidi; Nelson, Peter J; Rosemann, Michael

    2016-01-01

    Mesenchymal stem cells (MSCs) are a source of adult multipotent cells important in tissue regeneration. Murine MSCs are known to proliferate poorly in vitro under normoxia. The aim of this study is to analyze the interaction of nonphysiological high oxygen and low-dose γ-irradiation onto growth, senescence, and DNA damage. Tri-potent bone marrow-derived MSCs from p53 wildtype and p53-/- mice were cultured under either 21% or 2% O2. Long-term observations revealed a decreasing ability of wildtype mMSCs to proliferate and form colonies under extended culture in normoxia. This was accompanied by increased senescence under normoxia but not associated with telomere shortening. After low-dose γ-irradiation, the normoxic wildtype cells further increased the level of senescence. The number of radiation-induced γH2AX DNA repair foci was higher in mMSCs kept under normoxia but not in p53-/- cells. P53-deficient MSCs additionally showed higher clonogeneity, lower senescence levels, and fewer γH2AX repair foci per cell as compared to their p53 wildtype counterparts irrespective of oxygen levels. These results reveal that oxygen levels together with γ-irradiation and p53 status are interconnected factors modulating growth capacity of BM MSCs in long-term culture. These efforts help to better understand and optimize handling of MSCs prior to their therapeutic use.

  13. p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation

    PubMed Central

    Ingawale, Yashodhara; Hertlein, Heidi; Nelson, Peter J.

    2016-01-01

    Mesenchymal stem cells (MSCs) are a source of adult multipotent cells important in tissue regeneration. Murine MSCs are known to proliferate poorly in vitro under normoxia. The aim of this study is to analyze the interaction of nonphysiological high oxygen and low-dose γ-irradiation onto growth, senescence, and DNA damage. Tri-potent bone marrow-derived MSCs from p53 wildtype and p53−/− mice were cultured under either 21% or 2% O2. Long-term observations revealed a decreasing ability of wildtype mMSCs to proliferate and form colonies under extended culture in normoxia. This was accompanied by increased senescence under normoxia but not associated with telomere shortening. After low-dose γ-irradiation, the normoxic wildtype cells further increased the level of senescence. The number of radiation-induced γH2AX DNA repair foci was higher in mMSCs kept under normoxia but not in p53−/− cells. P53-deficient MSCs additionally showed higher clonogeneity, lower senescence levels, and fewer γH2AX repair foci per cell as compared to their p53 wildtype counterparts irrespective of oxygen levels. These results reveal that oxygen levels together with γ-irradiation and p53 status are interconnected factors modulating growth capacity of BM MSCs in long-term culture. These efforts help to better understand and optimize handling of MSCs prior to their therapeutic use. PMID:26788069

  14. The effects of different schedules of total-body irradiation in heterotopic vascularized bone transplantation. An experimental study in the Lewis rat

    SciTech Connect

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J. )

    1990-12-01

    To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease in bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation.

  15. Physics must join with biology in better assessing risk from low-dose irradiation.

    PubMed

    Feinendegen, L E; Neumann, R D

    2005-01-01

    This review summarises the complex response of mammalian cells and tissues to low doses of ionising radiation. This thesis encompasses induction of DNA damage, and adaptive protection against both renewed damage and against propagation of damage from the basic level of biological organisation to the clinical expression of detriment. The induction of DNA damage at low radiation doses apparently is proportional to absorbed dose at the physical/chemical level. However, any propagation of such damage to higher levels of biological organisation inherently follows a sigmoid function. Moreover, low-dose-induced inhibition of damage propagation is not linear, but instead follows a dose-effect function typical for adaptive protection, after an initial rapid rise it disappears at doses higher than approximately 0.1-0.2 Gy to cells. The particular biological response duality at low radiation doses precludes the validity of the linear-no-threshold hypothesis in the attempt to relate absorbed dose to cancer. In fact, theory and observation support not only a lower cancer incidence than expected from the linear-no-threshold hypothesis, but also a reduction of spontaneously occurring cancer, a hormetic response, in the healthy individual.

  16. Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2017-09-08

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Congenital Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Severe Combined Immunodeficiency; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

  17. Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

    ClinicalTrials.gov

    2016-08-01

    Acute Undifferentiated Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  18. Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies

    ClinicalTrials.gov

    2017-01-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenström Macroglobulinemia

  19. Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia

    ClinicalTrials.gov

    2017-02-16

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Fanconi Anemia; Previously Treated Myelodysplastic Syndromes

  20. Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

    ClinicalTrials.gov

    2016-10-10

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Chronic Lymphocytic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Renal Cell Carcinoma; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; T-cell Large Granular Lymphocyte Leukemia; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Waldenström Macroglobulinemia

  1. Effect of low-dose electron beam irradiation on quality of ground beef patties and raw, intact carcass muscle pieces.

    PubMed

    Kundu, Devapriya; Holley, Richard

    2013-06-01

    The objectives of this study were to determine the effects of a low-dose (≤1 kGy), low-penetration electron beam on the sensory qualities of (1) raw muscle pieces of beef and (2) cooked ground beef patties. Outside flat, inside round, brisket and sirloin muscle pieces were used as models to demonstrate the effect of irradiation on raw beef odor and color, as evaluated by a trained panel. Ground beef patties were also evaluated by a trained panel for tenderness, juiciness, beef flavor, and aroma at 10%, 20%, and 30% levels of fat, containing 0% (control), 10%, 20%, 50%, and 100% irradiated meat. With whole muscle pieces, the color of controls appeared more red (P < 0.05) than irradiated muscles, however, both control and treatments showed a gradual deterioration in color over 14 d aerobic storage at 4 °C. Off-aroma intensity of both control and treatments increased with storage time, but by day 14, the treated muscles showed significantly (P < 0.05) less off-aroma than the controls, presumably as a result of a lower microbial load. It was found that a 1 kGy absorbed dose had minimal effects on the sensory properties of intact beef muscle pieces. Irradiation did not have a significant effect (P > 0.05) on any of the sensory attributes of the patties. Low-dose irradiation of beef trim to formulate ground beef appears to be a viable alternative processing approach that does not affect product quality.

  2. Low Doses of Gamma-Irradiation Induce an Early Bystander Effect in Zebrafish Cells Which Is Sufficient to Radioprotect Cells

    PubMed Central

    Pereira, Sandrine; Malard, Véronique; Ravanat, Jean-Luc; Davin, Anne-Hélène; Armengaud, Jean; Foray, Nicolas; Adam-Guillermin, Christelle

    2014-01-01

    The term “bystander effect” is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01–0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of γ-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less γ-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less γ-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors. PMID:24667817

  3. Effect of low dose electron beam irradiation on the alteration layer formed during nuclear glass leaching

    NASA Astrophysics Data System (ADS)

    Mougnaud, S.; Tribet, M.; Renault, J.-P.; Jollivet, P.; Panczer, G.; Charpentier, T.; Jégou, C.

    2016-12-01

    This investigation concerns borosilicate glass leaching mechanisms and the evolution of alteration layer under electron beam irradiation. A simple glass doped with rare earth elements was selected in order to access mechanistic and structural information and better evaluate the effects of irradiation. It was fully leached in initially pure water at 90 °C and at high glass surface area to solution volume ratio (S/V = 20 000 m-1) in static conditions. Under these conditions, the system quickly reaches the residual alteration rate regime. A small particle size fraction (2-5 μm) was sampled in order to obtain a fairly homogeneous altered material enabling the use of bulk characterization methods. External irradiations with 10 MeV electrons up to a dose of 10 MGy were performed either before or after leaching, to investigate respectively the effect of initial glass irradiation on its alteration behavior and the irradiation stability of the alteration layer. Glass dissolution rate was analyzed by regular leachate samplings and the alteration layer structure was characterized by Raman, luminescence (continuous or time-resolved), and 29Si MAS NMR and EPR spectroscopy. It was shown that the small initial glass evolutions under irradiation did not induce any modification of the leaching kinetic nor of the structure of the alteration layer. The alteration process seemed to "smooth over" the created defects. Otherwise, the alteration layer and initial glass appeared to have different behaviors under irradiation. No Eu3+ reduction was detected in the alteration layer after irradiation and the defect creation efficiency was much lower than for initial glass. This can possibly be explained by the protective role of pore water contained in the altered material (∼20%). Moreover, a slight depolymerization of the silicon network of the altered glass under irradiation with electrons was evidenced, whereas in the initial glass it typically repolymerizes.

  4. [Cytogenetic indices for somatic mutagenesis in mammals exposed to chronic low-dose irradiation].

    PubMed

    Kostenko, S A; Ermakova, O V; Sushko, S N; Fyedorova, E V; Dzhus, P P; Baschlykova, L A; Kurylenko, Yu F; Raskosha, O V; Savin, A O; Shaforost, A S

    2015-01-01

    We used cytogenetic analysis in the studies of the biological effects of a radiation factor of natural and artificial origin (under conditions ofthe 30-km exclusion zone ofthe Chernobyl experimental landfills in Ukraine, Belarus and Russia). The studies have been performed on various types of mammals: domestic animals--cows, pigs, horses and rodents--root voles, the Af mouse line, and yellow necked field mouse, bank voles. We found significant changes in the level of MN and chromosomal aberrations in the animals that were exposed to the conditions of chronic low-dose radiation for a long time (bothin the habitat and upon exposure in the Chernobyl zone) regardless of the type of animal and nature of contamination.

  5. Cyanocobalamin solutions as potential dosimeters in low-dose food irradiations.

    PubMed

    Prakasan, Velayudhan; Sanyal, Bhaskar; Pritamdas Chawla, Surinder; Chander, Ramesh; Sharma, Arun

    2014-04-01

    Potential of aqueous solutions of cyanocobalamin in gamma radiation dosimetry was investigated. The solutions are inexpensive, nontoxic and easy-to-prepare dosimeters, which could be useful for measuring gamma radiation doses in various applications, such as quarantine treatment of fruit or insect disinfestation of grains and pulses. The optical absorbance of cyanocobalamin solutions of the optimal concentration 0.08 mM decreases with increasing radiation dose. The reproducible dependence of the absorbance decrease on the dose can be described with a polynomial. Pre- and post-irradiation stability of the solution absorbance, as well as effects of the irradiation temperature and dose rate, were studied. The response is not significantly affected by storage of the irradiated dosimeters under ambient conditions for 20 days. The performance characteristics of this chemical dosimetry system suggest that it can be useful to measure doses in irradiations of food. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells.

    PubMed

    Ermakov, Aleksei V; Konkova, Marina S; Kostyuk, Svetlana V; Smirnova, Tatiana D; Malinovskaya, Elena M; Efremova, Liudmila V; Veiko, Natalya N

    2011-07-01

    The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10cGy. The fragments of extracellular genomic DNA (ecDNA(R)) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNA(R), followed by analysing the cells along the series of parameters (bystander effect). The exposed cells and bystander endotheliocytes showed similar response to low doses: approximation of the 1q12 loci of chromosome 1 and their transposition into the cellular nucleus, change in shape of the endotheliocytic nucleus, activation of the nucleolus organizing regions (NORs), actin polymerization, and an elevated level of DNA double-stranded breaks. Following blockade of TLR9 receptors with oligonucleotide-inhibitor or chloroquine in the bystander cells these effects - except of activation of NORs - on exposure to ecDNA(R) disappeared, with no bystander response thus observed. The presence of the radiation-induced apoptosis in the bystander effect being studied suggests a possibility for radiation-modified ecDNA fragments (i.e., stress signaling factors) to be released into the culture medium, whereas inhibition of TLR9 suggests the binding these ligands to the recipient cells. A similar DNA-signaling pathway in the bystander effect we previously described for human lymphocytes. Integrity of data makes it possible to suppose that a similar signaling mechanism which we demonstrated for lymphocytes (humoral system) might also be mediated in a monolayer culture of cells (cellular tissue) after the development of the bystander effect in them and transfer of stress signaling factors (ecDNA(R)) through the culture medium. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Acute hematological tolerance to multiple fraction, whole body, low dose irradiation in an experimental murine system

    SciTech Connect

    Melamed, J.S.; Chen, M.G.; Brown, J.W.; Katagiri, C.A.

    1980-02-01

    Using a dose fractionation scheme patterned after the current regimen for treatment of disseminated non-Hodgkin lymphoma, the authors studied the effects of irradation on progenitor and effector cells for hematopoiesis in five-month-old BC3F/sub 1/ mice. Fractions of 20 or 50 rad (0.2 or 0.5 Gy) total body irradation were given twice weekly to a final total dose of 200 or 500 rad (2 or 5 Gy), respectively. Weekly assays revealed a marked, sustained depression of stem cell activity, measured as numbers of spleen colony-forming units (CFU-S) and in vitro colony-forming cells (CFU-C), without corresponding depression of effector cells (red and white cells, and platelets). The lack of correlation between numbers of stem cells and peripheral elements is relevant to clinical assessment of marrow reserve.

  8. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females.

    PubMed

    Silasi, Greg; Diaz-Heijtz, Rochellys; Besplug, Jill; Rodriguez-Juarez, Rocio; Titov, Viktor; Kolb, Bryan; Kovalchuk, Olga

    2004-12-24

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes.

  9. The effect of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1974-01-01

    Cellular response and cell population kinetics were studied during lymphopoiesis in the thymus of the mouse under continuous gamma irradiation using autoradiographic techniques and specific labeling with tritiated thymidine. On the basis of tissue weights, it is concluded that the response of both the thymus and spleen to continuous low dose-rate irradiation is multiphasic. That is, alternating periods of steady state growth, followed by collapse, which in turn is followed by another period of homeostasis. Since there are two populations of lymphocytes - short lived and long-lived, it may be that different phases of steady state growth are mediated by different lymphocytes. The spleen is affected to a greater extent with shorter periods of steady-state growth than exhibited by the thymus.

  10. Total Body Irradiation, Toward Optimal Individual Delivery: Dose Evaluation With Metal Oxide Field Effect Transistors, Thermoluminescence Detectors, and a Treatment Planning System

    SciTech Connect

    Bloemen-van Gurp, Esther J. Mijnheer, Ben J.; Verschueren, Tom A.M.; Lambin, Philippe

    2007-11-15

    Purpose: To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. Methods and Materials: A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. Results: The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. Conclusions: The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

  11. [Effect of long-term exposure to low dose gamma-irradiation on the rat thyroid status].

    PubMed

    Nadol'nik, L I; Netsetskaia, Z V; Vinogradov, V V

    2004-01-01

    The effect of long-term exposure to low-dose external radiation on the rat thyroid status was studied. The experiments were carried out on Wistar female rats. The single doses absorbed were 0.1; 0.25; 0.5 Gy. The rats were irradiated 20 times (5 days x 4 weeks). The animals were decapitated after 1, 30 and 180 days following the last irradiation. Blood serum was assayed for content of thyroxin (T4) and triiodothyronine (T3) radioimmunologically. The liver was spectrophotometrically assayed for thyroid-induced NADP-malatedehydrogenase (NADP-MDH). It was shown that the long-term 0.5-Gy irradiation of the animals induced a decrease in blood T4 and T3 concentrations 1.34-1.71-fold and 1.24-1.43-fold after 1, 30 and 180 days, respectively. The T3 level was diminished most pronouncedly after 1 day, whereas that of T4--after 30 days following the exposure. With the doses of 0.1 and 0.25 Gy absorbed, the T4 and T3 concentration remained unchanged throughout all the periods studied. The activity of NADP-MDH was decreased 1.55-2.46-fold in all the experimental animals, and it was held decreased after 180 days (1.43-1.50-fold) in 0.25- and 0.5-Gy-irradiated groups, which indicates a disturbance in thyroid hormone metabolism in rats exposed chronically to low-dose radiation. After 180 days, the experimental animals experienced an elevation of thyroid gland weight on 15-20%. The thyroid status disturbance seemed to be due to both inhibited T4 and T3 biosynthesis in thyroid and disturbed hormone peripheral metabolism under radiation exposure.

  12. Total body calcium analysis using the Ca-12(n, alpha) Ar-37 reaction

    NASA Technical Reports Server (NTRS)

    Lewellen, T. K.; Nelp, W. B.

    1977-01-01

    A low dose neutron activation technique was developed to measure total body calcium in vivo. The effort had included development of irradiation and processing facilities and conduction of human studies to determine the accuracy and precision of measurement attainable with the systems.

  13. Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

    SciTech Connect

    Hiniker, Susan M.; Agarwal, Rajni; Modlin, Leslie A.; Gray, Christine C.; Harris, Jeremy P.; Million, Lynn; Kiamanesh, Eileen F.; Donaldson, Sarah S.

    2014-05-01

    Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

  14. Triphasic low-dose response in zebrafish embryos irradiated by microbeam protons.

    PubMed

    Choi, Viann Wing Yan; Yum, Emily Hoi Wa; Konishi, Teruaki; Oikawa, Masakazu; Cheng, Shuk Han; Yu, Kwan Ngok

    2012-01-01

    The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed to irradiate dechorionated zebrafish embryos at the 2-cell stage at 0.75 h post fertilization (hpf) by microbeam protons. Either one or both of the cells of the embryos were irradiated with 10, 20, 40, 50, 80, 100, 160, 200, 300 and 2000 protons each with an energy of 3.37 MeV. The embryos were then returned back to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay, with the apoptotic signals captured by a confocal microscope. The results revealed a triphasic dose-response for zebrafish embryos with both cells irradiated at the 2-cell stage, namely, (1) increase in apoptotic signals for < 200 protons (< 30 mGy), (2) hormesis to reduce the apoptotic signals below the spontaneous number for 200-400 protons (at doses of 30-60 mGy), and (3) increase in apoptotic signals again for > 600 protons (at doses > 90 mGy). The dose response for zebrafish embryos with only one cell irradiated at the 2-cell stage was also likely a triphasic one, but the apoptotic signals in the first zone (< 200 protons or < 30 mGy) did not have significant differences from those of the background. At the same time, the experimental data were in line with induction of radiation-induced bystander effect as well as rescue effect in the zebrafish embryos, particular in those embryos with unirradiated cells.

  15. The influence of low dose neutron irradiation on the thermal conductivity of Allcomp carbon foam

    SciTech Connect

    Burchell, Timothy D.; Porter, Wallace D.; McDuffee, Joel Lee

    2016-03-01

    Oak Ridge National Laboratory was contracted via a Work for Others Agreement with Allcomp Inc. (NFE-14-05011-MSOF: Carbon Foam for Beam Stop Applications ) to determine the influence of low irradiation dose on the thermal conductivity of Allcomp Carbon Foam. Samples (6 mm dia. x 5 mm thick) were successfully irradiated in a rabbit capsule in a hydraulic tube in the target region of the High Flux Isotope Reactor at the Oak Ridge National Laboratory. The specimens were irradiated at Tirr = 747.5 C to a neutron damage dose of 0.2 dpa. There is a small dimensional and volume shrinkage and the mass and density appear reduced (we would expect density to increase as volume reduces at constant mass). The small changes in density, dimensions or volume are not of concern. At 0.2 dpa the irradiation shrinkage rate difference between the glassy carbon skeleton and the CVD coating was not sufficient to cause a large enough irradiation-induced strain to create any mechanical degradation. Similarly differential thermal expansion was not a problem. It appears that only the thermal conductivity was affected by 0.2 dpa. For the intended application conditions, i.e. @ 400 C and 0 DPA (start- up) the foam thermal conductivity is about 57 W/m.K and at 700 C and 0.2 DPA (end of life) the foam thermal conductivity is approx. 30.7 W/m.K. The room temp thermal conductivity drops from 100-120 W/m.K to approximately 30 W/m.K after 0.2 dpa of neutron irradiation.

  16. Effect of irradiation temperature and strain rate on the mechanical properties of V-4Cr-4Ti irradiated to low doses in fission reactors

    SciTech Connect

    Zinkle, S.J.; Snead, L.L.; Rowcliffe, A.F.; Alexander, D.J.; Gibson, L.T.

    1998-09-01

    Tensile tests performed on irradiated V-(3-6%)Cr-(3-6%)Ti alloys indicate that pronounced hardening and loss of strain hardening capacity occurs for doses of 0.1--20 dpa at irradiation temperatures below {approximately}330 C. The amount of radiation hardening decreases rapidly for irradiation temperatures above 400 C, with a concomitant increase in strain hardening capacity. Low-dose (0.1--0.5 dpa) irradiation shifts the dynamic strain aging regime to higher temperatures and lower strain rates compared to unirradiated specimens. Very low fracture toughness values were observed in miniature disk compact specimens irradiated at 200--320 C to {approximately}1.5--15 dpa and tested at 200 C.

  17. The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-CSF stimulates hematopoiesis and enhances survival from lethal total-body gamma-irradiation

    PubMed Central

    Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

    2013-01-01

    Purpose We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the Acute Radiation Syndrome (ARS), to enhance discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematological parameters and dynamics of cell loss/recovery following irradiation provide a convenient means to compare efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials Male Gottingen minipigs, 4–5 months old and weighing 9–11 kg were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen®, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body gamma-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results Results indicate G-CSF enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusion These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing numbers of circulating granulocytes. PMID:23845847

  18. Effects of low-dose prenatal irradiation on the central nervous system

    SciTech Connect

    Not Available

    1992-04-01

    Scientists are in general agreement about the effects of prenatal irradiation, including those affecting the central nervous system (CNS). Differing concepts and research approaches have resulted in some uncertainties about some quantitative relationships, underlying interpretations, and conclusions. Examples of uncertainties include the existence of a threshold, the quantitative relationships between prenatal radiation doses and resulting physical and functional lesions, and processes by which lesions originate and develop. A workshop was convened in which scientists with varying backgrounds and viewpoints discussed these relationships and explored ways in which various disciplines could coordinate concepts and methodologies to suggest research directions for resolving uncertainties. This Workshop Report summarizes, in an extended fashion, salient features of the presentations on the current status of our knowledge about the radiobiology and neuroscience of prenatal irradiation and the relationships between them.

  19. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1975-01-01

    The mechanism of cell proliferation is studied in the lymphoid tissue of the mouse spleen under the stress of continuous irradiation at a dose-rate of 10 roentgens per day for 105 days. Autoradiography and specific labeling with tritiated thymidine were utilized. It was found that at least four compensatory mechanisms maintained a near-steady state of cellular growth: (1) an increase in the proportion of PAS-positive cells which stimulate mitotic activity, (2) maturation arrest of proliferating and differentiating cells which tend to replenish the cells damaged or destroyed by irradiation, (3) an increase in the proportion of cells proliferating, and (4) an increase in the proportion of precursor cells. The results are compared to previous findings observed in the thymus.

  20. Effects of low-dose prenatal irradiation on the central nervous system

    SciTech Connect

    Not Available

    1992-04-01

    Scientists are in general agreement about the effects of prenatal irradiation, including those affecting the central nervous system (CNS). Differing concepts and research approaches have resulted in some uncertainties about some quantitative relationships, underlying interpretations, and conclusions. Examples of uncertainties include the existence of a threshold, the quantitative relationships between prenatal radiation doses and resulting physical and functional lesions, and processes by which lesions originate and develop. A workshop was convened in which scientists with varying backgrounds and viewpoints discussed these relationships and explored ways in which various disciplines could coordinate concepts and methodologies to suggest research directions for resolving uncertainties. This Workshop Report summarizes, in an extended fashion, salient features of the presentations on the current status of our knowledge about the radiobiology and neuroscience of prenatal irradiation and the relationships between them.

  1. A different perception of the linear, nonthreshold hypothesis for low-dose irradiation.

    PubMed Central

    Bond, V P; Benary, V; Sondhaus, C A

    1991-01-01

    Two equally useful dosimetric quantities, both of which are called dose, are used in toxicology. With radiation measurement, only one--the energy per unit mass D--is called dose. The other--the total energy in the irradiated system--is here distinguished from D by assigning it the name collective energy, epsilon. The collective energy is a more complete statement of dose because it is the product of the energy concentration D and the mass irradiated m. Especially in radioepidemiology, in which epsilon is the total energy imparted to all persons irradiated, the quantity m must be specified because it is situation specific and thus highly variable. At present, radioepidemiological dose-response curves are given only in terms of the toxicological model--i.e., the fraction (probability) of radiation-attributable cancers occurring as a function of D. Because this relation does not involve the number of persons at each value of D, it fosters the illusion that any dose, no matter how small, can result in cancer. However, we show that if the dose-response relationship is expressed in terms of the absolute number of attributable cancers as a function of epsilon, cancer occurs, on average, only if the collective energy exceeds a relatively large minimum value, the magnitude of which will be estimated. Therefore, we conclude that the nonthreshold aspect of the linear hypothesis is misleading and quite probably invalid. For example, in or around a facility in which exposure of humans to relatively low values of D occurs, attributable cancers are most unlikely to appear unless the epsilon to the irradiated population exceeds this minimum value. PMID:1924328

  2. A different perception of the linear, nonthreshold hypothesis for low-dose irradiation

    SciTech Connect

    Bond, V.P. ); Benary, V. Tel Aviv Univ. ); Sondhaus, C.A. )

    1991-10-01

    Two equally useful dosimetric quantities, both of which are called dose, are used in toxicology. With radiation measurement, only one - the energy per unit mass D - is called dose. The other - the total energy in the irradiated system - is here distinguished from D by assigning it the name collective energy, {epsilon}. The collective energy is a more complete statement of dose because it is the product of the energy concentration D and the mass irradiated m. Especially in radioepidemiology, in which {epsilon} is the total energy imparted to all persons irradiated, the quantity m must be specified because it is situation specific and thus highly variable. At present, radioepidemiological dose-response curves are given only in terms of the toxicological model - i.e., the fraction (probability) of radiation-attributable cancers occurring as a function of D. Because this relation does not involve the number of persons at each value of D, it fosters the illusion that any dose, no matter how small, can result in cancer. However, the authors show that if the dose-response relationship is expressed in terms of the absolute number of attributable cancers as a function of {epsilon}, cancer occurs, on average, only if the collective energy exceeds a relatively large minimum value, the magnitude of which will be estimated. Therefore, they conclude that the nonthreshold aspect of the linear hypothesis is misleading and quite probably invalid. For example, in or around a facility in which exposure of humans to relatively low values of D occurs, attributable cancers are most unlikely to appear unless the {epsilon} to the irradiated population exceeds this minimum value.

  3. Low-dose carbon ion irradiation effects on DNA damage and oxidative stress in the mouse testis

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Long, Jing; Zhang, Luwei; Zhang, Hong; Liu, Bin; Zhao, Weiping; Wu, Zhehua

    2011-01-01

    To investigate the effects of low-dose carbon ion irradiation on reproductive system of mice, the testes of outbred Kunming strain mice were whole-body irradiated with 0, 0.05, 0.1, 0.5 and 1 Gy, respectively. We measured DNA double-strand breaks (DNA DSBs) and oxidative stress parameters including malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and testis weight and sperm count at 12 h, 21 d and 35 d after irradiation in mouse testis. At 12 h postirradiation, a significant increase in DNA DSB level but no pronounced alterations in MDA content or SOD activity were observed in 0.5 and 1 Gy groups compared with the control group. At 21 d postirradiation, there was a significant reduction in sperm count and distinct enhancements of DSB level and MDA content in 0.5 and 1 Gy groups in comparison with control. At 35 d postirradiation, the levels of DNA DSBs and MDA, and SOD activity returned to the baseline except for the MDA content in 1 Gy (P < 0.05), while extreme falls of sperm count were still observed in 0.5 (P < 0.01) and 1 Gy (P < 0.01) groups. For the 0.05 or 0.1 Gy group, no differences were found in DNA DSB level and MDA content between control and at 12 h, 21 d and 35 d after irradiation, indicating that lower doses of carbon ion irradiation have no significant influence on spermatogenesis processes. In this study, male germ cells irradiated with over 0.5 Gy of carbon ions are difficult to repair completely marked by the sperm count. Furthermore, these data suggest that the deleterious effects may be chronic or delayed in reproductive system after whole-body exposure to acute high-dose carbon ions.

  4. Influence of germ cells upon Sertoli cells during continuous low-dose rate gamma-irradiation of adult rats.

    PubMed

    Pinon-Lataillade, G; Vélez de la Calle, J F; Viguier-Martinez, M C; Garnier, D H; Folliot, R; Maas, J; Jégou, B

    1988-07-01

    The effects of continuous gamma-irradiation of adult rats at two low-dose rates (7 cGy and 12 cGy/day; up to a total dose of 9.1 Gy and 10.69 Gy 60Co gamma-ray, respectively) were investigated. Over a period of 3-131 days of irradiation, groups of experimental and control animals were killed. Body weight, testis, epididymis, prostate and seminal vesicle weights, the number of germ cells and Sertoli cells, tubular ultrastructure, epididymal and testicular levels of biologically active androgen-binding protein (ABP), and the plasma concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were monitored. Irradiation had no effect on body weight, whereas testicular and epididymal weight began to decrease following 35 and 50 days of irradiation at 7 and 12 cGy, respectively. At 7 cGy the target cells of the gamma-rays were essentially A spermatogonia, whereas at 12 cGy A spermatogonia and preleptotene spermatocytes were primarily affected. This resulted in a progressive and sequential dose-related reduction in the number of pachytene spermatocytes, round spermatids and late spermatids (LS). Under both irradiation procedures the Sertoli cell number remained unchanged whereas partial (7 cGy) or no change (12 cGy) was seen at the Leydig cell level. Whatever the irradiation protocol, from the time LS numbers decreased, vacuolisation of the Sertoli cell cytoplasm progressively occurred, followed by thickening and folding of the peritubular tissue. Moreover, in parallel to the drop in the number of these germ cell types, ABP production fell whereas FSH levels rose. A highly significant positive correlation was found between LS numbers and these Sertoli cell parameters. This study supports our previous concept of a control of certain important aspects of Sertoli cell function by late spermatids in the adult rat.

  5. Anionic triphenylmethane dye solutions for low-dose food irradiation dosimetry

    NASA Astrophysics Data System (ADS)

    El-Assy, Nasef B.; Yun-Dong, Chen; Walker, M. L.; Al-Sheikhly, M.; McLaughlin, W. L.

    1995-09-01

    The radiolytic bleaching of aryl sulfonic-substituted para-diethyl-amino triphenylmethane dye solutions can be used for dosimetry in the absorbed dose range 10 to 400 Gy. The sulfonic anions provide solubility of these acid dyes in water. Two of these dyes are supplied as stable greenish-blue biological stains when dissolved in weakly-acidic aqueous solution, Light Green SF Yellowish and Fast Green FCF. They have, respectively, linear molar absorption coefficients of 7.14 × 103(at pH5.4) and 10.0 × 103 (at pH4.2) m2mol-1, when measured at the peaks of the primary absorption bands, 630 nm and 622 nm, respectively. The bleaching due to irradiation with gamma rays shows a linear function with a positive slope between the negative logarithm of the absorbance and the absorbed dose. The effect of pH on the response is studied, as well as the effects of light and temperature on pre- and post-irradiation stability. A mechanism, based mainly on radiolytic oxidation of the protonated phenolic or sulfonated phenyl group by .OH, with the abstraction of H-atom to water, is postulated for neutral to slightly acidic aerated aqueous solutions. The influence of alcohol on diminishing the negative yield is demonstrated. Alkaline aqueous solutions of these dyes (pH 10.2) have a shorter-wavelength absorption maximum than acidic aqueous solutions. The effect of irradiation is to cause acidification (to pH 7) due to displacement of OH groups and degradation of the dye molecule to lower molecular weight organic acids.

  6. Development of microstructure and irradiation hardening of Zircaloy during low dose neutron irradiation at nominally 358 C

    SciTech Connect

    Cockeram, Brian V; Smith, Richard W; Leonard, Keith J; Byun, Thak Sang; Snead, Lance Lewis

    2011-01-01

    Wrought Zircaloy-2 and Zircaloy-4 were neutron irradiated at nominally 358 C in the high flux isotope reactor (HFIR) at relatively low neutron fluences between 5.8 1022 and 2.9 1025 n/m2 (E > 1 MeV). The irradiation hardening and change in microstructure were characterized following irradiation using tensile testing and examinations of microstructure using Analytical Electron Microscopy (AEM). Small increments of dose (0.0058, 0.11, 0.55, 1.08, and 2.93 1025 n/m2) were used in the range where the saturation of irradiation hardening is typically observed so that the role of microstructure evolution and hai loop formation on irradiation hardening could be correlated. An incubation dose between 5.8 1023 and 1.1 1024 n/m2 was needed for loop nucleation to occur that resulted in irradiation hardening. Increases in yield strength were consistent with previous results in this temperature regime, and as expected less irradiation hardening and lower hai loop number density values than those generally reported in literature for irradiations at 260 326 C were observed. Unlike previous lower temperature data, there is evidence in this study that the irradiation hardening can decrease with dose over certain ranges of fluence. Irradiation induced voids were observed in very low numbers in the Zircaloy-2 materials at the highest fluence.

  7. Changes in compartments of hemospoietic and stromal marrow progenitor cells after continuous low dose gamma-irradiation

    NASA Astrophysics Data System (ADS)

    Domaratskaya, E.; Starostin, V.

    The low dose continuous gamma-irradiation chosen corresponded with that affected the organisms onboard a spacecraft (Mitrikas, Tsetlin, 2000). F1 (CBAxC57Bl/6) male and female mice were used at 3 4 months of age. Experimental mice were- irradiated during 10 days to a total dose of 15 mGy (Co60 gamma-sources, mean dose rate of 1.5-2.0 mGy/day). Another group of intact mice served as control. Younger and advanced hemopoietic progenitors measured at day 11 (i.e. CFU -S-11) and day 7 (i.e. CFU-S-7), respectively, after transplantation of test donor cells were assayed by the method of Till and McCulloch (1961). Stromal changes were evaluated by estimation of in vitro fibroblastic colony-forming units (CFU -F ) content and by the ability of ectopically grafted (under renal capsule) stroma to regenerate the new bone marrow organ. CFU-S-11 number increased of 40% as compared with control and almost 2-fold higher than that of CFU-S-7. The CFU-F content increased almost of 3-fold. Size of ectopic marrow transplants was estimated at day 70 following grafting by counting myelokariocyte and CFU -S number that repopulated the newly formed bone marrow organ. It was found more than 2-fold increase of myelokariocytes in transplants produced by marrow stroma of irradiated donors. CFU -S contents in transplants increased strikingly in comparison to control level. CFU-S-7 and CFU-S-11 increased of 7.5- and of 3.7-fold, respectively, i.e. the rate of advanced CFU - S predominated. It should be noted a good correlation between number of stromal progenitor cells (CFU-F) and ectopic transplant sizes evaluated as myelokaryocyte counts when irradiated donors used. In the same time, if sizes of transplants was measured as CFU-S-7 and CFU - S-11 numbers, their increases were more pronounced. Therefore, continuous low dose gamma- irradiation augments significantly both hemopoietic and stromal progenitor cell number in bone marrow. Additionally, the ratio of distinct CFU -S subpopulations

  8. Unexpected acute renal injury after high-dose etoposide phosphate and total body irradiation in children undergoing hematopoietic stem cell transplantation.

    PubMed

    Cordero, C; Loboda, C; Clerc-Urmès, I; Clément, L; Pochon, C; Chastagner, P

    2017-07-11

    High-dose etoposide phosphate, a water-soluble prodrug of etoposide, may be used after total body irradiation (TBI) in pediatric allogeneic bone marrow transplantation for lymphoblastic leukemia. In a retrospective study of 21 children treated at the Nancy University Hospital (2000-2014), we identified unprecedentedly an unexpectedly high incidence (57%) of acute renal injury following etoposide phosphate infusion. Patients who developed renal function impairment experienced more severe mucositis but had outcomes similar to those who did not. No risk factors were identified. We speculate that the etoposide phosphate diluent, dextran 40, may have been the causative agent in these post-TBI renal toxicity cases. © 2017 Wiley Periodicals, Inc.

  9. [Radiation situation prognosis for deep space: reactions of water and living systems to chronic low-dose ionizing irradiation].

    PubMed

    Ushakov, I B; Tsetlin, V V; Moisa, S S

    2013-01-01

    The authors review the findings of researches into the effects of low-dose ionizing irradiation on diverse biological objects (embryonic Japanese quails, Aspergillus niger, Spirostomum ambiguum Ehrbg., mesenchymal stem cells from mouse marrow, dry higher plants seeds, blood lymphocytes from pilots and cosmonauts). Model experiments with chronic exposure to ionizing radiation doses comparable with the measurements inside orbital vehicles and estimations for trips through the interplanetary space resulted in morphological disorders (embryonic Japanese quails, Aspergillus niger), radiation hormesis (Aspergillus niger, MSCs from mouse marrow), increase in the seed germination rate, inhibition of Spirostomum spontaneous activity, DNA damages, chromosomal aberrations, and increase of the blood lymphocytes reactivity to additional radiation loading. These facts give grounds to assume that the crucial factor in the radiation outcomes is changes in liquid medium. In other words, during extended orbiting within the magnetosphere region and interplanetary missions ionizing radiation affects primarily liquids of organism and, secondarily, its morphofunctional structures.

  10. FT-IR spectroscopy assessment of aesthetic dental materials irradiated with low-dose therapeutic ionizing radiation

    NASA Astrophysics Data System (ADS)

    Cruz, A. D.; Almeida, S. M.; Rastelli, A. N. S.; Bagnato, V. S.; Byscolo, F. N.

    2009-03-01

    The aim of the present study was to evaluate the effects of low-dose therapeutic ionizing radiation on different aesthetic dental materials. Forty five specimens ( n = 45) of three different aesthetic restorative materials were prepared and randomly divided into five groups: G1 (control group); G2, G3, G4, G5 experimental groups irradiated respectively with 0.25, 0.50, 0.75, and 1.00 Gy of gamma radiation by the 60Co teletherapy machine. Chemical analyses were performed using a FT-IR Nicolet 520 spectrophotometer with reflectance diffuse technique. Even a minimal exposition at ionizing radiation in therapeutic doses can provide chemical changes on light-cured composite resins. The three studied restorative materials showed changes after exposure at gamma radiation, however the increase of the radiation dose did not contribute to an increase in this effect.

  11. Intensification of acute Trypanosoma cruzi myocarditis in BALB/c mice pretreated with low doses of cyclophosphamide or gamma irradiation.

    PubMed Central

    Silva, J. S.; Rossi, M. A.

    1990-01-01

    This study was carried out to examine the development of acute myocarditis in Trypanosoma cruzi-infected BALB/c mice after they were treated with low doses of cylophosphamide or gamma irradiation. It has been claimed that, in mice, such treatments temporarily interfere with the host-immune suppressor network, but cause no immunodepression. A severe extensive and diffuse acute myocarditis developed in the treated mice infected with T. cruzi, whereas a slight to moderate focal or occasionally diffuse acute myocarditis developed in control mice infected with T. cruzi. It is very likely that the transient abolition of T-suppressor activity facilitates the anti-myocardium immune response in the acute phase of experimental Chagas' disease in mice. Images Fig. 3 PMID:2138024

  12. Effects of low-dose carbon ion irradiation on the proliferation of splenocytes and the concentration of interferon in mice

    NASA Astrophysics Data System (ADS)

    Li, Ning

    AIM: To investigate the changes in the proliferation response of splenic lymphocytes and the concentration of serum interferon (IFN-γ) in mice induced by low doses carbon ion irradiation. METHODS: The experiment was carried out in the laboratory of physical medicine, Institute of Modern Physics, Chinese Academy of Sciences in November 2006. 1. Thirty Kunming mice were randomly divided into five groups with six animals in each group and irradiated with 0, 0.01, 0.03, 0.05 and 0.10 Gy carbon ion at Heavy Ion Research Facility Laboratory of Lanzhou. Twenty-four hours after irradiation, the eyeballs of mice were taken out under anesthesia and blood was harvested. 2. The concentration of IFN-γ in serum was detected by ELISA kit. After the mice were executed, the spleen was harvested under sterile condition to prepare spleen mononuclear cell suspension. The effects of concanavalin A(ConA) and lipopolysaccharide(LPS) on the proliferations of mononuclear cells was tested by MTT assay. RESULTS: All thirty mice were involved in the result analysis. 1. The concentration of IFN-γ in serum remarkably increased after irradiation with 0.01 Gy and 0.03 Gy compared with that in controls (p<0.05). However, the concentration of IFN-γ decreased after irradiation with 0.05 Gy and 0.1 Gy. 2. Compared with control group, the proliferation of T lymphocytes induced by ConA and B lymphocytes induced by LPS remarkably increased after irradiation with 0.01 Gy (p<0.001) and the effect was of significant difference compared with that of 0.03 Gy (p<0.01). The irradiation with 0.05 Gy presented an inhibition to the proliferation of splenic lymphocytes. This inhibition was also obvious when irradiated with 0.10 Gy. CONCLUSION: 0.01 Gy and 0.03 Gy carbon ion irradiation can stimulate the proliferation of splenocytes, induce the secretion of IFN-γ and, in consequence, enhance the immune function.

  13. Management of high-grade stage I adenocarcinoma of the endometrium: hysterectomy following low dose external beam pelvic irradiation

    SciTech Connect

    Shimm, D.S.; Wang, C.C.; Fuller, A.F. Jr.; Nelson, J.H. Jr.; Nikrui, N.; Young, R.H.; Scully, R.E.

    1986-02-01

    Sixty-eight patients with FIGO stage I, grade 2 or 3 adenocarcinoma of the endometrium were treated according to a protocol involving 10 Gy external pelvic irradiation, prompt hysterectomy with surgical staging, and postoperative therapy individualized according to surgical-pathologic findings. Five-year survival for the entire group was 78%, 87% for those with grade 2 disease, and 59% for those with grade 3 disease. For patients whose disease was found to be confined to the uterus, surgical stage I, the 5-year survival was 98%. Patients with surgical stage I, grades 2 and 3 disease had 97 and 100% probabilities of surviving 5 years, respectively. Five-year disease-free probability was 96% for all patients with surgical stage I carcinoma, 97% for patients with grade 2 disease, and 94% for patients with grade 3 disease. Myometrial penetration influenced survival; no patient with less than 50% myometrial penetration died or suffered a relapse, while only 40% of patients with deeper penetration survived 5 years. Twenty-three percent of patients with surgically confirmed disease spread beyond the corpus survived 5 years; 29% remained disease-free at this interval. Ten of the 68 patients developed recurrences, none has had a known pelvic recurrence. Two major complications, one requiring surgery, were seen, both in patients receiving postoperative external beam irradiation. The rationale behind low-dose, preoperative external pelvic irradiation is described, and an approach to high-grade, FIGO stage I adenocarcinoma of the endometrium is outlined.

  14. The effect of low dose rate irradiation on the swelling of 12% cold-worked 316 stainless steel.

    SciTech Connect

    Allen, T. R.

    1999-03-02

    In pressurized water reactors (PWRs), stainless steel components are irradiated at temperatures that may reach 400 C due to gamma heating. If large amounts of swelling (>10%) occur in these reactor internals, significant swelling related embrittlement may occur. Although fast reactor studies indicate that swelling should be insignificant at PWR temperatures, the low dose rate conditions experienced by PWR components may possibly lead to significant swelling. To address these issues, JNC and ANL have collaborated to analyze swelling in 316 stainless steel, irradiated in the EBR-II reactor at temperatures from 376-444 C, at dose rates between 4.9 x 10{sup {minus}8} and 5.8 x 10{sup {minus}7} dpa/s, and to doses of 56 dpa. For these irradiation conditions, the swelling decreases markedly at temperatures less than approximately 386 C, with the extrapolated swelling at 100 dpa being around 3%. For temperatures greater than 386 C, the swelling extrapolated to 100 dpa is around 9%. For a factor of two difference in dose rate, no statistically significant effect of dose rate on swelling was seen. For the range of dose rates analyzed, the swelling measurements do not support significant (>10%) swelling of 316 stainless steel in PWRs.

  15. Thyroid gland morphology in young adults: normal subjects versus those with prior low-dose neck irradiation in childhood

    SciTech Connect

    Hanson, G.A.; Komorowski, R.A.; Cerletty, J.M.; Wilson, S.D.

    1983-12-01

    Thyroid glands obtained at autopsy from young adults were studied to establish more accurately the ''normal'' morphology in the groups 20 to 40 years of age. A total of 56 autopsy specimens (many obtained from trauma victims) were examined in detail by totally embedding and sectioning the thyroid glands. The morphology of these thyroid glands also was compared to that of surgically removed thyroid glands from 47 young adult patients with prior low-dose neck irradiation. The ''normal'' thyroid specimens frequently showed morphologic features, such as thyroid tissue outside the recognizable capsule of the gland (40 of 56 patients) and in the strap muscles of the neck (six of 56 patients), which are conditions commonly considered as evidence for invasive thyroid carcinoma. The thyroid glands from the ''normal'' young adult population were significantly different from those thyroid glands surgically removed from patients who had received irradiation. The irradiated thyroid glands invariably showed multiple nodules of a wide variety of histologic types, extensive lymphocytic infiltrates, and distorting fibrosis as well as a high incidence of malignancy (27 of 47 patients). A single 0.1 cm focus of papillary carcinoma was found in one specimen in the nonirradiated thyroid group. This study suggests that ''occult'' thyroid carcinomas in the group 20 to 40 years of age are rare and are significantly fewer in number than in the older population (P less than 0.02).

  16. Sequential changes in bone marrow architecture during continuous low dose gamma irradiation

    SciTech Connect

    Seed, T.M.; Chubb, G.T.; Tolle, D.V.

    1981-01-01

    Beagles continuously exposed to low daily doses (10 R) of whole-body /sup 60/Co ..gamma..-radiation are prone to develop either early occurring aplasstic anemia or late occurring myeloproliferative disorders. In this study, we have examined by a combination of light microscopy and scanning and transmission electron microscopy the sequential changes in the morphology of biopsied rib bone marrow of continuously irradiated dogs that developed either aplastic anemia, myelofibrosis, or myelogenous leukemia. Characteristic modifications of key elements of marrow architecture have been observed during preclinical and clinical phases of these hemopathological conditions. These architectural changes during preclinical phases appear to be related to the pathological progression to each of the radiation-induced hemopathological end points.

  17. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

    PubMed

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  18. DELAYED EFFECTS OF ACUTE RADIATION EXPOSURE IN A MURINE MODEL OF THE H-ARS: MULTIPLE-ORGAN INJURY CONSEQUENT TO <10 GY TOTAL BODY IRRADIATION

    PubMed Central

    Unthank, Joseph L.; Miller, Steven J.; Quickery, Ariel K.; Ferguson, Ethan L.; Wang, Meijing; Sampson, Carol H.; Chua, Hui Lin; DiStasi, Matthew R.; Feng, Hailin; Fisher, Alexa; Katz, Barry P.; Plett, P. Artur; Sandusky, George E.; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P.; MacVittie, Thomas J.; Orschell, Christie M.

    2015-01-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a 137Cs radiation source and studied 1–21 months later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ~22 to 34 ± 3.8 and 69±6.0 mg/dl, p<0.01 vs non-irradiated controls) and correlated with glomerosclerosis (29±1.8% vs 64±9.7% of total glomeruli, p<0.01 vs non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peri-bronchial fibrosis/collagen deposition was observed from ~9–21 mo post-TBI in kidney, heart and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs. PMID:26425910

  19. Sequential changes in bone marrow architecture during continuous low dose gamma irradiation

    SciTech Connect

    Seed, T.M.; Chubb, G.T.; Tolle, D.V.

    1981-01-01

    Beagles continuously exposed to low daily doses (10 R) of whole-body 60Co gamma-radiation are prone to develop either early occurring aplastic anemia or late occurring myeloproliferative disorders (Seed et al., 1977). In this study, we have examined by a combination of light microscopy and scanning and transmission electron microscopy the sequential changes in the morphology of biopsied rib bone marrow of continuously irradiated dogs that developed either aplastic anemia, myelofibrosis, or myelogenous leukemia. Characteristic modification of key elements of marrow architecture have been observed during preclinical and clinical phases of these hemopathological conditions. The more prominent of these changes include the following. (i) In developing aplastic anemia: severe vascular sinus and parenchymal cord compression, and focally degenerate endosteal surfaces. (ii) In developing myelofibrosis: hyperplasia of endosteal and reticular stomal elements. (iii) In developing leukemia: hypertrophy of reticular and endothelial elements in the initial restructuring of the stromal matrix and the subsequent aberrant hemopoietic repopulation of the initially depleted stromal matrix. These architectural changes during preclinical phases appear to be related to the pathological progression to each of the radiation-induced hemopathological end points.

  20. Dose equivalence for high-dose-rate to low-dose-rate intracavitary irradiation in the treatment of cancer of the uterine cervix

    SciTech Connect

    Akine, Y.; Tokita, N.; Ogino, T.; Kajiura, Y.; Tsukiyama, I.; Egawa, S. )

    1990-12-01

    By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.

  1. Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection.

    PubMed

    Byrum, Stephanie D; Burdine, Marie S; Orr, Lisa; Mackintosh, Samuel G; Authier, Simon; Pouliot, Mylene; Hauer-Jensen, Martin; Tackett, Alan J

    2017-01-01

    Acute radiation syndrome (ARS) is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI) in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy) with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.

  2. Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection

    PubMed Central

    Burdine, Marie S.; Orr, Lisa; Mackintosh, Samuel G.; Authier, Simon; Pouliot, Mylene; Hauer-Jensen, Martin; Tackett, Alan J.

    2017-01-01

    Acute radiation syndrome (ARS) is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI) in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy) with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure. PMID:28350824

  3. Induction of a Radio-Adaptive Response by Low-dose Gamma Irradiation in Mouse Cardiomyocytes

    NASA Technical Reports Server (NTRS)

    Westby, Christian M.; Seawright, John W.; Wu, Honglu

    2011-01-01

    One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137Cs gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value < or = 0.003) 4hr after H, but not after 4hr LH compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio

  4. Enhancement of Peroxidase Release from Non-Malignant and Malignant Cells through Low-Dose Irradiation with Different Radiation Quality.

    PubMed

    Abdelrazzak, Abdelrazek B; Pottgießer, Stefanie J; Hill, Mark A; O'Neill, Peter; Bauer, Georg

    2016-02-01

    The release of peroxidase by nontransformed or transformed fibroblasts or epithelial cells (effector cells) triggers apoptosis induction selectively in transformed fibroblasts or transformed epithelial cells (target cells) through intercellular apoptosis-inducing signaling. The release of peroxidase can be induced either by treatment with transforming growth factor beta 1 or by low doses of alpha particles, gamma rays or ultrasoft X rays. In addiation, data indicates that radiation quality does not determine the overall efficiency of peroxidase release and the effects among a wide range of radiation doses are indistinguishable. These findings suggested that peroxidase release might be being triggered through intercellular bystander signaling. We show here that maximal peroxidase release does indeed occur after coculture of a small number of irradiated cells with an excess of unirradiated cells and demonstrate an enhanced effector function of nontransformed cells after the addition of a small number of irradiated cells. These data strongly indicate that peroxidase release is indeed triggered through bystander signaling mechanisms in mammalian cells.

  5. Hodgkin's disease in children: Treatment with MOPP and low-dose, extended field irradiation without laparotomy. Late results and toxicity

    SciTech Connect

    Jenkin, D.; Doyle, J.; Berry, M.; Blanchette, V.; Chan, H.; Doherty, M.; Freedman, M.; Greenberg, M.; Panzarella, T.; Saunders, F. )

    1990-01-01

    The 10 year results of a trial of bimodal treatment of Hodgkin's disease in children with 6 cycles of MOPP and low-dose extended field irradiation, without staging laparotomy, were for 57 children in all stages as follows: survival 85%, relapse-free survival 80%, and survival-free of second relapse 86%. There were three fatal toxic events, two due to viral infection and one to a second malignant tumor (NHL). Three other patients developed a second malignant tumour, and one developed a thyroid adenoma. No patient developed acute leukemia. These results are compared with the results of treatment of surgically staged children by extended field irradiation alone, with bimodal treatment reserved for relapse or advanced disease at diagnosis. Initial bimodal treatment improved the overall 10 year survival free from a second relapse rate by 20% (86% vs. 66%). No major difference in treatment toxicity between these two groups has emerged during the first 10 years of follow-up. We conclude that, except for favourable CS-1 presentations, children with Hodgkin's disease confined to the lymphatic system should be given bimodal treatment, but that the least morbid effective combination remains to be determined.

  6. Identification of low-dose responsive metabolites in X-irradiated human B lymphoblastoid cells and fibroblasts

    PubMed Central

    Tsuyama, Naohiro; Mizuno, Hajime; Katafuchi, Atsushi; Abe, Yu; Kurosu, Yumiko; Yoshida, Mitsuaki; Kamiya, Kenji; Sakai, Akira

    2015-01-01

    Ionizing radiation (IR) induces cellular stress responses, such as signal transduction, gene expression, protein modification, and metabolite change that affect cellular behavior. We analyzed X-irradiated human Epstein-Barr virus-transformed B lymphoblastoid cells and normal fibroblasts to search for metabolites that would be suitable IR-responsive markers by Liquid Chromotography–Mass spectrometry (LC–MS). Mass spectra, as analyzed with principal component analysis, showed that the proportion of peaks with IR-induced change was relatively small compared with the influence of culture time. Dozens of peaks that had either been upregulated or downregulated by IR were extracted as candidate IR markers. The IR-changed peaks were identified by comparing mock-treated groups to 100 mGy-irradiated groups that had recovered after 10 h, and the results indicated that the metabolites involved in nucleoside synthesis increased and that some acylcarnitine levels decreased in B lymphoblastoids. Some peaks changed by as much as 20 mGy, indicating the presence of an IR-sensitive signal transduction/metabolism control mechanism in these cells. On the other hand, we could not find common IR-changed peaks in fibroblasts of different origin. These data suggest that cell phenotype-specific pathways exist, even in low-dose responses, and could determine cell behavior. PMID:25227127

  7. [Morphometric analysis of follicular structure of the thyroid gland after chronic low-dose gamma-irradiation].

    PubMed

    Pavlov, A V; Ermakova, O V; Korableva, T V; Raskosha, O V

    2013-01-01

    A quantitative study of follicle average cross-sectional diameter distribution was conducted in the thyroid gland (TG) of mouse like rodents (25 tundra voles, 24 CBA mice, 16 Wistar rats) after chronic exposure to low-level external y-radiation both in the environment and under the experimental condition (absorbed dose range 0.05-0.5 Gy). Spectrum analysis of TG follicle cross-sectional diameter distribution in the irradiated animals has demonstrated a universal regularity: in comparison with the unirradiated animals there was a significant (1.3-1.7-fold) increase in content of small follicles (with a cross-sectional diameter lower than 36-41 microm in the studied animal species). A similar phenomenon was reproduced in the model experiments (TG regeneration in rats after hemithyroidectomy). The observed activation of the folliculogenesis processes after chronic low-dose irradiation in small doses may be interpreted as a nonspecific adaptive reaction of TG to radiation induced damage of its parenchyma.

  8. Low dose irradiation of thyroid cells reveals a unique transcriptomic and epigenetic signature in RET/PTC-positive cells.

    PubMed

    Abou-El-Ardat, Khalil; Monsieurs, Pieter; Anastasov, Nataša; Atkinson, Mike; Derradji, Hanane; De Meyer, Tim; Bekaert, Sofie; Van Criekinge, Wim; Baatout, Sarah

    2012-03-01

    The high doses of radiation received in the wake of the Chernobyl incident and the atomic bombing of Hiroshima and Nagasaki have been linked to the increased appearance of thyroid cancer in the children living in the vicinity of the site. However, the data gathered on the effect of low doses of radiation on the thyroid remain limited. We have examined the genome wide transcriptional response of a culture of TPC-1 human cell line of papillary thyroid carcinoma origin with a RET/PTC1 translocation to various doses (0.0625, 0.5, and 4Gy) of X-rays and compared it to response of thyroids with a RET/PTC3 translocation and against wild-type mouse thyroids irradiated with the same doses using Affymetrix microarrays. We have found considerable overlap at a high dose of 4Gy in both RET/PTC-positive systems but no common genes at 62.5mGy. In addition, the response of RET/PTC-positive system at all doses was distinct from the response of wild-type thyroids with both systems signaling down different pathways. Analysis of the response of microRNAs in TPC-1 cells revealed a radiation-responsive signature of microRNAs in addition to dose-responsive microRNAs. Our results point to the fact that a low dose of X-rays seems to have a significant proliferative effect on normal thyroids. This observation should be studied further as opposed to its effect on RET/PTC-positive thyroids which was subtle, anti-proliferative and system-dependent. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Establishment of ku70-deficient lung epithelial cell lines and their hypersensitivity to low-dose x-irradiation.

    PubMed

    Koike, Manabu; Yutoku, Yasutomo; Koike, Aki

    2011-05-01

    In clinical situations, cellular resistance to chemotherapy and radiotherapy is a significant component of tumor treatment failure. The DNA repair protein Ku70 is a key contributor to chemoresistance to anticancer agents, e.g., etoposide and bleomycin, or radioresistance. Ku70 plays a key role as a sensor of DNA double-strand breaks (DSBs) induced following exposure to ionizing radiation as well as treatment with some chemotherapeutic drugs. The responses of different organs to radiation vary widely and likely depend on the cell population in the organs. However, it is not clear whether Ku70 plays a role in the low-dose radioresistance of lung epithelial cells. In this study, we established Ku70-deficient epithelial cell lines from murine lungs lacking Ku70. Ku70-/- lung epithelial cells exhibited reduced Ku80 expression. Moreover, Ku70-/- lung epithelial cells were more sensitive than controls (Ku70+/- lung epithelial cells) to low-dose X-irradiation (< 0.5 Gy). We also found that consistent with the Ku70 function as a sensor of DSBs, Ku70 mainly localized in the nuclei of murine lung epithelial cells. These findings clearly indicate that Ku70 plays a key role in regulation of the Ku80 expression level in and the radioresistance of lung epithelial cells. Our data also suggest that these cell lines might be useful not only for study of Ku70 functions and the DSB repair pathway, but also for study of the molecular mechanism underlying the sensitivity to chemotherapeutic drugs and radiation in lung epithelial cells.

  10. Modulation of in utero total body irradiation induced newborn mouse growth retardation by maternal manganese superoxide dismutase-plasmid liposome (MnSOD-PL) gene therapy.

    PubMed

    Epperly, M W; Smith, T; Zhang, X; Goff, J P; Franicola, D; Greenberger, B; Komanduri, P; Wang, H; Greenberger, J S

    2011-06-01

    To determine the effects of manganese superoxide dismutase (MnSOD) plasmid liposome (PL) maternal radioprotection on fetal mice, timed pregnant female mice (E14 gestation) were irradiated to 3.0 Gy total body irradiation (TBI) dose, and the number, weight and growth and development over 6 months after birth of newborn mice was quantitated compared with irradiated controls. Maternal MnSOD-PL treatment at E13 improved pup survival at birth (5.4±0.9 per litter) compared with non-irradiated 3.0 Gy controls 4.9±1.1. There was no statistically significant difference in newborn abnormalities, male to female ratio in newborn litters, or other evidence of teratogenesis in surviving newborn mice from MnSOD-PL treated compared with irradiated controls. However, E14 3 Gy irradiated pups from gene therapy-treated mothers showed a significant increase in both growth and overall survival over 6 months after birth (P=0.0022). To determine if transgene product crossed the placenta pregnant E13 mice were injected intravenously with hemagglutinin-epitope-tagged MnSOD (100 μg plasmid in 100 μl liposomes), then after 24 h, fetal mice, placentas and maternal tissues were removed and tested by both immunohistochemistry and reverse transcriptase-PCR for transgene and product. There was no evidence of transgene or product in placenta or any fetal tissue while maternal liver was positive by both assays. The data provide evidence for fetal radioprotection by maternal MnSOD-PL gene therapy before irradiation, which is mediated by an indirect bystander effect and is associated with a significant improvement in both survival at birth and growth and development of newborn mice.

  11. Low-dose dental irradiation decreases oxidative stress in osteoblastic MC3T3-E1 cells without any changes in cell viability, cellular proliferation and cellular apoptosis.

    PubMed

    Pramojanee, Sakarat N; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2012-03-01

    Cellular responses following low-dose irradiation have been widely debated. Several studies have revealed detrimental effects of low-dose irradiation; however, some studies have shown contrasting results. Moreover, the effects of periapical irradiation on osteoblastic cells have not yet been revealed. Therefore, in this study, we tested the hypothesis that low-dose dental irradiation of osteoblastic cells reduces reactive oxygen species (ROS) production and leads to increased cellular proliferation and high-dose dental irradiation of osteoblastic cells increases ROS production and leads to cellular apoptosis. We irradiated MC3T3-E1 cells with various doses of periapical irradiation (0, 1, 2, 5 and 10 doses, 1.5 mGy/dose). We evaluated cell viability using MTT assay, the expression of Bax and Bcl-2, as markers for apoptosis and the expression of cyclin D1 as a marker for cell proliferation 24h after each irradiation. We also measured ROS production 4h following each irradiation. ROS production was significantly reduced after one dose of periapical irradiation (1.5 mGy); however, after 10 doses (15 mGy), ROS production was significantly increased (p<0.05). None of the doses of dental radiation affected cell viability as determined by MTT assay, nor did they change the apoptotic marker: (the Bax/Bcl-2 ratio). However, 10 doses of dental irradiation significantly decreased the expression of cyclin D1. Our findings suggest that low-dose dental radiation may help to detoxify osteoblastic cells by reducing ROS production without any changes in cell viability, cellular apoptosis or proliferation. However, high-dose dental radiation impairs osteoblastic proliferation via increase ROS production without any changes in cell viability or apoptotic responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Chronic low-dose γ-irradiation of Drosophila melanogaster larvae induces gene expression changes and enhances locomotive behavior

    PubMed Central

    Kim, Cha Soon; Seong, Ki Moon; Lee, Byung Sub; Lee, In Kyung; Yang, Kwang Hee; Kim, Ji-Young; Nam, Seon Young

    2015-01-01

    Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and the rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy γ-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. The pupation height of the LDR-treated group at the first larval instar was significantly higher (∼2-fold increase in PHI value, P < 0.05). The locomotive behavior of LDR-treated male flies (∼3 − 5 weeks of age) was significantly increased by 7.7%, 29% and 138%, respectively (P < 0.01), but pupation and eclosion rates and life spans were not significantly altered. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with in control larvae. We identified several genes belonging to larval behavior functional groups such as locomotion (1.1%), oxidation reduction (8.0%), and genes involved in conventional functional groups modulated by irradiation such as defense response (4.9%), and sensory and perception (2.5%). Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR (>2-fold change). These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR. PMID:25792464

  13. Induction of rhodanese, a detoxification enzyme, in livers from mice after long-term irradiation with low-dose-rate gamma-rays.

    PubMed

    Nakajima, Tetsuo; Taki, Keiko; Wang, Bing; Ono, Tetsuya; Matsumoto, Tsuneya; Oghiso, Yoichi; Tanaka, Kimio; Ichinohe, Kazuaki; Nakamura, Shingo; Tanaka, Satoshi; Nenoi, Mitsuru

    2008-11-01

    The health effects of low-dose radiation exposure are of public concern. Although molecular events in the cellular response to high-dose-rate radiation exposure have been fully investigated, effects of long-term exposure to extremely low-dose-rate radiation remain unclear. Protein expression was analyzed by two-dimensional electrophoresis in livers from mice irradiated for 485 days (22 hr/day) at low-dose-rates of 0.032 microGy/min, 0.65 microGy/min and 13 microGy/min (total doses of 21 mGy, 420 mGy and 8000 mGy, respectively). One of the proteins that showed marked changes in expression was identified as rhodanese (thiosulfate sulfurtransferase). Rhodanese expression was increased after irradiation at 0.65 microGy/min and 13 microGy/min, while its expression was not changed at 0.032 microGy/min. Rhodanese is a detoxification enzyme, probably related to the regulation of antioxidative function. However, antioxidative proteins, such as superoxide dismutase (SOD)1 (also known as Cu,Zn-SOD) and SOD2 (also known as Mn-SOD), which can be induced by high-dose-rate radiation, were not induced at any low-dose-rates tested. These findings indicate that rhodanese is a novel protein induced by low-dose-rate radiation, and further analysis could provide insight into the effects of extremely low-dose-rate radiation exposure.

  14. Interaction between total body gamma-irradiation and choline deficiency triggers immediate modulation of choline and choline-containing moieties.

    PubMed

    Batra, Vipen; Kislay, Binita; Devasagayam, Thomas Paul Asir

    2011-12-01

    The objective of this study was to examine the effect of 60Co-gamma (γ) radiation on acute phase modulation, if any, of choline and choline-containing moieties in choline-deficient subjects. Corresponding results could provide information that might be useful in the management of adverse effects of γ-radiation. Male Swiss mice maintained on a choline-sufficient diet (CSD) and choline-free diet (CFD) based on AIN-93M formula, were subjected to whole body γ-irradiation (2-6 Gy). Liver, serum and brain samples from each group were then tested for: (i) Alterations in choline and choline-containing moieties such as phosphatidylcholine (PC) and sphingomyeline (SM); and (ii) modulation of choline profile modulating enzymes such as phospholipase D (PLD) and total sphingomyelinase (t-SMase). Liver and brain samples were also subjected to histo-pathological examinations. No significant changes were observed in folate, choline, choline-containing moieties and choline-modulating enzymes in choline-sufficient mice. In contrast, interaction between cytotoxic effects of γ-radiation and choline deficiency modulated choline and choline-containing moieties. Feeding CFD reduced hepatic concentrations of choline, PC and SM whereas PLD and t-SMase activities were significantly raised. The decrease in liver choline and choline-containing moieties was accompanied by an increase in blood choline concentration. Despite choline deficiency, the level of choline and acetylcholine synthesizing enzyme choline acetyltransfease (ChAT) significantly increased in the brain. We propose that choline deprivation and γ-radiation interact to modulate choline reserves of hepatic tissue, which might release choline to blood. Our studies also clearly showed that interaction between choline deficiency and γ-radiation might substantially enhance liver adipogenesis.

  15. Possible use of EPDM in radioactive waste disposal: Long term low dose rate and short term high dose rate irradiation in aquatic and atmospheric environment

    NASA Astrophysics Data System (ADS)

    Hacıoğlu, Fırat; Özdemir, Tonguç; Çavdar, Seda; Usanmaz, Ali

    2013-02-01

    In this study, changes in the properties of ethylene propylene diene terpolymer (EPDM) irradiated with different dose rates in ambient atmosphere and aqueous environment were investigated. Irradiations were carried out both with low dose and high dose rate irradiation sources. EPDM samples which were differentiated from each other by peroxide type and 5-ethylidene 2-norbornene (ENB) contents were used. Long term low dose rate irradiations were carried out for the duration of up to 2.5 years (total dose of 1178 kGy) in two different irradiation environments. Dose rates (both high and low), irradiation environments (in aquatic and open to atmosphere), and peroxide types (aliphatic or aromatic) were the parameters studied. Characterization of irradiated EPDM samples were performed by hardness, compression, tensile, dynamic mechanical analysis (DMA), TGA-FTIR, ATR-FTIR, XRD and SEM tests. It was observed that the irradiation in water environment led to a lower degree of degradation when compared to that of irradiation open to atmosphere for the same irradiation dose. In addition, irradiation environment, peroxide type and dose rate had effects on the extent of change in the properties of EPDM. It was observed that EPDM is relatively radiation resistant and a candidate polymer for usage in radioactive waste management.

  16. Cytogenetic studies in dogs after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells: observations in long-term chimeras

    SciTech Connect

    Carbonell, F.; Calvo, W.; Fliedner, T.M.; Kratt, E.; Gerhartz, H.; Koerbling, M.; Nothdurft, W.; Ross, W.M.

    1984-03-01

    Cytogenetic studies were performed on two dog groups after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells. The first group of dogs was transfused with unseparated leukocytes and suffered from graft-versus-host disease (GvHD). Cytogenetic studies demonstrated only cells of donor origin in all dogs of this group. The second group of animals was transfused with fraction 2 of a discontinuous albumin gradient. The dogs of this group did not develop GvHD, and the cytogenetic studies showed the presence of a mosaic of cells from donor and recipient origin in all of them. These results suggest that the GvHD may suppress autochthonous regeneration.

  17. Evidences for amelioration of reserpine-induced fibromyalgia in rat by low dose of gamma irradiation and duloxetine.

    PubMed

    Shibrya, Eman E; Radwan, Rasha R; Abd El Fattah, Mai A; Shabaan, Esmat A; Kenawy, Sanaa A

    2017-05-01

    Fibromyalgia is a prevalent disorder characterized by chronic widespread pain and complex symptoms. This study was conducted to investigate the potential therapeutic effect of low-dose irradiation (LDI) alone or in combination with duloxetine on the reserpine-induced fibromyalgia in rats. Fibromyalgia was induced by administration of reserpine (1 mg/kg/s.c) for 3 consecutive days. Duloxetine (30 mg/kg, p.o) was administered 60 min before a forced swimming test (FST), and rats were exposed to a single dose of γ-radiation (0.5 Gy) 1 day before the FST. Reserpine significantly increased immobility time in the FST, decreased the amount of 5-hydroxytryptamine, dopamine, and norepinephrine in cerebral cortex. It also increased malondialdehyde and nitric oxide and reduced glutathione contents in brain tissue. LDI alone or combined with duloxetine completely antagonized reserpine-induced fibromyalgia as assessed by the measured parameters. One of the most significant findings in this study was that the therapeutic effect of duloxetine was more pronounced by its combination with LDI. A possible mechanism of action of LDI and duloxetine responsible for their therapeutic effect was discussed. On the basis of the presented evidences, it could be concluded that LDI alone or combined with duloxetine could be of value in the management of fibromyalgia.

  18. Mobilization of LINE-1 in irradiated mammary gland tissue may potentially contribute to low dose radiation-induced genomic instability.

    PubMed

    Luzhna, Lidia; Ilnytskyy, Yaroslav; Kovalchuk, Olga

    2015-01-01

    It is known that cellular stresses such as ionizing radiation activate LINE-1 (long interspersed nuclear element type 1, L1), but the molecular mechanisms of LINE-1 activation have not been fully elucidated. There is a possibility that DNA methylation changes induced by genotoxic stresses might contribute to LINE-1 activation in mammalian cells. L1 insertions usually cause major genomic rearrangements, such as deletions, transductions, the intrachromosomal homologous recombination between L1s, and the generation of pseudogenes, which could lead to genomic instability. The purpose of this study was to evaluate the effects of low and high doses of ionizing radiation on the DNA methylation status of LINE-1 transposable elements in rat mammary glands. Here we describe radiation-induced hypomethylation and activation of LINE-1 ORF1 in rat mammary gland tissues. We show that radiation exposure has also led to the translation of the LINE-1 element, whereby the 148 kDa LINE-1 protein level was increased 96 hours after treatment with a low dose and low energy level radiation and remained elevated for 24 weeks after treatment. The mobilization of LINE-1 in irradiated tissue may potentially contribute to genomic instability. The observed activation of mobile elements in response to radiation exposure is consistently discussed as a plausible mechanism of cancer etiology and development.

  19. Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with a dose of 2.4 Gy.

    PubMed

    Nothdurft, W; Selig, C; Fliedner, T M; Hintz-Obertreis, P; Kreja, L; Krumwieh, D; Kurrle, R; Seiler, F R; Weinsheimer, W

    1992-04-01

    It was the specific aim of this study to test the stimulatory effects of recombinant human GM-CSF (rhGM-CSF) on haemopoietic regeneration in dogs which had received total-body irradiation (TBI) with a dose of 2.4 Gy. In normal dogs rhGM-CSF given subcutaneously at 10 microgram/kg per day or 30 microgram/kg per day for 21 days caused strong but transient increases in the peripheral blood neutrophils. The monocyte counts also showed a transient rise during treatment in a dose-dependent fashion, whereas the lymphocyte counts increased only at the higher dose of rhGM-CSF and the platelet counts were transiently depressed during the course of the treatment. In the irradiated animals treatment with rhGM-CSF decreased the severity and shortened the duration of neutropenia but had no significant influence on monocyte or lymphocyte recovery. The granulocyte values showed a characteristic pattern of fluctuations with the first peak occurring at the same time (day 10 to day 13) when the abortive rise was observed in the untreated dogs. In contrast the GM-CFC in the peripheral blood remained depressed during the whole treatment course, similar to the untreated irradiated controls. These results indicate that treatment with GM-CSF can be an effective biological monotherapy for radiation-induced bone marrow failure, but that for higher radiation doses the number of GM-CSF responsive target cells will become a critical determinant of therapeutic efficacy.

  20. Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin mitigates total body irradiation-induced long-term bone marrow suppression.

    PubMed

    Li, Hongliang; Wang, Yong; Pazhanisamy, Senthil K; Shao, Lijian; Batinic-Haberle, Ines; Meng, Aimin; Zhou, Daohong

    2011-07-01

    Our recent studies showed that total body irradiation (TBI) induces long-term bone marrow (BM) suppression in part by induction of hematopoietic stem cell (HSC) senescence through reactive oxygen species (ROS). In this study, we examined if Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin (MnTE), a superoxide dismutase mimetic and potent antioxidant, can mitigate TBI-induced long-term BM injury in a mouse model. Our results showed that post-TBI treatment with MnTE significantly inhibited the increases in ROS production and DNA damage in HSCs and the reduction in HSC frequency and clonogenic function induced by TBI. In fact, the clonogenic function of HSCs from irradiated mice after MnTE treatment was comparable to that of HSCs from normal controls on a per-HSC basis, suggesting that MnTE treatment inhibited the induction of HSC senescence by TBI. This suggestion is supported by the finding that MnTE treatment also reduced the expression of p16(Ink4a) (p16) mRNA in HSCs induced by TBI and improved the long-term and multilineage engraftment of irradiated HSCs after transplantation. Therefore, the results from this study demonstrate that MnTE has the potential to be used as a therapeutic agent to mitigate TBI-induced long-term BM suppression by inhibiting ionizing radiation-induced HSC senescence through the ROS-p16 pathway.

  1. Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner.

    PubMed

    Shao, Lijian; Feng, Wei; Li, Hongliang; Gardner, David; Luo, Yi; Wang, Yong; Liu, Lingbo; Meng, Aimin; Sharpless, Norman E; Zhou, Daohong

    2014-05-15

    Exposure to total body irradiation (TBI) induces not only acute hematopoietic radiation syndrome but also long-term or residual bone marrow (BM) injury. This residual BM injury is mainly attributed to permanent damage to hematopoietic stem cells (HSCs), including impaired self-renewal, decreased long-term repopulating capacity, and myeloid skewing. These HSC defects were associated with significant increases in production of reactive oxygen species (ROS), expression of p16(Ink4a) (p16) and Arf mRNA, and senescence-associated β-galacotosidase (SA-β-gal) activity, but not with telomere shortening or increased apoptosis, suggesting that TBI induces residual BM injury via induction of HSC premature senescence. This suggestion is supported by the finding that SA-β-gal(+) HSC-enriched LSK cells showed more pronounced defects in clonogenic activity in vitro and long-term engraftment after transplantation than SA-β-gal(-) LSK cells isolated from irradiated mice. However, genetic deletion of p16 and/or Arf had no effect on TBI-induced residual BM suppression and HSC senescence, because HSCs from irradiated p16 and/or Arf knockout (KO) mice exhibited changes similar to those seen in HSCs from wild-type mice after exposure to TBI. These findings provide important new insights into the mechanism by which TBI causes long-term BM suppression (eg, via induction of premature senescence of HSCs in a p16-Arf-independent manner).

  2. Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage.

    PubMed

    Ganapathi, Ramya; Manda, Kailash

    2017-05-01

    To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. MicroRNA-145 sensitizes cervical cancer cells to low-dose irradiation by downregulating OCT4 expression

    PubMed Central

    Yan, Siqi; Li, Xiangjun; Jin, Qiao; Yuan, Jun

    2016-01-01

    Poor elucidation of the mechanisms involved in regulating the radiosensitivity of cancers prevents the extensive application of low-dose radiotherapy in clinical settings. The present study was conducted to investigate the role of microRNA-145 (miR-145) in the modulation of cervical cancer cell radiosensitivity, as well as to identify the underlying target of miR-145 during this process. Cervical cancer tera cells were initially exposed to doses of radiation between 1 and 6 Gy before the assessments of the cell viability and apoptosis rate. Irradiation at dose of 1 Gy was screened as optimum dose and used in subsequent experiments. A dual luciferase reporter assay was performed to demonstrate that octamer-binding transcription factor 4 (OCT4) is a target of miR-145 in cervical cancer. Consequently, OCT4 was suggested to be a target of miR-145, as a dual luciferase vector that was ligated to a fragment corresponding to the predicted target site of miR-145 in OCT4 3′-UTR showed an 83% reduction in fluorescence. Following exposure to 1 Gy irradiation, tera cells transfected with miR-145 mimics, which showed downregulation of OCT4 and cyclin D1, had lower cell viability and cell migration rate and higher apoptosis rate compared to non-transfected cells. However, the co-transfection of miR-145 mimics and OCT4 expression vector restored OCT4 and cyclin D1 expression levels and made no significant difference in terms of cell viability, cell migration rate and apoptosis rate. The present results indicate that miR-145 increases the radiosensitivity of cervical cancer cells by silencing OCT4, that cyclin D1 is putatively under the positive regulation of OCT4 and mediates miR-145 function. PMID:27882128

  4. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    DOE PAGES

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; ...

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

  5. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    SciTech Connect

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L.; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; Moulder, John E.; Baker, John E.

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  6. In vitro quantitation of lethal and physiologic effects of total body irradiation on stromal and hematopoietic stem cells in continuous bone marrow cultures from Rf mice

    SciTech Connect

    Greenberger, J.S.; Eckner, R.J.; Otten, J.A.; Tennant, R.W.

    1982-07-01

    The effects of in vivo total body irradiation (TBI) and interval from TBI to explant of marrow on: stromal cell proliferation in vitro; stromal cell support of hematopoiesis in continuous bone marrow culture; and generation of WEHI-3 growth factor (GF)-dependent lines of hematopoietic progenitor cells were evaluated. Explant of marrow at 2, 4, 5, or 6 months after single fraction TBI (300-800 rad) was associated with decreased longevity of hemopoiesis and a decrease in the proliferative capacity of fibroblastic adherent-stromal colony forming cells (CFUf) as measured by colony size at 14 days and number of colonies per 10/sup 6/ cells plated. In contrast, explant of marrow 8 to 24 months after TBI produced cultures with longevity that was indistinguishable from age-matched control cultures (19-24 weeks). Marrow from irradiated first and second generation recipients of serially transferred marrow demonstrated a similar 7-month in vivo recovery period; however, the plateau maximum duration of hemopoiesis did not return to control levels. Purified stromal cell cultures were prepared by corticosteroid-deprivation of explanted marrow for 28 days and were then engrafted in vitro with marrow from C57BL/6J or RfM/UN mice that had been irradiated 1 month previously. Hemopoiesis in these cultures was restored, and they produced GM-CFUc and granulocytes for 15-24 weeks. Thus, healthy stroma supported growth of recently irradiated hemopoietic cells in vitro. Indirect effects of x-irradiation on hemopoietic stem cells through damage and repair in the stromal cell compartment can be effectively studied with the present bone marrow culture system. (JMT)

  7. Efficacy of integrated treatment of UV light and low dose gamma irradiation on Escherichia coli O157:H7 and Salmonella enterica on grape tomatoes

    USDA-ARS?s Scientific Manuscript database

    Efficacy of integrated treatment of UVC and low dose Gamma irradiation to inactivate mixed Strains of Escherichia coli O157:H7 and Salmonella enterica inoculated on whole Grape tomatoes was evaluated. A mixed bacterial cocktail composed of a three strain mixture of E. coli O157:H7 (C9490, E02128 an...

  8. The effects of low-dose electron-beam irradiation and storage time and temperature on xanthophyllis, antioxidant capacity, and phenolics in the potato cultivar Atlantic

    USDA-ARS?s Scientific Manuscript database

    The effects of storage and low-dose electron-beam (e-beam) irradiation on health-promoting compounds were evaluated in the potato cultivar Atlantic. Tubers were either not exposed or subjected to 200 Gy and were either sampled immediately or stored at either 4 degrees C or ambient temperature for 10...

  9. Low-dose ionizing irradiation triggers a 53BP1 response to DNA double strand breaks in mouse spermatogonial stem cells.

    PubMed

    Le, Wei; Qi, Lixin; Li, Jiaxuan; Wu, DengIong; Xu, Jun; Zhang, Jinfu

    2016-01-01

    The present study aims to examine the effect of low-dose ionizing irradiation on DNA double strand breaks (DSB) in mouse spermatogonial stem cells (SSCs) and reveal the underlying pathways for the DNA repair for DSB in SSCs. Eighteen one-month-old mice were divided into 6 groups and sacrificed separately at 45 minutes, 2 hours, 24 hours, 48 hours, and 72 hours after 0.1Gy X-ray irradiation (mice without receiving ionizing irradiation served as control). After perfusion fixation, testes were removed, sectioned, and followed by staining of γH2AX, 53BP1, Caspase 3, and promyelocytic leukemia zinc-finger (PLZF) for analysis among the different groups. The staining was observed by immunofluorescence visualized by confocal laser scanning. After low-dose irradiation, only 53BP1, but not Caspase3 or γH2AX was upregulated in PLZF positive SSCs within 45 minutes. The expression level of 53BP1 gradually decreased 24 hours after irradiation. Moreover, low-dose irradiation had no effect on the cell number and apoptotic status of SSCs. However other spermatogenic cells highly expressed γH2AX shortly after irradiation which was dramatically reduced following the events of DNA repair. It appears that low-dose ionizing irradiation may cause the DNA DSB of mouse spermatogenic cells. 53BP1, but not γH2AX, is involved in the DNA repair for DSB in SSCs. Our data indicates that 53BP1 plays an important role in the pathophysiological repair of DNA DSB in SSCs. This may open a new avenue to understanding the mechanisms of DNA repair of SSCs and male infertility.

  10. Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

    PubMed

    Seawright, John W; Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A; Hauer-Jensen, Martin; Boerma, Marjan

    2017-01-01

    Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and

  11. Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart

    PubMed Central

    Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A.; Hauer-Jensen, Martin; Boerma, Marjan

    2017-01-01

    Purpose Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Methods Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. Results The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. Conclusions This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress

  12. TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice

    PubMed Central

    Altaner, Čestmír; Altanerova, Veronica; Ebbesen, Peter

    2015-01-01

    Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation. PMID:26673923

  13. TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice.

    PubMed

    Edin, Nina Jeppesen; Altaner, Čestmír; Altanerova, Veronica; Ebbesen, Peter

    2015-01-01

    Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation.

  14. Modeling cell response to low doses of photon irradiation: Part 2--application to radiation-induced chromosomal aberrations in human carcinoma cells.

    PubMed

    Cunha, Micaela; Testa, Etienne; Komova, Olga V; Nasonova, Elena A; Mel'nikova, Larisa A; Shmakova, Nina L; Beuve, Michaël

    2016-03-01

    The biological phenomena observed at low doses of ionizing radiation (adaptive response, bystander effects, genomic instability, etc.) are still not well understood. While at high irradiation doses, cellular death may be directly linked to DNA damage, at low doses, other cellular structures may be involved in what are known as non-(DNA)-targeted effects. Mitochondria, in particular, may play a crucial role through their participation in a signaling network involving oxygen/nitrogen radical species. According to the size of the implicated organelles, the fluctuations in the energy deposited into these target structures may impact considerably the response of cells to low doses of ionizing irradiation. Based on a recent simulation of these fluctuations, a theoretical framework was established to have further insight into cell responses to low doses of photon irradiation, namely the triggering of radioresistance mechanisms by energy deposition into specific targets. Three versions of a model are considered depending on the target size and on the number of targets that need to be activated by energy deposition to trigger radioresistance mechanisms. These model versions are applied to the fraction of radiation-induced chromosomal aberrations measured at low doses in human carcinoma cells (CAL51). For this cell line, it was found in the present study that the mechanisms of radioresistance could not be triggered by the activation of a single small target (nanometric size, 100 nm), but could instead be triggered by the activation of a large target (micrometric, 10 μm) or by the activation of a great number of small targets. The mitochondria network, viewed either as a large target or as a set of small units, might be concerned by these low-dose effects.

  15. Selective Resistance of CD44hi T Cells to p53 Dependent Cell Death Results in Persistence of Immunologic Memory after Total Body Irradiation1,2,3

    PubMed Central

    Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

    2011-01-01

    Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation (TLI) markedly changes the balance of residual T cell subsets to favor CD4+CD44hi natural killer T (NKT) cells due to differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results show that CD4+ T cells were markedly more resistant than CD8+ T cells, and CD44hi T cells including NKT cells and memory T cells were markedly more resistant than CD44lo (naïve) T cells. The memory T cells immunized to alloantigens persisted even after myeloabloative (1,000cGy) TBI, and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1,000cGy was prevented in p53−/− mice, there was progressive T cell death in p53−/− mice at higher doses. Whereas, p53 dependent T cell death changed the balance of subsets, the p53 independent T cell death did not. In conclusion, resistance of CD44hi T cells to p53 dependent cell death results in the persistence of immunological memory after TBI, and can explain the immune mediated rejection of marrow transplants in sensitized recipients. PMID:21930972

  16. Selective resistance of CD44hi T cells to p53-dependent cell death results in persistence of immunologic memory after total body irradiation.

    PubMed

    Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

    2011-10-15

    Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation markedly changes the balance of residual T cell subsets to favor CD4(+)CD44(hi) NKT cells because of the differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results showed that CD4(+) T cells were markedly more resistant than CD8(+) T cells, and CD44(hi) T cells, including NKT cells and memory T cells, were markedly more resistant than CD44(lo) (naive) T cells. The memory T cells immunized to alloantigens persisted even after myeloablative (1000 cGy) TBI and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1000 cGy was prevented in p53(-/-) mice, there was progressive T cell death in p53(-/-) mice at higher doses. Although p53-dependent T cell death changed the balance of subsets, p53-independent T cell death did not. In conclusion, resistance of CD44(hi) T cells to p53-dependent cell death results in the persistence of immunological memory after TBI and can explain the immune-mediated rejection of marrow transplants in sensitized recipients.

  17. In vitro radiation studies on Ewing's sarcoma cell lines and human bone marrow: application to the clinical use of total body irradiation (TBI)

    SciTech Connect

    Kinsella, T.J.; Mitchell, J.B.; McPherson, S.; Miser, J.; Triche, T.; Glatstein, E.

    1984-07-01

    Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, the authors have studied in the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc. The Ewing's lines showed a larger D/sub 0/ and anti-n compared to the bone marrow CFU. No repair of potentially lethal radiation damage (PLDR) was found after 4.5 Gy in plateau phase Ewing's sarcoma cells. A theoretical split dose survival curve for both the Ewing's sarcoma lines and human bone marrow CFUc using this TBI schedule shows a significantly lower surviving fraction (10/sup -4/-10/sup -5/) for the bone marrow CFUc. Based on these in vitro results, two 4.0 Gy fractions separated by 24 hours is proposed as the TBI regimen. Because of the potentially irreversible damage to bone marrow, autologous bone marrow transplantation following the TBI is felt to be necessary. The details of this clinical protocol in high risk Ewing's sarcoma patients are outlined.

  18. Total body irradiation in a patient with fragile X syndrome for acute lymphoblastic leukemia in preparation for stem cell transplantation: A case report and literature review.

    PubMed

    Collins, D T; Mannina, E M; Mendonca, M

    2015-10-01

    Fragile X syndrome (FXS) is a congenital disorder caused by expansion of CGG trinucleotide repeat at the 5' end of the fragile X mental retardation gene 1 (FMR1) on the X chromosome that leads to chromosomal instability and diminished serum levels of fragile X mental retardation protein (FMRP). Afflicted individuals often have elongated features, marfanoid habitus, macroorchidism and intellectual impairment. Evolving literature suggests the condition may actually protect from malignancy while chromosomal instability would presumably elevate the risk. Increased sensitivity to ionizing radiation should also be predicted by unstable sites within the DNA. Interestingly, in this report, we detail a patient with FXS diagnosed with acute lymphoblastic leukemia treated with induction followed by subsequent cycles of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with a complete response who then was recommended to undergo peripheral stem cell transplantation. The patient underwent total body irradiation (TBI) as a component of his conditioning regimen and despite the concern of his clinicians, developed minimal acute toxicity and successful engraftment. The pertinent literature regarding irradiation of patients with FXS is also reviewed.

  19. 16,16-Dimethyl prostaglandin E2 and/or syngeneic bone marrow transplantation increase mouse survival after supra-lethal total body irradiation

    SciTech Connect

    Berk, L.B.; Patrene, K.D.; Boggs, S.S. )

    1990-06-01

    We evaluated the effects of 16,16-dimethyl prostaglandin E2 (dm-PGE2), with and without syngeneic bone marrow transplantation (BMT) on the survival and hematopoietic recovery of mice given 14-20 Gy total body irradiation (TBI). Survival of mice given combined dm-PGE2 and BMT was improved significantly over that of mice given either treatment alone. The 30-day survival after 14, 15, 16 or 18 Gy TBI for combined treatment was 97, 90, 20 or 10 percent, respectively. The corresponding 30-day survival rates for mice given BMT alone were 69, 60, 7 or 0 percent, respectively. For dm-PGE2 alone, 30-day survival was 63, 20, 10 or 0 percent, respectively. Deaths in both dm-PGE2 treated groups generally occurred after day 10 whereas deaths in the BMT group occurred before day 10. All irradiated controls were dead on or before day 10; after larger doses, deaths clustered around day 5. After 20 Gy TBI, all mice in all groups were dead by day 7. Studies of white blood cell recovery 1-9 days after 14 Gy TBI showed improvement with BMT, whereas dm-PGE2 did not enhance recovery. Nucleated cells per humerus, spleen weight, and spleen iron uptake (erythropoiesis) were also improved by BMT but not dm-PGE2.

  20. Mitigating the effects of Xuebijing injection on hematopoietic cell injury induced by total body irradiation with γ rays by decreasing reactive oxygen species levels.

    PubMed

    Li, Deguan; Lu, Lu; Zhang, Junling; Wang, Xiaochun; Xing, Yonghua; Wu, Hongying; Yang, Xiangdong; Shi, Zhexin; Zhao, Mingfeng; Fan, Saijun; Meng, Aimin

    2014-06-12

    Hematopoietic injury is the most common side effect of radiotherapy. However, the methods available for the mitigating of radiation injury remain limited. Xuebijing injection (XBJ) is a traditional Chinese medicine used to treat sepsis in the clinic. In this study, we investigated the effects of XBJ on the survival rate in mice with hematopoietic injury induced by γ ray ionizing radiation (IR). Mice were intraperitoneally injected with XBJ daily for seven days after total body irradiation (TBI). Our results showed that XBJ (0.4 mL/kg) significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This effect may be attributable to improved preservation of white blood cells (WBCs) and hematopoietic cells, given that bone marrow (BM) cells from XBJ-treated mice produced more granulocyte-macrophage colony forming units (CFU-GM) than that in the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species (ROS) by increasing glutathione (GSH) and superoxide dismutase (SOD) levels in serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In conclusion, these findings suggest that XBJ enhances the survival rate of irradiated mice and attenuates the effects of radiation on hematopoietic injury by decreasing ROS production in BM cells, indicating that XBJ may be a promising therapeutic candidate for reducing hematopoietic radiation injury.

  1. Mitigating the Effects of Xuebijing Injection on Hematopoietic Cell Injury Induced by Total Body Irradiation with γ rays by Decreasing Reactive Oxygen Species Levels

    PubMed Central

    Li, Deguan; Lu, Lu; Zhang, Junling; Wang, Xiaochun; Xing, Yonghua; Wu, Hongying; Yang, Xiangdong; Shi, Zhexin; Zhao, Mingfeng; Fan, Saijun; Meng, Aimin

    2014-01-01

    Hematopoietic injury is the most common side effect of radiotherapy. However, the methods available for the mitigating of radiation injury remain limited. Xuebijing injection (XBJ) is a traditional Chinese medicine used to treat sepsis in the clinic. In this study, we investigated the effects of XBJ on the survival rate in mice with hematopoietic injury induced by γ ray ionizing radiation (IR). Mice were intraperitoneally injected with XBJ daily for seven days after total body irradiation (TBI). Our results showed that XBJ (0.4 mL/kg) significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This effect may be attributable to improved preservation of white blood cells (WBCs) and hematopoietic cells, given that bone marrow (BM) cells from XBJ-treated mice produced more granulocyte-macrophage colony forming units (CFU-GM) than that in the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species (ROS) by increasing glutathione (GSH) and superoxide dismutase (SOD) levels in serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In conclusion, these findings suggest that XBJ enhances the survival rate of irradiated mice and attenuates the effects of radiation on hematopoietic injury by decreasing ROS production in BM cells, indicating that XBJ may be a promising therapeutic candidate for reducing hematopoietic radiation injury. PMID:24927144

  2. Neuroprotective effect of EGb761® and low-dose whole-body γ-irradiation in a rat model of Parkinson's disease.

    PubMed

    El-Ghazaly, Mona A; Sadik, Nermin A H; Rashed, Engy R; Abd-El-Fattah, Amal A

    2015-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The present study was undertaken to investigate the pretreatment effects of standardized Ginkgo biloba extract (EGb761(®)) and low-dose whole-body γ-irradiation on the neurological dysfunction in the reserpine model of PD. Male Wistar rats were pretreated orally with EGb761 or fractionated low-dose whole-body γ-irradiation or their combination, then subjected to intraperitoneal injection of reserpine (5 mg/kg body weight) 24 h after the final dose of EGb761 or radiation. Reserpine injection resulted in the depletion of striatal dopamine (DA) level, increased catalepsy score, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels, decreased DA metabolites metabolizing enzymes; indicated by inhibition by glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate (NADPH)-quinone oxidoreductase (NQO) activities, mitochondrial dysfunction; indicated by declined complex I activity, and adenosine triphosphate (ATP) level and increased apoptosis; indicated by decreased mitochondrial B cell lymphoma-2 (Bcl-2) protein level and by transmission electron microscope. EGb761 and low-dose γ-radiation ameliorated the reserpine-induced state of oxidative stress, mitochondrial dysfunction, and apoptosis in brain. It can be concluded that EGb761, a widely used herbal medicine and low dose of γ-irradiation have protective effects for combating Parkinsonism possibly via replenishment of GSH levels.

  3. Zinc sulfate in the prevention of total-body irradiation-induced early hematopoietic toxicity: a controlled study in a rat model.

    PubMed

    Ertekin, Mustafa Vecdi; Karslioğlu, Ihsan; Erdem, Fuat; Sezen, Orhan; Gepdiremen, Akçahan; Serifoğlu, Korkmaz

    2004-07-01

    Exposure to ionizing total-body radiation suppresses hematopoiesis, resulting in decreased production of blood cells. Many researchers have demonstrated the critical role of zinc (Zn) in diverse physiological processes, such as growth and development, maintenance and priming of the immune system, and tissue repair. The aim of the present study was to determine the effects of zinc sulfate (40 mg/kg and 80 mg/kg) on early hematopoietic toxicity, caused by total-body irradiation (TBI) of rats with a single dose of 8 Gy. Both in the Zn 40 and in the Zn 80 groups, there were significantly increased white blood cell (WBC) count, when compared with control group. The WBC count was higher in the control group than in the TBI group. This result was statistically significant (p<0.05). Both the TBI+Zn 40 and the TBI+Zn 80 groups had a significantly protected WBC count against TBI. No difference was detected in any final measurement of thrombocyte count and hemoglobin level with direct comparison among all groups, with the exception that the hemoglobin level in the Zn 80 group compared to the control group. Whereas hemoglobin level in the control group was at a median figure of 13.98 g/dL (13.30-14.80), it was at a median figure of 14.25 g/dL (14.10-15.50) in the Zn 80 group. It would be worthwhile studying the effect of oral zinc sulfate supplements in radiation-treated cancer patients, in the hope of reducing radiation-induced toxicity.

  4. SU-E-T-515: Field-In-Field Compensation Technique Using Multi-Leaf Collimator to Deliver Total Body Irradiation (TBI) Dose

    SciTech Connect

    Lakeman, T; Wang, IZ

    2014-06-01

    Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been used conventionally to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern field-in-field (FIF) technique with the multi-leaf collimator (MLC) to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the FIF technique to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Treatment fields include one pair of opposed open large fields (collimator=45°) with a specific weighting and a succession of smaller fields (collimator=90°) each with their own weighting. The smaller fields are shaped by moving MLC to block the sections of the patient which have already received close to 100% of the prescribed dose. The weighting factors for each of these fields were calculated using the attenuation coefficient of the initial lead compensators and the separation of the patient in different positions in the axial plane. Results: Dose-volume histograms (DVH) were calculated for evaluating the FIF compensation technique. The maximum body doses calculated from the DVH were reduced from the non-compensated 179.3% to 148.2% in the FIF plans, indicating a more uniform dose with the FIF compensation. All calculated monitor units were well within clinically acceptable limits and exceeded those of the original lead compensation plan by less than 50 MU (only ~1.1% increase). Conclusion: MLC FIF technique for TBI will not significantly increase the beam on time while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.

  5. Increased health care utilization by survivors of childhood lymphoblastic leukemia is confined to those treated with cranial or total body irradiation: a case cohort study

    PubMed Central

    2014-01-01

    Background Previous studies have indicated that survivors of childhood acute lymphoblastic leukemia (ALL) have an increased morbidity measured in terms of health care utilization. However, earlier studies have several potentially important limitations. To overcome some of these, we investigated hospital contact rates, and predictors thereof, among 5-year survivors of ALL in a population-based setting, and compared them to a control cohort regarding outcome measures from a comprehensive nation-wide health register. Methods All individuals diagnosed with ALL before the age of 18 in Southern Sweden during 1970–1999 and alive January 2007 (n = 213; male = 107) were identified through the Swedish Cancer Register. Each subject was matched to fifty controls, identified in the Swedish Population Register. All study subjects were linked to the National Hospital Register and detailed information was obtained on all hospital contacts (hospital admissions and outpatients visits) starting five years after cancer diagnosis, and the corresponding date for the controls, until 2009. Results The median follow-up among the 5-year survivors of ALL was 16 years (range 5–33), accruing a total of 3,527 person-years. Of the 213 5-year survivors, 105 (49.3%) had at least one hospital contact compared to 3,634 (34.1%) of the controls (p < 0.001). Survivors had more hospital contacts (3 [1–6] vs. 2 [1–4] contacts, p < 0.001) and more total days in hospital (6 [2–18] vs. 3 [1–7] days, p < 0.001) than the controls during the study period. Logistic regression analysis showed that survivors treated with cranial irradiation and/or total body irradiation (45% and 7%, respectively) had an increased risk of at least one hospital contact (OR 2.3, 95%CI; 1.5–3.6 and OR 11.0, 95%CI; 3.2–50.7, respectively), while there was no significant difference between the non-irradiated survivors and controls. Conclusions We show that irradiated survivors of childhood ALL have

  6. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation

    PubMed Central

    Kataoka, Takahiro

    2013-01-01

    Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation. PMID:23420683

  7. Administration of rat acute-phase protein α(2)-macroglobulin before total-body irradiation initiates cytoprotective mechanisms in the liver.

    PubMed

    Bogojević, Desanka; Poznanović, Goran; Grdović, Nevena; Grigorov, Ilijana; Vidaković, Melita; Dinić, Svetlana; Mihailović, Mirjana

    2011-03-01

    Previously, we showed that administration of the acute-phase protein α(2)-macroglobulin (α(2)M) to rats before total-body irradiation with 6.7 Gy (LD(50/30)) of X-rays provides the same level of radioprotection as amifostine. Here, we compare the cytoprotective effects of α(2)M and amifostine on rat liver. The potential of the liver to replenish cells destroyed by ionizing radiation was assessed by immunoblot analysis with antibody to proliferating cell nuclear antigen (PCNA). After irradiation, in unprotected rats PCNA decreased 6-fold from the basal level. In rats pretreated with either α(2)M or amifostine, PCNA was increased throughout a 4 week follow-up period, indicating that hepatocyte proliferation was unaffected. Since PCNA is an important component of the repair machinery, its increased expression was accompanied by significantly lower DNA damage in α(2)M- and amifostine-treated rats. At 2 weeks after irradiation, the Comet assay revealed a 15-fold increase in DNA damage in unprotected rats, while in α(2)M- and amifostine-treated rats we observed 3- and 4-fold rise in damage, respectively. The improved protection to DNA damage was supported by elevated activity of the antioxidant systems. Compared to untreated rats, pretreatments with α(2)M and amifostine led to similar increases in levels of the inflammatory cytokine IL-6 and the redox-sensitive transcription factor NFκB, promoting upregulation of MnSOD, the major component of the cell's antioxidant axis, and subsequent increases in Mn/CuZnSOD and catalase enzymatic activities. The results show that α(2)M induces protein factors whose interplay underlies radioprotection and support the idea that α(2)M is the central effector of natural radioprotection in the rat.

  8. Short communication: Survival of Mycobacterium avium ssp. paratuberculosis in tissues of cows following low-dose exposure to electron beam irradiation.

    PubMed

    Bode, John F; Thoen, Charles O

    2016-08-01

    This investigation was designed to determine the effects of low-dose electron beam irradiation on the survival of Mycobacterium avium ssp. paratuberculosis in tissue samples collected at necropsy from clinically affected cows. Mycobacterium avium ssp. paratuberculosis was isolated from the ileum and ileocecal valve of one cow and from the ileum of another cow irradiated at 4.0 kGy, but was not isolated from the ileum, ileocecal valve, or mesenteric lymph node of 11 other cows irradiated at 4 kGy.

  9. Circulating IL-18 Binding Protein (IL-18BP) and IL-18 as Dual Biomarkers of Total-Body Irradiation in Mice.

    PubMed

    Ha, Cam T; Li, XiangHong; Fu, Dadin; Xiao, Mang

    2016-04-01

    We have previously reported that circulating interleukin-18 (IL-18) can be used as a radiation biomarker in mice, minipigs and nonhuman primates. In this study, we further determined the serum levels of IL-18 binding protein (IL-18BP), a natural endogenous antagonist of IL-18, in CD2F1 mice 1-13 days after total-body gamma irradiation (TBI) with different doses (5-10 Gy). We compared the changes in blood lymphocyte, neutrophil and platelet counts as well as the activation of the proapoptotic executioner caspase-3 and caspase-7, and the expression of the inflammatory factor cyclooxygenase 2 (COX-2) in spleen cells, with the changes of IL-18BP and IL-18 in mouse serum. We also evaluated the significance, sensitivity and specificity of alterations in radiation-induced IL-18BP. IL-18 increased from day 1-13 after TBI in a dose-dependent manner that was paralleled with an increase in IL-18 receptor alpha (IL-18Rα) in irradiated mouse spleen cells. IL-18BP rapidly increased (25-63 fold) in mouse serum on day 1 after different doses of TBI. However, it returned to baseline within 3 days after 5-7 Gy doses and within 7 days after 8 Gy dose, and was unaltered thereafter. In contrast, high doses of radiation (9 and 10 Gy) significantly sustained a higher level of IL-18BP in mouse serum and later induced a second phase of increase in IL-18BP on day 9-13 after irradiation, which coincided with the onset of animal mortality. Consistent with this observation, highly activated caspase-3 and -7 in 8-10 Gy irradiated mouse spleen cells exhibited reduced or no activity 24 h after 5 Gy, although radiation induced an inflammatory response, as shown by COX-2 expression in all irradiated cells. Our data suggest that the radiation-induced differential elevation of IL-18 and IL-18BP in animal serum is a dynamic and discriminative indicator of the severity of injury after exposure to ionizing radiation. These findings support the inclusion of the dual biomarkers IL-18BP and IL-18 in the

  10. Effect of Low Doses (5-40 cGy) of Gamma-irradiation on Lifespan and Stress-related Genes Expression Profile in Drosophila melanogaster

    PubMed Central

    Zhikrevetskaya, Svetlana; Peregudova, Darya; Danilov, Anton; Plyusnina, Ekaterina; Krasnov, George; Dmitriev, Alexey; Kudryavtseva, Anna; Shaposhnikov, Mikhail; Moskalev, Alexey

    2015-01-01

    Studying of the effects of low doses of γ-irradiation is a crucial issue in different areas of interest, from environmental safety and industrial monitoring to aerospace and medicine. The goal of this work is to identify changes of lifespan and expression stress-sensitive genes in Drosophila melanogaster, exposed to low doses of γ-irradiation (5 – 40 cGy) on the imaginal stage of development. Although some changes in life extensity in males were identified (the effect of hormesis after the exposure to 5, 10 and 40 cGy) as well as in females (the effect of hormesis after the exposure to 5 and 40 cGy), they were not caused by the organism “physiological” changes. This means that the observed changes in life expectancy are not related to the changes of organism physiological functions after the exposure to low doses of ionizing radiation. The identified changes in gene expression are not dose-dependent, there is not any proportionality between dose and its impact on expression. These results reflect nonlinear effects of low dose radiation and sex-specific radio-resistance of the postmitotic cell state of Drosophila melanogaster imago. PMID:26248317

  11. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    SciTech Connect

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-11-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.

  12. Augmentation of the antileukemia potency of total-body irradiation (TBI) by a novel P-site inhibitor of spleen tyrosine kinase (SYK).

    PubMed

    Uckun, F M; Dibirdik, I; Qazi, S

    2010-10-01

    A novel spleen tyrosine kinase (SYK) P-site inhibitor, 1,4-Bis (9-O dihydroquinidinyl) phthalazine/hydroquinidine 1,4-phathalazinediyl diether (C-61), (but not vehicle) markedly enhanced H(2)O(2)-induced apoptosis of primary leukemia cells from each of five relapsed B-lineage acute lymphoblastic leukemia (ALL) patients, as measured by in vitro TUNEL assays. A highly radiation-resistant subclone of the murine B-lineage leukemia cell line BCL-1 was next used to investigate the in vivo radiosensitizing effects of C-61. C-61 enhanced the antileukemia potency of 7 Gy total-body irradiation (TBI) in the context of syngeneic bone marrow transplantation (BMT) at 20% of its nonobservable adverse effect level (NOAEL) that does not exhibit detectable single-agent activity against BCL-1 leukemia in vivo. Based on this preclinical proof-of-principle study, we hypothesize that the incorporation of C-61 into the pretransplant TBI regimens of patients with recurrent or high-risk B-lineage acute lymphoblastic leukemia (ALL) will help overcome the radiochemotherapy resistance of their leukemia cells and thereby improve their treatment response and survival outcome after BMT.

  13. Pathways analysis of differential gene expression induced by engrafting doses of total body irradiation for allogeneic bone marrow transplantation in mice.

    PubMed

    Chen, Xinjian; Wang, Yuanyuan; Li, Qiuxia; Tsai, Schickwann; Thomas, Alun; Shizuru, Judith A; Cao, Thai M

    2013-08-01

    A major challenge in allogeneic bone marrow (BM) transplantation is overcoming engraftment resistance to avoid the clinical problem of graft rejection. Identifying gene pathways that regulate BM engraftment may reveal molecular targets for overcoming engraftment barriers. Previously, we developed a mouse model of BM transplantation that utilizes recipient conditioning with non-myeloablative total body irradiation (TBI). We defined TBI doses that lead to graft rejection, that conversely are permissive for engraftment, and mouse strain variation with regards to the permissive TBI dose. We now report gene expression analysis, using Agilent Mouse 8x60K microarrays, in spleens of mice conditioned with varied TBI doses for correlation to the expected engraftment phenotype. The spleens of mice given engrafting doses of TBI, compared with non-engrafting TBI doses, demonstrated substantially broader gene expression changes, significant at the multiple testing-corrected P <0.05 level and with fold change ≥2. Functional analysis revealed significant enrichment for a down-regulated canonical pathway involving B-cell development. Genes enriched in this pathway suggest that suppressing donor antigen processing and presentation may be pivotal effects conferred by TBI to enable engraftment. Regardless of TBI dose and recipient mouse strain, pervasive genomic changes related to inflammation was observed and reflected by significant enrichment for canonical pathways and association with upstream regulators. These gene expression changes suggest that macrophage and complement pathways may be targeted to overcome engraftment barriers. These exploratory results highlight gene pathways that may be important in mediating BM engraftment resistance.

  14. Total body irradiation must be delivered at high dose for efficient engraftment and tolerance in a rhesus stem cell gene therapy model

    PubMed Central

    Uchida, Naoya; Weitzel, R Patrick; Shvygin, Anna; Skala, Luke P; Raines, Lydia; Bonifacino, Aylin C; Krouse, Allen E; Metzger, Mark E; Donahue, Robert E; Tisdale, John F

    2016-01-01

    Reduced intensity conditioning (RIC) is desirable for hematopoietic stem cell (HSC) gene therapy applications. However, low gene marking was previously observed in gene therapy trials, suggesting that RIC might be insufficient for (i) opening niches for efficient engraftment and/or (ii) inducing immunological tolerance for transgene-encoded proteins. Therefore, we evaluated both engraftment and tolerance for gene-modified cells using our rhesus HSC gene therapy model following RIC. We investigated a dose de-escalation of total body irradiation (TBI) from our standard dose of 10Gy (10, 8, 6, and 4Gy), in which rhesus CD34+ cells were transduced with a VSVG-pseudotyped chimeric HIV-1 vector encoding enhanced green fluorescent protein (GFP) (or enhanced yellow fluorescent protein (YFP)). At ~6 months after transplantation, higher-dose TBI resulted in higher gene marking with logarithmic regression in peripheral blood cells. We then evaluated immunological tolerance for gene-modified cells, and found that lower-dose TBI allowed vigorous anti-GFP antibody production with logarithmic regression, while no significant anti-VSVG antibody formation was observed among all TBI groups. These data suggest that higher-dose TBI improves both engraftment and immunological tolerance for gene-modified cells. Additional immunosuppression might be required in RIC to induce tolerance for transgene products. Our findings should be valuable for developing conditioning regimens for HSC gene therapy applications. PMID:27652288

  15. Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1-, IL-17-, and G-CSF-dependent manner.

    PubMed

    Capitano, Maegan L; Nemeth, Michael J; Mace, Thomas A; Salisbury-Ruf, Christi; Segal, Brahm H; McCarthy, Philip L; Repasky, Elizabeth A

    2012-09-27

    Neutropenia is a common side effect of cytotoxic chemotherapy and radiation, increasing the risk of infection in these patients. Here we examined the impact of body temperature on neutrophil recovery in the blood and bone marrow after total body irradiation (TBI). Mice were exposed to either 3 or 6 Gy TBI followed by a mild heat treatment that temporarily raised core body temperature to approximately 39.5°C. Neutrophil recovery was then compared with control mice that received either TBI alone heat treatment alone. Mice that received both TBI and heat treatment exhibited a significant increase in the rate of neutrophil recovery in the blood and an increase in the number of marrow hematopoietic stem cells and neutrophil progenitors compared with that seen in mice that received either TBI or heat alone. The combination treatment also increased G-CSF concentrations in the serum, bone marrow, and intestinal tissue and IL-17, IL-1β, and IL-1α concentrations in the intestinal tissue after TBI. Neutralizing G-CSF or inhibiting IL-17 or IL-1 signaling significantly blocked the thermally mediated increase in neutrophil numbers. These findings suggest that a physiologically relevant increase in body temperature can accelerate recovery from neutropenia after TBI through a G-CSF-, IL-17-, and IL-1-dependent mechanism.

  16. Longitudinal trajectory of sexual functioning after hematopoietic cell transplantation: impact of chronic graft-versus-host disease and total body irradiation.

    PubMed

    Wong, F Lennie; Francisco, Liton; Togawa, Kayo; Kim, Heeyoung; Bosworth, Alysia; Atencio, Liezl; Hanby, Cara; Grant, Marcia; Kandeel, Fouad; Forman, Stephen J; Bhatia, Smita

    2013-12-05

    This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51% (P = .01) in men and increased to 48% (P = .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P ≤ .001). Orgasm (P = .002) and drive/relationship (P < .001) declined in men, but sexual cognition/fantasy (P = .01) and sexual behavior/experience (P = .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P = .003) and orgasm (P = .006) in men and sexual arousal (P = .05) and sexual satisfaction (P = .005) in women. All male sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being.

  17. PERSONALIZED DOSING OF CYCLOPHOSPHAMIDE IN THE TOTAL BODY IRRADIATION - CYCLOPHOSPHAMIDE CONDITIONING REGIMEN: A PHASE II TRIAL IN PATIENTS WITH HEMATOLOGIC MALIGNANCY

    PubMed Central

    McCune, Jeannine S.; Batchelder, Ami; Guthrie, Katherine A.; Witherspoon, Robert; Appelbaum, Frederick R.; Phillips, Brian; Vicini, Paolo; Salinger, David H.; McDonald, George B.

    2009-01-01

    This study investigates the efficacy and safety of personalized cyclophosphamide (CY) dosing in 50 patients receiving CY with total body irradiation (TBI). Participants received CY 45 mg/kg with subsequent therapeutic drug monitoring with Bayesian parameter estimation to personalize the second CY dose to a target area under the curve for carboxyethylphosphoramide mustard (a reporter for CY-derived toxins) and for hydroxycyclophosphamide (to ensure engraftment). The mean second CY dose was 66 mg/kg; the total dose ranged from 45–145 mg/kg. After completion of this phase II study, we compared participants’ clinical outcomes to those of concurrent controls (N=100) who received TBI with standard CY doses of 120 mg/kg. Patients receiving personalized CY dosing had significantly lower post-conditioning peak total serum bilirubin (p=0.03); a 38% reduction in the hazard of acute kidney injury (p=0.03); and similar non-relapse and overall survival (p=0.70 and 0.63, respectively) despite lower doses of CY in most patients. PMID:19295506

  18. Longitudinal trajectory of sexual functioning after hematopoietic cell transplantation: impact of chronic graft-versus-host disease and total body irradiation

    PubMed Central

    Wong, F. Lennie; Francisco, Liton; Togawa, Kayo; Kim, Heeyoung; Bosworth, Alysia; Atencio, Liezl; Hanby, Cara; Grant, Marcia; Kandeel, Fouad; Forman, Stephen J.

    2013-01-01

    This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51% (P = .01) in men and increased to 48% (P = .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P ≤ .001). Orgasm (P = .002) and drive/relationship (P < .001) declined in men, but sexual cognition/fantasy (P = .01) and sexual behavior/experience (P = .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P = .003) and orgasm (P = .006) in men and sexual arousal (P = .05) and sexual satisfaction (P = .005) in women. All male sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being. PMID:24159171

  19. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    SciTech Connect

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. )

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

  20. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

    SciTech Connect

    Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

    1989-01-01

    Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.

  1. Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1–, IL-17–, and G-CSF–dependent manner

    PubMed Central

    Capitano, Maegan L.; Nemeth, Michael J.; Mace, Thomas A.; Salisbury-Ruf, Christi; Segal, Brahm H.; McCarthy, Philip L.

    2012-01-01

    Neutropenia is a common side effect of cytotoxic chemotherapy and radiation, increasing the risk of infection in these patients. Here we examined the impact of body temperature on neutrophil recovery in the blood and bone marrow after total body irradiation (TBI). Mice were exposed to either 3 or 6 Gy TBI followed by a mild heat treatment that temporarily raised core body temperature to approximately 39.5°C. Neutrophil recovery was then compared with control mice that received either TBI alone heat treatment alone. Mice that received both TBI and heat treatment exhibited a significant increase in the rate of neutrophil recovery in the blood and an increase in the number of marrow hematopoietic stem cells and neutrophil progenitors compared with that seen in mice that received either TBI or heat alone. The combination treatment also increased G-CSF concentrations in the serum, bone marrow, and intestinal tissue and IL-17, IL-1β, and IL-1α concentrations in the intestinal tissue after TBI. Neutralizing G-CSF or inhibiting IL-17 or IL-1 signaling significantly blocked the thermally mediated increase in neutrophil numbers. These findings suggest that a physiologically relevant increase in body temperature can accelerate recovery from neutropenia after TBI through a G-CSF–, IL-17–, and IL-1–dependent mechanism. PMID:22806894

  2. Comparison of total body irradiation plus cyclophosphamide with busulfan plus cyclophosphamide as conditioning regimens in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplant.

    PubMed

    Eroglu, Celalettin; Pala, Cigdem; Kaynar, Leylagül; Yaray, Kadir; Aksozen, M Tarkan; Bankir, Mehmet; Zararsız, Gökmen; Orhan, Okan; Gündog, Mete; Yıldız, Oguz G; Eser, Bülent; Cetin, Mustafa; Unal, Ali

    2013-11-01

    Conditioning regimens used during stem cell transplant provide prolonged control or cure of the disease in patients with acute lymphoblastic leukemia (ALL). In this study, we present a comparison of treatment results for 95 patients with ALL who underwent allogeneic hematopoietic stem cell transplant (AHSCT) with total body irradiation plus cyclophosphamide (TBI + Cy) or busulfan plus cyclophosphamide (Bu + Cy) as conditioning regimen. Median age was 25 (range: 9-54) years. Median follow-up was 24 (range: 3-107) months. Median overall survival (OS) was found to be 29 months. Median event-free survival (EFS) was 9 months. Median OS was 37 months in the TBI + Cy arm, while it was 12 months in the Bu + Cy arm, suggesting a significant advantage favoring the TBI + Cy arm (p = 0.003). Median EFS was 13 months in the TBI + Cy arm, while it was 4 months in the Bu + Cy arm, indicating a significant difference (p = 0.006). In univariate and multivariate analysis, it was found that high OS and EFS were significantly correlated with TBI + Cy conditioning regimen and lack of transplant-related mortality (p < 0.05). The TBI + Cy conditioning regimen was found to be superior to the Bu + Cy regimen in patients with ALL undergoing AHSCT regarding both OS and EFS.

  3. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores.

    PubMed

    Burt, Richard K; Cohen, Bruce A; Russell, Eric; Spero, Kenneth; Joshi, Akash; Oyama, Yu; Karpus, William J; Luo, Kehuan; Jovanovic, Borko; Traynor, Ann; Karlin, Karyn; Stefoski, Dusan; Burns, William H

    2003-10-01

    There were 21 patients with rapidly progressive multiple sclerosis (MS) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell (HSC) support with no 1-year mortality. Following transplantation, one patient had a confirmed acute attack of MS. Neurologic progression defined by the expanded disability status scale (EDSS) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less. In 8 of 12 patients with high pretransplantation disability scores (EDSS > 6.0), progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration. There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment. Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation (HSCT) are not effective for patients with progressive disease and high pretransplantation disability scores. Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity. Specifically, more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup.

  4. DOSE AND GAMMA-RAY SPECTRA FROM NEUTRON-INDUCED RADIOACTIVITY IN MEDICAL LINEAR ACCELERATORS FOLLOWING HIGH-ENERGY TOTAL BODY IRRADIATION.

    PubMed

    Keehan, S; Taylor, M L; Smith, R L; Dunn, L; Kron, T; Franich, R D

    2016-12-01

    Production of radioisotopes in medical linear accelerators (linacs) is of concern when the beam energy exceeds the threshold for the photonuclear interaction. Staff and patients may receive a radiation dose as a result of the induced radioactivity in the linac. Gamma-ray spectroscopy was used to identify the isotopes produced following the delivery of 18 MV photon beams from a Varian 21EX and an Elekta Synergy. The prominent radioisotopes produced include (187)W, (63)Zn, (56)Mn, (24)Na and (28)Al in both linac models. The dose rate was measured at the beam exit window (12.6 µSv in the first 10 min) following 18 MV total body irradiation (TBI) beams. For a throughput of 24 TBI patients per year, staff members are estimated to receive an annual dose of up to 750 μSv at the patient location. This can be further reduced to 65 μSv by closing the jaws before re-entering the treatment bunker. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Combined effect of low-dose irradiation and acidified sodium chlorite washing on Escherichia coli O157:H7 inoculated on mung bean seeds.

    PubMed

    Nei, Daisuke; Bari, Md Latiful; Inatsu, Yasuhiro; Kawasaki, Susumu; Todoriki, Setsuko; Kawamoto, Shinichi

    2010-10-01

    The effect of low-dose irradiation (0.75 and 1.5 kGy) in combination with acidified sodium chlorite (ASC) on the reduction of Escherichia coli O157:H7 on mung bean seeds was examined. Washing with ASC (0.2, 0.5, 0.8, and 1.2 g/L sodium chlorite and 1.0 g/L citric acid) for 2 h reduced the E. coli O157:H7 population from 5.2 to 2.3-3.3 log CFU/g, depending on the concentrations of sodium chlorite. Gamma ray irradiation at 0.75 and 1.5 kGy resulted in reductions of about 1.8 and 2.8 log CFU/g, respectively. Therefore, a single treatment with ASC washing or gamma ray irradiation at 0.75 or 1.5 kGy could not achieve the complete elimination of E. coli O157:H7 on mung bean seeds. Conversely, low-dose irradiation (0.75 and 1.5 kGy) followed by washing with ASC (0.5-1.2 g/L) reduced the population of E. coli O157:H7 to below the detection limit (<1 log CFU/g). However, E. coli O157:H7 was detected in most samples in the enrichment and germination studies. When the treatment order was reversed (ASC washing followed by low-dose irradiation), the E. coli O157:H7 population was also observed to be below the detection limit. Under this treatment, fewer samples (16.7%) were shown to be positive in the enrichment and germination studies, and complete elimination was not achieved. The germination rates of mung bean seeds were not affected by ASC washing and gamma irradiation; however, the yield and length of sprouts were decreased by gamma irradiation.

  6. Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation

    PubMed Central

    Yeom, Mi Young; Kim, Yoo Jin; Chung, Nack Gyun; Lee, Jae Wook; Jang, Pil Sang; Cho, Bin; Kye, Chul Seung

    2015-01-01

    Background The outcome of hematopoietic stem cell transplantation (HSCT) is poor in patients with secondary iron overload (SIO). We evaluated the relationship between SIO and veno-occlusive disease (VOD) in an animal model with radiation for HSCT. Methods We used a 6-week-old female BDF1 (H-2b/d) and a male C57/BL6 (H-2b) as recipient and donor, respectively. Recipient mice were injected intraperitoneally with 10 mg of iron dextran (cumulative doses of 50 mg, 100 mg, and 200 mg). All mice received total body irradiation for HSCT. We obtained peripheral blood for alanine transaminase (ALT) and liver for pathologic findings, lipid hyperoxide (LH) as reactive oxygen species (ROS), and liver iron content (LIC) on post-HSCT day 1 and day 7. The VOD score was assessed by pathologic findings. Results ALT levels increased depending on cumulative iron dose, with significant differences between days 1 and 7 for mice loaded with 200 mg of iron (P<0.01). LH levels significantly increased in mice loaded with 200 mg of iron compared to those in other groups (P<0.01). For mice loaded with 100 mg of iron, the LH level depended on the radiation dose (P<0.01). There was a statistically significant relationship among ALT, LH, and LIC parameters (P<0.05). Pathologic scores for VOD correlated with LIC (P<0.01). Conclusion Livers with SIO showed high ROS levels depending on cumulative iron dose, and correlations with elevated liver enzyme and LIC. The pathologic score for VOD was associated with the LIC. Our results suggest that SIO may induce VOD after HSCT with irradiation. PMID:26457280

  7. SU-E-T-475: Improvements to Total Body Irradiation Dosimetry Efficiency with EBT3 Radiochromic Film and a Template System

    SciTech Connect

    Butson, M; Pope, D; Whitaker, M

    2015-06-15

    Purpose: Total Body Irradiation (TBI) treatments are mainly used in a preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. Our standard regimen is a 12 Gy / 6 fraction bi-daily technique. To evaluate the delivered dose homogeneity to the patient, EBT3 Gafchromic film is positioned at the head, neck, chest, pelvis and groin for all fractions. A system has been developed to simply and accurately prepare and readout the films for patient dose assessment. Methods: A process involving easy preparation and analysis has been produced to minimise the time requirements for TBI dosimetry. One sheet of EBT3 film is used to prepare treatment dosimeters for all fractions, including calibration films, and an automated dose analysis system for easy evaluation and calculation of estimated in-vivo doses was developed. A desktop scanner is used with a dedicated TBI film template to accurately position the films for Image J analysis and extraction. Dental wax bolus and zip-lock bag holders are used to hold the EBT3 film in place during irradiation. Results: To adequately provide dosimetry information for a 6 fraction, TBI patient, only one sheet of Gafchromic EBT3 film is required. The dosimeters are cut, using a template, into 19 mm squares which are then placed between two 30 mm x 30 mm x 4.5 mm wax blocks for bolus. All packages are prepared before the first treatment fraction. The scanning and analysis process can be completed in less than 10 minutes after a 240 min development period. Results have shown that a high level of accuracy and reproducibility can be achieved using the template system provided. Conclusion: Gafchromic EBT3 film provides an adequate in-vivo dosimetry measure for TBI patients. Using a template based system on a dedicated desktop scanner, in-vivo results can be ascertained quickly and accurately.

  8. Renal Shielding and Dosimetry for Patients with Severe Systemic Sclerosis Receiving Immunoablation with Total Body Irradiation on the SCOT (Scleroderma: Cyclophosphamide or Transplantation) Trial

    PubMed Central

    Cracinescu, Oana I.; Steffey, Beverly A.; Kelsey, Chris R.; Larrier, Nicole A.; Paarz-Largay, Cathy J.; Prosnitz, Robert G.; Chao, Nelson; Chute, John; Gasparetto, Cristina; Horwitz, Mitchell; Long, Gwynn; Rizzieri, David; Sullivan, Keith M.

    2010-01-01

    Purpose To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled on a hematopoietic stem cell transplant protocol. Methods and Materials The SCOT protocol employs a lymphoablative preparative regime including 800cGy TBI delivered in two 200 cGy fractions twice a day before CD34+ selected autologous hematopoietic stem cell transplantation. Lung and kidney dose is limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated and guidelines were developed for acceptable lumbar area TBI dosing. Information on kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose were recorded and in vivo dosimetry was performed at several locations to determine doses of irradiation delivered. Results Eleven patients were treated at our center with an AP/PA TBI technique. A 10–20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4–5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and non-contrast CT (computerized tomography) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. Conclusions The dose to the kidneys can be attenuated while maintaining a 10–20% dose inhomogeneity in the lumbar spine area. The kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved and the study continues to enroll. PMID:20800376

  9. A rationally designed combined treatment with an alphavirus-based cancer vaccine, sunitinib and low-dose tumor irradiation completely blocks tumor development.

    PubMed

    Draghiciu, Oana; Boerma, Annemarie; Hoogeboom, Baukje Nynke; Nijman, Hans W; Daemen, Toos

    2015-10-01

    The clinical efficacy of therapeutic cancer vaccines remains limited. For effective immunotherapeutic responses in cancer patients, multimodal approaches capable of both inducing antitumor immune responses and bypassing tumor-mediated immune escape seem essential. Here, we report on a combination therapy comprising sunitinib (40 mg/kg), single low-dose (14 Gy) tumor irradiation and immunization with a therapeutic cancer vaccine based on a Semliki Forest virus vector encoding the oncoproteins E6 and E7 of human papillomavirus (SFVeE6,7). We previously demonstrated that either low-dose irradiation or sunitinib in single combination with SFVeE6,7 immunizations enhanced the intratumoral ratio of antitumor effector cells to myeloid-derived suppressor cells (MDSCs). On the basis of these results we designed a triple treatment combinatorial regimen. The trimodal sunitinib, low-dose irradiation and SFVeE6,7 immunization therapy resulted in stronger intratumoral MDSC depletion than sunitinib alone. Concomitantly, the highest levels of intratumoral E7-specific CD8(+) T cells were attained after triple treatment. Approximately 75% of these cells were positive for the early activation marker CD69. The combination of sunitinib, low-dose tumor irradiation and SFVeE6,7 immunization dramatically changed the intratumoral immune compartment. Whereas control tumors contained 0.02 E7-specific CD8(+) T cells per MDSC, triple treatment tumors contained more than 200 E7-specific CD8(+) T cells per MDSC, a 10,000-fold increased ratio. As a result, the triple treatment strongly enhanced the immunotherapeutic antitumor effect, blocking tumor development altogether and leading to 100% tumor-free survival of tumor-bearing mice. This study demonstrates that this multimodal approach elicits superior antitumor effects and should be considered for clinical applications.

  10. Synergistic Effects of Incubation in Rotating Bioreactors and Cumulative Low Dose 60Co γ-ray Irradiation on Human Immortal Lymphoblastoid Cells

    NASA Astrophysics Data System (ADS)

    Wei, Lijun; Han, Fang; Yue, Lei; Zheng, Hongxia; Yu, Dan; Ma, Xiaohuan; Cheng, Huifang; Li, Yu

    2012-11-01

    The complex space environments can influence cell structure and function. The research results on space biology have shown that the major mutagenic factors in space are microgravity and ionizing radiation. In addition, possible synergistic effects of radiation and microgravity on human cells are not well understood. In this study, human immortal lymphoblastoid cells were established from human peripheral blood lymphocytes and the cells were treated with low dose (0.1, 0.15 and 0.2 Gy) cumulative 60Co γ-irradiation and simulated weightlessness [obtained by culturing cells in the Rotating Cell Culture System (RCCS)]. The commonly used indexes of cell damage such as micronucleus rate, cell cycle and mitotic index were studied. Previous work has proved that Gadd45 (growth arrest and DNA-damage-inducible protein 45) gene increases with a dose-effect relationship, and will possibly be a new biological dosimeter to show irradiation damage. So Gadd45 expression is also detected in this study. The micronucleus rate and the expression of Gadd45α gene increased with irradiation dose and were much higher after incubation in the rotating bioreactor than that in the static irradiation group, while the cell proliferation after incubation in the rotating bioreactor decreased at the same time. These results indicate synergetic effects of simulated weightlessness and low dose irradiation in human cells. The cell damage inflicted by γ-irradiation increased under simulated weightlessness. Our results suggest that during medium- and long-term flight, the human body can be damaged by cumulative low dose radiation, and the damage will even be increased by microgravity in space.

  11. Alanine/EPR dosimetry applied to the verification of a total body irradiation protocol and treatment planning dose calculation using a humanoid phantom

    SciTech Connect

    Schaeken, B.; Lelie, S.; Meijnders, P.; Van den Weyngaert, D.; Janssens, H.; Verellen, D.

    2010-12-15

    Purpose: To avoid complications in total body irradiation (TBI), it is important to achieve a homogeneous dose distribution throughout the body and to deliver a correct dose to the lung which is an organ at risk. The purpose of this work was to validate the TBI dose protocol and to check the accuracy of the 3D dose calculations of the treatment planning system. Methods: Dosimetry based on alanine/electron paramagnetic resonance (EPR) was used to measure dose at numerous locations within an anthropomorphic phantom (Alderson) that was irradiated in a clinical TBI beam setup. The alanine EPR dosimetry system was calibrated against water calorimetry in a Co-60 beam and the absorbed dose was determined by the use of ''dose-normalized amplitudes'' A{sub D}. The dose rate of the TBI beam was checked against a Farmer ionization chamber. The phantom measurements were compared to 3D dose calculations from a treatment planning system (Pinnacle) modeled for standard dose calculations. Results: Alanine dosimetry allowed accurate measurements which were in accordance with ionization chamber measurements. The combined relative standard measurement uncertainty in the Alderson phantom was U{sub r}(A{sub D})=0.6%. The humanoid phantom was irradiated to a reference dose of 10 Gy, limiting the lung dose to 7.5 Gy. The ratio of the average measured dose midplane in the craniocaudal direction to the reference dose was 1.001 with a spread of {+-}4.7% (1 sd). Dose to the lung was measured in 26 locations and found, in average, 1.8% lower than expected. Lung dose was homogeneous in the ventral-dorsal direction but a dose gradient of 0.10 Gy cm{sup -1} was observed in the craniocaudal direction midline within the lung lobe. 3D dose calculations (Pinnacle) were found, in average, 2% lower compared to dose measurements on the body axis and 3% lower for the lungs. Conclusions: The alanine/EPR dosimetry system allowed accurate dose measurements which enabled the authors to validate their TBI

  12. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    SciTech Connect

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.

    2012-12-01

    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  13. Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice.

    PubMed

    Pietzner, J; Merscher, B M; Baer, P C; Duecker, R P; Eickmeier, O; Fußbroich, D; Bader, P; Del Turco, D; Henschler, R; Zielen, S; Schubert, R

    2016-04-01

    Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a co-conditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atm-deficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model.

  14. TU-CD-304-04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

    SciTech Connect

    Yi, B; Xu, H; Mutaf, Y; Prado, K

    2015-06-15

    Purpose: Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI. Methods: Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speed of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements. Results: Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity-oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min. Conclusion: This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC-based thickness compensation and partial lung blocking are also possible.

  15. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation

    PubMed Central

    Vendetti, Frank P.; Leibowitz, Brian J.; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F.; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O’Connor, Mark J.; Yu, Jian; Beumer, Jan H.; Bakkenist, Christopher J.

    2017-01-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21CIP/WAF1)−/− mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21CIP/WAF1)−/− mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21CIP/WAF1)−/−, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21CIP/WAF1)−/− mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI. PMID:28145510

  16. Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation

    SciTech Connect

    Gandola, L.; Siena, S.; Bregni, M.; Sverzellati, E.; Piotti, P.; Stucchi, C.; Gianni, A.M.; Lombardi, F. )

    1990-09-01

    Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: (a) cyclophosphamide (7 g/m2); (b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); (c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.

  17. TU-F-CAMPUS-T-01: Dose and Energy Spectra From Neutron Induced Radioactivity in Medical Linear Accelerators Following High Energy Total Body Irradiation

    SciTech Connect

    Keehan, S; Taylor, M; Franich, R; Smith, R; Dunn, L; Kron, T

    2015-06-15

    Purpose: To assess the risk posed by neutron induced activation of components in medical linear accelerators (linacs) following the delivery of high monitor unit 18 MV photon beams such as used in TBI. Methods: Gamma spectroscopy was used to identify radioisotopes produced in components of a Varian 21EX and an Elekta Synergy following delivery of photon beams. Dose and risk estimates for TBI were assessed using dose deliveries from an actual patient treatment. A 1 litre spherical ion chamber (PTW, Germany) has been used to measure the dose at the beam exit window and at the total body irradiation (TBI) treatment couch following large and small field beams with long beam-on times. Measurements were also made outside of the closed jaws to quantify the benefit of the attenuation provided by the jaws. Results: The radioisotopes produced in the linac head have been identified as {sup 187}W, {sup 56}Mn, {sup 24}Na and {sup 28}Al, which have half-lives from between 2.3 min to 24 hours. The dose at the beam exit window following an 18 MV 2197 MU TBI beam delivery was 12.6 µSv in ten minutes. The dose rate at the TBI treatment couch 4.8 m away is a factor of ten lower. For a typical TBI delivered in six fractions each consisting of four beams and an annual patient load of 24, the annual dose estimate for a staff member at the treatment couch for ten minutes is 750 µSv. This can be further reduced by a factor of about twelve if the jaws are closed before entering the room, resulting in a dose estimate of 65 µSv. Conclusion: The dose resulting from the activation products for a representative TBI workload at our clinic of 24 patients per year is 750 µSv, which can be further reduced to 65 µSv by closing the jaws.

  18. Total Body Irradiation Compared With BEAM: Long-Term Outcomes of Peripheral Blood Autologous Stem Cell Transplantation for Non-Hodgkin's Lymphoma

    SciTech Connect

    Liu, Hong-Wei; Seftel, Matthew D.; Rubinger, Morel; Szwajcer, David; Demers, Alain

    2010-10-01

    Purpose: The optimal preparative regimen for non-Hodgkin's lymphoma patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) is unknown. We compared a total body irradiation (TBI)-based regimen with a chemotherapy-alone regimen. Methods and Materials: A retrospective cohort study was performed at a Canadian cancer center. The TBI regimen consisted of cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse-free survival, and overall survival (OS). Results: Of 73 patients, 26 received CY/E/TBI and 47 received BEAM. The median follow-up for the CY/E/TBI group was 12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in acute toxicity were seen between the two groups. The 5-year disease relapse-free survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM groups, respectivey (p = .492). The univariate analysis results indicated that patients with Stage IV, with chemotherapy-resistant disease, and who had received PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that transplantation before 2000, rather than the conditioning regimen, was a more important predictive factor of long-term outcome (p = .034). Conclusion: A 12-Gy TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in disease relapse-free survival and OS similar to that after BEAM. PBSCT before 2000, and not the conditioning regimen, was an important predictor of long-term outcomes. TBI was not associated with more acute toxicity or pneumonitis. We found no indication that the TBI regimen was inferior or superior to BEAM.

  19. SU-E-T-436: Feasibility of Using the 'Irregular Surface Compensator' Planning Feature of the Eclipse TPS for Total Body Irradiation (TBI) Treatment Planning.

    PubMed

    Ayan, A; Lu, L; Rong, Y; Cunningham, M; Weldon, M; Welliver, M; Woollard, J; Gupta, N

    2012-06-01

    To investigate the feasibility of using the Irregular Surface Compensator (ISC) planning feature of the Eclipse treatment planning system (TPS) for Total Body Irradiation (TBI). TBI treatments require that the whole body receives within +-10% of the prescribed dose. Different body parts with different thicknesses compared to the umbilicus separation may receive higher or lower doses compared to the prescribed dose. Another challenge is to keep the lung dose below 10Gy to avoid complications. To mitigate this problem, physical compensators and blocks are used during the treatment for different body parts and lungs. This method presents a challenge during the treatment delivery and prolongs the treatment time due to patient setup, in-vivo on-line dosimetric monitoring and the adjustment of the compensators frequently during the treatment. We investigated the use of ISC planning feature of Eclipse TPS which is an electronic compensation method that calculates a fluence map based on the body contour from the CT image. The fluence map is delivered with dynamic MLCs . This TBI treatment technique was tested using a Rando phantom in Head First Supine position with lateral beams at SSD=250cm.The calculated fluence were edited so that the lung received <∼10Gy for 12Gy prescription. A single fraction of 2Gy was delivered and the in-vivo measurements were performed in the neck, lung and the umbilicus by using OSLDs. OSLD measurements and the Eclipse TPS predictionswere 200.4/195.0, 162.2/168.9, and 196.1/208.9 cGy for the neck, lung and the umbilicus respectively. The feasibility of using the 'Irregular Surface Compensator' feature of Eclipse TPS for TBI treatment planning was demonstrated. Good agreement (<6%) between the predicted and measured doses was obtained. The proposed planning and delivery simplifies the compensation and blocking to achieve uniform dose distributions and reduces the treatment time. © 2012 American Association of Physicists in Medicine.

  20. SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

    SciTech Connect

    Lee, M; Suh, T; Han, B; Xing, L; Jenkins, C

    2015-06-15

    Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery.

  1. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

    PubMed

    Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

    2017-02-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21(CIP/WAF1))-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21(CIP/WAF1))-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21(CIP/WAF1))-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21(CIP/WAF1))-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

  2. Vitamin E prevents increase in oxidative damage to lipids and DNA in liver of ODS rats given total body X-ray irradiation.

    PubMed

    Yoshimura, Mika; Kashiba, Misato; Oka, Jun; Sugisawa, Ayako; Umegaki, Keizo

    2002-01-01

    We examined the effects of dietary vitamin E (VE) on oxidative damage to DNA and lipids in the liver a few days after total body irradiation (TBI). ODS rats, which lack vitamin C synthesis, were fed either a low VE diet (4.3 mg VE/kg) or a basal VE diet (75.6 mg VE/kg) for 5 weeks while vitamin C was supplied in the drinking water. The VE level in the liver of the low VE group was lower and the levels of lipid peroxides were higher compared to those of the basal VE group: the relative levels in the two groups were 1:30 for VE, 18:1 for 4-hydroxynonenal (HNE), and 10:1 for hexanal (HA). The level of 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative DNA damage, did not differ between the low VE and the basal VE groups. When the rats received TBI at the dose of 3 Gy and were killed on day 6, the levels of HNE, HA and 8OHdG increased by 2.2-, 2-, and 1.5-times, respectively, in the low VE group, but TBI did not cause such increases in the basal VE group. Changes in antioxidative enzymes (glutathione peroxidase, catalase, and Cu/Zn-SOD) in the liver could not explain the different responses of the two diet groups to TBI-induced oxidative damage. The concentrations of vitamin C and glutathione in the liver did not differ between the two groups. These results suggest that dietary VE can prevent the oxidative damage to DNA and lipids in the liver which appear a few days after TBI at dose of 3 Gy.

  3. SU-E-T-92: Achieving Desirable Lung Doses in Total Body Irradiation Based On in Vivo Dosimetry and Custom Tissue Compensation

    SciTech Connect

    Cui, G; Shiu, A; Zhou, S; Cui, J; Ballas, L

    2015-06-15

    Purpose: To achieve desirable lung doses in total body irradiation (TBI) based on in vivo dosimetry and custom tissue compensation. Methods: The 15 MV photon beam of a Varian TrueBeam STx linac was used for TBI. Patients were positioned in the lateral decubitus position for AP/PA treatment delivery. Dose was calculated using the midpoint of the separation distance across the patient’s umbilicus. Patients received 200 cGy twice daily for 3 days. The dose rate at the patient’s midplane was approximately 10 cGy/min. Cerrobend blocks with a 5-HVL thickness were used for the primary lung shielding. A custom styrofoam holder for rice-flour filled bags was created based on the lung block cutouts. This was used to provide further lung shielding based on in vivo dose measurements. Lucite plates and rice-flour bags were placed in the head, neck, chest, and lower extremity regions during the treatment to compensate for the beam off-axis output variations. Two patients were included in the study. Patients 1 and 2 received a craniospinal treatment (1080 cGy) and a mediastinum treatment (2520 cGy), respectively, before the TBI. During the TBI nanoDot dosimeters were placed on the patient skin in the forehead, neck, umbilicus, and lung regions for dose monitoring. The doses were readout immediately after the treatment. Based on the readings, fine tuning of the thickness of the rice-flour filled bags was exploited to achieve the desirable lung doses. Results: For both patients the mean lung doses, which took into consideration all treatments, were controlled within 900 +/−10% cGy, as desired. Doses to the forehead, neck, and umbilicus were achieved within +/−10% of the prescribed dose (1200 cGy). Conclusion: A reliable and robust method was developed to achieve desirable lung doses and uniform body dose in TBI based on in vivo dosimetry and custom tissue compensator.

  4. SU-E-T-556: Integration of Lung Blocks in the Inverse Planning Process of Modulated Arc Total Body Irradiation Using Cone Beam CT.

    PubMed

    Morin, O; Held, M; Kirby, N; Perez-Andujar, A; Chuang, C; Pouliot, J

    2012-06-01

    The sizing and placement of lung blocks for total-body irradiation (TBI) is critical to prevent lung toxicities and maintain effective treatments. During modulated-arc TBI (MATBI) treatment, the patient is stationary near the floor while open-field beams with varying exposures are delivered. The inverse planning process currently aims for a uniform dose to the body, without accounting for the presence of lung blocks. This study investigates the possibility of including the effect of these blocks in the MATBI optimization process. Dosimetric comparisons were performed using a water tank and a simple stack of solid water slabs. Lungs blocks made of cerrobend were fabricated and imaged using on-board megavoltage CBCT (MVCBCT). The reconstructed MVCBCT images were precisely registered with the reference CT for inverse planning. The cerrobend blocks were contoured in the planning system and the density was overridden to 9.3 g/cm(3) . Simulated doses in Pinnacle were compared to ion chamber, diode array and gaf-chromic film measurements obtained at 1.0, 5.0, 10.0 and 20.0 cm depths. Specific optimization objectives on the lungs were tested on 5 patients including a lung re-treatment. The maximum difference between ion chamber measurements and the treatment planning predictions was 2.4%. The measurements profiles with the diode array correlated reasonably well (<5%) with predictions. Gaf-chromic films demonstrated good accuracy at depth but large differences (>10%) on the surface. Lung blocks reconstructed with MVCBCT were structuraly accurate without significant metal artifacts. A comparison of MATBI plans on patients shows that inclusion of lung blocks during optimization can reduce hot and cold areas in the lungs and the sternum. Reasonable predictions of the lung block transmission can be obtained following the developed technique using megavoltage CBCT. Thus, lung blocks can be included in the MATBI inverse planning process, which can help prevent complications and

  5. Renal Shielding and Dosimetry for Patients With Severe Systemic Sclerosis Receiving Immunoablation With Total Body Irradiation in the Scleroderma: Cyclophosphamide or Transplantation Trial

    SciTech Connect

    Craciunescu, Oana I.; Steffey, Beverly A.; Kelsey, Chris R.; Larrier, Nicole A.; Paarz-Largay, Cathy J.; Prosnitz, Robert G.; Chao, Nelson; Chute, John; Gasparetto, Cristina; Horwitz, Mitchell; Long, Gwynn; Rizzieri, David; Sullivan, Keith M.

    2011-03-15

    Purpose: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. Methods and Materials: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34{sup +} selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. Results: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 {+-} 18.1 cGy, with an average dkB of 5.0 {+-} 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 {+-} 5.1 cGy. Conclusions: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.

  6. A myeloablative conditioning regimen for patients with impaired cardiac function undergoing allogeneic stem cell transplantation: reduced cyclophosphamide combined with etoposide and total body irradiation.

    PubMed

    Yoshimi, Akihide; Nannya, Yasuhito; Sakata-Yanagimoto, Mamiko; Oshima, Kumi; Takahashi, Tsuyoshi; Kanda, Yoshinobu; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-08-01

    To circumvent the cardiac toxicity of high-dose cyclophosphamide (CY) in the myeloablative conditioning for those with cardiac comorbidity, we developed a new cardiac sparing conditioning regimen (VP/rCY/TBI) composed of 12 Gy of total body irradiation (TBI), etoposide (VP-16) (40 mg/kg), and reduced CY (40 mg/kg). We assessed the feasibility of this regimen by retrospectively comparing the outcome of VP/rCY/TBI recipients (n = 18) with that of CY/TBI recipients (n = 140). VP/rCY/TBI recipients had significantly higher cumulative dose of anthracyclines, lower ejection fraction (EF), and poorer Karnofsky performance scales (KPS) than CY/TBI recipients. The cumulative incidences of disease progression were 34.9% in VP/rCY/TBI recipients and 19.0% in CY/TBI recipients (P = 0.33). Despite poorer KPS and more cardiac comorbidity in the VP/rCY/TBI recipients, no difference in the nonprogression mortality rates was observed among recipients of the two regimens (17.5 and 14.3%, respectively, P = 0.96). Severe cardiac toxicity within 28 days after transplantation occurred in 5.9 and 3.6% of VP/rCY/TBI and CY/TBI recipients, respectively (P = 0.64). Graft rejection was not observed in VP/rCY/TBI recipients. There is a possibility that VP/rCY/TBI regimen can be safely administered for patients with pretransplantation cardiac comorbidity while preserving antineoplastic effects. These observations merit further prospective study.

  7. Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate ovalbumin-induced allergic asthma in mice.

    PubMed

    Park, Bum Soo; Hong, Gwan Ui; Ro, Jai Youl

    2013-05-01

    Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice.

  8. [French experience in paediatric total body irradiation: A study from the radiotherapy committee of the Société française des cancers de l'enfant (SFCE)].

    PubMed

    Demoor-Goldschmidt, C; Supiot, S; Claude, L; Carrie, C; Mazeron, R; Helfré, S; Alapetite, C; Jouin, A; Coche, B; Padovani, L; Muracciole, X; Bernier, V; Vigneron, C; Noël, G; Leseur, J; Le Prisé, É; Stefan, D; Habrand, J L; Kerr, C; Bondiau, P Y; Ruffier, A; Chapet, S; Mahé, M A

    2016-06-01

    A survey was conducted in 2015 in France on the care of children in radiotherapy services. We present the results for total body irradiation in children, a specific technique of radiation treatment, which needs dedicated controls for this particular population. Of the 17 centres interviewed, 16 responded, and 13 practiced total body irradiation. Patients are positioned in lateral decubitus in 11 centres and supine/prone in two centres. Doses used for total body irradiation in myeloablative bone marrow transplantation are the same in all centres (12Gy); treatments are always fractionated. Lung shielding is positioned to limit the dose at an average of 8Gy with extremes ranging from 6 to 10Gy. The shape of the shieldings varies depending on departments' protocol, with a smaller size in case of mediastinal mass. Four centres have experience of total body irradiation under general anaesthesia, despite twice-daily fractions. In total, practice is relatively homogeneous throughout France and is inspired by the knowledge obtained in adults. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  9. Multivariate Analysis of Radiation Responsive Proteins to Predict Radiation Exposure in Total-Body Irradiation and Partial-Body Irradiation Models.

    PubMed

    Sproull, Mary; Kramp, Tamalee; Tandle, Anita; Shankavaram, Uma; Camphausen, Kevin

    2017-02-01

    In the event of a radiological or nuclear attack, advanced clinical countermeasures are needed for screening and medical management of the exposed population. In such a scenario, minimally invasive biomarkers that can accurately quantify radiation exposure would be useful for triage management by first responders. In this murine study, we evaluated the efficacy of a novel combination of radiation responsive proteins, Flt3 ligand (FL), serum amyloid A (SAA), matrix metalloproteinase 9 (MMP9), fibrinogen beta (FGB) and pentraxin 3 (PTX3) to predict the received dose after whole- or partial-body irradiation. Ten-week-old female C57BL6 mice received a single whole-body or partial-body dose of 18 Gy from a Pantak X-ray source at a dose rate of 2.28 Gy/min. Plasma was collected by cardiac puncture at 24, 48, 72 h and 1 week postirradiation. Plasma protein levels were determined via commercially available ELISA assay. A multivariate discriminant analysis was utilized to generate best-fit dose prediction models for whole-body exposures using the selected biomarker panel and its potential application to partial-body exposures was examined. The combination of values from FL, SAA, MMP9, FGB and PTX3 between 24 h and 1 week postirradiation yielded novel dose-response relationships. For day 1 postirradiation, the best-fit model yielded a predictive accuracy of 81% utilizing FL alone. The use of additional proteins did not enhance the model accuracy whereas, at day 2 postirradiation, the addition of PTX3 and FGB to FL increased the accuracy to 100%. At day 3 the use of FL and PTX3 yielded a predictive accuracy of 93% and at day 7 use of FL and SAA had an accuracy of 90%. Dose prediction of partial-body exposures based on the TBI model had a higher predictive accuracy when the percentage of the body exposed to radiation increased. Our findings indicate that this novel combination of radiation responsive biomarker proteins are an efficient method for predicting radiation exposure

  10. Low Dose Gamma Irradiation Does Not Affect the Quality or Total Ascorbic Acid Concentration of “Sweetheart” Passionfruit (Passiflora edulis)

    PubMed Central

    Golding, John B.; Blades, Barbara L.; Satyan, Shashirekha; Spohr, Lorraine J.; Harris, Anne; Jessup, Andrew J.; Archer, John R.; Davies, Justin B.; Banos, Connie

    2015-01-01

    Passionfruit (Passiflora edulis, Sims, cultivar “Sweetheart”) were subject to gamma irradiation at levels suitable for phytosanitary purposes (0, 150, 400 and 1000 Gy) then stored at 8 °C and assessed for fruit quality and total ascorbic acid concentration after one and fourteen days. Irradiation at any dose (≤1000 Gy) did not affect passionfruit quality (overall fruit quality, colour, firmness, fruit shrivel, stem condition, weight loss, total soluble solids level (TSS), titratable acidity (TA) level, TSS/TA ratio, juice pH and rot development), nor the total ascorbic acid concentration. The length of time in storage affected some fruit quality parameters and total ascorbic acid concentration, with longer storage periods resulting in lower quality fruit and lower total ascorbic acid concentration, irrespective of irradiation. There was no interaction between irradiation treatment and storage time, indicating that irradiation did not influence the effect of storage on passionfruit quality. The results showed that the application of 150, 400 and 1000 Gy gamma irradiation to “Sweetheart” purple passionfruit did not produce any deleterious effects on fruit quality or total ascorbic acid concentration during cold storage, thus supporting the use of low dose irradiation as a phytosanitary treatment against quarantine pests in purple passionfruit. PMID:28231212

  11. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    SciTech Connect

    Mikell, John L.; Waller, Edmund K.; Switchenko, Jeffrey M.; Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael; Hall, William A.; Langston, Amelia A.; Esiashvili, Natia; Khoury, H. Jean; Khan, Mohammad K.

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was