Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality

Following exposure to high doses of ionizing radiation, diverse strains of vertebrate species will manifest varying levels of radiation sensitivity. To understand the inter-strain cellular and molecular mechanisms of radiation sensitivity, two mouse strains with varying radiosensitivity (C3H/HeN, and CD2F1), were exposed to total body irradiation (TBI). Since Insulin-like Growth Factor-1 (IGF-1) signaling pathway is associated with radiosensitivity, we investigated the link between systemic or tissue-specific IGF-1 signaling and radiosensitivity. Adult male C3H/HeN and CD2F1 mice were irradiated using gamma photons at Lethal Dose-70/30 (LD_70/30), 7.8 and 9.35 Gy doses, respectively. Those mice that survived up to 30 days post-irradiation, were termed the survivors. Mice that were euthanized prior to 30 days post-irradiation due to deteriorated health were termed decedents. The analysis of non-irradiated and irradiated survivor and decedent mice showed that inter-strain radiosensitivity and post-irradiation survival outcomes are associated with activation status of tissue and systemic IGF-1 signaling, nuclear factor erythroid 2–related factor 2 (Nrf2) activation, and the gene expression profile of cardiac mitochondrial energy metabolism pathways. Our findings link radiosensitivity with dysregulation of IGF-1 signaling, and highlight the role of antioxidant gene response and mitochondrial function in radiation sensitivity.     

Radiation effects on methyl vinyl polysilicone foam

The effects on methyl vinyl polysilicone foam of ⁶⁰Co γ‐ray radiation at room temperature was studied in air, in vacuo, and in an inert gas atmosphere. The unirradiated and irradiated samples were analyzed by Fourier transform infrared spectroscopy, scanning electron microscopy, pyrolysis gas chromatography/mass spectroscopy, and thermogravimetric analysis, and the gas products after radiation were analyzed by gas chromatography/mass spectroscopy. The changes of the gel fraction, compression properties, and the stress–relaxation ratio with dose for irradiated samples were observed. The results show that the second crosslinking reaction in the polysilicone after chemical crosslinking took place at a low dose (2 × 10⁵ Gy), but radiation degradation was predominant, with the dose increasing step by step. The mechanical properties of polysilicone foam gradually became low grade after it was irradiated by any dose in excess of 2 × 10⁵ Gy. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3437–3441, 2003     

Epigenetic Regulation of the Hippocampus,with Special Reference to Radiation Exposure

The hippocampus is crucial in learning, memory and emotion processing, and is involved in the development of different neurological and neuropsychological disorders. Several epigenetic factors, including DNA methylation, histone modifications and non-coding RNAs, have been shown to regulate the development and function of the hippocampus, and the alteration of epigenetic regulation may play important roles in the development of neurocognitive and neurodegenerative diseases. This review summarizes the epigenetic modifications of various cell types and processes within the hippocampus and their resulting effects on cognition, memory and overall hippocampal function. In addition, the effects of exposure to radiation that may induce a myriad of epigenetic changes in the hippocampus are reviewed. By assessing and evaluating the current literature, we hope to prompt a more thorough understanding of the molecular mechanisms that underlie radiation-induced epigenetic changes, an area which can be further explored.     

Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling

Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9–2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.     

Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos

The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos (Danio rerio), as well as a non-targeted effect in bystander naïve embryos partnered with irradiated embryos, and examined the influence of exogenous nitric oxide (NO) on these targeted and non-targeted effects. The exogenous NO was generated using an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). The targeted and non-targeted effects, as well as the toxicity of the SNAP, were assessed using the number of apoptotic events in the zebrafish embryos at 24 h post fertilization (hpf) revealed through acridine orange (AO) staining. SNAP with concentrations of 20 and 100 µM were first confirmed to have no significant toxicity on zebrafish embryos. The targeted effect was mitigated in zebrafish embryos if they were pretreated with 100 µM SNAP prior to irradiation with an X-ray dose of 75 mGy but was not alleviated in zebrafish embryos if they were pretreated with 20 µM SNAP. On the other hand, the non-targeted effect was eliminated in the bystander naïve zebrafish embryos if they were pretreated with 20 or 100 µM SNAP prior to partnering with zebrafish embryos having been subjected to irradiation with an X-ray dose of 75 mGy. These findings revealed the importance of NO in the protection against damages induced by ionizing radiations or by radiation-induced bystander signals, and could have important impacts on development of advanced cancer treatment strategies.     

Radioprotection of mice by dietary squalene

Male C3H mice were fed a diet containing 2% squalene for 14 d prior to and 30 d subsequent to exposure to 6, 7 or 8 Gy of whole body γ-irradiation (Cesium-137). After 14 d on squalene-supplemented diet, plasma and jejunal tissue squalene levels were 2X and 15X that of controls. Seven days after irradiation, total white cell counts and total lymphocyte counts were substantially depressed in a radiation dose-dependent manner. Although counts in the squalene group were consistently (18–119%) higher than those in the corresponding dietary control group, the differences between dietary groups at any single dose were not significant. Nuclear area of villus cells in the jejunum of both dietary groups was significantly reduced (20%) by day 11 post-irradiation but the nuclear area in squalene-fed mice was significantly greater (15%) than in controls, before and after irradiation. There were no differences in body weight as a function of either diet or radiation dose prior to the first observations of animal lethality. Animal survival was decreased from 100 to 0% at 30 d post-irradiation by radiation doses of 6–8 Gy, with the greatest difference between dietary groups being observed at 7 Gy (median survival times of 12 and 16 d for control and squalene groups, respectively). Overall, survival of squalene-fed mice was significantly prolonged compared with control-fed mice (P=0.0054 by censored multiple regression analysis). It is concluded that squalene conferred some cellular and systemic radioprotection to mice receiving these lethal whole-body radiation doses.     

Mitigating the Effects of Xuebijing Injection on Hematopoietic Cell Injury Induced by Total Body Irradiation with γ rays by Decreasing Reactive Oxygen Species Levels

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.     

Effects of polymethylvinylsilicone oil with side tetraphenylphenyl groups on the radiation resistance of addition‐type silicone rubber

Polymethylvinylsilicone oil with side tetraphenylphenyl groups (called C₂ gum for short) as a low molecular additive was used in two kinds of addition‐type silicone rubber, polymethylvinyl silicone rubber and poly (dimethyl‐diphenyl) silicone rubber, and the radiation resistance of silicone rubbers obtained was investigated by γ‐rays radiation with the dose rate of 117 Gy/min at doses up to 350, 500, and 850 kGy, respectively. Moreover, the average molecular weight between crosslinks and mechanical properties of silicone rubbers after irradiated in air and N₂ were determined by toluene‐swelling method and on a XLS‐A rubber test instrument, respectively. The results show that C₂ gum can effectively improve the radiation resistance of silicone rubber. When C₂ gum is used in poly(dimethyl‐diphenyl) silicone rubber, phenyl groups and tetraphenylphenyl groups may have synergistic effect, and the radiation resistance is improved greatly. The suitable amount of C₂ gum used in silicone rubber is 10– 14 phr. The crosslinking density of vulcanizates irradiated in N₂ is higher than that of vulcanizates irradiated in air because of the oxidative degradation. The radiation protection mechanism of C₂ gum was also discussed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 4144–4148, 2007     

Radiation-Induced Changes in Serum Lipidome of Head and Neck Cancer Patients

Cancer radiotherapy (RT) induces response of the whole patient’s body that could be detected at the blood level. We aimed to identify changes induced in serum lipidome during RT and characterize their association with doses and volumes of irradiated tissue. Sixty-six patients treated with conformal RT because of head and neck cancer were enrolled in the study. Blood samples were collected before, during and about one month after the end of RT. Lipid extracts were analyzed using MALDI-oa-ToF mass spectrometry in positive ionization mode. The major changes were observed when pre-treatment and within-treatment samples were compared. Levels of several identified phosphatidylcholines, including (PC34), (PC36) and (PC38) variants, and lysophosphatidylcholines, including (LPC16) and (LPC18) variants, were first significantly decreased and then increased in post-treatment samples. Intensities of changes were correlated with doses of radiation received by patients. Of note, such correlations were more frequent when low-to-medium doses of radiation delivered during conformal RT to large volumes of normal tissues were analyzed. Additionally, some radiation-induced changes in serum lipidome were associated with toxicity of the treatment. Obtained results indicated the involvement of choline-related signaling and potential biological importance of exposure to clinically low/medium doses of radiation in patient’s body response to radiation.     

Preliminary Model of Radiation Damage in Ceramics

A preliminary model of radiation damage in binary ceramic oxides has been developed. The model described here accounts in an approximate way for some of the major differences between metallic alloys and ceramics that are believed to be responsible for the fact that ceramic materials appear in some cases to behave differently than metallic alloys when exposed to displacive irradiation. The model considers the influence of the existence of a second lattice and the additional constraint of stoichiometric point defects absorption by dislocation loops on the concentrations of point defects that would be observed at steady state in an irradiated ceramic. These point defect concentrations are then used to compute various measures of the sensitivity of these materials to the type of microstructural evolution that is observed in irradiated metals. Initial results indicate that both the lattice and stoichiometry effects can help to mitigate radiation damage in ceramics. However, the effect is not necessarily large. In agreement with recent data, the results indicate that at least some ceramic oxides may exhibit a sensitivity to displacement damage that is similar to metals.     

Energetic polymer subjected to high energy radiation

PolyNIMMO is regarded as an energetic polymer. It consists of a nitrated ester group and an ether linkage. When polyNIMMO is subjected gamma radiation up to doses of 250 kGy there is no evidence of degradation, however, at higher levels of gamma radiation up to 750 kGy structural changes in the polyNIMMO backbone were observed [Polymer 44 (2003) 7617-7624]. These observations were based on polyNIMMO which was gamma irradiated in the bulk phase [Polymer 44 (2003) 7617-7624; Polymer 42 (2001) 7711-7718]. The results presented in investigation are from polyNIMMO which has been irradiated in solution. PolyNIMMO dissolved in halogenated and aromatic solvents was found to undergo structural changes when subjected to doses of gamma radiation up to 250 kGy. An increase in molecular weight and glass transition temperature was observed with the formation of water and an aldehyde. End chain linking together with hydrogen abstraction of the pendant methyl group were the two suggested reaction schemes.     

The effect of γ radiation on the physical structure and mechanical properties of ultrahigh molecular weight polyethylene

Ultrahigh molecular weight polyethylene has been irradiated using a cobalt 60 source to give received dose between zeor and 50 Mrad. Irradiacted specimens were subjected to tensile characterization, dynamic mechanical analysis, and differential scanning calorimetry. Changes in tensile and dynamic mechnaical properties following irradiation arise from both molecular rearrangement and from increased crystallinity following scissionof long interlamella tie chains. The effects of post-irradiation aging on mechanical properties are associated with increasing crystallinity resulting from decomposition of metastable groups formed in the amorphous region during irradiation. Irradiated materials have been subject to sinusoidal stressing between 0.275 and 0.55 of yield stress for 100,000 cycies, and changes in mechnaical and physical properties measured. Increased resistance to creep during stressing was observed with the irradiated materials, behavior which is consistent with previsouly observed changes in crystallinity and crosslink density. Overall property changes measured following stressing were small compared with those induced by the initial irradiation.     

聚偏氟乙烯中空纤维膜的耐辐射性能研究

研究了较低剂量的γ辐射对聚偏氟乙烯中空纤维膜的结构与性能的影响。在试验中,选用44.57 Gy/min的剂量率,分别采用2,4,6,10 kGy剂量对浸泡在pH=10的氢氧化钠溶液中的中空纤维膜进行辐照。对辐照前后的样品作相关的性能测试,结果表明:随着辐射剂量的增加,透水通量先增大后减小,最大孔径持续减小,最大幅度至14.9%,分离性能增强。在≤10 kGy的剂量内,断裂强力呈现增大趋势,断裂伸长率呈现下降趋势,爆破强度先增大后减小。工艺优化的剂量为2 kGy。微观形貌和红外分析表明,辐射对膜的外表面化学基团及内表面的形貌产生一定的影响。热分析表明,辐照使膜的结晶度有所提高。     

Mixed radiation field effects from a nuclear reactor on poly(aryl ether ether ketone): A melt viscosity study

Poly(aryl ether ether ketone) (PEEK) is a high‐temperature engineering thermoplastic used in the aerospace industry. To assess its suitability for nuclear industry applications, the effects of mixed field radiation from a nuclear reactor were investigated on two industrial semicrystalline PEEK grades (VICTREX 150P and 450P). Specimens were first processed on an ENGEL55 injection molder and then irradiated in the pool of a SLOWPOKE‐2 nuclear research reactor. Specimens were thus exposed to a mixed field of radiation including gamma, electrons, protons, and neutrons, for exposures resulting in doses ranging from 0.15 to 15 MGy. Irradiated samples were characterized by viscosity measurements in the melt, differential scanning calorimetry (DSC), and density measurements. Melt viscosity of irradiated samples proved to be significant in detecting early molecular weight changes in PEEK and helped explain the interaction of competing chain scission and crosslinking reactions at various stages of the radiolysis. All results pointed toward the following transformation of the resin with increased dosage: chain scission of the tie‐molecules between the amorphous and crystalline phases, crosslinking in the amorphous phase, followed by a general degradation of the molecular weight dominated by chain‐scission. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2713–2719, 2002     

Gamma-radiation stabilization of polypropylene

Especially synthesized compounds, together with conventional antioxi-dants, were evaluated as radiation stabilizers of isotactic polypropylene. Electron spin resonance (ESR) determinations of free radical populations in stabilized and unstabilized samples were carried out after irradiation and at periods of up to 460 h. The same samples were mechanically tested and a correlation was found to exist between the concentration of trapped peroxy radicals and the radiation deterioration in the polymer. Post-irradiation effects were evaluated using accelerated aging at 70°C and carbonyl index determinations at periods of up to 110 days indicated that some of the stabilizers examined are efficient inhibitors of post-irradiation oxidation. The results are discussed in the light of the free radical mechanism of the radiation-induced auto-oxidative degradation of polymers.     

A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage

The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage in irradiated mice, more than half of mice eventually died, thus indicating that better approach was needed. We then investigated a more effective therapy for radiation-induced gastrointestinal damage. Mice receiving abdominal radiation at 13 Gy were orally administered ascorbic acid (250 mg/kg/day) for three days before radiation (pretreatment), one shot of engulfment (250 mg/kg) at 8 h before radiation, or were administered the agent for seven days after radiation (post-treatment). None of the control mice survived the abdominal radiation at 13 Gy due to severe gastrointestinal damage (without bone marrow damage). Neither pretreatment with ascorbic acid (20% survival), engulfment (20%), nor post-treatment (0%) was effective in irradiated mice. However, combination therapy using ascorbic acid, including pretreatment, engulfment and post-treatment, rescued all of the mice from lethal abdominal radiation, and was accompanied by remarkable improvements in the gastrointestinal damage (100% survival). Omitting post-treatment from the combination therapy with ascorbic acid markedly reduced the mouse survival (20% survival), suggesting the importance of post-treatment with ascorbic acid. Combination therapy with ascorbic acid may be a potent therapeutic tool for radiation-induced gastrointestinal damage.     

Apparent Polyploidization after Gamma Irradiation: Pitfalls in the Use of Quantitative Polymerase Chain Reaction (qPCR) for the Estimation of Mitochondrial and Nuclear DNA Gene Copy Numbers

Quantitative polymerase chain reaction (qPCR) has been widely used to quantify changes in gene copy numbers after radiation exposure. Here, we show that gamma irradiation ranging from 10 to 100 Gy of cells and cell-free DNA samples significantly affects the measured qPCR yield, due to radiation-induced fragmentation of the DNA template and, therefore, introduces errors into the estimation of gene copy numbers. The radiation-induced DNA fragmentation and, thus, measured qPCR yield varies with temperature not only in living cells, but also in isolated DNA irradiated under cell-free conditions. In summary, the variability in measured qPCR yield from irradiated samples introduces a significant error into the estimation of both mitochondrial and nuclear gene copy numbers and may give spurious evidence for polyploidization.     

Effects of gamma radiation on properties of halogen‐free flame retardant EPDM‐PVMQ rubber blends

In this study, the effects of gamma radiation on properties of ethylene–propylene–diene monomer (EPDM) and its blends with phenyl vinyl methyl silicon rubber (PVMQ) were studied. The samples were irradiated with the dose rate of 171.7 Gy/min, and the total dose was up to 500 kGy. Mechanical properties, electrical insulation, limiting oxygen index (LOI), crosslink density, and ATR‐FTIR spectroscopy of the rubber were carried out to characterize the properties via irradiation. The results indicated that PVMQ acted as an irradiation degradation retarder for EPDM. After a postvulcanized period corresponding to 50 kGy dose, the elongation at break and electrical insulation decreased with LOI unaffected, while the crosslink density and tensile strength presented a complicated change with the increasing of radiation dose. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

硅橡胶泡沫伽马辐照后结构和元素分布研究

在密闭的氮气气氛下,用伽马射线辐照聚二甲基硅橡胶泡沫,采用全反射红外光谱(ATR)和X射线光电子能谱(XPS)对辐照后的化学结构和元素含量变化进行了表征.结果表明:化学结构单元Si-CH3最容易受到伽马射线的影响,在低的辐照剂量下表面Si-CH3成分随着辐照剂量增加而减小;高剂量下材料的元素分布发生了变化,近表面C元素含量要比泡沫体中部的C元素含量高.因此,在密闭环境下辐照老化后的硅橡胶泡沫的表面性能和体内性能存在差异.