Effects Of Chronic Irradiation Research Articles

Radiological consequence assessment from long term station blackout nuclear accident on Buyende nuclear power plant of Uganda

Uganda’s energy policy of 2023 and Vision 2040 plans to address the country’s electricity shortage by introducing nuclear power of 24,000 MW capacity by 2040. The pioneer nuclear power plants with a generation capacity of 8,400 MW will be built in Buyende District. This study focused on assessing the radiological consequences of potential nuclear accident on any of the four technologies of APR1400, VVER1200, HPR1000, and APR1000. Evaluation of acute and chronic radiation effects from a long-term station blackout accident using RASCAL and GENII codes identified the order of minimum health risks to the public as APR100, HPR1000, VVER1200, and APR1400 if single units are constructed. The total effective dose equivalents and thyroid doses at the exclusion area boundary and emergency protection zone were within the regulatory limits of 250 mSv and 3,000 mSv, respectively for all the reactor technologies.

Irradiation Affects Adipose-Derived Stem Cells and Wound Healing Depending on Radiation Dose and Frequency.

Radiation therapies are often associated with permanent devitalization in the surrounding tissue. The authors hypothesized that stem cells are damaged depending on each irradiation dose and frequency of fractionated radiotherapies, which results in impaired tissue function, including wound-healing capacity. Susceptibility of human adipose-derived stem cells (ASCs) to a single irradiation (0 to 10 Gy) was assessed in vitro. In vivo chronic radiation effects were also assessed on mouse dorsal skin ( n = 4 to 5) for 6 months after a total of 40 Gy irradiation (0 Gy as control) using 1 of 3 fractionated protocols (2 Gy daily for 20 days, 10 Gy weekly for 4 weeks, or 10 Gy monthly for 4 months). Oxygen partial pressure, oxygen saturation of hemoglobin, and dorsal skin viscoelasticity were measured periodically, and wound healing and tissue immunohistology were compared at 6 months. A single irradiation of cultured human ASCs resulted in a dose-dependent increase in cell death up to 2 Gy but with no further increases between 2 and 10 Gy. Most of the apoptotic ASCs were in the proliferation phase. Among the 3 in vivo irradiation protocols, the 2 Gy×20 group had the most severe chronic tissue damage (ie, skin dysfunction, subcutaneous atrophy, depletion of CD34 + stem cells) 6 months after the irradiation. Wound healing was also impaired most significantly in the 2 Gy×20 group. These results have important clinical implications for surgeons and radiotherapists in the timing of surgical interventions and the optimization of fractionation protocols. Irradiation damages stem cells depending on the radiation dose and frequency. Using the ultimately optimized protocol, surgeons can minimize the long-term functional deficits of radiated tissue without losing the anticancer efficacy of radiation therapy.

Comparison of Hematological Parameters between Diagnostic Radiation Workers and Non-Radiation Workers

Purpose: Radiation workers are exposed to chronic effects due to long-term exposure to low levels of ionizing radiation. One of the biological indicators to evaluate these chronic radiation effects is the study of the hematopoietic system. The purpose of this study is to compare the changes in blood parameters of radiology staff and staff of other wards of the hospital.
 Materials and Methods: In this study, 47 radiology staff working in the radiology department of the hospital as the study group and 94 personnel in other departments as the control group were included. Demographic data including age, gender, and work experience were obtained. Hematological parameters were extracted from the complete blood count tests of participants.
 Results: The results of this study showed that the Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) parameters significantly decreased in the male study group, whereas no significant differences were observed in the blood parameters of the female study group in comparison to those of the control group. There was a significant positive correlation between the parameters of Hemoglobin and age. There was a significant negative correlation between work experience and white blood cells, while there was a significant positive correlation between work experience and Hemoglobin.
 Conclusion: Correlation between collective absorbed dose and changes in blood parameters is suggested for future studies. Based on the results of this study and other studies, it can be concluded that long-term exposure to low levels of radiation may change blood parameters. Therefore, regular and periodic complete blood count tests along with absorbed dose monitoring of radiation workers are recommended.

Mutational effects of chronic gamma radiation throughout the life cycle of Arabidopsis thaliana: Insight into radiosensitivity in the reproductive stage

Organisms living on Earth have always been exposed to natural sources of ionizing radiation, but following recent nuclear disasters, these background levels have often increased regionally due to the addition of man-made sources of radiation. To assess the mutational effects of ubiquitously present radiation on plants, we performed a whole-genome resequencing analysis of mutations induced by chronic irradiation throughout the life cycle of Arabidopsis thaliana grown under controlled conditions. We obtained resequencing data from 36 second generation post-mutagenesis (M2) progeny derived from 12 first generation (M1) lines grown under gamma-irradiation conditions, ranging from 0.0 to 2.0 Gray per day (Gy/day), to identify de novo mutations, including single base substitutions (SBSs) and small insertions/deletions (INDELs). The relationship between de novo mutation frequency and radiation dose rate from 0.0 to 2.0 Gy/day was assessed by statistical modeling. The increase in de novo mutations in response to irradiation dose fit the negative binomial model, which accounted for the high variability of mutation frequency observed. Among the different types of mutations, SBSs were more prevalent than INDELs, and deletions were more frequent than insertions. Furthermore, we observed that the mutational effects of chronic radiation were greater during the reproductive stage. These results will provide valuable insights into practical strategies for analyzing mutational effects in wild plants growing in environments with various mutagens.

Biological and cellular responses of humans to high-level natural radiation: A clarion call for a fresh perspective on the linear no-threshold paradigm

There remains considerable uncertainty in obtaining risk estimates of adverse health outcomes of chronic low-dose radiation. In the absence of reliable direct data, extrapolation through the linear no-threshold (LNT) hypothesis forms the cardinal tenet of all risk assessments for low doses (≤ 100 mGy) and for the radiation protection principle of As Low As Reasonably Achievable (ALARA). However, as recent evidences demonstrate, LNT assumptions do not appropriately reflect the biology of the cell at the low-dose end of the dose-response curve. In this regard, human populations living in high-level natural radiation areas (HLNRA) of the world can provide valuable insights into the biological and cellular effects of chronic radiation to facilitate improved precision of the dose-response relationship at low doses. Here, data obtained over decades of epidemiological and radiobiological studies on HLNRA populations is summarized. These studies do not show any evidence of unfavourable health effects or adverse cellular effects that can be correlated with high-level natural radiation. Contrary to the assumptions of LNT, no excess cancer risks or untoward pregnancy outcomes have been found to be associated with cumulative radiation dose or in-utero exposures. Molecular biology-driven studies demonstrate that chronic low-dose activates several cellular defence mechanisms that help cells to sense, recover, survive, and adapt to radiation stress. These mechanisms include stress-response signaling, DNA repair, immune alterations and most importantly, the radiation-induced adaptive response. The HLNRA data is consistent with the new evolving paradigms of low-dose radiobiology and can help develop the theoretical framework of an alternate dose-response model. A rational integration of radiobiology with epidemiology data is imperative to reduce uncertainties in predicting the potential health risks of chronic low doses of radiation.

Stochastic parametric skeletal dosimetry model for humans: General approach and application to active marrow exposure from bone-seeking beta-particle emitters.

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that "run through" the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949-1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90Sr and 89Sr intake to humans.

Abstract 129: Transdermal Deferoxamine Mitigates Radiation-induced Skin Fibrosis

Background: Radiation therapy (RT) is an important curative and palliative treatment for several types of cancer, but pathological and progressive skin fibrosis is an inevitable and unfavorable side effect. Current treatment options for radiation-induced fibrosis (RIF) are limited, however, the iron chelator deferoxamine (DFO) has been shown to improve skin vascularization when injected into radiated tissue prior to fat grafting. In this study, we asked whether topical delivery of DFO prior to irradiation could mitigate the chronic effects of irradiation damage in the skin. Methods: CD-1 Nude immunodeficient mice were split into four experimental groups (n=5/group); 1) irradiation with no DFO, 2) irradiation with therapeutic DFO, 3) irradiation with continuous (prophylactic and therapeutic) DFO, and 4) no irradiation and no DFO (control group). DFO was administrated to the mouse scalp using a novel transdermal drug delivery system (TDDS). Prophylactic DFO started 2 weeks prior to irradiation and continued for 6 weeks following irradiation. Therapeutic DFO started 4 weeks after irradiation, when chronic skin fibrosis had developed. Mice scalps were irradiated with a total of 30 Gy. Skin perfusion was monitored with Laser Doppler immediately following irradiation and at 6 weeks after irradiation, at which point the skin was harvested and evaluated histologically for vascularization and fibrosis. Results: Immediately following RT, skin perfusion was significantly improved in mice receiving prophylactic DFO. Six weeks following RT, the mice receiving DFO treatment had the greatest perfusion and increased immunohistological evidence of vascularity. Skin fibrosis was significantly reduced in mice receiving DFO, evidenced by decreased dermal thickness, decreased skin collagen content, and more regenerative pattern of collagen fiber networks. The greatest benefits in fibrosis and vascularization were found in mice receiving continuous DFO treatment. Conclusions: Prophylactic and therapeutic transdermal delivery of deferoxamine improves skin vascularity and reduces the chronic effects of radiation on skin fibrosis, and thus may play an important therapeutic role in patients requiring RT for treatment of their cancer.

Chronic irradiation with 222-nm UVC light induces neither DNA damage nor epidermal lesions in mouse skin, even at high doses.

Surgical site infections (SSIs) represent an important clinical problem associated with increased levels of surgical morbidity and mortality. UVC irradiation during surgery has been considered to represent a possible strategy to prevent the development of SSI. 254-nm UVC induces marked levels of DNA damage by generating cyclobutyl pyrimidine dimers (CPD) in microorganisms. However, this effect is elicited not only in microorganisms, but also in human cells, and chronic exposure to 254-nm UVC has been established to represent a human health hazard. In contrast, despite short wavelength-UVC light, especially 222-nm UVC, having been demonstrated to elicit a bactericidal effect, single irradiation with a high dose of 222-nm UVC energy has been reported to not induce mutagenic or cytotoxic DNA lesions in mammalian cells. However, the effect of chronic irradiation with a high dose of 222-nm UVC to mammalian cells has not been determined. In this study, it was demonstrated that large numbers of CPD-expressing cells were induced in the epidermis of mice following treatment with a small amount of single exposure 254-nm UVC, and then less than half of these cells reduced within 24 h. Chronic 254-nm UVC irradiation was revealed to induce sunburn and desquamation in mouse skin. Histological analysis demonstrated that small numbers of CPD-expressing cells were detected only in hyperkeratotic stratum corneum after chronic irradiation with a high dose of 254-nm UVC, and that significant hyperplasia and intercellular edema were also induced in the epidermis of mice. In contrast, chronic irradiation with 222-nm UVC light was revealed not to induce mutagenic or cytotoxic effects in the epidermis of mice. These results indicated that 222-nm UVC light emitted from the lamp apparatus (or device), which was designed to attenuate harmful light present in wavelengths of more than 230 nm, represents a promising tool for the reduction of SSI incidence in patients and hospital staff.

Impact of Environmental Radiation on the Health and Reproductive Status of Fish from Chernobyl.

Aquatic organisms at Chernobyl have now been chronically exposed to environmental radiation for three decades. The biological effects of acute exposure to radiation are relatively well documented, but much less is known about the long-term effects of chronic exposure of organisms in their natural environment. Highly exposed fish in freshwater systems at Chernobyl showed morphological changes in their reproductive system in the years after the accident. However, the relatively limited scope of past studies did not allow robust conclusions to be drawn. Moreover, the level of the radiation dose at which significant effects on wildlife occur is still under debate. In the most comprehensive evaluation of the effects of chronic radiation on wild fish populations to date, the present study measures specific activities of 137Cs, 90Sr, and transuranium elements (238Pu, 239,240Pu, and 241Am), index conditions, distribution and size of oocytes, as well as environmental and biological confounding factors in two fish species perch ( Perca fluviatilis) and roach ( Rutilus rutilus) from seven lakes. In addition, relative species abundance was examined. The results showed that both fish species are, perhaps surprisingly, in good general physiological and reproductive health. Perch, however, appeared to be more sensitive to radiation than roach: in the most contaminated lakes, a delay of the maturation of the gonads and the presence of several undeveloped phenotypes were evident only for perch and not for roach.

Stromal Progenitor Cells in Mitigation of Non-Hematopoietic Radiation Injuries.

Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries. We have developed stem cell based therapies for the mitigation of acute radiation syndrome (ARS) and radiation-induced gastrointestinal syndrome (RIGS). This is a promising option because of the robustness of standardized isolation and transplantation of stromal cells protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet derived growth factors (PDGF), keratinocyte growth factor (KGF), R-spondins (Rspo), and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases. This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and epithelium, (d) and secrete regenerative and immunomodulatory paracrine signals to control inflammation, ulceration, wound healing and fibrosis.

RESPOSTAS BIOLÓGICAS DE Anagasta kuehniella E DE SEU PARASITÓIDE, Bracon hebetor, À RADIAÇÃO POR MICROONDAS (2450 MHz)

RESPOSTAS BIOLÓGICAS DE Anagasta kuehniella E DE SEU PARASITÓIDE, Bracon hebetor, À RADIAÇÃO POR MICROONDAS (2450 MHz)

Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma.

Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.

Gastric injury from (90)Y to left hepatic lobe tumors adjacent to the stomach: fact or fiction?

Radioembolization with (90)Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of (90)Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe (90)Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma ± tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with (90)Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. Ninety-seven patients successfully underwent left hepatic lobe (90)Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 ± 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 ± 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 ± 41 Gy. There were no reportable or recordable medical events. Of the patients, 34% reported abdominal pain that was grade 1-2; 65% of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass microspheres.

The effects of chronic radiation of gamma ray on protein expression and oxidative stress in Brachypodium distachyon

Purpose: To compare the effects of gamma-irradiation on biochemical responses and growth, six-week-old Brachypodium plants were chronically exposed to gamma-irradiation for 30 days at various dosages.Materials and methods: Growth surveys of Brachypodium plants in response to different dosages of gamma-irradiation were conducted to compare physiological changes between irradiated and non-irradiated plants. Photosynthetic pigments, soluble sugar content, activities of antioxidant enzymes, and malonaldehyde (MDA) induced by reactive oxygen species (ROS) production were also measured.Results: Gamma-irradiation had a negative influence on the average plant height, leaf length, leaf width, and fresh weight. Photosynthetic pigment levels decreased with increasing dosages of gamma-irradiation, while soluble sugar content slightly increased. Gamma-irradiation responsive proteins were detected and identified by two-dimensional gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF). The proteins had a role in photosynthetic carbon fixation, anabolic pathway glycolysis, mitochondrial ATP production, and oxidative stress response regulation. MDA levels and activities of antioxidant enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD) increased with the increase in gamma-irradiation dosage level.Conclusions: This study provides some basic information regarding responses to gamma-irradiation, and provides valuable physiological and biological data on the effects of different gamma-irradiation dosages on Triticeae species.

Forecasting Radiation Effects on Wildlife in Japan After the Fukushima Nuclear Accident, Based on Limited Information of Post-Accident Early Stage in 2011

Abstract. Due to the 11 March 2011 Tohoku earthquake, massive radioactive materials were released from the Fukushima Daiichi Nuclear Power Plant (Fukushima NPP). It is crucial to predict the regional distribution and magnitude of the effects on wildlife by radioactive materials. However, during the post-accident early stage in 2011, limited information on large-scale pollution and prediction maps was open to public. Hence, this paper aimed to provide (1) the pollution map covering areas within 300 km from the Fukushima NPP where the radiation intensity exceeded 0.5 μSv/h, (2) pollution maps which predicted air dose for the next 30 years after the accident, and (3) maps of areas where wildlife might be affected by radioactive isotopes by the Fukushima nuclear accident. First, the relative contributions of 131I, 134Cs, and 137Cs were estimated from time series observation data. Second, a 30-year prediction of the pollution was calculated based on the isotope half-lives. Third, the chronic radiation effects on vertebrates were estimated using the threshold dose rate proposed by Sazykina et al. (2009). We examined the chronic radiation effects on morbidity, reproduction, and longevity. The results indicated that radioactive materials could have affected vertebrate morbidity within a 350 km2 area in early April 2011; the threshold level was the median result of Sazykina et al. (2009) with bootstrapping. Based on the prediction, a 15.5 km2 region will remain affected after 30 years. These areas should be monitored to confirm the effects of radioactivity on wildlife.

Analysis of Hematopoiesis Dynamics in Residents of Techa Riverside Villages Chronically Exposed to Nonuniform Radiation

A profound approach to the analysis of clinical data on the dynamics of major hematopoietic lineages (granulocytopoietic, thrombocytopoietic, and erythrocytopoietic systems) in chronically irradiated humans is proposed. It is based on recently developed mathematical models of these systems in humans, which enable one to study and interpret clinical hematological data. The developed approach is applied to the analysis of statistically processed clinical data, which were obtained under hematological examinations of residents of Techa riverside villages. These people were exposed to chronic irradiation with varying dose rate due to the radioactive contamination of the river basin by the Mayak Production Association. In the course of modeling studies, the relationship between the dynamics of aforementioned systems in examined individuals and the variation of chronic exposure dose rate over the considered period of time is revealed. It is found that the models are capable of reproducing common regularities and peculiarities of the dynamics of systems on hand, including the decreased stationary levels of blood cell concentrations during the period of maximum radiation exposure, the recovery processes during the period of decrease of exposure dose rate, and the prevalence of younger bone marrow granulocytopoietic cells over more mature ones during the entire period. The mechanisms of such effects of chronic irradiation on the hematopoietic lineages are revealed on the basis of modeling studies. All this testifies to the efficiency of employment of the developed models in the analysis, investigation, and prediction of effects of chronic irradiation on human hematopoietic system.

Modeling analysis of the lymphocytopoiesis dynamics in chronically irradiated residents of Techa riverside villages

A biologically motivated dynamical model of the lymphocytopoietic system in irradiated humans is applied here to analyze the data obtained under hematological examinations of residents of Techa riverside villages. Those people were exposed to chronic irradiation with varying dose rates, due to the radioactive contamination of the river basin by the Mayak Production Association. Modeling studies revealed the relationship between the dynamics of the lymphocytopoietic system in the examined individuals and the variation of dose rate over the considered period of time. It is found that the developed model is capable of reproducing the decreased level of blood lymphocyte concentration observed during the period of maximum radiation exposure, the recovery processes in the system observed during the period of decreasing dose rate, as well as the enhanced mitotic activity of bone marrow precursor cells in this hematopoietic lineage observed during the entire period under consideration. Mechanisms of these effects of chronic irradiation on the human lymphocytopoietic system are elucidated based on the applied model. The results obtained demonstrate the efficiency of the developed model in the analysis, investigation, and prediction of effects of chronic irradiation with varying dose rate on the human lymphocytopoietic system. In particular, the developed model can be used for predicting any radiation injury of this vital system in people exposed to chronic irradiation due to environmental radiological events, such as anthropogenic radiation accidents or radiological terroristic attacks.

Ninth Annual Warren K. Sinclair Keynote Address

The acute and chronic effects of radiation on children have been and will continue to be of great social, public health, scientific, and clinical importance. The focus of interest on ionizing radiation and children has been clear for over half a century and ranges from the effects of fallout from nuclear weapons testing to exposures from accidents, natural radiation, and medical procedures. There is a loosely stated notion that "children are three to five times more sensitive to radiation than adults." Is this really true? In fact, children are at greater risk for some health effects, but not all. For a few sequelae, children may be more resistant than adults. Which are those effects? How and why do they occur? While there are clear instances of increased risk of some radiation-induced tumors in children compared to adults, there are other tumor types in which there appears to be little or no difference in risk by age at exposure and some in which published models that assume the same relative increase in risks for child compared to adult exposures apply to nearly all tumor types are not supported by the scientific data. The United Nations Scientific Committee on Effects of Atomic Radiation (UNSCEAR) has a task group producing a comprehensive report on the subject. The factors to be considered include relevant radiation sources; developmental anatomy and physiology; dosimetry; and stochastic, deterministic, and hereditary effects.

Abstract 4431: TRAIL resistance by radiation induced hypermethylation of DR4 CpG island in recurrent laryngeal squamous cell carcinoma .

Abstract The radiotherapy has been known as one of standard treatment methods in larynx cancer, and the many targeted therapies have been developed for improving radiotherapy. In this regard, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be one promising candidate, because TRAIL has a high selectivity for tumor cells and radiation efficiently sensitizes tumor cells towards apoptosis induction by TRAIL. It has been showing that irradiation strongly sensitizes malignant cells to TRAIL-induced apoptosis without any synergistic effects in normal tissues. Up to now, however, most studies have focused on immediate TRAIL-effect after small amount of irradiation. In this study, we aim to investigate the effect of chronic irradiation on TRAIL response to see if TRAIL could be an effective targeted therapy in recurrent laryngeal squamous cell carcinoma. Using previously established AMC-HN3 cell line from laryngeal SCCa patient, we have generated isogenic model of chronic irradiated HN3R cell line after every 2 or 3 day irradiation of 2 Gy/day of X-rays (70 Gy cumulative doses). Interestingly, through MTS assay, HN3R cells show much more resistance to TRAIL induced apoptosis than HN3 cells. Among suggested mechanisms, we found that a significantly reduced DR4 receptor is the cause of this resistance. Reverse transcription-PCR, western blotting and FACS analysis for DR4 receptors show that the expression of mRNA and the total amount, and surface expression of DR4 protein was much less in HN3R cells. Inhibition of DR4 by antagonistic antibody or si-DR4 significantly decreased TRAIL sensitivity in HN3 cells, and overexpression of DR4 enhanced the TRAIL sensitivity in HN3R cells. To evaluate this result in laryngeal cancer specimens, tissue microarray with 81 advanced laryngeal cancer specimens was constructed. Immunohistochemical assessment score of DR4 staining in 23 salvage surgical specimens after radiation failure shows statistically significant lower score than 58 surgical specimens without radiation treatment (3.09±2.23 vs. 4.43±3.36, p=0.040). Postulating that DR4 gene might be silenced by hypermethylation after long-term irradiation, methylation-specific PCR for DR4 was undertaken. Compared to HN3 cells, HN3R cells had a methylated 5’ regulatory CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2’-deoxycytidine (5-AZAdC). In conclusion, chronic irradiation induces the TRAIL resistance by hypermethylation of CpG island of DR4 receptor in recurrent laryngeal squamous cell carcinoma. Thus, the status of receptor methylation might be one of biomarker to predict TRAIL response especially after radiation failure. Citation Format: Jong Cheol Lee, Won Hyeok Lee, Young Joo Min, Yoon-Se Lee, Jung Je Park, Seong Who Kim, Sang Yoon Kim. TRAIL resistance by radiation induced hypermethylation of DR4 CpG island in recurrent laryngeal squamous cell carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4431. doi:10.1158/1538-7445.AM2013-4431

Effect of chronic irradiation on plant resistance to biotic stress in 30-km chernobyl nuclear power plant exclusion zone

It was established in greenhouse experiments that infection with powdery moldew (Erysiphe graminis DC. f. sp. tritici Em. Marchal) and brown rust (Puccinia triticana Erikss. & Henn.) of three wheat (Triticum aestivum L.) cultivars (Mironovskaya 808, Polesskay 70, and Kiyanka) grown from seeds, collected in the Chernobyl exclusion zone, was 1.5–2.0 times higher than of plants grown from control seeds. On field trials in the Chernobyl zone, wheat plant resistance to biotic stress was reduced. At artificial infection with brown rust, the disease development was enhanced on plots with increased radiation background. One of the mechanisms of the declined phytoimmunity potential under the action of low doses of chronic irradiation is evidently a reduced activity of plant proteinase inhibitors. Thus, in wheat and rye (Secale cereale L., cv. Saratovskaya) grains, their activity reduced by 35–60% as compared to control. Active form and race formation in the population of the cereal stem rust causal agent (Puccinia graminis Pers.) was observed in the Chernobyl zone. A “new” population of this fungus with high frequency of more virulent clones than in other Ukraine regions was distinguished. The results obtained independently in greenhouse and field trials performed in the Chernobyl zone demonstrated radiation stress influence on the pathogen-plant interactions. They indicate a necessity of monitoring the microevolutionary processes occurring in both plants and their pathogens under conditions of technogenic stresses.