Acute Radiation Effects Research Articles

Ultraviolet Keratitis: From the Pathophysiological Basis to Prevention and Clinical Management

Ultraviolet keratitis is caused by the toxic effects of acute high-dose ultraviolet radiation (UVR) reflecting the sensitivity of the ocular surface to photochemical injury. The clinical syndrome presents with ocular pain, tearing, conjunctival chemosis, blepharospasm, and deterioration of vision typically several hours after exposure, lasting up to 3 days. Mountaineers, skiers, and beach recreationalists are particularly at risk to suffer from ultraviolet (UV) keratitis as the reflectivity of UVR in these environments is extremely high. The aim of this review is to raise awareness about the potential of UV damage on the eye with an emphasis on UV keratitis, to highlight the pathophysiological basis of corneal phototoxicity, and to provide practical guidance for the prevention and clinical management of UV keratitis commonly known as snow blindness.

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.

Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice.

PurposePelvic irradiation for the treatment of cancer can affect normal cells, such as the rapidly proliferating spermatogenic cells of the testis, leading to infertility, a common post-irradiation problem. The present study investigated the radioprotective effect of rolipram, a specific phosphodiesterase type-IV inhibitor known to increase the expression and phosphorylation of the cyclic adenosine monophosphate response element-binding protein (CREB), a key factor for spermatogenesis, with the testicular system against pelvic irradiation.Materials and MethodsMale C57BL/6 mice were treated with pelvic irradiation (2 Gy) and rolipram, alone or in combination, and were sacrificed at 12 hours and 35 days after irradiation.ResultsRolipram protected germ cells from radiation-induced apoptosis at 12 hours after irradiation and significantly increased testis weight compared with irradiation controls at 35 days. Rolipram also ameliorated radiation-induced testicular morphological changes, such as changes in seminiferous tubular diameter and epithelial height. Additionally, seminiferous tubule repopulation and stem cell survival indices were higher in the rolipram-treated group than in the radiation group. Moreover, rolipram treatment counteracted the radiation-mediated decrease in the sperm count and mobility in the epididymis.ConclusionsThese protective effects of rolipram treatment prior to irradiation may be mediated by the increase in pCREB levels at 12 hours post-irradiation and the attenuated decrease in pCREB levels in the testis at 35 days post-irradiation in the rolipram-treated group. These findings suggest that activation of CREB signaling by rolipram treatment ameliorates the detrimental effects of acute irradiation on testicular dysfunction and the related male reproductive functions in mice.

Effects of acute gamma radiation on the reproductive ability of the earthworm Eisenia fetida

Earthworms are the most suitable biological indicators of radioactive pollution because they are the parts of nutritional webs, and are present in relatively high numbers. Four months old Eisenia fetida were exposed to different doses of gamma radiation, namely 1, 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 & 60 Gy to study the effects of radiation on different reproductive parameters. The number of cocoons laid and the hatchlings emerged were recorded for all the selected doses. There was no reduction in cocoon production, however; decreasing size and weight of the cocoons was observed from the samples exposed to 20 Gy and above doses. Significant reductions in the hatchlings were recorded in earthworms exposed to 10 Gy and above doses. The dose response curves for a percentage reduction in hatchlings were constructed. Exposure to radiation dose of 1 and 2 Gy did not show any reduction, however, there was ≈10%, ≈50% and ≈90% decrease in the hatchlings in samples exposed to 3, 15 and 45, 50, 55 and 60 Gy doses respectively. Delayed hatchability was also reported at al exposure level. Histology of irradiated earthworms revealed that the structural damage in the seminal vesicles was prominent at the exposed dose of 3 Gy onwards with complete degeneration on exposure to 60 Gy of gamma radiation.

Abstract A22: The impact of dose reduction upon local tumor control for stereotactic radiation therapy in an orthotopic rat model of osteosarcoma

Abstract Purpose: Primary bone tumors such as osteosarcoma (OSA) are rare but devastating tumors that most commonly affect young people. For adolescents and dogs with OSA, local tumor control can be difficult to achieve with finely fractionated radiation therapy. Stereotactic radiation therapy (SRT) is a promising treatment modality that results in the delivery of ablative radiation dose to the tumor, while preferentially minimizing dose to the surrounding normal tissues. In our clinical experience with SRT in dogs, a total dose of 36Gy delivered in three fractions has been associated with excellent local tumor control based upon clinical response and histopathology of the irradiated tumor. The risk of post radiation fracture is related to pre-existing tumor associated osteolysis and the effect of irradiation upon normal bone. A previously established orthotopic rat model was used to perform a dose reduction study in an effort to optimize the SRT protocol. Methods &amp; Materials: Twenty-four nude rats were injected with 1 x 10^6 canine osteosarcoma cells into the distal femoral metaphyses. Two weeks after tumor inoculation, rats were treated with SRT delivered once daily in three equal fractions. The tumor affected bone of six rats each were treated to a total dose of 36Gy (12Gy/fx), 33Gy (11Gy/fx), 30Gy (10Gy/fx), or 27Gy (9Gy/fx). Tumor viability and response to SRT were evaluated once weekly for six weeks via bioluminescence imaging, radiographs of the femur, and urine pyridinoline levels (PYD). Acute radiation effects of the skin were evaluated by Veterinary Radiation Therapy Oncology Group (VROTG) normal tissue toxicity scoring rubric. Post mortem histology provided an objective measure of tumor necrosis. Results: In all treatment groups, PYD levels were significantly increased two weeks after tumor inoculation (p&amp;lt;0.0001) and were significantly decreased three weeks after SRT (p &amp;lt;0.0001) as compared to baseline. No statistical difference in PYD levels was noted between radiation groups. Mean tumor necrosis for each radiation dose group was: 87% for 36Gy, 58% for 33Gy, 63% for 30Gy, and 74% for 27Gy. The mean overall tumor necrosis was 70%. There was no statistically significant difference between treatment groups. None of the animals experienced greater than grade I skin toxicity. Conclusions: All four protocols were well tolerated and associated with mild, transient skin toxicity. In canine and human osteosarcoma data, improved duration of local tumor control is correlated with tumor necrosis of 80% or higher. While there was no statistical significance between treatment groups, only the 36Gy group achieved that benchmark of tumor control. Consideration of SRT as a therapeutic option for adolescents with OSA requires further evaluation via orthotopic models. Future dose reduction studies evaluating the clinically relevant concurrent administration of carboplatin and SRT are warranted. Citation Format: James T. Custis, Anthony L. Schwartz, Joseph F. Harmon, Barbara E. Powers, Laura S. Chubb, Susan M. LaRue, Nicole P. Ehrhart, Stewart D. Ryan. The impact of dose reduction upon local tumor control for stereotactic radiation therapy in an orthotopic rat model of osteosarcoma. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr A22.

Genotoxicity in earthworm after combined treatment of ionising radiation and mercury.

This study was performed to investigate the acute genotoxic effects of mercury and radiation on earthworms (Eisenia fetida). The levels of DNA damage and the repair kinetics in the coelomocytes of E. fetida treated with mercuric chloride (HgCl₂) and ionising radiation (gamma rays) were analysed by means of the comet assay. For detection of DNA damage and repair, E. fetida was exposed to HgCl₂ (0-160 mg kg(-1)) and irradiated with gamma rays (0-50 Gy) in vivo. The increase in DNA damage depended on the concentration of mercury or dose of radiation. The results showed that the more the oxidative stress induced by mercury and radiation the longer the repair time that was required. When a combination of HgCl₂ and gamma rays was applied, the cell damage was much higher than those treated with HgCl₂ or radiation alone, which indicated that the genotoxic effects were increased after the combined treatment of mercury and radiation.

Acute effects of solar particle event radiation

A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animals exposed to space flight stressors combined with the types of radiation expected during an SPE. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations: gamma rays or electrons). All animal studies described have been approved by the University of PA IACUC. Some conclusions from recent CARR investigations are as follows: (i) the relative biological effectiveness (RBE) values for SPE-like protons compared with standard reference radiations (gammas or electrons) for white blood cells (WBCs) vary greatly between mice, ferrets and pigs, with the RBE values being greater in ferrets than those in mice, and considerably greater in pigs compared with those in ferrets or mice [1, 2]. This trend for the data suggests that the RBE values for WBCs in humans could be considerably greater than those observed in small mammals, and SPE proton radiation may be far more hazardous to humans than previously estimated from small animal studies. (ii) Very low doses of SPE proton radiation (25 cGy) increase blood clotting times in ferrets, and the low SPE-like dose rate has more severe effects than high dose rate radiation [3]. (iii) Results from pig and ferret studies suggest that disseminated intravascular coagulation is a major cause of death at doses near the LD50 level for SPE-like proton and gamma radiation. (iv) Exposure to SPE-like proton or gamma radiation, in combination with simulated microgravity (hindlimb suspension), leads to a very high level of morbidity/mortality in mice given a bacterial challenge with non-toxic levels of Pseudomonas aeruginosa or Klebsiella pneumoniae; the threshold for this effect was 1.5 Gy. (v) T-cell activation was reduced in mice exposed to SPE-like radiation with or without simulated hypogravity (either partial weight suspension or hindlimb suspension) (e.g. [4]). (vi) Radiation and simulated hypogravity had synergistic effects on immune system biological endpoints (e.g. [5]). (vii) Pigs exposed to simulated SPE radiation exhibited increases in intracranial pressure that remained elevated over the 90-day experimental period. (viii) A major sparing effect of SPE-like low dose rate radiation (compared with the results for high dose rate radiation) was observed for ferret emesis parameters, such that the differences between the results for ferret exposure to low dose rate radiation (50 cGy/h) and controls were not statistically significant (for doses up to 2 Gy). For high dose rate SPE proton radiation, the threshold value for retching was 75 cGy, and for ferret vomiting, it was 1 Gy.

Acute effects of ionizing radiation on human endothelial barrier function

The human vasculature is critical to healthy functioning of the tissues of the body and a major factor in maintaining homeostasis is the endothelial barrier. In the brain, the blood–brain barrier (BBB) is highly specialized in order to sustain the neural tissue.Here, we have examined the effects of radiation on BBB models using a unique variety of endpoints to assess barrier function. These include trans-endothelial electrical resistance (TEER), morphological effects, localization of adhesion and cell junction proteins (in two-dimensional monolayers and in three-dimensional tissue models) and permeability of molecules through the endothelial barrier. Two culture conditions were used to represent conditions on the inside or the lumen of vessels and conditions on the outside or ablumenal side of vessels. For the lumen, cells were cultured in serum and growth factor containing media, and for the ablumenal side of vessels, cells were cultured in serum-free defined media.Initial experiments with gamma rays in serum-free conditions revealed a previously unknown acute effect involving cell detachment and the loss of the clinically relevant cell adhesion molecule—cell platelet endothelial adhesion molecule (PECAM)-1 [ 1]. Gamma radiation (5 Gy) induced a rapid and transient decrease in TEER at 3 h, with effects also seen at the lower radiotherapy dose of 2 Gy. This dip in resistance correlated with the transient loss PECAM-1 in discrete areas where cells often detached from the monolayer leaving gaps. Loss in PECAM-1 occurred at least in part as detached microparticles. Redistribution of PECAM-1 microparticles was also seen in three-dimensional human tissue models. By 6 h, the remaining cells had migrated to reseal the barrier, coincident with TEER returning to control levels. Resealed monolayers contained fewer cells per unit area and their barrier function was weakened as corroborated by an increased permeability over 24 h. Because PECAM-1 is involved in barrier function and platelet aggregation, this effect is likely highly relevant to cancer radiotherapy using gamma rays.These studies were extended to include low linear energy transfer (LET) photons of X-rays and ion particles present in the space environment—low LET ion particles including high energy (1 GeV) protons and helium ions. X-rays under serum-free conditions also showed an acute response involving a dip in TEER at 3 h and the loss of PECAM-1 between cells as microparticles. Ion particles, however, did not show these effects of photons under serum-free conditions. Both protons and helium ions at doses up to 5 Gy did not produce this transient change in TEER or PECAM-1, although some longer term effects in TEER were noted.In the presence of serum and growth factors, however, all radiations tested showed short-term effects in TEER, that of a series of symmetrical peaks which diminished in size over several hours. For 1 GeV protons and helium ions, this effect could be fitted to an equation for under-damped oscillation, a pattern typical of a mechanism for timing of events in periodic processes. For gamma and X-rays, the underdamped oscillation was present but superimposed on a drop in resistance at 3 h similar to that seen in serum-free conditions.In conclusion, we have shown two acute effects of low LET radiation on the human endothelial barrier. First, a short-term effect of photons but not ion particles involving a single dip in TEER and the loss of PECAM-1 at 3 h after irradiation, and second an underdamped oscillation of TEER induced by both photons and ion particles that to date does not appear to be associated with the loss of PECAM-1 or any other junction molecules.

Organotypical vascular model for characterization of radioprotective compounds: studies on antioxidant 2,3-diaryl-substituted indole-based cyclooxygenase-2 inhibitors.

Radiotherapy of various cancers is closely associated with increased cardiovascular morbidity and mortality. Arachidonic acid metabolites are supposed to play a key role in radiation-induced vascular dysfunction. This study was designed to evaluate the effects of novel, antioxidative 2,3-diaryl-substituted indole-based selective cyclooxygenase-2 (COX-2) inhibitors (2,3-diaryl-indole coxibs) on radiation-induced formation of arachidonic acid metabolites via COX-2 and oxidant stress pathways in an organotypical vascular model of rat aortic rings. Acute and subacute effects of X-ray radiation (4 and 10 Gy; 1 and 3 days post irradiation) with or without the presence of 1 μM of the 2,3-diaryl-indole coxib 2-[4-(aminosulfonyl)phenyl]-3-(4-methoxyphenyl)-1H-indole (C1) or celecoxib as reference compared to sham-irradiated controls were assessed. The following parameters were measured: metabolic activity of the aortic rings; induction and regulation of COX-2 expression; release of prostaglandin E2 and F2α-isoprostane. Irradiation without presence of coxibs resulted in a dose-dependent augmentation of all parameters studied. When aortic rings were exposed to the 2,3-diaryl-indole coxib 1 h before irradiation, metabolic activity was restored and the release of both prostaglandin and isoprostane was inhibited. The latter indicates a direct interaction with oxidant stress pathways. By contrast, celecoxib exhibited only slight effects on the formation of isoprostane. The reduction of radiation-induced vascular dysfunction by antioxidative coxibs may widen the therapeutic window of COX-2 targeted treatment.

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.

Effect of ionizing radiation on human skeletal muscle precursor cells

BackgroundLong term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures.Materials and methodsHuman skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin – 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death.ResultsCompared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70).ConclusionsOur results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions.

Acute Hematological Effects of Solar Particle Event Proton Radiation in the Porcine Model

Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel.

Infrared irradiation alters the expression of matrix metalloproteinases and glycosaminoglycans in the cornea and crystalline lens

Prolonged exposure to infrared (IR) radiation is associated with different types of damage to cornea and lens. The aim of our study was to investigate the effect of acute and chronic exposure to IR radiation on the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 and on the expression of glycosaminoglycans (GAG) in the rabbit cornea and crystalline lens. New Zealand rabbits were subjected to IR radiation for 4 months (chronic exposure to IR) or to normal light (control group). In experiments regarding acute exposure, animals were subjected to IR radiation or normal light for 12 h, in the presence of 0.1% diclofenac sodium (eye drops instilled in the right eye of animals) or saline (instilled in the left eye of animals). The cornea and lens were dissected away and homogenized. The activity of MMP-2 and MMP-9 was assayed by gelatine zymography. Total GAG were isolated from tissue specimens after lipid extraction and extensive digestion with pronase and DNase and characterized by treatment with GAG-degrading enzymes, followed by electrophoresis on cellulose acetate membranes. Acute or chronic exposure to IR radiation induced the activity of MMP-2 in cornea and lens, whereas only acute IR radiation increased the content of heparan sulphate in crystalline lens. Local administration of diclofenac sodium did not prevent the above effects of acute IR radiation. The detrimental effects of excessive or prolonged exposure of the eyes to IR radiation are associated with induced activity of MMP-2 in cornea and lens and alterations in the content of heparan sulphate in lens. Thus, MMP and GAG may offer alternative targets for pharmacological intervention to confront ocular damages associated with IR radiation.

Nursing-led management of side effects of radiation: evidence-based recommendations for practice

Nursing-led management of side effects of radiation: evidence-based recommendations for practice Patricia PoirierUniversity of Maine School of Nursing, Orono, ME, USAAbstract: It has been estimated that 50%&ndash;60% of patients diagnosed with cancer will receive radiation therapy at some point in their treatment. Although radiation therapy can play a significant role in the cure or control of cancer, and the palliation of symptoms, it also has side effects. Side effects of radiation therapy can interfere with patient quality of life and daily functioning. Severe side effects can lead to delays in treatment, potentially affecting the outcome of treatment. All patients receiving radiation therapy are at risk of fatigue and skin reactions in the area of the body being treated. Other side effects of radiation therapy are specific to the part of the body being treated. Radiation therapy to the head and neck area may cause oral mucositis, dryness, and nutritional deficiencies. Radiation therapy to the chest or lung area may lead to difficulty in swallowing and eating. Radiation therapy to the pelvis frequently causes diarrhea. There are many nursing interventions available to manage the side effects of treatment based on best available evidence and expert opinion. Nurses in all settings are essential in helping patients manage the side effects of treatment and maintain their quality of life. The purpose of this review is to provide nurses with evidence-based recommendations and suggestions for managing common acute side effects of radiation therapy.Keywords: evidence-based practice, radiation therapy, side effects, nursing management

Predicted ionisation in mitochondria and observed acute changes in the mitochondrial transcriptome after gamma irradiation: A Monte Carlo simulation and quantitative PCR study

It is a widely accepted that the cell nucleus is the primary site of radiation damage while extra-nuclear radiation effects are not yet systematically included into models of radiation damage.We performed Monte Carlo simulations assuming a spherical cell (diameter 11.5μm) modelled after JURKAT cells with the inclusion of realistic elemental composition data based on published literature. The cell model consists of cytoplasm (density 1g/cm3), nucleus (diameter 8.5μm; 40% of cell volume) as well as cylindrical mitochondria (diameter 1μm; volume 0.5μm3) of three different densities (1, 2 and 10g/cm3) and total mitochondrial volume relative to the cell volume (10, 20, 30%). Our simulation predicts that if mitochondria take up more than 20% of a cell's volume, ionisation events will be the preferentially located in mitochondria rather than in the cell nucleus.Using quantitative polymerase chain reaction, we substantiate in JURKAT cells that human mitochondria respond to gamma radiation with early (within 30min) differential changes in the expression levels of 18 mitochondrially encoded genes, whereby the number of regulated genes varies in a dose-dependent but non-linear pattern (10Gy: 1 gene; 50Gy: 5 genes; 100Gy: 12 genes).The simulation data as well as the experimental observations suggest that current models of acute radiation effects, which largely focus on nuclear effects, might benefit from more systematic considerations of the early mitochondrial responses and how these may subsequently determine cell response to ionising radiation.

Quality of life and acute radiation effects in patients with breast cancer who have received radiotherapy

Quality of life and acute radiation effects in patients with breast cancer who have received radiotherapy

Evidence of Delayed Gastrointestinal Syndrome in High-dose Irradiated Mice

The acute effects of irradiation on the gastrointestinal (GI) system are well documented, but the longer-term effects are less well known. Increased incidence of adenocarcinoma has been noted, but apart from descriptions of fibrosis, the development of other pathologies specific to survivors of acute radiation is poorly understood. Samples were taken from C57BL/6 mice irradiated with partial-body irradiation where the thorax, head, and forelimbs were shielded (i.e., sparing 40% of the bone marrow). Tissue from age-matched controls was also collected. There were clear pathological changes in the intestine associated with DEARE (Delayed Effects of Acute Radiation Exposure) at doses greater than 12 Gy, with a dose-related increase in observed pathologies. Mice maintained on the synthetic antibiotic ciprofloxacin during the acute phase (days 4 to 20), however, had a lower or delayed incidence of symptoms. After 20 d, mice developed structures similar to early adenomas. Abnormally high levels of apoptotic and mitotic cells were present in some crypts, along with the early adenomas, suggesting tissue regeneration and areas of deregulated cell turnover. Over time, there was inhibited crypt cell proliferation in animals with advanced symptoms, a blunting of the crypts and villi, and an enlargement of villus girth, with an increasingly acellular and fibrotic extracellular matrix (a characteristic that has been demonstrated previously in aging mice). Together these changes may lead to a reduced functional surface area and less motile intestine. These observations are similar to those seen in geriatric animals, suggesting a premature aging of the GI tract.

Early Reduction of Microglia Activation by Irradiation in a Model of Chronic Glaucoma

Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, the mechanisms leading to onset and progression of the disease remain unknown. Molecular analysis in various glaucoma models has revealed involvement of non-neuronal cell populations, including astrocytes, Mueller glia and microglia, at early stages of glaucoma. High-dose irradiation was reported to have a significant long-term protective effect in the DBA/2J (D2) mouse model of glaucoma, although the cellular and molecular basis for this effect remains unclear. In particular, the acute effects of irradiation on specific cell populations, including non-neuronal cells, in the D2 retina and nerve have not been assessed. Here we report that irradiation induces transient reduction in proliferating microglia within the optic nerve head and glial lamina within the first week post-irradiation. This was accompanied by reduced microglial activation, with no effect on astrocyte gliosis in those regions. At later stages we confirm that early high-dose irradiation of the mouse head results in improvement of axonal structural integrity and anterograde transport function, without reduction of intraocular pressure. Thus reduced microglial activation induced by irradiation at early stages is associated with reduced optic nerve and retinal neurodegeneration in the D2 mouse model of glaucoma.

Radiation Induces Acute Alterations in Neuronal Function

Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABAARs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

Evaluation of acute radiation effects on mandibular movements of patients with head and neck cancer

To evaluate radiotherapy effects (RT) on mandibular movements of patients with head and neck cancer (H&NC) and associate them to the variables: functional capacity, radiation field, disease staging, type of feeding, concomitant chemotherapy and total dose of RT. Twenty-six patients with H&NC were followed up at the RT service. Physical examination was performed in 3 follow up time points: before the beginning of RT (T0), between 14th and 17th session of RT (T1) and after the last session of RT (T2). The physical examination consisted of the assessment of the following variables: mouth opening without pain (MO), maximum mouth opening (MMO), right lateral excursion (RLE), left lateral excursion (LLE) and protrusion (PR) of the jaw. The feeding type and the Karnofsky Performance Status Scale (KPS) were evaluated in each follow up time point. Data with regards to the tumor lesion and the RT were collected from the patient's clinical notes. There was a statistical significant reduction in the values of MO (p=0.006), MMO (p=0.001), LLE (p=0.006) and KPS (p=0.001). There was significant a statistical association among the reduction in KPS and decreased measure of MO (r=0.390, p=0.048) and MMO (r=0.435, p=0.026). The mouth and oropharynx radiation fields when combined showed a significant reduction for both the measure of MO (p=0.005) and for MMO (p=0.004). Patients who used nasoenteric tube feeding (NTF) had greater reduction in the measurement of MMO (p=0.031). The remaining variables showed no statistically significant difference. Patients with H&NC present reduction of the measures of MO and MMO during the RT, especially if they present reduced functional capacity, have radiation in the mouth and oropharynx fields and used NTF.