Mobile equipment use of wireless fidelity (Wi-Fi) signal modulation has increased exponentially in the past few decades. However, there is inconclusive scientific evidence concerning the potential risks associated with the energy deposition in the brain from Wi-Fi and whether Wi-Fi electromagnetism interacts with cognitive function. In this study we investigated possible neurocognitive effects caused by Wi-Fi exposure. First, we constructed a Wi-Fi exposure system from commercial parts. Dosimetry was first assessed by free space radiofrequency field measurements. The experimental exposure system was then modeled based on real geometry and physical characteristics. Specific absorption rate (SAR) calculations were performed using a whole-body, realistic human voxel model with values corresponding to conventional everyday Wi-Fi exposure (peak SAR_10g level was 99.22 mW/kg with 1 W output power and 100% duty cycle). Then, in two provocation experiments involving healthy human volunteers we tested for two hypotheses: 1. Whether a 60 min long 2.4 GHz Wi-Fi exposure affects the spectral power of spontaneous awake electroencephalographic (sEEG) activity (N = 25); and 2. Whether similar Wi-Fi exposure modulates the sustained attention measured by reaction time in a computerized psychomotor vigilance test (PVT) (N = 19). EEG data were recorded at midline electrode sites while volunteers watched a silent documentary. In the PVT task, button press reaction time was recorded. No measurable effects of acute Wi-Fi exposure were found on spectral power of sEEG or reaction time in the psychomotor vigilance test. These results indicate that a single, 60 min Wi-Fi exposure does not alter human oscillatory brain function or objective measures of sustained attention.

Previously reported studies have demonstrated the involvement of p21^Waf1/CIP1 in radiation-induced bystander effects (RIBE). Mouse embryonic fibroblasts (MEFs) lacking Hus1 fail to proliferate in vitro, but inactivation of p21 allows for the continued growth of Hus1-deficient cells, indicating the close connection between p21 and Hus1 cells. In this study, wild-type MEFs, Hus1 ^/ p21^–/– MEFs and p21^–/–Hus1^–/– MEFs were used in a series of radiation-induced bystander effect experiments, the roles of p21 and Hus1 in the induction and transmission of radiation-induced damage signals were investigated. Our results showed that after 5 cGy α particle irradiation, wild-type MEFs induced significant increases in γ-H2AX foci and micronuclei formation in bystander cells, whereas the bystander effects were not detectable in p21^–/–Hus1 ^/ MEFs and were restored again in p21^–/–Hus1^–/– MEFs. Media transfer experiments showed that p21^–/–Hus1 ^/ MEFs were deficient in the production bystander signals, but could respond to bystander signals. We further investigated the mitogen-activated protein kinases (MAPKs) that might be involved in the bystander effects. It was found that although knocking out p21 did not affect the expression of connexin43 and its phosphorylation, it did result in inactivation of some MAPK signal pathway kinases, including JNK1/2, ERK1/2 and p38, as well as a decrease in reactive oxygen species (ROS) levels in irradiated cells. However, the activation of MAPK kinases and the ROS levels in irradiated cells were restored in the cell line by knocking out Hus1. These results suggest that p21^Waf1/CIP1 and Hus1 play crucial roles in the generation and transmission of bystander damage signals after low-dose α-particle irradiation.

A unique feature of the space radiation environment is the presence of high-energy charged particles, which can be significantly hazardous to space flight crews who are exposed during a mission. Health risks associated with high-LET radiation exposure include cognitive injury. The pathogenesis of this injury is unknown but may involve modifications to dendritic structure and/or alterations in dendritic spine density and morphology. In this study, 24 two-month-old C57BL6/J male mice were either whole-body irradiated with 0.5 Gy ⁵⁶Fe (600 MeV/n; n = 12) or sham irradiated (n = 12). Three months postirradiation animals were tested for locomotor activity and habituation. After behavioral testing, animals were euthanized and the brains were flash frozen. Compared to sham-irradiated mice, irradiated mice moved less when first introduced to the environment, although they did recognize the environment when re-exposed to it one day later. Exposure to ⁵⁶Fe radiation significantly compromised the dendritic architecture and reduced spine density throughout the hippocampal tri-synaptic network. To our knowledge, these data represents the first reported evidence that high-LET radiation has deleterious effects on mature neurons associated with hippocampal learning and memory.

The Thyrotoxicosis Therapy Follow-up Study (TTFUS) is comprised of 35,593 hyperthyroid patients treated from the mid-1940s through the mid-1960s. One objective of the TTFUS was to evaluate the long-term effects of high-dose iodine-131 (¹³¹I) treatment (1–4). In the TTFUS cohort, 23,020 patients were treated with ¹³¹I, including 21,536 patients with Graves disease (GD), 1,203 patients with toxic nodular goiter (TNG) and 281 patients with unknown disease. The study population constituted the largest group of hyperthyroid patients ever examined in a single health risk study. The average number (±1 standard deviation) of ¹³¹I treatments per patient was 1.7 ± 1.4 for the GD patients and 2.1 ± 2.1 for the TNG patients. The average total ¹³¹I administered activity was 380 ± 360 MBq for GD patients and 640 ± 550 MBq for TNG patients. In this work, a biokinetic model for iodine was developed to derive organ residence times and to reconstruct the radiation-absorbed doses to the thyroid gland and to other organs resulting from administration of ¹³¹I to hyperthyroid patients. Based on ¹³¹I data for a small, kinetically well-characterized sub-cohort of patients, multivariate regression equations were developed to relate the numbers of disintegrations of ¹³¹I in more than 50 organs and tissues to anatomical (thyroid mass) and clinical (percentage thyroid uptake and pulse rate) parameters. These equations were then applied to estimate the numbers of ¹³¹I disintegrations in the organs and tissues of all other hyperthyroid patients in the TTFUS who were treated with ¹³¹I. The reference voxel phantoms adopted by the International Commission on Radiological Protection (ICRP) were then used to calculate the absorbed doses in more than 20 organs and tissues of the body. As expected, the absorbed doses were found to be highest in the thyroid (arithmetic means of 120 and 140 Gy for GD and TNG patients, respectively). Absorbed doses in organs other than the thyroid were much smaller, with arithmetic means of 1.6 Gy, 1.5 Gy and 0.65 Gy for esophagus, thymus and salivary glands, respectively. The arithmetic mean doses to all other organs and tissues were more than 100 times less than those to the thyroid gland. To our knowledge, this work represents the most comprehensive study to date of the doses received by persons treated with ¹³¹I for hyperthyroidism.

Radiation-induced heart injury is one of the major side effects of radiotherapy for thoracic malignancies. Previous studies have shown that radiotherapy induced myocardial fibrosis and intensified myocardial remodeling. In this study, we investigated whether atorvastatin could inhibit radiation-induced heart fibrosis in Sprague-Dawley rats, which were randomly divided into six groups: control; radiation only; and four treatment groups receiving atorvastatin plus radiation (E1, E2, E3 and E4). All rats, except the control group, received local heart irradiation in 7 daily fractions of 3 Gy for a total of 21 Gy. Rats in groups E1 (10 mg/kg/day) and E2 (20 mg/kg/day) received atorvastatin and radiation treatment until week 12 after exposure. Rats in groups E3 (10 mg/kg/day) and E4 (20 mg/kg/day) received atorvastatin treatment from 3 months before irradiation to week 12 after irradiation. The expressions of TGF-β₁, Smad2, Smad3, fibronectin, ROCK I and p-Akt in heart tissues were evaluated using real-time PCR or Western blot analyses. Atorvastatin significantly reduced the expression of TGF-β₁, Smad3/P-Smad3, ROCK I and p-Akt in rats of the E1–E4 groups and in a dose-dependent manner. Fibronectin exhibited a similar pattern of expression changes. In addition, echocardiography showed that atorvastatin treatment can inhibit the increase of left ventricular end-diastolic dimension, left ventricular end-systolic diameter and left ventricular posterior wall thickness, and prevent the decrease of ejection fraction and fraction shortening in E1–E4 groups compared with the radiation only group. This study demonstrated that radiation exposure increased the expression of fibronectin in cardiac fibroblasts and induced cardiac fibrosis through activation of the TGF-β₁/Smad3, RhoA/ROCK, and PI3K/AKT signaling pathways. Statins ameliorated radiation-induced cardiac fibrosis in Sprague-Dawley rats. Our results suggest that atorvastatin is effective for the treatment of radiation-induced cardiac fibrosis, especially with longer and higher dose atorvastatin treatment, as demonstrated in experimental group E4.

Inflammatory cytokines have been implicated in the regulation of radiation-induced genomic instability in the hematopoietic system and have also been shown to induce chronic DNA damage responses in radiation-induced senescence. We have previously shown that human bronchial epithelial cells (HBEC3-KT) have increased genomic instability and IL-8 production persisting at day 7 after exposure to high-LET (600 MeV/nucleon ⁵⁶Fe ions) compared to low-LET (320 keV X rays) radiation. Thus, we investigated whether IL-8 induction is part of a broader pro-inflammatory response produced by the epithelial cells in response to damage, which influences genomic instability measured by increased micronuclei and DNA repair foci frequencies. We found that exposure to radiation induced the release of multiple inflammatory cytokines into the media, including GM-CSF, GROα, IL-1α, IL-8 and the inflammation modulator, IL-1 receptor antagonist (IL-1RA). Our results suggest that this is an IL-1α-driven response, because an identical signature was induced by the addition of recombinant IL-1α to nonirradiated cells and functional interference with recombinant IL-1RA (Anakinra) or anti-IL-1α function-blocking antibody, decreased IL-8 production induced by radiation exposure. However, genomic instability was not influenced by this pathway as addition of recombinant IL-1α to naive or irradiated cells or the presence of IL-1 RA under the same conditions as those that interfered with the function of IL-8, did not affect micronuclei or DNA repair foci frequencies measured at day 7 after exposure. While dose-response studies revealed that genomic instability and IL-8 production are the consequences of targeted effects, experiments employing a co-culture transwell system revealed the propagation of pro-inflammatory responses but not genomic instability from irradiated to nonirradiated cells. Collectively, these results point to a cell-autonomous mechanism sustaining radiation-induced genomic instability in this model system and suggest that while molecules associated with these mechanisms could be markers for persisting damage, they reflect two different outcomes.

Radiation therapy prior to surgery has increasingly become the standard of care for locally advanced prostate cancer, however tumor radioresistance remains a major clinical problem. While restoration of microRNA-145 (miR-145) expression reduces chemoradioresistance in glioblastoma and suppress prostate cancer proliferation, migration and invasion, the role of miR-145 in response to radiation therapy for prostate cancer is still unknown. The aim of this study was to investigate the role of miR-145 in determining the tumor response to radiation treatment in prostate cancer. Human prostate cancer cells LNCAP and PC3 were transfected with miR-145 mimic. Clonogenic assay was used to determine whether overexpression of miR-145 could alter radiation response in vitro. Immunofluorescence of γ-H2AX and flow cytometric analysis of phosphorylated histone H3 were performed to investigate the potential mechanisms contributing to the enhanced radiation-induced cell killing induced by miR-145. In addition, a qPCR-based array was used to detect the possible miR-145-mediated regulated genes involved. Tumor growth delay assays and survival curves were then analyzed in an animal model to investigate whether miR-145 induced radiosensitivity in vivo. Furthermore, miR-145 expression was assessed in 30 prostate tumor tissue biopsies taken prior to neoadjuvant radiotherapy using miRNA arrays. Our current study suggested that ectopic expression of miR-145 significantly sensitized prostate cancer cells to radiation and we used γ-H2AX phosphorylation as a surrogate marker of radiotherapy response versus miR-145 expression levels. We observed significantly more foci per cell in the group treated with miR-145 and radiation. In addition, mitotic catastrophe was significantly increased in cells receiving miR-145 and radiation. The above results suggest that miR-145 appears to reduced the efficiency of the repair of radiation-induced DNA double-strand breaks in cells. A detailed examination of the involvement of the DNA repair pathway showed that miR-145 reduced the expression of 10 genes involved in DNA repair according to a qPCR-based array data. Irradiation of subcutaneous PC3 tumors in mice treated with R11-miR-145 (a cellular permeable peptide, previously reported) resulted in an increase in radiation-induced tumor growth delay and lived the longest after combination treatment. Moreover, miR-145 expression was significantly increased in patients demonstrating good response (PSA < 2.0 ng/ml/year) to neoadjuvant radiotherapy, while expression of the miR-145-regulated DNA repair genes was significantly decreased. In conclusion, these data suggest a possible mechanism for miR-145 radiosensitivity, potentially through down regulating of DNA repair. This novel study shows a role for miR-145 in modulating radiosensitivity in vivo and highlights the need for further study investigating the potential role of miR-145 as both a predictive marker of response and a novel therapeutic agent with which to enhance the efficacy of radiation therapy.

Exposure of the lung to radiation produces injury and inflammatory responses that result in microenvironmental alterations, which can promote the development of pneumonitis and/or pulmonary fibrosis. It has been shown that after other toxic insults, macrophages become phenotypically polarized in response to microenvironmental signals, orchestrating the downstream inflammatory responses. However, their contribution to the development of the late consequences of pulmonary radiation exposure remains unclear. To address this issue, fibrosis-prone C57BL/6J mice or pneumonitis-prone C3H/HeJ mice were whole-lung irradiated with 0 or 12.5 Gy and lung digests were collected between 3 and 26 weeks after radiation exposure. CD45 leukocytes were isolated and characterized by flow cytometry, and alveolar, interstitial and infiltrating macrophages were also detected. Ly6C, expressed by pro-inflammatory monocytes and macrophages, and mannose receptor (CD206), a marker of alternative activation, were assessed in each subpopulation. While the total number of pulmonary macrophages was depleted at 3 weeks after lung irradiation relative to age-matched controls in both C57 and C3H mice, identification of discrete subpopulations showed that this loss in cell number occurred in the alveolar, but not the interstitial or infiltrating, subsets. In the alveolar macrophages of both C57 and C3H mice, this correlated with a loss in the proportion of cells that expressed CD206 and F4/80. In contrast, in interstitial and infiltrating macrophages, the proportion of cells expressing these markers was increased at several time points after irradiation, with this response generally more pronounced in C3H mice. Radiation exposure was also associated with elevations in the proportion of alveolar and interstitial macrophage subpopulations expressing Ly6C and F4/80, with this response occurring at earlier time points in C57 mice. Although the radiation dose used in this study was not isoeffective for the inflammatory response in the two strains, the differences observed in the responses of these discrete macrophage populations between the fibrosis-prone versus pneumonitis-prone mice nonetheless suggest a possible role for these cells in the development of long-term consequences of pulmonary radiation exposure.

Synchrotron radiation is an excellent tool for investigating bystander effects in cell and animal models because of the well-defined and controllable configuration of the beam. Although synchrotron radiation has many advantages for such studies compared to conventional radiation, the contribution of dose exposure from scattered radiation nevertheless remains a source of concern. Therefore, the influence of scattered radiation on the detection of bystander effects induced by synchrotron radiation in biological in vitro models was evaluated. Radiochromic XRQA2 film-based dosimetry was employed to measure the absorbed dose of scattered radiation in cultured cells at various distances from a field exposed to microbeam radiotherapy and broadbeam X-ray radiation. The level of scattered radiation was dependent on the distance, dose in the target zone and beam mode. The number of γ-H2AX foci in cells positioned at the same target distances was measured and used as a biodosimeter to evaluate the absorbed dose. A correlation of absorbed dose values measured by the physical and biological methods was identified. The γ-H2AX assay successfully quantitated the scattered radiation in the range starting from 10 mGy and its contribution to the observed radiation-induced bystander effect.

The potent inhibitor of the cell cycle checkpoint regulatory factor Wee-1, MK-1775, has been reported to enhance non-small cell lung cancer (NSCLC) cell sensitivity to photon radiation by abrogating radiation-induced G₂ arrest. However, little is known about the effects of this sensitizer after exposure to carbon (C)-ion radiation. The purpose of this study was therefore to investigate the effects of C ions in combination with MK-1775 on the killing of NSCLC cells. Human NSCLC H1299 cells were exposed to X rays or C ions (290 MeV/n, 50 keV/μm at the center of a 6 cm spread-out Bragg peak) in the presence of MK-1775. The cell cycle was analyzed using flow cytometry and Western blotting. Radiosensitivity was determined using clonogenic survival assays. The mechanisms underlying MK-1775 radiosensitization were studied by observing H2AX phosphorylation and mitotic catastrophe. G₂ checkpoint arrest was enhanced 2.3-fold by C-ion exposure compared with X-ray exposure. Radiation-induced G₂ checkpoint arrest was abrogated by MK-1775. Exposure to radiation resulted in a significant reduction in the mitotic ratio and increased phosphorylation of cyclin-dependent kinase 1 (Cdk1), the primary downstream mediator of Wee-1-induced G₂ arrest. The Wee-1 inhibitor, MK-1775 restored the mitotic ratio and suppressed Cdk1 phosphorylation. In addition, MK-1775 increased H1299 cell sensitivity to C ions and X rays independent of TP53 status. MK-1775 also significantly increased H2AX phosphorylation and mitotic catastrophe in irradiated cells. These results suggest that the G₂ checkpoint inhibitor MK-1775 can enhance the sensitivity of human NSCLC cells to C ions as well as X rays.