As a society published journal, Radiation Research has been a successful and enduring project of the Radiation Research Society (RRS). In 59 years of publication, the journal has produced 732 issues and 10,712 articles. As a nonprofit organization, RRS, like most societies, has used revenues from subscriptions to support, in part, the life of the organization (meetings, conferences and grants to new scholars). The model for scientific publishing, however, continues to evolve. Radiation Research has weathered the rise of electronic publishing, consolidation in the commercial publishing industry, the aggregation of library subscriptions and library subscription cuts. Recent years have seen dramatic changes in how scholarly publishing is financed and new funder and institution policies will accelerate these changes. The growth of open access to journal articles reflects the information habits of readers and facilitates the dissemination of new knowledge. The Radiation Research Society, however, will need to account for and adapt to changes in the publishing market if it intends to support the communication of peer reviewed scholarship in the future.

A recent report shows that more than 30% of the astronauts returning from Space Shuttle missions or the International Space Station (ISS) were diagnosed with eye problems that can cause reduced visual acuity. We investigate here whether spaceflight environment-associated retinal damage might be related to oxidative stress-induced mitochondrial apoptosis. Female C57BL/6 mice were flown in the space shuttle Atlantis (STS-135), and within 3–5 h of landing, the spaceflight and ground-control mice, similarly housed in animal enclosure modules (AEMs) were euthanized and their eyes were removed for analysis. Changes in expression of genes involved in oxidative stress, mitochondrial and endothelial cell biology were examined. Apoptosis in the retina was analyzed by caspase-3 immunocytochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Levels of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation were also measured. Evaluation of spaceflight mice and AEM ground-control mice showed that expression of several genes playing central roles in regulating the mitochondria-associated apoptotic pathway were significantly altered in mouse ocular tissue after spaceflight compared to AEM ground-control mice. In addition, the mRNA levels of several genes, which are responsible for regulating the production of reactive oxygen species were also significantly up-regulated in spaceflight samples compared to AEM ground-control mice. Further more, the level of HNE protein was significantly elevated in the retina after spaceflight compared to controls. Our results also revealed that spaceflight conditions induced significant apoptosis in the retina especially inner nuclear layer (INL) and ganglion cell layer (GCL) compared to AEM ground controls. The data provided the first evidence that spaceflight conditions induce oxidative damage that results in mitochondrial apoptosis in the retina. This data suggest that astronauts may be at increased risk for late retinal degeneration.

Surface plasmon resonance (SPR) is a sensitive, rapid, simple and low cost method for detection of biological molecules. In this study, SPR technology with alkaline phosphatase as a probe was utilized to measure DNA strand breaks induced by ⁶⁰Co gamma rays. The doses were from 0.01–10 Gy with a dose rate of 0.1 Gy/min. The results demonstrate that the SPR technology can be used to estimate strand breaks of calf thymus DNA. SPR signals of the calf thymus DNA samples increased with increasing gamma ray doses and the relationship of y = sqrt (3297x 582.6) (r = 0.99) between the SPR signal and gamma dose was obtained. Estimation of DNA strand breaks in irradiated lymphocytes by SPR also demonstrated an increase in SPR signal with increasing dose and the exponential relationship of y = 169.43 × (1 – exp^–0.89x) (r = 0.93) was obtained. The initial yield of the SPR signal is about 150.79 mdeg · Gy⁻¹ and compared to the sensitivity of 0.05 Gy achieved by the neutral single cell gel electrophoresis (SCGE), the SPR-based assay of DNA strand breaks was found to be more sensitive (0.02 Gy). We therefore propose that SPR technology with alkaline phosphatase as the probe is a sensitive, simple and quick method for detection of DNA strand breaks in gamma-irradiated lymphocytes.

Free radicals generated by mitochondria are candidates for mediating long-lasting effects of radiation on cells, including genetic instability. To better understand the significance of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in these long-term effects we assayed ROS and RNS levels, the mitochondrial membrane potential and mass, and the frequency of DNA strand breaks, apoptosis and necrosis in human leukemic cells (K562 and HL60) after 12 Gy of X irradiation. An increase in intracellular ROS level was observed immediately post-irradiation, and about 24 h later a second increase of ROS was accompanied by increase in nitrogen oxide, mitochondrial potential and mitochondrial mass in both cell types. The second peak of ROS level was partially inhibited by rotenone, an inhibitor of mitochondrial complex I, in K562 but not in HL60 cells suggesting that the sources of ROS differed in the two cell types. The frequency of DNA breaks showed kinetics similar to ROS levels, with a sharp peak immediately after irradiation and a second increase 24 and 48 h later, which was significantly higher in K562 cells. Forty-eight hours after irradiation an increase in the frequency of apoptotic cells was observed in both cell lines, which became larger and statistically significant in K562 cells after inhibition of mitochondrial complex I. Our results show that ionizing radiation activates cellular processes which produce long-lasting ROS and RNS radicals, which may have different sources in different cell types and could participate in cellular signaling networks important for radiosensitivity and mode of cell death.

Understanding the mechanisms underlying the bystander effects of low doses/low fluences of low- or high-linear energy transfer (LET) radiation is relevant to radiotherapy and radiation protection. Here, we investigated the role of gap-junction intercellular communication (GJIC) in the propagation of stressful effects in confluent normal human fibroblast cultures wherein only 0.036–0.144% of cells in the population were traversed by primary radiation tracks. Confluent cells were exposed to graded doses from monochromatic 5.35 keV X ray (LET ∼6 keV/μm), 18.3 MeV/u carbon ion (LET ∼103 keV/μm), 13 MeV/u neon ion (LET ∼380 keV/μm) or 11.5 MeV/u argon ion (LET ∼1,260 keV/μm) microbeams in the presence or absence of 18-α-glycyrrhetinic acid (AGA), an inhibitor of GJIC. After 4 h incubation at 37°C, the cells were subcultured and assayed for micronucleus (MN) formation. Micronuclei were induced in a greater fraction of cells than expected based on the fraction of cells targeted by primary radiation, and the effect occurred in a dose-dependent manner with any of the radiation sources. Interestingly, MN formation for the heavy-ion microbeam irradiation in the absence of AGA was higher than in its presence at high mean absorbed doses. In contrast, there were no significant differences in cell cultures exposed to X-ray microbeam irradiation in presence or absence of AGA. This showed that the inhibition of GJIC depressed the enhancement of MN formation in bystander cells from cultures exposed to high-LET radiation but not low-LET radiation. Bystander cells recipient of growth medium harvested from 5.35 keV X-irradiated cultures experienced stress manifested in the form of excess micronucleus formation. Together, the results support the involvement of both junctional communication and secreted factor(s) in the propagation of radiation-induced stress to bystander cells. They highlight the important role of radiation quality and dose in the observed effects.

Cancer of the prostate is a highly prevalent disease with a heterogeneous aetiology and prognosis. Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionizing radiation exposure, including cancer induction, is surprisingly limited for both high- and low-dose exposures. As population exposure to radiation increases, largely through medical imaging, a better understanding of the response of the prostate to radiation exposure is required. Low-dose radiation-induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse models, largely for hematological cancers. This study examines the effects of high- and low-dose whole-body radiation exposure on prostate cancer development using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2 Gy), low (50 mGy) and repeated low (5 × 50 mGy) doses of X rays to evaluate both the potential prostate cancer promoting effects of high-dose radiation and low-dose adaptive response phenomena in this prostate cancer model. Prostate weights and histopathology were examined to evaluate gross changes in cancer development and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined. Proliferation (Ki-67), apoptosis, DNA damage (γ-H2AX) and transgene expression (large T-antigen) were examined within TRAMP prostate sections. Neither high- nor low-dose radiation-induced effects on prostate cancer progression were observed for any of the endpoints studied. Lack of observable effects of high- or low-dose radiation exposure suggests that modulation of tumorigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate and in those that are not driven by SV40 large T antigen.

Recent evidence has shown that irradiation can promote the invasiveness of hepatocellular carcinoma cells and have an impact on the invasive behavior of nonirradiated surrounding cancer cells, which may enhance overall tumor aggressiveness. However, the role of the TP53 tumor suppressor gene in the invasion of irradiated hepatoma cells and their nonirradiated bystanders remain largely unknown. In the present study, we found that irradiation increased the invasiveness of human hepatoma HepG2 cells, and pretreatment of the cells with SU1498 (an inhibitor of vascular endothelial growth factor receptor 2, VEGFR2) and GM6001 (an inhibitor of matrix metalloproteinases 2, MMP2) demonstrated that radiation-enhanced invasiveness is associated with the interplay between MMP2 and VEGF signaling. In addition, while radiation-induced expression and phosphorylation of p53, inhibition of p53 function with pifithrin-α or transfection of cells with p53 siRNA significantly reduced the activation of both MMP2 and VEGF and resulted in a reduction of radiation-induced invasiveness. Interestingly, we also found that the invasiveness of the nonirradiated bystander cells was also elevated after co-culturing with irradiated cells and that bystander invasive potential was regulated paracrine in a manner by MMP2 and VEGF from the irradiated cells through a p53-dependent mechanism. Taken together, our data demonstrate that radiation-induced up-regulation of p53 is responsible for the promotion of VEGF-MMP2 pathway involved in the enhancement of invasiveness of both irradiated and bystander hepatoma cells.

The consequences of radiation exposure alone are relatively well understood, but in the wake of events such as the World War II nuclear detonations and accidents such as Chernobyl, other critical factors have emerged that can substantially affect patient outcome. For example, ∼70% of radiation victims from Hiroshima and Nagasaki received some sort of additional traumatic injury, the most common being thermal burn. Animal data has shown that the addition of thermal insult to radiation results in increased morbidity and mortality. To explore possible synergism between thermal injury and radiation on brain, C57BL/6J female mice were exposed to either 0 or 5 Gy whole-body gamma irradiation. Irradiation was immediately followed by a 10% total-body surface area full thickness thermal burn. Mice were sacrificed 6 h, 1 week or 6 month post-injury and brains and plasma were harvested for histology, mRNA analysis and cytokine ELISA. Plasma analysis revealed that combined injury synergistically upregulates IL-6 at acute time points. Additionally, at 6 h, combined injury resulted in a greater upregulation of the vascular marker, ICAM-1 and TNF-α mRNA. Enhanced activation of glial cells was also observed by CD68 and Iba1 immunohistochemistry at all time points. Additionally, doublecortin staining at 6 months showed reduced neurogenesis in all injury conditions. Finally, using a novel object recognition test, we observed that only mice with combined injury had significant learning and memory deficits. These results demonstrate that thermal injury lowers the threshold for radiation-induced neuroinflammation and long-term cognitive dysfunction.

This study demonstrates that mice, similar to humans, have a common mitochondrial DNA deletion (3,860 bp) that encodes 5 transfer RNA genes and 5 polypeptide genes that is related to aging, tissue type and radiotoxicity. Our research indicates that the deletion ratio in the liver was significantly higher than in the brain and gut tissues of 8-month-old mice, as compared to 8-week-old mice. Our results also demonstrate that tissue type, oxidative metabolic capacity and radiosensitivity influence the 3,860-bp deletion level. Therefore, this 3,860-bp deletion content may serve as a biomarker of aging and oxidative damage in mice.

Epidermal growth factor receptor (EGFR) inhibition using cetuximab improves the efficacy of radiotherapy in only a subgroup of head and neck squamous cell carcinoma (HNSCC) patients. Therefore, to improve patient selection a better understanding of tumor characteristics that affect treatment is necessary. Here, we investigated the effect of cetuximab on repair of radiation-induced DNA damage in a HNSCC xenograft model, which shows a synergistic effect to cetuximab and radiotherapy (SCCNij185) and a HNSCC model, which shows no additive effect of cetuximab to radiotherapy (SCCNij153). In both tumor models, clear increases were seen in the number of 53BP1 and Rad51 foci after irradiation. 53BP1 foci were present at comparable levels in hypoxic and normoxic tumor areas of the tumor xenografts, while the number of Rad51 foci was significantly higher in normoxic areas compared to hypoxic areas (P < 0.05). In both SCCNij185 and SCCNij153 xenografts an increased number of 53BP1 foci was observed in tumors treated with cetuximab and radiotherapy compared to radiotherapy alone. In SCCNij185 this increase was statistically significant in normoxic tumor areas (P = 0.04) and in SCCNij153 in both hypoxic and normoxic areas (P = 0.007 and P = 0.02, respectively). The number of Rad51 foci was not significantly different when cetuximab was added to radiotherapy compared to radiotherapy alone. Levels of pEGFR and pERK1/2 were decreased when cetuximab was added to radiotherapy in SCCNij185, but not in SCCNij153. Apoptosis was also only increased in SCCNij185 tumors at 4 days after cetuximab and radiotherapy treatment (P < 0.01). In conclusion, cetuximab inhibited DNA repair in both HNSCC models, but this effect was not predictive for the radiosensitizing effect of cetuximab in vivo. This lack of correlation may be related to differential effects of cetuximab and radiotherapy on ERK1/2 signaling and a decreased induction of apoptosis by cetuximab and radiotherapy in the resistant model.

Radiation has been associated with increases in noncancerous diseases. An effect of low-dose radiation on the prevalence of clinically detected glaucoma has not been previously reported. We therefore investigated the prevalence of glaucoma in A-bomb survivors and its possible association with radiation dose. A total of 1,589 people who participated in the clinical examination program for A-bomb survivors at the Radiation Effects Research Foundation (RERF) between October 2006 and September 2008 and who had reconstructed radiation doses, were recruited into this cross-sectional screening study. The prevalence of glaucoma and its dose-response relationship to A-bomb radiation were measured. Each subject underwent an initial screening consisting of an interview and ophthalmological examination. Questionable cases with any indication of ocular disease, including glaucoma, were referred to local hospitals for more comprehensive evaluation. A diagnosis of glaucoma was made based on specific optic disc appearance, perimetric results and other ocular findings. Of 1,589 eligible people, we detected 284 (17.9%) cases of glaucoma overall, including 36 (2.3%) cases of primary open-angle glaucoma with intraocular pressure levels greater than 21 mmHg, 226 (14.2%) cases of normal-tension glaucoma and 25 (1.6%) cases of primary angle-closure glaucoma. Seven glaucoma risk factors were examined as potential confounders but only two needed to be included in the final model. Binary regression using a generalized estimating equation method, with adjustment for gender, age, city, cataract surgery or diabetes mellitus, revealed an odds ratio at 1 Gy of 1.31 (95% confidence interval 1.11–1.53, P = 0.001) in the case of normal-tension glaucoma, but no association for other types of glaucoma. The prevalence of normal-tension glaucoma may increase with A-bomb radiation dose, but uncertainties associated with nonparticipation (59% participation) suggest caution in the interpretation of these results until they are confirmed by other studies.