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Emerging evidence indicates that mesenchymal stromal cells (MSCs) have an important role in cancer metastasis. Although tumor microenvironment, which includes MSCs and immune cells, can be altered by ionizing radiation (IR), whether irradiation can promote metastasis through MSCs remains unclear. Using the lung colonization model of transplanted 4T1 breast cancer cells, we found an increased lung metastasis in mice exposed to ionizing radiation, even when the thorax was shielded during whole-body irradiation. This radiation-induced lung metastasis can be replicated using irradiated MSCs. cGAS-STING signaling pathway was found to be activated in MSCs, accompanied by upregulation of type I interferon-related genes, including chemokine CCL5. Disruption of cGAS-STING signaling in MSCs abolished their pro-metastatic effect. Deletion of CCL5 in MSCs also abrogated the pro-metastatic effect endowed by IR. Furthermore, we showed that the lung pro-metastatic effect of irradiated MSCs required the presence of macrophages. Our results indicate that radiation-induced alterations in distant mesenchymal stromal cells facilitate cancer metastasis.

Photodynamic therapy (PDT) has emerged as an attractive option for cancer treatment. However, conventional PDT is activated by light that has poor tissue penetration depths, limiting its applicability in the clinic. Recently the idea of using X-ray sources to activate PDT and overcome the shallow penetration issue has garnered significant interest. This can be achieved by external beam irradiation and using a nanoparticle scintillator as transducer. Alternatively, research on exploiting Cherenkov radiation from radioisotopes to activate PDT has also begun to flourish. In either approach, the most auspicious success is achieved using nanoparticles as either a scintillator or a photosensitizer to mediate energy transfer and radical production. Both X-ray induced PDT (X-PDT) and Cherenkov radiation PDT (CR-PDT) contain a significant radiation therapy (RT) component and are essentially PDT and RT combination. Unlike the conventional combination, however, in X-PDT and CR-PDT, one energy source simultaneously activates both processes, making the combination always in synchronism and the synergy potential maximized. While still in early stage of development, X-PDT and CR-PDT address important issues in the clinic and hold great potential in translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2018 Wiley Periodicals, Inc.)

It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of <0.1 Gy occurred at non-significant levels. The mutation spectrum in HPRT-deficient mutants revealed that the type of mutations induced by low-dose exposures was similar to that seen in spontaneous mutants. An apparent change in mutation type was observed for mutants induced by doses of >0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events.

Hyper-radiosensitivity (HRS) is a well-known bioresponse under low-dose or low-dose-rate exposures. Although disorder of the DNA repair function, non-targeted effects and accumulation of cells in G2 have been experimentally observed, the mechanism for inducing HRS by long-term irradiation is still unclear. On the basis of biological experiments and a theoretical study, we have shown that change in the amount of DNA associated with accumulation of cells in G2 enhances radiosensitivity. To demonstrate continuous irradiation with 250 kVp X-rays, we adopted a fractionated regimen of 0.186 or 1.00 Gy per fraction at intervals of 1 h (i.e. 0.186 Gy/h, 1.00 Gy/h on average) to Chinese Hamster Ovary (CHO)-K1 cells. The change in the amount of DNA during irradiation was quantified by flow cytometric analysis with propidium iodide (PI). Concurrently, we attempted a theoretical evaluation of the DNA damage by using a microdosimetric-kinetic (MK) model that was modified to incorporate the change in the amount of DNA. Our experimental results showed that the fraction of the cells in G2/M phase increased by 6.7% with 0.186 Gy/h and by 22.1% with 1.00 Gy/h after the 12th irradiation. The MK model considering the change in amount of DNA during the irradiation exhibited a higher radiosensitivity at a high dose range, which could account for the experimental clonogenic survival. The theoretical results suggest that HRS in the high dose range is associated with an increase in the total amount of DNA during irradiation., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

This study aims to investigate the influence of high linear energy transfer (LET) heavy ion ( 12 C 6+ ) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion ( 12 C 6+ ) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion ( 12 C 6+ ). High LET heavy ion ( 12 C 6+ ) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion ( 12 C 6+ ) presented special advantages in terms of treating malignant melanoma. Impact statement Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate. In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to overcome its lower sensitivity to radiation. This study can provide theoretical basis for clinical trials, in which malignant melanoma is treated by heavy ion ( 12 C 6+ ), in order to accurately determine the clinical efficacy of heavy ion therapy. Clinical applications has revealed that local tumor control rate is high when heavy ion is used to treat malignant melanoma, indicating that heavy ion is an important direction in treating melanoma in the future.

During radiotherapy procedures, radiation-induced bystander effect (RIBE) can potentially lead to genetic hazards to normal tissues surrounding the targeted regions. Previous studies showed that RIBE intensities in cell cluster models were much higher than those in monolayer cultured cell models. On the other hand, low-concentration carbon monoxide (CO) was previously shown to exert biological functions via binding to the heme domain of proteins and then modulating various signaling pathways. In relation, our previous studies showed that exogenous CO generated by the CO releasing molecule, tricarbonyldichlororuthenium (CORM-2), at a relatively low concentration (20 µM), effectively attenuated the formation of RIBE-induced DNA double-strand breaks (DSB) and micronucleus (MN). In the present work, we further investigated the capability of a low concentration of exogenous CO (CORM-2) of attenuating or inhibiting RIBE in a mixed-cell cluster model. Our results showed that CO (CORM-2) with a low concentration of 30 µM could effectively suppress RIBE-induced DSB (p53 binding protein 1, p53BP1), MN formation and cell proliferation in bystander cells but not irradiated cells via modulating the inducible nitric oxide synthase (iNOS) andcyclooxygenase-2 (COX-2). The results can help mitigate RIBE-induced hazards during radiotherapy procedures., Competing Interests: The authors declare no conflict of interest.

The equilibrium between proliferation and apoptosis is tightly balanced to maintain tissue homeostasis in normal tissues and even in tumors. Achieving and maintaining such a balance is important for cancer regrowth and spreading after cytotoxic treatments. Caspase-3 activation and tumor cell death following anticancer therapy as well as accompanying cell death pathways are well characterized, but their association to homeostasis of cancerous tissue and tumor progression remains poorly understood. Here we proposed a novel mechanism of cancer spreading induced by caspase-3. RhoGDIβ, known as a direct cleavage substrate of caspase-3, is overexpressed in many epithelial cancers. The N-terminal-truncated RhoGDIβ (ΔN-RhoGDIβ) is accumulated in caspase-3-activated cells. Stable expression of ΔN-RhoGDIβ in HeLa cells did not induce apoptosis, but impaired directional cell migration in a wound-healing assay accompanied by a perturbed direction of cell division at the wound edge. Subcellular protein fractionation experiments revealed that ΔN-RhoGDIβ but not wild-type RhoGDIβ was present in the detergent-soluble cytoplasmic and nuclear fractions and preferentially associated with Cdc42. Furthermore, Cdc42 activity was constitutively inhibited by stable expression of ΔN-RhoGDIβ, resulting in increased radiation-induced compensatory proliferation linking to RhoA activation. Thus, ΔN-RhoGDIβ dominant-negatively regulates Cdc42 activity and contributes to loss of polarity-related functions. The caspase-3-cleaved RhoGDIβ is a possible determinant to promote cancer spreading due to deregulation of directional organization of tumor cell population and inhibition of default equilibrium between proliferation and apoptosis after cytotoxic damage. J. Cell. Physiol. 231: 2493-2505, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

This study examines acute and degenerative tissue responses to space-like radiation doses in a rodent model of simulated microgravity. We have studied four groups of rats, control (CON), irradiated (IR), irradiated and hindlimb suspended (IR-HLS), and suspended (HLS) that were maintained for two weeks. IR and IR+HLS groups were exposed to five sessions of X-ray irradiation (1.2 Gy each, at 3-4 days intervals). Body weights, soleus muscle weights, and hindlimb bone mineral density (BMD) were measured. Results show that compared to CON animals, IR, HLS, and IR+HLS group reduced the body weight gain significantly. IR-associated growth retardation appeared to be closely linked to acute and transient post-IR 'anorexia' (a decrease in food intake). HLS but not IR induced major changes in the musculoskeletal system, consisting in decreases in soleus muscle mass and bone mineral density of distal femur and proximal tibia. Additional dosimetric studies showed that the effect of IR on weight is detectable at 0.3 Gy X-ray doses, while no threshold dose for the IR-produced decrease in food intake could be observed. This study suggests that space flight-associated anorexia and musculoskeletal degenerative changes may be driven by different, radiation- and microgravity-associated (respectively) mechanisms., (© 2016 by the Association of Clinical Scientists, Inc.)

Accurate assessment of the individual exposure dose based on easily accessible samples (e.g. blood) immediately following a radiological accident is crucial. We aimed at developing a robust transcription-based signature for biodosimetry from human peripheral blood mononuclear cells irradiated with different doses of X-rays (0.1 and 1.0 Gy) at a dose rate of 0.26 Gy/min. Genome-wide radiation-induced changes in mRNA expression were evaluated at both gene and exon level. Using exon-specific qRT-PCR, we confirmed that several biomarker genes are alternatively spliced or transcribed after irradiation and that different exons of these genes exhibit significantly different levels of induction. Moreover, a significant number of radiation-responsive genes were found to be genomic neighbors. Using three different classification models we found that gene and exon signatures performed equally well on dose prediction, as long as more than 10 features are included. Together, our results highlight the necessity of evaluating gene expression at the level of single exons for radiation biodosimetry in particular and transcriptional biomarker research in general. This approach is especially advisable for practical gene expression-based biodosimetry, for which primer- or probe-based techniques would be the method of choice.

To clarify the nature of the genes that contribute to the radiosensitivity of human hematopoietic stem/progenitor cells (HSPCs), we analyzed the gene expression profiles detected in HSPCs irradiated with 2 Gy X-rays after culture with or without an optimal combination of hematopoietic cytokines. Highly purified CD34(+) cells from human placental/umbilical cord blood were used as HSPCs. The cells were exposed to 2 Gy X-irradiation and treated in serum-free medium under five different sets of conditions for 6 h. The gene expression levels were analyzed by cDNA microarray, and then the network of responsive genes was investigated. A comprehensive genetic analysis to search for genes associated with cellular radiosensitivity was undertaken, and we found that expression of the genes downstream of MYC oncogene increased after X-irradiation. In fact, the activation of MYC was observed immediately after X-irradiation, and MYC was the only gene still showing activation at 6 h after irradiation. Furthermore, MYC had a significant impact on the biological response, particularly on the tumorigenesis of cells and the cell cycle control. The activated gene regulator function of MYC resulting from irradiation was suppressed by culturing the HSPCs with combinations of cytokines (recombinant human thrombopoietin + interleukin 3 + stem cell factor), which exerted radioprotective effects. MYC was strongly associated with the radiosensitivity of HSPCs, and further study and clarification of the genetic mechanisms that control the cell cycle following X-irradiation are required., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The current cone beam computed tomography (CBCT) system on the small animal radiation research platform (SARRP) is less effective in localizing soft-tissue targets. On the contrary, molecular optical imaging techniques, such as bioluminescence tomography (BLT) and fluorescence tomography (FT), can provide high contrast soft tissue images to complement CBCT and offer functional information. In this study, we present a dual-use optical imaging system that enables BLT/FT for both on-board and stand-alone applications. The system consists of a mobile cart and an imaging unit. Multi-projection optical images can be acquired in a range of -90°~90° angles. An optical fiber driven by an X-Y-Z Cartesian stage serves as an excitation light source specifically for FT. Our results show that the accuracy and reproducibility of the system meets the requirements set by the pre-clinical workflow (<;0.1 mm and 0.5 degree error). Preliminary experiments demonstrate the feasibility of bioluminescent imaging in a tissue-simulating phantom with a luminescent source embedded. In a considerable light-tight environment, we can achieve average background optical intensity significantly lower than the luminescent signal (<; 5%).

Unlabelled: The aim of this study was to investigate peculiarities of ascorbic acid effect on radiation-induced chromosomal aberrations frequency and range in the cultured peripheral blood lymphocytes (PBL) of healthy donors and cancer patients depending on doses of radiation and drug, as well as cells radiosensitivity (in vitro)., Methods: Test system of human PBL, metaphase analysis of chromosomal aberrations. Cells were cultivated according to the standard procedures with some modifications. PBL culture was exposed to x-ray radiation in G0- and G2-phases of cell cycle. Immediately after the irradiation the culture was treated with ascorbic acid in concentrations of 20.0-80.0 µg/ml of blood., Results: Cell culture irradiation in low dose (0.3 Gy) and treatment with ascorbic acid in therapeutic concentration (20.0 μg/ml of blood) resulted in radioprotective effect, decreasing overall chromosome aberrations frequency as opposed to radiation effects. It has been established that post-irradiation effect of ascorbic acid upon the PBL culture in concentrations of 40.0 and 80.0 μg/ml, which exceeding therapeutic concentration value 2 and 4 times correspondingly, increased overall chromosome aberrations frequency 1.4 times compared with irradiation effect in a low dose (0.3 Gy). This bears evidence of ascorbic acid co-mutagenic activity in the range of concentrations exceeding therapeutic values. The peak of mitotic activity inhibition was observed at 2.0 Gy irradiation dose. Addition ascorbic acid in therapeutic concentration increased radiation effect this number ≈ 2 times (exceeding even intact control value). Compared with G0-phase, co-mutagenic effect of ascorbic acid in G2-phase appears earlier, starting with dose of 1.0 Gy. In the blood lymphocytes of cancer patients, the level of genetic damage was increased 1.7 times after combined treatment with low dose irradiation and ascorbic acid in comparison with irradiation alone which suggest the co-mutagenic instead of radioprotective effect of ascorbic acid., Conclusions: Genome destabilization enhancement of irradiated in vitro human somatic cells under ascorbic acid effect is due to its co-mutagenic properties. The formation of co-mutagenic effects of ascorbic acid depend on its concentration, irradiation dose and the efficiency of repair processes. Co-mutagenes may pose high carcinogenic hazard at low (above background) radiation levels.

Background: Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress., Objective: The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms., Methods: Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured., Results: HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks., Conclusion: These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

Background: Deferoxamine (DFO) is an iron-chelating agent that has also been shown to increase angiogenesis. We hypothesize that the angiogenic properties of DFO will improve bone regeneration in distraction osteogenesis (DO) after x-ray radiation therapy (XRT) by restoring the vascularity around the distraction site., Material and Methods: Three groups of Sprague-Dawley rats underwent distraction of the left mandible. Two groups received pre-operative fractionated XRT, and one of these groups was treated with DFO during distraction. After consolidation, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics., Results: Radiation inflicted a severe diminution in the vascular metrics of the distracted regenerate and consequently led to poor clinical outcome. The DFO treated group revealed improved DO bone regeneration with a substantial restoration and proliferation of vascularity., Conclusions: This set of experiments quantitatively demonstrates the ability of DFO to temper the anti-angiogenic effect of XRT in mandibular DO. These exciting results suggest that DFO may be a viable treatment option aimed at mitigating the damaging effects of XRT on new bone formation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Poor local control and tumor escape are of major concern in head-and-neck cancers treated by conventional radiotherapy or hadrontherapy. Reduced glutathione (GSH) is suspected of playing an important role in mechanisms leading to radioresistance, and its depletion should enable oxidative stress insult, thereby modifying the nature of DNA lesions and the subsequent chromosomal changes that potentially lead to tumor escape.This study aimed to highlight the impact of a GSH-depletion strategy (dimethylfumarate, and L-buthionine sulfoximine association) combined with carbon ion or X-ray irradiation on types of DNA lesions (sparse or clustered) and the subsequent transmission of chromosomal changes to the progeny in a radioresistant cell line (SQ20B) expressing a high endogenous GSH content. Results are compared with those of a radiosensitive cell line (SCC61) displaying a low endogenous GSH level. DNA damage measurements (γH2AX/comet assay) demonstrated that a transient GSH depletion in resistant SQ20B cells potentiated the effects of irradiation by initially increasing sparse DNA breaks and oxidative lesions after X-ray irradiation, while carbon ion irradiation enhanced the complexity of clustered oxidative damage. Moreover, residual DNA double-strand breaks were measured whatever the radiation qualities. The nature of the initial DNA lesions and amount of residual DNA damage were similar to those observed in sensitive SCC61 cells after both types of irradiation. Misrepaired or unrepaired lesions may lead to chromosomal changes, estimated in cell progeny by the cytome assay. Both types of irradiation induced aberrations in nondepleted resistant SQ20B and sensitive SCC61 cells. The GSH-depletion strategy prevented the transmission of aberrations (complex rearrangements and chromosome break or loss) in radioresistant SQ20B only when associated with carbon ion irradiation. A GSH-depleting strategy combined with hadrontherapy may thus have considerable advantage in the care of patients, by minimizing genomic instability and improving the local control.

Understanding the effects of ionizing radiations are key to determining their optimal use in therapy and assessing risks from exposure. The development of microbeams where radiations can be delivered in a highly temporal and spatially constrained manner has been a major advance. Several different types of radiation microbeams have been developed using X-rays, charged particles and electrons. For charged particles, beams can be targeted with sub-micron accuracy into biological samples and the lowest possible dose of a single particle track can be delivered with high reproducibility. Microbeams have provided powerful tools for understanding the kinetics of DNA damage and formation under conditions of physiological relevance and have significant advantages over other approaches for producing localized DNA damage, such as variable wavelength laser beam approaches. Recent studies have extended their use to probing for radiosensitive sites outside the cell nucleus, and testing for mechanisms underpinning bystander responses where irradiated and non-irradiated cells communicate with each other. Ongoing developments include the ability to locally target regions of 3D tissue models and ultimately to target localized regions in vivo. With future advances in radiation delivery and imaging microbeams will continue to be applied in a range of biological studies., (2010 Elsevier B.V. All rights reserved.)

Radiation-induced bystander effects are established consequences of exposure to ionizing radiation. The operation of this mechanism has been seen in vitro and also between fish, mammals, and plants in vive where stress signals from treated organisms induce responses in neighbors. In vitro research shows that DNA repair deficient cells produce more toxic bystander responses. To test this in vivo two strains of Japanese medaka were tested. One is a mutant, repair deficient strain (ric2) and the other, the wildtype repair proficient strain (CAB). Irradiated fish swam with unirradiated partners in a strain mix and match protocol. The data suggest that medaka produce signals, when exposed to radiation, that induce unirradiated fish ofthe same strain swimming with them to produce an altered response to that seen in bystanders to sham irradiated fish. More apoptosis was seen in bystanders to repair deficient fish. When the strains are mixed, the bystanders of either strain respond like the donor strain. Measurements of Bcl-2 and cmyc proteins in the explants confirmed these observations. A possible role for p53 was also identified in that the use of reporters with mutant p53 demonstrated that CAB signals killed all the reporter cells by apoptosis. Use of a similar but p53 wildtype cell line had no such effect. The data add to the body of knowledge showing that bystander signals operate at hierarchical levels of organization greater than the individual and may therefore have relevance in radioecology and (eco)systems biology.

We undertook a survey to determine the public acceptance of medical radiation exposure throughout Japan, and 1,357 responses (67.9% response rate) were obtained using a two-stage systematic stratified random sampling method. The acceptance of exposure of children was generally similar to that of adults. For each of the attributes, 45-60% of the participants were accepting of exposure for cancer treatment and diagnosis, but only 30% were accepting of exposure for X-ray diagnoses of bone fractures and dental caries. In general, the presence of a child did not markedly affect women's acceptance of exposure. Factor analyses identified 3 factors influencing the acceptance of child exposure: symptomatic diseases to determine treatment, the possibility of high-risk diseases (or major organ diseases), and the association with cancer. Cluster analysis showed 4 clusters: a positive group regarding children's exposure for the diagnosis of bone fractures and dental caries (12.9% of all participants), a positive group for major organ disease and cancer (15.5%), a negative group excluding cancer (55.2%), and a positive group for all cases (16.4%). The cluster distributions revealed that mothers with 10-to 18-year-old firstborn children showed a tendency to accept the medical radiation exposure of their children in all cases.

The comprehensive characterization of As(V)-bearing iron minerals from the Gunma iron deposit, which were probably formed by biomineralization, was carried out by utilizing multiple synchrotron radiation (SR)-based analytical techniques at BL37XU at SPring-8. SR microbeam X-ray fluorescence (SR-mu-XRF) imaging showed a high level of arsenic accumulation in the iron ore as dots of ca. 20 microm. Based on SEM observations and SR X-ray powder diffraction (SR-XRD) analysis, it was found that arsenic is selectively accumulated in strengite (FePO4 x 2H2O) with a concentric morphology, which may be produced by a biologically induced process. Furthermore, the X-ray absorption fine structure (XAFS) analysis showed that arsenic in strengite exists in the arsenate (AsO4(3-)) form and is coordinated by four oxygen atoms at 1.68 angstroms. The results suggest that strengite accumulates arsenic by isomorphous substitution of AsO4(3-) for PO4(3-) to form a partial solid-solution of strengite and scorodite (FeAsO4 x 2H2O). The specific correlation between the distribution of As and biominerals indicates that microorganisms seems to play an important role in the mineralization of strengite in combination with an arsenic-accumulating process.

Atomic-resolution diffraction imaging of biological particles using x-ray free-electron lasers (XFELs) at 1 A wavelength requires a detailed understanding of the photon-induced damage processes. We discuss how several aspects of existing continuum damage models can be tested during early operation of XFELs at lower x-ray energies in the range of 0.8-5 keV and low fluences, focusing particularly on macroscopic collective effects such as particle charging, expansion, and average ionization of nanospheres.

Irradiation of murine subcutaneous stroma before implantation of tumor cells leads to retarded tumor growth. This effect is called Tumor Bed Effect (TBE) and can be used to assess the sensitivity of stromal tissue to radiation. We tested the ability of stromal tissue to recover from X-ray-induced damage as a function of the time interval between X-irradiation and implantation of tumor cells over a period of 195 days. We also assessed the effects of a second test treatment of X-irradiation before implantation to assess residual damage by the first radiation treatment. The tumor bed effect in C57Bl10xDBA2 mice observed after X-ray treatment and implantation of M8013 cells (from a transplantable mouse mammary carcinoma) declines with the time that elapses between X-rays and implantation. Implantation of tumor cells 195 days after initial irradiation of 10 or 20 Gy resulted in a considerably smaller TBE. The half-time of the decay is estimated as about 50 days. The extent of the recovery was then tested in two-fraction experiments, with radiation fractions separated by intervals of 30 or 180 days. In the experiment with re-irradiation at an interval of 30 days after the first radiation dose of 20 Gy hardly any recovery was observed, whereas at an interval of 180 days a considerable recovery was observed. We presume that the recovery in TBE that was observed a long time after the irradiation results from a proliferative stimulus to endothelial cells which takes place during the post-irradiation period. The proliferative response leads to cell death of the X-ray damaged endothelial cells and thereafter these are replaced by healthy cells.

Radiation chemistry studies began in the early 20th century with observations involving the decomposition of various materials by X rays and radium. Hugo Fricke recognized that the chemical effects of radiation should be studied to help understand the response of living systems to radiation, and in 1928 he established a laboratory to conduct such studies. Early radiation chemists were intimately involved in the founding of the Radiation Research Society and contributed substantially to its interdisciplinary culture. In this historical review, the highlights of research in radiation chemistry leading up to the founding of the Radiation Research Society in 1952 are discussed. The status of the field is established at that point, and a sampling of the major accomplishments from then until the present is presented, with emphasis on those scientists who have contributed substantially to the life and culture of the Radiation Research Society.

Highly brilliant synchrotron radiation sources have opened up the possibility of using coherent X-rays in spectroscopy and imaging. Coherent X-rays are characterized by a large lateral coherence length. Speckle spectroscopy is extended to hard X-rays, improving the resolution to the nm range. It has become possible to image opaque objects in phase contrast with a sensitivity far superior to imaging in absorption contrast. All the currently available X-ray sources are chaotic sources. Their characterization in terms of coherence functions of the first and second order is introduced. The concept of coherence volume, defined in quantum optics terms, is generalized for scattering experiments. When the illuminated sample volume is smaller than the coherence volume, the individuality of the defect arrangement in a sample shows up as speckle in the scattered intensity. Otherwise, a configurational average washes out the speckle and only diffuse scattering and possibly Bragg reflections will survive. The loss of interference due to the finite detection time, to the finite detector pixel size and to uncontrolled degrees of freedom in the sample is discussed at length. A comparison between X-ray scattering, neutron scattering and mesoscopic electron transport is given. A few examples illustrate the possibilities of coherent X-rays for imaging and intensity correlation spectroscopy.

Rationale and Objectives: The purpose of this study was to determine if male radiologists predominantly father daughters and, if so, to investigate the association between this skewed sex ratio of offspring and radiation exposure., Materials and Methods: Questionnaires completed by 586 male radiologists in Japan provided data regarding the radiologist's age, length of employment in radiology, if he had ever received radiation doses higher than that recommended by the International Commission on Radiological Protection, the sex of each child fathered, and the birth date of each child., Results: As a group, male radiologists tended to father a lower proportion of boys (48.47%) compared with the control group (51.46%), and the relative risk was 1.13 (95% confidence interval [CI]: 1.00, 1.27). Offspring of highly irradiated radiologists, however, had a reduced proportion of males (34.48%), with a significantly (P = .002) increased relative risk of 2.01 (95% CI: 1.29, 3.13)., Conclusion: X-ray exposure may explain the reduced percentage of sons in the offspring of male radiologists.

An intercomparison of medium energy x-ray and 60Co gamma radiation exposure standards held by the Australian Radiation Laboratory and the National Radiation Laboratory (New Zealand) is reported. The standards agree within 0.4%.

The penumbra from a 10-MV x-ray beam has been measured using various field-shaping blocks located in the normal blocking tray position and compared to the penumbra of the adjustable photon jaws of the machine. The results showed that the penumbra was substantially degraded by these blocks only for field sizes greater than 15 x 15 cm2 and at the depth of maximum dose, dmax. At depths of 11 cm or greater, there was a significant difference only for the same range of field sizes in the 80% to 50% dose region. There was no significant difference at these depths for either the 95%-50% or the 90%-50% dose regions. No significant difference was observed between the use of lead and tungsten blocks and also between lead blocks with a straight edge and those with either an 0.5-mm or a 1-mm step in the face. Since the width of the 95% dose relative to the 50% dose is of greatest interest clinically, straight-edged blocks are as effective as divergent blocks in most situations. These results imply that the design and complexity of a multileaf collimator can be greatly simplified from a double focusing device to one that is single focusing in the plane orthogonal to the leaves.

Maximum x-ray field sizes on many linear accelerators are obtained only with truncated corners. Transmissions through the corners of such fields has been measured utilizing film and ion chamber dosimetry for a number of accelerators. Transmissions are found to be significantly larger than for the movable jaws.

Ionization chambers of varying inside diameter have been used to investigate the penumbral region of 60Co, 6-MV, and 31-MV x-ray beams. Measurements were made in water at varying depths up to 25 cm for a square field of side length 10 cm. The dependence of the penumbral widths on both the inside diameter of the ionization chamber and the depth in water is established along with the asymmetry of the penumbral distributions about the 50% level. A standard correction is indicated to eliminate the dependence of the measured penumbral widths on the inside diameter of the ionization chamber.

A cloned mouse embryo-derived fibroblast cell line was used to study morphological transformation induced by X-rays and 254-nm ultraviolet light (UV). The transformation frequency increased exponentially with increasing dose from 10 to 400 rads for X-rays and 1.0 to 7.5 J/sq m for UV exposure. Split-dose X-ray exposures led to an enhancement in transformation at total doses below 100 rads and a reduction at doses of 300 to 400 rads. The induced transformation frequency varied among serum lots and was very dependent upon the initial cell density. Spontaneous transformants were observed in 10 of 22 consecutive experiments; the spontaneous transformation frequency was generally about 1 to 2 X 10(-5) as compared to induced frequencies which ranged up to 3 X 10(-3) for X-rays and 7.5 X 10(-4) for UV exposure. Further results indicate that this cell line has several potential advantages over the mouse 10T1/2 line for studies with relatively weak in vitro carcinogens such as radiation. These include (a) a reduced overall expression time for the appearance of transformed foci (4 weeks); (b) a high cloning efficiency (50 to 60%); and (c) the fact that about 20 times as many viable cells may be plated per dish for optimal results, allowing transformation frequencies as low as 10(-5) to be measured easily. On the other hand, there was more variability in the results among experiments with the 3T3 cell line.

Electron irradiation (45 MeV) with the chosen doses modifies the molecule composition of isolated dry yeast RNA. High-energy irradiation will crack the RNA which then forms new chains of macromolecular nucleic acids. Other radiation types (60Co, photons, X-rays) do not modify dry RNA, but when irradiated in aqueous solution, these macromolecular bands will be built, too. After UV irradiation with 254 nm delivered over 24 hours these macromolecular bands disappear completely in the electrophoretic diagram. This wavelength corresponds to the absorption maximum of purines, thus stimulating them and reducing their stability.

The relative merits of tungsten and molybdenum targets for mammography have been the subject of much discussion. Therefore the spectra and outputs (at constant potential) from molybdenum and tungsten targets, interchangeable in the same tube, have been measured with a Ge(Li) detector and ion chamber respectively. All conditions apart from the target material were unaltered. The spectra have been corrected for the distortions produced by the detector. The effects of filtration on spectra and exposure rates have been calculated and are in agreement with measured values. The spectra and outputs from molybdenum and tungsten targets filtered by aluminium and molybdenum have been investigated and the results are discussed with reference to mammography and the radiography of specimens.

A very pure diamond with contacts of graphite has a linear current-voltage characteristic when subjected to irradiation. The resistivity is inversely proportional to the dose rate and the sensitivity is extremely high for gamma- and X-rays and electron beams. It is concluded that diamond resistors are suitable for clinical radiation dosimetry. This conclusion is also based on earlier work in which diamonds were used as pinpoint counters.

When a beam-modifying filter such as a wedge or a compensator is placed in an x-ray beam, scattered photons are generated in the filter material. The magnitude of the dose contribution from these photons for a 4-MV x-ray beam was measured. At a distance of 30 cm from the filter, a copper sheet of 1-cm thickness produced a dose contribution on the centerline of about 6% of the transmitted primary dose in a 20 X 20 cm2 field. At the edges of the beam, this contribution was only about one-half that on the centerline. The presence of these scattered photons leads to only minor dose errors in clinical applications if simple procedures are followed to account for their contribution.