The 8th Auger Symposium: Preface

The 8th International Symposium on Physical, Molecular, Cellular, and Medical Aspects of Auger Processes was held from May 20-22, 2015 at the Kansai Photon Science Institute (KPSI) of the Japanese Atomic Energy Agency (JAEA-Kizu), Kyoto, Japan, as a Satellite Symposium of the 15th International Congress of Radiation Research (ICRR 2015). The 8th Auger Symposium was attended by 30 scientists from 8 countries, and began with a presentation by Michel Terrisol which featured an old video clip of Pierre Auger. This was followed by the with a keynote address by Roger Martin who gave an insightful overview of the progress of Auger research towards clinical translation over the past 50 years. The conference lecture was presented by Katherine Vallis, emphasized the applications of Auger emitters in cancer therapy. Symposium participants contributed over 30 presentations, reporting their latest findings, and participating in lively discussions and information exchange spanning physics, dosimetry, molecular and cellular radiobiology, in vivo therapy, photon activation, spectroscopy and low energy electrons. To close the symposium, a meeting summary was given by Linda Yasui

Do bromine atoms incorporated into DNA obscure the photon-induced Auger effect on damage induction?

Despite the efforts by many groups, photon-induced Auger effects of halogenated DNA have not shown us a noticeable biological enhancement. Using monochromatized synchrotron X-rays above and below K-edges of bromine or iodine atom, the Auger enhancement ratios by these halogens have been revealed to be mostly less than 1.5, which were considerably lower than initially expected values [1]. On the other hand, conventional X-ray irradiation are well know to induce pronouced radiobiological rensitizations regardless of the halogenous Auger effect. The scarce Auger ehnancements could be interpreted as an obscuring effect of the strong halogeneous radiosensitization. Monte Calro simulation study suggested that an increase of DNA strand break yields due to Br/IdU incorporation could be explained by radical formation by interaction with hydrated electrons (eaq-) and direct energy deposition along radiation tracks, and also energy transfer in the DNA, resulting damage clustering [2]. To understand the radiosensitizaion mechanism of halogens, apart from their Ager effects, we studies electronic properties of BrU or BrdUMP using soft X-ray absorption or photoelectron spectroscopy, and specific heat measurement for estimating the microscopic state number. Evidences accumulated are as follows.1)The core (1s) levels of the molecules are not affected by exsistence of the bromine atom.2)Resonance from the core to LUMO states are also not affected by exsistence of the bromine atom. 3)Bromine atom may not significantly contribute to the electronic states, but the state related to the excitation of lattice vibration (oscillation and rotation in the molecule). It could be shown that valence electrons or much lower energy phonon excitation might play an important role for DNA damage enhancement rather than core level electronic states.[1] Yokoya, A. and Ito, T., Int. J. Radiat. Biol. 93, 743-756 (2017).[2] Watanabe, R. and Nikjoo, H., Int. J. Radiat. Biol. 78, 953-966 (2002).The 9th International Symposium on Physical, Molecular, Cellular, and Medical Aspects of Auger Processe

High Brilliance Synchrotron Radiation as a Tool for Studies of Radiation Damage to DNA and resulting cellular responses

Synchrotron Radiation from accelerators has been used as a radiation source for many studies of radiobiological effects. In 1980s, first generation synchrotron accelerators provided us intense vacuum ultraviolet light photos (1-20 eV) to induce DNA strand breaks via super-excitation states [1]. The energy region was gradually expanded to the X-ray energy region (~30keV) in second generation facilities in 1990s, and high-resolution monochromators for the X-rays realized targeting inner-shell electrons in a particular atom and following Auger effect in DNA molecule [2,3]. These studies provided us many fruitful evidences on Auger enhancement of the biological effects. Development of insertion devices in third generation facilities (so called undulators) in 2000s, the brilliant photon sources have been used not only as a source of irradiation, but also a probe to explore the electric states of DNA and its excitation/ionization states by various methods such as X-ray Absorption Structure (XAS), desorbed ion spectroscopy, electron paramagnetic resonance (EPR), or photoelectron spectroscopy (PES) [3]. Recently, by applying not only its high intensity, but also the other properties of synchrotron radiation, such as circular polarization or coherent fraction, new approaches have also been tested in the quest for non-crystallized protein structures in a solution or visualization of biological samples, which could not be achieved by conventional methods. In the present talk, physicochemical processes of DNA damage induction and cellular responses revealed by the synchrotron applications in radiation biology will be reviewed. [1] Ito T, Ito A. Effects of broad-band vacuum-UV synchrotron radiation on wet yeast cells. Radiat Res. 82:364-373 (1980).[2] Chetioui A, Despiney I, Guiraud L, Adoui L, Sabatier L, Dutrillaux B. Possible role of inner-shell ionization phenomena in cell inactivation by heavy ions. Int J Radiat Biol. 65:511-22 (1994).[3] Yokoya A, Ito T. Photon-induced Auger Effect in Biological Systems: A Review. Int. J. Radiat. Biol. (2017) Epub ahead of print.[4] Yokoya, A., Fujii, K., Shikazono, N. and Ukai, M. Chapter 20. Spectroscopic study of radiation-induced DNA lesions and their susceptibility to enzymatic repair. In: Charged particle and photon interactions with matter-recent advances, applications and interfaces, Eds., Y. Hatano, Y. Katsumura, and A. Mozumder, CRC/Taylor & Francis Group, USA, pp543-574. (2011).第1回QST国際シンポジウム「量子生命科学　-Quantum Life Science-

Low-dose radiation risk and individual variation in radiation sensitivity in Fukushima

Although it has been gradually recognized that a range of low-dose (or low-dose-rate) radiation effects on living cells are possible key factors in evaluating \u27low-dose radiation risk\u27, there remains little of the coherence required among robust data that can be used with confidence in risk assessments. At present, residents of Fukushima continue to be gripped by fear of contamination by radioactive substances; however, regardless of difficulties, medical personnel continue to cultivate close relationships with the patients. From the viewpoint of precision medicine, we note a possible issue: there might be Fukushima residents, including young children, with greater than average radiation sensitivity because of their genetic background. The investigation of individual variation in radiation sensitivity in Fukushima seems to be insufficient because the sensitivity substantially varies depending on individual genetic background. We hereby propose that not only a radiation exposure assessment but also additional medical checkups for cancer, such as ultrasonography, gastrointestinal endoscopy, measurements of tumor markers in blood and urine, and genetic testing, should be combined in a balanced fashion to minimize the number of local residents who will develop advanced cancers in the future

Targeting Specific Sites in Biological Systems with Synchrotron X-Ray Microbeams for Radiobiological Studies at the Photon Factory

X-ray microbeams have been used to explore radiobiological effects induced by targeting a specific site in living systems. Synchrotron radiation from the Photon Factory, Japan, with high brilliance and highly parallel directionality is a source suitable for delivering a particular beam size or shape, which can be changed according to target morphology by using a simple metal slit system (beam size from 5 μm to several millimeters). Studies have examined the non-targeted effects, called bystander cellular responses, which are thought to be fundamental mechanisms of low-dose or low-dose-rate effects in practical radiation risk research. Narrow microbeams several tens of micrometers or less in their size targeted both the cell nucleus and the cytoplasm. Our method combined with live-cell imaging techniques has challenged the traditional radiobiological dogma that DNA damage is the only major cause of radiation-induced genetic alterations and is gradually revealing the role of organelles, such as mitochondria, in these biological effects. Furthermore, three-dimensionally cultured cell systems have been used as microbeam targets to mimic organs. Combining the spatial fractionation of X-ray microbeams and a unique ex vivo testes organ culture technique revealed that the tissue-sparing effect was induced in response to the non-uniform radiation fields. Spatially fractionated X-ray beams may be a promising tool in clinical radiation therapy

Targeting Specific Sites in Biological Systems with Synchrotron X-Ray Microbeams for Radiobiological Studies at the Photon Factory

X-ray microbeams have been used to explore radiobiological effects induced by targeting a specific site in living systems. Synchrotron radiation from the Photon Factory, Japan, with high brilliance and highly parallel directionality is a source suitable for delivering a particular beam size or shape, which can be changed according to target morphology by using a simple metal slit system (beam size from 5 μm to several millimeters). Studies have examined the non-targeted effects, called bystander cellular responses, which are thought to be fundamental mechanisms of low-dose or low-dose-rate effects in practical radiation risk research. Narrow microbeams several tens of micrometers or less in their size targeted both the cell nucleus and the cytoplasm. Our method combined with live-cell imaging techniques has challenged the traditional radiobiological dogma that DNA damage is the only major cause of radiation-induced genetic alterations and is gradually revealing the role of organelles, such as mitochondria, in these biological effects. Furthermore, three-dimensionally cultured cell systems have been used as microbeam targets to mimic organs. Combining the spatial fractionation of X-ray microbeams and a unique ex vivo testes organ culture technique revealed that the tissue-sparing effect was induced in response to the non-uniform radiation fields. Spatially fractionated X-ray beams may be a promising tool in clinical radiation therapy

Photon-induced Auger Effect in Biological Systems: A Review

We review interesting findings reported in the studies of the biological effects induced by inner-shell ionization with the aim of interpreting them from a mechanistic viewpoint of Auger effect of a particular atom on biological systems.Materials and Methods: Cited more than 70 published papers on the Auger effects ranging from DNA related elements (carbon, nitrogen, oxygen and phosphorus) to mammalian cells for the present endeavor. Externally administrated bromine, iodine, and platinum have also been included. Those significant work all needed a highly monochromatized X-rays from brilliant synchrotron light sources. We have produced a coherent view on the inner-shell effects of Aurger process that contrasted to the overall effects with ordinary outer-shell ionization processes. Some of these studies have reported that the Augur effect significantly enhances the biological effects as compared with ordinary radiation. Auger-specific molecular degradation mode of DNA, involving extensive fragmentation of the deoxypentose moiety, has also been revealed. We believe that the selectively localized effect on the specified atoms through inner-shell ionization in the Auger process should have a definite impact on classical radiation effect studies, which are largely based on non-selective outer-shell ionizations