المؤلفون: Tomita M; Radiation Safety Research Center, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae, Tokyo 201-8511, Japan. Electronic address: mstomita@criepi.denken.or.jp., Matsumoto H; Division of Oncology, Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuoka-Shimoaitsuki, Eiheiji-cho, Fukui 910-1193, Japan., Funayama T; Microbeam Radiation Biology Group, Radiation Biology Research Division, Quantum Beam Science Center, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292, Japan., Yokota Y; Microbeam Radiation Biology Group, Radiation Biology Research Division, Quantum Beam Science Center, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292, Japan., Otsuka K; Radiation Safety Research Center, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae, Tokyo 201-8511, Japan., Maeda M; Radiation Safety Research Center, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae, Tokyo 201-8511, Japan; Proton Medical Research Group, Research and Development Department, The Wakasa Wan Energy Research Center, 64-52-1 Nagatani, Tsuruga-shi, Fukui 914-0192, Japan., Kobayashi Y; Microbeam Radiation Biology Group, Radiation Biology Research Division, Quantum Beam Science Center, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292, Japan.

المصدر: Life sciences in space research [Life Sci Space Res (Amst)] 2015 Jul; Vol. 6, pp. 36-43. Date of Electronic Publication: 2015 Jun 25.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Ltd Country of Publication: Netherlands NLM ID: 101632373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2214-5532 (Electronic) Linking ISSN: 22145524 NLM ISO Abbreviation: Life Sci Space Res (Amst) Subsets: MEDLINE

مواضيع طبية MeSH: Bystander Effect/*radiation effects , Cell Communication/*radiation effects , Cell Death/*radiation effects , DNA Repair/*radiation effects , Nitric Oxide/*metabolism, Argon ; Astronauts ; Cell Line ; Cell Survival/radiation effects ; Coculture Techniques ; Cyclooxygenase 2/metabolism ; DNA Breaks, Double-Stranded/radiation effects ; Environmental Exposure/adverse effects ; Extraterrestrial Environment ; Fibroblasts/radiation effects ; Heavy Ions ; Humans ; NF-kappa B/metabolism ; Phosphorylation/radiation effects ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction

مستخلص: In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time after irradiation.
(Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

المؤلفون: Maeda M; Proton Medical Research Group, Research and Development Department, The Wakasa Wan Energy Research Center, 64-52-1 Nagatani, Tsuruga-shi, Fukui 914-0192, Japan., Kobayashi K, Matsumoto H, Usami N, Tomita M

المصدر: Journal of radiation research [J Radiat Res] 2013 Nov 01; Vol. 54 (6), pp. 1043-9. Date of Electronic Publication: 2013 May 09.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0376611 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1349-9157 (Electronic) Linking ISSN: 04493060 NLM ISO Abbreviation: J Radiat Res Subsets: MEDLINE

مواضيع طبية MeSH: Bystander Effect/*physiology , Bystander Effect/*radiation effects , Chromosome Aberrations/*radiation effects , Fibroblasts/*physiology , Mutation/*genetics , Nitric Oxide/*metabolism, Animals ; Apoptosis/genetics ; Apoptosis/radiation effects ; Cell Line ; Cricetinae ; Cricetulus ; Fibroblasts/radiation effects ; Mutation/radiation effects ; Radiation Dosage

مستخلص: The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm(2) 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10(-)(5) (background level), and the frequency decreased to 5.3 × 10(-)(6) with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations.

المؤلفون: Matsumoto H; Division of Oncology, Biomedical Imaging Research Center, University of Fukui, Matsuoka-Shimoaitsuki, Eiheiji-cho, Japan. hidekim@u-fukui.ac.jp, Tomita M, Otsuka K, Hatashita M, Hamada N

المصدر: Current molecular pharmacology [Curr Mol Pharmacol] 2011 Jun; Vol. 4 (2), pp. 126-34.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Review

بيانات الدورية: Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101467997 Publication Model: Print Cited Medium: Internet ISSN: 1874-4702 (Electronic) Linking ISSN: 18744672 NLM ISO Abbreviation: Curr Mol Pharmacol Subsets: MEDLINE

مواضيع طبية MeSH: Adaptation, Physiological/*physiology , Adaptation, Physiological/*radiation effects , Bystander Effect/*radiation effects , Nitric Oxide/*metabolism, Animals ; Bystander Effect/physiology ; Models, Biological ; Signal Transduction/radiation effects

مستخلص: A classical paradigm of radiation biology asserts "targeted effect" that all radiation effects on cells, tissues and organisms are due to the direct action of radiation. However, over the past two decades, a paradigm of radiation biology has undergone a shift away from "targeted effect" relationships and towards complex ongoing "intra- and inter-cellular responses", which involve not only targeted but also non-targeted ones. These responses include now familiar, but still fully unknown, phenomena associated with low-dose/low-dose-rate radiation exposure such as adaptive responses, bystander responses, low-dose hypersensitivity, and genomic instability. The mechanisms underlying these responses often involve biochemical/molecular signals that respond to targeted and non-targeted events. Matsumoto et al. have previously found that nitric oxide functions as initiators of radiation-induced bystander and adaptive responses. These findings suggest correlations between the radioadaptive and bystander responses. The present review focuses on these two phenomena by summarizing observations supporting their existence, and discussing the linkage between them from the aspect of production of reactive nitrogen species.