{"created":"2023-05-15T14:45:57.455984+00:00","id":62782,"links":{},"metadata":{"_buckets":{"deposit":"084e8438-d904-4150-b64f-972a27f1f747"},"_deposit":{"created_by":1,"id":"62782","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"62782"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00062782","sets":["10:29"]},"author_link":["620074","620061","620063","620072","620073","620064","620070","620066","620068","620069","620071","620067","620065","620062"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2008-10-16","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"In contradiction to classical paradigm, which assumes that radiation effects are directly proportional to energy deposit, numerous in vitro, in vivo and in utero studies described the existence in various models of a radiation-induced adaptive response (AR), according to which pre-exposure to low priming dose of ionizing radiations decreases the biological effects of a subsequent higher challenging dose. Space radiations are both from solar and cosmic origin. Galactic cosmic rays (GCR) consist of high-charge and high-energy particles (C, Fe, H, He, N and O ions), with an elevated relative biological efficiency (RBE). All these radiations can generate secondary radiations, such as neutrons and gamma-rays. Among the numerous problems that have to be resolved before considering long-term space journeys, exposure to high levels of cosmic rays would result in major health risks. Solar activity is highly fluctuating and unpredictable, and astronauts are susceptible to receive high amounts of radiation in a condensed time. Considering that chronic exposure of astronauts to space radiation could induce an AR and decrease their sensitivity to high radiation levels caused by solar activity, it is crucial to study in an adapted model the possibility of triggering an AR by such radiations. Furthermore, high-LET heavy-ion radiations produce non-randomly distributed DNA damage in the form of clusters, or locally multiply damaged sites (LMDS). In this research project, we tried to verify whether this kind of damage can trigger an \"AR specific\" DNA repair, and whether AR could protect against LMDS induction by challenging radiations.\nBiological effects of low and high-LET irradiation (performed at HIMAC, Chiba) were studied in three cultured human lymphoblastoid cell lines: TK6 (expressing wild-type p53 protein), AHH-1 (heterozygous for p53 expression) and NH32 (p53 knock-out). Cells were exposed to priming radiation, either X-Rays or heavy-ions, incubated for 6 hours, then exposed to challenging radiation at different LETs (X-Rays, Carbon-ion: 15 and 40 keV.microm-1, Neon-ion: 150 keV.microm-1). Resulting mutations frequencies (MF) at HPRT locus were measured. We also assessed cell cycle modulations, radiation-induced cell death and DNA double-strand break (DSB) induction and repair by studying ganma-H2AX phosphorylation kinetics using flow cytometry, within 48 hours after challenging irradiation.\nMF after challenging exposure was dependant on radiation LET, but surprisingly, carbon-ion radiation at 40 keV.microM-1 had repeatedly a higher mutagenic effect than at a higher LET (40 keV.microM-1). Our results show that exposure to priming low doses of X-rays resulted in a significantly lower MF after high-LET challenging radiation. MF in cells primed with low-dose high-LET radiation in currently under investigation. No cell cycle modulation was observed after exposure to priming low dose. On the contrary, exposure to challenging dose resulted in an increased proportion of cells in G2/M phase (G2 block), as expected. No difference was observed between adapted and non-adapted cells, suggesting that AR in this model is not related to cell cycle effects. gamma-H2AX phosphorylation levels peaked after priming and challenging radiation, and then decreased, reflecting the involvement of DNA DSB repair mechanisms. As observed previously, gamma-H2AX phosphorylation kinetics depended on LET. Interestingly, gamma-H2AX levels peaked earlier in TK6 adapted cells, suggesting that DSB repair might be involved in AR in this model.\nIn conclusion, our results suggested the existence of an adaptive response to mutagenic effects of heavy-ion radiation in lymphoblastoid cells, and pointed to a possible involvement of DSB repair mechanisms. The ability of high LET heavy-ion radiation (at low dose and low dose-rate) to induce AR is under investigation. Moreover, role of DSB repair will be evaluated by using siRNA specific to homologous recombination and non-homologous end-joining proteins (respectively Rad54 and DNA-PKcs.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"The 7th Japan-France Workshop on Radiation Biology","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Vares, Guillaume"}],"nameIdentifiers":[{"nameIdentifier":"620061","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Bing, Wang"}],"nameIdentifiers":[{"nameIdentifier":"620062","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Murakami, Masahiro"}],"nameIdentifiers":[{"nameIdentifier":"620063","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tanaka, Kaoru"}],"nameIdentifiers":[{"nameIdentifier":"620064","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"KAKIMOTO, AYANA"}],"nameIdentifiers":[{"nameIdentifier":"620065","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Eguchi-Kasai, Kiyomi"}],"nameIdentifiers":[{"nameIdentifier":"620066","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nenoi, Mitsuru"}],"nameIdentifiers":[{"nameIdentifier":"620067","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ｇｕｉｌｌａｕｍｅ Ｖａｒｅｓ","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"620068","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王 冰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"620069","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"村上 正弘","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"620070","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"田中 薫","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"620071","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"柿本 彩七","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"620072","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"笠井 清美","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"620073","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"根井 充","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"620074","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Adaptive response and high-LET radiation","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Adaptive response and high-LET radiation"}]},"item_type_id":"10005","owner":"1","path":["29"],"pubdate":{"attribute_name":"公開日","attribute_value":"2008-10-17"},"publish_date":"2008-10-17","publish_status":"0","recid":"62782","relation_version_is_last":true,"title":["Adaptive response and high-LET radiation"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T21:26:50.373230+00:00"}