{"created":"2023-05-15T14:39:43.032602+00:00","id":54545,"links":{},"metadata":{"_buckets":{"deposit":"c8d2b73e-446a-48d2-80f6-2a5388f5864f"},"_deposit":{"created_by":1,"id":"54545","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"54545"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00054545","sets":["2"]},"author_link":["557173","557175","557180","557172","557177","557179","557174","557178","557171","557176"],"item_10003_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2014-09","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageStart":"S784","bibliographicVolumeNumber":"90","bibliographic_titles":[{"bibliographic_title":"International Journal of Radiation Oncology Biology Physics"}]}]},"item_10003_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Purpose/Objective(s): In a previous study, we reported that some zinc (II) chelators suppress radiation-induced p53-dependent apoptosis through inhibition of p53-dependent apoptotic pathways. As a result of further screening, we found an 8-quinolinol derivative KH-3 as a radioprotector that has an ability to modulate p53 transcription resulting in the up-regulation of p21, and that can protect mice from a sublethal dose of 7.5 Gy total-body irradiation (TBI), but not of a higher dose of TBI (8.0 Gy). These data indicate that KH-3 is effective only in a narrow range of radiation dose that causes sublethal hematopoietic syndrome in mouse TBI. In this study, we further investigated the effects and mechanism of KH-3, including RNA interference-mediated silencing analysis of p21. In addition, p53 and p21 have been reported as resistant factors in radiation-induced gastrointestinal (GI) syndrome in mice. The fact raises the possibility that KH-3 protects mice from GI syndrome by up-regulating p21. We then tested the possibility using the technique of abdominal subtotal-body irradiation (SBI) to avoid the hematopoietic syndrome.\n\\n Materials /Methods: In cell analysis, highly radiosensitive cell line MOLT-4, derived from human T-cell leukemia, was used and 10 Gy-irradiated. The suppressive effect of KH-3 and the reference compound PFTm on radiation-induced MOLT-4 apoptosis was evaluated using Annexin V-FITC or MitoTracker Red staining, and WST-8 colorimetric assay. To examine the specificity of KH-3 for p21 in the p53-mediated apoptosis, we used MOLT-4 cells and its p21-knockdown transformant. In mouse SBI model, ICR female mice, aged 8-week old, were irradiated with a gamma-ray generator with shielding lead walls at least 3.0 cm thick. KH-3 (60 mg/kg) or vehicle was ip injected 30 minutes before 18 or 24 Gy SBI, and the mice were anesthetized 5-10 minutes before SBI. The abdomen of the anesthetized mice was exposed to gamma rays at a dose rate of 0.70 Gy/min.\n\\n Results: RNA interference-mediated silencing of p21 revealed that KH-3 was ineffective against the radiation-induced apoptosis of p21-knockdown transformant, indictating that suppression of radiation-induced apoptosis by KH-3 was specifically mediated through p53-p21 signaling pathways. For the 30-day survival study, survival rates of mice in KH-3-treated groups were 90% (18 Gy-SBI) and 40% (24-Gy SBI) respectively, whereas those of the control vehicle-injected groups were 40% (18 Gy-SBI) and 0% (24-Gy SBI) respectively. The dose-reduction factor (DRF) of KH-3 in the SBI was about 1.3.\n \n Conclusion: KH-3 is a novel kind of radioprotector that upregulates p53-p21 pathway and protects mice from GI death. KH-3 may serve as a therapeutic radioprotector for protecting normal tissues against adverse side effects of radiation/chemotherapy in abdominal cancer.","subitem_description_type":"Abstract"}]},"item_10003_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Tarrytown Ny : Elsevier Science Inc"}]},"item_10003_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":": http://dx.doi.org/10.1016/j.ijrobp.2014.05.2268","subitem_relation_type_select":"DOI"}}]},"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":"高橋, 一平"}],"nameIdentifiers":[{"nameIdentifier":"557171","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森田, 明典"}],"nameIdentifiers":[{"nameIdentifier":"557172","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"青木, 伸"}],"nameIdentifiers":[{"nameIdentifier":"557173","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王, 冰"}],"nameIdentifiers":[{"nameIdentifier":"557174","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"笹谷, めぐみ"}],"nameIdentifiers":[{"nameIdentifier":"557175","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"有安, 真也"}],"nameIdentifiers":[{"nameIdentifier":"557176","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"神谷, 研二"}],"nameIdentifiers":[{"nameIdentifier":"557177","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"細井, 義夫"}],"nameIdentifiers":[{"nameIdentifier":"557178","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"稲葉, 俊哉"}],"nameIdentifiers":[{"nameIdentifier":"557179","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王 冰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"557180","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 paper","resourceuri":"http://purl.org/coar/resource_type/c_5794"}]},"item_title":"KH-3, a Transcriptional Modulator of p53, Protects Mice from Radiation-Induced Gastrointestinal Syndrome","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"KH-3, a Transcriptional Modulator of p53, Protects Mice from Radiation-Induced Gastrointestinal Syndrome"}]},"item_type_id":"10003","owner":"1","path":["2"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-01-14"},"publish_date":"2015-01-14","publish_status":"0","recid":"54545","relation_version_is_last":true,"title":["KH-3, a Transcriptional Modulator of p53, Protects Mice from Radiation-Induced Gastrointestinal Syndrome"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T22:59:37.772732+00:00"}