{"created":"2023-05-15T14:33:22.928993+00:00","id":43291,"links":{},"metadata":{"_buckets":{"deposit":"d2571ea0-e55a-483d-a680-6b977668bca1"},"_deposit":{"created_by":1,"id":"43291","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"43291"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00043291","sets":["1"]},"author_link":["430628","430629","430625","430621","430624","430619","430622","430620","430623","430627","430626"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2003","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"261","bibliographicPageStart":"251","bibliographicVolumeNumber":"190","bibliographic_titles":[{"bibliographic_title":"Toxicology and Applied Pharmacology"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The classic controversy of whether genotoxic chemicals induce cancers with or without a certain low-dose limit, i.e., the threshold, is revisited because of a number of current publications available addressing the plausibility of practical thresholds even for genotoxic carcinogens, the mechanism of which may be hypothesized to be due, in part, to a repair system composed of ordinarily available various defense mechanisms under the steady-state DNA damage. The question of whether an absolute nonthreshold or a relative nonthreshold, i.e., a practical threshold specifically in the low-dose level, is present may not be answered even with the use of a prohibitively large number of wild-type mice. Could the excessive incidence of tumorigenesis in p53-deficient mice contribute to our understanding of the threshold vs nonthreshold issue in genotoxic carcinogenesis? This is considered because an exaggeration of tumorigenesis in p53-deficient mice is hypothesized to reduce or eliminate the range of threshold due to the p53-deficiency-mediated reduction of DNA repair and apoptosis. The present study of chemical leukemogenesis in p53-deficient mice by transplantation assay was designed to answer this question. Briefly, 218 C3H/He mice were lethally irradiated and repopulated with bone marrow cells from wild-type, heterozygous p53-deficinet, and homozygous p53-deficient C3H/He mice. This was followed by treatment with a single and graded dose of methyl nitrosourea at 6.6, 14.8, 33.3, 50.0, and 75.0 mg/kg body wt, with the vehicle-treated control groups treated with zero dose for each genotype. Whereas mice repopulated with p53-deficient bone marrow cells showed a marked reduction of the threshold for leukemogenicity, mice repopulated with wild-type bone marrow cells did not exhibit leukemia at a dose of 33.3 mg/kg body wt and showed a curve with a high probability for the linear regression model with a positive dose intercept, predicting a threshold by the likelihood ratio test. Thus, the failure of wild-type mice to show an increase in incidence of leukemogenesis at low doses genotoxic carcinogens may be due not to a statistical rarity, but to various p53-related pharmacophysiological functions, possibly including DNA repair and apoptosis that may account for a threshold.","subitem_description_type":"Abstract"}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0041-008X","subitem_source_identifier_type":"ISSN"}]},"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":"Hirabayashi, Yoko"}],"nameIdentifiers":[{"nameIdentifier":"430619","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yoshida, Kazuko"}],"nameIdentifiers":[{"nameIdentifier":"430620","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Aizawa, Shin-ichi"}],"nameIdentifiers":[{"nameIdentifier":"430621","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kodama, Yukio"}],"nameIdentifiers":[{"nameIdentifier":"430622","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kanno, Jun"}],"nameIdentifiers":[{"nameIdentifier":"430623","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kurokawa, Yuji"}],"nameIdentifiers":[{"nameIdentifier":"430624","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yoshimura, Isao"}],"nameIdentifiers":[{"nameIdentifier":"430625","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Inoue, Tohoru"}],"nameIdentifiers":[{"nameIdentifier":"430626","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"平林 容子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"430627","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"吉田 和子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"430628","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"井上 達","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"430629","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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Evaluation of nonthreshold leukemogenic response to methyl nitrosourea in p53-deficient C3H/He mice","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Evaluation of nonthreshold leukemogenic response to methyl nitrosourea in p53-deficient C3H/He mice"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2003-12-03"},"publish_date":"2003-12-03","publish_status":"0","recid":"43291","relation_version_is_last":true,"title":["Evaluation of nonthreshold leukemogenic response to methyl nitrosourea in p53-deficient C3H/He mice"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-16T00:29:03.487135+00:00"}