WEKO3
アイテム
{"_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"], "permalink_uri": "https://repo.qst.go.jp/records/43291", "pubdate": {"attribute_name": "公開日", "attribute_value": "2003-12-03"}, "publish_date": "2003-12-03", "publish_status": "0", "recid": "43291", "relation": {}, "relation_version_is_last": true, "title": ["Evaluation of nonthreshold leukemogenic response to methyl nitrosourea in p53-deficient C3H/He mice"], "weko_shared_id": -1}
Evaluation of nonthreshold leukemogenic response to methyl nitrosourea in p53-deficient C3H/He mice
https://repo.qst.go.jp/records/43291
https://repo.qst.go.jp/records/43291d3005a33-4cd2-4d02-91e5-da446ab154eb
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2003-12-03 | |||||
タイトル | ||||||
タイトル | Evaluation of nonthreshold leukemogenic response to methyl nitrosourea in p53-deficient C3H/He mice | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Hirabayashi, Yoko
× Hirabayashi, Yoko× Yoshida, Kazuko× Aizawa, Shin-ichi× Kodama, Yukio× Kanno, Jun× Kurokawa, Yuji× Yoshimura, Isao× Inoue, Tohoru× 平林 容子× 吉田 和子× 井上 達 |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
書誌情報 |
Toxicology and Applied Pharmacology 巻 190, p. 251-261, 発行日 2003 |
|||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0041-008X |