{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670319314814720.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.90.7.2965"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.90.7.2965"}},{"identifier":{"@type":"NAID","@value":"30016296103"}}],"dc:title":[{"@value":"Chemical and molecular regulation of enzymes that detoxify carcinogens."}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Inductions of detoxication (phase 2) enzymes, such as glutathione transferases and NAD(P)H:(quinone-acceptor) oxidoreductase, are a major mechanism for protecting animals and their cells against the toxic and neoplastic effects of carcinogens. These inductions result from enhanced transcription, and they are evoked by diverse chemical agents: oxidizable diphenols and phenylenediamines; Michael reaction acceptors; organic isothiocyanates; other electrophiles--e.g., alkyl and aryl halides; metal ions--e.g., HgCl2 and CdCl2; trivalent arsenic derivatives; vicinal dimercaptans; organic hydroperoxides and hydrogen peroxide; and 1,2-dithiole-3-thiones. The molecular mechanisms of these inductions were analyzed with the help of a construct containing a 41-bp enhancer element derived from the 5' upstream region of the mouse liver glutathione transferase Ya subunit gene ligated to the 5' end of the isolated promoter region of this gene, and inserted into a plasmid containing a human growth hormone reporter gene. When this construct was transfected into Hep G2 human hepatoma cells, the concentrations of 28 compounds (from the above classes) required to double growth hormone production, and the concentrations required to double quinone reductase specific activities in Hepa 1c1c7 cells, spanned a range of four orders of magnitude but were closely linearly correlated. Six compounds tested were inactive in both systems. A 26-bp subregion of the above enhancer oligonucleotide (containing the two tandem \"AP-1-like\" sites but lacking the preceding ETS protein binding sequence) was considerably less responsive to the same inducers. We conclude that the 41-bp enhancer element mediates most, if not all, of the phase 2 enzyme inducer activity of all of these widely different classes of compounds.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1581980076319825792","@type":"Researcher","foaf:name":[{"@value":"T Prestera"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185."}]},{"@id":"https://cir.nii.ac.jp/crid/1380294663228060674","@type":"Researcher","foaf:name":[{"@value":"W D Holtzclaw"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185."}]},{"@id":"https://cir.nii.ac.jp/crid/1380294663228060672","@type":"Researcher","foaf:name":[{"@value":"Y Zhang"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185."}]},{"@id":"https://cir.nii.ac.jp/crid/1380294663228060673","@type":"Researcher","foaf:name":[{"@value":"P Talalay"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"1993-04","prism:volume":"90","prism:number":"7","prism:startingPage":"2965","prism:endingPage":"2969"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.90.7.2965"}],"createdAt":"2006-05-31","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002217477004288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Discovery of the Negative Regulator of Nrf2, Keap1: A Historical Overview"}]},{"@id":"https://cir.nii.ac.jp/crid/1360009142695069824","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565166126078592","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679475649152","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Metabolic Activation of Proestrogens in the Environment by Cytochrome P450 System"}]},{"@id":"https://cir.nii.ac.jp/crid/1520853832376648320","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@value":"親電子性物質応答の分子機構"},{"@language":"ja-Kana","@value":"シンデン シ セイ ブッシツ オウトウ ノ ブンシ キコウ"}]},{"@id":"https://cir.nii.ac.jp/crid/1524232505050830976","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@value":"発生工学を利用して環境循環への適応の分子機構を探る--酸化ストレス応答と赤血球系転写因子"},{"@language":"ja-Kana","@value":"ハッセイ コウガク オ リヨウ シテ カンキョウ ジュンカン エ ノ テキオウ"}]},{"@id":"https://cir.nii.ac.jp/crid/1573950400607545088","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Expression and regulation of glutathione S-transferase P1-1 in cultured human epidermal cells"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.90.7.2965"},{"@type":"CIA","@value":"30016296103"},{"@type":"CROSSREF","@value":"10.1089/ars.2010.3222_references_DOI_8k8ASiuvx9JijBUZx020tZi2uQY"},{"@type":"CROSSREF","@value":"10.1128/mcb.00099-20_references_DOI_8k8ASiuvx9JijBUZx020tZi2uQY"},{"@type":"CROSSREF","@value":"10.1248/jhs.54.343_references_DOI_8k8ASiuvx9JijBUZx020tZi2uQY"},{"@type":"CROSSREF","@value":"10.1016/j.taap.2009.03.005_references_DOI_8k8ASiuvx9JijBUZx020tZi2uQY"}]}