{"@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/1363670320350337024.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.83.16.5825"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.83.16.5825"}}],"dc:title":[{"@value":"Activating mutations of the c-Ha-ras protooncogene in chemically induced hepatomas of the male B6C3 F1 mouse."}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Activated c-Ha-ras protooncogenes have recently been identified in the DNA of some spontaneous hepatic tumors found in 2-year-old B6C3 F1 mice. Activation of c-Ha-ras has now been demonstrated in DNA from well-differentiated hepatomas initiated by a single dose of carcinogen given to male B6C3 F1 mice at 12 days of age. DNA from each of 25 hepatomas, induced by N-hydroxy-2-acetylaminofluorene, vinyl carbamate, or 1'-hydroxy-2',3'-dehydroestragole, containing transforming activity in the NIH 3T3 transfection assay. Southern analysis of NIH 3T3 cells transformed by DNA from 24 of these hepatomas revealed amplified and/or rear-ranged restriction fragments homologous to a Ha-ras probe. The other tumor contained an activated Ki-ras gene. Immunoprecipitation and NaDodSO4/PAGE analysis of p21 ras proteins in NIH 3T3 transformants derived from a majority of the hepatomas suggested that the activating mutations were localized in the 61st codon of the c-Ha-ras gene. Creation of a new Xba I restriction site by an AT----TA transversion at the second position of codon 61 was detected in DNA from primary tumors and NIH 3T3 cells transformed by DNA from 6 of 7 vinyl carbamate- and 5 of 10 1'-hydroxy-2',3'-dehydroestragole-induced hepatomas. Selective oligonucleotide hybridization demonstrated a CG----AT transversion at the first position of the 61st codon in NIH 3T3 transformants derived from 7 of 7 N-hydroxy-2-acetylaminofluorene-induced hepatomas. By the same criterion, an AT----GC transition at the second position of codon 61 was the activating mutation in 1 of 7 vinyl carbamate- and 5 of 10 1'-hydroxy-2',3'-dehydroestragole-induced tumors. Thus, c-Ha-ras activation is apparently an early event in B6C3 F1 mouse hepatocarcinogenesis that results directly from reaction of ultimate chemical carcinogens with this gene in vivo.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380014416854107526","@type":"Researcher","foaf:name":[{"@value":"R W Wiseman"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343604327170","@type":"Researcher","foaf:name":[{"@value":"S J Stowers"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343604327172","@type":"Researcher","foaf:name":[{"@value":"E C Miller"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343604327171","@type":"Researcher","foaf:name":[{"@value":"M W Anderson"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343604327169","@type":"Researcher","foaf:name":[{"@value":"J A Miller"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00278424"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"1986-08","prism:volume":"83","prism:number":"16","prism:startingPage":"5825","prism:endingPage":"5829"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.83.16.5825"}],"createdAt":"2006-05-31","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360292619009169920","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"RAS oncogenes: the first 30 years"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204414476288","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Analysis of Ras Gene Mutations in Main Spontaneously-occurring Non-epithelial Tumors of B6C3F1 Mouse."}]},{"@id":"https://cir.nii.ac.jp/crid/1390282680019869952","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Effect of Mouse Intestinal Bacteria on Incidence of Colorectal Tumors Induced by 1,2-dimethylhydrazine Injection in Gnotobiotic Transgenic Mice Harboring Human Prototype c-Ha-ras Genes."},{"@language":"ja-Kana","@value":"Effect of Mouse Intestinal Bacteria on"}]},{"@id":"https://cir.nii.ac.jp/crid/2050307416984348288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Evaluation of in vivo mutagenesis for assessing the health risk of air pollutants"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.83.16.5825"},{"@type":"CROSSREF","@value":"10.1038/nrc1097_references_DOI_8kMYfG7nVOBqTcRt5hdzwpB0BNe"},{"@type":"CROSSREF","@value":"10.1186/s41021-016-0064-6_references_DOI_8kMYfG7nVOBqTcRt5hdzwpB0BNe"},{"@type":"CROSSREF","@value":"10.1293/tox.12.65_references_DOI_8kMYfG7nVOBqTcRt5hdzwpB0BNe"},{"@type":"CROSSREF","@value":"10.1538/expanim.47.111_references_DOI_8kMYfG7nVOBqTcRt5hdzwpB0BNe"}]}