{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:16:46Z","timestamp":1764688606868},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":4067,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>N<\/jats:italic>\u2010Methylnitrosourea (NMU)\u2014induced codon 12 Ki\u2010<jats:italic>ras<\/jats:italic> mutations were analyzed in premalignant thymic lymphomas from C57BL\/6J mice by using a selective polymerase chain reaction amplification strategy. The frequency of codon 12 Ki\u2010<jats:italic>ras<\/jats:italic> mutations was 67% (16 of 24) in NMU\u2010treated animals with premalignant stage I disease. Previously, animals with different stages of disease had been analyzed for cytogenetic changes and for mutations in the p53 tumor suppressor gene. The genetic changes observed were early\u2010activating codon 12 G<jats:sup>35<\/jats:sup>\u2192A transition mutations of the Ki\u2010<jats:italic>ras<\/jats:italic> gene, followed closely by trisomy 15 and infrequent mutation of the p53 gene late in tumor development. The consistent and early detection of Ki\u2010<jats:italic>ras<\/jats:italic> mutations in NMU\u2010treated animals but not in untreated controls suggests that the mutations result from direct carcinogen exposure. Alternate pathways of NMU\u2010induced thymic lymphomagenesis were implicated. One pathway involved putative NMU\u2010induced mutations in other, non\u2010<jats:italic>ras<\/jats:italic> oncogenes that cooperate with trisomy 15 to produce similar T\u2010cell tumors. The frequency of p53 gene mutations in human and murine T\u2010cell tumors is similar but low. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.2940130205","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T20:58:03Z","timestamp":1172091483000},"page":"89-95","source":"Crossref","is-referenced-by-count":14,"title":["<i>N<\/i>\u2010methylnitrosourea\u2014lnduced Ki\u2010<i>ras<\/i> codon 12 mutations: Early events in mouse thymic lymphomas"],"prefix":"10.1002","volume":"13","author":[{"given":"Elizabeth W.","family":"Newcomb","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Bayona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sobha","family":"Pisharody","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,20]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.56.070187.004023"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60222-5"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-5523-6_15"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1289\/ehp.898133","article-title":"Radiation and chemical activation of ras oncogenes in different mouse strains","volume":"81","author":"Newcomb EW","year":"1989","journal-title":"Environ Health Perspect"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-74700-7_3"},{"key":"e_1_2_1_7_2","first-page":"647","article-title":"Oncogene detection at the single cell level","volume":"3","author":"Kumar R","year":"1988","journal-title":"Oncogene"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)92452-2"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2188364"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.4.1593"},{"key":"e_1_2_1_11_2","first-page":"3497","article-title":"Multiple K\u2010ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique","volume":"51","author":"Levi S","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(91)90293-3"},{"key":"e_1_2_1_13_2","first-page":"1079","article-title":"Rapid and sensitive nonradioactive detection of mutant K\u2010ras genes via \u2018enriched\u2019 PCR amplification","volume":"6","author":"Kahn SM","year":"1991","journal-title":"Oncogene"},{"key":"e_1_2_1_14_2","first-page":"2295","article-title":"Identification and quantification of a carcinogen\u2010induced molecular initiation event in cell transformation","volume":"7","author":"Nakazawa H","year":"1992","journal-title":"Oncogene"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.3749"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/322078a0"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.538"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/315382a0"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910490125"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3629242"},{"key":"e_1_2_1_21_2","first-page":"5305","article-title":"Relationship between the formation of promutagenic adducts and the activation of the K\u2010ras protooncogene in lung tumors from A\/J mice treated with nitrosamines","volume":"49","author":"Belinsky SA","year":"1989","journal-title":"Cancer Res"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.718"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940040507"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940040608"},{"key":"e_1_2_1_25_2","first-page":"845","article-title":"Thymomas induced by simple alkylating agents in C57BL\/Cbi mice: Kinetics of the dose response","volume":"64","author":"Frei JV","year":"1980","journal-title":"J Natl Cancer Inst"},{"key":"e_1_2_1_26_2","first-page":"5514","article-title":"ras oncogenes and phenotypic staging in N\u2010methylnitrosourea\u2010and \u03b3\u2010irradiation\u2010induced thymic lymphomas in C57BL\/6J mice","volume":"48","author":"Newcomb EW","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/4.12.1591"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.3109\/07357908409104376"},{"key":"e_1_2_1_29_2","first-page":"3791","article-title":"p53 mutations in C57BL\/6J murine thymic lymphomas induced by \u03b3\u2010irradiation and N\u2010methylnitrosourea","volume":"52","author":"Brathwaite O","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_1_30_2","first-page":"115","article-title":"Identification of a specific marker chromosome early in tumor development in \u03b3\u2010irradiated C57BL\/6J mice","volume":"2","author":"McMorrow LE","year":"1988","journal-title":"Leukemia"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.1.405"},{"key":"e_1_2_1_32_2","first-page":"5129","article-title":"Differential expression of the normal and mutated K\u2010ras alleles in chemically induced thymic lymphomas","volume":"51","author":"Corominas M","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_1_33_2","first-page":"1627","article-title":"Staging of T\u2010cell receptor \u03b2 chain gene rearrangements and ras oncogene mutations in the development of murine thymic lymphomas","volume":"51","author":"Sloan SR","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.5.2233"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940050105"},{"key":"e_1_2_1_36_2","first-page":"1032","article-title":"Infrequent p53 mutation in mouse tumors with deregulated myc","volume":"52","author":"Gutierrez Ml","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940090108"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940090204"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940090309"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199310283291807"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8266092"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428199509056825"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870040102"},{"key":"e_1_2_1_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1697983"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940030305"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb07676.x"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/362857a0"},{"key":"e_1_2_1_48_2","first-page":"2231","article-title":"p53 mutation and MDM2 amplification in human soft tissue sarcomas","volume":"53","author":"Leach FS","year":"1993","journal-title":"Cancer Res"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.23.9268"},{"key":"e_1_2_1_50_2","first-page":"4682","article-title":"ras oncogenes in human cancer: A review","volume":"49","author":"Bos JL","year":"1989","journal-title":"Cancer Res"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.12.3205.3205"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.2940130205","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.2940130205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:57:10Z","timestamp":1698368230000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.2940130205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,6]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1995,6]]}},"alternative-id":["10.1002\/mc.2940130205"],"URL":"https:\/\/doi.org\/10.1002\/mc.2940130205","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,6]]}}}