{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:58:17Z","timestamp":1771469897338,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":5679,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1991,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rat neoplasms induced by methylating carcinogens frequently contain <jats:italic>ras<\/jats:italic> genes activated by a single point mutation. Rat prostatic tumors induced by a combination of a single injection of <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (MNU) and long\u2010term treatment with testosterone were examined for the presence of such activating point mutations in <jats:italic>ras<\/jats:italic> genes. These tumors, which arose exclusively in the dorsolateral prostate, included both adenocarcinomas and sarcomas. Activating mutations in codon 12 of the Ki\u2010<jats:italic>ras<\/jats:italic> gene were found in 7 of 10 carcinomas and 4 of 5 sarcomas, using selective oligonucleotide hybridization analysis of DNA amplified by the polymerase chain reaction (PCR). However, no mutated Ha\u2010<jats:italic>ras<\/jats:italic> oncogenes were detected. The presence of PCR\u2010engineered Hphl restriction sites created by the existence of a G<jats:sup>35<\/jats:sup>\u2192A mutation in the rat Ki\u2010<jats:italic>ras<\/jats:italic> oncogene identified the mutation as a GC\u2192A transition at the second position of codon 12. Production of <jats:italic>O<\/jats:italic><jats:sup>6<\/jats:sup>\u2010methylguanine adducts in the Ki\u2010<jats:italic>ras<\/jats:italic> codon 12 followed by base mispairing during replicative DNA synthesis is thus the likely molecular mechanism of initiation of prostatic carcinogenesis by MNU in the rat. Three of the four sarcomas positive for the Ki\u2010<jats:italic>ras<\/jats:italic> G<jats:sup>35<\/jats:sup>\u2192A mutation were immunohistochemically defined as of Schwann cell origin, indicating that involvement of the <jats:italic>ras<\/jats:italic> gene family is possible in tumorigenesis of this cell lineage. Loss of the wild\u2010type Ki\u2010<jats:italic>ras<\/jats:italic> allele was also observed in all four of these sarcomas.<\/jats:p>","DOI":"10.1002\/mc.2940040507","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T20:15:31Z","timestamp":1172088931000},"page":"362-368","source":"Crossref","is-referenced-by-count":33,"title":["Frequent activation of the Ki\u2010<i>ras<\/i> oncogene at codon 12 in <i>N<\/i>\u2010methyl\u2010<i>N<\/i>\u2010nitrosourea\u2010induced rat prostate adenocarcinomas and neurogenic sarcomas"],"prefix":"10.1002","volume":"4","author":[{"given":"Saraswati","family":"Sukumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost 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