{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:24:56Z","timestamp":1762100696312},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,9,11]],"date-time":"2007-09-11T00:00:00Z","timestamp":1189468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alterations of the <jats:italic>Rassf1a<\/jats:italic> gene were investigated in pancreatic duct adenocarcinomas (PDAs) induced by N\u2010nitrosobis(2\u2010oxopropyl)amine (BOP) in hamsters. Female Syrian golden hamsters received 70 mg\/kg BOP, followed by repeated exposures to an augmentation pressure regimen consisting of a choline\u2010deficient diet combined with a sequential course of <jats:sc>DL<\/jats:sc>\u2010ethionine, <jats:sc>L<\/jats:sc>\u2010methionine, and 20 mg\/kg BOP. A total of 15 PDAs were obtained, and total RNAs were assessed by real\u2010time quantitative reverse transcription (RT)\u2010polymerase chain reaction (PCR). Expression of the Rassf1a was significantly reduced in PDAs (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.005) compared with normal pancreatic tissues. For analysis of methylation status, bisulfite sequencing was performed. Normal tissues were all unmethylated in the 5\u2032 upstream region of Rassf1a. In contrast, four PDAs were highly methylated, correlating with reduced expression of the <jats:italic>Rassf1a<\/jats:italic> gene. Using reverse transcription (RT)\u2010polymerase chain reaction (PCR)\u2010single strand conformation polymorphism (SSCP) analysis, mutations were detected in 3 out of 15 PDAs (20%). These results suggested that alterations of the <jats:italic>Rassf1a<\/jats:italic> gene may be involved in development of PDAs induced by BOP in hamsters. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20250","type":"journal-article","created":{"date-parts":[[2007,9,11]],"date-time":"2007-09-11T15:46:40Z","timestamp":1189525600000},"page":"80-87","source":"Crossref","is-referenced-by-count":5,"title":["Reduced expression of the <i>Rassf1a<\/i> gene and its aberrant DNA methylation in pancreatic duct adenocarcinomas induced by N\u2010nitrosobis(2\u2010oxopropyl)amine in 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