{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T19:41:43Z","timestamp":1700250103856},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,4,17]],"date-time":"2002-04-17T00:00:00Z","timestamp":1019001600000},"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":[[2002,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study was conducted to assess whether <jats:italic>Fhit<\/jats:italic> gene alterations are a feature of hepatocellular carcinomas (HCCs) induced by <jats:italic>N<\/jats:italic>\u2010nitrosodiethylamine (DEN) in male Fischer 344 rats. Animals, 6 wk old, received a single intraperitoneal injection of DEN at a dose of 10 mg\/kg body weight, followed by combined treatment with partial hepatectomy and colchicine to induce cell\u2010cycle disturbance and a selection procedure, consisting of 2\u2010acetylaminofluorene and carbon tetrachloride. Fourteen HCCs were obtained 42 wk after the beginning of the experiment; total RNA was extracted for the assessment of aberrant transcription of the <jats:italic>Fhit<\/jats:italic> gene by reverse transcriptase\u2013polymerase chain reaction analysis. Aberrant transcripts were detected in nine of the 14 HCCs (64.3%). Sequence analysis showed that these resulted from the absence of nt \u22129 to 279, nt \u22129 to 348, nt \u221298 to 279, nt \u221226 to 365, or nt \u221298 to 348. Western blot analysis demonstrated reduced expression of Fhit protein in six of 10 HCCs (60.0%), with a perfect correlation with <jats:italic>Fhit<\/jats:italic> gene alterations. These results indicated that changes in the <jats:italic>Fhit<\/jats:italic> gene occur frequently and may thus play some role in the development of HCCs induced by DEN in rats. \u00a92002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.10044","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:24:15Z","timestamp":1030317855000},"page":"19-24","source":"Crossref","is-referenced-by-count":10,"title":["Alterations of the <i>Fhit<\/i> gene in hepatocellular carcinomas induced by <i>N<\/i>\u2010nitrosodiethylamine in 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