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Alterations of the Fhit gene in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats

✍ Scribed by Toshifumi Tsujiuchi; Yasutaka Sasaki; Tadahiko Kubozoe; Masahiro Tsutsumi; Yoichi Konishi; Dai Nakae

Publisher
John Wiley and Sons
Year
2002
Tongue
English
Weight
115 KB
Volume
34
Category
Article
ISSN
0899-1987

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✦ Synopsis

The present study was conducted to assess whether Fhit gene alterations are a feature of hepatocellular carcinomas (HCCs) induced by N-nitrosodiethylamine (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-cycle disturbance and a selection procedure, consisting of 2-acetylaminofluorene 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 Fhit gene by reverse transcriptase-polymerase 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 -9 to 279, nt -9 to 348, nt -98 to 279, nt -26 to 365, or nt -98 to 348. Western blot analysis demonstrated reduced expression of Fhit protein in six of 10 HCCs (60.0%), with a perfect correlation with Fhit gene alterations. These results indicated that changes in the Fhit gene occur frequently and may thus play some role in the development of HCCs induced by DEN in rats.

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