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Alterations of the Fhit gene in hepatocellular carcinomas induced by N ‐nitrosodiethylamine in rats
Author(s) -
Tsujiuchi Toshifumi,
Sasaki Yasutaka,
Kubozoe Tadahiko,
Tsutsumi Masahiro,
Konishi Yoichi,
Nakae Dai
Publication year - 2002
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10044
Subject(s) - hccs , fhit , biology , hepatocellular carcinoma , gene expression , gene , microbiology and biotechnology , intraperitoneal injection , cancer research , western blot , medicine , endocrinology , tumor suppressor gene , carcinogenesis , genetics
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. ©2002 Wiley‐Liss, Inc.