Document Detail

Fhit gene alterations in hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet in rats.
MedLine Citation:
PMID:  12619037     Owner:  NLM     Status:  MEDLINE    
Alterations of the fragile histidine triad (Fhit) gene were investigated in rat hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined (CDAA) diet. Males of the F344 strain, 6 wk of age, were fed a CDAA diet, and subgroups were killed at 2, 4, 12, 20, and 75 wk after the beginning of the experiment. Fifteen hepatocellular carcinomas (HCCs) were noted in rats by the last time point; they were dissected free from the surrounding tissue. Normal control liver specimens were obtained from 6-wk-old rats. Total RNAs were extracted from whole livers of animals fed the CDAA diet for 2, 4, 12, and 20 wk and from HCCs, for assessment of aberrant transcription of the Fhit gene by reverse transcription-polymerase chain reaction. Aberrant transcripts were detected in livers of rats fed the CDAA diet for 4, 12, and 20 wk, but not 2 wk, as well as in 11 of 15 HCCs (73.3%). Southern blot analysis showed a genomic DNA abnormality in one of seven informative HCCs (14.3%), while Western blot analysis showed reduction of Fhit protein expression in seven of nine HCCs (77.8%). No abnormal expression was evident in the livers after exposure to the CDAA diet for 2-20 wk. These results suggest that Fhit alterations may play important roles in hepatocarcinogenesis due to choline deficiency in rats.
Toshifumi Tsujiuchi; Yasutaka Sasaki; Yasuo Oka; Yoichi Konishi; Masahiro Tsutsumi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular carcinogenesis     Volume:  36     ISSN:  0899-1987     ISO Abbreviation:  Mol. Carcinog.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-05     Completed Date:  2003-04-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8811105     Medline TA:  Mol Carcinog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  147-52     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Nara, Japan.
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MeSH Terms
Acid Anhydride Hydrolases*
Amino Acids
Blotting, Southern
Carcinoma, Hepatocellular / chemically induced,  genetics*
Choline Deficiency / complications*
Liver Neoplasms, Experimental / chemically induced,  genetics*
Neoplasm Proteins / drug effects,  genetics*,  metabolism
Rats, Inbred F344
Reference Values
Reg. No./Substance:
0/Amino Acids; 0/Neoplasm Proteins; 0/fragile histidine triad protein; EC 3.6.-/Acid Anhydride Hydrolases

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