Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Fukuda, H.
Right arrow Articles by Watayo, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fukuda, H.
Right arrow Articles by Watayo, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol. 23, No. 12, 2019-2023, December 2002
© 2002 Oxford University Press

CANCER BIOLOGY

Increased metabolizing activities of the tricarboxylic acid cycle and decreased drug metabolism in hepatocellular carcinoma

Hiroyuki Fukuda1,4, Masaaki Ebara1, Mitsunobu Okuyama2, Nobuyuki Sugiura1, Masaharu Yoshikawa1, Hiromitsu Saisho1, Ryo Shimizu2, Naomi Motoji2, Akiyo Shigematsu2 and Takaho Watayo3

1 Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi, Chiba 260-0856, Japan,
2 Institute of Whole Body Metabolism, Nauchi 340-2, Shiroi, Chiba 270-1407, Japan and
3 Department of Surgery, Tokyo Metropolitan Ebara General Hospital, Higashiyukigaya 4-5-10, Ohta-ku, Tokyo 145-0065, Japan

The aim of this study was to determine the metabolizing activities in the liver of patients with hepatocellular carcinoma (HCC). Thin-layer chromatography autoradioluminography was used to measure metabolizing activities. Succinate-producing activity (SPA) was used as an indicator of metabolizing activity of the tricarboxylic acid (TCA) cycle in mitochondria, and diazepam-N-demethylating activity (DZ-DA), diazepam-3-hydroxylating activity (DZ-HA) and tolbutamide-methyl-hydroxylating activity (TB-HA) as indicators of drug metabolizing activities by P-450. SPA and drug-metabolizing activity of HepG2 cells were examined to compare with those of human liver specimens. Liver biopsy specimens of 30 patients and surgical specimens of eight patients with HCC were studied. SPA of HepG2 cells was as high as that of human tumor tissue, and DZ-DA, DZ-HA and TB-HA were undetectable in HepG2 cells. SPA and DZ-HA of non-tumor tissue in biopsy samples were significantly higher than those in resected liver specimens (P < 0.05). In biopsy specimens, SPA was significantly higher in tumor tissue than in non-tumor tissue (P < 0.05), and DZ-DA, DZ-HA and TB-HA were significantly lower in tumor tissue (P < 0.01). SPA was significantly higher in large tumors (>=30 mm) than in small tumors <30 mm (P < 0.05), and TB-HA was significantly lower in large tumors than in small tumors (P < 0.01). DZ-DA and TB-HA significantly decreased with the progression of the tumor differentiation (P < 0.05). In conclusion, HCC has increased metabolizing activities of the TCA cycle and decreased drug-metabolizing activities.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. G. K. Tan, L. L. P. J. Ooi, S. E. Aw, and K. M. Hui
Cloning and Identification of Hepatocellular Carcinoma Down-regulated Mitochondrial Carrier Protein, a Novel Liver-specific Uncoupling Protein
J. Biol. Chem., October 22, 2004; 279(43): 45235 - 45244.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.