Increased metabolizing activities of the tricarboxylic acid cycle and decreased drug metabolism in hepatocellular carcinoma
| Autor: | Hiroyuki Fukuda, Akiyo Shigematsu, Naomi Motoji, Mitsunobu Okuyama, Takaho Watayo, Masaaki Ebara, Hiromitsu Saisho, Masaharu Yoshikawa, Nobuyuki Sugiura, Ryo Shimizu |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
medicine.medical_specialty Carcinoma Hepatocellular Tolbutamide Citric Acid Cycle Succinic Acid Radiation-Protective Agents Mitochondrion Andrology Internal medicine Biopsy Tumor Cells Cultured medicine Humans chemistry.chemical_classification Diazepam biology medicine.diagnostic_test Liver Neoplasms Cytochrome P450 General Medicine Metabolism Tricarboxylic acid medicine.disease Fibrosis Mitochondria Endocrinology Liver chemistry Liver biopsy Hepatocellular carcinoma biology.protein Chromatography Thin Layer Drug metabolism |
| Zdroj: | Carcinogenesis. 23:2019-2023 |
| ISSN: | 1460-2180 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|