The Effects of the Berberine on N-Acetylation of 2-Aminofluorene and Cell Growth in Human Lung Tumor Cells in virto and 2-Aminofluorene Metabolism in Spreque-Dawley Rat's Tissue in vivo
| Autor: | Yao-Chen, Chuang, 莊曜禎 |
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| Rok vydání: | 2001 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 89 The Effects of the Berberine on N-Acetylation of 2-Aminofluorene and Cell Growth in Human Lung Tumor Cells and 2-Aminofluorene Metabolism in Spreque-Dawley Rat’s Tissue Chuang, Yao-Chen Institute of Medical Science and Department of Microbiology and Immunology, China Medical Collage N-acetylation, is a major pathway in the metabolism of arylamine carcinogens, and is also catalyzed by host cytosolic arylamine N-acetyltransferase (NAT) using acetylcoenzyme A as an acetyl group donor. After exposure to 2-aminofluorene (2-AF), the mice had DNA-AF adducts in liver, bladder and circulating leukocytes. It was also discovered that berberine affected NAT activity in human colon tumor cells. Epidemiological and statistical studies have indicates that polymorphism of NAT is closely associated with certain human cancers such as colon and bladder cancer. Therefore, variation in NAT activity which are genetically mediated within target organs may induce different risk for arylamine-induced neoplasm in human populations. In the present study, berberine was used to determine the inhibition of N-arylamine acetyltransferase (NAT) activity and cell growth in human lung tumor cell lines (A549) and Sprague-Dawley (SD) rat’s tissues and also to detect the 2-aminofluorene metabolism in Sprague-Dawley rat. The activity of NAT was determined by high performance liquid chromatography (HPLC) assaying for the amounts of N-acetyl-2-aminofouorene and remaining 2-aminofluorene. The cell’s and tissue’s cytosols and intact cells (human lung tumor cells and white blood cells) were used for examining NAT activity determination. The results demonstrated that NAT activity in normal SD rat’s tissues (bladder, colon and lung) were promoted by berberine in a dose-dependent manner. Dietary treatment of berberine on the rat resulted in affecting the 2-aminofluorene metabolism and distribution of 2-aminofluorene metabolites by berberine in examined tissues. Berberine was also used to determine the effect on the human lung tumor cells : to determine the cytotoxicity, DNA damage, cell morphology and cycle, and cell apoptosis of human lung tumor cells. The results demonstrate that the cell proliferation, G1 phase in cell cycle, nucleus and cell morphology of human lung tumor cells were inhibited by berberine. The effects of cell by berberine were also dose-dependent manner. |
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