Doxorubicin ,Curcumin和Dithiocarbamates

• Main Authors: Tsao, Shou-Yuh, 曹守
• Other Authors: Fu-Chuo Peng
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/21529273705327885643

碩士 === 國立臺灣大學 === 毒理學研究所 === 86 === The thesis of this study is on the factors of different types of chemicals on the rat C6 Glioma cells -->focusing on these chemicals and the type of impact they have on the following relationship between cells: oxidation-reduction, copper content, transcription factor and apoptosis. Doxorubicin is commonly used for cancer treatment in the medical practice. It can induce superoxide. Treating C6 cells with Doxorubicin can also induce apoptosis. Combining with N-acetyl-cysteine the cytotoxicity shows no sign of decreasing. However, when in combination with H2O2, the H2O2 level within a cell increases and the cytotoxicity of Doxorubicin remain the same. Hence the conclusion is that apoptosis induced by Doxorubicin is not effected by superoxide. Further, a detected p53 increment i ated a correlation between the p53 and C6 cells apoptosis and DNA damage. Curcumin has been known of having the anti-oxidation and anti-apoptosis quality. A study result from this research shows that through apoptosis, Curcumin can induce C6 cells deterioration. An observed fact from the study show that Curcumin emits fluorescent light when excited. This emission interfere the analysis of Flow Cytometry, and therefore a more in-depth study is required for the mechanism behind Curcumin's induction of C6 apoptosis. PDTC and DETC are also able to induce the apoptosis of C6 cells. In particular, when comparing with astrocytes and other cell lines, C6 glioma is more sensitive to PDTC and DETC. When treated with BCDS, it can prevent toxicity. By the same token, BCDS can also defend itself from the combined toxicity of dithiocarbamates and copper. This can prove that toxicity induced by PDTC and DETC is in fact resulted from the entry of chelated copper into the cells. Also note that Doxorubicin is able to chelat pper. A result from atomic-absorption spectrophotometer shows that without adding copper, PDTC can increase the copper content within the cells and yet, Doxorubicin dose not have the same ablity. On the other hand, when copper is added, PDTC and Doxorubicin can both increase the copper content within the cells. In comparison with cytoxicity, it is observed that copper does not reinforce the toxicity of Doxorubicin but can reinforce the toxicity of PDTC. In addition, copper does not increase the p53 cont ent induced by Doxorubicin, and yet it indeed increase the p53 content induced by PDTC. Judging from the various results, copper in fact plays an important role in apoptosis, and its end result of Doxorubicin and PDTC chelation can be different as well. To sum up, C6 is more sensitive to the toxicity of PDTC and DETC, comparing with other cells. Doxorubicin can activate p53 through the damage it has on DNA and this process can eventually cause apoptosis. PDTC and DETC can chelate copper into cells. PDTC in union with copper can increase the p53 level and copper can induce apoptosis.