Objective: The aim of this study was to determine the anti-oxidative activity of a new chemopreventive agent--dehydroepiandrosterone (DHEA), and the mechanisms of action by which DHEA protect the thymocytes and DNA from oxidative damage. Methods: Agarose gel electrophoresis, flow cytometry, single cel! gel electrophoresis, chemiluminescence assay, triazolyl blue tetrazolumbromide (MTT) colorimetry, and three dimensional collagen gel assay were used. Results: In agarose gel electrophoresis, 10 nmol/L DHEA blocked the typical DNA degradation (DNA Ladder) induced by H2O2. DHEA 2. 5 nmol/L and 10 nmol/L both significantly decreased the percentage of characteristic apoptotic DNA peak in flow cytometry. In single cell gel electrophoresis assay of thymocytes, the results revealed that DHEA could block DNA damage induced by H2O2. Small strand breaks of DNA like comet were seldom observed, and the cells treated with 10 nmol/L DHEA more like dots. Using chemiluminescence methods, 25 nmol/L DHEA exhibited its potential of scavenging free radicals. The results also suggested that DHEA had the capacity of increasing the migration of lymphocytes damaged by H2O2 in three dimensional collagen gel assay. The adhesions of lymphocytes exposed to DHEA (10 nmol/L, 1 nmol/L) for 4 hours were significantly increased by 15%, 14% respectively. Conclusions: Protection of thymocytes and DNA from oxidative damage and inhibitory effect on apoptosis induced by H2O2 might be closely related to its mechanisms of anti-mutation and immune enhancing activity of DHEA.
Yang S, Han R. Antioxidation activity of DHEA and its mechanisms. Chin J Cancer. 2001; 20(12):1349-1354.
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