| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
Epidemiological evidence indicates that regular consumption of the Allium genus is associated with a decrease of risk for stomach and intestine cancers in human. Some polysulfides from the Allium vegetables, such as garlic and onions, have been shown the chemoprotective effect in rodents. It has been suggested that this effect is due to their induction activity for phase II enzymes. In contrast, toxic effects have been reported in domestic and farm animals after consumption of garlic and onions, involving oxidative damage to erythrocytes and consequent hemolytic anemia. In the present study, we compared the ability of mono-, di-and trisulfides to generate ROS and induce GST activity in RL34 cells. We successfully demonstrated that trisulfides with thiols potently generated ROS by means of DCF fluorescence in RL34 cells. All sulfides without thiols and monosulfide with thiols did not generate any ROS. Upon incubation of plasmid DNA with trisulfides and thiols, the conversion of supercoiled DNA to its open circular form was detected in vitro. Under the same conditions, thiol-activated DNA cleavage was partially inhibited by the addition of radical scavengers, metal chelator or catalase. These data suggested that superoxide was generated through the thiol-polysulfide pathway. We also found that trisulfides showed the most potent induction activity of GST in RL34 cells. Therefore, redox stress could be effectively underwent by trisulfides with thiols inside the cells, and trisulfides may truly contribute to induce both cytotoxic and cancer-protective effects of Allimn vegetables.
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