| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
It has been reported that radicals play some role in the induction of apoptosis by irradiation or TNFa. However, the body has scavengers of these radicals. In the present study, we attempted to investigate the effect of inhibition of these scavengers, particularly of cytoplasmic Cu, Zn-SOD that scavenge oxygen radicals, and the induction of apoptosis. Apoptosis was confirmed by the formation of an apoptosis body observed by light microscopy and fragmentation of DNA detected by agarose gel electrophoresis. Treatment of DDC caused a significant decrease in SOD activity. As the SOD activity decreased, the appearance of an apoptosis body increased in frequency. Pretreatment of NAC decreased induction of apoptosis by DDC.The above results suggested that elevation of intracytoplasmic oxygen radicals relative to decrease in the activity of Cu, Zn-SOD may lead to the induction of apoptosis.
Some malignant tumors are resistant to TNF-alpha or several antineoplastic agents which exert antitumoral effects mediated by the radicals. One predicted reason for this resistance is induction of an mitochondrial enzyme, Mn-SOD,which scavenges O_2 radicals by TNF-alpha. We investigated whether or not inhibition of this induction recovers the antitumoral effects of TNF-alpha. In the cell strain cultivated in a medium containing TNF-alpha, there were no dead cells. Addition of TNF-alpha significantly increased both the concentration and activity of Mn-SOD,which indicated the induction of Mn-SOD by TNF-alpha in the cell strain. This induction was inhibited by the addition of inhibitor. Further addition of TNF-alpha after the addition of inhibitor caused cell death in 50.3% of the cells.
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