| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1985: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Polyhalogenated alkanes are known to undergo anaerobic dehalogenation reaction to radical intermediates which induce liver injury. Recently it was revealed that cytochrome <b_5> (cyt.b5) reduces radical intermediates, indicating that cyt. <b_5> may participate in preventing cytotoxicities of polyhalogenated alkanes. To clarify the effect of cyt. <b_5> on the dehalogenation reaction, debrominations of halothane and 1,2-dibromoethane(DBE) were investigated in a reconstituted system containing phenobarbital-inducible P-450, NADPH-P-450 reductase, phospholipids, and NADPH under aerobic and anaerobic conditions. Liberated bromide ion was detected by bromide electrode. Under aerobic conditions, cyt. <b_5> enhanced the hydroxylations of halothane and DBE followed by <alpha> -elimination of bromide. A radical signal was detected by ESR only under anaerobic conditions. Under anaerobic conditions, halothane and DBE are known to undergo one electron reduction followed by <alpha> -elimination of bromide to form radical intermediates, and subsequently <beta> -elimination of halogens occurs when second electron is supplied. Cyt. <b_5> stimulated the anaerobic debromination rate of DBE, but did not affect the debromination of halothane possessing no bromine at <beta> -position. Thus, cyt. <b_5> seems to stimulate <beta> -elimination of halogens by supply of second electron, presumably resulting in the decrease of radical intermediates.
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