Relationship between debromination reaction of halogen compounds and organ toxicity
Project/Area Number |
60570131
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Pathological medical chemistry
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Research Institution | Osaka University |
Principal Investigator |
SUGIYAMA Toshihiro (1986) Associate Professor of Biochemistry, 医学部, 講師 (00127242)
山野 俊雄 (1985) 大阪大学, 医学部, 教授
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Project Period (FY) |
1985 – 1986
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Project Status |
Completed (Fiscal Year 1986)
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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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Keywords | debromination / cytochrome P-450 / cytochrome <b_5> / halothane / radical / dibromoethane / ジブロムエタン |
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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Report
(1 results)
Research Products
(11 results)
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[Publications] Tamura, S., Sugiyama, T., Minami, Y., Tarui, S., Okamoto, M., and Yamano, T.: "Cytochrome P-450-dependent debromination of 1,2-dibromoethane and halothane in a reconstituted enzyme system" J. Toxicol. Sci.10. 251 (1985)
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[Publications] Tamura, S., Sugiyama, T., Minami, Y., Tarui, S., Okamoto, M., and Yamano, T.: "Analysis of debromination of 1,2-dibromoethane by cytochrome P-450-linked hydroxylation systems as observed by bromide electrode" J. Biochem.99. 163-171 (1986)
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[Publications] Kitagawa, Y., Okamoto, M., Sugiyama, T., Kitamura, H., Nakahara, K., Kawashima, Y., and Yamano, T.: "3-Methylcholanthrene-induced ethoxyresorufin O-deethylase activity in alveolar type <II> cells of rabbit lung" Arch. Toxicol.59. 1-3 (1986)
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[Publications] Katagiri, M., Murakami, H., Yabusaki, Y., Sugiyama, T., Okamoto, M., Yamano, T., and Ohkawa, H.: "Molecular cloning and sequence analysis of full-length cDNA for rabbit liver NADPH-cytochrome P-450 reductase m RNA" J. Biochem.100. 945-954 (1986)
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