INITIAL METABOLISM OF GAMMA-HEXACHLOROCYCLOHEXANE (γ-HCH) BY RAT LIVER MICROSONES
スポンサーリンク
概要
- 論文の詳細を見る
γ-Hexachlorocycloexane (γ-HCH) was metabolized by dehydrochlorination, dehydrogenation and dechlorination in rat liver microsomes and these initial metabolites of γ-HCH were identified as γ-pentachlorocyclohexene (γ-PCCH), γ-hexachlorocyclohexene (γ-HCCH) and γ-tetrachlorocyclohexene (γ-TCCH) by gas chromatography-mass spectrometry (GC/MS). The dehydrochlorination and dehydrogenation were performed in incubation media containing NADPH and p, p'-tetramethyldiaminodiphenyl methane (TPD, 30 nmol) which is known to inhibit the degradation of initial metabolites formed during an aerobic incubation of γ-HCH with microsomes at 25℃. The dechlorination was found to proceed well under anaerobic conditions. The dehydrogenation was inhibited by SKF 525-A, CO, piperonyl butoxide, N_2 and the absence of NADPH, but not by cyanide. Additionally, pretreatment of rats with phenobarbital (PB), but not with 3-methylcholanthrene (3-MC), induced the dehydrogenation of γ-HCH. These results suggest that cytochrome P-450 is involved in this reaction.The cytochrome b_5 system may not be involved. The dehydrochlorination was inhibited by N_2,CO, piperonyl butoxide, KCN and the absence of NADPH, but not by SKF 525-A. This reaction was enhanced by pretreatment of rats with SKF 525-A, CoCl_2 and piperonyl butoxide. Pretreatment with PB and 3-MC did not show a significant effect on the dehydrochlorination activity. Thus, the results suggest that the dehydrochlorination could be catalyzed by a specific species of cytochrome P-450 and cytochrome b_5 system and/or other microsomal enzyme systems.
- 公益社団法人日本薬学会の論文
著者
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Yamamoto T
Showa Univ. Tokyo Jpn
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Yamamoto Toshinori
Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa University
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Yoshida Tomoko
Department Of Nuclear Engineering Nagoya University
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Yoshida Teiji
Department Of Physics Faculty Of Science Tohoku University
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YOSHIDA Takemi
School of Parmaceutical Sciences, Showa University
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YAMAMOTO TOSHINORI
Medical College of Oita
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EGASHIRA TORU
Medical College of Oita
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YAMANAKA YASUMITSU
Medical College of Oita
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KUROIWA YUKIO
School of Pharmaceutical Sciences, Showa University
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Yoshida Takahiko
Department Of Environmental Health Division Of Community And Environmental Health Tokai University S
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Yamanaka Yasumitsu
Department Of Pharmacology Oita Medical University
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Yoshida Takemi
School Of Pharmaceutical Sciences Showa University
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Yamanaka Y
Department Of Pharmacology Oita Medical University
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Yoshida Takemi
School Of Parmaceutical Sciences Showa University
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Kuroiwa Y
Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa University
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Yoshida Takemi
Pfizer Japan Inc. Drug Safety R&d Pfizer Global R&d
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Kuroiwa Yukio
School Of Pharmaceutical Sciences Showa University
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