2000 Fiscal Year Annual Research Report

環境汚染物質の生体内代謝と内分泌撹乱作用

Research Project

Project/Area Number	11557199
Research Institution	Hiroshima University School of Medicine
Principal Investigator	北村繁幸広島大学, 医学部, 助教授 (40136057)
Co-Investigator(Kenkyū-buntansha)	太田茂広島大学, 医学部, 教授 (60160503) 渡邊敦光広島大学, 原爆放射能医学研究所, 教授 (00034653) 有薗幸司熊本県立大学, 環境共生学部, 教授 (70128148) 杉原数美広島大学, 医学部, 教務員 (20271067) 吉原新一広島大学, 医学部, 助教授 (00037607)
Keywords	内分泌撹乱物質 / 内分泌撹乱前駆物質 / エストロゲン / 代謝的活性化 / 薬物代謝酵素 / トランス-スチルベン / ビフェニール / ビテロゲニン
Research Abstract	1。内分泌撹乱物質の代謝と活性内分泌撹乱物質のin vitro代謝と培養細胞を用いたエストロゲン活性について検討したところ、p,p'-DDTおよびo,p'-DDTの活性はともにチトクロームP450系による代謝の影響を受けなかったが、ビスフェノールAおよびノニルフェノールは本系によって、不活性化された。 2。内分泌撹乱前駆物質の環境中からの検出生体内で代謝されることによって、初めてエストロゲン活性を現わす内分泌撹乱前駆物質として、トランス-スチルベン、ジフェニール、ジフェニールメタン、ジベンチール、2、2-ジフェニールプロパン、カルコン、ベンジリデンアセトン、スチレンモノマー、ジフェニールアミン、ジフェニールスルフォンおよびピレンを見出した。 3。内分泌撹乱前駆物質の代謝的活性化何れの内分泌撹乱前駆物質もチトクロームP450系によって生成されるそれらの4位水酸化体がエストロゲン活性を示したことから、体内での芳香環の酸化反応が内分泌撹乱前駆物質の活性化に重要であること認めた。 4。内分泌撹乱物質の生殖毒性トランスースチルベンをマウスに投与した場合、生殖毒性を認めるには至らなかったが、その代謝物である4、4'-ジヒドロキシスチルベン投与で精巣毒性を認めた。 5。魚類におけるエストロゲン活性トランスースチルベンおよびジフェニールは雄キンギョの薬浴実験において、血中ビテロゲニンを産生させた。これらの物質のキンギョin vivoおよび肝ミクロゾームによる代謝物として4位水酸体を見出したことから、魚類においても内分泌撹乱前駆物質は体内で活性化されてエストロゲン活性を発現することを明らかにした。 6。内分泌撹乱物質の神経毒性 DDT類を始めとする幾つかの内分泌撹乱物質のラット小脳顆粒細胞に対する毒性を認めた。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] Shigeyuki Kitamura: "Reductive dechlorination of p,p'-DDT mediated by hemoproteins in hepatopancreas and blood of goldfish, Carassius auratus."Journal of Health Science. 45(4). 217-221 (1999)
[Publications] Shigeyuki Kitamura: "Reductive metabolism in vivo of trans-4-phenyl-3-buten-2-one in rats and dogs."Drug Metabolism and Disposition. 27(7). 767-769 (1999)
[Publications] Kazumi Sugihara: "Ah-receptor mediated induction of liver xanthine oxidase/xanthine dehydrogenase by 2,3,7,8-TCDD"Organohalogen compounds. 42. 425-428 (1999)
[Publications] Shigeyuki Kitamura: "Conversion of dieldrin to aldrin by intestinal bacteria in rats"Biological and Pharmaceutical Bulletin. 22(8). 880-882 (1999)
[Publications] Shigeyuki Kitamura: "Interconversion between fenthion and fenthion sulfoxide in goldfish, Carassius auratus."Journal of Health Science. 45(5). 266-270 (1999)
[Publications] Shigeyuki Kitamura: "Effect of fenthion on the level of vitellogenin in goldfish, Carassius auratus."Journal of Health Science. 45(5). 262-265 (1999)
[Publications] Shigeyuki Kitamura: "Pseudoenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene Mediated by Cytochrome P450"Carcinogenesis. 20(2). 347-350 (1999)
[Publications] Yuji Okamoto: "Microsomal Carbonyl Reductase Responsible for Reduction of 4-Phenyl-3-buten-2-one in Rats."IUBMB Life. 48(5). 543-547 (1999)
[Publications] Shigeyuki Kitamura: "Whole-body Metabolism of the Organophosphorus Pesticide, Fenthion, in Goldfish, Carassius Auratus."Comparative Biochemistry and Physiology. 126. 259-266 (2000)
[Publications] Shigeyuki Kitamura: "Nonenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene by Heme in the Presence of Hydroquinones"Journal of Health Science. 46(1). 66-69 (2000)
[Publications] Kazumi Sugihara: "Reduction of Hydroxamic Acids to the Corresponding Amides Catalyzed by Rabbit Blood."Xenobiotica. 30(5). 457-467 (2000)
[Publications] Shigeyuki Kitamura: "Reduction of Stilbene Oxide and Styrene Oxide to the Corresponding Alkenes by Intestinal Bacteria."Xenobiotica. 30(4). 359-369 (2000)
[Publications] Shigeyuki Kitamura: "Reductive Metabolism of Stilbene Oxide and Styrene Oxide to the Olefins in Rats"Biological and Pharmaceutical Bulletin. 23(2). 265-268 (2000)
[Publications] Kazumi Sugihara: "Induction of Liver Xanthine Dehydrogenase/Xanthine Oxidase by 2,3,7,8-TCDD and Cobalt Chloride."Organohalogen Compounds. 49. 247-250 (2000)
[Publications] Kazumi Sugihara: "Metabolic Activation of the Proestrogens trans-Stilbene and trans-Stilbene Oxide by Rat Liver Microsomes."Toxicology and Applied Pharmacology. 167. 46-54 (2000)
[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, and 2-Acetylaminofluorene in Fish."Bull.Environ.Contam.Toxicol.. 66(3). 371-378 (2001)
[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, 2-Aminofluorene and 2-Acetylaminofluorene in Rat and Dog and the Role of Intestinal Bacteria."Xenobiotica. (in press). (2001)
[Publications] Kazumi Sugihara: "Aryl Hydrocarbon Receptor-Mediated Induction of Xanthine Oxidase/Xanthine Dehydrogenase Activity by TCDD."Biochemical and Biophysical Research Communications. (in press). (2001)
[Publications] 北村繁幸: "新しい臨床検査:内分泌撹乱物質の検査"株式会社現代医療社(印刷中). (2001)

2000 Fiscal Year Annual Research Report

環境汚染物質の生体内代謝と内分泌撹乱作用

Principal Investigator

北村 繁幸 広島大学, 医学部, 助教授 (40136057)

Research Products

[Publications] Shigeyuki Kitamura: "Reductive dechlorination of p,p'-DDT mediated by hemoproteins in hepatopancreas and blood of goldfish, Carassius auratus."Journal of Health Science. 45(4). 217-221 (1999)

[Publications] Shigeyuki Kitamura: "Reductive metabolism in vivo of trans-4-phenyl-3-buten-2-one in rats and dogs."Drug Metabolism and Disposition. 27(7). 767-769 (1999)

[Publications] Kazumi Sugihara: "Ah-receptor mediated induction of liver xanthine oxidase/xanthine dehydrogenase by 2,3,7,8-TCDD"Organohalogen compounds. 42. 425-428 (1999)

[Publications] Shigeyuki Kitamura: "Conversion of dieldrin to aldrin by intestinal bacteria in rats"Biological and Pharmaceutical Bulletin. 22(8). 880-882 (1999)

[Publications] Shigeyuki Kitamura: "Interconversion between fenthion and fenthion sulfoxide in goldfish, Carassius auratus."Journal of Health Science. 45(5). 266-270 (1999)

[Publications] Shigeyuki Kitamura: "Effect of fenthion on the level of vitellogenin in goldfish, Carassius auratus."Journal of Health Science. 45(5). 262-265 (1999)

[Publications] Shigeyuki Kitamura: "Pseudoenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene Mediated by Cytochrome P450"Carcinogenesis. 20(2). 347-350 (1999)

[Publications] Yuji Okamoto: "Microsomal Carbonyl Reductase Responsible for Reduction of 4-Phenyl-3-buten-2-one in Rats."IUBMB Life. 48(5). 543-547 (1999)

[Publications] Shigeyuki Kitamura: "Whole-body Metabolism of the Organophosphorus Pesticide, Fenthion, in Goldfish, Carassius Auratus."Comparative Biochemistry and Physiology. 126. 259-266 (2000)

[Publications] Shigeyuki Kitamura: "Nonenzymatic Reduction of N-Hydroxy-2-acetylaminofluorene to 2-Acetylaminofluorene by Heme in the Presence of Hydroquinones"Journal of Health Science. 46(1). 66-69 (2000)

[Publications] Kazumi Sugihara: "Reduction of Hydroxamic Acids to the Corresponding Amides Catalyzed by Rabbit Blood."Xenobiotica. 30(5). 457-467 (2000)

[Publications] Shigeyuki Kitamura: "Reduction of Stilbene Oxide and Styrene Oxide to the Corresponding Alkenes by Intestinal Bacteria."Xenobiotica. 30(4). 359-369 (2000)

[Publications] Shigeyuki Kitamura: "Reductive Metabolism of Stilbene Oxide and Styrene Oxide to the Olefins in Rats"Biological and Pharmaceutical Bulletin. 23(2). 265-268 (2000)

[Publications] Kazumi Sugihara: "Induction of Liver Xanthine Dehydrogenase/Xanthine Oxidase by 2,3,7,8-TCDD and Cobalt Chloride."Organohalogen Compounds. 49. 247-250 (2000)

[Publications] Kazumi Sugihara: "Metabolic Activation of the Proestrogens trans-Stilbene and trans-Stilbene Oxide by Rat Liver Microsomes."Toxicology and Applied Pharmacology. 167. 46-54 (2000)

[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, and 2-Acetylaminofluorene in Fish."Bull.Environ.Contam.Toxicol.. 66(3). 371-378 (2001)

[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, 2-Aminofluorene and 2-Acetylaminofluorene in Rat and Dog and the Role of Intestinal Bacteria."Xenobiotica. (in press). (2001)

[Publications] Kazumi Sugihara: "Aryl Hydrocarbon Receptor-Mediated Induction of Xanthine Oxidase/Xanthine Dehydrogenase Activity by TCDD."Biochemical and Biophysical Research Communications. (in press). (2001)

[Publications] 北村繁幸: "新しい臨床検査:内分泌撹乱物質の検査"株式会社 現代医療社(印刷中). (2001)

北村繁幸広島大学, 医学部, 助教授 (40136057)

[Publications] 北村繁幸: "新しい臨床検査:内分泌撹乱物質の検査"株式会社現代医療社(印刷中). (2001)