2002 Fiscal Year Annual Research Report

内分泌撹乱化学物質の生体内における代謝的活性化

Research Project

Project/Area Number	13672343
Research Institution	HIROSHIMA UNIVERSITY
Principal Investigator	北村繁幸広島大学, 大学院・医歯薬学総合研究科, 助教授 (40136057)
Co-Investigator(Kenkyū-buntansha)	太田茂広島大学, 大学院・医歯薬学総合研究科, 教授 (60160503) 渡邊敦光広島大学, 原爆放射線医科学研究所, 教授 (00034653) 藤本成明広島大学, 原爆放射線医科学研究所, 助教授 (40243612) 杉原数美広島大学, 医学部, 教務員 (20271067)
Keywords	エストロゲン / 抗アンドロゲン / 甲状腺ホルモン様物質 / ビテロゲニン / 内分泌撹乱物質 / 薬物代謝酵素 / 代謝的活性化 / 環境汚染物質
Research Abstract	1.エストロゲン前駆物質の代謝的活性化環境中より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、ジフェニール、スチルベン、カルコン、ニトロフローレン、ペリメトリン、スチレンオリゴマーおよびある種のフタール酸エステルを検出し、それらの動物肝での活性代謝物を同定するとともに、それらの代謝に関与する酵素系を明らかにした。 2.抗アンドロゲン物質のスクリーニングと代謝による活性変動ビスフェノールA類、フローレン類、ピレン類、DDT類およびある種の有機燐系農薬に抗アンドロゲン作用があることを見出した。また、フェンチオンを肝ミクロゾームと反応させると、活性を消失したが、その代謝物であるフェンチオンスルホキシドは肝可溶性画分によって代謝されることによって、活性が発現されることを見いだした。 3.甲状腺ホルモン撹乱物質の環境中よりの検出難燃材テトラブロモビスフェノールAはそれ自身で、甲状腺ホルモン作用を示すが、PCBはその代謝物である4位水酸化PCBによって作用が発現された。 4.内分泌撹乱物質の生殖毒性スチルベンあるいはニトロフローレンをマウスに投与した場合、子宮重量の増加を認め、生体内においてもこれらの物質が代謝的に活性化されていることを認めた。またフェンチオンを投与するとテストステロンによる前立腺の肥大を抑制することから、in vivoレベルでも抗アンドロゲン作用が発現されることを示した。 5.魚類における代謝的活性化オスキンギョをエストロゲン前駆物質スチルベン、ビフェニール、ニトロフローレンおよびペリメトリンの溶液に薬浴させることで、ビテロゲニンが産生されることから、キンギョ体内でこれらの内分泌撹乱前駆物質が代謝されることによって、内分泌撹乱作用を示すことを認めた。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] Koji Takekawa: "Enzymatic and Nonenzymatic Reduction of Brucine N-Oxide by Aldehyde Oxidase and Catalase"Xenobiotica. 31(11). 769-782 (2001)
[Publications] Shigeyuki Kitamura: "Extremely High Drug-Reductase Activity Based on Aldehyde Oxidase in Monkey Liver"Biological and Pharmaceutical Bulletin. 24(7). 856-859 (2001)
[Publications] Kazumi Sugihara: "Aryl Hydrocarbon Receptor (AhR)-Mediated Induction of Xanthine Oxidase/Xanthine Dehydrogenase Activity by 2,3,7,8-Tetrachlorodibenzo-p-dioxin"Biochemical and Biophysical Research Communications. 281(5). 1093-1099 (2001)
[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, and 2-Acetylaminofluorene in Fish"Bulletin of Environmental Contamination and Toxicology. 31(1). 371-378 (2001)
[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, 2-Aminofluorene and 2-Acetylaminofluor in Rat and Dog and the Role of Intestinal Bacteria"Xenobiotica. 31(1). 33-49 (2001)
[Publications] Koji Takekawa: "Nonenzymatic Reduction of Aliphatic Tertiary Amine N-Oxides Mediated by the Hame Moiety of Cytochrome P450"Xenobiotica. 31(1). 11-23 (2001)
[Publications] Osamu Ueda: "Deacylation of N-Arylformides and N-Arylacetamides by Formamidase in Rat Liver"Drug Metabolism and Disposition. 31(12). 1297-1299 (2002)
[Publications] Shigeyuki Kitamura: "Thyroid Hormonal Activity of the Flame Retardants Tetrabromobisphenol A and Tetrachlorobisphenol A"Biochemical and Biophysical Research Communications. 293(1). 554-559 (2002)
[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, by Liver Preparations of Sea Bream, Pagrus major"Xenobiotica. 32(8). 667-682 (2002)
[Publications] Shigeyuki Kitamura: "Reductive Metabolism of α,β-Ketoalkyne, 4-Phenyl-3-butyn-2-one, by Rat Liver Preparations"Drug Metabolism and Disposition. 30(4). 414-420 (2002)
[Publications] Seigo Sanoh: "Cytochrome P450 1A1/2 Mediated Metabolism of frans-Stilbene in Rats and Humans"Biological and Pharmaceutical Bulletin. 25(3). 397-400 (2002)
[Publications] Shigeyuki Kitamura: "Reductive Metabolism of p, p'-DDT and o, p'-DDT by Rat Liver Cytochrome P450"Drug Metabolism and Disposition. 30(2). 113-118 (2002)
[Publications] Kazumi Sugihara: "Ah-receptor-mediated Induction of Drug-metabolizing Enzymes by Indirubin and Indigo"Organohalogen Compounds. 59. 453-456 (2002)
[Publications] Shigeyuki Kitamura: "In Vitro Metabolism of Fenthion and Fenthion Sulfoxide by Liver Preparations of Sea Bream. Goldfish and Rats"Drug Metabolism and Disposition. 31(2). 179-186 (2003)
[Publications] Takashi Fujimoto: "Estrogenic Activity of an Environmental Pollutant, 2-Nitrofluorene, after Metabolic Activation by Rat Liver Microsomes"Biochemical and Biophysical Research Communications. (In press).
[Publications] Osamu Ueda: "Xanthine Oxidase-Catalyzed Metabolism of 2-Nitrofluorene, a Carcinogenic Air Pollutant, in Rat Skin"Drug Metabolism and Disposition. (In press).
[Publications] Shigeyuki Kitamura: "Estrogenic Activity of Styrene Oligomers after Metabolic Activation by Rat Liver Microsomes"Environmental Health Perspectives. 111(3). 329-334 (2003)
[Publications] Shigeyuki Kitamura: "Antiandrogenic Activity of the Organophosphorus Pesticide Fenthion and Related Compounds, and the Effect of Metabolism"Environmental Health Perspectives. (In press).
[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. 6 (2001)

2002 Fiscal Year Annual Research Report

内分泌撹乱化学物質の生体内における代謝的活性化

Principal Investigator

北村 繁幸 広島大学, 大学院・医歯薬学総合研究科, 助教授 (40136057)

Research Products

[Publications] Koji Takekawa: "Enzymatic and Nonenzymatic Reduction of Brucine N-Oxide by Aldehyde Oxidase and Catalase"Xenobiotica. 31(11). 769-782 (2001)

[Publications] Shigeyuki Kitamura: "Extremely High Drug-Reductase Activity Based on Aldehyde Oxidase in Monkey Liver"Biological and Pharmaceutical Bulletin. 24(7). 856-859 (2001)

[Publications] Kazumi Sugihara: "Aryl Hydrocarbon Receptor (AhR)-Mediated Induction of Xanthine Oxidase/Xanthine Dehydrogenase Activity by 2,3,7,8-Tetrachlorodibenzo-p-dioxin"Biochemical and Biophysical Research Communications. 281(5). 1093-1099 (2001)

[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, and 2-Acetylaminofluorene in Fish"Bulletin of Environmental Contamination and Toxicology. 31(1). 371-378 (2001)

[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, 2-Aminofluorene and 2-Acetylaminofluor in Rat and Dog and the Role of Intestinal Bacteria"Xenobiotica. 31(1). 33-49 (2001)

[Publications] Koji Takekawa: "Nonenzymatic Reduction of Aliphatic Tertiary Amine N-Oxides Mediated by the Hame Moiety of Cytochrome P450"Xenobiotica. 31(1). 11-23 (2001)

[Publications] Osamu Ueda: "Deacylation of N-Arylformides and N-Arylacetamides by Formamidase in Rat Liver"Drug Metabolism and Disposition. 31(12). 1297-1299 (2002)

[Publications] Shigeyuki Kitamura: "Thyroid Hormonal Activity of the Flame Retardants Tetrabromobisphenol A and Tetrachlorobisphenol A"Biochemical and Biophysical Research Communications. 293(1). 554-559 (2002)

[Publications] Osamu Ueda: "Metabolism of 2-Nitrofluorene, an Environmental Pollutant, by Liver Preparations of Sea Bream, Pagrus major"Xenobiotica. 32(8). 667-682 (2002)

[Publications] Shigeyuki Kitamura: "Reductive Metabolism of α,β-Ketoalkyne, 4-Phenyl-3-butyn-2-one, by Rat Liver Preparations"Drug Metabolism and Disposition. 30(4). 414-420 (2002)

[Publications] Seigo Sanoh: "Cytochrome P450 1A1/2 Mediated Metabolism of frans-Stilbene in Rats and Humans"Biological and Pharmaceutical Bulletin. 25(3). 397-400 (2002)

[Publications] Shigeyuki Kitamura: "Reductive Metabolism of p, p'-DDT and o, p'-DDT by Rat Liver Cytochrome P450"Drug Metabolism and Disposition. 30(2). 113-118 (2002)

[Publications] Kazumi Sugihara: "Ah-receptor-mediated Induction of Drug-metabolizing Enzymes by Indirubin and Indigo"Organohalogen Compounds. 59. 453-456 (2002)

[Publications] Shigeyuki Kitamura: "In Vitro Metabolism of Fenthion and Fenthion Sulfoxide by Liver Preparations of Sea Bream. Goldfish and Rats"Drug Metabolism and Disposition. 31(2). 179-186 (2003)

[Publications] Takashi Fujimoto: "Estrogenic Activity of an Environmental Pollutant, 2-Nitrofluorene, after Metabolic Activation by Rat Liver Microsomes"Biochemical and Biophysical Research Communications. (In press).

[Publications] Osamu Ueda: "Xanthine Oxidase-Catalyzed Metabolism of 2-Nitrofluorene, a Carcinogenic Air Pollutant, in Rat Skin"Drug Metabolism and Disposition. (In press).

[Publications] Shigeyuki Kitamura: "Estrogenic Activity of Styrene Oligomers after Metabolic Activation by Rat Liver Microsomes"Environmental Health Perspectives. 111(3). 329-334 (2003)

[Publications] Shigeyuki Kitamura: "Antiandrogenic Activity of the Organophosphorus Pesticide Fenthion and Related Compounds, and the Effect of Metabolism"Environmental Health Perspectives. (In press).

[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. 6 (2001)

北村繁幸広島大学, 大学院・医歯薬学総合研究科, 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. 6 (2001)