1999 Fiscal Year Annual Research Report

PCBの薬物代謝酵素誘導効果発現における3-メチルスルホン代謝物の役割とその毒性

Research Project

Project/Area Number	09680531
Research Institution	University of Shizuoka
Principal Investigator	加藤善久静岡県立大学, 薬学部, 講師 (90161132)
Keywords	PCB / メチルスルホン代謝物 / 甲状腺ホルモン / UDP-glucuronosyltransferase / 薬物代謝酵素 / 酵素誘導 / δ-アミノレブリン酸合成酵素 / ラット
Research Abstract	本研究は、PCBの薬物代謝酵素誘導効果発現における3-メチルスルホン(3-MeSO_2)代謝物の役割を明確にし、さらに、MeSO_2-PCBの毒性を明らかにする目的で行った。健常人の母乳、肝臓及び脂肪組織、多数の野生ホ乳動物の組織中に比較的高濃度に蓄積が認められる9種類のMeSO_2-PCBs、すなわち、3-MeSO_2-CB49、3-MeSO_2-CB70、3-MeSO_2-CB87、3-MeSO_2-CB101、4-MeSO_2-CB101、3-MeSO_2-CB132、3-MeSO_2-CB141、3-MeSO_2-CB149及び4-MeSO_2-CB149(MeSO_2誘導体は、PCBのIUPAC numberにMeSO_2基を付して示す)を合成した。今回、CB101(2,2',4,5,5'-pentachlorobiphenyl)のMeSO_2代謝物の生成にはその前駆体の胆汁中への排泄が必須であること、腸内細菌C-S lyaseによる代謝過程が含まれることを明らかにした。それに加えて、母PCBの薬物代謝酵素及びヘム生合成律速酵素、δ-アミノレブリン酸合成酵素の誘導効果はその3-MeSO_2代謝物、3-MeSO_2-CB101が作用本体であることをつきとめた。また、9種類の3-及び4-MeSO_2-PCBsは、ラット血清中甲状腺ホルモン(サイロキシン(T_4)、トリヨードサイロニン)量を低下させ、甲状腺刺激ホルモン量を上昇させる作用のあることを見い出し、これらのMeSO_2-PCBsが甲状腺ホルモン攪乱化学物質であることを明らかにした。さらに、これらの内8種類のMeSO_2-PCBsの血清中T_4濃度の低下は、それらが肝臓のUGT1A1及びUGT1A6を誘導し、T_4の代謝を亢進することにより引き起こされることを明らかにした。

Research Products

(9 results)

All Other

All Publications (9 results)

[Publications] Yoshihisa Kato: "Reduction of thyroid hormone levels by methylsulfonyl metabolites of tetra-and pentachlorinated biphenyls in male Sprague-Dawley rats"Toxicol.Sci.. 48. 51-54 (1999)
[Publications] Koichi Haraguchi: "Tissue distribution of methylsulfonyl metabolites derived from 2,2',4,5,5'-penta-and 2,2'3,4',5',6-hexachlorobiphenyls in rats"Arch,Environ.Contam.Toxicol.. 37. 135-142 (1999)
[Publications] 原口浩一: "3,3'4,4',5-penta-および2,2',3,3',4,4'-Hexachlorobiphenylの代謝研究"福岡医学雑誌. 90. 210-219 (1999)
[Publications] Yoshihisa Kato: "The role of 3-methylsulfony1-2,2',4',5,5'-pentachlorobiphenyl,a metabolite of 2,2',4,5,5'-pentachlorobiphenyl,in the induction of hepatic microsomal drug-metabolizing enzymes by 2,2',4,5,5'-pentachlorobiphenyl in rats"Environ.Toxicol.Pharmacol.. 8. 39-47 (1999)
[Publications] Tomoo Shibahara: "Reduction of thyroid hormone levels by methylsulfonyl metabolites of PCB congeners in rats"J.Health Sci.. 45. P-4 (1999)
[Publications] Yoshihisa Kato: "Contribution of the 3-methylsulfonyl metabolite of 2,2',4,5,5'-pentachlorobiphenyl to heme metabolic enzyme induction by the parent compound in rat liver"J.Health Sci.. 45. P-21 (1999)
[Publications] Yoshihisa Kato: "Induction of hepatic microsomal UDP-glucuronosyltransferase by methyl-sulfonyl metabolites of polychlorinated biphenyl congeners in rats"Organohalogen Compounds. 42. 337-340 (1999)
[Publications] Yoshihisa Kato: "Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-,penta- and hexachlorinated biphenyls in male Sprague-Dawley rats"Chemosphere. 40. 1233-1240 (2000)
[Publications] Yoshihisa Kato: "The induction of hepatic microsomal UDP-glucuronosyltransferase by the methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats"Chem.-Biol.Interact.. 125. 107-115 (2000)

1999 Fiscal Year Annual Research Report

PCBの薬物代謝酵素誘導効果発現における3-メチルスルホン代謝物の役割とその毒性

Principal Investigator

加藤 善久 静岡県立大学, 薬学部, 講師 (90161132)

Research Products

[Publications] Yoshihisa Kato: "Reduction of thyroid hormone levels by methylsulfonyl metabolites of tetra-and pentachlorinated biphenyls in male Sprague-Dawley rats"Toxicol.Sci.. 48. 51-54 (1999)

[Publications] Koichi Haraguchi: "Tissue distribution of methylsulfonyl metabolites derived from 2,2',4,5,5'-penta-and 2,2'3,4',5',6-hexachlorobiphenyls in rats"Arch,Environ.Contam.Toxicol.. 37. 135-142 (1999)

[Publications] 原口浩一: "3,3'4,4',5-penta-および2,2',3,3',4,4'-Hexachlorobiphenylの代謝研究"福岡医学雑誌. 90. 210-219 (1999)

[Publications] Yoshihisa Kato: "The role of 3-methylsulfony1-2,2',4',5,5'-pentachlorobiphenyl,a metabolite of 2,2',4,5,5'-pentachlorobiphenyl,in the induction of hepatic microsomal drug-metabolizing enzymes by 2,2',4,5,5'-pentachlorobiphenyl in rats"Environ.Toxicol.Pharmacol.. 8. 39-47 (1999)

[Publications] Tomoo Shibahara: "Reduction of thyroid hormone levels by methylsulfonyl metabolites of PCB congeners in rats"J.Health Sci.. 45. P-4 (1999)

[Publications] Yoshihisa Kato: "Contribution of the 3-methylsulfonyl metabolite of 2,2',4,5,5'-pentachlorobiphenyl to heme metabolic enzyme induction by the parent compound in rat liver"J.Health Sci.. 45. P-21 (1999)

[Publications] Yoshihisa Kato: "Induction of hepatic microsomal UDP-glucuronosyltransferase by methyl-sulfonyl metabolites of polychlorinated biphenyl congeners in rats"Organohalogen Compounds. 42. 337-340 (1999)

[Publications] Yoshihisa Kato: "Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-,penta- and hexachlorinated biphenyls in male Sprague-Dawley rats"Chemosphere. 40. 1233-1240 (2000)

[Publications] Yoshihisa Kato: "The induction of hepatic microsomal UDP-glucuronosyltransferase by the methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats"Chem.-Biol.Interact.. 125. 107-115 (2000)

加藤善久静岡県立大学, 薬学部, 講師 (90161132)