2000 Fiscal Year Annual Research Report

核磁気共鳴装置による家畜生殖遺伝毒性の構造生物学的評価法

Research Project

Project/Area Number	09356008
Research Institution	KYOTO UNIVERSITY
Principal Investigator	宮本元京都大学, 農学研究科, 教授 (00026618)
Co-Investigator(Kenkyū-buntansha)	佐藤英明東北大学, 農学研究科, 教授 (80093243) 丹羽晧二岡山大学, 農学部, 教授 (40089115) 眞鍋昇京都大学, 農学研究科, 助教授 (80243070) 葛西孫三郎高知大学, 農学部, 教授 (60152617) 小倉淳郎国立感染症研究所, 獣医科学部, 室長 (20194524)
Keywords	生体核磁気共鳴装置 / 外因性内分泌撹乱物質 / 環境汚染物質 / DNAアルキル化障害 / ステロイドホルモン受容体 / 共焦点走査型レーザー顕微鏡 / 生体核磁気共鳴画像解析 / 生殖遺伝毒性
Research Abstract	が農学研究の新たな目標に、従来からの食料の安定供給技術のみならず、人類の生存にとって必須の環境を維持しながら食料の安全性を的確に評価して健康な生活を保証する技術を創出することが加わった。近代の科学技術は、人々を飢えや疾病から救うために様々な化合物を創り出してきたが、これらが環境中に拡散して毒物として人類の生存を脅かしつつある。環境汚染物質は家畜体内で濃縮し、食料としてヒト体内に取り込まれるが、これらよる生殖遺伝毒性の適切な評価方法が未だ開発されていない。本研究の目的は、生体や生細胞を用い、生体核磁気共鳴画像解析装置や共焦点走査型レーザー顕微鏡等の最先端機器を駆使して環境汚染物質による家畜生殖遺伝毒性の評価法を新たに開発・確立することである。 (1)In vivo生殖遺伝毒性検出評価法の確立:実験動物を用いた基盤研究の成果を実証レベルに展開すべく、家畜の生殖腺、着床胚などの1Hや31Pシグナルを部位特異的にリアルタイムに検出できる最適測定条件を決定し、遺伝子情報障害の3次元的定量解析法の基盤を固めた。特に、DNAの3次元構造の安定性を阻害するDNAアルキル化障害の観測のためにアルキル化DNAシグナルの解析、およびDNAのメチル化による転写制御系の分子レベルでの異常を観測するためのメチル化チミジン特異的シグナルの検出と解析法の開発することができ、ビスフェノールAなどの安全性評価を進めた。 (2)In vitro評価法の確立:家畜の培養卵子や初期胚を培養系にて維持し、in vivoと同様の生理特性の解析を完成させ、実際に環境汚染物質を添加して、その影響を評価する。特に、細胞内におけるシグナル伝達系の攪乱、すなわち2次メッセンジャーの細胞内動態の解析ならびに脂溶性シグナル伝達物質の細胞内受容体mRNAの発生ステージ特異的発現と局在の3次元解析に注力し、構造生物学的評価法の基盤となる研究を進めることができた。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Noboru Manabe,Miki Sugimoto,Maki Morita,Hajime Miyamoto et al.: "A novel in vivo 31P-nuclear magnetic resonance technique for assessment of teratogenicity induced by environmental endocrine disrupters in mice."Japanese Journal of Clinical Medicine. 58・2. 108-111 (2000)
[Publications] Noboru Manabe,Miki Sugimoto,Maki Morita,Hajime Miyamoto et al.: "In vivo noninvasive nuclear magnetic resonance technique for assessment of teratogenicity induced by environmental pollutants."Environment Measurement and Chemical Analysis. 27・1. 60-66 (2000)
[Publications] Noboru Manabe,Yasuyoshi Azuma,Hajime Miyamoto et al.: "Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism and blood flow in dietary hypoferric anemic mice."British Journal of Nutrition. 83・2. 197-204 (2000)
[Publications] Noboru Manabe,Akira Myoumoto,Chiemi Tajima,Hajime Miyamoto et al.: "Immunochemical characteristics of a novel cell death receptor and a decoy receptor on granulosa cells of porcine ovarian follicles."Cytotechnology. 33・2. 189-201 (2000)
[Publications] Mizuho Nakayama,Noboru Manabe,Hajime Miyamoto et al.: "Species specific differences in apoptotic cell localization in granulosa and theca interna cells during follicular atresia in porcine and bovine ovaries."Journal of Reproduction and Development. 46・2. 147-156 (2000)
[Publications] Susumu Nishihara,Noboru Manabe,Hajime Miyamoto et al.: "Changes in cell adhesion molecules during follicular atresia in porcine ovaries."Journal of Reproduction and Development. 46・3. 325-334 (2000)
[Publications] Mizuho Nakayama,Noboru Manabe,Hajime Miyamoto et al.: "Changes in localization of type I, III and IV collagens and their mRNA expression during follicular atresia in bovine and porcine ovaries."Journal of Reproduction and Development. 47・1. 27-36 (2001)
[Publications] Kozue Uchio,Noboru Manabe,Kotaro Tamura,Matoto Miyamoto et al.: "Decreased matrix metalloproteinase activity in the kidneys of hereditary nephrotic mice (ICGN strain)."Nephron. 86・1. 145-141 (2000)
[Publications] Kotaro Tamura,Noboru Manabe,Kozue Uchio,Makoto Miyamoto et al.: "Characteristic changes in carbohydrate profile in the kidneys of hereditary nephrotic mice (ICGN strain)."The Journal of Veterinary Medical Science. 52・2. 379-390 (2000)
[Publications] Noboru Manabe,Akiko Kinoshita,,Kozue Yamada-Uchio et al.: "Changes in quantitative profile of extracellular matrix components in the kidneys of rats with adriamycin-induced nephropathy."The Journal of Veterinary Medical Science. 53・1. 125-133 (2001)
[Publications] Miki Sugimoto,Noboru Manabe,Hajime Miyamoto.: "Future functional-morphological studies in embryology."Journal of Reproduction and Development. 46・1. 71-77 (2000)
[Publications] Noboru Manabe,Hajime Miyamoto et al.: "Immunohistochemical quantification of fast-myosin in upper hind limb muscles of the pig."Animal Science Journal. 72・2. 154-163 (2000)
[Publications] Miki Sugimoto,Noboru Manabe,Hajime Miyamoto.: "Development of infantile rat ovaries autotransplanted after cryopreservation by vitrification."Theriogenology. 53・11. 1093-1103 (2000)
[Publications] Noboru Manabe,Akira Myoumoto,Chiemi Tajima,Hajime Miyamoto et al.: "A novel cell death receptor and a decoy receptor on granulosa cells of porcine ovarian follicles."Tohoku University Press, Sendai, Japan.. 357 (2000)

2000 Fiscal Year Annual Research Report

核磁気共鳴装置による家畜生殖遺伝毒性の構造生物学的評価法

Principal Investigator

宮本 元 京都大学, 農学研究科, 教授 (00026618)

Research Products

[Publications] Noboru Manabe,Miki Sugimoto,Maki Morita,Hajime Miyamoto et al.: "A novel in vivo 31P-nuclear magnetic resonance technique for assessment of teratogenicity induced by environmental endocrine disrupters in mice."Japanese Journal of Clinical Medicine. 58・2. 108-111 (2000)

[Publications] Noboru Manabe,Miki Sugimoto,Maki Morita,Hajime Miyamoto et al.: "In vivo noninvasive nuclear magnetic resonance technique for assessment of teratogenicity induced by environmental pollutants."Environment Measurement and Chemical Analysis. 27・1. 60-66 (2000)

[Publications] Noboru Manabe,Yasuyoshi Azuma,Hajime Miyamoto et al.: "Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism and blood flow in dietary hypoferric anemic mice."British Journal of Nutrition. 83・2. 197-204 (2000)

[Publications] Noboru Manabe,Akira Myoumoto,Chiemi Tajima,Hajime Miyamoto et al.: "Immunochemical characteristics of a novel cell death receptor and a decoy receptor on granulosa cells of porcine ovarian follicles."Cytotechnology. 33・2. 189-201 (2000)

[Publications] Mizuho Nakayama,Noboru Manabe,Hajime Miyamoto et al.: "Species specific differences in apoptotic cell localization in granulosa and theca interna cells during follicular atresia in porcine and bovine ovaries."Journal of Reproduction and Development. 46・2. 147-156 (2000)

[Publications] Susumu Nishihara,Noboru Manabe,Hajime Miyamoto et al.: "Changes in cell adhesion molecules during follicular atresia in porcine ovaries."Journal of Reproduction and Development. 46・3. 325-334 (2000)

[Publications] Mizuho Nakayama,Noboru Manabe,Hajime Miyamoto et al.: "Changes in localization of type I, III and IV collagens and their mRNA expression during follicular atresia in bovine and porcine ovaries."Journal of Reproduction and Development. 47・1. 27-36 (2001)

[Publications] Kozue Uchio,Noboru Manabe,Kotaro Tamura,Matoto Miyamoto et al.: "Decreased matrix metalloproteinase activity in the kidneys of hereditary nephrotic mice (ICGN strain)."Nephron. 86・1. 145-141 (2000)

[Publications] Kotaro Tamura,Noboru Manabe,Kozue Uchio,Makoto Miyamoto et al.: "Characteristic changes in carbohydrate profile in the kidneys of hereditary nephrotic mice (ICGN strain)."The Journal of Veterinary Medical Science. 52・2. 379-390 (2000)

[Publications] Noboru Manabe,Akiko Kinoshita,,Kozue Yamada-Uchio et al.: "Changes in quantitative profile of extracellular matrix components in the kidneys of rats with adriamycin-induced nephropathy."The Journal of Veterinary Medical Science. 53・1. 125-133 (2001)

[Publications] Miki Sugimoto,Noboru Manabe,Hajime Miyamoto.: "Future functional-morphological studies in embryology."Journal of Reproduction and Development. 46・1. 71-77 (2000)

[Publications] Noboru Manabe,Hajime Miyamoto et al.: "Immunohistochemical quantification of fast-myosin in upper hind limb muscles of the pig."Animal Science Journal. 72・2. 154-163 (2000)

[Publications] Miki Sugimoto,Noboru Manabe,Hajime Miyamoto.: "Development of infantile rat ovaries autotransplanted after cryopreservation by vitrification."Theriogenology. 53・11. 1093-1103 (2000)

[Publications] Noboru Manabe,Akira Myoumoto,Chiemi Tajima,Hajime Miyamoto et al.: "A novel cell death receptor and a decoy receptor on granulosa cells of porcine ovarian follicles."Tohoku University Press, Sendai, Japan.. 357 (2000)

宮本元京都大学, 農学研究科, 教授 (00026618)