1996 Fiscal Year Annual Research Report

環境因子に対する感受性を支配する遺伝的要因

Research Project

Project/Area Number	05278118
Research Institution	Kitasato University
Principal Investigator	井村伸正北里大学, 薬学部, 教授 (70012606)
Co-Investigator(Kenkyū-buntansha)	工藤一郎昭和大学, 薬学部, 教授 (30134612) 市橋正光神戸大学, 医学部, 教授 (00030867) 内海英雄九州大学, 薬学部, 教授 (20101694) 鎌滝哲也北海道大学, 薬学部, 教授 (00009177)
Keywords	重金属の毒性発現 / 種差 / 薬物代謝 / 遺伝的多型性 / 紫外線B / 皮膚癌危険因子 / 抗酸化酵素 / ホスホリパーゼA_2
Research Abstract	本研究は、(1)環境因子に対する感受性を支配する遺伝的素因の有無、(2)感受性因子の本態と遺伝的多型性、(3)環境因子に対する感受性の変化の原因の生化学的機構、を検討することにより、環境因子による生体影響の個体差を決定する要因を明らかにすることを目的とする。本年度は以下の成果が得られた。経口摂取したCdの腎臓への蓄積性の動物種差を左右する因子として消化管におけるCdの保持時間と小腸粘膜のメタロチオネインレベルが関与している可能性を見いだした(井村)。タバコ煙中のニトロソアミン類の代謝活性化を行うチトクロムP450(CYP2A6)のpoor metabolizerでは、CYP2A6遺伝子が全欠損していること、この遺伝子の変異と発癌感受性に関連があることを見いだした(鎌滝)。河川水中に検出されるクロロフェノール類の毒性が抗酸化酵素によって変動することを生体計測ESRを用いてin vivoで明らかにした(内海)。紫外線Bを浴びると日焼けで赤くなりやすいskin type Iが皮膚癌の危険因子となりうることを疫学調査で明らかにした(市橋)。分泌型ホスホリパーゼA_2を欠損したマウスで大腸癌の発生頻度が著しく高いことから、本酵素が細胞増殖に果たす役割を明らかにした(工藤)。

Research Products

(10 results)

All Other

All Publications (10 results)

[Publications] Nakagawa I.et al.: "Effect of glutathione depletion on metallothionein synthesis induced by paraquat in mice" Tohoku J.Exp.Med.177. 249-262 (1995)
[Publications] Kamataki T.et al.: "Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes" J.Pharmacol.Exptl.Therap.277. 1010-1015 (1996)
[Publications] Kamataki,T.et al.: "A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanese population associated with poor metabolizer phenotype" Pharmacogenetics. 6. 395-401 (1996)
[Publications] Utsumi H.et al.: "In vivo ESR measurements of free radical reactions in living mice" Toxicol.Lett.82/83. 561-565 (1996)
[Publications] Han J-Y.et al.: "In vivo measurement of radical reaction induced by diesel exhaust particle in lung" Proc.Free Radical Res.321- (1996)
[Publications] Oka M.et al.: "Enhanced expression of protein kinase C subspecies in melanogenic compartments in B16 melanoma cells by UVB or MSH" J.Invest.Deramtol.106. 377-378 (1996)
[Publications] Ueda M.et al.: "The expression of retinoblastoma protein in epidermis is induced by ultraviolet B exposure" Br.J.Dermatol. 135. 406-411 (1996)
[Publications] Ashraf MD.M.et al.: "Type II phospholipase A_2 is linked to cyclooxygenase-2-mediated delayed prostaglandin D_2 generation by cultured mouse mast cells following FcεPI-and cytokine-dependent activation" Biochem.Biophys.Res.Commun.229. 726-732 (1996)
[Publications] Murakami M.et al.: "Type II secretory phospholipase A_2 associated with cell surfaces via C-terminal heparin-binding lysine residues augments stimulus-initiated delayed prostaglandin generation" J.Biol.Chem.271. 30041-30051 (1996)
[Publications] Kitahara J.et al.: "Genetic Response to Metals" DNA strand breakage and lipid peroxidation as possible mechanisms of selenium toxicity, (1995)

1996 Fiscal Year Annual Research Report

環境因子に対する感受性を支配する遺伝的要因

Principal Investigator

井村 伸正 北里大学, 薬学部, 教授 (70012606)

Research Products

[Publications] Nakagawa I.et al.: "Effect of glutathione depletion on metallothionein synthesis induced by paraquat in mice" Tohoku J.Exp.Med.177. 249-262 (1995)

[Publications] Kamataki T.et al.: "Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes" J.Pharmacol.Exptl.Therap.277. 1010-1015 (1996)

[Publications] Kamataki,T.et al.: "A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanese population associated with poor metabolizer phenotype" Pharmacogenetics. 6. 395-401 (1996)

[Publications] Utsumi H.et al.: "In vivo ESR measurements of free radical reactions in living mice" Toxicol.Lett.82/83. 561-565 (1996)

[Publications] Han J-Y.et al.: "In vivo measurement of radical reaction induced by diesel exhaust particle in lung" Proc.Free Radical Res.321- (1996)

[Publications] Oka M.et al.: "Enhanced expression of protein kinase C subspecies in melanogenic compartments in B16 melanoma cells by UVB or MSH" J.Invest.Deramtol.106. 377-378 (1996)

[Publications] Ueda M.et al.: "The expression of retinoblastoma protein in epidermis is induced by ultraviolet B exposure" Br.J.Dermatol. 135. 406-411 (1996)

[Publications] Ashraf MD.M.et al.: "Type II phospholipase A_2 is linked to cyclooxygenase-2-mediated delayed prostaglandin D_2 generation by cultured mouse mast cells following FcεPI-and cytokine-dependent activation" Biochem.Biophys.Res.Commun.229. 726-732 (1996)

[Publications] Murakami M.et al.: "Type II secretory phospholipase A_2 associated with cell surfaces via C-terminal heparin-binding lysine residues augments stimulus-initiated delayed prostaglandin generation" J.Biol.Chem.271. 30041-30051 (1996)

[Publications] Kitahara J.et al.: "Genetic Response to Metals" DNA strand breakage and lipid peroxidation as possible mechanisms of selenium toxicity, (1995)

井村伸正北里大学, 薬学部, 教授 (70012606)