1997 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 / 薬物代謝 / 遺伝的多型性 / 紫外線B / 皮膚癌危険因子 / 酸化ストレス / 抗酸化酵素 / 大腸癌形成
Research Abstract	経口摂取したCdの腎臓への蓄積性の動物種差、系統差を左右する因子としての小腸粘膜のメタロチオネイン(MT)の役割を検討したところ、低レベルのCd摂取の場合には、MT以外の因子の役割も無視できないが、MT誘導を起こす濃度のCd汚染がある場合にはMTが主要なcarrierとなることを明らかにした(井村)。煙草の煙の中のprocarcinogenを代謝活性化するCYP2D6について、poor metabolizerから新しい変異として、エクソン5に1塩基Cの挿入がある変異を見いだした。この変異を簡便に検出する診断法を確立し、日本人健常人に本変異をヘテロで有する者がいることを明らかにした(鎌滝)。2,4,6-trichlorophenol(TCP)による生体内フリーラジカル産生及び消去機構をSOD遺伝子組換えマウスを用いて生体計測ESRによって無侵襲測定したところ、初期肝代謝時に・OHが生成していること、抗酸化剤投与やSOD過剰発現は・OH消去によって肝障害を抑制する可能性を明らかにした(内海)。兵庫県加西市の5年間の皮膚癌検診の調査結果から、女より男、戸外労働の人、スキンタイプIの人、脂漏性角化症を6個以上持つ人、小児期に強い日焼けを経験した人において、皮膚の前癌症の有病率が高いことが明かとなり、これらの因子が皮膚癌の危険因子と推定された(市橋)。分泌型ホスホリパーゼA2(sPLA2-IIA型)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、sPLA_2から切り出されたアラキドン酸をプロスタグランジンに変換する酵素(Cox2)が大腸癌形成に関わっていることから、これら酵素の役割を検討したところ、_sPLA_2とCox2はアラキドン酸の遅発応答の増強因子であること、_sPLA_2と類縁の酵素であるV型_sPLA_2がIIA型_sPLA_2と類似した性状を示すことを明らかにした(工藤)。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] T.Urano et al.: "Inhibitory effect of selenium on biliary secretion of methyl mercury in rats" Biochem.Biophys.Res. Commun.239. 862-867 (1997)
[Publications] A.Naganuma et al.: "Overexpression of manganese-superoxide dismutase prevents methylmercury toxicity in HeLa cells" Life Sci.(in press). (1997)
[Publications] T.Tanaka-Kagawa et al.: "Strain difference in sensitivity of mice to renal toxicity of inorganic mercury" J.Pharmacol.Exp.Therap.(in press). (1998)
[Publications] T.Yokoi et al.: "A new deleted allele in human cytochrome P4502A6(CYP2A6)gene found in human liver subjects showing poor metabolic capacity to coumarin and(+)+cis-3,5-dimethyl-2-(3-pyridyl)-thiazolidin-4-one hydrochloride(SM-12502)" Pharmacogenetics. (in press). (1997)
[Publications] K.Nakamura et al.: "Oxidation of histamine H1 antagonist mequitazine is catalysed by cytochrom P450 2D6 in human liver microsomes" J.Pharmacol.Exp.Therap.284. 437-442
[Publications] T.Iwatsubo et al.: "Prediction of in vivo hepatic metabolic clearance of YM796 from in vitro data using human liver microsomes and recombinant P-450 isozymes" J.Pharmacol.Exp.Therap.282. 909-919 (1997)
[Publications] Y.Li et al.: "In vivo activation of aflatoxin B1 in C57BL/6N mice carrying a human fet us-specific CYP3A7 gene" Cancer Res.57. 641-645 (1997)
[Publications] S-、K.Han et al.: "Generation of p-semiquinone radicals from chlorophenols in water during ozonation" Water Res.(in press). (1998)
[Publications] H.Utsumi et al.: "Non-invasive measurement of free radical reaction in disease using in vivo ESR-CT technique" Physics Med.Biol.43(in press). (1998)
[Publications] H.Sano et al: "Synthesis and imaging of blood-brain-barrier permeable nitroxyl-probes forfree radical reactions in brain of living mice" Biochem.Mol.Biol.Int.42. 641-647 (1997)
[Publications] T.Suzuki et al.: "Incidence of actinic keratosis of Japanese in Kasai City,Hyogo" J.Dermatol.Sci.(in press).
[Publications] K.Naruse et al.: "Prevalence of actinic Keratosis in Japan" J.Dermatol.Sci.15. 183-187 (1997)
[Publications] N.U.Ahmed et al.: "Increased level of c-erbB-2/new/HER-2 protein in cutaneous squamous cell carcinoma" Br.J.Dermatol.136. 908-912 (1997)
[Publications] T.Suzuki et al.: "Doses of solar ultraviolet radiation correlate with skin cancer rates in Japan" Kobe J.Med.Sci.42. 375-388 (1996)
[Publications] H.Kuwata et al.: "Cytosolic phospholipase A_2 is required for cytokine-induced expression of type IIA phospholipase A_2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E_2 generation in rat 3Y1 fibroblasts" J.Biol.Chem.(in press).
[Publications] M.Murakami et al.: "Prostaglandin E_2 amplifies cytosolic phospholipase A_2 and cyclooxygenase-2-dependent delayed prostaglandin E_2 generation in mouse osteoblast cells:Enhancement by secretory phospholipase A_2" J.Biol.Chem.272. 19891-19897 (1997)
[Publications] Q.-R.Chen et al.: "Activation of cytosolic phospholipase A_2 by platelet-derived growth factor is essential for cyclooxygenase-2-dependent prostaglandin E_2 synthesis in mouse osteoblasts cultured with interleukin-" J.Biol.Chem.272. 5952-5958 (1997)
[Publications] H.Matsumoto et al.: "Concordant induction of prostaglandin E_2 synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E_2 to thromoboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat" Biochem.Biophys.Res.Commun.230. 110-114 (1997)
[Publications] 井村伸正他: "環境と健康II" 池永満生他編集へるす出版, 310 (1998)

1997 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] T.Urano et al.: "Inhibitory effect of selenium on biliary secretion of methyl mercury in rats" Biochem.Biophys.Res. Commun.239. 862-867 (1997)

[Publications] A.Naganuma et al.: "Overexpression of manganese-superoxide dismutase prevents methylmercury toxicity in HeLa cells" Life Sci.(in press). (1997)

[Publications] T.Tanaka-Kagawa et al.: "Strain difference in sensitivity of mice to renal toxicity of inorganic mercury" J.Pharmacol.Exp.Therap.(in press). (1998)

[Publications] T.Yokoi et al.: "A new deleted allele in human cytochrome P4502A6(CYP2A6)gene found in human liver subjects showing poor metabolic capacity to coumarin and(+)+cis-3,5-dimethyl-2-(3-pyridyl)-thiazolidin-4-one hydrochloride(SM-12502)" Pharmacogenetics. (in press). (1997)

[Publications] K.Nakamura et al.: "Oxidation of histamine H1 antagonist mequitazine is catalysed by cytochrom P450 2D6 in human liver microsomes" J.Pharmacol.Exp.Therap.284. 437-442

[Publications] T.Iwatsubo et al.: "Prediction of in vivo hepatic metabolic clearance of YM796 from in vitro data using human liver microsomes and recombinant P-450 isozymes" J.Pharmacol.Exp.Therap.282. 909-919 (1997)

[Publications] Y.Li et al.: "In vivo activation of aflatoxin B1 in C57BL/6N mice carrying a human fet us-specific CYP3A7 gene" Cancer Res.57. 641-645 (1997)

[Publications] S-、K.Han et al.: "Generation of p-semiquinone radicals from chlorophenols in water during ozonation" Water Res.(in press). (1998)

[Publications] H.Utsumi et al.: "Non-invasive measurement of free radical reaction in disease using in vivo ESR-CT technique" Physics Med.Biol.43(in press). (1998)

[Publications] H.Sano et al: "Synthesis and imaging of blood-brain-barrier permeable nitroxyl-probes forfree radical reactions in brain of living mice" Biochem.Mol.Biol.Int.42. 641-647 (1997)

[Publications] T.Suzuki et al.: "Incidence of actinic keratosis of Japanese in Kasai City,Hyogo" J.Dermatol.Sci.(in press).

[Publications] K.Naruse et al.: "Prevalence of actinic Keratosis in Japan" J.Dermatol.Sci.15. 183-187 (1997)

[Publications] N.U.Ahmed et al.: "Increased level of c-erbB-2/new/HER-2 protein in cutaneous squamous cell carcinoma" Br.J.Dermatol.136. 908-912 (1997)

[Publications] T.Suzuki et al.: "Doses of solar ultraviolet radiation correlate with skin cancer rates in Japan" Kobe J.Med.Sci.42. 375-388 (1996)

[Publications] H.Kuwata et al.: "Cytosolic phospholipase A_2 is required for cytokine-induced expression of type IIA phospholipase A_2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E_2 generation in rat 3Y1 fibroblasts" J.Biol.Chem.(in press).

[Publications] M.Murakami et al.: "Prostaglandin E_2 amplifies cytosolic phospholipase A_2 and cyclooxygenase-2-dependent delayed prostaglandin E_2 generation in mouse osteoblast cells:Enhancement by secretory phospholipase A_2" J.Biol.Chem.272. 19891-19897 (1997)

[Publications] Q.-R.Chen et al.: "Activation of cytosolic phospholipase A_2 by platelet-derived growth factor is essential for cyclooxygenase-2-dependent prostaglandin E_2 synthesis in mouse osteoblasts cultured with interleukin-" J.Biol.Chem.272. 5952-5958 (1997)

[Publications] H.Matsumoto et al.: "Concordant induction of prostaglandin E_2 synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E_2 to thromoboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat" Biochem.Biophys.Res.Commun.230. 110-114 (1997)

[Publications] 井村伸正 他: "環境と健康II" 池永満生 他編集 へるす出版, 310 (1998)

井村伸正北里大学, 薬学部, 教授 (70012606)

[Publications] 井村伸正他: "環境と健康II" 池永満生他編集へるす出版, 310 (1998)