「人間地球系」-人類生存のための地球本位型社会の実現手法-環境因子に対する感受性を支配する遺伝子的要因

• 研究課題/領域番号: 05278118
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 北里大学
• 研究代表者: 井村 伸正 北里大学, 薬学部, 教授 (70012606)
• 研究分担者: 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) ; 工藤 一郎 昭和大学, 薬学部, 教授 (30134612) ; 巽 純子 京都大学, 医学部, 助手 (80128222) ; 西村 泰治 熊本大学, 大学院・医学系研究科, 教授 (10156119) ; 八木 孝司 京都大学, 医学部, 助教授 (80182301)
• 研究期間 (年度): 1993 – 1997
• 研究課題ステータス: 完了 (1997年度)
• 配分額: 88,000千円 (直接経費: 88,000千円); 1997年度: 19,000千円 (直接経費: 19,000千円); 1996年度: 20,000千円 (直接経費: 20,000千円); 1995年度: 15,000千円 (直接経費: 15,000千円); 1994年度: 18,000千円 (直接経費: 18,000千円); 1993年度: 16,000千円 (直接経費: 16,000千円)
• キーワード: 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 / 酸化ストレス / 抗酸化酵素 / 大腸癌形成 / ホスホリパーゼA_2 / 活性酸素消去因子 / 重金属 / ダニアレルギー / HLAクラスII分子 / 電磁場 / 突然変異頻度 / 水銀化合物の腎毒性 / γ-グルタミルトランスペプチダーゼ / 抗原ペプチド / 極低周波電磁場 / DNA鎖修復 / 活性酸素 / 化学物質の毒性発現 / 免疫応答 / HLA分子 / 紫外線 / 色素性乾皮症

研究概要

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、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の役割は、特にCd汚染がある場合に顕著に作用することを明らかにした(井村)。CYP2D6の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が明らかになった(内海)。5年間の皮膚癌検診の調査結果から、戸外労働、スキンタイプI、脂漏性角化症、小児期の強い日焼け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Cox2とともにアラキドン酸代謝に及ぼす影響を明らかにし、さらに類縁酵素の性状を明らかにした(工藤)。

研究成果

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  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Man-Earth Project Member: "1997 Research Results Report"113 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
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