放射線感受性予測の基礎研究

• 研究課題/領域番号: 09255102
• 研究種目: 特定領域研究(A)
• 配分区分: 補助金
• 研究機関: 東京大学
• 研究代表者: 鈴木 紀夫 東京大学, 大学院・医学系研究科, 教授 (10010050)
• 研究分担者: 小松 賢志 広島大学, 原爆放射能医学研究所, 教授 (80124577) ; 奥村 寛 長崎大学, 医学部, 教授 (00073130) ; 大西 武雄 奈良県立医科大学, 医学部, 教授 (60094554) ; 平岡 真寛 京都大学, 大学院・医学研究科, 教授 (70173218) ; 小川 恭弘 高知医科大学, 医学部, 助教授 (90152397)
• 研究期間 (年度): 1999
• 研究課題ステータス: 完了 (1999年度)
• 配分額: 102,000千円 (直接経費: 102,000千円); 1999年度: 34,000千円 (直接経費: 34,000千円); 1998年度: 34,000千円 (直接経費: 34,000千円); 1997年度: 34,000千円 (直接経費: 34,000千円)
• キーワード: 放射線感受性 / 先行指導 / p53 / DNA-PK / NBS1 / 放射線誘導タンパク / 細胞死(アポトーシス) / 感受性修飾 / 先行指標 / DNA・PK / リン酸化・脱リン酸化

研究概要

放射線による細胞死のメカニズムの解明とその感受性予測(治療法選択のための)への応用研究や感受性制御法の開発のための基礎研究がp53,DNA-PK,NBS1を中心に、シグナル伝達経路・細胞死過程への関与とその作用の解明について進展した。
NBS1は昨年までに遺伝子のクローニングが終わり、その機能について研究が進み、細胞周期制御への関与やそのC末側ドメインが感受性には重要であること、ATM/p53経由のシグナル伝達に関与していることが解明された。
p53に関しては、昨年までのデータに加えて、p53が感受性に関与する重要な因子になっている場合とその他の複数の因子が関与している場合について解明が進み、一層複雑となった。すなわち、p53が野生型か変異型かというだけでは予測に不十分で、他の複数の因子を含め判定することが必要である。一方、変異p53が抵抗性の原因となっている場合にはグリセロールやNaCl等で感受性を回復する可能性について基礎研究が進展した。
DNA-PKについては、従来から考えられているDNA二重鎖切断修復やシグナル伝達への関与のメカニズムに加え、DNA-PK(サブユニット)の変異株解析や各種細胞、特にゲッシ類細胞とヒト細胞の感受性比較検討から温熱感受性への関与についても研究が進展した。一方、DNA-PKをターゲットとした放射線感受性の制御についてはS-オリゴヌクレオチド,Wortmannin,温熱処理などによる可能性を示唆する結果が得られた。
放射線の感受性に関与する重要因子について、解明が進むに従って、その因子の多いこと、また、メカニズムの複雑なことが判明しつつあり、治療法選択に有用な指標(群)や新しい感受性制御法の確立には多くの研究が必要である。

研究成果

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