1996 Fiscal Year Annual Research Report

放射線感受性予測の基礎研究

Research Project

Project/Area Number	08266104
Research Institution	The University of Tokyo
Principal Investigator	鈴木紀夫東京大学, 医学部, 教授 (10010050)
Co-Investigator(Kenkyū-buntansha)	平岡真寛京都大学, 大学院・医学研究科, 教授 (70173218) 法村俊之産業医科大学, 医学部, 教授 (20039530) 佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857) 小松賢志広島大学, 原爆放射能医学研究所, 教授 (80124577) 小川恭弘高知医科大学, 医学部, 助教授 (90152397)
Keywords	DNA依存性プロテインキナーゼ / Ataxia telangiectasia遺伝子 / p53 / 放射線感受性 / ナイミ-ヘン症候群 / p53欠失マウス / 奇形 / 温熱による放射線の増感
Research Abstract	腫瘍治療における放射線感受性に関与する因子を大別すると増殖性腫瘍細胞の数、血流及び酸素濃度のような生理的特性、宿主との相互作用(免疫、増殖制御因子など)、腫瘍細胞固有の感受性などがある。本研究は腫瘍細胞固有の感受性のメカニズム、関与因子の解明を通して、新しい感受性予測法、感受性制御法の開発を目的としている。本年は、放射線による二重鎖切断に依存し、放射線感受性に関与すると考えられているDNA依存性プロテインキナーゼ(DNA-PK)とがん抑制遺伝子であり細胞死、細胞周期制御に関与するp53遺伝子、放射線感受性に関与する他の遺伝子病ataxia telangiectasia遺伝子(ATM)や、未解明のナイミ-ヘン染色体不安定症候群、XRCC2、XRCC8感受性相補群について解明が進められた。精製しDNA-PKをサブユニットに分離し、特性を調べた研究から温熱による放射線の増感作用が、そのKu-サブユニットの熱不安定性のためであることが解明された。 p53欠失のトランスジェニックスマウスを用いた放射線誘発奇形・胎児死の研究から、正常型p53が放射線照射後アポトーシスによる受精卵・胎児死をおこすことにより、奇形児の増加を阻止していることが分かった。一方、培養腫瘍細胞においてもp53の遺伝子操作により細胞を感受性に転換することが一般的には容易でなく、感受性に関与する他の未知因子の存在をもっと考慮すべきという結果が得られた。腫瘍細胞のp53をモニターすることにより放射線感受性を予測又操作するためにはこれから多くの研究が必要であることが示された。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Matsumoto,Y.et al.: "A possible mechanism for hyperthermic radiosensitization mediated through byperthermic lability of Ku subunits in DNA-dependent protein kinase." Biochemical and Biophysical Research Communications. (in press). (1997)
[Publications] Morimatsu,A.et al.: "Identification and characterization of a protein appeared after X-irradiation in human T cell leukemia." J.Radiat.Res.37. 1-11 (1996)
[Publications] Ogawa,Y.et al.: "Sequential alteration of proto-oncogene expression in liver,spleen,kidney and brain of mice subjected to whole body irradiation." Oncology. 53. 412-416 (1996)
[Publications] Ogawa,Y.et al.: "Ferric anmonium citrate-cellulose paste for opacification the esophageal lumen on MRI." J.Comput.Assist.Tomogr.20. 455-459 (1996)
[Publications] Inomata,T.at al.: "Immune reaction induced by X-rays and pions and its stimulation by schizo phyllan(SPG)." British Journal of Cancer. 74. S122-S125 (1996)
[Publications] Komatsu,K.et al.: "The Gene for Nijmegen Breakage Syndrome(V2)Is Not Lacated on Chromosome 11." Am.J.Hum.Genet.58. 885-888 (1996)
[Publications] Komatsu,K.et al.: "Inhibitory action of (-)-epigallocatechin gallate on radiation-induced mouse oncogenic transformation." Cancer Lett.(in press). (1997)
[Publications] Endo,S.et al.: "Determination of the Relative Neutron Sensitivityof a C-CO_2 Ionization Chamber." Phys.Med.Biol.41. 1037-1043 (1996)
[Publications] H.Tauchi et al.: "Accumulation of cells at G_2/M stage by low dose-rate irradiation renders the cell population more susceptible to the subsequent induction of 6-thioguanine-resistant mutations by ^<252>Cf fission neutrons." J.Rad.Res.37. 49-57 (1996)
[Publications] Nakayama,T.et al.: "Fracture healing is a process independent of p53 function." In Vivo. 10. 553-558 (1996)
[Publications] Honda,T.et al.: "Spontaneous immortalization of cultured skin fibroblasts obtained from a high-dose atomic bomb survivor." Mutat.Res.354. 15-26 (1996)
[Publications] Yamada,K.et al.: "High level of tritium-remainingin brain of rats exposed to tritiated water as infants." In Vivo. 10. 489-494 (1996)
[Publications] Kato,M.V.et al.: "Loss of heterozygosity on chromosome 17 and mutation of the p53 gene in retinoblastoma." Cancer Letters.106. 75-82 (1996)
[Publications] Yamaguchi,T.et al.: "Loss of heterozygosity and tumor suppressor gene mutations in chondrosarcomas." Anticancer Res.16. 2009-2016 (1996)
[Publications] Norimura,T.et al.: "p53-dependent apotosis suppresses radiation-induced teratogenesis." Nature Medicine. 2. 577-580 (1996)
[Publications] Shibata,T.et al.: "Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation." Jpn.J.Cancer Res.87(1). 98-104 (1996)

1996 Fiscal Year Annual Research Report

放射線感受性予測の基礎研究

Principal Investigator

鈴木 紀夫 東京大学, 医学部, 教授 (10010050)

Research Products

[Publications] Matsumoto,Y.et al.: "A possible mechanism for hyperthermic radiosensitization mediated through byperthermic lability of Ku subunits in DNA-dependent protein kinase." Biochemical and Biophysical Research Communications. (in press). (1997)

[Publications] Morimatsu,A.et al.: "Identification and characterization of a protein appeared after X-irradiation in human T cell leukemia." J.Radiat.Res.37. 1-11 (1996)

[Publications] Ogawa,Y.et al.: "Sequential alteration of proto-oncogene expression in liver,spleen,kidney and brain of mice subjected to whole body irradiation." Oncology. 53. 412-416 (1996)

[Publications] Ogawa,Y.et al.: "Ferric anmonium citrate-cellulose paste for opacification the esophageal lumen on MRI." J.Comput.Assist.Tomogr.20. 455-459 (1996)

[Publications] Inomata,T.at al.: "Immune reaction induced by X-rays and pions and its stimulation by schizo phyllan(SPG)." British Journal of Cancer. 74. S122-S125 (1996)

[Publications] Komatsu,K.et al.: "The Gene for Nijmegen Breakage Syndrome(V2)Is Not Lacated on Chromosome 11." Am.J.Hum.Genet.58. 885-888 (1996)

[Publications] Komatsu,K.et al.: "Inhibitory action of (-)-epigallocatechin gallate on radiation-induced mouse oncogenic transformation." Cancer Lett.(in press). (1997)

[Publications] Endo,S.et al.: "Determination of the Relative Neutron Sensitivityof a C-CO_2 Ionization Chamber." Phys.Med.Biol.41. 1037-1043 (1996)

[Publications] H.Tauchi et al.: "Accumulation of cells at G_2/M stage by low dose-rate irradiation renders the cell population more susceptible to the subsequent induction of 6-thioguanine-resistant mutations by ^<252>Cf fission neutrons." J.Rad.Res.37. 49-57 (1996)

[Publications] Nakayama,T.et al.: "Fracture healing is a process independent of p53 function." In Vivo. 10. 553-558 (1996)

[Publications] Honda,T.et al.: "Spontaneous immortalization of cultured skin fibroblasts obtained from a high-dose atomic bomb survivor." Mutat.Res.354. 15-26 (1996)

[Publications] Yamada,K.et al.: "High level of tritium-remainingin brain of rats exposed to tritiated water as infants." In Vivo. 10. 489-494 (1996)

[Publications] Kato,M.V.et al.: "Loss of heterozygosity on chromosome 17 and mutation of the p53 gene in retinoblastoma." Cancer Letters.106. 75-82 (1996)

[Publications] Yamaguchi,T.et al.: "Loss of heterozygosity and tumor suppressor gene mutations in chondrosarcomas." Anticancer Res.16. 2009-2016 (1996)

[Publications] Norimura,T.et al.: "p53-dependent apotosis suppresses radiation-induced teratogenesis." Nature Medicine. 2. 577-580 (1996)

[Publications] Shibata,T.et al.: "Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation." Jpn.J.Cancer Res.87(1). 98-104 (1996)

鈴木紀夫東京大学, 医学部, 教授 (10010050)