• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2000 Fiscal Year Annual Research Report

低線量・低線量率放射線による細胞応答の発現機構

Research Project

Project/Area Number 12358010
Research InstitutionNara Medical University

Principal Investigator

大西 武雄  奈良県立医科大学, 医学部, 教授 (60094554)

Co-Investigator(Kenkyū-buntansha) 小松 賢志  広島大学, 原爆放射能医学研究所, 教授 (80124577)
丹羽 太貫  京都大学, 放射線生物研究センター, 教授 (80093293)
内海 博司  京都大学, 原子炉実験所, 教授 (20025646)
渡辺 正巳  長崎大学, 薬学部, 教授 (20111768)
法村 俊之  産業医科大学, 医学部, 教授 (20039530)
Keywords低線量・低線量率放射線 / p53 / 情報伝達 / 適応 / アポトーシス / 細胞周期 / 突然変異誘発 / 遺伝的不安定性
Research Abstract

本研究では低線量・低線量率放射線に対する細胞応答様式とそれによる影響について下記項目を解析した。
(1)センサー(受容;何が放射線を受容しているのか)
・低線量・低線量率放射線によるiNOSの蓄積誘導がp53遺伝子型依存性であることを明らかにした。(NOラジカルの関与:福井医大・松本)
・低線量の放射線誘発DNA損傷に対して、NBS1は放射線損傷を定量してDNA修復するか、アポトーシスにより排除するかの判定機構を明らかにする目的で、NBS1フォーカス形成過程やp53誘導とNBS1蛋白との関連性について解析した。(NBS1による低線量放射線損傷細胞の認識機能:広大・小松)
(2)情報伝達(応答)
・低線量・低線量率放射線によるアポトーシスの誘導までの情報伝達経路についてWestern blot、免疫組織染色法等の分子生物学的手法を用いて調べた。(p53を中心とした情報伝達誘導機構:奈良医大・大西)
・低線量の2〜5cGyになるとp53タンパクの蓄積は起こらないがERK1/2のリン酸化が起きることを明らかにした。(遺伝子転写活性促進効果:長崎大・渡辺)
(3)適応を含む機能発現
・低線量放射線により誘発されるアポトーシスに、細胞周期チェックポイント制御因子が関与していることを明らかにした。(細胞周期チェックポイント遺伝子の機能:広大・鈴木)
・ニワトリ DT40細胞の変異細胞系を用いて、分割照射回復現象が相同組換え系のDSB修復系によることを明らかにした。さらに低線量率では、相同組換えではなく非相同組換えが主要な経路であることを示唆する結果を得た。(DNA2重鎖切断修復の役割:京大・内海)
・高線量率あるいは低線量率で照射し、照射マウス脾細胞のTCR遺伝子突然変異発現頻度の線量率依存性及びp53遺伝子機能との関係を解析した。低線量放射線のTCR突然変異誘発リスクは、線量率とp53依存性アポトーシス活性に依存することを明らかにした。(アポトーシス:産業医大・法村)
・各臓器別の突然変異測定系のMutaマウスを用い、睾丸における低線量多数回照射による突然変異特性を明らかにした。(突然変異誘発機構:東北大・小野)
・低線量・低線量率放射線照射した雄より生よれたELマウスで母親由来ミニサテライト配列の突然変異の誘発を観察した。(遺伝的不安定性の誘導:京大・丹羽)

  • Research Products

    (72 results)

All Other

All Publications (72 results)

  • [Publications] Harima,Y., et al.: "Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women."Int.J.Mol.Medicine. (in press). (2001)

  • [Publications] Harima,Y., et al.: "Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy."Int.J.Oncol.. (in press). (2001)

  • [Publications] Ohtsubo,T., et al.: "Effect of acidic environment and p53 on apoptosis induction by hyperthermia."Int.J.Hyperthermia. 16. 481-491 (2000)

  • [Publications] Kubota,N., et al.: "Wortmannin sensitizes human glioblastoma cell lines carrying mutant or wild type TP53 gene to radiation."Cancer Lett.. 161. 141-147 (2000)

  • [Publications] Ohnishi,K., et al.: "Glycerol restores p53 dependent radiosensitivity of human head and neck cancer cells bearing mutant."Br.J.Cancer. 83. 1735-1739 (2000)

  • [Publications] Oka,A., et al.: "Determination of p53-mediated transactivationl ability in radiation-treated cervical cancer."Cancer Detect.Prevent.. 24. 275-282 (2000)

  • [Publications] Kanata,H., et al.: "CDDP induces p53-dependent apotosis in tongue cancer cells."Int.J.Oncol.. 17. 513-518 (2000)

  • [Publications] Xie,X., et al.: "p53 status plays no role in radiosensitizing effects of SN-38, a camptothecin derivative."Cancer Chemother.Pharmacol.. 45. 362-368 (2000)

  • [Publications] Ohnishi,T., et al.: "Heat-induced accumulation of p53 and hsp72 is suppressed in lung fibroblasts from SCID mouse."Int.J.Radiat.Biol.. 76. 711-715 (2000)

  • [Publications] Ota,I., et al.: "Transfection with mutant p53 gene inhibits heat-induced apoptosis in a head and neck cell line of human squamous cell carcinoma."Int.J.Radiat.Oncol.Biol.Phys.. 47. 495-501 (2000)

  • [Publications] Takahashi,A., et al.: "The dependence of p53 on the radiation enhancement of thermosensitivity at different LET."Int.J.Radiat.Oncol.Biol.Phys.. 47. 489-494 (2000)

  • [Publications] Takahashi.A., et al.: "Induction of WAF1 accumulation by carbon-ion beam and α-particle irradiation in human glioblastoma cultured cells."Int.J.Radiat.Biol.. 76. 335-341 (2000)

  • [Publications] Nakamura,S., et al.: "Characteristics of mutations generated through digestion with restriction enzyme and ligation in plasmid DNA."Environ.Mol.Mutagenesis. (印刷中). (2001)

  • [Publications] Komura,J., et al.: "Mapping psoralen cross-links at the nucleotide level in mammalian cells : Suppression of cross-linking at transcription factor-or nucleosome-binding sites."Biochem.. (印刷中). (2001)

  • [Publications] Ikehata,H., et al.: "Distribution of spontaneous CpG-associated G : C→A : T mutations in the lacZ gene of MutaTM mice : Effects of CpG methylaiton, the sequence context of CpG sites, and severity of mutations on the activity of the lacZ gene product."Environ.Mol.Mutagenesis. 36. 301-311 (2000)

  • [Publications] Ono,T., et al.: "Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse."Mutat.Res.. 447. 165-177 (2000)

  • [Publications] Nakamura,S., et al.: "Radiation-induced mutations in the spleen and brain of lacZ transgenic mice."Int.J.Radiat.Biol.. 76. 431-440 (2000)

  • [Publications] Niwa,O., et al.: "Untargeted mutation of the maternally derived mouse hypervariable minisatellite allele in F1 mice born to irradiated spermatozoa."Proc.Natl.Acad.Sci.USA. 98. 1705-1710 (2001)

  • [Publications] Ohtaki,M., et al.: "Mathematical implication for radiation carcinogenesis based on hypothesis of induction of genomic instability."Jpn.J.Biometrics. 21. 77-84 (2000)

  • [Publications] Taga,M., et al.: "Increased frequencies of gene and chromosome mutations after X-irradiation in mouse embryonal carcinoma cells transfected with the bcl-2 gene."Jpn.J.Cancer Res.. 91. 994-1000 (2000)

  • [Publications] Taga,M., et al.: "The effect of caffeine on p53 dependent radioresponses in undifferentiated Mouse embryonal carcinoma cells after X-ray and UV-irradiations."J.Radiat,Res.. 41. 227-241 (2000)

  • [Publications] Uchimura,E., et al.: "Transient infiltration of neutrophils into the thymus in association with apoptosis induced by whole-body X-irradiation."J.Leukoc.Biol.. 67. 780-784 (2000)

  • [Publications] 達家雅明 他: "低レベル放射線被曝による胸腺細胞のアポトーシス誘発過程における2型サイクリン依存的キナーゼ活性化現象"長崎医学会雑誌. 75. 291-293 (2000)

  • [Publications] 数藤志帆 他: "M期チェックポイント・キナーゼScMPS1結合タンパクScMOB1のヒト・ホモローグの解析"長崎医学会雑誌. 75. 294-296 (2000)

  • [Publications] 矢島浩彦 他: "熱ショックタンパク質とBcl-2ファミリータンパク質によるapoptosomeの制御"放射線生物研究. 35・4. 358-369 (2000)

  • [Publications] Matsumoto,H., et al.: "Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated cells of human glioblastoma."Int.J.Radiat.Biol.. 76. 1649-1657 (2000)

  • [Publications] Matsumoto,H., et al.: "Interactive effects of nitric oxide and p53 on cellular thermosensitivity."Jpn.J.Hyperthermic Oncol.. 16. 69-82 (2000)

  • [Publications] Hatashita M., et al.: "Effect of the p53 gene on synchronization of cells with hydro-xyurea and on the cell phase response to hyperthermia in vitro."Jpn.J.Hyperthermic Oncol.. 16. 107-115 (2000)

  • [Publications] Matsumoto,H., et al.: "Induction of radioresistance by a nitric oxide-mediated bystander effect."Radiat.Res.. 155(印刷中). (2001)

  • [Publications] Kato,F., et al.: "Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis"Int.J.Radiat.Biol.. 77・1. 13-19 (2001)

  • [Publications] 法村俊之 他: "奇形の発生を防ぐp53遺伝子:ノックアウトマウスを用いたp53依存性監視機構の解析"アニテックス. (印刷中). (2001)

  • [Publications] 加藤文雄 他: "p53による放射線誘発催奇性障害の防御機構"放射線生物研究. 35・3. 226-236 (2000)

  • [Publications] 岡崎龍史 他: "アポトーシスとFas,p53"整形・災害外科. 43・7. 768-769 (2000)

  • [Publications] Ootsuyama,A., et al.: "Effect of extended exposure of low-dose radiation on autoimmune diseases of immunologically depressed MRL/MpJ-gld/gld mice"Proceedings of the 10^<th> international congress of the international radiation protection association. (2000)

  • [Publications] Kato,F., et al.: "Dose rate effectiveness in radiation-induced teratogenesis in mice"Proceedings of the 10^<th> international congress of the international radiation protection association. (2000)

  • [Publications] Tauchi,H., et al.: "The FHA domain of NBS1 is essential for nuclear foci formation after irradiation, but not essential for hRAD50/hMRE11/NBS1 complex DNA Repair activity"J.Biol.Chem.. 276. 12-15 (2001)

  • [Publications] Ubagai,T., et al.: "Comparative genomic hybridization analysis suggests a gain of chromosome 7p associated with lymph node metastasis is non small cell lung cancer"Oncology Reports. 8. 83-88 (2001)

  • [Publications] Sakata,K., et al.: "Expression of genes involvedin repair of DNA double-strand breaks in tumors"Int.J.Radiat.Oncology. (印刷中). (2001)

  • [Publications] Winter,J.P., et al.: "Isolation of a cDNA representing the Fanconi anemia complementation group E gene"Am.J.Hum.Genet.. 67. 1306-1308 (2000)

  • [Publications] Matsuura,S., et al.: "Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic-spindle checkpoint"Am.J.Hum.Genet.. 67. 483-486 (2000)

  • [Publications] Tauchi,H., et al.: "Mutation spectrum of MSH3-deficient cells HHUA/chr.2 refrects in vivo activity of the MSH3 gene product in mismatch repair"Mutat.Res.. 447. 155-164 (2000)

  • [Publications] Tauchi,H., et al.: "Cell cycle and LET dependence for radiation-induced mutation : possible mechanism for reversed dose-rate effect"J.Radiat.Res.. 40. 45-52 (2000)

  • [Publications] Tauchi,H., et al.: "Altered splicing of the ATDC message in AT group D cells results in the absence of a functional protein"Mutagenesis. 15. 105-108 (2000)

  • [Publications] Tauchi,H., et al.: "Positional cloning and functional analysis of the gene responsible for Nijmegen Breakage Syndrome, NBS1"J.Rad.Res.. 41. 9-17 (2000)

  • [Publications] Hama,S., et al.: "Absence of mutation in the NBS1 gene in B-cell malignant lymphoma patients"Anticancer Res.. 20. 1897-1900 (2000)

  • [Publications] Hiel,J.A., et al.: "Nijmegen breakage syndrome. The International Nijmegen Breakage Syndrome Study Group"Arch.Dis.Child.. 82. 400-406 (2000)

  • [Publications] Ishihawa,S., et al.: "Japanese family with an autosomal dominant chromosome instability syndrome : a new neurodegerative disease?"Am.J.Med.Gener.. 94. 265-270 (2000)

  • [Publications] 中村麻子 他: "ナイミーヘン症候群における2本鎖DNA切断修復の異常"蛋白質、核酸、酵素. (印刷中). (2001)

  • [Publications] 小林純也 他: "チェックポイントとDNA修復のクロストーク"細胞工学. 19. 1463-1470 (2000)

  • [Publications] 田内広 他: "Nijmegen症候群と毛細血管拡張性運動失調症"医学のあゆみ. 9. 667-671 (2000)

  • [Publications] 小松賢志: "放射線で切れたDNA修復の仕組み解明の現状-放射線治療と発がんの分子接点-"Isotope News. 6. 2-7 (2000)

  • [Publications] 田中公夫 他: "低エネルギー中性子のヒトリンパ球での初期DNA損傷と染色体再構成におよぼす影響"広島医学. 53. 168-171 (2000)

  • [Publications] 田内広 他: "機能相補性試験によるDNA二重鎖切断修復遺伝子NBS1の重要ドメイン解析"広島医学. 53. 212-214 (2000)

  • [Publications] 森島賢一 他: "放射線高感受遺伝病NBS近傍の新規多型マーカーの単離と多型解析"広島医学. 53. 215-216 (2000)

  • [Publications] 小林純也 他: "NBS細胞及びAT細胞におけるγ線誘導アポトーシス"広島医学. 53. 222-224 (2000)

  • [Publications] 松浦伸也 他: "ナイミーヘン染色体不安定症候群遺伝子のマウスホモログの単離"広島医学. 53. 217-219 (2000)

  • [Publications] 中村麻子 他: "ナイミーヘン染色体不安定症候群(NBS)におけるテロメア維持機構"広島医学. 53. 220-221 (2000)

  • [Publications] kodama,S., et al.: "Culture condition dependent senescence like growth arrest and immortalization in rodent embryo cells"Radiat.Res.. 155. 254-262 (2001)

  • [Publications] Suzuki,K., et al.: "Radiation-induced senescence-like growth arrest requires p53 function, but not telomere shortening"Radiat.Res.. 155. 248-253 (2001)

  • [Publications] Roy,K., et al.: "Hypoxia relieves x-ray-induced delayed effect in normal human embryo cells"Radiat.Res.. 154. 659-666 (2000)

  • [Publications] Ghosh,C, et al.: "Dose-Dependent biphasic accumulation of p53 protein in normal human embryo cells following X-irradiation"Radiat.Res.. 153. 305-311 (2000)

  • [Publications] Suzuki,M., et al.: "Influence of the sampling time on chromosomal aberrations at G_2 phase in Syrian hamster embryonic cells irradiated with different types of radiation"Int.J.Radiat.Biol.. 76. 814-821 (2000)

  • [Publications] Kumagai,J., et al.: "Electron spin echo study of long-lived radicals which cause mutation in gammaray irradiated mammalian cells"Spectrochimica Acta Part A : Mol.Biomol.Spectroscopy. 56. 2509-2516 (2000)

  • [Publications] Matsuda,N., et al.: "Differential activation of ERK1/2 and JNK in normal human fibroblast-like cells in responese to UVC radiation under different oxygen tensions"Photochem.Photobiol.. 72. 334-339 (2000)

  • [Publications] Utsumi,H., et al.: "Requirement for repari of dna double strand breaks by homologous recombinational in split-dose recovery"Radiat.Res.. 155(in press). (2001)

  • [Publications] Sugimoto,M., et al.: "Proficient repair of potentially lethal damage sensitive to hypertonic treatment in osteosarcoma cells"Radiat.Res.. 154. 347-350 (2000)

  • [Publications] 内海博司: "古典放射線生物学を分子レベルで何処まで語れるか?-電離放射線の生物影響とDNA2重鎖切断の修復機構"放射線生物研究. 35. 268-283 (2000)

  • [Publications] 内海博司: "古典的放射線生物学における回復現象の分子生物学的解析"環境と健康. 13. 79-89 (2000)

  • [Publications] 太田一郎 他: "癌放射線療法2000"篠原出版(印刷中). (2001)

  • [Publications] Yonezawa,M., et al.: "The effects of low and very low doses of ionizing radiation on human health"Elsevier Science, Amsterdam. 6 (2000)

  • [Publications] Takahashi,A., et al.: "Biological effects of low dose radiation"Elsevier Science, Amsterdam. 8 (2000)

  • [Publications] M.Watanabc: "Thermotherapy : Principles and Practice-Applications in Neoplasia, Inflammation, and Pain"Springcr-Vcrlag Tokyo, Inc., Tokyo. 550 (2000)

URL: 

Published: 2002-04-03   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi