1995 年度実績報告書

放射線応答の遺伝子制御

研究課題

研究課題/領域番号	06304049
研究機関	京都大学
研究代表者	佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857)
研究分担者	江島洋介京都大学, 放射線生物研究センター, 助教授 (50127057) 丹羽太貫広島大学, 原爆放射能医学研究所, 教授 (80093293) 米井修治京都大学, 理学部, 助教授 (60093340) 石崎寛治愛知県がんセンター研究所, 放射線部, 部長 (70111987) 大西武雄奈良県立医科大学, 教授 (60094554)
キーワード	放射線応答 / 遺伝子発現 / 情報伝達 / 細胞周期制御 / 酸化ストレス / 突然変異 / 遺伝子的不安定性 / 放射線感受性
研究概要	放射線応答、すなわち放射線を刺激として捉える放射線生物作用の概念は新しく、本研究はその放射線応答の遺伝子制御の機構を明らかにし放射線影響の新しい生物学的基盤の確立を目指している。哺乳動物細胞は微量の放射線に対しても鋭敏に反応し、初期応答遺伝子であるjunやfos遺伝子を発現させる。刺激分子種としては、酸化ラジカルが働き、その情報はフォスフォリパーゼCからCキナーゼおよびp38キナーゼへ伝達される放射線固有の伝達系があることが分かった(佐々木)。細胞応答の初期過程を大腸菌の酸化ストレス高感受性株でその遺伝子制御の機構を解析してきたが、本年度は特にチオレドキシン変異株について解析し、過酸化水素によるヒドロペルオキシダーゼI遺伝子の発現にはOxyR遺伝子が関係していることが分かった(米井)。放射線応答の生物学意義として細胞周期制御に関わる遺伝子、特にp53及びp21遺伝子、の挙動と機能に注目してきた。p53遺伝子の発現はγ線やX線によって誘導され、蛋白質が蓄積される。これには熱ショック蛋白との分子会合が働いているが、p53蛋白p21遺伝子の発現を制御している。このp21遺伝子の発現はp53蛋白依存的でありその挙動は重荷電粒子による照射でも同じであった(大西)。p53欠損マウスの細胞に紫外線を照射し、supF遺伝子を標的として調べたところ、誘発される突然変異に質的な違いがあることが明らかとなった(石崎)。マウス精細胞のγ線照射はDNA反復配列によるミニサテライトの突然変異を高率に起こし、遺伝的不安定性を誘導する。これは核分裂中性子でも同様であり、その効果はγ線より数倍高かった(丹羽)ヒトの放射線感受性を支配する遺伝子としてアタキシア・テランギエクタシア症の原因遺伝子を追跡してきたが、最近単離されたATM遺伝子とは別の遺伝子が存在する可能性が示唆された(江島)。

研究成果
(27件)

すべてその他

すべて文献書誌 (27件)

[文献書誌] Sasaki, M. S.: "On the rection kinetcs of the radioadaptive response in cultured mouse cells." International Journal of Radiation Biology. 68. 281-291 (1995)
[文献書誌] Kitahori, Y. et al: "Frequent matations of Ki-ras codon 12 in N-bis(2-hydroxypropyl)-niousadioa2aptive response in cultured mousoamine-initiated thryroid, kidney and lung tumors in Wister rats." Cancer Letters. 96. 155-161 (1995)
[文献書誌] Yano, T. et al.: "Enhancement effect of an anto-angiogenic agents, TNP-470, on hyperthemia-induced growth suppression of human esophageal and gastric cancers transplantable to nude mice." Anti-Cancer Research. 15. 1355-1358 (1995)
[文献書誌] Matsumoto, H, et al.: "Binding between wild-type p53 and hsp 72 accumulated after UV and γ-ray irradiation." Cancer Letters. 92. 127-133 (1995)
[文献書誌] Ohnishi, T. et al.: "Accumulation of mutant p53 and HSP72 by heat treatment, and their association in a human glioblastoma cell line." International Journal of Hypertherthemia. 11. 663-671 (1995)
[文献書誌] Matsumoto, H. et al.: "Preferential inhibition of nucleosome assembly by ulatraviolet-induced(6-4) photoproducts." Photochemistry and Photobiology. 19. 459-462 (1995)
[文献書誌] Nakano, T. et al.: "Mutation of shuttle vector plasmid, pZ189, in Escherichia coli induced by boron neutron capture beam (BNCB) containing α-particles." Mutation Research. 335. 153-159 (1995)
[文献書誌] Okaichi, K. et al.: "Unique DNA repair property of UV-sensitive (radC) mutant to Dictyostelium discoideum." Photochemistry and Photobiology. 61. 281-284 (1995)
[文献書誌] Kato, M. V. et al.: "Delayed development of retinoblastoma associated with loss of a maternal allele on chromosome 13." International Journal of Cancer. 64. 3-8 (1995)
[文献書誌] Shibagaki, I. et al.: "p53 mutation, MDM2 amplification and human papilloma virus infection are frequently involved but no associated with each other in esophageal squamous cell carcinoma." Clinical Cancer Resarch. 1. 769-773 (1995)
[文献書誌] Nkai, H. et al.: "Hemizygous expression of the wild-type p53 allele may confer a selective growth advantage before complete inactivation of the p53 gene in the progression of CML." British Journal of Hematology. 90. 147-155 (1995)
[文献書誌] Zhang, Q. M. et al.: "The sensitivity of three soi mutants of Eschrichia coli oxidizing mutants." Environmental Mutagen Research Communication. 16. 397-402 (1995)
[文献書誌] Zhang, Q. M. et al.: "Enzymatic repair of 5-formyl uracil in DNA caused by ionizing radiation in cell extract from mouse liver." International Journal of Radiation Biology. 68. 603-607 (1995)
[文献書誌] Taketo, M. et al.: "Homologs of Drosphila fushitarazu factor 1 map to mouse chromosome 2 and human chromosome 9q33." Genomics. 25. 565-567 (1995)
[文献書誌] Numoto, M. et al.: "Over-expressed ZF5 gene product, a c-myc-binding protein related to GL1-Kruppel protein, has a growth-suppressive activity in mouse cell lines." International Journal of Cancer Research. 86. 277-283 (1995)
[文献書誌] Fan, Y. -J., et al.: "Dose response of radiation indction of germline mutation at a hypervariable mouse minisatellile locus." International Journal of Radiation Biology. 68. 177-183 (1995)
[文献書誌] Nimomiya, Y. et al.: "Genomic organization and isoforms of the mouse ELP gene." Journal of Biochemistry. 118. 380-389 (1995)
[文献書誌] Huang, N. et al.: "Expression of CD21 antigen on myeloma cells and its involvement in their adhesion to bone marrow stromal cells." Blood. 85. 3704-3712 (1995)
[文献書誌] Shinoda, K. et al.: "Developmental defects of the ventromedial hypothalamic mucleus and pituitary gonadotroph in the Ftz-Fl disrupted mice." Developmental Dynamcs. 204. 22-29 (1995)
[文献書誌] Niwa, O. et al.: "Association of minisatellite sequence instability with c-myc gene amplification and K-ras gene mutation in mthylcholantrene-induced mouse sarcomas." Cancer Research. 55. 5670-5676 (1995)
[文献書誌] Tashiro, S. et al.: "Nuclear proteins binding to nthe recombination hotspots region of the retinoic acid receptor alpha gene." Cancer Research in Therapy and Control. 4. 293-300 (1995)
[文献書誌] Sasaki, M. S.: "Radioadaptive response : an implication for the biological consequences of low doserate exposure to radiations." Mutation Research. (印刷中). (1996)
[文献書誌] Kitahori, Y. et al.: "G-A mutation of ras genes and infrequent p53 gene mutaion in rat thyroid carcinoma lines from tumors induced in vivo by N-bis(2-hydroxy-propyl) nitrosoamine." Cancer Letter. (印刷中). (1996)
[文献書誌] Nakahashi, K. et al.: "Establishment of a rat thyroid Carcinoma cell line in vitro demonstrating high DNA synthesis in response to insulin-like growth factor I(IGF-I)." Cancer Letter. (印刷中). (1996)
[文献書誌] Ohnishi, T. et al.: "Cellular content of p53 protein in rat skin after exposure to space environment." Journal of Applied Physiology. (印刷中). (1996)
[文献書誌] Muramatsu, T. et al.: "Age-related decrease of heat shock protein 72 induction in normal human skin." British Journal of Dermatology. (印刷中). (1996)
[文献書誌] Tanaka, H. et al.: "Characterization of p53 gene mutations in esophageal squamous carcinoma cell lines : Increased frequency and different spectrum of mutations from primary thmors." International Journal of Cancer. (印刷中). (1996)

1995 年度 実績報告書

放射線応答の遺伝子制御

研究代表者

佐々木 正夫 京都大学, 放射線生物研究センター, 教授 (20013857)

研究成果

[文献書誌] Sasaki, M. S.: "On the rection kinetcs of the radioadaptive response in cultured mouse cells." International Journal of Radiation Biology. 68. 281-291 (1995)

[文献書誌] Kitahori, Y. et al: "Frequent matations of Ki-ras codon 12 in N-bis(2-hydroxypropyl)-niousadioa2aptive response in cultured mousoamine-initiated thryroid, kidney and lung tumors in Wister rats." Cancer Letters. 96. 155-161 (1995)

[文献書誌] Yano, T. et al.: "Enhancement effect of an anto-angiogenic agents, TNP-470, on hyperthemia-induced growth suppression of human esophageal and gastric cancers transplantable to nude mice." Anti-Cancer Research. 15. 1355-1358 (1995)

[文献書誌] Matsumoto, H, et al.: "Binding between wild-type p53 and hsp 72 accumulated after UV and γ-ray irradiation." Cancer Letters. 92. 127-133 (1995)

[文献書誌] Ohnishi, T. et al.: "Accumulation of mutant p53 and HSP72 by heat treatment, and their association in a human glioblastoma cell line." International Journal of Hypertherthemia. 11. 663-671 (1995)

[文献書誌] Matsumoto, H. et al.: "Preferential inhibition of nucleosome assembly by ulatraviolet-induced(6-4) photoproducts." Photochemistry and Photobiology. 19. 459-462 (1995)

[文献書誌] Nakano, T. et al.: "Mutation of shuttle vector plasmid, pZ189, in Escherichia coli induced by boron neutron capture beam (BNCB) containing α-particles." Mutation Research. 335. 153-159 (1995)

[文献書誌] Okaichi, K. et al.: "Unique DNA repair property of UV-sensitive (radC) mutant to Dictyostelium discoideum." Photochemistry and Photobiology. 61. 281-284 (1995)

[文献書誌] Kato, M. V. et al.: "Delayed development of retinoblastoma associated with loss of a maternal allele on chromosome 13." International Journal of Cancer. 64. 3-8 (1995)

[文献書誌] Shibagaki, I. et al.: "p53 mutation, MDM2 amplification and human papilloma virus infection are frequently involved but no associated with each other in esophageal squamous cell carcinoma." Clinical Cancer Resarch. 1. 769-773 (1995)

[文献書誌] Nkai, H. et al.: "Hemizygous expression of the wild-type p53 allele may confer a selective growth advantage before complete inactivation of the p53 gene in the progression of CML." British Journal of Hematology. 90. 147-155 (1995)

[文献書誌] Zhang, Q. M. et al.: "The sensitivity of three soi mutants of Eschrichia coli oxidizing mutants." Environmental Mutagen Research Communication. 16. 397-402 (1995)

[文献書誌] Zhang, Q. M. et al.: "Enzymatic repair of 5-formyl uracil in DNA caused by ionizing radiation in cell extract from mouse liver." International Journal of Radiation Biology. 68. 603-607 (1995)

[文献書誌] Taketo, M. et al.: "Homologs of Drosphila fushitarazu factor 1 map to mouse chromosome 2 and human chromosome 9q33." Genomics. 25. 565-567 (1995)

[文献書誌] Numoto, M. et al.: "Over-expressed ZF5 gene product, a c-myc-binding protein related to GL1-Kruppel protein, has a growth-suppressive activity in mouse cell lines." International Journal of Cancer Research. 86. 277-283 (1995)

[文献書誌] Fan, Y. -J., et al.: "Dose response of radiation indction of germline mutation at a hypervariable mouse minisatellile locus." International Journal of Radiation Biology. 68. 177-183 (1995)

[文献書誌] Nimomiya, Y. et al.: "Genomic organization and isoforms of the mouse ELP gene." Journal of Biochemistry. 118. 380-389 (1995)

[文献書誌] Huang, N. et al.: "Expression of CD21 antigen on myeloma cells and its involvement in their adhesion to bone marrow stromal cells." Blood. 85. 3704-3712 (1995)

[文献書誌] Shinoda, K. et al.: "Developmental defects of the ventromedial hypothalamic mucleus and pituitary gonadotroph in the Ftz-Fl disrupted mice." Developmental Dynamcs. 204. 22-29 (1995)

[文献書誌] Niwa, O. et al.: "Association of minisatellite sequence instability with c-myc gene amplification and K-ras gene mutation in mthylcholantrene-induced mouse sarcomas." Cancer Research. 55. 5670-5676 (1995)

[文献書誌] Tashiro, S. et al.: "Nuclear proteins binding to nthe recombination hotspots region of the retinoic acid receptor alpha gene." Cancer Research in Therapy and Control. 4. 293-300 (1995)

[文献書誌] Sasaki, M. S.: "Radioadaptive response : an implication for the biological consequences of low doserate exposure to radiations." Mutation Research. (印刷中). (1996)

[文献書誌] Kitahori, Y. et al.: "G-A mutation of ras genes and infrequent p53 gene mutaion in rat thyroid carcinoma lines from tumors induced in vivo by N-bis(2-hydroxy-propyl) nitrosoamine." Cancer Letter. (印刷中). (1996)

[文献書誌] Nakahashi, K. et al.: "Establishment of a rat thyroid Carcinoma cell line in vitro demonstrating high DNA synthesis in response to insulin-like growth factor I(IGF-I)." Cancer Letter. (印刷中). (1996)

[文献書誌] Ohnishi, T. et al.: "Cellular content of p53 protein in rat skin after exposure to space environment." Journal of Applied Physiology. (印刷中). (1996)

[文献書誌] Muramatsu, T. et al.: "Age-related decrease of heat shock protein 72 induction in normal human skin." British Journal of Dermatology. (印刷中). (1996)

[文献書誌] Tanaka, H. et al.: "Characterization of p53 gene mutations in esophageal squamous carcinoma cell lines : Increased frequency and different spectrum of mutations from primary thmors." International Journal of Cancer. (印刷中). (1996)

1995 年度実績報告書

佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857)