1996 Fiscal Year Annual Research Report

放射線応答の遺伝子制御

Research Project

Project/Area Number	06304049
Research Institution	KYOTO UNIVERSITY
Principal Investigator	佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857)
Co-Investigator(Kenkyū-buntansha)	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) 米井脩治京都大学, 理学部, 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)
Keywords	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 / 遺伝的不安定性 / 放射線感受性
Research Abstract	放射線を刺激として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きた。哺乳動物細胞は微量の放射線に対しても鋭敏に反応し、適応応答と呼ばれる耐性を獲得するとともに、増殖刺激となって一過性の細胞増殖が誘導される。適応応答はCキナーゼとp38MAPキナーゼを介した情報伝達ループによって誘導され、長時間持続する。伝達された情報はDNA組換え機構を制御し、誤りの少ない修復が優先される(佐々木)。この過程にp53蛋白が関係していることが明らかになったが、p38MAPキナーゼとp53蛋白の関係は明らかでない。p53はHSP72などの熱ショック蛋白と会合することが分かったので(大西)、HSPを介した制御が考えられる。p53蛋白は低線量の放射線でも蓄積されるが、微小重力の下でも蓄積誘導が認められる(大西)。p53遺伝子がストレス応答のキ-遺伝子となっていることを示唆する。p53欠損マウスの細胞では低線量放射線に対する適応応答が誘導されないが(佐々木)、この細胞での突然変異は野生型マウスの細胞と紫外線誘発突然変異の型の分布が異なる(石崎)。p53蛋白がDNAの修復を制御し、突然変異の効率と型を変えていることが考えられる。DNAの酸化損傷の中で最も重要と考えられるフォルミルウラシルの修復実験経が確立された(米井)。ショウジョウバエを使った実験で精子を照射した場合に受精後雌側のミニサテライトが変異することが分かった(丹羽)。損傷の認識が細胞全体の遺伝的不安定性を誘導することが確実なものとなった。ヒトの放射線感受性遺伝子ΛTMの類似遺伝子の分離には至らなかったが、アタキシア・テランジェクタシア患者でATM遺伝子の新しい突然変異が明らかになった(江島)。

Research Products
(26 results)

All Other

All Publications (26 results)

[Publications] Sasaki,M.S.: "Radioadaptive response : an implication for the biological consequences of low dose-rate exposure to radiations." Mutation Research. 358. 207-213 (1996)
[Publications] Miwa,O: "Delayed effects and induction of genetic instability by radiation." Journal of Toxicological Sciences. 21. 61-63 (1996)
[Publications] Nakayama,T.et al.: "Fracture healing is a process independent of p53 function." In Vivo. 10. 553-558 (1996)
[Publications] Kato,M.V.et al.: "Genomic imprinting of the human serotonin-receptor(HTR2)gene involved in development of retinoblastoma." American Journal of Human Genet5cs. 59. 1084-1090 (1996)
[Publications] Kato,M.V.et al.: "Loss of heterozygocity on chromosome 17 and mutation of the p53 gene in retinoblastoma." Cancer Letters. 106. 75-82 (1996)
[Publications] Wang,X.et al.: "p53 accumulation in various organs of rats after whole-body exposure to low dose X-ray irradiation." Anticancer Reserach. 16. 1671-1674 (1996)
[Publications] Wang,X.et al.: "p53 accumulation in the organs of low-dose X-ray-irradiated mice." Cancer Letters. 104. 79-84 (1996)
[Publications] Ohnishi,T.et al.: "Cellular content of p53 protein in rat skin after exposure to a space environment." Journal of Applied Physiology. 81. 183-185 (1996)
[Publications] Ohnishi,T.et al.: "p53-dependent induction of WAF1 by heat treatment in human glioblastoma cells." Journal of Biological Chemistry. 271. 14510-14513 (1996)
[Publications] Matsumoto,H.et al.: "Suppression of heat-induced hsp72 accumulation by cisplatin in human glioblastoma cells." Cancer Letters. 110. 253-257 (1996)
[Publications] Ohnishi,K.et al.: "Heat shock transcription factor,HSF,is activated by ultraviolet irradiation." Photochemistry and Photobiology. 64. 949-952 (1996)
[Publications] Muramatsu,T.et al.: "DNA-damaging agents induce the 72-kD heat shock protein in SV40-transformed normal human fibroblasts." Journal of Dermatology. 23. 589-593 (1996)
[Publications] Nakabayashi,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." Cancer Letters. 101. 247-255 (1996)
[Publications] Muramatsu,T.et al.: "Age-related decrease in the inductability of heat shock protein in normal human skin." British Journal of Dermatology. 134. 1035-1038 (1996)
[Publications] Yane,K.et al.: "Lack pf p16/CDKN2 alterations in thyroid carcinomas." Cancer Letters. 101. 85-92 (1996)
[Publications] Kitahori,Y.et al.: "G-A mutation of ras genes and infrequent p53 gene mutation in rat transplantable thyroid carcinoma lines from tumors induced in vivo by N-bis(2-hydroxypropyl)nitrosoamine." Cancer Letters. 100. 55-62 (1996)
[Publications] Tanaka,H.et al.: "Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines : Increased frequency and different spectrum of mutations from primary tumors." International Journal of Cancer. 65. 372-376 (1996)
[Publications] Kato,V.M.et al.: "No significant changes in the expression of the fas,fasl,bc12 and bax genes in apoptosis of an erythroleukemia cell line by p53." International Journal of Oncology. 9. 269-277 (1996)
[Publications] Ishizaki,K.et al.: "UV-induced mutations of supF gene on a shuttle vector plasmid in p53-deficient mouse cells are qualitatively different from those in wild-type cells." Mutation Research. 364. 43-49 (1996)
[Publications] Zhang,Q.M.et al.: "Induction of repair capa-city for oxidatively damaged DNA as a component of peroxide stress in Escherichia coli." Journal of Radiation Research. 37. 171-175 (1996)
[Publications] Sugiyama,H.et al.: "New synthetic method of 5-formyluracil-containing oligonucleotides and their melting behavior." Tetrahedron Letters. 37. 9067-9070 (1996)
[Publications] Niwa,O.et al.: "Induction of a germline mutation at a hypervariable mouse minisatellite locus by 252-Cf radiation." Journal of Radiation Research. 37. 217-224 (1996)
[Publications] Komeda,K.et al.: "Induction of cell killing,mutation and umu gene expression by 6-mercaptopurine or 2-thiouracil with UVA irradiation." Photochemistry and Photobiology. 65. 115-118 (1997)
[Publications] Abe,Y.et al.: "A defect in cell to cell adhesion via integrin-fibronectin interactions observed in a highly metastatic tumor cell line." Japanese Journal of Cancer Research. 88. 67-71 (1997)
[Publications] Kotomura,N.et al.: "Transcriptional regulation by competition between ELP isoforms and nuclear receptors." Biochemical and Biophysical Reserch Communication. 230. 407-412 (1997)
[Publications] Yamamoto,K.et al.: "Enzymatic repair echanisms for base modifications induced by oxygen radicals." Journal of Radiation Research. (in press). (1997)

1996 Fiscal Year Annual Research Report

放射線応答の遺伝子制御

Principal Investigator

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

Research Products

[Publications] Sasaki,M.S.: "Radioadaptive response : an implication for the biological consequences of low dose-rate exposure to radiations." Mutation Research. 358. 207-213 (1996)

[Publications] Miwa,O: "Delayed effects and induction of genetic instability by radiation." Journal of Toxicological Sciences. 21. 61-63 (1996)

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

[Publications] Kato,M.V.et al.: "Genomic imprinting of the human serotonin-receptor(HTR2)gene involved in development of retinoblastoma." American Journal of Human Genet5cs. 59. 1084-1090 (1996)

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

[Publications] Wang,X.et al.: "p53 accumulation in various organs of rats after whole-body exposure to low dose X-ray irradiation." Anticancer Reserach. 16. 1671-1674 (1996)

[Publications] Wang,X.et al.: "p53 accumulation in the organs of low-dose X-ray-irradiated mice." Cancer Letters. 104. 79-84 (1996)

[Publications] Ohnishi,T.et al.: "Cellular content of p53 protein in rat skin after exposure to a space environment." Journal of Applied Physiology. 81. 183-185 (1996)

[Publications] Ohnishi,T.et al.: "p53-dependent induction of WAF1 by heat treatment in human glioblastoma cells." Journal of Biological Chemistry. 271. 14510-14513 (1996)

[Publications] Matsumoto,H.et al.: "Suppression of heat-induced hsp72 accumulation by cisplatin in human glioblastoma cells." Cancer Letters. 110. 253-257 (1996)

[Publications] Ohnishi,K.et al.: "Heat shock transcription factor,HSF,is activated by ultraviolet irradiation." Photochemistry and Photobiology. 64. 949-952 (1996)

[Publications] Muramatsu,T.et al.: "DNA-damaging agents induce the 72-kD heat shock protein in SV40-transformed normal human fibroblasts." Journal of Dermatology. 23. 589-593 (1996)

[Publications] Nakabayashi,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." Cancer Letters. 101. 247-255 (1996)

[Publications] Muramatsu,T.et al.: "Age-related decrease in the inductability of heat shock protein in normal human skin." British Journal of Dermatology. 134. 1035-1038 (1996)

[Publications] Yane,K.et al.: "Lack pf p16/CDKN2 alterations in thyroid carcinomas." Cancer Letters. 101. 85-92 (1996)

[Publications] Kitahori,Y.et al.: "G-A mutation of ras genes and infrequent p53 gene mutation in rat transplantable thyroid carcinoma lines from tumors induced in vivo by N-bis(2-hydroxypropyl)nitrosoamine." Cancer Letters. 100. 55-62 (1996)

[Publications] Tanaka,H.et al.: "Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines : Increased frequency and different spectrum of mutations from primary tumors." International Journal of Cancer. 65. 372-376 (1996)

[Publications] Kato,V.M.et al.: "No significant changes in the expression of the fas,fasl,bc12 and bax genes in apoptosis of an erythroleukemia cell line by p53." International Journal of Oncology. 9. 269-277 (1996)

[Publications] Ishizaki,K.et al.: "UV-induced mutations of supF gene on a shuttle vector plasmid in p53-deficient mouse cells are qualitatively different from those in wild-type cells." Mutation Research. 364. 43-49 (1996)

[Publications] Zhang,Q.M.et al.: "Induction of repair capa-city for oxidatively damaged DNA as a component of peroxide stress in Escherichia coli." Journal of Radiation Research. 37. 171-175 (1996)

[Publications] Sugiyama,H.et al.: "New synthetic method of 5-formyluracil-containing oligonucleotides and their melting behavior." Tetrahedron Letters. 37. 9067-9070 (1996)

[Publications] Niwa,O.et al.: "Induction of a germline mutation at a hypervariable mouse minisatellite locus by 252-Cf radiation." Journal of Radiation Research. 37. 217-224 (1996)

[Publications] Komeda,K.et al.: "Induction of cell killing,mutation and umu gene expression by 6-mercaptopurine or 2-thiouracil with UVA irradiation." Photochemistry and Photobiology. 65. 115-118 (1997)

[Publications] Abe,Y.et al.: "A defect in cell to cell adhesion via integrin-fibronectin interactions observed in a highly metastatic tumor cell line." Japanese Journal of Cancer Research. 88. 67-71 (1997)

[Publications] Kotomura,N.et al.: "Transcriptional regulation by competition between ELP isoforms and nuclear receptors." Biochemical and Biophysical Reserch Communication. 230. 407-412 (1997)

[Publications] Yamamoto,K.et al.: "Enzymatic repair echanisms for base modifications induced by oxygen radicals." Journal of Radiation Research. (in press). (1997)

佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857)