1994 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
研究種目	総合研究(A)
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) 米井脩治京都大学, 理学部, 助教授 (60093340) 石崎寛治愛知県がんセンター研究所, 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 / 適応応答 / 細胞内情報伝達 / 遺伝子発現 / 細胞周期制御 / 酸化ストレス / 放射線感受性遺伝子 / ゲノム不安定性
研究概要	生体は放射線に対して鋭敏に応答し、多様な生理活性を発現する。その放射線応答の遺伝子制御と生物学的意義を明らかにする目的で総合的研究を開始した。その結果、以下のことが明らかとなった。 1.哺乳動物細胞は0.1Gy以下の放射線に対して適応的に応答し、その後の放射線に対する致死感受性、突然変異感受性が低下する。応答の刺激分子種は酸化ラジカルと考えられ、情報はCキナーゼ(PKC)を介して増幅され、即発応答遺伝子の発現を誘導する(佐々木)。数時間後には細胞周期制御に働くwaf-1蛋白質が増加するが、この過程は熱ショック蛋白質による安定化を介してp53蛋白質の制御を受けている(大西)。 2.p53遺伝子をノックアウトした細胞では紫外線照射後のDNA複製の停止が見られず、姉妹染色分体交換(SCE)が高発する。p53がDNA損傷に対するチェック機能をしていることが明らかである(石崎)。 3.活性酸素高感受性の大腸菌変異株の分離に成功した。これから新しいスーパーオキサイド誘導遺伝子(soi)3種類を単離し、一次構造を決定した。この遺伝子は細胞内の酸化還元のバランスに応答して発現が誘導されることから、刺激分子種は活性酸素そのものではないとする新しい概念が考えられる(米井)。 4.ヒトの放射線高感受性遺伝病であるアタキシアテランジエクタシアの原因遺伝子の単離に取り組み、ヒトの第11染色体のq23領域の数センチモルガンの領域に限定することができた(江島)。 5.放射線照射された雄マウスで交配して生まれたF1マウスではDNA反復配列の変化が高頻度で起こっていることが明らかとなった。DNAを標的とした標的理論では説明できない新しい現象であり、放射線応答が遺伝的不安定性を誘導するとと考えられ、その遺伝子制御の機構が注目される(丹羽)。

研究成果
(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Sasaki,M.S.: "Dissociation between radioresistant DNA replication and chromosomal readiosensitivity in ataxia telangiectasia." Mutation Research. 307. 107-113 (1994)
[文献書誌] Shimizu,T.et al.: "Detection of mutations of the RB1 gene in retinoblastoma Patients by using exon-by-exon PCR-SSCP analysis." American Journal of Human Genetics. 54. 793-800 (1994)
[文献書誌] Kato,M.V.et al.: "Parental origin of germ-line and somatic mutations in the retinoblastoma gene." Human Genetics. 94. 31-38 (1994)
[文献書誌] Kato,M.V.et al.: "Mutations in the retinoblastoma gene and their expression in somatic cells of patients with hereditary retinoblastoma." Human Mutation. 3. 44-51 (1994)
[文献書誌] Saijo,M.et al.: "Inactivation of oncoprotein binding by a single Cys^<706>-to-Tyr substitution in the retinoblastoma protein." FEBS Letters. 340. 181-184 (1994)
[文献書誌] Matsubara,S.et al.: "The effects of X-ray energy and an iodine-based contrast agent on chromosome aberrations." Radiation Research. 137. 231-237 (1994)
[文献書誌] Matsumoto,H.et al.: "p53 proteins accumulated by heat stress associated with heat shock proteins HSP72/HSC73 in human glioblastoma cell lines." Cancer Letter. 87. 39-46 (1994)
[文献書誌] Gunge,N.et al.: "UV hypersensitivity of yeast linear plasmids." Current Genetics. 26. 369-373 (1994)
[文献書誌] Matsumoto,H.et al.: "The effects of ultraviolet light C (UVC) on in vitro nucleosome assembly and stability." Photochemistry and Photobiology. 60. 134-138 (1994)
[文献書誌] Takimoto,K.et al.: "Spectrum of proton-induced mutagenesis of the Escherichia coll crp gene." Mutation Research. 314. 1-9 (1994)
[文献書誌] Shibagaki,I.et al.: "Allelotype analysis of esophageal squamous cell carcinoma." Cancer Research. 54. 3107-3110 (1994)
[文献書誌] Nishida,N.et al.: "Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma." Cancer Research. 54. 2996-3000 (1994)
[文献書誌] Ishizaki,K.et al.: "Increased UV-induced SCEs but normal repair of DNA damage in p53-deficient mouse cells." International Journal of Cancer. 58. 254-257 (1994)
[文献書誌] Wadayama,B.et al.: "Mutation spectrum of the retinoblastoma gene in osteosarcomas." Cancer Research. 54. 3042-3048 (1994)
[文献書誌] Fujikawa,K.et al.: "Assignment of six patients with xeroderma pigmentosum in Hokkaido area to a variant form." Journal of Radiation Research. 35. 168-178 (1994)
[文献書誌] Kato,T.Jr.et al.: "Cloning of a marsupial DNA photolyase gene and lack of related nucleotide sequences in placental mammals." Nucleic Acid Research. 22. 4119-4124 (1994)
[文献書誌] Yonei,S.et al.: "Isolation and characterization of Escherichia coli strains containing new gene fusions (soi::lacZ) inducible by superoxide stress." Frontiers of Reactive Oxygen Species in Biology and Medicine. 277-278 (1994)
[文献書誌] Zhang,Q.M.et al.: "Molecular cloning and characterization of new members of the soxRS regulon in Escherichia coli." Frontiers of Reactive Oxygen Species in Biology and Medicine. 281-282 (1994)
[文献書誌] Takemoto,T.et al.: "Isolation and characterization of new soi genes inducible by superoxide radicals in Eschericia coli K12." Frontiers of Reactive Oxygen Species in Biology and Medicine. 279-280 (1994)
[文献書誌] Hori,H.et al.: "A convenient screening test for hypoxic cell radiosensitizers/cytotoxins." Biological and Pharmacological Bulletin. 17. 1676-1678 (1994)
[文献書誌] Zhang,Q.M.et al.: "The sensitivity of three soi mutants of Escherichia coli to oxidizing mutagenes." Environmental Mutagen Research Communication. 16. 407-412 (1994)
[文献書誌] Kamiya,K.et al.: "Susceptibility of mammary glangs to carcinogenesis." Pathology of the SAging Rats. 2. 477-482 (1994)
[文献書誌] Sadamoto,S.et al.: "Radiation induction of germline mutation at a hypervariable mouse minisatellite locus." International Journal of Radiation Biology. 65. 549-557 (1994)
[文献書誌] Morohashi,K.et al.: "Functional difference between Ad4BP and ELP,and their distribution in steroidgenic tissues." Molecular Endocrinology. 8. 643-653 (1994)
[文献書誌] Tashiro,S.et al.: "Identification of illegitimate recombination hot spot of the retinoic acid receptor alpha gene involved in 15;17 chromosome translocation." Oncogene. 9. 1939-1945 (1994)
[文献書誌] Kotomura,N.et al.: "Repression of retinoic acid-induced transactivation by embryonal long terminal repeat binding protein." Journal of Biochemistry. 116. 1309-1316 (1994)

1994 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.: "Dissociation between radioresistant DNA replication and chromosomal readiosensitivity in ataxia telangiectasia." Mutation Research. 307. 107-113 (1994)

[文献書誌] Shimizu,T.et al.: "Detection of mutations of the RB1 gene in retinoblastoma Patients by using exon-by-exon PCR-SSCP analysis." American Journal of Human Genetics. 54. 793-800 (1994)

[文献書誌] Kato,M.V.et al.: "Parental origin of germ-line and somatic mutations in the retinoblastoma gene." Human Genetics. 94. 31-38 (1994)

[文献書誌] Kato,M.V.et al.: "Mutations in the retinoblastoma gene and their expression in somatic cells of patients with hereditary retinoblastoma." Human Mutation. 3. 44-51 (1994)

[文献書誌] Saijo,M.et al.: "Inactivation of oncoprotein binding by a single Cys^<706>-to-Tyr substitution in the retinoblastoma protein." FEBS Letters. 340. 181-184 (1994)

[文献書誌] Matsubara,S.et al.: "The effects of X-ray energy and an iodine-based contrast agent on chromosome aberrations." Radiation Research. 137. 231-237 (1994)

[文献書誌] Matsumoto,H.et al.: "p53 proteins accumulated by heat stress associated with heat shock proteins HSP72/HSC73 in human glioblastoma cell lines." Cancer Letter. 87. 39-46 (1994)

[文献書誌] Gunge,N.et al.: "UV hypersensitivity of yeast linear plasmids." Current Genetics. 26. 369-373 (1994)

[文献書誌] Matsumoto,H.et al.: "The effects of ultraviolet light C (UVC) on in vitro nucleosome assembly and stability." Photochemistry and Photobiology. 60. 134-138 (1994)

[文献書誌] Takimoto,K.et al.: "Spectrum of proton-induced mutagenesis of the Escherichia coll crp gene." Mutation Research. 314. 1-9 (1994)

[文献書誌] Shibagaki,I.et al.: "Allelotype analysis of esophageal squamous cell carcinoma." Cancer Research. 54. 3107-3110 (1994)

[文献書誌] Nishida,N.et al.: "Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma." Cancer Research. 54. 2996-3000 (1994)

[文献書誌] Ishizaki,K.et al.: "Increased UV-induced SCEs but normal repair of DNA damage in p53-deficient mouse cells." International Journal of Cancer. 58. 254-257 (1994)

[文献書誌] Wadayama,B.et al.: "Mutation spectrum of the retinoblastoma gene in osteosarcomas." Cancer Research. 54. 3042-3048 (1994)

[文献書誌] Fujikawa,K.et al.: "Assignment of six patients with xeroderma pigmentosum in Hokkaido area to a variant form." Journal of Radiation Research. 35. 168-178 (1994)

[文献書誌] Kato,T.Jr.et al.: "Cloning of a marsupial DNA photolyase gene and lack of related nucleotide sequences in placental mammals." Nucleic Acid Research. 22. 4119-4124 (1994)

[文献書誌] Yonei,S.et al.: "Isolation and characterization of Escherichia coli strains containing new gene fusions (soi::lacZ) inducible by superoxide stress." Frontiers of Reactive Oxygen Species in Biology and Medicine. 277-278 (1994)

[文献書誌] Zhang,Q.M.et al.: "Molecular cloning and characterization of new members of the soxRS regulon in Escherichia coli." Frontiers of Reactive Oxygen Species in Biology and Medicine. 281-282 (1994)

[文献書誌] Takemoto,T.et al.: "Isolation and characterization of new soi genes inducible by superoxide radicals in Eschericia coli K12." Frontiers of Reactive Oxygen Species in Biology and Medicine. 279-280 (1994)

[文献書誌] Hori,H.et al.: "A convenient screening test for hypoxic cell radiosensitizers/cytotoxins." Biological and Pharmacological Bulletin. 17. 1676-1678 (1994)

[文献書誌] Zhang,Q.M.et al.: "The sensitivity of three soi mutants of Escherichia coli to oxidizing mutagenes." Environmental Mutagen Research Communication. 16. 407-412 (1994)

[文献書誌] Kamiya,K.et al.: "Susceptibility of mammary glangs to carcinogenesis." Pathology of the SAging Rats. 2. 477-482 (1994)

[文献書誌] Sadamoto,S.et al.: "Radiation induction of germline mutation at a hypervariable mouse minisatellite locus." International Journal of Radiation Biology. 65. 549-557 (1994)

[文献書誌] Morohashi,K.et al.: "Functional difference between Ad4BP and ELP,and their distribution in steroidgenic tissues." Molecular Endocrinology. 8. 643-653 (1994)

[文献書誌] Tashiro,S.et al.: "Identification of illegitimate recombination hot spot of the retinoic acid receptor alpha gene involved in 15;17 chromosome translocation." Oncogene. 9. 1939-1945 (1994)

[文献書誌] Kotomura,N.et al.: "Repression of retinoic acid-induced transactivation by embryonal long terminal repeat binding protein." Journal of Biochemistry. 116. 1309-1316 (1994)

1994 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)