1994 Fiscal Year Annual Research Report

放射線応答の遺伝子制御

Research Project

Project/Area Number	06304049
Research Category	Grant-in-Aid for Co-operative Research (A)
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, 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)
Keywords	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
Research Abstract	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)。

Research Products

(26 results)

All Other

All Publications (26 results)

[Publications] Sasaki,M.S.: "Dissociation between radioresistant DNA replication and chromosomal readiosensitivity in ataxia telangiectasia." Mutation Research. 307. 107-113 (1994)
[Publications] 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)
[Publications] Kato,M.V.et al.: "Parental origin of germ-line and somatic mutations in the retinoblastoma gene." Human Genetics. 94. 31-38 (1994)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Gunge,N.et al.: "UV hypersensitivity of yeast linear plasmids." Current Genetics. 26. 369-373 (1994)
[Publications] 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)
[Publications] Takimoto,K.et al.: "Spectrum of proton-induced mutagenesis of the Escherichia coll crp gene." Mutation Research. 314. 1-9 (1994)
[Publications] Shibagaki,I.et al.: "Allelotype analysis of esophageal squamous cell carcinoma." Cancer Research. 54. 3107-3110 (1994)
[Publications] Nishida,N.et al.: "Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma." Cancer Research. 54. 2996-3000 (1994)
[Publications] 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)
[Publications] Wadayama,B.et al.: "Mutation spectrum of the retinoblastoma gene in osteosarcomas." Cancer Research. 54. 3042-3048 (1994)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Hori,H.et al.: "A convenient screening test for hypoxic cell radiosensitizers/cytotoxins." Biological and Pharmacological Bulletin. 17. 1676-1678 (1994)
[Publications] 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)
[Publications] Kamiya,K.et al.: "Susceptibility of mammary glangs to carcinogenesis." Pathology of the SAging Rats. 2. 477-482 (1994)
[Publications] Sadamoto,S.et al.: "Radiation induction of germline mutation at a hypervariable mouse minisatellite locus." International Journal of Radiation Biology. 65. 549-557 (1994)
[Publications] Morohashi,K.et al.: "Functional difference between Ad4BP and ELP,and their distribution in steroidgenic tissues." Molecular Endocrinology. 8. 643-653 (1994)
[Publications] 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)
[Publications] 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 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.: "Dissociation between radioresistant DNA replication and chromosomal readiosensitivity in ataxia telangiectasia." Mutation Research. 307. 107-113 (1994)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

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

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

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

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

[Publications] 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)

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

佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857)