1997 年度実績報告書

活性酸素の生物作用と生物の防御戦略

研究課題

研究課題/領域番号	08308032
研究機関	東北大学
研究代表者	山本和生東北大学, 大学院・理学研究科, 教授 (20093536)
研究分担者	井出博広島大学, 理学部, 教授 (30223126) 石井直明東海大学, 医学部, 助教授 (60096196) 湯川修身放射線医学総合研究所, 生物影響研究部第2研究室, 室長 (80166850) 米井脩治京都大学, 大学院・理学研究科, 教授 (60093340) 葛西宏産業医科大学, 産業生態科学研究所, 教授 (40152615)
キーワード	thymine glycol / アポトーシス誘導 / カタラーゼ欠損細胞 / 5-フォルミルウラシル / 酸化ストレス応答 / riboflavin光化学反応 / OxyR蛋白 / mutM遺伝子
研究概要	久保はHeLa細胞核抽出液中の2つのthymine glycol-DNAの切断活性を分離・精製した。桑原は過酸化水素によるアポトーシス誘導には、SAPK/JNKの膜から細胞質への移行とリン酸化が必要条件であることを明らかにした。葛西は8-OH-dGTPおよび2-OH-dATPを大腸菌に導入したところ、前者はAT→CG変異を、後者はGC→TA変異を特異的に誘発することを観察した。石井は寿命を短縮させる突然変異体、mev-1に遺伝子本体がcytochrome bであることを明らかにした。田野はカタラーゼ欠損細胞では、加齢とは無関係にカタラーゼ活性が低下することを観察した。米井はチオレドキシンの酸化還元が酸化ストレス応答の発現を制御することを証明した。張はin vitro DNA合成系で、鋳型中の5-ホミルウラシルの向かいにはdAMPとdCMPが転入されることを明らかにした。滝本はリボフラビン光増感反応でGC-MSにより8-OHdG以外にFapyGuaの生成を確認した。井出は塩基酸化損傷5-ホルミルウラシルは大腸菌AlkAタンパク質により修復されるが、ヒトホモログMPGはこれを修復しないことを明らかにした。森明は分裂酵母のcDNAやゲノムDNAの解析から生体防御に関連する多数の新規遺伝子を同定した。湯川は初代培養肝細胞で、放射線によるプロテインキナーゼの活性化は、細胞膜内に2相性のジアシルグリセロールが生ずるためであることを明らかにした。垰はOxyR蛋白の機能に必須のアミノ酸を同定し、また、大腸菌の新規酸化ストレス遺伝子を同定した。山本は大腸菌mutM遺伝子のヒトhomologueをクローニングし、酵素の特性を明らかにした。

研究成果
(47件)

すべてその他

すべて文献書誌 (47件)

[文献書誌] Abe,H.: "Involvement of both type I and type II mechanisms in M13 virus inactivation by methylene blue photosensitization." Photochemistry and Photobiology. 66. 204-208 (1997)
[文献書誌] Abe,H.: "Factors affecting M13 bacteriophage inactivation by methylene blue photosensitization." Photochemistry and Photobiology. 65. 873-876 (1997)
[文献書誌] Aburatani,H: "Cloning and characterization of mammalian 8-hydroxyguaninespecific DNA glycosylase/apurinic,apyrimidinic lyase,a functional mutM homologue." Cancer Res.57. 2151-2156 (1997)
[文献書誌] Asaeda,A: "Repair kinetics of abasic sites in mammalian cells selectively monitored by aldehyde reactive probe (ARP)" Nucleosides and Nucleotides. 16(印刷中). (1997)
[文献書誌] Asaeda,A: "Highly sensitive assay of DNA abasic sites in mammalian cells-optimization of the aldehyde reactive probe (ARP)" Anal.Chim.Acta. (印刷中). (1997)
[文献書誌] Asaeda,A: "Repair kinetics of abasic sites in mammalian cells selectively monitored by the aldehyde reactive prove (ARP)." Nucleosides and Nucleotides. (印刷中). (1997)
[文献書誌] Asami,S.: "Cigarette smoking induces an increase in oxidative DNA damage,8-hydroxydeoxyguanosine,in a central site of the human lung." Carcinogenesis. 18. 1763-1766 (1997)
[文献書誌] Hirano,T: "Inhibition of 8-hydroxyguanine repair in testes after administration of cadmium chloride to GSH-depleted rats." Toxicology and applied pharmacology. 147. 9-14 (1997)
[文献書誌] Hiraoka,W.: "Concentration-dependent modes of cell death in Chinese hamster V79 cells after treaments with H_2O_2." J.Radiat.Res.38. 95-102 (1997)
[文献書誌] Ide,H.: "Antibodies to oxidative DNA damage : Characterization of antibodies to 8-oxopurines." Cell Biol.Toxicol.13. 405-417 (1997)
[文献書誌] Ide,H.: "Mechanisms of the genotoxic effects associated with 5-formyluracil-Effect of exogenous 5-formyl-2′-deoxyuridine." Nucleic Acids Res.Symp.Ser.37. 165-166 (1997)
[文献書誌] Izumi,T.: "Molecular cloning and characterization of the promoter of the human N-methylpurin DNA glycosylase (MPG) gene." Carcinogenesis. 18. 1837-1839 (1997)
[文献書誌] Kamath-Loeb,A.S.: "Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by reverse transcriptases and mammalian DNA polymerases." J.Biol.Chem.272. 5892-5898 (1997)
[文献書誌] Kamiya,H.: "Mutations induced by 2-hydroxyadenine on a shuttle vector during leading and lagging strand syntheses in mammalian cells." Biochemistry. 36. 11125-11130 (1997)
[文献書誌] Kamiya,H.: "Substitution and deletion mutations induced by 2-hydroxyadenine in Escherichia coli・Effects of sequence contexts in leading and lagging strands." Nucleic Acide Res.25. 304-310 (1997)
[文献書誌] Kanbashi,K: "Frameshifts,base substitutions and minute deletions constitute X-ray-induced mutations in the endogenous tonB gene of Escherichia coli K12." Mutation Res.(印刷中). (1998)
[文献書誌] Kuwabara,M: "The increased formation of alkali labile sites by a spin-trapping agent alpha-phenyl-N-tert-butylnitrone in gamma-irradiated frozen aqueous solution of DNA." J.Radiat.Res.38. 153-155 (1997)
[文献書誌] Mita,K.: "Comprehensive cloning of Schizosacharomyces pombe genes encoding translation elongation factors." Gene. 187. 259-266 (1997)
[文献書誌] Mori,T.: "Formation of 8-hydroxyguanine and 2,6-diamino4-hydroxy-formamidopyrimidine in DNA by riboflavin mediated photosensitization." Biochem.Biophys.Res.Comun.(印刷中). (1998)
[文献書誌] Murata-Kamiya,N.: "Comparision of oxidation products from DNA components by γ-irradiation and Fenton-type reactions." J.Radiat.Res.38. 121-131 (1997)
[文献書誌] Murata-Kamiya,N.: "Glyoxal,a major product of DNA oxidation,induces mutations at G : C sites on a shuttle vector plasmid replicated in mammalian cells." Nucleic Acid Res.25. 1897-1902 (1997)
[文献書誌] Murata-Kamiya,N.: "Types of mutations induced by glyoxal,a major oxidative DNA-damage product,in Salmonella typhimurium." Mutation Res.377. 13-16 (1997)
[文献書誌] Murata-Kamiya,N.: "Mutational specificity of glyoxal,a product of DNA oxidation,in the lacI gene of wild-type Escherichia coli W3110." Mutation Res.377. 255-262 (1997)
[文献書誌] Nakajima,S.: "Cloning and characterization of a gene (UVR3) required for photorepair of 6-4 products in Arabidopsis thaliana." Nucleic Acid Res.26. 638-644 (1998)
[文献書誌] Nagashima,M.: "Presence of human cellular protein(s) that specifically binds and cleaves 8-hydroxyguanine containing DNA." Mutation Res.383. 49-59 (1997)
[文献書誌] Ohshima,H.: "Reactions between hydroxyl-radical-induced 7,8-dihydro-8-oxo-2′-deoxyguanosine precursor and the spin trap alpha-phenyl-N-tert-butylnitrone." J.Radiat.Res.38. 15-25 (1997)
[文献書誌] Ono,T.: "X-ray-and ultraviolet-radiation-induced mutations in Muta^<TM> Mouse." Radiation Res.148. 123-128 (1997)
[文献書誌] Saito,Y.: "Characterization of endonuclease III (nth) and endonuclease VIII (nei) mutants of Escherichia coli K-12." J.Bacteriol.179. 3783-3785 (1997)
[文献書誌] Shimamura,H.: "Mutational Specificity of the ferrous ion a sup F gene of endonuclease III/VIII deficient Escherichia coli." J.Radiat・Res.38. 165-171 (1997)
[文献書誌] Shimuzu,H.: "Replication bypass and mutagenic effect of alpha-deoxyadenosine site-specifically incorporated into single-stranded vector." Nucleic Acids Res.25. 597-603 (1997)
[文献書誌] Shinmura,K.: "8-hydroxyguanine (7,8-dihydro-8-oxoguanine) DNA glycosylase and AP lyase activities of hOGG1 protein and their substrate specificity." Mutation Res.385. 75-82 (1997)
[文献書誌] Suzuki,T.: "Deglycosylation susceptibility and base-pairing stability of 2′-deoxyoxanosine in oligodeoxynucleotide." Biochemistry. 36. 8013-8019 (1997)
[文献書誌] Takahashi,K.: "Relationship between asbestos exposures and 8-hydroxydeoxyguanosine levels in leukocytic DNA of workers at a Chinese asbestos-material plant." Int.J.Occup.Environ.Health. 3. 111-119 (1997)
[文献書誌] Takemoto,T.: "Different mechanisms of thioredoxin in its reduced and oxidized forms in defense against hydrogen peroxide in Escherichia coli." Free Rad.Biol.Med.(印刷中). (1998)
[文献書誌] Takimoto,K: "Spectrum of spontaneous mutations in the cyclic AMP receptor protein gene on chromosomal DNA of Escherichia coli." J.Radiat.Res.38. 27-36 (1997)
[文献書誌] Tano,K.: "Amplification of the DNA repair gene O6-methylguanine-DNA methyltransferase associated with resistant to alkylating agents drugs in mammalian cell line." J.Biol.Chem.272. 13250-13254 (1997)
[文献書誌] Tao,K.: "OxyR-dependent induction of Escherichia coli grx gene expression by peroxide stress." J.Bacteriol.179. 5967-5970 (1997)
[文献書誌] Terato,H.: "Novel modification of 5-formyluracil by cysteine derivatives in aqueous solution." Nucleosides Nucleotides. (印刷中). (1998)
[文献書誌] Terato,H.: "Formation of highly fluorescent adducts between 2′-deoxyguanosine and amino acids by ionizing radiation." Anal.Chim.Acta. (印刷中). (1998)
[文献書誌] Yamamoto,K.: "Enzymatic repair mechanisms for base modifications induced by oxygen radicals." J.Radiat.Res.38. 1-4 (1997)
[文献書誌] Yamashita,T.: "Progressive effect of alpha-phenyl-N-tert-butylnitrone (PBN) rat embryo development in vitro." Free Radical Biol.Med.23. 1073-1077 (1997)
[文献書誌] Yonemasu,R.: "Chracterization of the alternative excision repair pathway of UV-damaged DNA in Schizosaccharomyces pombe." Nucleic Acids Res.25. 1553-1559 (1997)
[文献書誌] Yoshida,M.: "Substrate and misparing properties of 5-formyl-2′-deoxyuridine 5′-triphosphate assessed by in vitro DNA polymerase reactions." Nucleic Acids Res.25. 1570-1577 (1997)
[文献書誌] Zhang,Q.M.: "Replication of DNA templates containing 5-formyluracil,a major oxidative lesion of thymine in DNA." Nucleic Acids Res.25. 3969-3973 (1997)
[文献書誌] Zhang,D.: "Vitamin E inhibits apoptosis,DNA modfication,and cancer incidence induced by iron-mediated peroxidation in Wister rat kidney." Cancer Res.57. 2410-2414 (1997)
[文献書誌] 山本和生: "活性酸素によるDNAの傷とその修復。" 「健康と環境II」、池永満生、野村大成、森本兼襄編集、株式会社へるす出版, 310(183-197) (1998)
[文献書誌] 石井直明: "老化と死" 「生物学のすすめ」黒田洋一郎、馬淵一誠編編集、筑摩書房, 205(55-84) (1997)

1997 年度 実績報告書

活性酸素の生物作用と生物の防御戦略

研究代表者

山本 和生 東北大学, 大学院・理学研究科, 教授 (20093536)

研究成果

[文献書誌] Abe,H.: "Involvement of both type I and type II mechanisms in M13 virus inactivation by methylene blue photosensitization." Photochemistry and Photobiology. 66. 204-208 (1997)

[文献書誌] Abe,H.: "Factors affecting M13 bacteriophage inactivation by methylene blue photosensitization." Photochemistry and Photobiology. 65. 873-876 (1997)

[文献書誌] Aburatani,H: "Cloning and characterization of mammalian 8-hydroxyguaninespecific DNA glycosylase/apurinic,apyrimidinic lyase,a functional mutM homologue." Cancer Res.57. 2151-2156 (1997)

[文献書誌] Asaeda,A: "Repair kinetics of abasic sites in mammalian cells selectively monitored by aldehyde reactive probe (ARP)" Nucleosides and Nucleotides. 16(印刷中). (1997)

[文献書誌] Asaeda,A: "Highly sensitive assay of DNA abasic sites in mammalian cells-optimization of the aldehyde reactive probe (ARP)" Anal.Chim.Acta. (印刷中). (1997)

[文献書誌] Asaeda,A: "Repair kinetics of abasic sites in mammalian cells selectively monitored by the aldehyde reactive prove (ARP)." Nucleosides and Nucleotides. (印刷中). (1997)

[文献書誌] Asami,S.: "Cigarette smoking induces an increase in oxidative DNA damage,8-hydroxydeoxyguanosine,in a central site of the human lung." Carcinogenesis. 18. 1763-1766 (1997)

[文献書誌] Hirano,T: "Inhibition of 8-hydroxyguanine repair in testes after administration of cadmium chloride to GSH-depleted rats." Toxicology and applied pharmacology. 147. 9-14 (1997)

[文献書誌] Hiraoka,W.: "Concentration-dependent modes of cell death in Chinese hamster V79 cells after treaments with H_2O_2." J.Radiat.Res.38. 95-102 (1997)

[文献書誌] Ide,H.: "Antibodies to oxidative DNA damage : Characterization of antibodies to 8-oxopurines." Cell Biol.Toxicol.13. 405-417 (1997)

[文献書誌] Ide,H.: "Mechanisms of the genotoxic effects associated with 5-formyluracil-Effect of exogenous 5-formyl-2′-deoxyuridine." Nucleic Acids Res.Symp.Ser.37. 165-166 (1997)

[文献書誌] Izumi,T.: "Molecular cloning and characterization of the promoter of the human N-methylpurin DNA glycosylase (MPG) gene." Carcinogenesis. 18. 1837-1839 (1997)

[文献書誌] Kamath-Loeb,A.S.: "Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by reverse transcriptases and mammalian DNA polymerases." J.Biol.Chem.272. 5892-5898 (1997)

[文献書誌] Kamiya,H.: "Mutations induced by 2-hydroxyadenine on a shuttle vector during leading and lagging strand syntheses in mammalian cells." Biochemistry. 36. 11125-11130 (1997)

[文献書誌] Kamiya,H.: "Substitution and deletion mutations induced by 2-hydroxyadenine in Escherichia coli・Effects of sequence contexts in leading and lagging strands." Nucleic Acide Res.25. 304-310 (1997)

[文献書誌] Kanbashi,K: "Frameshifts,base substitutions and minute deletions constitute X-ray-induced mutations in the endogenous tonB gene of Escherichia coli K12." Mutation Res.(印刷中). (1998)

[文献書誌] Kuwabara,M: "The increased formation of alkali labile sites by a spin-trapping agent alpha-phenyl-N-tert-butylnitrone in gamma-irradiated frozen aqueous solution of DNA." J.Radiat.Res.38. 153-155 (1997)

[文献書誌] Mita,K.: "Comprehensive cloning of Schizosacharomyces pombe genes encoding translation elongation factors." Gene. 187. 259-266 (1997)

[文献書誌] Mori,T.: "Formation of 8-hydroxyguanine and 2,6-diamino4-hydroxy-formamidopyrimidine in DNA by riboflavin mediated photosensitization." Biochem.Biophys.Res.Comun.(印刷中). (1998)

[文献書誌] Murata-Kamiya,N.: "Comparision of oxidation products from DNA components by γ-irradiation and Fenton-type reactions." J.Radiat.Res.38. 121-131 (1997)

[文献書誌] Murata-Kamiya,N.: "Glyoxal,a major product of DNA oxidation,induces mutations at G : C sites on a shuttle vector plasmid replicated in mammalian cells." Nucleic Acid Res.25. 1897-1902 (1997)

[文献書誌] Murata-Kamiya,N.: "Types of mutations induced by glyoxal,a major oxidative DNA-damage product,in Salmonella typhimurium." Mutation Res.377. 13-16 (1997)

[文献書誌] Murata-Kamiya,N.: "Mutational specificity of glyoxal,a product of DNA oxidation,in the lacI gene of wild-type Escherichia coli W3110." Mutation Res.377. 255-262 (1997)

[文献書誌] Nakajima,S.: "Cloning and characterization of a gene (UVR3) required for photorepair of 6-4 products in Arabidopsis thaliana." Nucleic Acid Res.26. 638-644 (1998)

[文献書誌] Nagashima,M.: "Presence of human cellular protein(s) that specifically binds and cleaves 8-hydroxyguanine containing DNA." Mutation Res.383. 49-59 (1997)

[文献書誌] Ohshima,H.: "Reactions between hydroxyl-radical-induced 7,8-dihydro-8-oxo-2′-deoxyguanosine precursor and the spin trap alpha-phenyl-N-tert-butylnitrone." J.Radiat.Res.38. 15-25 (1997)

[文献書誌] Ono,T.: "X-ray-and ultraviolet-radiation-induced mutations in Muta^<TM> Mouse." Radiation Res.148. 123-128 (1997)

[文献書誌] Saito,Y.: "Characterization of endonuclease III (nth) and endonuclease VIII (nei) mutants of Escherichia coli K-12." J.Bacteriol.179. 3783-3785 (1997)

[文献書誌] Shimamura,H.: "Mutational Specificity of the ferrous ion a sup F gene of endonuclease III/VIII deficient Escherichia coli." J.Radiat・Res.38. 165-171 (1997)

[文献書誌] Shimuzu,H.: "Replication bypass and mutagenic effect of alpha-deoxyadenosine site-specifically incorporated into single-stranded vector." Nucleic Acids Res.25. 597-603 (1997)

[文献書誌] Shinmura,K.: "8-hydroxyguanine (7,8-dihydro-8-oxoguanine) DNA glycosylase and AP lyase activities of hOGG1 protein and their substrate specificity." Mutation Res.385. 75-82 (1997)

[文献書誌] Suzuki,T.: "Deglycosylation susceptibility and base-pairing stability of 2′-deoxyoxanosine in oligodeoxynucleotide." Biochemistry. 36. 8013-8019 (1997)

[文献書誌] Takahashi,K.: "Relationship between asbestos exposures and 8-hydroxydeoxyguanosine levels in leukocytic DNA of workers at a Chinese asbestos-material plant." Int.J.Occup.Environ.Health. 3. 111-119 (1997)

[文献書誌] Takemoto,T.: "Different mechanisms of thioredoxin in its reduced and oxidized forms in defense against hydrogen peroxide in Escherichia coli." Free Rad.Biol.Med.(印刷中). (1998)

[文献書誌] Takimoto,K: "Spectrum of spontaneous mutations in the cyclic AMP receptor protein gene on chromosomal DNA of Escherichia coli." J.Radiat.Res.38. 27-36 (1997)

[文献書誌] Tano,K.: "Amplification of the DNA repair gene O6-methylguanine-DNA methyltransferase associated with resistant to alkylating agents drugs in mammalian cell line." J.Biol.Chem.272. 13250-13254 (1997)

[文献書誌] Tao,K.: "OxyR-dependent induction of Escherichia coli grx gene expression by peroxide stress." J.Bacteriol.179. 5967-5970 (1997)

[文献書誌] Terato,H.: "Novel modification of 5-formyluracil by cysteine derivatives in aqueous solution." Nucleosides Nucleotides. (印刷中). (1998)

[文献書誌] Terato,H.: "Formation of highly fluorescent adducts between 2′-deoxyguanosine and amino acids by ionizing radiation." Anal.Chim.Acta. (印刷中). (1998)

[文献書誌] Yamamoto,K.: "Enzymatic repair mechanisms for base modifications induced by oxygen radicals." J.Radiat.Res.38. 1-4 (1997)

[文献書誌] Yamashita,T.: "Progressive effect of alpha-phenyl-N-tert-butylnitrone (PBN) rat embryo development in vitro." Free Radical Biol.Med.23. 1073-1077 (1997)

[文献書誌] Yonemasu,R.: "Chracterization of the alternative excision repair pathway of UV-damaged DNA in Schizosaccharomyces pombe." Nucleic Acids Res.25. 1553-1559 (1997)

[文献書誌] Yoshida,M.: "Substrate and misparing properties of 5-formyl-2′-deoxyuridine 5′-triphosphate assessed by in vitro DNA polymerase reactions." Nucleic Acids Res.25. 1570-1577 (1997)

[文献書誌] Zhang,Q.M.: "Replication of DNA templates containing 5-formyluracil,a major oxidative lesion of thymine in DNA." Nucleic Acids Res.25. 3969-3973 (1997)

[文献書誌] Zhang,D.: "Vitamin E inhibits apoptosis,DNA modfication,and cancer incidence induced by iron-mediated peroxidation in Wister rat kidney." Cancer Res.57. 2410-2414 (1997)

[文献書誌] 山本和生: "活性酸素によるDNAの傷とその修復。" 「健康と環境II」、池永満生、野村大成、森本兼襄 編集、株式会社へるす出版, 310(183-197) (1998)

[文献書誌] 石井直明: "老化と死" 「生物学のすすめ」黒田洋一郎、馬淵一誠編 編集、筑摩書房, 205(55-84) (1997)

1997 年度実績報告書

山本和生東北大学, 大学院・理学研究科, 教授 (20093536)

[文献書誌] 山本和生: "活性酸素によるDNAの傷とその修復。" 「健康と環境II」、池永満生、野村大成、森本兼襄編集、株式会社へるす出版, 310(183-197) (1998)

[文献書誌] 石井直明: "老化と死" 「生物学のすすめ」黒田洋一郎、馬淵一誠編編集、筑摩書房, 205(55-84) (1997)