2001 Fiscal Year Annual Research Report

酸化ストレスによる塩基配列特異的DNA損傷の解析と発がんおよび老化の予防

Research Project

Project/Area Number	12470084
Research Institution	Mie University
Principal Investigator	川西正祐三重大学, 医学部, 教授 (10025637)
Co-Investigator(Kenkyū-buntansha)	平工雄介三重大学, 医学部, 助手 (30324510) 及川伸二三重大学, 医学部, 講師 (10277006) 村田真理子三重大学, 医学部, 講師 (10171141)
Keywords	酸化ストレス / 塩基配列特異的DNA損傷 / 発がん / 老化 / テロメア / がん化学予防 / 活性酸素 / 酸化促進作用
Research Abstract	本研究は、環境因子、特に環境化学物質や食品成分、食品添加物およびその代謝物、紫外線(特にUVA)等と生体内物質(微量金属や還元物質、光増感物質)の共存下において生成される各種活性酸素種による塩基配列特異的DNA損傷を単離したがん関連遺伝子断片を用いて検討した。さらに、培養細胞、実験動物を用いてDNA損傷と活性酸素種生成についても解析を行った。本年度は、たばこの煙に含まれている発がん物質4-アミノビフェニルや自動車の排気ガスに含まれる大気汚染物質で発がん性のあるベンゾ[a]ピレンおよびベンゼン、2-ニトロプロパン、ニトロピレンの代謝物、産業化学物質のアクリロニトリル、アニリン、アニシジン、発酵食品に含まれるウレタン、医薬品に用いられているヒドロキシウアやダントロン等の発がん物質またはその代謝物が銅イオンの存在下で活性酸素を生成し塩基配列特異的にDNAを損傷することを認めた。また、培養細胞や実験動物においても活性酸素生成とDNA損傷を認めている。以上の結果から単環芳香族や低分子の化合物の発がん性には活性酸素が関与していることを初めて明らかにし、さらに今までDNA付加対の形成で説明されてきた多環芳香族化合物の発がん性に酸化的DNA損傷も重要な役割を果たしうる可能性を本研究で示した。 UVAが老化に関与しているテロメアのGGG配列を特異的に切断することにより、ヒト繊維芽細胞のテロメア領域の短縮促進に関与することが示唆された。発がんや老化の予防を有効に進めるため化学予防物質の安全性についてDNA損傷を指標に検討した。その結果、ルテオニンやフィチン酸はDNA損傷性が認められ無かったことから安全で有効ながん化学予防物質になりうると考えられる。今後、さらに酸化ストレスによる塩基配列特異的DNA損傷の解析を行い、発がんおよび老化の予防を目指す。

Research Products
(26 results)

All Other

All Publications (26 results)

[Publications] S.Ohnishi: "DNA damage induced by hypochlorite and hypobromite with reference to inflammation-associated carcinogenesis"Cancer Lett.. 178. 37-42 (2002)
[Publications] K.Hirakawa: "Catechol and Hydroquinone Have Different Redox Properties Responsible for Their Differential DNA-damaging Ability"Chem.Res.Toxicol. 15. 76-82 (2002)
[Publications] S.Ohnishi: "Double Base Lesions of DNA by a Metabolite of Carcinogenic Benzo[a]pyrene"Biochem.Biophys.Res.Commun.. 290. 778-782 (2002)
[Publications] S.Kawanishi: "Mechanism of Guanine-specific DNA Damage by Oxidative Stress and Its Role in Carcinogenesis and Aging"Mutation Res.(Reviews in Mutation Research). 488. 65-76 (2001)
[Publications] S.Kawanishi: "Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds"Free.Radic.Biol.Med.. 31. 108-116 (2001)
[Publications] T.Hishita: "Caspase-3 Activation by Lysosomal Enzymes in Cytochrome c-independent Apoptosis in a Myelodysplastic Syndrome(MDS)-derived Cell Line P39"Cancer Res.. 61. 2878-2884 (2001)
[Publications] S.Oikawa: "Site-specific DNA Damage at GGG Sequence by UVA Involves Acceleration of Telomere Shortening"Biochemistry. 40. 4763-4768 (2001)
[Publications] K.Midorikawa: "Superoxide dismutases enhance H_2O_2-induced DNA damage and alter its site specificity"FEBS Lett.. 495. 187-190 (2001)
[Publications] M.Murata: "Acrylonitril Enhances H_2O_2-Mediated DNA Damage via Nitrogen-Centered Radical Formation"Chem.Res.Toxicol.. 14. 1421-1427 (2001)
[Publications] S.Oikawa: "Site Specificity and Mechanism of Oxidative DNA Damage Induced by Carcinogenic Catechol"Carcinogenesis. 22. 1239-1245 (2001)
[Publications] M.Murata: "Mechanism of Oxidative DNA Damage Induced by Carcinogenic 4-Aminobiphenyl"Free Radic.Biol Med.. 30. 765-773 (2001)
[Publications] M.Murata: "Requirement of Glutathione and Cysteine in Guanine-specific Oxidation of DNA by Carcinogenic Potassium Bromate"Chem.Res.Toxicol.. 14. 678-685 (2001)
[Publications] K.Sakano: "Hydroxyurea Induces Site-specific DNA Damage via Formation of Hydrogen Peroxide and Nitric Oxide"Jpn.J.Cancer Res.. 92. 1166-1174 (2001)
[Publications] Y.Ohkuma: "Sequence-specific DNA damage induced by carcinogenic danthron and anthraquinone in the presence of Cu(II),cytochrome P450 reductase and NADPH"Free.Radic.Res.. 34. 595-604 (2001)
[Publications] S.Ohnishi: "Oxidative DNA damage induced by an N-hydroxy metabolite of carcinogenic 4-dimethylaminoazobenzene"Jpn.J.Cancer Res. 92. 23-29 (2001)
[Publications] K.Sakano: "Mechanism of Metal-mediated DNA Damage Induced by Metabolites of Carcinogenic 2-Nitropropane"Mutat.Res.. 479. 101-111 (2001)
[Publications] S.Ohnishi: "Oxidative DNA Damage by an N-Hydroxy Metabolite of the Mutagenic Compound Formed from Norharman and Aniline"Mutat.Res.. 494. 63-72 (2001)
[Publications] K.Midorikawa: "Protective Effect of Phytic Acid on Oxidative Damage with Reference to Cancer Chemoprevention"Biochem.Biophys.Res.Commun. 288. 552-557 (2001)
[Publications] Y.Ohkuma: "Oxidative DNA Damage Induced by a Metabolite of Carcinogenic o-Anisidine:Enhancement of DNA Damage and Alteration in its Sequence-Specificity by Superoxide Dismutase"Arch Biochem.Biophys.. 389. 49-56 (2001)
[Publications] S.Ohnishi: "Oxidative DNA Damage by a Metabolite of Carcinogenic 1-Nitropyrene"Biochem.Biophys.Res.Commun.. 280. 48-52 (2001)
[Publications] Y.Hiraku: "Amplification of Bleomycin-induced DNA Cleavage at Cytosine Residues 3'to GGG Sequences by Pyrrole Triamide"Biochem.Pharmaco. 61. 351-356 (2001)
[Publications] Y.Hiraku: "Catechol Estrogens Induce Oxidative DNA Damage and Estradiol Enhances Cell Proliferation"Int.J.Cancer. 92. 333-337 (2001)
[Publications] 及川伸二: "環境因子による酸化的DNA損傷とがん、老化"Environ.Mut.Res.Commun.. 23. 207-213 (2001)
[Publications] S.Kawanishi: "Oxidants and Anitoxidants in Cutaneous Biology"J.Thiele and P.Elsner. 193 (2001)
[Publications] 川西正祐: "中毒学-基礎・臨床・社会医学-"朝倉書店(荒記俊一編). 408 (2002)
[Publications] 川西正祐: "別冊医学のあゆみ酸化ストレス-フリーラジカル医学生物学の最前線"医歯薬出版(吉川敏一編). 326 (2001)

2001 Fiscal Year Annual Research Report

酸化ストレスによる塩基配列特異的DNA損傷の解析と発がんおよび老化の予防

Principal Investigator

川西 正祐 三重大学, 医学部, 教授 (10025637)

Research Products

[Publications] S.Ohnishi: "DNA damage induced by hypochlorite and hypobromite with reference to inflammation-associated carcinogenesis"Cancer Lett.. 178. 37-42 (2002)

[Publications] K.Hirakawa: "Catechol and Hydroquinone Have Different Redox Properties Responsible for Their Differential DNA-damaging Ability"Chem.Res.Toxicol. 15. 76-82 (2002)

[Publications] S.Ohnishi: "Double Base Lesions of DNA by a Metabolite of Carcinogenic Benzo[a]pyrene"Biochem.Biophys.Res.Commun.. 290. 778-782 (2002)

[Publications] S.Kawanishi: "Mechanism of Guanine-specific DNA Damage by Oxidative Stress and Its Role in Carcinogenesis and Aging"Mutation Res.(Reviews in Mutation Research). 488. 65-76 (2001)

[Publications] S.Kawanishi: "Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds"Free.Radic.Biol.Med.. 31. 108-116 (2001)

[Publications] T.Hishita: "Caspase-3 Activation by Lysosomal Enzymes in Cytochrome c-independent Apoptosis in a Myelodysplastic Syndrome(MDS)-derived Cell Line P39"Cancer Res.. 61. 2878-2884 (2001)

[Publications] S.Oikawa: "Site-specific DNA Damage at GGG Sequence by UVA Involves Acceleration of Telomere Shortening"Biochemistry. 40. 4763-4768 (2001)

[Publications] K.Midorikawa: "Superoxide dismutases enhance H_2O_2-induced DNA damage and alter its site specificity"FEBS Lett.. 495. 187-190 (2001)

[Publications] M.Murata: "Acrylonitril Enhances H_2O_2-Mediated DNA Damage via Nitrogen-Centered Radical Formation"Chem.Res.Toxicol.. 14. 1421-1427 (2001)

[Publications] S.Oikawa: "Site Specificity and Mechanism of Oxidative DNA Damage Induced by Carcinogenic Catechol"Carcinogenesis. 22. 1239-1245 (2001)

[Publications] M.Murata: "Mechanism of Oxidative DNA Damage Induced by Carcinogenic 4-Aminobiphenyl"Free Radic.Biol Med.. 30. 765-773 (2001)

[Publications] M.Murata: "Requirement of Glutathione and Cysteine in Guanine-specific Oxidation of DNA by Carcinogenic Potassium Bromate"Chem.Res.Toxicol.. 14. 678-685 (2001)

[Publications] K.Sakano: "Hydroxyurea Induces Site-specific DNA Damage via Formation of Hydrogen Peroxide and Nitric Oxide"Jpn.J.Cancer Res.. 92. 1166-1174 (2001)

[Publications] Y.Ohkuma: "Sequence-specific DNA damage induced by carcinogenic danthron and anthraquinone in the presence of Cu(II),cytochrome P450 reductase and NADPH"Free.Radic.Res.. 34. 595-604 (2001)

[Publications] S.Ohnishi: "Oxidative DNA damage induced by an N-hydroxy metabolite of carcinogenic 4-dimethylaminoazobenzene"Jpn.J.Cancer Res. 92. 23-29 (2001)

[Publications] K.Sakano: "Mechanism of Metal-mediated DNA Damage Induced by Metabolites of Carcinogenic 2-Nitropropane"Mutat.Res.. 479. 101-111 (2001)

[Publications] S.Ohnishi: "Oxidative DNA Damage by an N-Hydroxy Metabolite of the Mutagenic Compound Formed from Norharman and Aniline"Mutat.Res.. 494. 63-72 (2001)

[Publications] K.Midorikawa: "Protective Effect of Phytic Acid on Oxidative Damage with Reference to Cancer Chemoprevention"Biochem.Biophys.Res.Commun. 288. 552-557 (2001)

[Publications] Y.Ohkuma: "Oxidative DNA Damage Induced by a Metabolite of Carcinogenic o-Anisidine:Enhancement of DNA Damage and Alteration in its Sequence-Specificity by Superoxide Dismutase"Arch Biochem.Biophys.. 389. 49-56 (2001)

[Publications] S.Ohnishi: "Oxidative DNA Damage by a Metabolite of Carcinogenic 1-Nitropyrene"Biochem.Biophys.Res.Commun.. 280. 48-52 (2001)

[Publications] Y.Hiraku: "Amplification of Bleomycin-induced DNA Cleavage at Cytosine Residues 3'to GGG Sequences by Pyrrole Triamide"Biochem.Pharmaco. 61. 351-356 (2001)

[Publications] Y.Hiraku: "Catechol Estrogens Induce Oxidative DNA Damage and Estradiol Enhances Cell Proliferation"Int.J.Cancer. 92. 333-337 (2001)

[Publications] 及川伸二: "環境因子による酸化的DNA損傷とがん、老化"Environ.Mut.Res.Commun.. 23. 207-213 (2001)

[Publications] S.Kawanishi: "Oxidants and Anitoxidants in Cutaneous Biology"J.Thiele and P.Elsner. 193 (2001)

[Publications] 川西正祐: "中毒学-基礎・臨床・社会医学-"朝倉書店(荒記俊一 編). 408 (2002)

[Publications] 川西正祐: "別冊 医学のあゆみ 酸化ストレス-フリーラジカル医学生物学の最前線"医歯薬出版(吉川敏一 編). 326 (2001)

川西正祐三重大学, 医学部, 教授 (10025637)

[Publications] 川西正祐: "中毒学-基礎・臨床・社会医学-"朝倉書店(荒記俊一編). 408 (2002)

[Publications] 川西正祐: "別冊医学のあゆみ酸化ストレス-フリーラジカル医学生物学の最前線"医歯薬出版(吉川敏一編). 326 (2001)