DNA damage induced by near ultraviolet (UVA) and signal transduction

• Project/Area Number: 23510063
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Okayama University
• Principal Investigator: NEGISHI Tomoe 岡山大学, 医歯(薬)学総合研究科, 准教授 (80116491)
• Co-Investigator(Kenkyū-buntansha): IBUKI Yuko 静岡県立大学, 食品栄養科学部, 教授 (30236781)
• Research Collaborator: FANG Xing ; TOYOOKA Tatsushi
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 近紫外光 / 紫外線 / DNA傷害 / 活性酸素種 / ヒストンリン酸化 / ショウジョウバエ / DNA傷害修復 / UVA / 体細胞突然変異 / DNA二本鎖切断 / 酸化傷害 / 尿酸 / ピリミジン二量体 / 長波長紫外線 / 突然変異 / DNA損傷 / 染色体組換え / 細胞毒性 / シグナル伝達

Outline of Final Research Achievements

We have investigated the involvement of UVA in mutations and DNA damage in somatic cells using Drosophila melanogaster larvae. 365-nm-LED (a high-dose-rate UVA source) was mutagenic in mei-41 than in mei-9. The mei-41 gene was shown to be an orthologue of the human ATR gene, which is involved in the repair of DSBs through phosphorylation of histone H2Ax. LED-UVA was mutagenic in the urate-null strain at doses that were non-mutagenic in the urate-positive strain. We also observed that reactive oxygen species were produced in larvae by LED-UVA irradiation. At higher doses of LED-UVA, levels of phosphorylated H2AvD (γ-H2AvD) increased significantly in the urate-null strain but not in wild-type. It was reported that ATR functions on DSB repair in D. melanogaster. Taken together, we propose a possible pathway for UVA-induced mutation, whereby DNA double-strand breaks resulting from oxidative stress might be responsible for UVA-induced mutation in somatic cells of D. melanogaster larvae.

Research Products

• [Journal Article] Somatic cell mutations caused by 365-nm LED-UVA due to DNA double-strand breaks through oxidative damage (2014)
  • Author(s): Xing Fang, Naohiro Ide, Sho-ichi Higashi, Yasuhiro Kamei, Tatsushi Toyooka, Yuko Ibuki, Kazuaki Kawai, Hiroshi Kasai, Keinosuke Okamoto, Sakae Arimoto-Kobayashi, Tomoe Negishi
  • Journal Title: Photochem. Photobiol. Sci. Volume: 13 Issue: 9 Pages: 1338-1346
  • DOI: 10.1039/c4pp00148f
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mutagenicity and NO formation from UVA irradiated N-nitrosoproline, and characterization of photoproduct formed in UVA-irradiated mixture of N-nitrosoproline with 2'-deoxyguanosine in neutral solution (2014)
  • Author(s): Sakae Arimoto-Kobayashi, Masaki Machida, Kayoko Sano, Shuhei Aoyama, Chiharu Asahi, Noriko Tanaka, Keinosuke Okamoto, Tomoe Negishi, Sachiko Kimura and Toshinori Suzuki
  • Journal Title: Genes and Environment Volume: 36 Pages: 47-53
  • NAID: 130004943659
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Oral Administration of Non-genotoxic Hepato-hypertrophic Compounds on Metabolic Potency of Rat Liver (2014)
  • Author(s): Fang, X., Nunoshiba, T., Yoshida, M., Nishikawa, A., Nemoto, K., Degawa, M., Arimoto, S., Okamoto, K., Takahashi, E., Negishi, T.
  • Journal Title: Genes and Environment Volume: 36 Issue: 1 Pages: 1-9
  • DOI: 10.3123/jemsge.2013.011
  • NAID: 130004481209
  • ISSN: 1880-7046, 1880-7062
  • Peer Reviewed / Open Access
• [Journal Article] Distinct pathways for repairing mutagenic lesions induced by methylating and ethylating agents (2013)
  • Author(s): Taira, K., Kaneto, S., Nakano, K., Satanabe, S., Takahashi, E., Arimoto S., Okamoto, K., Schaaper, R.M., Negishi, K., Negishi, T.
  • Journal Title: Mutagenesis Volume: 28 Issue: 3 Pages: 341-350
  • DOI: 10.1093/mutage/get010
  • Peer Reviewed
• [Journal Article] Near ultraviolet radiation-mediated reaction between N-nitrosoproline and DNA: Isolation and identificatio of two new adducts, (R)- and (S)-8-(2-pyrrolidyl)-2’-deoxyguanosine (2013)
  • Author(s): Aoyama, S., Sano, K., Asahi, C., Machida, M., Okamoto, K., Negishi, T, Kimura, S., Suzuki, T., Hatano, T., Arimoto-Kobayashi, S.
  • Journal Title: J. Photochem. Photobilo. A: Chemistry Volume: 276 Pages: 1-7
  • DOI: 10.1016/j.jphotochem.2013.11.009
  • Peer Reviewed
• [Journal Article] Chemopreventive effects of the juice of Vitis coignetiae pulliat on two-stage mouse skin carcinogenesis (2013)
  • Author(s): Arimoto-Kobayashi, S., Zhang, X., Yuhara, Y., Kamiya. T., Negishi, T.
  • Journal Title: Nutrition and Cancer Volume: 65 Issue: 3 Pages: 440-450
  • DOI: 10.1080/01635581.2013.767916
  • Peer Reviewed
• [Journal Article] Novel Antimutagenic Proteins in The Edible Mushroom Agrocybe cylindracea (2012)
  • Author(s): Yoneda, K., Shiozawa A., Kitahara, A., Takahashi, E., Arimoto, S., Okamoto K., Negishi, T.
  • Journal Title: Genes & Environment Volume: 34 Pages: 9-17
  • NAID: 10030121728
  • Peer Reviewed
• [Journal Article] Effect of aflatoxin B1 on UDP-glucuronosyltransferase mRNA expression in HepG2 cells (2012)
  • Author(s): Hanioka N., Nonaka, Y., Saito K., Negishi, T., Okamoto, K., Kataoka, H., Narimatsu, S.
  • Journal Title: Chemosphere Volume: 89 Issue: 5 Pages: 526-529
  • DOI: 10.1016/j.chemosphere.2012.05.039
  • Peer Reviewed
• [Journal Article] Exposure to Cigarette Smoke Increases Urate Level and Decreases Glutathione Level in Larval Drosophila melanogaster (2011)
  • Author(s): Fujiwara, M., Hamatake, Y., Arimoto, S., Okamoto, K., Suzuki, T., Negishi, T.
  • Journal Title: Genes & Environment Volume: 33 Pages: 89-95
  • NAID: 10029337333
  • Peer Reviewed
• [Presentation] 長波長紫外線の突然変異誘発機構 (2015)
  • Author(s): 根岸友惠、樊星、鈴木利典、亀井保博、伊吹裕子
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] ショウジョウバエを用いた、紫外線およびアルキル化剤により誘発される突然変異の要因となるDNA傷害とその修復に関する研究 (2014)
  • Author(s): 根岸友惠
  • Organizer: 日本環境変異原学会第43回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-04 – 2014-12-05
  • Invited
• [Presentation] 長波長紫外線（365 nm-UVA）の変異誘発傷害とその修復機構 (2014)
  • Author(s): 樊 星、有元佐賀惠、豊岡達士、伊吹裕子、趙 暁旭、鈴木利典、根岸友惠
  • Organizer: 日本環境変異原学会第43回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-04 – 2014-12-05
• [Presentation] 長波長紫外線（365 nm-UVA）の変異誘発傷害とその修復機構 (2014)
  • Author(s): 樊 星、有元佐賀惠、豊岡達士、伊吹裕子、亀井保博、根岸友惠
  • Organizer: 第36回日本光医学光生物会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-25 – 2014-07-26
• [Presentation] ショウジョウバエ尿酸欠損株を用いた突然変異の研究 (2014)
  • Author(s): 小池亮太、内山友世、有元佐賀惠、岡本敬の介、根岸友惠
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] 長波長紫外線によるDNA傷害と体細胞突然変異 (2014)
  • Author(s): 樊 星、有元佐賀惠、岡本敬の介、豊岡達士、伊吹裕子、根岸友惠
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] Somatic mutation induced by LED-UVA irradiation (2013)
  • Author(s): Tomoe Negishi, Fang Xing, Norihiro Ide, Sho-ichi Higashi, Yasuhiro Kamei, Tatsushi Toyooka, Yuko Ibuki
  • Organizer: 6th Asia and Oceania Conference on Photobiology
  • Place of Presentation: Sydney, Australia
• [Presentation] クロロエチル化抗がん剤による変異とその修復機構 (2013)
  • Author(s): 渡部慎司、山田よう子、有元佐賀惠、岡本敬の介、根岸友惠
  • Organizer: 日本環境変異原学会第42回大会
  • Place of Presentation: 岡山
• [Presentation] 尿酸欠損が体細胞突然変異に及ぼす影響 (2013)
  • Author(s): 小池亮太、有元佐賀惠、岡本敬の介、根岸友惠
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] Somatic cell mutation induced by environmental cigarette smoke in Drosophila (2012)
  • Author(s): Tomoyo Uchiyama, Ryota Koike, Yoko Yuma, Keinosuke Okamoto, Sakae Arimoto, Tomoe Negishi
  • Organizer: 3rd Asian Conference on Environmental Mutagens
  • Place of Presentation: タイ（パタヤ）
• [Presentation] Phototoxicity of titanium dioxide nano-particles on Drosophila melanogaster (2012)
  • Author(s): Xing Fang, Keinosuke Okamoto, Sakae Arimoto, Tomoe Negishi
  • Organizer: 3rd Asian Conference on Environmental Mutagens
  • Place of Presentation: タイ（パタヤ）
• [Presentation] LED-UVAの遺伝毒性 (2012)
  • Author(s): 根岸友惠、樊 星、井出直宏、東 正一、豊岡達士、伊吹裕子
  • Organizer: 第34回日本光医学光生物会
  • Place of Presentation: 神戸
• [Presentation] 尿酸欠損が体細胞突然変異に及ぼす影響 (2012)
  • Author(s): 小池亮太、有元佐賀惠、岡本敬の介、根岸友惠
  • Organizer: 第51回日本薬学会中国四国支部大会
  • Place of Presentation: 松江
• [Presentation] ナノ粒子の光毒性 (2012)
  • Author(s): 樊 星、有元佐賀惠、根岸友惠、岡本敬の介、伊吹裕子、豊岡達士
  • Organizer: 第51回日本薬学会中国四国支部大会
  • Place of Presentation: 松江
• [Presentation] LED-UVAの遺伝毒性 (2012)
  • Author(s): 根岸友惠、樊 星、井出直宏、東 正一、豊岡達士、伊吹裕子
  • Organizer: 第41回日本環境変異原学会
  • Place of Presentation: 静岡
• [Presentation] バイオフォトン測定による酸化・抗酸化活性の新たな測定方法の検討 (2012)
  • Author(s): 橋本和政、勝又政和、有元佐賀惠、岡本敬の介、根岸友惠
  • Organizer: 第41回日本環境変異原学会
  • Place of Presentation: 静岡
• [Presentation] タバコ副流煙の体細胞突然変異誘発活性 (2012)
  • Author(s): 内山友世，遊間陽子，岡本敬の介，有元佐賀惠，根岸友惠
  • Organizer: 日本薬学会
  • Place of Presentation: 札幌
• [Presentation] ショウジョウバエミスマッチ修復欠損株の突然変異誘導脳と遺伝子不安定性について (2011)
  • Author(s): 宮本敬子，岡本敬の介，有元佐賀惠，根岸友惠
  • Organizer: 日本環境変異原学会
  • Place of Presentation: 東京
• [Presentation] 尿酸欠損が体細胞突然変異に及ぼす影響 (2011)
  • Author(s): 内山友世，岡本敬の介，有元佐賀惠，根岸友惠
  • Organizer: 日本環境変異原学会
  • Place of Presentation: 東京