UVA activated N-nitrosoproline induced damages on DNA, protein and membrane, and disturbance of signal transduction

• Project/Area Number: 23510075
• 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: ARIMOTO Sakae 岡山大学, 医歯(薬)学総合研究科, 准教授 (90212654)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ニトロソプロリン / UVA / DNA損傷 / 一酸化窒素 / アルキルラジカル / DNA付加体 / 遺伝毒性 / 小核形成 / 光化学反応 / 8-オキソグアニン / ヌクレオチド付加体 / 光毒性 / 光遺伝毒性 / ヒトケラチノサイト

Research Abstract

We investigated near-ultraviolet radiation (UVA) mediated chemical reaction of N-nitrosoproline (NPRO) with DNA, deoxynucleosides, amino acids and membrane lipids, and isolated several new products from the UVA-irradiated mixture. Photogenotoxicity was found with NPRO towards human derived keratinocyte cells. Nitric oxide was released during photoreaction of NPRO to create active radicals that can give phototoxicity.

Research Products

• [Journal Article] Mutagenicity and NO Formation from UVA Irradiated <i>N</i>-Nitrosoproline, and Characterization of Photoproduct Formed in UVA-irradiated Mixture of <i>N</i>-Nitrosoproline with 2&prime;-Deoxyguanosine in Neutral Solution (2014)
  • Author(s): Arimoto-Kobayashi, S., Machida, M., Sano, K., Aoyama, S., Asahi, C., Tanaka, N., Okamoto, K., Negishi, T., Kimura, S. and Suzuki, T
  • Journal Title: Genes and Environment Volume: 36 Issue: 2 Pages: 47-53
  • DOI: 10.3123/jemsge.2014.004
  • NAID: 130004943659
  • ISSN: 1880-7046, 1880-7062
  • 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] Photomicronucleus assay of phototoxic and pseudophotoclastogenic chemicals in human keratinocyte NCTC2544 cells (2011)
  • Author(s): Mayumi Horinouchi, Sakae Arimoto-Kobayashi
  • Journal Title: Mutation Research Volume: 725 Issue: 1 Pages: 43-50
  • DOI: 10.1016/j.mrgentox.2011.04.005
  • Peer Reviewed
• [Presentation] Release of nitric oxide and formation of mutagenic substance from UVA irradiated N-nitrosoproline in non-aqueous lipids (2014)
  • Author(s): Arimoto-Kobayashi,S., Moriwaki, N., Tanaka, N., Okamoto, K. and Negishi, T
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International (SFRRI2014)
  • Place of Presentation: 京都
• [Presentation] Release of nitric oxide and formation of mutagenic substance from UVA irradiated N-nitrosoproline in non-aqueous lipids (2014)
  • Author(s): Sakae Arimoto-Kobayashi, Naofumi Moriwaki, Noriko Tanaka, Keinosuke Okamoto and Tomoe Negishi
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International
  • Place of Presentation: 京都
• [Presentation] 日本環境変異原学会シンポジウムII「光遺伝毒性の最近の動向」 (2013)
  • Author(s): 有元佐賀惠
  • Organizer: 「変異原性物質とDNA の光化学反応」、日本環境変異原学会42回大会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] Near ultraviolet light-mediated reaction between N-nitrosoproline and DNA : Isolation and identification of new adducts (2013)
  • Author(s): Arimoto-Kobayashi, S., Aoyama, S., Asahi, C., Sano, K., Machida, M., Okamoto, K., Negishi, T., Kimura, S., Suzuki, T. and Hatano, T
  • Organizer: The 6th Asia and Oceania Conference on Photobiology
  • Place of Presentation: シドニー
• [Presentation] UVA 活性化N-ニトロソプロリンによるヒトケラチノサイト由来細胞への遺伝毒性 (2013)
  • Author(s): 田中範子、森脇直史、岡本敬の介、根岸友恵、佐藤聡、有元佐賀惠
  • Organizer: 第35回日本光医学・光生物学会
  • Place of Presentation: 浜松
• [Presentation] N-ニトロソプロリンのUVA 光反応によるDNA 付加体形成 (2013)
  • Author(s): 旭千春、青山周平、岡本敬の介、根岸友恵、波多野力、有元佐賀惠
  • Organizer: 第35回日本光医学・光生物学会
  • Place of Presentation: 浜松
• [Presentation] Near ultraviolet light-mediated reaction between N-nitrosoproline and DNA: Isolation and identification of new adducts (2013)
  • Author(s): Arimoto-Kobayashi S, Aoyama S, Asahi C, Sano K, Machida M, Okamoto K, Negishi T, Kimura S, Suzuki T and Tsutomu Hatano
  • Organizer: The 6th Asia and Oceania Conference on Photobiology
  • Place of Presentation: Sydney
• [Presentation] N-ニトロソプロリンのUVA光反応によるDNA付加体形成 (2013)
  • Author(s): 旭千春、青山周平、岡本敬の介、根岸友恵、波多野力、有元佐賀惠
  • Organizer: 第３５回日本光医学・光生物学会
  • Place of Presentation: 浜松
• [Presentation] UVA活性化N-ニトロソプロリンによるヒトケラチノサイト由来細胞への遺伝毒性 (2013)
  • Author(s): 田中範子、森脇直史、岡本敬の介、根岸友恵、佐藤聡、有元佐賀惠
  • Organizer: 第３５回日本光医学・光生物学会
  • Place of Presentation: 浜松
• [Presentation] 変異原性物質とDNA の光化学反応 (2013)
  • Author(s): 有元佐賀惠
  • Organizer: 日本環境変異原学会42回大会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] UVA 活性化N-ニトロソプロリンによる新規核酸付加体 (2012)
  • Author(s): 有元佐賀惠、青山周平、田中範子、佐野嘉容子、根岸友恵、波多野力、鈴木利典、木村幸子
  • Organizer: 第34回日本光医学・光生物学会
  • Place of Presentation: 神戸
• [Presentation] UVA活性化N-ニトロソプロリンによる新規核酸付加体 (2012)
  • Author(s): 有元佐賀惠、青山周平、田中範子、佐野嘉容子、根岸友恵、波多野力、鈴木利典、木村幸子
  • Organizer: 第33回日本光医学・光生物学会
  • Place of Presentation: 神戸市
• [Presentation] 培養ヒトケラチノサイトによる化学物質の光細胞毒性・光遺伝毒性試験 (2011)
  • Author(s): 堀ノ内眞弓、有元佐賀惠
  • Organizer: 日本環境変異原学会第40回大会
  • Place of Presentation: 東京
• [Presentation] Analysis of photoproducts from a UVA-irradiated mixture of N-nitrosoproline with 2'-deoxyadenosine or 2'-deoxyguanosine (2011)
  • Author(s): Aoyama, S., Sano, K., Hatano, T., Kimura, S. and Arimoto-Kobayashi, S
  • Organizer: The 5th Asia and Oceania Conference on Photobiology
  • Place of Presentation: 奈良
• [Presentation] N-ニトロソプロリンの光活性化による核酸修飾 (2011)
  • Author(s): 青山周平、佐野嘉容子,波多野力、木村幸子、有元佐賀惠
  • Organizer: 第33回日本光医学・光生物学会
  • Place of Presentation: 大阪