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

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  • Arimoto-Kobayashi Sakae
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Machida Masaki
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Sano Kayoko
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Aoyama Shuhei
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Asahi Chiharu
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Tanaka Noriko
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Okamoto Keinosuke
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Negishi Tomoe
    Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Kimura Sachiko
    School of Human Science and Environment, University of Hyogo
  • Suzuki Toshinori
    Faculty of Pharmaceutical Sciences, Shujitsu University

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タイトル別名
  • 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′-Deoxyguanosine in Neutral Solution
  • Mutagenicity and NO Formation from UVA Irradiated N-Nitrosoproline, and Characterization of Photoproduct Formed in UVA-irradiated Mixture of N-Nitrosoproline with 2^|^prime;-Deoxyguanosine in Neutral Solution

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説明

Earlier studies in our laboratory showed that UVA-irradiated N-nitrosoproline (NPRO) could produce mutagenic compounds and strand breaks in treated DNA with the release of nitric oxide and active oxygen species. In the present study, we investigated the phosphate-dependence of photomutagenicity and solvent effects on nitric oxide release from irradiated NPRO. We also investigated the UVA-driven reaction of NPRO with 2′-deoxyguanosine (dG) in neutral solution, and identified the chemical structure of the photoproduct. A mixture of NPRO and dG dissolved in neutral solution was irradiated with UVA at 320-400 nm for 6 h, and the solution was then subjected to HPLC analysis. The photoproduct isolated from the NPRO and dG mixture in neutral buffer was identified as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). We propose a photoreaction mechanism involving the absorption of UVA photons by NPRO followed by UVA-driven photolysis of NPRO, and subsequent production of active oxygen radicals that generate 8-oxodG.<br>

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