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

Genes and Environment

Kayoko Sano¹  Toshinori Suzuki³  Noriko Tanaka¹  Sachiko Kimura²  Shuhei Aoyama¹  Chiharu Asahi¹  Sakae Arimoto-Kobayashi¹  Keinosuke Okamoto¹  Tomoe Negishi¹  Masaki Machida¹ 

[1] Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University;School of Human Science and Environment, University of Hyogo;Faculty of Pharmaceutical Sciences, Shujitsu University

关键词: photoreaction;    N-nitrosamine;    DNA adduct;    8-oxo-deoxyguanosine;    NO radical;   

DOI  :  10.3123/jemsge.2014.004

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(29)Cited-By(1)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.

【 授权许可】

Unknown