Screening of X-ray responsive substances for the next generation of radiosensitizers

Akihiro Moriyama, Takema Hasegawa, Lei Jiang, Hitoshi Iwahashi, Takashi Mori, Junko Takahashi*

*この研究の対応する著者

研究成果: Article査読

抄録

X-ray responsivity resulting in the generation of reactive oxygen species (ROS) was investigated in 9600 organic compounds that were selected by considering their structural diversity. We focused on superoxides that were primarily detected using dihydroethidium (DHE) and hydroxyl radicals, that were identified fluorometrically using 3’-(p-aminophenyl) Fluorescein (APF). Many organic compounds were discovered that responded to the DHE and/or APF assay using X-ray irradiation. These results suggest that some of these organic compounds emit either superoxides or hydroxyl radicals whereas others emit both under the influence of X-ray irradiation. The response of the derivatives of a hit compound with a partial change in the structure was also investigated. The products produced from DHE by X-ray irradiation were identified by HPLC to confirm the integrity of the process. Although, the reactions were suppressed by the superoxide dismutase (SOD), not only 2-hydroxyethidium (2-OH-E+), but also ethidium (E+) were detected. The results suggest that apart from a direct reaction, an indirect reaction may occur between DHE and the superoxides. Although X-ray responsiveness could not be inferred due to the molecular complexity of the investigated compounds, delineation of these reactions will facilitate the development of the next generation of radiosensitizers.

本文言語English
論文番号18163
ジャーナルScientific reports
9
1
DOI
出版ステータスPublished - 2019 12 1
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ASJC Scopus subject areas

  • 一般

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