Screening of X-ray responsive substances for the next generation of radiosensitizers
Screening of X-ray responsive substances for the next generation of radiosensitizers
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DOI：
10.1038/s41598-019-54649-2
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发表时间：
2019-12-03
影响因子：
4.6
通讯作者：
Takahashi, Junko
中科院分区：
文献类型：
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作者：
Moriyama, Akihiro;Hasegawa, Takema;Takahashi, Junko
在 9600 种有机化合物中研究了导致活性氧 (ROS) 生成的 X 射线响应性，这些有机化合物是通过考虑其结构多样性而选择的。我们重点关注主要使用二氢乙锭 (DHE) 检测的超氧化物和使用 3'-(对氨基苯基) 荧光素 (APF) 进行荧光测定的羟基自由基。发现许多有机化合物对使用 X 射线照射的 DHE 和/或 APF 测定有反应。这些结果表明，其中一些有机化合物会释放超氧化物或羟基自由基，而其他有机化合物在 X 射线照射的影响下会同时释放两者。还研究了结构部分改变的热门化合物的衍生物的响应。通过 X 射线照射 DHE 生产的产品通过 HPLC 进行鉴定，以确认该过程的完整性。尽管反应被超氧化物歧化酶（SOD）抑制，但不仅检测到2-羟基乙锭（2-OH-E+），而且还检测到乙锭（E+）。结果表明，除了直接反应外，DHE 与超氧化物之间还可能发生间接反应。尽管由于所研究化合物的分子复杂性而无法推断 X 射线反应性，但对这些反应的描述将有助于下一代放射增敏剂的开发。
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.