Abstract
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.
Highlights
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 two types of free radical, superoxides and hydroxyl radicals
To examine the integrity of our methodology using DHE and APF probes, the products from DHE or APF due to X-ray irradiation was confirmed by HPLC. 2-OH-E+ is the dominant product of the reaction between DHE and the superoxides[12]
Summary
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. Exogenous porphyrin selectively accumulates in cancer cells and generate ROS to induce localized cellular damage when irradiated with light. Using this process, photodynamic therapy has been developed as a treatment for cancer[2,3]. In low LET radiation such as X-rays and γ rays, apart from cleavage of the DNA chain by direct action, damage to various bases owing to indirect action is caused[7]. This indirect action involves ROS generated by X-rays. Our study will contribute to a fundamental understanding of the chemical reactions between organic compounds and X-rays irradiation to facilitate the development of new radiosensitizers
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