Dna strand break properties of protoporphyrin ix by x-ray irradiation against melanoma

Takema Hasegawa, Junko Takahashi*, Shinsuke Nagasawa, Motomichi Doi, Akihiro Moriyama, Hitoshi Iwahashi

*この研究の対応する著者

研究成果: Article査読

4 被引用数 (Scopus)

抄録

Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3’-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2 •- ). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2 •- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.

本文言語English
論文番号2302
ジャーナルInternational journal of molecular sciences
21
7
DOI
出版ステータスPublished - 2020 4月 1
外部発表はい

ASJC Scopus subject areas

  • 触媒
  • 分子生物学
  • 分光学
  • コンピュータ サイエンスの応用
  • 物理化学および理論化学
  • 有機化学
  • 無機化学

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