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Open AccessArticle

DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma

1
The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan
2
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
3
Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
4
DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
*
Author to whom correspondence should be addressed.
These authors equally contributed.
Int. J. Mol. Sci. 2020, 21(7), 2302; https://doi.org/10.3390/ijms21072302
Received: 29 February 2020 / Revised: 20 March 2020 / Accepted: 24 March 2020 / Published: 26 March 2020
(This article belongs to the Special Issue Skin Cancer: From Pathophysiology to Novel Therapeutic Approaches)
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. View Full-Text
Keywords: protoporphyrin IX; X-ray; DNA double-strand break; reactive oxygen species (ROS); radiotherapy; melanoma; radiodynamic therapy; photodynamic therapy protoporphyrin IX; X-ray; DNA double-strand break; reactive oxygen species (ROS); radiotherapy; melanoma; radiodynamic therapy; photodynamic therapy
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MDPI and ACS Style

Hasegawa, T.; Takahashi, J.; Nagasawa, S.; Doi, M.; Moriyama, A.; Iwahashi, H. DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma. Int. J. Mol. Sci. 2020, 21, 2302.

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