D-methionine (D-met), a dextrorotatory isoform of the amino acid L-methionine (L-met), can prevent oral mucositis and salivary hypofunction in mice exposed to radiation. However, the mechanism of its radioprotection is unclear, especially with regard to the stereospecific functions of D-met. Radiation is known to cause injury to normal tissue by triggering DNA damage in cells. Thus, in this study we sought to determine whether the chirality of D-/L-met affects radiation-induced events at the DNA level. We selected plasmid DNA assays to examine this effect in vitro, since these assays are highly sensitive and allow easy detection of DNA damage. Samples of supercoiled pBR322 plasmid DNA mixed with D-met, L-met or dimethylsulfoxide (DMSO) were prepared and irradiated with a Bragg peak beam of carbon ions (∼290 MeV/u) with a 6-cm spread. DNA strand breaks were indicated by the change in the form of the plasmid and were subsequently quantified using agarose gel electrophoresis. We found that D-met yielded approximately equivalent protection from carbon-ion-induced DNA damage as DMSO. Thus, we propose that the protective functions of methionine against plasmid DNA damage could be explained by the same mechanism as that for DMSO, namely, hydroxyl radical scavenging. This stereospecific radioprotective mechanism occurred at a level other than the DNA level. There was no significant difference between the radioprotective effect of D-met and L-met on DNA.
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June 2020
Research Article|
March 27 2020
Potential Mechanisms for Protective Effect of D-Methionine on Plasmid DNA Damage Induced by Therapeutic Carbon Ions
Katsunori Yogo;
Katsunori Yogo
1
Graduate School of Medicine, Nagoya University, Aichi 461-8673, Japan
1 Address for correspondence: Graduate School of Medicine, Nagoya University, 1-1-20 Daiko-minami, Higashi-ku, Nagoya, Aichi 461-8673, Japan; email: yogo@met.nagoya-u.ac.jp.
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Chieko Murayama;
Chieko Murayama
Tokai University School of Medicine, Kanagawa 259-1193, Japan
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Yoshiki Fujisawa;
Yoshiki Fujisawa
Graduate School of Medical Science, Kitasato University, Kanagawa 252-0373, Japan
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Takuya Maeyama;
Takuya Maeyama
Graduate School of Science, Kitasato University, Kanagawa 252-0373, Japan
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Ryoichi Hirayama;
Ryoichi Hirayama
National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, Japan
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Yukihiro Ogawa;
Yukihiro Ogawa
National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, Japan
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Ken-ichiro Matsumoto;
Ken-ichiro Matsumoto
National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, Japan
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Ikuo Nakanishi;
Ikuo Nakanishi
National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, Japan
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Hiroshi Yasuda;
Hiroshi Yasuda
Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan
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Hiromichi Ishiyama;
Hiromichi Ishiyama
Graduate School of Medical Science, Kitasato University, Kanagawa 252-0373, Japan
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Kazushige Hayakawa
Kazushige Hayakawa
Graduate School of Medical Science, Kitasato University, Kanagawa 252-0373, Japan
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Radiat Res (2020) 193 (6): 513–519.
Article history
Received:
August 22 2019
Accepted:
February 28 2020
Citation
Katsunori Yogo, Chieko Murayama, Yoshiki Fujisawa, Takuya Maeyama, Ryoichi Hirayama, Yukihiro Ogawa, Ken-ichiro Matsumoto, Ikuo Nakanishi, Hiroshi Yasuda, Hiromichi Ishiyama, Kazushige Hayakawa; Potential Mechanisms for Protective Effect of D-Methionine on Plasmid DNA Damage Induced by Therapeutic Carbon Ions. Radiat Res 1 June 2020; 193 (6): 513–519. doi: https://doi.org/10.1667/RR15502.1
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