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Myricetin causes site-specific DNA damage via reactive oxygen species generation by redox interactions with copper ions
http://hdl.handle.net/10076/0002001113
http://hdl.handle.net/10076/0002001113044779ec-eb4d-414b-aded-fffa25e49c0c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2024DM0914.pdf (4 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2024-12-18 | |||||||||
| タイトル | ||||||||||
| タイトル | Myricetin causes site-specific DNA damage via reactive oxygen species generation by redox interactions with copper ions | |||||||||
| 言語 | en | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | 8-oxo-7 | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | 8-dihydro-2′-deoxyguanosine | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Mutagen | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Pharmacological activity | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Phenolic compound | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Pro-oxidant | |||||||||
| 資源タイプ | ||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| 資源タイプ | doctoral thesis | |||||||||
| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| 著者 |
平生, 祐一郎
× 平生, 祐一郎
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Myricetin (MYR), found in tea and berries, may have preventive effects on diseases, including Alzheimer's disease and cancer. However, MYR is also a mutagen, inducing DNA damage in the presence of metal ions. We have studied the molecular mechanisms of DNA damage by MYR in the presence of Cu(II) (MYR+Cu). Using ³²P-5'-end-labeled DNA fragments, we analyzed site-specific DNA damage caused by MYR+Cu. MYR+Cu caused concentration-dependent DNA strand breaks and base alterations, leading to cleavage of DNA at thymine, cytosine, and guanine nucleotides. Formation of the oxidative DNA damage indicator, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in calf thymus DNA was increased by MYR+Cu. The production of 8-oxodG in MYR-treated HL-60 cells was significantly higher than in HP100 cells, which are more resistant to H₂O₂ than are HL-60 cells. Reactive oxygen species (ROS) scavengers were used to elucidate the mechanism of DNA damage. DNA damage was not inhibited by typical free hydroxyl radical (•OH) scavengers such as ethanol, mannitol, or sodium formate. However, methional, catalase, and bathocuproine inhibited DNA damage induced by MYR+Cu. These results suggest that H₂O₂, Cu(I), and ROS other than •OH are involved in MYR+Cu-induced DNA damage. We conclude that the Cu(I)/Cu(II) redox cycle and concomitant H₂O₂ production via autoxidation of MYR generate a complex of H₂O₂ and Cu(I), probably Cu(I)-hydroperoxide, which induces oxidative DNA damage. | |||||||||
| 言語 | en | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 本文/Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 8p | |||||||||
| 書誌情報 |
発行日 2024-09-25 |
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| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | 10.1016/j.mrgentox.2023.503694 | |||||||||
| フォーマット | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
| 出版者 | ||||||||||
| 出版者 | 三重大学 | |||||||||
| 出版者（ヨミ） | ||||||||||
| ミエダイガク | ||||||||||
| 学位名 | ||||||||||
| 学位名 | 博士(医学) | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 14101 | |||||||||
| 学位授与機関名 | 三重大学 | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2024-09-25 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲医学第2283号 | |||||||||
| ノート | ||||||||||
| 資源タイプ（三重大） | ||||||||||
| Doctoral Dissertation / 博士論文 | ||||||||||
