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A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients
http://hdl.handle.net/10271/00004218
http://hdl.handle.net/10271/0000421843cbefd2-3c21-48ed-b495-3dd5c9dfc137
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (1.5 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2022-12-01 | |||||||
| タイトル | ||||||||
| タイトル | A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | DNA adduct | |||||||
| キーワード | ||||||||
| 主題 | DNA adductome | |||||||
| キーワード | ||||||||
| 主題 | DNA adductomics | |||||||
| キーワード | ||||||||
| 主題 | C5-hydroxymethyl-2′-deoxycytidine | |||||||
| キーワード | ||||||||
| 主題 | Renal cell carcinoma | |||||||
| キーワード | ||||||||
| 主題 | Upper urinary tract urothelial carcinoma | |||||||
| キーワード | ||||||||
| 主題 | Oxidative DNA damage | |||||||
| 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 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | DNAアダクトーム解析によって、尿路上皮がん患者の非腫瘍部上部尿路粘膜において、C5-ヒドロキシメチル-2′-デオキシシチジンが低下していることを明らかにした | |||||||
| 著者 |
松下, 雄登
× 松下, 雄登
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| 書誌情報 |
en : Genes and Environment 巻 43, p. 52, 発行日 2021-12-02 |
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| 出版者 | ||||||||
| 出版者 | Springer Nature | |||||||
| 言語 | en | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | Copyright The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Background: DNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, and has been implicated in carcinogenesis in humans due to the down-regulation of tumor suppressor genes. Difficulties are associated with demonstrating the existence of DNA adducts or chemically modified bases in the human urological system. Apart from aristolochic acid-DNA adducts, which cause urothelial carcinoma and endemic nephropathy in a particular geographical area (Balkan), limited information is currently available on DNA adduct profiles in renal cell carcinoma and upper urinary tract urothelial carcinoma, including renal pelvic cancer and ureteral cancer. Method: To elucidate the significance of DNA adducts in carcinogenesis in the urothelial system, we investigated 53 DNA adducts in the non-tumoral renal parenchyma and non-tumoral renal pelvis of patients with renal cell carcinoma, upper urinary tract urothelial carcinoma, and other diseases using liquid chromatography coupled with tandem mass spectrometry. A comparative analysis of tissue types, the status of malignancy, and clinical characteristics, including lifestyle factors, was performed. Results: C5-Methyl-2′-deoxycytidine, C5-hydroxymethyl-2′-deoxycytidine (5hmdC), C5-formyl-2′-deoxycytidine, 2′-deoxyinosine, C8-oxo-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine (8-OHdG) were detected in the renal parenchyma and renal pelvis. 8-OHdG was more frequently detected in the renal pelvis than in the renal cortex and medulla (p=0.048 and p=0.038, respectively). 5hmdC levels were significantly lower in the renal pelvis of urothelial carcinoma patients (n=10) than in the urothelium of patients without urothelial carcinoma (n=15) (p=0.010). Regarding 5hmdC levels in the renal cortex and medulla, Spearman’s rank correlation test revealed a negative correlation between age and 5hmdC levels (r=-0.46, p=0.018 and r=-0.45, p=0.042, respectively). Conclusions: The present results revealed a reduction of 5hmdC levels in the non-tumoral urinary tract mucosa of patients with upper urinary tract urothelial carcinoma. Therefore, the urothelial cell epithelia of patients with upper urinary tract cancer, even in non-cancerous areas, may be predisposed to urothelial cancer. |
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| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 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 | 13802 | |||||||
| 学位授与機関名 | 浜松医科大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2022-03-14 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第904号 | |||||||
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| 収録物識別子タイプ | PISSN | |||||||
| 収録物識別子 | 1880-7046 | |||||||
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| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1880-7062 | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 34852853 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.1186/s41021-021-00228-9 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
