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Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors
http://hdl.handle.net/10271/00004201
http://hdl.handle.net/10271/000042019ce4e57c-3164-4421-875a-2f1e56ecd338
名前 / ファイル | ライセンス | アクション |
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論文本文 (1.7 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2022-11-18 | |||||
タイトル | ||||||
タイトル | Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | DNA adduct | |||||
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言語 | en | |||||
主題Scheme | Other | |||||
主題 | DNA adductome | |||||
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言語 | en | |||||
主題Scheme | Other | |||||
主題 | DNA adductomics | |||||
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言語 | en | |||||
主題Scheme | Other | |||||
主題 | Mutagen | |||||
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言語 | en | |||||
主題Scheme | Other | |||||
主題 | Exposure | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Stomach | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Gastric cancer | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Liquid chromatography/tandem mass spectrometry | |||||
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 | 環境因子による損傷と関連する、ヒトの胃におけるDNA付加体の質量分析プロファイリング | |||||
言語 | ja | |||||
著者 |
大西, 一平
× 大西, 一平 |
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書誌情報 |
en : Genes and Environment 巻 43, p. 12, 発行日 2021-04-09 |
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出版者 | ||||||
出版者 | Springer Nature | |||||
言語 | en | |||||
出版者 | ||||||
出版者 | 日本環境変異原ゲノム学会 = The Japanese Environmental Mutagen and Genome Society | |||||
言語 | ja | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | Copyright The Author(s) 2021. | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | 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: A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this “DNA adductome approach” in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. Aim: Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. Materials and methods: From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrosprayionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. Results: Seven DNA adducts, including modified bases, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2′-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2′-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2′-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. Conclusions: We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future. |
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言語 | en | |||||
学位名 | ||||||
言語 | ja | |||||
学位名 | 博士(医学) | |||||
学位の区分 | ||||||
内容記述タイプ | Other | |||||
内容記述 | doctoral | |||||
言語 | en | |||||
学位の分野 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 医学系研究科 | |||||
言語 | ja | |||||
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 | |||||
言語 | ja | |||||
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 | 2021-07-16 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲第883号 | |||||
ISSN | ||||||
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 | 33836837 | |||||
出版社DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1186/s41021-021-00186-2 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |