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博士論文
国立国会図書館館内限定公開
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国立国会図書館デジタルコレクション
デジタルデータあり(Springer Nature)
Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors
- 国立国会図書館永続的識別子
- info:ndljp/pid/12651308
国立国会図書館での利用に関する注記
資料に関する注記
一般注記:
- doctoral医学系研究科Background: A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, espec...
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デジタル
- 資料種別
- 博士論文
- 著者・編者
- 大西, 一平
- 著者標目
- 出版事項
- 出版年月日等
- 2021-04-09
- 出版年(W3CDTF)
- 2021-04-09
- 並列タイトル等
- 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
- 授与機関名
- 浜松医科大学
- 授与年月日
- 2021-07-16
- 授与年月日(W3CDTF)
- 2021-07-16
- 報告番号
- 甲第883号
- 学位
- 博士(医学)
- 本文の言語コード
- eng
- 件名標目
- 対象利用者
- 一般
- 一般注記
- doctoral医学系研究科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.
- 国立国会図書館永続的識別子
- info:ndljp/pid/12651308
- コレクション(共通)
- コレクション(障害者向け資料:レベル1)
- コレクション(個別)
- 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
- 収集根拠
- 博士論文(自動収集)
- 受理日(W3CDTF)
- 2023-03-02T11:18:10+09:00
- 記録形式(IMT)
- application/pdf
- オンライン閲覧公開範囲
- 国立国会図書館内限定公開
- デジタル化資料送信
- 図書館・個人送信対象外
- 遠隔複写可否(NDL)
- 可
- 連携機関・データベース
- 国立国会図書館 : 国立国会図書館デジタルコレクション