Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors

大西, 一平

doi:https://doi.org/10.1186/s41021-021-00186-2

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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

名前 / ファイル	ライセンス	アクション
論文本文 (1.7 MB)

Item type

学位論文 / Thesis or Dissertation(1)

公開日

2022-11-18

タイトル

Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors

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

Mutagen

キーワード

主題

Exposure

キーワード

主題

Stomach

キーワード

主題

Gastric cancer

キーワード

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

open access

アクセス権URI

http://purl.org/coar/access_right/c_abf2

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

著者

大西, 一平

書誌情報

en : Genes and Environment

巻 43, p. 12, 発行日 2021-04-09

出版者

Springer Nature

言語

出版者

日本環境変異原ゲノム学会 = The Japanese Environmental Mutagen and Genome Society

言語

権利

言語

権利情報

権利

言語

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.

言語

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

2021-07-16

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

EISSN

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

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2023-06-20 16:18:15.108708

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Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors

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