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

松下, 雄登

doi:https://doi.org/10.1186/s41021-021-00228-9

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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

名前 / ファイル	ライセンス	アクション
論文本文 (1.5 MB)

Item type

学位論文 / Thesis or Dissertation(1)

公開日

2022-12-01

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

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

open access

アクセス権URI

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

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

書誌情報

en : Genes and Environment

巻 43, p. 52, 発行日 2021-12-02

出版者

Springer Nature

言語

権利

言語

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.

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

2022-03-14

学位授与番号

甲第904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 16:17:42.281321

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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

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