Potential role of lipid peroxidation derived DNA damage in human colon carcinogenesis: studies on exocyclic base adducts as stable oxidative stress markers

被引:75
作者
Bartsch, H [1 ]
Nair, J [1 ]
机构
[1] German Canc Res Ctr, DKFZ, Div Toxicol & Canc Risk Factors, D-69120 Heidelberg, Germany
来源
CANCER DETECTION AND PREVENTION | 2002年 / 26卷 / 04期
关键词
etheno-DNA adducts; oxidative damage; colon cancer; biomarkers;
D O I
10.1016/S0361-090X(02)00093-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Molecular pathways to colorectal cancer involve multiple genetic changes that may be caused by overproduction of reactive oxygen species in cancer-related genes. Our aim was to investigate, whether besides direct oxidative DNA damage, reactive oxygen and nitrogen species induce lipid peroxidation (LPO) that could yield etheno-DNA adducts via trans-4-hydroxy-2-nonenal, a major aldehyde generated by LPO, in colon tissue. We analyzed the etheno-DNA adducts by a highly specific, ultrasensitive method involving immunoaffinity chromatography coupled with P-32-postlabelling [Carcinogenesis 16 (1995) 613] in affected colon epithelium from ulcerative colitis, Crohn's disease and familial adenomatous polyposis (FAP) and compared them with asymptomatic colon tissue. In all these cancer prone colon tissues, the formation of markedly enhanced etheno adduct levels was demonstrated for the first time. Etheno-DNA adducts are promutagenic and cause genomic instability that could drive the inflamed colonic epithelia to malignancy. Etheno-DNA adducts appear promising biomarkers for (i) quantifying increased DNA damage in early stages of colon carcinogenesis and for (ii) verifying the efficacy of new antioxidants (e.g. [Lancet Oncol. 1 (2000) 107]) and chemopreventive agents in lowering oxidative stress and related cancer risk. (C) 2002 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:308 / 312
页数:5
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