Exocyclic DNA adducts as oxidative stress markers in colon carcinogenesis: Potential role of lipid peroxidation, dietary fat and antioxidants

被引:64
作者
Bartsch, H [1 ]
Nair, J [1 ]
Owen, RW [1 ]
机构
[1] German Canc Res Ctr, Div Toxicol & Canc Risk Factors, D-69120 Heidelberg, Germany
关键词
biomarkers; colon cancer; etheno-DNA adducts; lipid peroxidation; olive oil; oxidative damage; phenolic antioxidants;
D O I
10.1515/BC.2002.098
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Molecular pathways to colorectal cancer involve multiple genetic changes, whereby extensive oxyradical damage causes mutations in cancerrelated genes and leads to a cycle of cell death and regeneration. Besides direct oxidative DNAdamage, reactive oxygen and nitrogen species can induce etheno ([epsilon])DNA adducts mainly via trans-4-hydroxy-2-nonenal, generated as the major aldehyde by lipid peroxidation (LPO) of [omega]-6 PUFAs. Patients with familial adenomatous polyposis (FAP) develop multiple colorectal adenomas. In affected tissues increased LPO could be triggered due to increased arachidonic acid metabolism as a result of elevated cyclooxygenases. Our studies demonstrated an increased [epsilon]DNA adduct level in affected colon epithelia of FAP patients. [epsilon]DNA adducts are promutagenic and can cause genomic instability that drives colorectal adenoma to malignancy. We have further investigated the potential chemopreventive properties of olive oil and its polyphenolic components. Mediterranean diet, of which olive oil is a major fatty acid source, has protective effects against human breast and colorectal cancers. Olive oil extracts and the newly identified lignan fractions showed high antioxidant capacity in vitro. As [epsilon]DNA adducts are biomarkers for oxidative stress and LPO induced DNA damage, they can verify the efficacy of newly identified antioxidants, e.g. from olive oil, as chemopreventive agents against colon carcinogenesis.
引用
收藏
页码:915 / 921
页数:7
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