Etheno-DNA base adducts as tools in human cancer aetiology and chemoprevention
Etheno-DNA base adducts as tools in human cancer aetiology and chemoprevention
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DOI：
10.1097/00008469-199712000-00007
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发表时间：
1997-01-01
影响因子：
2.4
通讯作者：
Velic, I
中科院分区：
文献类型：
--
作者：
Bartsch, H;Nair, J;Velic, I
DNA 中的乙烯加合物由致癌物质氯乙烯和氨基甲酸乙酯形成，也由脂质过氧化 (LPO) 产物（例如反式 4-羟基-2-壬烯醛）形成。使用超灵敏检测方法，在发展为肝炎和肝细胞癌的 LEC 大鼠（一种具有遗传性铜代谢异常的品系）的肝脏中证实了乙烯-DNA 加合物的形成。威尔逊氏病和原发性血色素沉着症是人类遗传性疾病，会导致铜或铁积累，从而导致原发性肝癌的高风险。这些患者肝脏中的乙烯加合物水平也显着升高。在一组控制饮食的男性和女性志愿者中，在白细胞 DNA 中测定了膳食脂肪酸成分对脂质过氧化衍生 DNA 加合物内源形成的影响。饮食中的 omega-6 多不饱和脂肪酸大大增加了女性体内 LPO 衍生的乙烯 DNA 加合物的含量。因此，环外DNA加合物是有前途的生物标志物，可用于阐明膳食脂肪摄入、氧化应激和保护性膳食抗氧化剂对内源性DNA损伤的影响，从而可能提供与饮食相关癌症风险升高之间可能的机制联系。
Etheno adducts in DNA are formed from the carcinogens vinyl chloride and urethane, and also from products of lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal. Using an ultrasensitive detection method, the formation of etheno-DNA adducts in the liver was demonstrated in LEC rats (a strain with hereditary abnormal copper metabolism) that develop hepatitis and hepatocellular carcinoma. Wilson's disease and primary haemochromatosis are human genetic disorders that cause copper or iron accumulation resulting in a high risk for primary liver cancers. Levels of etheno adducts were also significantly elevated in the liver of these patients. In a group of male and female volunteers kept on a controlled diet, the effect of dietary fatty acid composition on the endogenous formation of lipid peroxidation-derived DNA adducts was determined in DNA from white blood cells. Dietary omega-6-polyunsaturated fatty acids greatly increased LPO-derived etheno-DNA adducts in vivo, in females. Thus, exocyclic DNA adducts are promising biomarkers for elucidating the effect of dietary fat intake, oxidative stress and protective dietary antioxidants on endogenous DNA damage and thus may provide a possible mechanistic link with elevated risk for diet-related cancers.