Accumulation of lipid peroxidation-derived DNA lesions: Potential lead markers for chemoprevention of inflammation-driven malignancies
Accumulation of lipid peroxidation-derived DNA lesions: Potential lead markers for chemoprevention of inflammation-driven malignancies
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DOI：
10.1016/j.mrfmmm.2005.04.013
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发表时间：
2005-12-11
影响因子：
2.3
通讯作者：
Nair, J
中科院分区：
文献类型：
--
作者：
Bartsch, H;Nair, J
慢性炎症过程通过脂质过氧化（LPO）产生过量的ROS和dna反应性醛，如反式4-羟基-2-壬烯醛（HNE）和丙二醛（MDA）。它可以改变细胞大分子并导致恶性肿瘤。乙烯修饰的DNA碱基是通过DNA与主要LPO产物的反应而产生的。HNE。我们正在研究与可导致恶性肿瘤的持续炎症过程相关的疾病器官中乙烯- dna加合物的稳态水平。我们已经开发出超灵敏和特异的方法来检测人体组织和尿液中的乙烯- dna碱基加合物。研究发现，慢性胰腺炎、溃疡性结肠炎和克罗恩病患者的受影响器官中乙醇- dna加合物水平显著升高。将酒精滥用相关性肝炎、脂肪肝、纤维化和肝硬化患者与无症状肝患者进行比较。后三组患者肝脏DNA均出现过度损伤。测定hbv感染者尿中乙基脱氧腺苷的排泄量。诊断为慢性肝炎、肝硬化和肝细胞癌的患者。与对照组相比，这些患者的尿水平增加了90倍。受损或不平衡的dna修复途径可能影响炎症组织中乙烯- dna加合物的稳态水平。总之，乙烯- dna加合物可能作为评估炎症性癌症易发疾病进展的潜在先导标记物。如果是这样，人类化学预防干预对恶性疾病预防的功效就可以得到验证。(c) 2005 Elsevier B.V.版权所有
Chronic inflammatory processes produce an excess of ROS and DNA-reactive aldehydes from lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA). which can modify cellular macromolecules and drive to malignancy. Etheno-modified DNA bases are generated inter alia by reaction of DNA with the major LPO product. HNE. We are investigating steady-state levels of etheno-DNA adducts in organs with diseases related to persistent inflammatory processes that can lead to malignancies. We have developed ultrasensitive and specific methods for the detection of etheno-DNA base adducts in human tissues and in urine. Etheno-DNA adduct levels were found to be significantly elevated in the affected organs of subjects with chronic pancreatitis, ulcerative colitis and Crohn's disease. When patients with alcohol abuse-related hepatitis, fatty liver, fibrosis and cirrhosis were compared with asymptomatic livers. excess hepatic DNA damage was seen in the three latter patient groups. Etheno-deoxyadenosine excreted in urine was measured in HBV-infected. patients diagnosed with chronic hepatitis, cirrhosis and hepatocellular carcinoma. As compared to controls, these patients had Lip to 90-fold increased urinary levels. Impaired or imbalanced DNA-repair pathways may influence the steady-state levels of etheno-DNA adducts in inflamed tissues. In conclusion, etheno-DNA adducts may serve as potential lead markers for assessing progression of inflammatory cancer-prone diseases. If so, the efficacy of human chemopreventive interventions for malignant disease prevention could be verified. (c) 2005 Elsevier B.V. All rights reserved.