Potential role of lipid peroxidation derived DNA damage in human colon carcinogenesis: studies on exocyclic base adducts as stable oxidative stress markers
Potential role of lipid peroxidation derived DNA damage in human colon carcinogenesis: studies on exocyclic base adducts as stable oxidative stress markers
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DOI：
10.1016/s0361-090x(02)00093-4
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发表时间：
2002-01-01
影响因子：
--
通讯作者：
Nair, J
中科院分区：
文献类型：
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作者：
Bartsch, H;Nair, J
结直肠癌的分子途径涉及多种遗传变化，这些变化可能是由癌症相关基因中活性氧的过度产生引起的。我们的目的是调查，是否除了直接氧化DNA损伤，活性氧和氮物种诱导脂质过氧化（LPO），可以产生乙烯基-DNA加合物通过反式-4-羟基-2-壬烯醛，一个主要的醛产生的LPO，在结肠组织。我们通过免疫亲和层析结合P-32-后标记的高特异性、超灵敏方法分析了溃疡性结肠炎、克罗恩病和家族性腺瘤性息肉病（FAP）受累结肠上皮中的乙烯基-DNA加合物[Carcinogenesis 16（1995）613]，并将其与无症状结肠组织进行了比较。在所有这些易患癌症的结肠组织中，首次证实了乙烯并加合物水平显著增强的形成。乙烯基-DNA加合物是前诱变剂，并引起基因组不稳定，可驱使发炎的结肠上皮细胞恶性化。乙烯基-DNA加合物似乎是有前景的生物标志物，用于（i）量化结肠癌发生的早期阶段中增加的DNA损伤和（ii）验证新抗氧化剂的功效（例如[Lancet Oncol. 1（2000）107]）和化学预防剂降低氧化应激和相关癌症风险。(C)2002年国际预防肿瘤学会。由爱思唯尔科技有限公司出版。保留所有权利。
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.