DNA repair is responsible for the presence of oxidatively damaged DNA lesions in urine
DNA repair is responsible for the presence of oxidatively damaged DNA lesions in urine
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DOI：
10.1016/j.mrfmmm.2005.01.022
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发表时间：
2005-07-01
影响因子：
2.3
通讯作者：
Olinski, R
中科院分区：
文献类型：
--
作者：
Cooke, MS;Evans, MD;Olinski, R
氧化损伤的DNA的修复对于维持基因组稳定性是不可或缺的，并且因此预防各种各样的病理状况，例如衰老、癌症和心血管疾病。非侵入性评估DNA修复的能力可以提供关于修复途径、修复能力的可变性和对疾病的易感性的信息。检测尿液DNA损伤的检测方法的发展提供了这种可能性，尽管很快就清楚饮食和细胞更新可能影响尿液损伤水平。虽然早期的研究试图解决这些问题，但到目前为止，许多数据似乎相互矛盾。然而，我们实验室最近的工作，其中人类志愿者被喂食高度氧化修饰的N-15标记的DNA，表明饮食似乎不会导致8-羟基鸟嘌呤和7，8-二氢-8-氧代-2 '-脱氧鸟苷的尿液水平。此外，我们提出，一些文献报告形成了一个论点，反对细胞死亡的贡献。事实上，我们和其他人已经提出了证据，这强烈表明细胞死亡的参与是最小的。总之，这些数据似乎排除了各种混杂因素，使DNA修复途径成为尿嘌呤（如果不是DNA）损伤的主要来源，从而使此类测量能够用作修复的指标。(c)2005 Elsevier B.V保留所有权利。
The repair of oxidatively damaged DNA is integral to the maintenance of genomic stability, and hence prevention of a wide variety of pathological conditions, such as aging, cancer and cardiovascular disease. The ability to non-invasively assess DNA repair may provide information regarding repair pathways, variability in repair capacity, and susceptibility to disease. The development of assays to measure urinary DNA lesions offered this potential, although it rapidly became clear that possible contribution from diet and cell turnover may influence urinary lesion levels. Whilst early studies attempted to address these issues, up until now, much of the data appears conflicting. However, recent work from our laboratories, in which human volunteers were fed highly oxidatively modified N-15-labelled DNA demonstrates that diet does not appear to contribute to urinary levels of 8-hydroxyguanine and 7,8-dihydro-8-oxo-2'-deoxyguanosine. Furthermore, we propose that a number of literature reports form an argument against a contribution from cell death. Indeed we, and others, have presented evidence, which strongly suggests the involvement of cell death to be minimal. Taken together, these data would appear to rule out various confounding factors, leaving DNA repair pathways as the principal source of urinary purine, if not DNA, lesions enabling such measurements to be used as indicators of repair. (c) 2005 Elsevier B.V All rights reserved.