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DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans.
Mass Spectrometry Reviews ( IF 6.6 ) Pub Date : 2018-06-11 , DOI: 10.1002/mas.21570
Byeong Hwa Yun 1 , Jingshu Guo 1 , Medjda Bellamri 1 , Robert J Turesky 1
Affiliation  

Hazardous chemicals in the environment and diet or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. In addition, reactive intermediates can be generated in the body through oxidative stress and damage the genome. The identification and measurement of DNA adducts are required for understanding exposure and the causal role of a genotoxic chemical in cancer risk. Over the past three decades, 32 P-postlabeling, immunoassays, gas chromatography/mass spectrometry, and liquid chromatography/mass spectrometry (LC/MS) methods have been established to assess exposures to chemicals through measurements of DNA adducts. It is now possible to measure some DNA adducts in human biopsy samples, by LC/MS, with as little as several milligrams of tissue. In this review article, we highlight the formation and biological effects of DNA adducts, and highlight our advances in human biomonitoring by mass spectrometric analysis of formalin-fixed paraffin-embedded tissues, untapped biospecimens for carcinogen DNA adduct biomarker research.

中文翻译:

DNA 加合物:形成、生物效应和用于人体质谱测量的新生物样本。

环境和饮食中的有害化学物质或其亲电子代谢物可以与基因组 DNA 形成加合物,从而导致突变和癌症的发生。此外,氧化应激可在体内产生反应中间体并损害基因组。为了了解基因毒性化学物质的暴露及其在癌症风险中的因果作用,需要对 DNA 加合物进行鉴定和测量。在过去的三十年中,已经建立了 32 P 后标记、免疫测定、气相色谱/质谱和液相色谱/质谱 (LC/MS) 方法,通过测量 DNA 加合物来评估化学物质的暴露情况。现在可以通过 LC/MS 测量人体活检样本中的一些 DNA 加合物,只需几毫克的组织。在这篇综述文章中,我们重点介绍了 DNA 加合物的形成和生物效应,并重点介绍了我们通过对福尔马林固定石蜡包埋的组织(用于致癌 DNA 加合物生物标志物研究的未开发生物样本)进行质谱分析在人类生物监测方面取得的进展。
更新日期:2019-11-18
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