Simultaneous detection of multiple DNA adducts in human lung samples by isotope-dilution UPLC-MS/MS.
Simultaneous detection of multiple DNA adducts in human lung samples by isotope-dilution UPLC-MS/MS.
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DOI：
10.1021/ac503803m
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发表时间：
2015-01-06
影响因子：
7.4
通讯作者：
Chesne, Christophe
中科院分区：
文献类型：
--
作者：
Monien, Bernhard H.;Schumacher, Fabian;Herrmann, Kristin;Glatt, Hansruedi;Turesky, Robert J.;Chesne, Christophe
最近的研究表明，利用液质联用技术(LC-MS/MS)可以在人体组织和体液中检测到多种DNA加合物。然而，单个DNA加合物在风险评估中作为生物标记物的效用是有争议的，因为人类暴露在许多遗传毒物中。我们建立了一种测定16种常见遗传毒物的DNA加合物的方法，并建立了超高效液相色谱-MS/MS同时定量的分析技术。对DNA水解物中DNA加合物的分离和分离方法进行了优化，并将该方法用于人肺活检标本中16种DNA加合物的同时分析。在所有组织样品中均未检测到11种加合物(包括苯并[a]芘、1-甲基芘、4-氨基联苯、2-amino-1-methyl-6-phenylimidazo[4，5-b]pyridine，-1-甲氧基-3-吲哚甲基硫代葡萄糖苷、5-羟甲基呋喃和丙二醛)(检出限：0.02-7.1Adducts/108个核苷)。3，N4-亚乙基-2‘-脱氧胞苷和1，N6-亚乙基-2’-脱氧腺苷由内源性脂质过氧化产物中的2，3-环氧醛形成(分别为16.9-115.3和27.2-179/108个核苷)。甲基亮酚的主要加合物N2-(trans-methylisoeugenol-3′-yl)-2′-deoxyguanosine，也是如此(1.723.7/108个核苷)。在几个肺标本中检测到少量甲基亮酚加合物和两个糠醇加合物。综上所述，我们开发了一种有针对性的方法，用于同时分析16种DNA加合物，这些加合物可以很容易地通过其他诱变剂形成的加合物进行扩展。该方法使人们能够在人的肺样本中检测到糠醇和甲基亮酚的加合物。
Recent studies have demonstrated that various DNA adducts can be detected in human tissues and fluids using liquid chromatography connected to tandem mass spectrometry (LC-MS/MS). However, the utility of a single DNA adduct as a biomarker in risk assessment is debatable because humans are exposed to many genotoxicants. We established a method to measure DNA adducts derived from 16 ubiquitous genotoxicants and developed an analytical technique for their simultaneous quantification by ultra performance liquid chromatography (UPLC)-MS/MS. Methods for the enrichment of the analytes from DNA hydrolysates and chromatographic separation preceding mass spectrometric analysis were optimized, and the resultant technique was used for the simultaneous analysis of the 16 DNA adducts in human lung biopsy specimens. Eleven adducts (formed by benzo[a]pyrene, 1-methylpyrene, 4-aminobiphenyl, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 1-methoxy-3-indolylmethylglucosinolate, 5-hydroxymethylfurfural, and malondialdehyde) were not detected in any tissue sample (limits of detection: 0.02–7.1 adducts/108 nucleosides). 3,N4-etheno-2′-deoxycytidine and 1,N6-etheno-2′-deoxyadenosine, formed from 2,3-epoxyaldehydes of endogenous lipid peroxidation products, were present in all subjects (16.9–115.3 and 27.2–179/108 nucleosides, respectively). The same was true for N2-(trans-methylisoeugenol-3′-yl)-2′-deoxyguanosine, the major adduct of methyleugenol (1.7–23.7/108 nucleosides). A minor adduct of methyleugenol and two adducts of furfuryl alcohol were detected in several pulmonary specimens. Taken together, we developed a targeted approach for the simultaneous mass spectrometric analyses of 16 DNA adducts, which can be easily extended by adducts formed from other mutagens. The method allowed one to detect adducts of furfuryl alcohol and methyleugenol in samples of human lung.
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影响因子：
4.1
作者：
Chen, Li;Wang, Mingyao;Hecht, Stephen S.
通讯作者：
Hecht, Stephen S.
DOI：
10.1016/j.ijheh.2007.01.024
发表时间：
2007-05-01
影响因子：
6
作者：
Angerer, Juergen;Ewers, Ulrich;Wilhelm, Michael
通讯作者：
Wilhelm, Michael
影响因子：
4.1
作者：
Chen, HJC;Chiang, LC;Chung, FL
通讯作者：
Chung, FL
影响因子：
4.1
作者：
LIN, DX;KADERLIK, KR;KADLUBAR, FF
通讯作者：
KADLUBAR, FF
影响因子：
4.7
作者：
Monien, Bernhard H.;Herrmann, Kristin;Glatt, Hansruedi
通讯作者：
Glatt, Hansruedi