Is high resolution a strict requirement for mass spectrometry-based cellular DNA adductomics?

doi:10.1016/j.chemosphere.2021.129991

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24017

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24017

Title:	Is high resolution a strict requirement for mass spectrometry-based cellular DNA adductomics?
Authors:	Chang, YJ;Cooke, MS;Chen, YR;Yang, SF;Li, PS;Hu, CW;Chao, MR
Keywords:	Formaldehyde;DNA adducts/Inter-strand crosslinks;DNA adductome;PLS-DA
Date:	2021
Issue Date:	2022-08-05T09:46:30Z (UTC)
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
ISSN:	0045-6535
Abstract:	Exposure to endogenous and exogenous factors can result in the formation of a wide variety of DNA adducts, and these may lead to gene mutations, thereby contributing to the development of cancer. DNA adductomics, a novel tool for exposomics, aims to detect the totality of DNA adducts. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) is the state-of-the-art method for DNA adductomic analysis, although its high cost has limited widespread use. In this study, we compared the analytical performance between HRMS and the more popular/accessible triple-quadrupole MS (QqQ-MS). We initially developed and optimized a hybrid quadrupole-linear ion trap-orbitrap MS (Q-LIT-OTMS) method, considering the detection of both purine and pyrimidine adducts. LC-Q-LIT-OT-MS and LC-QqQ-MS methods were compared by non-targeted screening of formaldehyde-induced DNA adducts. Using the results from Q-LIT-OT-MS as the gold standard, QqQ-MS successfully detected 12 out of 18 formaldehyde-induced DNA adducts/inter-strand crosslinks (ICLs). QqQ-MS however also produced nine false-positive results owing to the inherent instrumental mass resolution limits. To discriminate the false-positive results from the accurate ones, we firstly introduced a statistical analysis, partial least squares-discriminant analysis, which efficiently excluded the false signals. Six DNA adducts/ICLs were not detected by QqQ-MS, due to insufficient sensitivity. This could be overcome by employing a selected reaction monitoring scan mode with multiple injections. Overall, this study demonstrated that high resolution may not be a strict requirement for MS-based DNA adductomics. LC-QqQ-MS with statistical analysis, could also provide a comparable performance as HRMS for pre-screening purposes. (C) 2021 Elsevier Ltd. All rights reserved.
URI:	http://dx.doi.org/10.1016/j.chemosphere.2021.129991 https://www.webofscience.com/wos/woscc/full-record/WOS:000642944800125 https://ir.csmu.edu.tw:8080/handle/310902500/24017
Relation:	CHEMOSPHERE ,2021,v274
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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