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Is high resolution a strict requirement for mass spectrometry-based cellular DNA adductomics?
- Source :
-
Chemosphere . Jul2021, Vol. 274, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
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-OT-MS) 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. [Display omitted] • LC-HRMS DNA adductomics approach was developed, covering purine/pyrimidine adducts. • LC-HRMS detected 18 DNA adducts induced by formaldehyde, including six novel ones. • QqQ-MS was compared with HRMS for screening the totality of DNA adducts. • QqQ-MS produced both false-positive and false negative results. • LC-QqQ-MS with statistical analysis could offer comparable results to LC-HRMS. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DNA adducts
*DNA
*MASS spectrometry
*DNA analysis
*GENETIC mutation
*FORMALDEHYDE
Subjects
Details
- Language :
- English
- ISSN :
- 00456535
- Volume :
- 274
- Database :
- Academic Search Index
- Journal :
- Chemosphere
- Publication Type :
- Academic Journal
- Accession number :
- 150125274
- Full Text :
- https://doi.org/10.1016/j.chemosphere.2021.129991