# Pre-processing: centered (5), scaled (5) Evaluation of inhaled low-dose formaldehyde-induced DNA adducts and DNA–protein cross-links by liquid chromatography–tandem mass spectrometry.# 4 classes: 'Bact', 'NotApplicable', 'Pneu', 'UTI' International Journal of Hygiene and Environmental Health 2019, 222 Determination of benchmark dose based on adduct and micronucleus formations in formaldehyde-exposed workers.
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Kan Wang, Tuan-wei Wang, Jie Xu, Yiliang Zhu, Le Jian, William Au, Zhao-lin Xia.DNA-protein crosslink formation by endogenous aldehydes and AP sites.
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Drug and Chemical Toxicology 2020, 8, 1-13.
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The endogenous and exogenous amounts of dG-Me-Cys in a human cell line treated with formaldehyde are analyzed by our new methodology. This quantification method with a wide dynamic range of at least 3 orders generates an interference-free spectrum for unbiased and unambiguous quantification, resulting in good intra- and interday precisions and accuracies with less than 10% variations.
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In the present work, we further demonstrate an accurate quantification method using a high-resolution, accurate-mass Orbitrap mass spectrometer for the measurement of the covalent linkage between 2′-deoxyguanosine (dG) and cysteine (Cys), specifically termed dG-Me-Cys, one kind of linkages derived from the formaldehyde-induced DPCs. To this end, our group previously reported a useful liquid chromatography-selected reaction monitoring (LC-SRM) approach coupled with stable isotope labeling and low mass resolution-triple quadrupole mass spectrometry. There is a need to develop an effective detection method for DPC analysis, including the structural differentiation of endogenous and exogenous formaldehyde-induced DPCs. In addition, endogenous formaldehyde-induced DPCs may increase the risks of bone marrow toxicity and leukemia. Formaldehyde has been classified as a genotoxic carcinogen. The covalent linkages between DNA and protein are induced by chemical reactions catalyzed by the endogenous metabolic intermediates and exogenous agents, such as aldehydes, chemotherapeutic agents, and ionizing radiation. Genomic instability caused by DNA–protein cross-link (DPCs)-induced DNA damage is implicated in disease pathogenesis, aging, and cancer development.