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Environmental exposure would cause DNA damage and epigenetic modification changes, potentially resulting in physiological dysfunction, thereby triggering diseases and even cancer. DNA damage and epigenetic modifications are thus promising biomarkers for environmental exposures and disease states. Benefiting from its high sensitivity and accuracy, high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is considered the "gold standard technique" for investigating epigenetic DNA modifications. This review summarizes the recent advancements of UHPLC-MS/MS-based technologies for DNA damage and epigenetic modifications analysis, mainly focusing on the innovative methods developed for UHPLC-MS/MS-related pretreatment technologies containing efficient genomic DNA digestion and effective removal of the inorganic salt matrix, and the new strategies for improving detection sensitivity of liquid chromatography-mass spectrometry. Moreover, we also summarized the novel hyphenated techniques of the advanced UHPLC-MS/MS coupled with other separation and analysis methods for the measurement of DNA damage and epigenetic modification changes in special regions and fragments of chromosomes. • Accelerated genomic DNA digestion strategies for LC-MS analysis. • Matrix desalination and salt interference mitigation. • New strategies for improving detection sensitivity of LC-MS. • Applications of DNA damage and epigenetic modification analysis via LC-MS and complementary techniques. [ABSTRACT FROM AUTHOR]

Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts. Our results demonstrated that BPF exposure disturbed the metabolome and lipidome of liver and kidney. Exposure induced reprogramming of the glutathione (GSH) biosynthesis and glycolytic metabolism by activating glycine, serine, cysteine, glutamine, lactate and pyruvate in liver and kidney tissues. It also perturbed the biosynthesis and degradation of glycerophospholipids (GPs) and glycerolipids (GLs), resulting in abnormality of membrane homeostasis and cellular functions in kidney tissues. Moreover, spatial distribution and profile of metabolites changed across renal cortex and medulla regions after BPF treatment. Levels of phosphatidylethanolamines (PE) and triacylglycerols (TAG) increased in renal medulla and pelvis, while the levels of phosphatidylcholines (PC) and phosphatidylinositols (PI) increased in cortex and pelvis. These observations offer a deeper understanding of critical role of metabolites and lipid reprogramming in BPF-induced biological effects. [ABSTRACT FROM AUTHOR]

Long-term exposures to environmental toxicants are causative factors for human health effects. DNA damages are of great interest in that they can serve as the potential biomarkers of environmental exposure and mutations. Qualitative and quantitative detection of their level in genomic DNA, are helpful for the understanding of the generation, transformation, repair and fate of DNA damages and for elucidating the mechanism underlying carcinogenesis. Methodologies based on liquid chromatography-mass spectrometry (LC-MS) have shown unique advantages in accurate and highly sensitive analysis of these structurally modified DNA damages. The present review summarizes our current knowledge on LC-MS analysis of genetic DNA damages, with special emphasis on structurally chemical DNA modifications induced by environmental exposure. Advances in LC-MS analysis and monitoring of oxidative DNA lesion, DNA adducts induced by heavy metals, persistent organic pollutants, bisphenols, fine particulate matters, aldehydes and halobenzoquinones are comprehensively summarized. • Highly sensitive LC-MS methods for DNA damages analysis. • Oxidative DNA damages, DNA adducts induced by environmental exposure. • DNA modifications caused by new emerging contaminants including PM2.5 and BPA. • Advances in DNA damage monitoring and adductomics benefited from LC-MS/MS. [ABSTRACT FROM AUTHOR]

Abstract Four DNA bases are essential biochemical elements for coding heritable life blueprint. Meanwhile, organisms utilize modifying enzymes to post chemical groups on DNA bases to regulate gene expression, chromosome structures, and transposase activity, and to defense pathogens. The researches on the biochemical modifications of DNA bases are at the cutting edge of life sciences and chemical biology. Up to date, along with fantastic progresses, liquid chromatography hyphenated with mass spectrometry (LC-MS)-based technologies become popular and powerful tools for chemical structure-dependent identification and quantification of diverse DNA modifications. Here we provided comprehensive review on LC-MS-based technologies and related pretreatment technologies for profiling of epigenetic DNA modifications, mainly focusing on innovative technologies developed for desalting, DNA digestion, and ionization for mass spectrometry detection. We also summarized the epigenetic progresses, which benefited from the development of the LC-MS methodologies and technologies, on the studies of specific DNA modifications, in particular, 5-hydroxymethylcytosine and 5-formylcytosine. Highlights • LC-MS/MS methods for detection of epigenetic DNA modifications. • DNA hydrolysis for generation of LC-MS detectable mononucleosides. • Chemical approaches for enhancing LC-MS signal. • Progresses on epigenetic DNA modifications benefited from LC-MS/MS analysis. [ABSTRACT FROM AUTHOR]

DNA N6-methyladenine modification (6mA) is a predominant epigenetic mark in prokaryotes but rarely present in multicellular metazoa. The analytical technologies have been developed for sensitive detection of 6mA, including ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) and single molecule real-time sequencing (SMRTseq). However, it remains challenging to detect 6mA at global level and/or in the context of sequence in multicellular metazoa (including mammals). This mini-review brings insights into current dilemma and potential solutions for the identification and quantifications of 6mA in mammals. [ABSTRACT FROM AUTHOR]

• A recyclable and reusable multi-enzymes cascade (SNSC-MNPs) for enzymatic digestion of genomic DNA was constructed. • SNSC-MNPs cascade enable fast digestion of genomic DNA into mono-nucleosides within 30 min. • Coupling SNSC-MNPs with HPLC-MS/MS, a sensitive and accurate method for quantitation of 5-hydroxymethylcytosine (5hmC) was developed. • TCBQ exposure induces elevated 5hmC levels in the genome of T24 cells. Long-term exposure to halobenzoquinones (HBQs) can induce genomic damages and abnormal epigenetic modifications. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) has shown unique advantages in identification and sensitive analysis of these structurally modified DNA lesions. Prior to MS analysis, genomic DNA needs to be fully digested into mono-nucleosides. Here, we prepared Supernuclease (SN)-, snake venom phosphodiesterase (SVP)- and calf intestinal alkaline phosphatase (CIP)- individually immobilized magnetic nanoparticles (MNPs), and combined them according to certain formula to construct a recyclable SN-SVP-CIP magnetic nanoparticles (SNSC-MNPs) cascade for rapid and efficient DNA digestion. The SNSC-MNPs cascade can fully digest genomic DNA into mono-nucleosides within 30 min. The SNSC-MNPs cascade coupled with HPLC-MS/MS method can accurately and sensitively detect 5-hydroxymethylcytosine (5hmC) changes in genome of human bladder cancer T24 cells induced by tetrachlorobenzoquinone. The immobilization of enzymes on MNPs can enhance the stability and enzymatic activity of the three enzymes, which guarantees the reusability and longtime preservation of the cascades. The relative digestive efficiencies are among 86% -106% up to ten times of reuse. The newly synthesized SNSC-MNPs cascade coupled with HPLC-MS/MS method is promising for fast identification and analysis of structural modifications in genomic DNA. [ABSTRACT FROM AUTHOR]