Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine

Erber, Luke; Goodman, Samantha; Krueger, Caitlin C Jokipii; Rusyn, Ivan; Tretyakova, Natalia

doi:10.3390/toxics9100247

Cited by 5 publications

(5 citation statements)

References 59 publications

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“…Today, liquid chromatography–mass spectrometry (LC-MS) techniques are a mainstay for DNA adduct analysis. ,− Many DNA modifications, such as the bulky PAH adducts and methylated and oxidized lesions, can be quantified in a single DNA sample. − High-resolution accurate mass spectrometry (HRAM) data on DNA adducts available from, for instance, Orbitrap high-resolution mass spectrometry (HRMS) facilitates the determination of their chemical structure, which can help exposure diagnostics. However, a nontargeted analysis is needed when no suitable DNA adduct library for the studied system is available.…”

Section: Introductionmentioning

confidence: 99%

DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments

Martella

Gorokhova

Sousa

et al. 2023

Environ. Sci. Technol.

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Exposure to chemical pollution can induce genetic and epigenetic alterations, developmental changes, and reproductive disorders, leading to population declines in polluted environments. These effects are triggered by chemical modifications of DNA nucleobases (DNA adducts) and epigenetic dysregulation. However, linking DNA adducts to the pollution load in situ remains challenging, and the lack of evidence-based DNA adductome response to pollution hampers the development and application of DNA adducts as biomarkers for environmental health assessment. Here, we provide the first evidence for pollution effects on the DNA modifications in wild populations of Baltic sentinel species, the amphipod Monoporeia affinis. A workflow based on high-resolution mass spectrometry to screen and characterize genomic DNA modifications was developed, and its applicability was demonstrated by profiling DNA modifications in the amphipods collected in areas with varying pollution loads. Then, the correlations between adducts and the contaminants level (polycyclic aromatic hydrocarbons (PAHs), trace metals, and pollution indices) in the sediments at the collection sites were evaluated. A total of 119 putative adducts were detected, and some (5-me-dC, N6-me-dA, 8-oxo-dG, and dI) were structurally characterized. The DNA adductome profiles, including epigenetic modifications, differed between the animals collected in areas with high and low contaminant levels. Furthermore, the correlations between the adducts and PAHs were similar across the congeners, indicating possible additive effects. Also, high-mass adducts had significantly more positive correlations with PAHs than low-mass adducts. By contrast, correlations between the DNA adducts and trace metals were stronger and more variable than for PAHs, indicating metal-specific effects. These associations between DNA adducts and environmental contaminants provide a new venue for characterizing genome-wide exposure effects in wild populations and apply DNA modifications in the effect-based assessment of chemical pollution.

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Section: Introductionmentioning

confidence: 99%

DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments

Martella

Gorokhova

Sousa

et al. 2023

Environ. Sci. Technol.

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“…The DNA adducts released are eventually excreted in urine and thus can also be used as urinary biomarkers. Although many BD-derived DNA adducts have been identified [ 7 ], so far only two DNA adducts, N 7-[1-(hydroxymethyl)-2-propen-1-yl]guanine (EB-GII) and 1,4- bis (gua-7-yl)-2,3-butanediol ( bis -N7G-BD), have been used as urinary biomarkers [ 130 , 131 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, this biomarker was not detected in urine of smokers and workers occupationally exposed to BD [ 113 ]. In urine of mice exposed to 590 ppm (1,300 mg/m 3 ) BD for two weeks, the bis -BDMA concentration was 8.09 ± 6.3 μg/mL [ 131 ].…”

Section: Introductionmentioning

confidence: 99%

“…The adduct can be detected in tissues of rats and mice exposed to BD [ 95 ]. Use of bis -N7G-BD as a urinary biomarker was reported just before the review is published [ 131 ]. In the study, very low concentrations of bis -N7G-BD (~570 pg/mg creatinine) were detected in urine of mice exposed to 590 ppm (1,300 mg/m 3 ) BD for two weeks [ 131 ].…”

Section: Introductionmentioning

confidence: 99%

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1,3-Butadiene: a ubiquitous environmental mutagen and its associations with diseases

Chen

Zhang

2022

Genes and Environ

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Abstract1,3-Butadiene (BD) is a petrochemical manufactured in high volumes. It is a human carcinogen and can induce lymphohematopoietic cancers, particularly leukemia, in occupationally-exposed workers. BD is an air pollutant with the major environmental sources being automobile exhaust and tobacco smoke. It is one of the major constituents and is considered the most carcinogenic compound in cigarette smoke. The BD concentrations in urban areas usually vary between 0.01 and 3.3 μg/m3 but can be significantly higher in some microenvironments. For BD exposure of the general population, microenvironments, particularly indoor microenvironments, are the primary determinant and environmental tobacco smoke is the main contributor. BD has high cancer risk and has been ranked the second or the third in the environmental pollutants monitored in most urban areas, with the cancer risks exceeding 10-5. Mutagenicity/carcinogenicity of BD is mediated by its genotoxic metabolites but the specific metabolite(s) responsible for the effects in humans have not been determined. BD can be bioactivated to yield three mutagenic epoxide metabolites by cytochrome P450 enzymes, or potentially be biotransformed into a mutagenic chlorohydrin by myeloperoxidase, a peroxidase almost specifically present in neutrophils and monocytes. Several urinary BD biomarkers have been developed, among which N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine is the most sensitive and is suitable for biomonitoring BD exposure in the general population. Exposure to BD has been associated with leukemia, cardiovascular disease, and possibly reproductive effects, and may be associated with several cancers, autism, and asthma in children. Collectively, BD is a ubiquitous pollutant that has been associated with a range of adverse health effects and diseases with children being a subpopulation with potentially greater susceptibility. Its adverse effects on human health may have been underestimated and more studies are needed.

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“…There is a growing number of reports where targeted approaches have been used to successfully detect specific, environmentally-induced DNA adducts in urine. Examples of urinary adducts include: 3-(4-dihydroxyphenyl)adenine, following benzene exposure of mice 78 ; aflatoxin N7-guanine, and 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxy-aflatoxin B1, following exposure of rats to aflatoxin 79 ; N7-(1-hydroxy-3-buten-2-yl)guanine following exposure of mice to 1,3-butadiene (BD) 80 , and occupationally- or recreationally- (tobacco smoke) exposed humans 81 ; N7-(1-hydroxy-3-buten-2-yl) guanine adducts were also detected in the same human urine samples from the previous citation 80 , and bis -N7-guanine DNA-DNA crosslinks in mice exposed to BD 82 . This work, using targeted approaches, is beginning to successfully link exposure to environmental agents to specific urinary DNA adducts.…”

Section: Introductionmentioning

confidence: 99%

Nucleic Acid Adductomics – the Next Generation of Adductomics for Assessing Environmental Health Risk

Cooke

Chang

Chen

et al. 2022

Preprint

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The exposome describes the totality of internal and external environmental exposures, across the life course. Components of the exposome have been linked to an increased risk of various, major diseases. To identify the precise nature, and size, of risk, in this complex mixture of exposures, powerful tools are needed to link exposure, cellular consequences, and health/disease. The most biologically informative biomarkers of the exposome should, to varying extents, reflect the dose of the exposure on the body or target organ(s), a subsequent effect on the biological system and, ideally, possess a role in disease. Modification of nucleic acids (NA) is a key consequence of environmental exposures, and while cellular DNA adductomics aims to evaluate the totality to DNA modifications in the genome, an approach which encompasses modifications of all nucleic acids, would be far more comprehensive, and therefore informative. To address this, we propose a cellular and urinary NA adductomics approach for the assessment of both DNA and RNA modifications, including modified (2-deoxy)ribonucleosides (2dN/rN), modified nucleobases (nB), plus: DNA-DNA, RNA-RNA, DNA-RNA, DNA-protein, and RNA-protein crosslinks (DDCL, RRCL, DRCL, DPCL, and RPCL, respectively). Supporting the feasibility of this approach, we presented preliminary, proof-of-principle results, which revealed the presence of over 1,000 modified NA moieties, and at least six types of NA modifications, in a representative, pooled urine from healthy subjects, including modified 2-dN, modified rN, modified nB, DRCL, RRCL and RPCL, many of which were novel/unexpected. We suggest that NA adductomics will provide a more comprehensive approach to the study of nucleic acid modifications, which will facilitate a range of advances, including the identification of novel, unexpected modifications e.g., RNA-RNA, and DNA-RNA crosslinks; key modifications associated with mutagenesis; agent-specific mechanisms; and adductome signatures of key environmental agents, leading to the dissection of the exposome, and its role in human health/disease, across the life course.

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Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine

Cited by 5 publications

References 59 publications

DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments

DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments

1,3-Butadiene: a ubiquitous environmental mutagen and its associations with diseases

Nucleic Acid Adductomics – the Next Generation of Adductomics for Assessing Environmental Health Risk

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