Epigenetic Markers Are Associated With Differences in Isocyanate Biomarker Levels in Exposed Spray-Painters

Taylor, Laura W.; French, John E.; Robbins, Zachary G.; Nylander‐French, Leena A.

doi:10.3389/fgene.2021.700636

Cited by 7 publications

(4 citation statements)

References 87 publications

(119 reference statements)

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“…In line with this, several EWAS have also linked CpG methylation to environmental exposures, e.g. air quality 23 , stress 24 , occupational exposure to chemicals 25,26 , prescribed medications 27 , dietary habits such as coffee and alcohol consumption 28,29 and supplement intake 30 .…”

Section: Introductionmentioning

confidence: 82%

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Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study

Demirkan,

van Dongen,

Finnicum

et al. 2023

Preprint

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Both gene methylation and the gut microbiome are partially determined by host genetics and partially by environment. We investigated the relations between gene methylation in blood and the abundance of common gut bacteria profiled by 16s rRNA gene sequencing in two population-based Dutch cohorts: LifeLines-Deep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbiome composition using data generated by shotgun metagenomic sequencing (n = 683). We then investigated if genetic and environmental factors can explain the methylation–microbiota associations in a set of 78 associated CpG–taxa pairs from the EWAS meta-analysis. In both cohorts, blood and stool samples were collected within 2 weeks of each other. Methylation was profiled in blood samples using the Illumina 450K array. Methylation and microbiome analysis pipelines were harmonized across cohorts. Epigenome-wide association study (EWAS) of microbial features were analysed using linear regression with adjustment for technical covariates.Discovery and replication analysis using 16s data identified two independent CpGs associated with the genusEggerthella: cg16586104 (Pmeta-analysis= 3.21 × 10-11) and cg12234533 (Pmeta-analysis= 4.29 × 10-10). While we did not find human genetic variants that could explain the associated CpG–taxa/pathway pairs, we show that microbiome can mediate the effect of environmental factors on epigenetics.In this first association study linking epigenome to microbiome, we found and replicated the associations of two CpGs to the abundance of genusEggerthellaand identified microbiome as a mediator of the exposome.

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Section: Introductionmentioning

confidence: 82%

“…, occupational exposure to chemicals 25,26 , prescribed medications 27 , dietary habits such as coffee and alcohol consumption 28,29 and supplement intake 30 .…”

mentioning

confidence: 99%

Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study

Demirkan,

van Dongen,

Finnicum

et al. 2023

Preprint

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“…Given the limited half-life of IgE antibodies, limited temporal presence of IgG antibodies after exposure, and variability in individual responses, reliance on antibodies as markers of exposure or disease may not be feasible [ 28 ]. While advancements in urinalysis and epigenome sequencing may provide future means of performing routine isocyanate exposure monitoring, no such method is currently widely available [ 40 , 41 ]. Difficulties in monitoring occupational exposure necessitate undertaking efforts to minimize isocyanate exposure.…”

Section: Discussionmentioning

confidence: 99%

Reduced Isocyanate Release Using a Waterproof, Resin-Based Cast Alternative Relative to Fiberglass Casts

Stefanescu,

Timlin,

Moy

et al. 2023

Toxics

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The effects of occupational isocyanate exposure range from asthma and contact dermatitis to neurotoxicity and cancer. Respiratory sensitization due to orthopedic cast application has been well documented. This study aims to compare the safety of standard-of-care fiberglass casts and a novel waterproof cast alternative by measuring the amount of isocyanate released during off-gassing over time. A 3D-printed arm simulator with comparable casing material amounts was placed in a sealed chamber. An isocyanate-sensing color-changing (SafeAir) tag was used to measure the levels of toxic exposure. Triplicate trials were conducted across all time periods (15 min, 1 h, and 24 h) and conditions. The bare arm simulator and freshly opened tags served as negative controls. Normalized pixel intensity indexes and isocyanate release estimates in ppb were derived from ImageJ-analyzed SafeAir tag photos. Fiberglass casts exhibited greater isocyanate release than both the waterproof alternative (p = 0.0002) and no-cast controls (p = 0.0006), particularly at 24 h. The waterproof alternative and no-cast control did not statistically differ (p = 0.1603). Therefore, the waterproof alternative released less isocyanate than the fiberglass casts. Waterproof cast alternatives may be safer than fiberglass by limiting medical professionals’ exposure to toxic isocyanates and, thus, decreasing their risk of suffering occupational asthma.

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“…The amount of HDI bound was quantified with HDA released after strong acidic hydrolysis. To date, all methods to quantify albumin adducts were performed with an immunological assay ,, or with chemical hydrolysis, followed by GC–mass spectrometry (MS) analysis. − For in vitro modified albumin, Wisnewski et al demonstrated a linear relationship between the immunological test and the chemical hydrolysis that releases HDA. Lysine adducts present in albumin modified in vitro with HDI appear to be crucial for the immunological response of antibodies present in exposed workers .…”

Section: Introductionmentioning

confidence: 99%

New Method to Biomonitor Workers Exposed to 1,6-Hexamethylene Diisocyanate

Sabbioni

Pugh²

2022

Chem. Res. Toxicol.

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Isocyanates such as 1,6-hexamethylene diisocyanate (HDI), 4,4′-methylenediphenyl diisocyanate, and toluene diisocyanate are highly reactive compounds that have a variety of commercial applications, including manufacturing polyurethane foam, elastomers, paints, adhesives, coatings, insecticides, and many other products. Their primary route of occupational exposure is through inhalation. Due to their high chemical reactivity, they are toxic and have adverse effects at the cellular and subcellular levels, leading to irritative and immunological reactions associated with lung disease. High concentrations of isocyanates are strong respiratory irritants. Bronchial sensitization and asthma are among the major adverse clinical reactions associated with low-level chronic exposure to isocyanates. Albumin adducts have been linked to the mechanism of occupational asthma caused by isocyanates. Isocyanates react in vivo with albumin, which is recognized by the immune system. Albumin adducts of isocyanates trigger immune responses and are probably the antigenic basis for isocyanate asthma. Sensitization to isocyanates is the main pathway for adverse health effects. Therefore, markers for the biologically effective dose such as albumin adducts of HDI are needed. A new isocyanate adduct of HDI with lysine�N ε -[(6-amino-hexyl-amino)carbonyl]-lysine (HDI-Lys)�was synthesized and characterized by 1 H-NMR, 13 C-NMR, and mass spectrometry (MS). Appropriate internal standards�HDI-Lys-4,4′-5,5′-d 4 (HDI-d 4 -Lys) and N ε -[(7amino-heptyl-amino)carbonyl]-lysine (Hep-Lys)�were synthesized to establish a LC−MS/MS method for the analysis of HDI adducts in in vitro modified albumin and in workers. The presence of HDI-Lys was found after pronase digestion of albumin and confirmed by two independent chromatographic approaches: with a C8 reversed-phase column and with a hydrophilic interaction liquid chromatography column. Quantification was performed with positive electrospray ionization (ESI)−MS. The adduct peak found in vivo was confirmed with the less sensitive negative ESI−MS. In summary, these are new compounds and methods to determine isocyanate-specific adducts with albumin in workers exposed to HDI.

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Epigenetic Markers Are Associated With Differences in Isocyanate Biomarker Levels in Exposed Spray-Painters

Cited by 7 publications

References 87 publications

Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study

Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study

Reduced Isocyanate Release Using a Waterproof, Resin-Based Cast Alternative Relative to Fiberglass Casts

New Method to Biomonitor Workers Exposed to 1,6-Hexamethylene Diisocyanate

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