Exposure to volatile organic compounds – acrolein, 1,3-butadiene, and crotonaldehyde – is associated with vascular dysfunction

Background: Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs (miRs) maintain cellular homeostasis and may regulate the response to environmental stress. Objectives: We tested the hypothesis that specific miRs are associated with liver disease and PCB exposures in a residential cohort. Methods: Sixty-eight targeted hepatotoxicity miRs were measured in archived serum from 734 PCB-exposed participants in the cross-sectional Anniston Community Health Survey. Necrotic and other liver disease categories were defined by serum keratin 18 (K18) biomarkers. Associations were determined between exposure biomarkers (35 ortho-substituted PCB congeners) and disease biomarkers (highly expressed miRs or previously measured cytokines), and Ingenuity Pathway Analysis was performed. Results: The necrotic liver disease category was associated with four up-regulated miRs (miR-99a-5p, miR-122-5p, miR-192-5p, and miR-320a) and five down-regulated miRs (let-7d-5p, miR-17-5p, miR-24-3p, miR-197-3p, and miR-221-3p). Twenty-two miRs were associated with the other liver disease category or with K18 measurements. Eleven miRs were associated with 24 PCBs, most commonly congeners with anti-estrogenic activities. Most of the exposure-associated miRs were associated with at least one serum hepatocyte death, pro-inflammatory cytokine or insulin resistance bioarker, or with both. Within each biomarker category, associations were strongest for the liver-specific miR-122-5p. Pathways of liver toxicity that were identified included inflammation/hepatitis, hyperplasia/hyperproliferation, cirrhosis, and hepatocellular carcinoma. Tumor protein p53 and tumor necrosis factor were well integrated within the top identified networks. Discussion: These results support the human hepatotoxicity of environmental PCB exposures while elucidating potential modes of PCB action. The MiR-derived liquid liver biopsy represents a promising new technique for environmental hepatology cohort studies. https://doi.org/10.1289/EHP9467

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“…2019 ; Pittman et al. 2020b ) or Bayesian kernel machine regression approaches, as we have published ( McGraw et al. 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey

Cave

Pinkston

Shesh

et al. 2022

Environ Health Perspect

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“…34 In a Chinese temple, the acrolein level was up to 3 times higher during incense burning than in the outside. 28 Williams et al 51 determined an average acrolein concentration of 5 -6 µg m -³ in 6 London smoking rooms exceeding those measured in comparison rooms. A comprehensive study targeting on carbonyl emissions in the exhaust of commercial kitchens in China was performed by Hu et al 54 revealing substantial amounts of acrolein in dependence of different cooking ingredients.…”

Section: Acrolein Levels In Outdoor and Indoor Airmentioning

confidence: 98%

“…The toxic effect is mainly based on the formation of protein and DNA adducts. 2 Irritant effects, 3 decreased respiratory function 4 and cardiovascular diseases 5,6 were also reported. The various exposure paths (inhalation, dermal, oral) are discussed by Faroon et al 7 The Office of Environmental Health Hazard Assessment (OEHHA) gives the following Reference Exposure Limits (REL) for the inhalation path: acute REL = 2.5 µg m -³; 8 h REL = 0.7 µg m -³; chronic REL = 0.35 µg m -³.…”

Section: Introductionmentioning

confidence: 97%

Determination of acrolein in ambient air and in the atmosphere of environmental test chambers

Schieweck

Uhde

Salthammer

2021

Environ. Sci.: Processes Impacts

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“…Similarly, another study performed in China even failed to detect MHBMA3 in 100 urine samples from children aged 6-12 years [ 153 ]. A possible explanation for the surprising observations reported in the two studies is that the authors used cis -MHBMA3 as the reference standard and the LOD in the latter study was somewhat high (3.13 ng/mL) [ 152 , 153 ], although in the studies of Alwis et al [ 139 ] and other authors [ 44 , 63 , 64 , 140 – 148 , 151 ], the configuration of the MHBMA3 standard was not specified.…”

Section: Introductionmentioning

confidence: 99%

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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Exposure to volatile organic compounds – acrolein, 1,3-butadiene, and crotonaldehyde – is associated with vascular dysfunction

Cited by 67 publications

References 75 publications

Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey

Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey

Determination of acrolein in ambient air and in the atmosphere of environmental test chambers

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

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