Polycyclic aromatic hydrocarbons are associated with insulin receptor substrate 2 methylation in adipose tissues of Korean women

Kim, Young Hun; Lee, Yoon Soon; Lee, Dong Hoon; Kim, Dong Sun

doi:10.1016/j.envres.2016.05.043

Cited by 28 publications

(22 citation statements)

References 29 publications

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“…Third, PAHs influence epigenetic modification, such as defects in DNA methylation. PAHs interfere with DNA methylation during pancreatic β-cell development 9 and DNA methylation of insulin receptor substrate 2 10 and PPAR-γ. 45 Other mechanisms include hepatic dysfunction, 41 skeletal muscle inflammation, and endothelial dysfunction, which reduce peripheral glucose uptake.…”

Section: Discussionmentioning

confidence: 99%

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<p>Association of Urinary Polycyclic Aromatic Hydrocarbons and Diabetes in Korean Adults: Data from the Korean National Environmental Health Survey Cycle 2 (2012–2014)</p>

Nam¹,

Kim²

2020

DMSO

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Purpose To investigate the associations between the urinary levels of polycyclic aromatic hydrocarbons (PAHs) and diabetes mellitus in Korean adults. Materials and Methods We examined the data of 6478 participants aged ≥19 years from the Korean National Environmental Health Survey (KoNEHS) cycle 2 (2012–2014). The urinary levels of 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenathrene (1-OHPhe), and 2-hydroxyfluorene (2-OHFlu) were measured by gas chromatography-mass spectrometry. Diabetes mellitus was defined as a self-report of physician-diagnosed diabetes mellitus or the use of oral hypoglycemics or insulin. Analyses were adjusted for sex, age, body mass index, household income, alcohol consumption, physical activity, urinary creatinine and cotinine, menopausal status, and quartiles of all other PAHs. Results The prevalence of diabetes was 6.5% in the study population. In men, the geometric means of the 2-NAP and 2-OHFlu levels were higher in participants with diabetes mellitus than in those without diabetes mellitus [4.11 vs 3.26 μg/L ( P <0.05) and 0.45 vs 0.40 μg/L ( P <0.05), respectively]. In women, the geometric mean of 2-NAP levels was also higher in participants with diabetes mellitus than in those without diabetes mellitus (1.81 vs 0.56 μg/L, P <0.05), but there were no significant differences in geometric means for other PAHs. A higher odds ratio (OR) of diabetes was found in participants with the highest quartiles of urinary 2-NAP [OR 1.83, 95% confidence interval (CI) 1.29–2.60] and 2-OHFlu (OR 1.81, 95% CI 1.10–2.98) than in those with the lowest quartiles. Conclusion The urinary 2-NAP and 2-OHFlu levels were associated with diabetes mellitus in Korean adults. Further studies are needed to determine a potential causal relationship between PAH exposure and diabetes mellitus and its underlying mechanism.

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Section: Discussionmentioning

confidence: 99%

“…In experimental studies, the possible mechanisms linking PAH exposure to diabetes include oxidative stress 6 and systemic inflammation, 7 , 8 which induce β-cell dysfunction 9 and disruption of the insulin signaling pathway. 10 …”

Section: Introductionmentioning

confidence: 99%

<p>Association of Urinary Polycyclic Aromatic Hydrocarbons and Diabetes in Korean Adults: Data from the Korean National Environmental Health Survey Cycle 2 (2012–2014)</p>

Nam¹,

Kim²

2020

DMSO

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“…The methylation of key genes related to breast cancer, like retinoic acid receptor beta (RARβ) and adenomatosis polyposis coli tumor suppressor (APC), has been associated with the presence of PAH adducts in breast tumor tissue and various sources of PAH exposure [ 268 , 269 ]. Additional genes that display altered DNA methylation due to PAH exposures play a role in insulin resistance [ 270 ] and cancer [ 267 ]. All the genes described above show PAHs-related DNA hypermethylation, suggesting a potential role for PAHs as an environmental factor that can silence gene expression via epigenetic mechanism at site-specific loci.…”

Section: Epigenetic Effects Associated With Carcinogenic Chemicals From Gasolinementioning

confidence: 99%

An Assessment on Ethanol-Blended Gasoline/Diesel Fuels on Cancer Risk and Mortality

Mueller

Dennison

Liu

2021

IJERPH

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Although cancer is traditionally considered a genetic disease, the epigenetic abnormalities, including DNA hypermethylation, histone deacetylation, and/or microRNA dysregulation, have been demonstrated as a hallmark of cancer. Compared with gene mutations, aberrant epigenetic changes occur more frequently, and cellular epigenome is more susceptible to change by environmental factors. Excess cancer risks are positively associated with exposure to occupational and environmental chemical carcinogens, including those from gasoline combustion exhausted in vehicles. Of note, previous studies proposed particulate matter index (PMI) as a measure for gasoline sooting tendency, and showed that, compared with the other molecules in gasoline, 1,2,4–Trimethylbenzene, 2–methylnaphthalene and toluene significantly contribute to PMI of the gasoline blends. Mechanistically, both epigenome and genome are important in carcinogenicity, and the genotoxicity of chemical agents has been thoroughly studied. However, less effort has been put into studying the epigenotoxicity. Moreover, as the blending of ethanol into gasoline substitutes for carcinogens, like benzene, toluene, xylene, butadiene, and polycyclic aromatic hydrocarbons, etc., a reduction of secondary aromatics has been achieved in the atmosphere. This may lead to diminished cancer initiation and progression through altered cellular epigenetic landscape. The present review summarizes the most important findings in the literature on the association between exposures to carcinogens from gasoline combustion, cancer epigenetics and the potential epigenetic impacts of biofuels.

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“…DNA methylation is one major type of epigenetic regulation that is fairly stable across time and is typically associated with repression of gene expression. 20 It has been shown in adults to be responsive to a multitude of environmental factors including PAHs, other toxicant exposures, 21 - 24 and stress. 25 We have previously shown differential blood DNA methylation in incumbent compared to new recruit firefighters, adjusted for age, and other covariates, as well as differential whole blood microRNA expression.…”

Section: Introductionmentioning

confidence: 99%

Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States

et al. 2021

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Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw P-value <.05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate ( q-value <.05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at q < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene SULT1C2 had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies ( FOXK2, GYLTL1B, ZBTB16, ARHGEF10, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.

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Polycyclic aromatic hydrocarbons are associated with insulin receptor substrate 2 methylation in adipose tissues of Korean women

Cited by 28 publications

References 29 publications

<p>Association of Urinary Polycyclic Aromatic Hydrocarbons and Diabetes in Korean Adults: Data from the Korean National Environmental Health Survey Cycle 2 (2012–2014)</p>

<p>Association of Urinary Polycyclic Aromatic Hydrocarbons and Diabetes in Korean Adults: Data from the Korean National Environmental Health Survey Cycle 2 (2012–2014)</p>

An Assessment on Ethanol-Blended Gasoline/Diesel Fuels on Cancer Risk and Mortality

Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States

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