Hypomethylation of Dual Specificity Phosphatase 22 Promoter Correlates With Duration of Service in Firefighters and Is Inducible by Low-Dose Benzo[a]Pyrene
Firefighters (FFs) are chronically exposed to smoke and products of incomplete combustion, which frequently contain polycyclic aromatic hydrocarbons (PAHs). This study examined the possibility of an association between PAH-induced epigenetic alterations and occupational firefighting exposure. Promoter methylation was analyzed in four genes in blood DNA from 18 FFs and 20 non-FFs (controls). Jurkat and human normal prostate epithelial cells were treated with benzo[a]pyrene to ascertain the epigenetic effects of this type of agent. Firefighters had a higher prevalence of dual specificity phosphatase 22-promoter hypomethylation in blood DNA (P = 0.03) and the extent of hypomethylation correlated with duration of firefighting service (P = 0.04) but not with age. Benzo[a]pyrene reduced promoter methylation and increased gene expression of the same gene in Jurkat and normal prostate epithelial cells. Cumulative occupational exposure to combustion-derived PAHs during firefighting can cause epigenetic changes in promoters of specific genes.
- [Show abstract] [Hide abstract] ABSTRACT: This review focuses on how environmental factors through epigenetics modify disease risk and health outcomes. Major epigenetic events, such as histone modifications, DNA methylation, and microRNA expression, are described. The function of dose, duration, composition, and window of exposure in remodeling the individual's epigenetic terrain and disease susceptibility are addressed. The ideas of lifelong editing of early-life epigenetic memories, transgenerational effects through germline transmission, and the potential role of hydroxylmethylation of cytosine in developmental reprogramming are discussed. Finally, the epigenetic effects of several major classes of environmental factors are reviewed in the context of pathogenesis of disease. These include endocrine disruptors, tobacco smoke, polycyclic aromatic hydrocarbons, infectious pathogens, particulate matter, diesel exhaust particles, dust mites, fungi, heavy metals, and other indoor and outdoor pollutants. We conclude that the summation of epigenetic modifications induced by multiple environmental exposures, accumulated over time, represented as broad or narrow, acute or chronic, developmental or lifelong, may provide a more precise assessment of risk and consequences. Future investigations may focus on their use as readouts or biomarkers of the totality of past exposure for the prediction of future disease risk and the prescription of effective countermeasures.0Comments 41Citations
- [Show abstract] [Hide abstract] ABSTRACT: Risk factors have not been identified that determine susceptibility for development of diisocyanate induced occupational asthma (DA). We hypothesized that diisocyanate exposure could modify gene promoter regions regulating transcription of cytokine mediators and thereby influence expression of DA. A cross-sectional study was designed to investigate the promoter methylation status of candidate genes in diisocyanate exposed workers. Subjects consisted of 131 workers in three groups: 40 cases with DA confirmed by a positive specific inhalation challenge (SIC) (DA+); 41 exposed workers with lower respiratory symptoms and negative SIC (DA-); and 50 asymptomatic exposed workers (AW). We studied four candidate genes (GSTM1, DUSP22, IFN-γ, and IL-4) for which altered promoter methylation has been previously investigated for relationships with a variety of other environmental exposures. Methylation status was determined using methylation-specific-quantitative PCR performed on genomic DNA extracted from whole blood. Results showed that relative methylation of IFN-γ promoter was significantly increased in DA+ in comparison to both comparator groups (DA- and AW); and it exhibited good sensitivity (77.5%) and specificity (80%) for identifying DA workers in a multivariate predictive model after adjusting for type of DI exposure, smoking status, methacholine PC20 and gender. IL-4 promoter was slightly less methylated only in DA+ compared to AW among non-smoking workers. Both GSTM1 and DUSP22 promoter methylations were found not associated with DA. Our finding suggests that exposure to occupational chemicals could play a heretofore undefined mechanistic role via epigenetic modification of specific genes in the promoter region.0Comments 12Citations
- [Show abstract] [Hide abstract] ABSTRACT: The health effects of ambient air pollution are well-described, but less is known about the biological mechanisms mediating these health effects. In recent years, the hypothesis that epigenetics may play a role in driving exposure-disease associations has gained traction, in part because epigenetic modifications are labile and may respond to environmental exposures in ways that directly affect gene transcription and disease risk. The purpose of this review is to provide an understanding of the latest evidence to support this hypothesis. The studies selected for this review were collected through a PubMed search for articles published between January 2010 and July 2013 using the following epigenetics keywords: epigenetics, histone, microRNA, and DNA methylation; along with air pollutant keywords: air pollution, benzo[a]pyrene, nitrogen dioxide, ozone, particulate matter 1.0 (PM1), particulate matter 2.5 (PM2.5), particulate matter 10 (PM10) and polycyclic aromatic hydrocarbon (PAH). A total of 38 original research articles were identified for our review. The scientific studies to date provide evidence that PAHs and PM2.5 may have modest effects on methylation levels of certain CpG sites within candidate genes of interest in cardiovascular and respiratory disease as well as cancer. However, the data remain too sparse to draw any meaningful conclusions with regard to histone modifications, miRNAs, or effects of other pollutants such as NO2, O3, and SO4.0Comments 6Citations
- [Show abstract] [Hide abstract] ABSTRACT: Firefighters are exposed to chemicals during fire events and may also experience chemical exposure in their fire stations. Dust samples from used vacuum cleaner bags were collected from 20 fire stations in California and analyzed for polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) using gas chromatography-mass spectrometry. Median dust concentrations were higher for PBDEs (e.g., 47,000 ng/g for BDE-209) than for PAHs (e.g., 220 ng/g for benzo[a]pyrene) or PCBs (e.g., 9.3 ng/g for PCB-180). BDE-209 concentrations in dust from California fire stations were among the highest of any previously documented homes or occupational settings in the world. We examined factors such as the frequency of emergency responses, the number of fire vehicles on site, and building age, but we could not account for the high levels of BDE-209 observed in fire station dust. Based on the findings of our pilot study, we hypothesize that possible sources of BDE-209 in fire stations include contaminated ash tracked back from fire events via boots, clothing, and other equipment as well as specialized equipment treated with BDE-209, including turnout gear and fire vehicles. We suggest possible follow-up studies to confirm these hypotheses.0Comments 3Citations
- [Show abstract] [Hide abstract] ABSTRACT: Nanoscale size and fiber like structure of carbon nanotubes (CNTs) may determine high reactivity and penetration, as well as the pathogenicity of asbestos and other mineral fibers. Despite many in vitro and in vivo studies, the absence of full-scale data on CNT effects on human health clearly point out the necessity for epidemiological studies. Currently, several projects are initiated worldwide on studying health risks associated with the inhalation of industrial CNTs, including NIOSH-promoted research (United States), the European CANTES study, and the Russian CNT-ERA project. Studies comprising several successive steps, such as CNT exposure assessment in occupational settings, toxicological evaluation, and epidemiological observations, are critical for determining material safety and use criteria.0Comments 3Citations
- [Show abstract] [Hide abstract] ABSTRACT: Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments.0Comments 0Citations