Hypomethylation of dual specificity phosphatase 22 promoter correlates with duration of service in firefighters and is inducible by low-dose benzo[a]pyrene.
ABSTRACT 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.
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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.Toxicological Sciences 03/2013; · 4.33 Impact Factor
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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.ILAR journal / National Research Council, Institute of Laboratory Animal Resources 12/2012; 53(3-4):289-305. · 1.58 Impact Factor