Biological Exposure Of Environmental Noise And Particulate Matter And Their Effects On DNA Methylation

Environment pollution including air pollution and noise pollution has been supposed as the most important problem in developing countries. Environmental noise, an important environmental stressor, is now recognized to cause important adverse health problems both in humans and other animals, such as cognitive deficits, sleep disturbances, and physical changes. A variety of epidemiological studies demonstrated that environmental noise might induce brain dysfunction, cardiovascular diseases, and hypertension. There is compelling evidence that particulate matter increases lung cancer risk by triggering systemic inflammation, and induces the release of reactive oxygen species, both locally and systemically.Epigenetics, including DNA methylation, histone modification and none coding RNA, refers to changes that alter gene transcription in the absence of direct alterations to the genome itself. DNA methylation, the best studied of the epigenetic processes, has been suggested to be one of the possible mechanisms to mediate the stress response of individuals. As a reversible mechanism of epigenetic regulation, many studies suggested that DNA methylation plays a key role in a wide variety of fundamental biological processes by affecting gene expression at the transcriptional level. Both in vitro and in vivo studies suggest that aberrant DNA methylation may lead to abnormal cell cycle arrest, uncontrolled cell proliferation, and apoptosis, all of which are known risk factors for carcinogenesis, aggressive tumor neovascularization, angiogenesis, and metastasis.The main objective of the first study was to investigate the association between EN exposure and DNA methylation changes in the regions of the brain, using rats as a model. We exposed Wistar rats to moderate intensity traffic noise (70-75dB,20Hz-4000Hz)12h per day (7:00pm-7:00am) for either3days or3weeks. Then methylation patterns of six stress-and memory-related fragments (Bdnf, Comt, Crhr1, Mc2r, Snca-f and Snca-sp) and two repetitive elements from LINE-1family(Ll-5utr and Ll-orf) by PCR-pyrosequencing in four regions of brain (frontal lobe, hippocampus, inferior colliculus, and medulla oblongata) were measured. Short-term exposure to EN caused aberrant methylation levels in Comt (medulla oblongata) and Snca-sp (frontal lobe, medulla oblongata). Hypermethylation in Comt (inferior colliculus), L1-5utr (medulla oblongata) and hypomethylation in Mc2r (hippocampus) were found after long-term EN exposure. We include that the acute exposure to nocturnal noise stress could induce some acute responses in the brain with transient and reversible effects. Chronic nocturnal noise might result in memory deficits, cognitive impairments, depression, and hypertension.In the second study, we investigated the association between short-term PM exposure (personal PM2.5and ambient PM10) and methylation of three tandem repeats in peripheral blood leukocytes. We measured methylation of three tandem repeats (SATα, NBL2, D4Z4) by polymerase chain reaction-pyrosequencing on blood samples from truck drivers and office workers (60per group) in Beijing, China. We used lightweight monitors to measure personal PM2.5(PM with aerodynamic diameter≤2.5μm) and elemental carbon (EC, a tracer of PM from vehicular traffic). Ambient PM10data were obtained from air quality measuring stations. Overall, an interquartile increase in personal PM2.5and ambient PM10levels was associated with a significant covariate-adjusted decrease in SATα methylation (-1.35%5-methyl cytosine [5mC], P=0.01; and-1.33%5mC; P=0.01, respectively). Effects from personal PM2.5and ambient PM10on SATa methylation were stronger in truck drivers (-2.34%5mC, P=0.02;-1.44%5mC, P=0.06) than office workers (-0.95%5mC, P=0.26;-1.25%5mC, P=0.12, respectively). Ambient PM10was negatively correlated with NBL2methylation in truck drivers (-1.38%5mC, P=0.03) but not in office workers (1.04%5mC, P=0.13). Our result suggests that PM exposure is associated with hypomethylation of selected tandem repeats. Measuring tandem-repeat hypomethylation in easy-to-obtain blood specimens might identify individuals with biological effects and potential cancer risk from PM exposure.However, to date, only a limited number of epidemiological studies is available that have studied the impact of exposure combined with EN and PM to human health. Together with previous studies, our results refers the combined effects may be aggravate the methylation changes which may also increase the potential cardiovascular diseases risk.