1713c Epigenetics in solvent induced neurobehavioral disorders


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Abstract

IntroductionIn order to prevent neurodegenerative diseases such as chronic solvent encephalopathy (CSE), it is important to elucidate the underlying mechanism. Cells are able to respond to occupational stressors by turning on or off specific genes mediated through epigenetic alterations. Consequently, epigenetic mechanisms can play an important role in mediating the effects of solvent exposure on the development of neurobehavioral disorders.MethodsWe have set-up several studies in a translational design using cell lines, mice and humans exposed to solvents and CSE patients. DNA methylation was measured with liquid chromatography coupled with tandem mass spectrometry for the assessment of 2’-deoxycytidine, 5-methyl-2’-deoxycytidine, 5-hydroxymethyl-2´-deoxycytidine, 5-formyl-2´-deoxycytidine, 5-carboxy-2´-deoxycytidine and pyrosequencing.ResultsGlobal DNA methylation and hydroxymethylation was mostly negatively associated with solvent exposure in both in vitro as in vivo studies. DNMT1 CpG1 gene-specific methylation levels were significantly higher in CSE patients as compared to controls, associations that persisted after adjustment for age, gender, alcohol abuse, smoking, level of education and the use of psychotropic medication (p=0.004 and p=0.017, respectively). In addition, in the group of CSE patients there was a positive correlation between the duration of solvent exposure and the percentage of BDNF CpG1 methylation (rs=0.374, p=0.017), which was maintained after adjustment for age and smoking (p<0.001).ConclusionThe study of epigenetic alterations gives us the possibility to study the immediate consequences of exposure and make projections for disease development. These epigenetic marks can be used to develop a set of biomarkers and used in the follow-up of humans.

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