1654a Epigenetic alterations as an underlying mechanism of the toxicity of metals

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Abstract

Introduction

Toxic metals are present at many workplaces as well as in food and drinking water, causing life-long daily exposure. In the last decade, epigenetic alterations have gained attention as underlying mechanisms of the adverse health effects observed in relation to exposure to metals. Epigenetic marks, broadly defined as dynamic changes to the genome other than changes in the DNA sequence itself, can lead to persistent changes in the regulation of gene expression. Epigenetic mechanisms have key functions in regulating cellular homeostasis, and lineage-specific gene expression, and perturbations may have long-lasting influence on future health, including risk of cancer.

Methods

Epigenetic changes in candidate genes and in the epigenome (pyrosequencing, MS-HRM, target-enrichment next-generation sequencing, RNA sequencing, histone modifications, and microRNA) have been measured in different tissues in relation to exposure to toxic metals (arsenic, cadmium, lead, welding particles) in samples collected from humans occupationally and/or environmentally exposed to metals.

Result

We have shown that exposure to particularly arsenic, but also cadmium and metal-containing particles, are significantly associated with changes of epigenetic marks, and some of these marks are linked to carcinogenesis, cardiovascular and immune function. The epigenetic changes seem to persist over several years and for arsenic and cadmium sex differences were found.

Discussion

Research during the last decade have shown that metals common at workplaces and in the general environment are associated with epigenetic alterations that in turn may have long-lasting effects on the gene regulation and risk of disease. Experimental and animal studies support that epigenetic perturbations are underlying mechanism for metal toxicity. Similar to what has been shown for smoking-related epigenetic marks, metal-related epigenetic marks may be promising exposure and effect biomarkers.

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