Investigation of epigenetically active substances in consumer products on embryonic stem cells
2010
Sittka,A. | Smirnova,L. | Schäfer | B. | Seiler,A. | Luch,A.
Alemán. Throughout lifespan humans are exposed to a variety of chemicals and other substances through diet, breathable air, and skin contact. Even though very often only present in traces the chronic exposure to certain compounds at a sustained basis may have yetunderestimated effects on human health. It now becomes more widely established that adverse effects on human health upon exposure to xenobiotics are not only mediated through mutagenesis or clastogenic damage to DNA, but also, more subtle, at the level of epigenetic changes.Since the German Federal Institute for Risk Assessment is committed to scientifically substantiate consumer health protection and food safety at the highest level possible, we recently started to look into the epigenetic effects of certain model compounds such as nickel, which might be released in low amounts from consumer products. Since epigenetic effects exerted by xenobiotics are mostly subtle we want to take advantage of the naïve and highly susceptible epigenetic state of murine embryonic stem cells (mESCs) to test epigenetically active substances present in and migrating from consumer products. The approach includes not only undifferentiated embryonic stem cells, but also a protocol established in house driving embryonic stem cells into neural differentiation. The substances we mainly focus on include nickel sulfate (NiSO4), sodium arsenite (NaAsO2), and curcumin. As polyphenol the latter compound serves as yellow color of the Indian spice tumeric and is being widely used as food additive (E100). All these substances have been shown in vitro and/or in vivo to exert epigenetic effects and to affect neural development. Chemical treatment of mESCs prior to and over the course of neural differentiation will enable simultaneous effect monitoring based on the evaluation of differentiation, and the specific analysis and characterization of affected methylation patterns and histone modifications in undifferentiated mESCs vs neural differentiated cells upon exposure
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