Chapter 8: Human Embryonic Stem Cells as Biological Models to Examine the Impact of Xenobiotics on the Genome and Epigenome Check Access

A number of human diseases are caused by environmental factors that can promote diseases by affecting changes in the genome or by affecting the epigenome, the regulatory network that controls the expression of genes. The primary focus of in vitro test systems used in safety assessment has been on direct cellular and molecular targets, apical measures of cellular health status, and DNA damage and toxicogenomic responses with limited direct measures of epigenomic impacts. Human embryonic stem cell-based biological assays can be used to assess traditional measures of cellular health status and determine the impact of toxicants on the genome and epigenome that regulates stem cell biology. Dysfunction from xenobiotic exposures of the highly regulated epigenetic programs that maintain stemness (self-renewal and pluripotency) and differentiation can produce aberrantly programmed descendent daughter cells leading to spontaneous abortions, birth defects, neurological disorders and other effects later in life as organisms respond to environmental and biochemical stimuli. Human embryonic stem cells offer a unique platform for developing bioassays aimed at assessing the impact of xenobiotics on the genome and epigenome that can be developed into short-term cell-based screening assays to predict reproductive and developmental toxicity.