Implications of DNA methylation in toxicology

This chapter explores the use of DNA methylation in toxicology studies with an emphasis on the modulation of DNA methylation by environmental exposures and modifiable risk factors. Epigenetic changes are a primary mechanism explaining the developmental origin of health and disease (DOHaD) and are central to toxicology due to their modulation of gene expression. Current safety paradigms do not include testing for agents that induce delayed manifestations of changes in phenotype independent of DNA mutations. This chapter surveys environmental risk factors that impact the epigenome in early life and result in effects later in life. The historical background of detecting DNA methylation is provided. Sections are devoted to discussing the topics of nutrient interactions, the impact of caloric restriction, macro- and micronutrient deficiencies, and macronutrient compositional shifts resulting in permanent changes to DNA methylation. Finally, sections are presented on how metals, organic toxicants, behavior, and stress interact with the methylome to alter gene expression and phenotype.