Genetics, epigenetics and genomic technologies: Importance and application to the study of endocrine-disrupting chemicals
Ferguson LR., Philpott M.
Early observations on endocrine-disrupting chemicals (EDCs) associated these with significant changes in the nature and diversity of animal populations, through environmental exposures. In human populations, dietary exposures to EDCs may be even more important. Most EDCs are classified as non-genotoxic and appear to interact with hormone receptors to disrupt normal differentiation of sex organs, leading to sexual dimorphism and under-masculinisation. Both animal and human populations show variations in susceptibility to endocrine disruption, which have been related to the frequencies of specific variant single nucleotide polymorphisms (SNPs) and trinucleotide repeats. Microarray technologies, especially using animal models, permit measurement of multiple effects of EDCs on the expression of genes in a tissue- and time-specific manner. Hierarchical gene network analyses reveal impacts on interlinking networks of genes, increasing the activity of some and decreasing that of others. Such approaches will continue to be important to understand the mechanism of new and novel EDCs, but are not appropriate to mass screening. Knowledge of the genes whose expression is impacted has been used to develop reporter gene assays to permit high numbers of chemicals to be interrogated for EDC capability. While such changes in gene expression may sometimes reflect classic mutational changes, there is increasing evidence to suggest that the major mechanism is epigenetic, via DNA methylation changes. The association with transgenerational effects suggests that new strategies of study, such as ChIP-chip arrays that combine chromatin immunoprecipitation with microarrays, may become an important approach to future understanding of the importance and mechanistic basis of this important group of chemicals. © 2009 Woodhead Publishing Limited All rights reserved.