The next innovation cycle in toxicogenomics: Environmental epigenetics

Abstract

Toxicogenomics is a field that emerged from the combination of conventional toxicology with functional genomics. In recent years, this field contributed immensely in defining adverse biological effects resulting from environmental stressors, toxins, drugs and chemicals. Through microarray technology, large-scale detection and quantification of mRNA transcripts and of microRNAs, related to alterations in mRNA stability or gene regulation became feasible. Other 'omics' technologies, notably proteomics and metabonomics soon joined in providing further fine tuning in the gathering and interpretation of toxicological data. A field that will inevitably modify the landscape for toxicogenomics is 'epigenetics', a term which refers to heritable changes in gene expression without accompanying alterations in the DNA sequence. These epigenetic changes are brought about by mechanisms such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression patterns. Epigenetic mechanisms are essential in normal development and differentiation, but these can be misdirected leading to diseases, notably cancer. Indeed, there is now a mounting body of evidence that environmental exposures particularly in early development can induce epigenetic changes, which may be transmitted in subsequent generations or serve as basis of diseases developed later in life. In either way, epigenetic mechanisms will help interpret toxicological data or toxicogenomic approaches to identify epigenetic effects of environmental exposures. Thus, a full understanding of environmental interactions with the genome requires keeping abreast of epigenetic mechanisms, as well as conducting routine analysis of epigenetic modifications as part of the mechanism of actions of environmental exposure. A number of approaches are currently available to study epigenetic modifications in a gene-specific or genome-wide manner. Here we describe our approaches in studying the epigenetic modification of the tumor-suppressor gene Tslc1 (Igsf4a) in lung tumors obtained from transgenic mouse models.