Frontiers in Toxicogenomics – The Grand Challenge: To Understand How the Genome and Epigenome Interact with the Toxic Environment

Frontiers in toxicogenomics – the grand challenge: to understand how the genome and epigenome interact with the toxic environment A recent advance that has revitalized toxicology studies in the past couple of decades is Frontiers in Genetics " toxicogenomics, " the study of the effects of environmental toxins on global changes within a cell or tissue as related to genomic variables. " Transcriptional toxicogenomics " is the study of global gene expression patterns after administering a toxin. Similarly, " toxicoproteomics " is the study of global changes in protein levels or post-trans-lational modifications; while " toxicome-tabolomics " is the study of global changes in metabolite levels after administering a toxin. A new field called " toxicoepigenom-ics " or more simply, the " epigenetics of toxicology, " is the study of global epigenetic changes in a cell that are caused by exposure of a cell, tissue, or organism to a toxin or drug. Frontiers in Toxicogenomics provides a format for presenting cutting-edge reviews and studies in the frontiers of all branches of toxicogenomics. One type of study within the area of transcriptional toxicogenomics called " genetical genomics " or " genetics of gene expression, " is the combination of quantitative trait-locus (QTL) and whole-genome expression analyses (Brem et al., 2002; Broman, 2005). In genetical genom-ics, the investigator treats the expression of each of the ∼20,000 genes in an organism as a quantitative trait and identifies cis-expression QTL (eQTL) in cis-regulatory sequences and trans-eQTL in transacting factors that regulate expression of co-regulated genes in specific pathways. Genetical toxicogenomics adds a new dimension to genetical genomics by studying the effects of an environmental toxin on global gene expression patterns (Ruden et al., 2009). Such studies are theoretically very powerful because they not only tell which genes are induced in a particular tissue (such as a brain region) by the toxin, but they also allow the identification of transacting factors and cis-acting sequences that are regulated by the toxin. Toxicogenetical genomic studies in mice have the advantage that thousands of recombinant inbred lines have recently been generated in a collaborative cross amongst eight different wild type strains of mice (Churchill et al., 2004). Rats are sometimes preferred models for toxicological screens because they have much larger organs than mice, allowing for easier gene and protein expression analyses because much more material can be obtained compared with mice. Recombinant inbred lines have also been developed …