Toxicogenomics: overview and potential applications for the study of non-covalent DNA interacting chemicals

Non-covalent DNA interacting agents, DNA-groove binding chemicals and DNA intercalators, are generally considered less cytotoxic than agents producing covalent DNA adducts and other DNA damage. Although the impact of non-covalent compound-DNA interactions on convoluted molecular and biochemical pathways is not well characterized, the most prominent effects include DNA conformational and related structural perturbations, interference with normal DNA protein interactions, such as topoisomerases, as well as effects on mitochondrial DNA and function. The cellular responses to such perturbations would be expected to include changes in transcription of a variety of genes. The emerging field of toxicogenomics seeks to exploit gene responses to define expression profiling signatures for various types of drugs and toxicants, and to provide mechanistic insight into their cellular effects. There are a variety of examples whereby different classes of genotoxicants and non-genotoxic agents can be distinguished by gene expression profiling using functional genomics approaches, which survey global transcriptional responses. In this review, we will discuss the promises and precautions in the use of functional genomics approaches to characterize stress agents including non-covalent DNA interacting agents.