Proteomics in mechanistic toxicology: history, concepts, achievements, caveats, and potential.

Toxicoproteomics can be defined as the application of proteomic approaches to the understanding of toxicology problems, and this review deals with the various types of applications that have been described in the literature. Toxicoproteomics has been applied to very different classes of toxicants, from drugs and natural products to metals, or from industrial chemicals to nanoparticles and nanofibers. It has also been applied to address questions at different levels, from the search of the primary molecular targets of toxicants to the deciphering of the molecular responses of cells and tissues to toxicants. Although restricted to mammalian cells and tissues, this paper reviews these two levels of investigation and the different application areas of toxicoproteomics, leading to the discussion of the advantages and drawbacks of the most popular proteomic platforms. Some of the pending questions in toxicoproteomics are also critically addressed, such as the specificity, validation, and result hierarchization issues. The question of shared mechanisms, which are encountered in many toxicoproteomic papers dealing with different toxicants, is also discussed. Finally, the future of toxicoproteomics is briefly outlined.