The Promise of Genomics and Proteomics in Immunotoxicology and Immunopharmacology (2006)

Genomics in Immunotoxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Introduction to Genomics and Single Nucleotide Polymorphisms (SNPs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Single Nucleotide Polymorphisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81An Overview of Results Relevant to Immunotoxicology . . . . . . . . . . . . . . . . 82 Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 Single Nucleotide Polymorphisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84Future Directions and Potential Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Single Nucleotide Polymorphisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86Proteomics in Immunotoxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 Introduction to Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 An Overview of Results Relevant to Immunotoxicology and Immunopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Future Directions and Potential Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91GenomicsThere are a number of examples in which histopathology and the functional immunotoxicity tests recommended by regulatory guidance documents would not detect knownimmunotoxicants.1-3 Furthermore, we are no better able today than we were 20 years ago to quantitatively estimate the effect that a particular amount of suppression of immune parameters will have on resistance to infections or cancer.1,2 In addition, very few mechanisms of immunotoxicity have been fully characterized. The incorporation of genomics and proteomics in immunotoxicology studies has the potential to impact all of these issues. Genomics and proteomics have stimulated the development of systems biology, and this fi eld is remarkably consistent with the goals of immunotoxicology, “Systems biology studies biological systems by systematically perturbing them (biologically, genetically, or chemically); monitoring the gene, protein, and informational pathway responses; integrating these data; and ultimately, formulating mathematical models that describe the structure of the system and its response to individual perturbations.”4 Progress toward analogous goals in other areas of toxicology5-9 suggests that these goals are feasible and that the results will be useful. Thus, in spite of valid concerns about diffi culties in determining the functional signifi cance of complex changes in gene expression, it seems that there are reasons to proceed with the use of microarray technology in immunotoxicology.