Toxicogenomics: "the call of the wild chip".

a new undertaking in the pursuit of human genes relevant to health risk from environmental toxicants and related stress. Such stress spans a range of dire threats in the human condition from ultraviolet to blue light, from particulate diesel exhaust to complex chemical mixtures in the air, from threats in reused airplane air to threats in herbal remedies, from threats in the food supply from pesticides to threats from genetically modified organisms. This incredible range of interest is embodied in the Environmental Genome Project, sponsored and maintained in the interest of health by the National Institute of Environmental Health Sciences (NIEHS), and about which much has already been written (1–4). The aims of the Environmental Genome Project include a characterization of important genetic polymorphisms that alter protein function to the benefit or to the determent of individuals upon exposure to environmental stress. The completion of the human genome sequencing and hopefully its successful annotation is a major spur to accelerated progress in the realm of environmental response genes. The program coordinates a robust suite of extramurally funded research grants, Environmental Health Centers and intramural research projects. An important part of toxicogenomics is the widespread use of high throughput expressed gene analysis or microarray technology (5–7). In an absolutely amazing reversal of our traditional abhor-rence of " descriptive " surveys, the scientific community has embraced this latest technology as a relatively cheap, reliable, fast, and effective way to protect populations and specific individuals from environmental risk. Why should we be interested in this approach to gene expression studies that uses high-level image processing , high-fidelity polymerase chain reaction (PCR), and clever hybridization protocols for the purpose of determining gene expression levels by comparison of different RNA populations? In a word—scale. The simultaneous examination of a hundred genes is descriptive; the simultaneous examination by comparison and clustering of tens of thousands of genes is a new way to do science. Basically oligonucleotides or small pieces of cDNA are spotted onto glass slides (or engineered into computer chips), and then RNAs to be compared are hybridized after labeling with two different fluo-rochromes: Cy3, which fluoresces red, and Cy5, which fluoresces green. The genes studied may be selected for specific purposes, such as those that are specific to environmental stress, or they may be broad based for gene discovery purposes. Fluorescence appears in the spots (or on the chip) and is detected with image …