Toxicogenomics and human disease risk assessment

Complete sequencing of human and other genomes, availability of large-scale gene expression arrays with ever-increasing numbers of genes displayed, and steady improvements in protein expression technology can have a great impact on the field of toxicology. However, we are a long way from devising effective standards for human risk assessments based upon these technologies. Current impediments to effective application of these technologies include appropriate normalization procedures (as "there is no fixed point in transcript space"), confirmation of data quality and demonstration of the functional significance of responses observed. Providing risk assessors with statistically and functionally unconfirmed, large-scale gene expression data sets that generally defy interpretation is not an appropriate approach. We propose that a logical process of data generation be developed, with risk assessment in mind from the outset. The basic principles of toxicology should be applied to selection of experimental systems, dose and duration of exposure, along with appropriate statistical analyses and biological interpretation. If mechanistically based interspecies extrapolation of risk is to be undertaken, suitable biochemical or other follow-up studies should be completed to confirm functional significance of transcriptional changes. © 2002 by ASP.

Duke Scholars

Author Daniel Todd Laskowitz Neurology, Neurocritical Care