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TOXICOGENOMICS AND HUMAN DISEASE RISK ASSESSMENT
Citation:
Morgan, K. T., H. Ni, R. H. Brown, G. R. Benavides, L. M. Crosby, D. Sprenger, L. Yoon, M. Easton, D. Morgan, D. Laskowitz, AND R. Tyler. TOXICOGENOMICS AND HUMAN DISEASE RISK ASSESSMENT. HEALTH EFFECTS IN RISK ASSESSMENT 8(6):1339-1353, (2001).
Description:
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. But, 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 intranscript 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.