Parallelogram Approach Using Rat-Human In Vitro and Rat In Vivo Toxicogenomics Predicts Acetaminophen-induced Hepatotoxicity in Humans

The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges ex-trapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicoge-nomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct comparison of toxicant-induced gene expression profiles and infers mechanisms between several systems. In the present study, acetaminophen (APAP) was used as a model compound to compare gene ex-pression responses between rat and human using in vitro cellular models, hepatocytes, and between rat in vitro and in vivo. Comparison at the level of modulated biochemical pathways and biological processes rather than at that of individual genes appears preferable as it increases the overlap between various systems. Pathway analysis by T-profiler revealed similar bio