42] Use of human hepatocytes to study P450 gene induction

Abstract

The human hepatocyte model system is useful for investigations of interspecies and interindividual differences in P450-related activities, including induction of gene expression in response to xenobiotic exposure and the molecular events controlling gene expression through the transfection of reporter gene constructs. The CYP3A family is the major steroid-inducible cytochrome P450s in rats, rabbits, and humans. No single animal model faithfully predicts the responses observed in human hepatocyte preparations. Hepatocytes can be cryopreserved and reestablished into culture, and the frozen/thawed cells still respond to P450-inducing compounds with enhanced gene transcription and drug-metabolizing capacity. It is crucial to gain a complete understanding of the genetic structure, regulation, and functional activity of human cytochrome P450s because of the relative importance of cytochrome P450s in the biotransformation of a variety of exogenous and endogenous compounds.