Culture Systems for Hepatocytes for Use in Toxicology and Differentiation Studies

Owing to the high level of biotransformation enzymes in the liver, hepatocyte cultures are potentially valuable in vitro test systems for determining the metabolic profiles of drugs as well as for measuring the activities and substrate specificities of the various hepatic enzyme systems involved in their biotransformation. Hepatocyte cultures are also of major interest as they can be used to determine the potential toxicity of newly formed metabolites. In this chapter, our aim is to describe both in vitro assays that can readily be adopted by several laboratories and prediction models that can easily be interpreted. To understand the benefits and, more importantly, the limitations of the different hepatocyte models used in toxicology and drug metabolism, it is necessary to be acquainted with the main features of those systems currently in use. This chapter updates the discussion of different model systems of hepatocyte primary cultures and examines one of the main functions of the cells, i.e., drug metabolism, in relation to proliferation, differentiation status or apoptotic response.