Prof Johannes Doehmer
Use and Value of in vitro Technologies in Metabolism
Metabolism determines pharmacological efficacy and toxicity of drugs and other chemicals. It is therefore of fundamental importance to evaluate metabolic details in pre-clinical studies, e.g. identification of the enzymes involved, drug stability, and metabolite profile. Traditionally, whole animals, and their organs and/or tissues have been applied for metabolism studies. However, the enzymes of concern, particularly cytochromes P450, are species specific in their structure and function. Therefore, metabolism data obtained from animal studies are of low predictive value for humans. Cloning cytochromes P450 and expressing them in cultivated cells provides an experimental opportunity to study human enzymes directly, yielding data with high predictive value.
In this instance, V79 Chinese hamster cells were genetically engineered for expression of cytochromes P450 from different species including human. As V79 cells have no cytochrome P450 background activity, the recombinant cell lines are defined for the cDNA encoded cytochrome P450. These cell lines can be applied in a specific way which allows for enzyme identification, metabolite profiling for a given drug, and checking on metabolite depending toxicity. Examples are shown for drugs and chemicals.