Received for publication September 13, 2006.
Revised November 9, 2006.
Accepted for publication November 10, 2006.

Induction of cytochrome P450; Assessment in an immortalized human hepatocyte cell line (Fa2N4) using a novel higher throughput cocktail assay

Abstract

Over recent years the application of cocktail studies to measure biological markers, have become increasingly popular. The current study investigated a novel approach in assessing P450 enzyme induction in an immortalized cell line, using a 'cocktail' of five cytochrome P450 substrate probes compared with the traditional single probe approach. The findings reported herein support use of a cocktail approach to assess the induction of the major P450s; namely CYP3A4, 1A2, 2C9. Cytochrome P450s 2C19 and 2D6 could also be followed as part of the cocktail approach reported. Response to prototypical inducers did not differ to those observed in the presence of the specific probes alone. Consequently this approach requires significantly fewer sample numbers, if screening the induction potential of >1 cytochrome P450. Moreover, these studies highlight the utility of the immortalized cell line, Fa2N4 as a robust model system for induction studies. In conclusion, the current experimental set-up is an improvement on current approaches employed to assess cytochrome P450 induction, significantly increasing sample throughput.

Key words: CYP induction, drug interactions, hepatocytes