TRANSGENIC YEAST EXPRESSING HUMAN CYTOCHROME P450S CAN SERVE AS A TOOL IN STUDIES OF THE MECHANISMS OF THEIR INDUCTION BY VARIOUS EFFECTORS

Transgenic Saccharomyces cerevisiae yeast strains were constructed whi ch express CYP2D6 and CYP3A4 genes under control of an artificial prom oter. When added to the growth medium, sparteine, a substrate for CYP2 D6, was shown to increase the content of this cytochrome P450 isoform in yeast cells. No such increase was observed when a proteinase-defici ent yeast mutant was used as a parent strain. Nifedipine, a substrate for CYP3A4, failed to affect the level of CYP3A4 expression even in wi ld yeast cells. These results suggest that expression of CYP2D6 in hum an liver can at least partially be controlled post-transcriptionally b y its inductors while for CYP3A4 such a mechanism is hardly possible. (C) 1996 Academic Press, Inc.