Short-term maintenance of phase I and II metabolism in precision-cut liver slices in dynamic organ culture.

Testosterone and 7-ethoxycoumarin were used as substrates to quantify the maintenance of phase I and II enzymes in precision-cut rat liver slices in dynamic organ culture. Testosterone hydroxylations, 7-ethoxycoumarin O-deethylation, 7-hydroxycoumarin sulfate, and 7-hydroxycoumarin glucuronide formation were all maintained at initial levels in the slice incubation media after incubation for up to 4 hr. The activities of various cytochrome P450 isozymes, measured using the stereospecific and regiospecific hydroxylation of testosterone and the maintenance of phase I and II metabolism using 7-ethoxycoumarin, are therefore suggested to be stable over short-term incubations in a physiological buffer. The testosterone hydroxylation assay is also suggested as a versatile slice metabolic viability marker for various P450 activities over longer periods.