SHORT-TERM MAINTENANCE OF PHASE-I AND PHASE-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 s lices in dynamic organ culture. Testosterone hydroxylations, 7-ethoxyc oumarin O-deethylation, 7-hydroxycoumarin sulfate, and 7-hydroxycoumar in 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 stereospecifi c and regiospecific hydroxylation of testosterone and the maintenance of phase I and II metabolism using 7-ethoxycoumarin, are therefore sug gested to be stable over short-term incubations in a physiological buf fer. The testosterone hydroxylation assay is also suggested as a versa tile slice metabolic viability marker for various P450 activities over longer periods.