ASSESSMENT OF RAT-LIVER SLICES AS A SUITABLE MODEL SYSTEM FOR STUDYING THE SIMULTANEOUS SULFATION AND GLUCURONIDATION OF PHENOLIC XENOBIOTICS

1. In most mammals, the xenobiotic 1-naphthol undergoes conjugation to produce predominantly the sulphate and glucuronide metabolites. 2. Us ing 1-naphthol, we established and validated rat liver slices as a mod el system to assess simultaneously the relative contributions of sulph ation and glucuronidation to the metabolism of simple phenolic xenobio tics. 3. Determination of kinetic parameters for 1-naphthol sulphation showed identical affinity (K-m similar to 5 mu M) in rat liver slices and in rat liver cytosol. 4. In liver slices, at low substrate concen trations (10 mu M 1-naphthol), sulphation was the predominant pathway but was readily saturated, whereas at high concentrations of 1-naphtho l (100 mu M) glucuronidation predominated. 5. In subcellular fractions , the K-m for sulphation of 1-naphthol (5 mu M) by liver cytosol was s ubstantially lower than the K-m for glucuronidation of 1-naphthol (48 mu M) in liver microsomes, indicating saturation of sulphation by acce ptor substrate was principally responsible for the shift towards glucu ronidation at higher concentrations of 1-naphthol.