Hep G2 cell line as a human model for sulphate conjugation of drugs

Abstract

1. The objective of this study was to examine the usefulness of the hepatoma cell line Hep G2 as a model for human sulphoconjugation of drugs, in particular stereoselective conjugation.

2. Using the substrates p-nitrophenol and dopamine, we found sulphation activities consistent with the presence of both the phenol (P) and the monoamine (M) form of the human phenolsulphotransferases in these cells.

3. The K_mapp was 3.0γM for the sulphation of p-nitrophenol. This activity was inhibited selectively by 2,6-dichloro-4-nitrophenol, IC₅₀ 6γM. The K_mapp was 39 γM for the sulphation of dopamine. This activity was selectively inhibited by elevated temperature.

4. The chiral adrenergic drugs (±)-terbutaline and (±)-4-hydroxypropranolol were both sulphated stereoselectively with K_mapp and F_maxapp values for each enantiomer virtually identical to previous observations with human liver cytosol.

5. In a direct comparison, the estimated activity of the P form of phenolsulphotrans-ferase in the Hep G2 cell line was 30% of that in human liver, whereas, surprisingly, the activity of the M form of phenolsulphotransferase was 4.5 times higher in the Hep G2 cells than in the liver.