Fig. 3.

Effects of 48-h Ro 48-8071 treatment on CYP3A4 and CYP2B6 expression in primary cultured human hepatocytes. A, four preparations of primary cultured human hepatocytes were treated for 48 h with standard medium alone or containing 3 or 10 μM Ro 48-8071, 0.1% DMSO, or 50 μM rifampicin (Rif). After treatment, hepatocytes were harvested for preparation of total RNA, and CYP3A4 and CYP2B6 mRNA levels were measured as described under Materials and Methods. The Ro 48-8071 data are presented as -fold changes relative to untreated controls, whereas the Rif data are presented as -fold changes relative to DMSO-treated controls. Data are presented as box and whisker plots, in which the horizontal lines within the boxes represent the median values, the tops and bottoms of the boxes represent the 25th and 75th percentile values, and the upper and lower error bars represent the maximum and minimum values. B, hepatocytes from two of the preparations described in A were harvested for preparation of microsomes, and CYP3A immunoreactive protein levels were measured by Western blot hybridization.