Table 1

Comparison of magnitude of rat P-450 enzyme induction in vivo with that observed in vitro in cultured hepatocytes prepared from freshly isolated or cryopreserved cells

P-450 Enzyme1-aIn Vivo Induction1-b in Male RatsIn Vitro InductionComparison of In Vivo with In Vitro
Freshly Isolated Hepatocytes1-cCryopreserved Hepatocytes1-cIn Vivo/Freshly IsolatedIn Vivo/ Cryopreserved
Enzyme activity (pmol/min/mg protein) Ratio of enzyme activity
 Control 233   43.3
 β-Naphthoflavone3,940 (17)1-d 1140 (26) 994 (19) 3.54.0
 Control 17.6 15.7
 Phenobarbital1,490 (85) 405 (26) 567 (100) 3.72.6
 Control 2,480 683 4503.65.5
 Dexamethasone12,200 (4.9) 4,300 (6.3) 3,930 (8.7) 2.83.2
 Control 475 166 1872.92.5
 Clofibric acid11,100 (23) 2370 (14) 3,750 (20) 4.73.0
  • 1-a Enzyme activity of CYP1A, CYP2B, CYP3A, and CYP4A enzymes was determined as EROD, PROD, testosterone 6β-hydroxylation, and lauric acid 12-hydroxylation respectively, as described inMaterials and Methods.

  • 1-b Liver microsomes from male Sprague-Dawley rats treated with P-450 enzyme inducers. Rats were dosed once per day for 4 days with isotonic saline, β-naphthoflavone, phenobarbital, dexamethasone, or clofibric acid at a dosage of 5 ml/kg, 100 mg/kg, 80 mg/kg, 50 mg/kg, and 200 mg/kg, respectively. Microsomes were provided by XenoTech, LLC, which also provided data on activity of P-450 enzymes. Data shown are averages of duplicate determinations from three to five experiments.

  • 1-c Liver microsomes from cultured rat hepatocytes (prepared from either freshly isolated or cryopreserved cells) were treated with P-450 enzyme inducers and activity of P-450 enzymes was determined as described in Materials and Methods. Data shown are averages of duplicate determination from a single experiment (Fig. 2A, 4A, 5A, and 6A). Data for induced samples are maximum rates extrapolated from the EC50 curves.

  • 1-d Values in parentheses show fold induction compared with controls.