PMID: 20650073Apr 1, 1995Paper

The activity of cytochrome P450IA1 in stable cultured rat hepatocytes

Toxicology in Vitro : an International Journal Published in Association with BIBRA
A RotemM L Yarmush

Abstract

In this study, a stable, differentiated culture format (primary hepatocytes cultured between two layers of collagen gel) was used to study the effect of the inducer 3,3',4,4'-tetrachlorobiphenyl (TCB) on the activity of cytochrome P50IA1. P450IA1 (ethoxyresorufin O-deethylase) enzymatic activity was measured using the rate of conversion of ethoxyresorufin (ER) to resorufin (R). After 14 days of induction with 10(-6), M TCB, hepatocytes in the double collagen gel configuration exhibited a maximum activity of 180.3 +/- 46.8 pmol R/mug, DNA/hr (3.6 +/- 0.9 nmol R/10(6), cells/hr) compared with 34.9 +/- 3.8 pmol R/mug DNA/hr for cells cultured on a single layer of gel. At a TCB level of 10(-5), m, the P450IA1 activity in the double-gel configuration peaked at 220.8 +/- 37.0 pmol R/mug DNA/hr. Cessation of 10(-6), M TCB induction produced a decrease in activity to 25.8 +/- 4.1 pmol R/mug DNA/hr within 4 hr. Subsequent re-application of the inducer caused an increase in activity to 76.5 +/- 11.1 pmolR/mug DNA/hr within 6 hr, reaching a maximal value of 131.0 +/- 38.6 pmol R/mug DNA/hr within 12 hr. Since TCB is rapidly metabolized by hepatocytes, a continuous perfusion culture system was developed to examine the effect of exposure to...Continue Reading

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Citations

Dec 1, 1997·Toxicology in Vitro : an International Journal Published in Association with BIBRA·S BekenV Rogiers
Aug 1, 1999·Toxicology in Vitro : an International Journal Published in Association with BIBRA·K De SmetV Rogiers
Mar 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dora Farkas, Steven R Tannenbaum
Jul 1, 1999·Alternatives to Laboratory Animals : ATLA·S CoeckeC Westmoreland

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