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Alternatives to Laboratory Animals - ATLA

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Effects of Inducers of Drug Metabolism on Cytosolic Glutathione S-transferase Activity in Rat Hepatoma-derived Fa32 Cells

Paul J. Dierickx

Established Fa32 cells, derived from a rat hepatoma, were investigated for their glutathione S-transferase (GST) induction capacity, which is an important characteristic of the detoxification capacity in normal liver. The cells were exposed to inducers of drug metabolism for 3 days in complete medium (containing 10% fetal calf serum). Neither dimethyl sulphoxide nor dimethyl formamide could be used as a vehicle to transport the inducers into the cells, because they also interacted with GST. Phenobarbital, butylated hydroxyanisole, allyl isothiocyanate and dimethyl fumarate (but not fumaric acid) all effectively increased the total specific GST activity. None of the test chemicals produced a very pronounced induction of specific GST subunits, but subunit 2 and subunit 8 were increased more than the others. The effects of inducers of drug metabolism on the GST activity in Fa32 cells are comparable with those in rat liver. These cells can therefore be used as a valuable alternative model for GST-dependent metabolic interactions in rat liver.