Monooxygenation, cytochrome P4501A1 and P4501A1-mRNA in rat liver slices exposed to beta-naphthoflavone and dexamethasone in vitro.
Precision-cut liver slices (0.5 mm) were incubated at 30 degrees C in a modified William's Medium E for up to 48 hrs. During the incubation, K+ and GSH/GSSG concentrations did not decrease. Cytochrome P450-dependent dealkylation rates of 7-ethoxycoumarin (ECOD), 7-allyloxycoumarin (ACOD) and 7-ethoxyresorufin (EROD) decreased to 1/3, 1/2 or did not change at all, respectively, after a 48 hrs incubation period. Exposure of the slices to 25 microM beta-naphthoflavone (beta NF) resulted in about 3 times higher monooxygenation rates. An exposure to a combination beta NF and dexamethasone (10(-6)M) caused a marked induction (6 times higher rates) after 48 hrs. Simultaneously an increase in P4501A1 content was observed. P4501A1-mRNA expression (measured by RT-PCR) was distinctly increased following beta NF exposure for 6 or 24 hrs. DMSO (0.2%) and dexamethasone alone modified monooxygenation rates, but did not have significant effects on P4501A1 content or, in the case of DMSO, P4501A1 gene expression (for dexamethasone not determined). Liver slices are a useful and simple tool for the detection of a beta NF-like induction within a few hours after preparation of the slices.
Müller
D
D
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany.
Glöckner
R
R
Rost
M
M
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D012333:RNA, Messenger; D019324:beta-Naphthoflavone; D003907:Dexamethasone; D019363:Cytochrome P-450 CYP1A1