Differential induction of ethoxyresorufin-O-deethylase in tissues of the rat placenta.
The placenta of the rat during late gestation is comprised of the yolk sac membranes, labyrinth and basal zone, which are of fetal origin, and the decidua basalis, which is derived maternally. Studies investigated whether the placental monooxygenase activity induced by administration of beta-naphthoflavone (beta-NF) and 3-methylcholanthrene (3-MC) to pregnant rats was localized differentially in these separate portions of the organ. Ethoxyresorufin-O-deethylation (EROD) was measured by fluorometric assay in homogenates of the respective placental tissues and of intact fetuses. EROD was very low or undetectable in feto-placental homogenates from untreated control animals. The administration of beta-NF and 3-MC increased EROD activity 50-fold over control in labyrinth and fetal homogenates, 10- to 15-fold in decidua, 8- to 20-fold in fetal membranes and 8-fold in basal zone preparations. The apparent Km value for ethoxyresorufin was significantly lower than control for EROD in labyrinth preparations from both beta-NF- and 3-MC-treated animals. Enzyme activity in labyrinth homogenates was maximally induced by 3-MC treatment for 1 to 3 days. In contrast, EROD activity was maximal after 1 to 2 days beta-NF administration, but declined markedly with longer duration of treatments. Subsequent studies compared the in vitro effects of alpha-naphthoflavone (alpha-NF) and beta-NF on induced EROD in feto-placental homogenates. The two benzoflavones were found to be equipotent as inhibitors with IC50 values less than 1 microM for labyrinth, maternal liver and fetal preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1; D007758:Ear, Inner / Q000201:enzymology; D004790:Enzyme Induction; D005260:Female; D007700:Kinetics; D008748:Methylcholanthrene / Q000494:pharmacology; D010088:Oxidoreductases / Q000096:biosynthesis*; D010920:Placenta / Q000166:cytology / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1