The effects of pretreatment with 7,8-benzoflavone on drug-metabolizing enzymes and diethylstilboestrol metabolism in male hamster liver microsomal preparations.
1. Pretreatment of male Syrian golden hamsters with 7,8-benzoflavone (7,8-BF, 0.4% in the diet) for 4 and 20 weeks resulted in a significant increase in the amount of cytochrome P-450 and cytochrome b5 in hepatic microsomes. The activities of microsomal 7-ethoxycoumarin-O-deethylase (ECOD) and 7-ethoxyresorufin-O-deethylase (EROD) increased by a factor of 2 and 5, respectively, whereas aryl hydrocarbon hydroxylase (AHH) activity was only marginally enhanced. 2. Because the relative increase in cytochrome b5 exceeded that of cytochrome P-450, the ratio of P-450 to b5 decreased from 2.2 in controls to 1.6 in 7,8-BF-treated animals. 3. Hepatic microsomes from untreated and 7,8-BF-pretreated hamsters metabolize E-diethylstilboestrol (E-DES) to its stereoisomer Z-DES and to several oxidative metabolites, of which 3-hydroxy-DES and Z,Z-dienestrol were unambiguously identified by g.l.c.-mass spectrometry. 4. Pretreatment with 7,8-BF led to a marked decrease in the formation of all oxidative DES metabolites but not in the isomerization to Z-DES. The possible implication of these data for the mechanism of liver tumour formation by the combined treatment of hamsters with 7,8-BF and DES is discussed.
Blaich
G
G
Institute of Pharmacology and Toxicology, University of Würzburg, FR Germany.
Metzler
M
M
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004054:Diethylstilbestrol / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism
D001571:Benzoflavones; D003573:Cytochrome b Group; D005419:Flavonoids; C011512:alpha-naphthoflavone; D004054:Diethylstilbestrol; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1