Induction of cytochrome P-450 by methylenedioxyphenyl compounds: importance of the methylene carbon.
Induction of hepatic microsomal cytochrome P-450 in Dub:ICR male mice treated with phenobarbital, 3-methylcholanthrene, safrole, isosafrole, 5-tert.-butyl-1,3-benzodioxole (BBD), 2-methyl-5-tert.-butyl-1,3-benzodioxole (MBBD), and 2,2-dimethyl-5-tert.-butyl-1,3-benzodiozole (DBBD) was evaluated by measuring the cytochrome P-450 content, Type II:Type 1 binding ratio, ethylisocyanide pH equilibrium point, biphenyl 2- and 4-hydroxylase, ethylmorphine N-demethylase, ethoxyresorufin O-deethylase, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Safrole and isosafrole treatment of mice produced a phenobarbital-type induction. BBD, but not MBBD and DBBD, induced cytochrome P-450 and formed a Type III metabolite-cytochrome P-450 complex, in vitro and in vivo. SDS-PAGE revealed that DBBD does induce proteins other than cytochrome P-450. These data suggest that the methylene carbon plays an important role in cytochrome P-450 induction.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004149:Dioxoles / Q000494:pharmacology*; D004790:Enzyme Induction; D005037:Ethylmorphine-N-Demethylase / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009570:Nitriles / Q000032:analysis; D010088:Oxidoreductases / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D012451:Safrole / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004149:Dioxoles; D009570:Nitriles; C037778:2,2-dimethyl-5-tert-butyl-1,3-benzodioxole; C001187:ethyl isocyanide; C037776:5-tert-butyl-1,3-benzodioxole; C037777:2-methyl-5-tert-butyl-1,3-benzodioxole; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C021775:biphenyl-2-hydroxylase; D005037:Ethylmorphine-N-Demethylase; D012451:Safrole; C015959:isosafrole; D010634:Phenobarbital