Induction of cytochrome P-450 by methylenedioxyphenyl compounds: importance of the methylene carbon

Toxicol Appl Pharmacol. 1983 Mar 30;68(1):131-9. doi: 10.1016/0041-008x(83)90362-9.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Dioxoles / pharmacology*
  • Enzyme Induction
  • Ethylmorphine-N-Demethylase / biosynthesis
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitriles / analysis
  • Oxidoreductases / biosynthesis
  • Phenobarbital / pharmacology
  • Safrole / pharmacology*
  • Structure-Activity Relationship


  • Dioxoles
  • Nitriles
  • 2,2-dimethyl-5-tert-butyl-1,3-benzodioxole
  • ethyl isocyanide
  • 5-tert-butyl-1,3-benzodioxole
  • 2-methyl-5-tert-butyl-1,3-benzodioxole
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1A1
  • biphenyl-2-hydroxylase
  • Ethylmorphine-N-Demethylase
  • Safrole
  • isosafrole
  • Phenobarbital