Induction of drug metabolizing enzymes by 1,7-phenanthroline and oltipraz in mice is unrelated to Ah-responsiveness

J Biochem Mol Toxicol. 1999;13(2):77-82. doi: 10.1002/(sici)1099-0461(1999)13:2<77::aid-jbt3>;2-#.


The protective effect of several classes of compounds against the toxic and neoplastic effects of xenobiotics has been attributed to the induction of noncytochrome P450 (P450) drug metabolizing enzymes. Glutathione S-transferases (GST), NAD(P)H: quinone oxidoreductase (QOR), and UDP-glucuronosyltransferases (UGT) play a prominent role in detoxification and can be induced by oltipraz and other N-heterocyclic compounds in rats. In contrast to the induction of these enzymes by aryl hydrocarbon (Ah)-receptor agonists, induction by oltipraz and 1,7-phenanthroline is not accompanied by CYP1A induction. This study investigated the induction of drug metabolizing enzymes following administration of oltipraz and 1,7-phenanthroline in four mouse strains (C57B6A-J, Frings x C57B6J, Frings, CF-1) exhibiting varying degrees of responsiveness to an Ah-receptor agonist. The relative Ah responsiveness was determined in all strains by the induction of hepatic Cypla after three daily doses of 3-methylcholanthrene (20 mg/kg). After treatment with 1,7-phenanthroline and oltipraz (150 mg/kg i.g.) daily for 3 days, all strains showed similar induction of GST and QOR activities for each inducer. Both compounds were equally effective in elevating GST activity, but 1,7-phenanthroline was more effective than oltipraz in elevating QOR activity. In addition to GST and QOR changes, 1,7-phenanthroline significantly elevated UGT (1-naphthol) activity in the Frings strain. Neither compound produced significant changes in Cypla parameters. The independence of 1,7-phenanthroline and oltipraz induction of GST and QOR from Cypla-responsiveness is in line with the concept that N-heterocycle-containing inducers act by mechanisms other than an Ah-receptor-dependent pathway in which the P450 response has been masked or prevented.

Publication types

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

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Induction
  • Glucuronosyltransferase / biosynthesis*
  • Glutathione Transferase / biosynthesis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
  • Phenanthrolines / pharmacology*
  • Pyrazines / pharmacology*
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Species Specificity
  • Thiones
  • Thiophenes


  • Phenanthrolines
  • Pyrazines
  • Receptors, Aryl Hydrocarbon
  • Thiones
  • Thiophenes
  • 1,7-phenanthroline
  • oltipraz
  • Cytochrome P-450 Enzyme System
  • NAD(P)H Dehydrogenase (Quinone)
  • Glucuronosyltransferase
  • Glutathione Transferase