Identification of the cyanopregnenolone-inducible form of hepatic cytochrome P-450 as a catalyst of aldrin epoxidation

Biochem Pharmacol. 1983 May 1;32(9):1529-31. doi: 10.1016/0006-2952(83)90477-x.


In light of recent suggestions that hepatic microsomal aldrin expoxidation activity selectively reflects the phenobarbital (PB)-inducible form(s) of cytochrome P-450 (P-450PB), we tested the effect of pregnenolone-16 alpha-carbonitrile (PCN), a synthetic steroid that induces P-450PCN, a form of the cytochrome biochemically and immunochemically distinguishable from P-450PB. In hepatic microsomes prepared from rats receiving PB, 3-methylcholanthrene (3-MC), or PCN, the latter compound produced a greater increase in aldrin epoxidation activity relative to control than did PB, whereas 3-MC decreased enzyme activity. Moreover, the aldrin epoxidation activity in microsomes prepared from PCN- or PB-pretreated rats was selectively inhibited by form-specific antibodies directed against P-450PCN or P-450PB, respectively, whereas anti-P-450MC antibodies gave no inhibition with microsomes prepared from induced or control animals. We conclude that P-450PCN, P-450PB, and probably other cytochromes P-450 catalyze aldrin epoxidation, precluding use of this enzyme as a specific marker of a single form of the cytochrome.

Publication types

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

MeSH terms

  • Aldrin / metabolism*
  • Animals
  • Cytochrome P-450 Enzyme System / genetics*
  • Epoxy Compounds / metabolism
  • Female
  • Male
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • Phenobarbital / pharmacology
  • Pregnenolone Carbonitrile / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Sex Factors


  • Epoxy Compounds
  • Pregnenolone Carbonitrile
  • Methylcholanthrene
  • Cytochrome P-450 Enzyme System
  • Aldrin
  • Phenobarbital