Composition of cytochrome P‐450 isozymes from hepatic microsomes of C57BL/6 and DBA/2 mice assessed by warfarin metabolism, immunoinhibition, and immunoelectrophoresis with anti‐(rat cytochrome P‐450)

Abstract

The composition of isozymes of hepatic microsomal cytochrome P‐450 (P‐450) from C57BL/6(B6) and DBA/2(D2) inbred strains of mice, uninduced and treated with phenobarbital (PB), pregnenolone‐16α‐carbonitrile (PCN), and β‐naphthoflavone (BNF), were assessed. The assessment was based on comparisons of the regioselectivity and stereoselectivity of warfarin metabolism, inhibition of metabolism by antibodies raised against highly purified rat P‐450 isozymes (the specificity of these antibodies in inhibiting rat microsomal metabolism of warfarin was also determined), and by immunoelectrophoresis using the anti‐(rat P‐450). Isozymes were considered to be the same or very similar if they exhibited the same substrate specificity, antigenicity. and molecular weight. Untreated D2 and B6 mice had similar‐compositions of P‐450 isozymes which were independent of the Ah receptor. Both strains contained an isozyme very similar to rat P‐450UT‐A. PB or PCN induction of the two mouse strains proceeded independently of the Ah receptor and yielded isozymes which are the same as or very similar to the rat P‐450UT‐A, P‐450PB‐B, P‐450PB‐C, and P‐450PB/PCN‐E isozymes. D2 and B6 mice had similar isozyme compositions when treated with PB or PCN, but isozyme compositions varied in differently induced mice. BNF treatment of the D2 mice was without effect, but the B6 mice produced an isozyme(s) which was different from rat P‐450BNF‐B, the major BNF‐induced isozyme in rat liver. Copyright © 1984, Wiley Blackwell. All rights reserved