Selective induction of rat liver microsomal cytochrome P-448 by 3,4,5,3',4'-pentachlorobiphenyl and its effect on liver microsomal drug metabolism.

Abstract

Pretreatment of rats with 3,4,5,3'',4''-pentachlorobiphenyl (PenCB) at a single i.p. dose of 10 mg/kg caused a marked increase of cytochrome P-448(P448) in liver microsomes. The liver microsomes of PenCB-treated rats(PenCB-microsomes) showed similar but somewhat different properties from those of 3-methylcholanthrene(MC)-treated rats(MC-microsomes) with respect to its CO difference spectrum, electrophoretic pattern on sodium dodecyl sulfate(SDS)-polyacrylamide gel and immunochemical reactivity with the antibodies prepared against the hemoproteins from phenobarbital(PB)- or .beta.-naphthoflavone(BNF)-treated rat liver microsomes. PenCB pretreatment decreased demethylation of aminopyrine and codeine, as well as hydroxylation of aniline, to which PenCB-microsomes showed lower affinity than MC-microsomes. Trace amounts of PenCB inhibited the metabolism of aniline and aminopyrine by MC-microsomes but not by untreated rat liver microsomes. On SDS-polyacrylamide gel electrophoretograms the ratio of cytochrome P-450(P450) to P448 in PenCB-microsomes was much smaller than that in MC-microsomes. Part of the differences between the catalytic properties of PenCB- and MC-microsomes is apparently due to the inhibitory effect of residual PenCB in PenCB-microsomes and/or the change of a relative ratio of P450 to P448 in PenCB-microsomes. The possibility that PenCB may induce a different P448 from that induced by MC is discussed.