Preferential inhibitions of hepatic P450IA2 expression and induction by lead nitrate in the rat.

Male F344 rats were treated with lead nitrate and changes in the expression and induction of P450IA subfamily enzymes and a placental form of glutathione-S-transferase (GST-P) in the liver were assessed by means of a bacterial mutation test, immunoblotting with a monoclonal antibody reactive to P450IA1/IA2 and anti-GST-P sera and Northern blotting with P450IA2 cDNA as a probe. Treatment of rats with lead nitrate (20, 50 or 100 mumol/kg body wt) decreased P450IA2 mRNA and protein in the liver in the dose-dependent fashion and also decreased the microsomal activity for P450IA2-dependent mutagenization of aromatic amines. Pretreatment of rats with lead nitrate suppressed the inductions of both P450IA2 mRNA and protein by an inducer of P450IA subfamily enzymes in the liver. In addition, amount of the induced P450IA2 was decreased along with increase in that of the induced GST-P.