IONIC LEAD, BUT NOT OTHER IONIC METALS (NI2-METHOXY-4-AMINOAZOBENZENE-MEDIATED CYTOCHROME P450IA2 (CYP1A2) INDUCTION IN RAT-LIVER(, CO2+ AND CD2+), SUPPRESSES 2)

Male F344 rats mere pretreated with lead nitrate, nickel chloride, cob alt chloride or cadmium chloride, and their effects on the induction o f cytochrome P450 (CYP) enzymes, mainly CYP1A2 enzyme, with 2-methoxy- 4-aminoazobenzene (2-MeO-AAB) in the livers were comparatively examine d by enzymatical, immunochemical, and molecular biological methods. Wh en rats were pretreated with each ionic metal, the total CYP amount in the liver microsomes decreased, as compared with that of rats treated with 2-MeO-AAB alone. However, among the ionic metals used only lead reduced the levels of the mRNA and protein of CYP1A2 induced with 2-Me O-AAB in the rat liver, and decreased the microsomal activity (per CYP ) for CYP1A2-mediated mutagenesis. Furthermore, ionic lead, but not ot her ionic metals, showed an ability to induce a placental form of glut athione S-transferase (GST-P). The level of CYP1A2 induced with 2-MeO- AAB was decreased along with increase in that of the induced GST-P.