IONIC LEAD, A UNIQUE METAL-ION AS AN INHIBITOR FOR CYTOCHROME P450IA2(CYP1A2) EXPRESSION IN THE RAT-LIVER

Male F344 rats were treated with lead nitrate, nickel chloride, cobalt chloride or cadmium chloride, and changes in the expression of cytoch rome P450IA2 (CYP1A2) in the livers were assessed by enzymatical, immu nochemical, and molecular biological methods. All ionic metals used si gnificantly decreased total CYP amount in the liver microsomes. Howeve r, among ionic metals used only lead showed inhibitory effects on the microsomal activity for CYP1A2-dependent mutagenesis of aromatic amine s and on the expression of mRNA and protein of the enzyme, indicating that ionic lead is a unique inhibitor for the expression of CYP1A2 enz yme in the rat liver. (C) 1994 Academic Press, Inc.