Ionic lead, but not other ionic metals (Ni2+, Co2+ and Cd2+), suppresses 2-methoxy-4-aminoazobenzene-mediated cytochrome P450IA2 (CYP1A2) induction in rat liver.
Male F344 rats were pretreated with lead nitrate, nickel chloride, cobalt chloride or cadmium chloride, and their effects on the induction of cytochrome P450 (CYP) enzymes, mainly CYP1A2 enzyme, with 2-methoxy-4-aminoazobenzene (2-MeO-AAB) in the livers were comparatively examined by enzymatical, immunochemical, and molecular biological methods. When 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-MeO-AAB in the rat liver, and decreased the microsomal activity (per CYP) for CYP1A2-mediated mutagenesis. Furthermore, ionic lead, but not other ionic metals, showed an ability to induce a placental form of glutathione 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.
Degawa
M
M
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Arai
H
H
Kubota
M
M
Hashimoto
Y
Y
D000818:Animals; D001483:Base Sequence; D002104:Cadmium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007854:Lead / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D009532:Nickel / Q000494:pharmacology; D010088:Oxidoreductases / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives* / Q000494:pharmacology
D002104:Cadmium; D007854:Lead; C053767:2-methoxy-4-aminoazobenzene; D003035:Cobalt; D010128:p-Aminoazobenzene; D009532:Nickel; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2