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 cytochrome P450IA2 (CYP1A2) in the livers were assessed by enzymatical, immunochemical, and molecular biological methods. All ionic metals used significantly decreased total CYP amount in the liver microsomes. However, among ionic metals used only lead showed inhibitory effects on the microsomal activity for CYP1A2-dependent mutagenesis of aromatic amines and on the expression of mRNA and protein of the enzyme, indicating that ionic lead is a unique inhibitor for the expression of CYP1A2 enzyme in the rat liver.
Degawa
M
M
Department of Hygienic Chemistry, Tohoku University, Sendai, Japan.
Arai
H
H
Kubota
M
M
Hashimoto
Y
Y
D000818:Animals; D001483:Base Sequence; D002104:Cadmium / Q000633:toxicity; D002412:Cations / Q000633:toxicity; D003035:Cobalt / Q000633:toxicity; D019388:Cytochrome P-450 CYP1A2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009532:Nickel / Q000633:toxicity; D015345:Oligonucleotide Probes / Q000235:genetics; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D002412:Cations; D065607:Cytochrome P-450 Enzyme Inhibitors; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D002104:Cadmium; D007854:Lead; D003035:Cobalt; D009532:Nickel; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2