Lead nitrate inhibits the induction of CYP1A mRNAs by aromatic amines but not by aryl hydrocarbons in the rat liver.
The effects of lead nitrate on the induction of hepatic cytochrome P450IA (CYP1A) isoforms, mainly CYP1A2, by aromatic amines (2-methoxy-4-aminoazobenzene, 2-amino-3-methyl-9H-pyrido [2,3-b]indole and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and aryl hydrocarbons (3-methylcholanthrene, benzo[a]pyrene and beta-naphthoflavone) in male F344 rats were examined at the levels of mRNA, protein and activity of the enzymes. Pretreatment of rats with lead nitrate suppressed the expression of hepatic CYP1A enzyme(s), especially CYP1A2, at both levels of protein and activity of the enzyme(s) by treatment with an aromatic amine or an aryl hydrocarbon. On the other hand, the lead nitrate pretreatment suppressed the induction of CYP1A mRNA(s) by an aromatic amine but not by an aryl hydrocarbon. These findings indicate that lead nitrate suppresses the expression of CYP1A enzymes at both stages of post-translation of mRNAs and transcriptional activation of the genes, and further suggest that the pathway for the transcriptional activation of the CYP1A genes by the aromatic amines is different from that by the aryl hydrocarbons.
Faculty of Pharmaceutical Sciences, Tohoku University, Sendai.
M
M
Degawa
K
K
Matsuda
H
H
Arai
Y
Y
Hashimoto
D000818:Animals; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D015345:Oligonucleotide Probes; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D019324:beta-Naphthoflavone / Q000494:pharmacology; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000494:pharmacology
D002243:Carbolines; D002273:Carcinogens; D007093:Imidazoles; D015345:Oligonucleotide Probes; C017821:2-amino-3-methyl-9H-pyrido(2,3-b)indole; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D010128:p-Aminoazobenzene; D019324:beta-Naphthoflavone; C044436:3-methoxy-4-aminoazobenzene; D003577:Cytochrome P-450 Enzyme System; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2