Bioactivation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine by liver microsomes from three different rat strains.
The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein binding of PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied using microsomes from PCB-pretreated or untreated male rats of the strains, Wistar, Fischer and Sprague-Dawley. The microsomal monooxygenases, P450IA1 and IA2, which are important for the biotransformation of heterocyclic amines, were quantified by immunoblots. The two metabolites detected, 2-amino-1-methyl-6-(4'-hydroxyphenyl)imidazo[4,5-b]pyridine (4'OH-PhIP) and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N2-OH-PhIP) were formed in similar amounts whereas no minor metabolites were found in our highly sensitive radiochemical assay. Irrespective of the rat strain used, pretreatment with PCB significantly induced both the activation and the detoxication in all three rat strains. Except for a significantly higher concentration of P450IA2 in microsomes from control and PCB induced Wistar rats, no major differences between the strains were found.
Dragsted
L O
LO
National Food Agency of Denmark, Søborg.
Alexander
J
J
Wallin
H
H
Frandsen
H
H
Vang
O
O
D000818:Animals; D001140:Aroclors / Q000008:administration & dosage*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism / Q000493:pharmacokinetics*; D015151:Immunoblotting; D007274:Injections, Intraperitoneal; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism / Q000493:pharmacokinetics*; D010088:Oxidoreductases / Q000378:metabolism; D011485:Protein Binding; D011804:Quinolines / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D001140:Aroclors; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D003577:Cytochrome P-450 Enzyme System; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2