BIOACTIVATION OF 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]-PYRIDINE BY LIVER-MICROSOMES FROM 3 DIFFERENT RAT STRAINS

The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyrid ine (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-Da wley. The microsomal monooxygenases, P450IA1 and IA2, which are import ant for the biotransformation of heterocyclic amines, were quantified by immunoblots. The two metabolites detected, -methyl-6-(4'-hydroxyphe nyl)imidazo[4,5-b]pyridine (4'OH-PhIP) and droxyamino-1-methyl-6-pheny limidazo[4,5-b]pyridine (N2-OH-PhIP) were formed in similar amounts wh ereas no minor metabolites were found in our highly sensitive radioche mical assay. Irrespective of the rat strain used, pretreatment with PC B significantly induced both the activation and the detoxication in al l three rat strains. Except for a significantly higher concentration o f P450IA2 in microsomes from control and PCB induced Wistar rats, no m ajor differences between the strains were found.