Adduct Formation at C-8 of Guanine on in vitro Reaction f the Ultimate Form of 2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridine with 2'-Deoxyguanosine and Its Phosphate Esters

We examined the reactivity of the N -hydroxyamino derivative of a carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP), after its O -acetylation with four 2'-deoxyribonucleoside 3'-monophosphates. ³²P-Postlabeling analysis demonstrated that the levels of adducts with 2'-deoxyguanosine 3'-moiiophosphate were much higher than those with the other three nucleotides. ¹H-NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N -acetoxy-PhIP with 2'-deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C-8 position of guanine, as previously demonstrated with other heterocyclic amines.