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

Abstract

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.