Adduct formation at C-8 of guanine on in vitro reaction of the ultimate form of 2-amino-1-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'-monophosphate 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-acetyoxy-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.
Nagaoka
H
H
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo.
Wakabayashi
K
K
Kim
S B
SB
Kim
I S
IS
Tanaka
Y
Y
Ochiai
M
M
Tada
A
A
Nukaya
H
H
Sugimura
T
T
Nagao
M
M
D000089:Acetic Anhydrides; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003849:Deoxyguanosine / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens / Q000737:chemistry* / Q000493:pharmacokinetics; D009711:Nucleotides / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D010761:Phosphorus Radioisotopes; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000089:Acetic Anhydrides; D007093:Imidazoles; D009153:Mutagens; D009711:Nucleotides; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D011725:Pyridines; C060533:2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C031800:acetic anhydride; D006147:Guanine; D003577:Cytochrome P-450 Enzyme System; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D003849:Deoxyguanosine