Identification of N-(deoxyguanosin-8-yl)-2-amino-3,4-dimethylimidazo[4,5-f]quinoline (dG-C8-MeIQ) as a major adduct formed by MeIQ with nucleotides in vitro with DNA in vivo.
The N-hydroxylamine of a carcinogenic heterocyclic amine, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), was reacted with four 2'-deoxynucleoside 3'-monophosphates after O-acetylation. 32P-Postlabeling analysis demonstrated that the adduct was formed with only the guanine nucleotide, and the structure of the compound in the obtained adduct spot was determined to be N-(deoxyguanosin-8-yl)-MeIQ 3',5'-diphosphate (3',5'-pdGp-C8-MeIQ). DNA samples from livers of mice fed MeIQ were also 32P labeled under standard conditions and additionally treated with nuclease P1 and phosphodiesterase I. A single adduct spot was obtained and the structure of the adduct was identified as 5'-pdG-C8-MeIQ. Thus, MeIQ binds at the C-8 position of guanine in vitro and in vivo, like other heterocyclic amines.
Tada
A
A
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Ochiai
M
M
Wakabayashi
K
K
Nukaya
H
H
Sugimura
T
T
Nagao
M
M
D000818:Animals; D004247:DNA / Q000378:metabolism*; D005260:Female; D006147:Guanine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D009153:Mutagens / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*
D009153:Mutagens; D009711:Nucleotides; D011804:Quinolines; D006147:Guanine; D004247:DNA; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline