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© 1994 Oxford University Press
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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 and with DNA in vivo
1Carcinogenesis Division, National Cancer Center Research Institute 1 – 1, Tsukiji 5-chome, Chuo-ku, Tokyo 104
2POLA R&D Laboratories POLA Corporation 560, Kashio-cho, Totsuka-ku, Yokohama 244
3School of Pharmaceutical Science, University of Shizuoka Yada 52-1, Shizuoka 422, Japan
4To whom correspondence should be addressed
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-Postlabeing 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 MelQ 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, MelQ binds at the C-8 position of guanine in vitro and in vivo, like other heterocyclic amines.