Structural identification of DNA adducts derived from 3-nitrobenzanthrone, a potent carcinogen present in the atmosphere.
3-Nitrobenzanthrone is a powerful bacterial mutagen and carcinogen to mammals. To obtain precise information on DNA-adduct formation by 3-nitrobenzanthrone, a number of DNA adducts, including N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (13 a), 2-(2'-deoxyguanosin-N2-yl)-3-aminobenzanthrone (14 a), N-(2'-deoxyadenosin-8-yl)-3-aminobenzanthrone (15 a), 2-(2'-deoxyadenosin-N6-yl)-3-aminobenzanthrone (16 a), and their N-acetylated counterparts 13 b, 14 b, 15 b, and 16 b were synthesized by palladium-catalyzed aryl amination of the corresponding nucleoside and bromobenzanthrone derivatives. Among these DNA adducts, DNA adducts 13 a, 13 b, 14 a, 14 b, and 16 a were identified in the reaction mixture of nucleosides (2'-deoxyguanosine, 2'-deoxyadenosine, or DNA) with N-acetoxy-3-aminobenzanthrone or N-acetyl-N-acetoxy-3-aminobenzanthrone, both of which are recognized as activated metabolites of 3-nitrobenzanthrone. The formation of these multiple DNA adducts may help explain the potent mutacarcinogenicity of 3-nitrobenzanthrone.
Takamura-Enya
Takeji
T
Department of Applied Chemistry, Kanagawa Institute of Technology, 1030 Shimo-Ogino, Atsugi-shi 243-0292, Japan. takamura@chem.kanagawa-it.ac.jp
Kawanishi
Masanobu
M
Yagi
Takashi
T
Hisamatsu
Yoshiharu
Y
D000393:Air Pollutants / Q000032:analysis*; D001551:Benz(a)Anthracenes / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods
D000393:Air Pollutants; D001551:Benz(a)Anthracenes; D002273:Carcinogens; D018736:DNA Adducts; C117220:3-nitrobenzanthrone