An unusual DNA adduct derived from the powerfully mutagenic environmental contaminant 3-nitrobenzanthrone

The covalent binding of an N-hydroxy metabolite of the powerfully mutagenic 3-nitrobenzanthrone (NBA) to 2'-deoxyguanosine (dG) and calf thymus DNA has been investigated in vitro. The major adduct obtained from the reaction of the N-acetoxy-N-acetyl derivative (N-Aco-N-Ac-ABA) of 3-aminobenzanthrone (ABA) and dG was identified as N-acetyl-3-amino-2-2'-deoxyguanosin-8-yl) benzanthrone (dG-N-Ac-ABA) by H-1 NMR and mass spectroscopies as well as by the reaction of N-Aco-N-Ac-ABA with the double-stranded calf thymus DNA. The coupling with the dG moiety occurred exclusively at C-2 of benzanthrone (BA), suggesting a significant contribution of a resonance-stabilized arenium ion intermediate derived from BA to the production of this new type of adduct. The preferred conformation of the adduct has been shown to be syn by H-1 and C-13 NMR.