title: Theoretical investigations on the formation of nitrobenzanthrone-DNA adducts.
abstract: 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. The thermochemical formation cascades were calculated for six 3-NBA-derived DNA adducts employing its arylnitrenium ion as precursor using density functional theory (DFT). Clear exothermic pathways were found for four adducts, i.e., 2-(2'-deoxyadenosin-N(6)-yl)-3-aminobenzanthrone, 2-(2'-deoxyguanosin-N(2)-yl)-3-aminobenzanthrone, N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone and 2-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone. All four have been observed to be formed in cell-free experimental systems. The formation of N-(2'-deoxyadenosin-8-yl)-3-aminobenzanthrone is predicted to be not thermochemically viable explaining its absence in either in vitro or in vivo model systems. However, 2-(2'-deoxyadenosin-8-yl)-3-aminobenzanthrone, can be formed, albeit not as a major product, and is a viable candidate for an unknown adenine adduct observed experimentally. 2-nitrobenzanthrone (2-NBA), an isomer of 3-NBA, was also included in the calculations; it has a higher abundance in ambient air than 3-NBA, but a much lower genotoxic potency. Similar thermochemical profiles were obtained for the calculated 2-NBA-derived DNA adducts. This leads to the conclusion that enzymatic activation as well as the stability of its arylnitrenium ion are important determinants of 2-NBA genotoxicity.
authors.affiliation: Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Volker M
authors.initials: VM
authors.lastname: Arlt
authors.forename: David H
authors.initials: DH
authors.lastname: Phillips
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
mesh_terms: D001551:Benz(a)Anthracenes / Q000737:chemistry* / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D009153:Mutagens / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001551:Benz(a)Anthracenes; D018736:DNA Adducts; D009153:Mutagens; C117220:3-nitrobenzanthrone