Theoretical investigations on the formation of nitrobenzanthrone-DNA Adducts (original) (raw)
* Corresponding authors
a Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, UK
b School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
E-mail: j.reynisson@auckland.ac.nz
Fax: +64-9-373-7422
Tel: +64-9-373-7599 Ext. 83746
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-N6-yl)-3-aminobenzanthrone, 2-(2′-deoxyguanosin-N2-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.
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Article information
DOI
https://doi.org/10.1039/C1OB05570D
Article type
Paper
Submitted
11 Apr 2011
Accepted
25 May 2011
First published
26 May 2011
Download Citation
Org. Biomol. Chem., 2011,9, 6100-6110
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Theoretical investigations on the formation of nitrobenzanthrone-DNA Adducts
V. M. Arlt, D. H. Phillips and J. Reynisson,Org. Biomol. Chem., 2011, 9, 6100DOI: 10.1039/C1OB05570D
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