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© 1990 Oxford University Press

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Molecular machanics and antibody binding in the structural analysis of polycyclic aromatic hydrocarbon-diol-epoxide-DNA adducts

Ainsley Weston, Mark J. Newman 1, Dean L. Mann and Bernard R. Brooks 2

Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health Bethesda, MD 20892
1School of Veterinary Medicine, Veterinary Medical Pathology, Louisiana State University Baton Rouge, LA 70803
2Division of Computer Research and Technology, National Insitutes of Health Bethesda, MD 20892

Analysis of polycyclic aromatic hydrocarbon (PAH)–DNA adducts using monoclonal antibodies raised against DNA that had been modified with (±)-r-7-,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo in an enzyme-linked Immunosorbent assay, as well as analysis using human serum antibodies and antibodies raised in laboratory animals, have suggested the presence on these adducts of both common and unique immunological epitopes. The molecular mechanics studies reported here establish a model for the analysis of PAN–DNA adducts through the identification of energetically favored binding conformations and they further reveal structural alterations in DNA due to the presence of carcinogen adducts. The data explain the antibody reactivity patterns by defining different molecular presenting surfaces that are available for antibody binding. The preferred orientation of the aromatic portions of the adducts, which align either 3' or 5' in the minor groove, were found to be correlated with antibody reactivity patterns. Examination of the topographical characteristics of the adducts facilitated correlation of adduct'antibody recognition and adduct presenting surface. Significant differences were found between benzo (BPDE)'DNA adducts, which align 5' in the minor groove, and benz [a] anthracene-diol-epoxide (BADE)'DNA and dibenz[a,c] anthracene-diol-epoxide-DNA adducts, which align 3' within the minor groove. Chrysene-diol-epoxide-DNA adducts were found to have only a weak preference for 5' alignment and therefore share topographical characteristics with both BPDE'DNA and BADE'DNA adducts.


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