The high concentrations of hydrogen ions recently predicted to be at the surface of DNA may be responsible for the catalytic properties of solutions of nucleic acids in the reactions of the ultimate carcinogens of the polycyclic aromatic hydrocarbon (PAH) class of environmental pollutants. Calculations acid surface where they undergo an acid- catalyzed reaction yielding a species that reacts with DNA. Calculations designed to test the hypothesis that the electric field at the DNA surface is responsible for the catalytic effect of DNA are also proposed. The overall goal is to understand the mechanism by which DNA catalyzes the generation of highly reactive molecules at its surface for subsequent covalent adduct formation. Comparison with existing experimental data for selected PAH's will determine the possibility of predicating the likelihood that a metabolic product of the PAH will attack DNA or will de detoxified; and further, if DNA is attacked, which regions of the genome are most likely to be attacked. The theoretical methods to be used in the project will be tested for accuracy by comparison with experiment. The formation of triple-helical DNA structures has been experimentally studied under a variety of conditions and these data will be used to calibrate the model used in the calculations. Comparisons with existing computational techniques will be performed where possible.
