Polynuclear aromatics, binding

The purpose of this eornpuLer project is Lo examine several polynuclear aromatic hydrocarbons and to relate their electron density patterns to their carcinogenic activity. If nucleophilic binding to DN.A is a significant step in blocking the normal transcription process of DN.A, electron density in the hydrocarbon should be positively correlated to its carcinogenic potency. To begin with, we shall rely on clinical evidence that benzene, naphthalene, and phenanthrene... 

Varanasi, U., D.J. Gmur, and M.M. Krahn. 1980. Metabolism and subsequent binding of benzo[a]pyrene to DNA in pleuronectid and salmonid fish. Pages 455-470 in A. Bjorseth and A.J. Dennis (eds.). Polynuclear Aromatic Hydrocarbons Chemistry and Biological Effects. Battelle Press, Columbus, OH. 

Further insight into molecular binding to the solid surface is possible from a determination of the surface area occupied by each molecule in a mono-layer. In a detailed study of the adsorption of a range of substances on silica gel (surface area 200 m2/g), Weis and coworkers9 found that a relatively small number of polynuclear aromatic substances occupied all available binding sites, indicating that the molecules are oriented parallel to the solid surface to... 

A number of publications reporting the competitive binding of polynuclear aromatic hydrocarbons appeared in the literature [487-490]. It is of interest to note that 3,9-dihydroxybenz[a ]anthracene, a potential metabolite of benz[a]anthracene, has both oestrogenic and antioestrogenic properties [487, 488,490]. The effect of DMBA and hormones on neoplasia was adequately discussed [491]. 

During the past few years, the general sequence of events in the formation of DNA adducts with polynuclear aromatic hydrocarbons (PAH) and its possible relationship to neoplasia has been determined (1.2). Of particular importance are the biotransformations that convert PAH first to hydroxylated primary metabolites, which are then conjugated to from secondary metabolites and excreted by the organism. In the metabolic processes associated with the formation of the primary metabolites highly reactive intermediates are formed which may bind to cell macromolecules including DNA fl-3). 

Varanasi, U., M. Nishimoto and J. Stover. Analyses of biliary conjugates and hepatic DNA binding in benzo(a)pyrene-exposed English sole. In Polynuclear Aromatic Hydrocarbons, Eighth Symposium, edited by M. Cook and A. Dennis, Columbus, OH, Battelle Press, 1986. 

Weyand EH, Amin S, Sodhi R, et al. 1991c. Effects of methyl substitution on the metabolism and binding of benz[e]acephenanthrylene. In Garriques P, Lamotte M, eds. Polycyclic aromatic compounds. Synthesis, properties, analytical measurements, occurence, and biological effects. Proceedings of the thirteenth international symposium on polynuclear aromatic hydrocarbons. Philadelphia, PA Gordon and Breach. 

Brookes, R, and Lawley, P. D. (1964). Evidence for the binding of polynuclear aromatic hydrocarbons to the nucleic acids of mouse skin relation between carcinogenic power of hydrocarbons and their binding to deoxyribonucleic acid. Nature 202, 781-784. 

Polynuclear aromatic hydrocarbons are thought to cause cancer by covalently binding to the DNA in cells and interfering with the correct replication of the DNA. Some of the mutations that result may cause a cell to begin to divide in an uncontrolled fashion, giving rise to a cancerous tumor. 

The fullerenes are the most recently discovered polynuclear aromatic com-pounds. Figure 5.8 shows how the ellipsoidal molecule C70 binds to Vaska s complex. Either only one of the many possible isomers is formed, or more likely, only one crystallized. Free Cw itself does not give crystallographically useful crystals, and so this structure confirmed the ellipsoidal structure previously deduced from its NMR spectrum. The junctions between six-mem-bered rings seem to be the most reactive in the fullerenes, and this is where... 

---