Kinetics of hydrolysis to tetraols and binding of benzo(a)pyrene-7,8-dihydrodiol-9,10-oxide and its tetraol derivatives to DNA. Conformation of adducts |
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Authors: | Nicholas E. Geacintov Victor Ibanez Antoine G. Gagliano Hiroko Yoshida Ronald G. Harvey |
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Affiliation: | 1. Chemistry Department, New York University, New York, N.Y. 10003, USA;2. Radiation and Solid State Laboratory, New York University, New York, N.Y. 10003, USA;3. Universite Paris XI, Institut Universitaire de Technologie, Cachan, France;4. Ben May Laboratory for Cancer Research, University of Chicago, Chicago, Illinois 60637 USA |
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Abstract: | When the major reactive metabolite of benzo(a)pyrene, -7,8-dihydroxy - -9,10-epoxy -7,8,9,10-tetrahydrobenzo(a)pyrene (-BPDE) is incubated with DNA in aqueous solution at 25°C, both covalent binding and hydrolysis of -BPDE to its tetraols occur. Using fluorescence and absorption spectroscopy it is shown that hydrolysis of -BPDE is markedly accelerated by DNA. In the presence of 5A260 units of DNA per ml in cacodylate buffer solution, at an initial concentration of DNA phosphate/-BPDE ratio of 100, both the extent of covalent binding to DNA ( < 7% of the total -BPDE initially present) and hydrolysis of -BPDE reach their maximum levels within less than five minutes after mixing. Absorption and electric linear dichroism spectra indicate that the tetraols bind non-covalently to DNA by an intercalation mechanism, whereas the covalent product displays the characteristics of an externally bound complex. |
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