Spectroscopic characterizations and comparisons of the structures of the covalent adducts derived from the reactions of 7, 8-dihydroxy-7,8,9,10-tetrahydrobenzo [a] pyrene-9,10-oxide, and the 9, 10-epoxides of 7,8,9,10-tetrahydrobenzo [a] pyrene and 9.10,11,12-tetrahydrobenzo [e] pyrene with DNA.
The conformation of covalent adducts derived from the reactions of racemic 7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a] pyrene (BaPDE), 9,10-epoxy-7,8,9,10-tetrahydrobenzo [a] pyrene (BaPE), and 9,10-epoxy-9,10,11,12-tetrahydrobenzo [e] pyrene (BePE) with calf thymus DNA in aqueous buffer solution (25 degrees C, pH 7.0) were investigated and compared by means of absorption, fluorescence and electric linear dichroism techniques. Two types of conformations are recognized. Site I is characterized by a red shift (approximately 10 nm) in the absorption maximum of the pyrene nucleus, a significantly reduced fluorescence yield, and a negative electric linear dichroism signal (delta A); this site is presumed to involve a near-parallel (within 25 degrees) orientation of the planar pyrene residue with the planes of the DNA bases, and a relatively strong interaction between the phi electrons of the nucleic acid bases and the pyrene residue. In site II, there is only a small red-shift in the absorption maximum (approximately 2 nm), a non-zero fluorescence yield, and a positive delta A throughout the absorption region of the pyrene residue; in this conformation the pyrene residue is presumed to lie on the outside of the DNA molecule, possibly in one of the grooves. The BaPDE-DNA complex displays predominantly a site II-type conformation while the BaPE- and BePE-DNA complexes display both site I and site II adducts, with site I conformations predominating. The lack of hydroxyl groups in BaPE and BePE lead to a loss in stereospecificity in covalent adduct formation. The 7 and 8 hydroxyl groups in covalent adduct formation. The 7 and 8 hydroxyl groups in BaPDE appear to reduce the probability of formation of site I-type of covalent adducts, and appear to be, at least in part, responsible for the enantiomeric stereospecificity in the covalent reaction between BaPDE and DNA.
D001580:Benzopyrenes / Q000032:analysis* / Q000378:metabolism; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
C029649:9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene; D001580:Benzopyrenes; D004247:DNA