Oxidative damage of DNA by chromium(V) complexes: relative importance of base versus sugar oxidation

Chromium(V)-mediated oxidative damage of deoxyribonucleic acids was investi gated at neutral pH in aqueous solution by utilizing bis(2-ethyl-2-hydroxyb utanato)oxochromate(V) (I) and bis(hydroxyethyl)amino-tris(hydroxymethyl)me thane)oxochromate(V) (II). Single-stranded and double-stranded (ds) calf th ymus and human placenta DNA, as well as two oligomers, 5'-GATCTAGTAGGAGGACA AATAGTGTPTG-3' and 5'-GATCCAAGCAAACACTATTTGTCCTCCTACTA-3', were reacted wit h the chromium(V) complexes. Most products were separated and characterized by chromatographic and spectroscopic methods, Polyacrylamide gel electroph oresis experiments reveal more damage at G sites in comparison to other bas es. Three primary oxidation products, 5-methylene-2-furanone (5-MF), furfur al and 8-oxo-2'-deoxyguanosine, were characterized, A minor product, which appears to be thymine propenal, was also observed. The dsDNA produces more furfural than furanone, The formation of these two products resulted from h ydrogen abstraction dr hydride transfer from C1' and C5' positions of the r ibose to the oxo-chromium(V) center. Since no enhancements of these product s (except propenal) were observed in the presence of oxygen, mechanisms per taining to the participation of activated oxygen species may be ruled out. The oxidation of the G base is most likely associated with an oxygen atom t ransfer from the oxo-metallates to the double bond between C8 and N7 of the purine ring. The formation of the propenal may be associated with an oxyge n-activated species, since a marginal enhancement of this product was obser ved in the presence of oxygen, The formation of furfural in higher abundanc e over 5-MF for dsDNA was attributed to the ease of hydrogen abstraction (o r hydride transfer) from the C5' compared to C1' position of the ribose wit hin a Cr(V)-DNA intermediate in which the metal center is bound to the phos phate diester moiety.