Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The reactions of oxidizing ((•)OH, N(3)(•), and SO(4)(•-)) and reducing (e(aq)(-)) radicals with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxoA) have been studied by pulse radiolysis to elucidate the initial free radical processes in their oxidation since these oxidized purines are readily oxidized in DNA. The second-order rate constants for the reaction of the (•)OH with 8-oxoA and 8-oxoG were determined to be 4.3 × 10(9) and 4.8 × 10(9) dm(3) mol(-1) s(-1), respectively. Similar values were also obtained with the N(3)(•) radical, the respective values being 8.8 × 10(9) and 3.8 × 10(9) dm(3) mol(-1) s(-1). The transient absorption spectrum following reaction of 8-oxoA with (•)OH is assigned to the C4- and C5-OH adducts which then undergo dehydration (k = 5.1 × 10(3) s(-1)) to give a reducing neutral N-centered radical. 8-oxoG, on the other hand, either reacts by H abstraction from the amino group attached to C2, which undergoes fast tautomerization or the resulting (•)OH adduct which rapidly dehydrates (k > 1.7 × 10(6) s(-1)) to give the species corresponding to the one-electron oxidized product. The transient absorption spectrum measured for the reaction of the N(3)(•) with 8-oxoG is identical to that obtained with the (•)OH at pH 10. The rate determining step is the formation of the radical cation which then rapidly loses a proton to form the neutral radical. It is estimated that 85% of (•)OH adducts are oxidizing while 13% are reducing. The yields of the reducing radicals on reaction of e(aq)(-) with 8-oxoA or 8-oxoG amount to ∼43 and 77% of the respective yield of e(aq)(-), whereas the extent of formation of any oxidizing radicals is ≤2%. In summary, radical intermediates from 8-oxoA or 8-oxoG and their redox potentials have been determined so that 8-oxoA and 8-oxoG, if preformed endogenously, may act as primary sinks for oxidized DNA damage if present close to DNA radicals induced radiolytically.

Original publication

DOI

10.1021/jp1070049

Type

Journal article

Journal

J Phys Chem B

Publication Date

16/12/2010

Volume

114

Pages

16611 - 16617

Keywords

Deoxyadenosines, Deoxyguanosine, Free Radicals, Molecular Structure, Pulse Radiolysis