DNA structural integrity and base composition affect ultraviolet light-induced oxidative DNA damage

We previously demonstrated that ultraviolet (UV) light (254 nm) induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA via a singlet oxygen mechanism. In the present paper, we provide novel findings that DNA structure and base composition significantly affect the yield of 8-OHdG by UV radiation. Unlike ionizing radiation that induces 8-OHdG both in free 2'-deoxyguanosine (dG) and in DNA, UV light induced 8-OHdG formation in intact DNA and polydG.dC, but not in dG. When thermally denatured DNA was irradiated with UV light, the yield of 8-OHdG was reduced by more than 80% compared to intact DNA. Oxygenation of the denatured DNA solution did not restore the yield of UV-induced 8-OHdG. Irradiation of DNA with different AT/GC ratios showed that the yield of UV-induced 8-OHdG varied in proportion to the AT content, suggesting that AT base pairs in DNA enhance generation of the oxidizing species and subsequent oxidation of dG. The natural antioxidants genistein, estradiol, protocatechuic acid (PCA), and oleanolic acid (OA) were investigated for their inhibition of UV-induced 8-OHdG. Genistein and estradiol, that intercalate into DNA as shown by a computer modeling, significantly quenched UV-induced 8-OHdG, whereas PCA and OA did not fit into DNA and exhibited weak or no effect. These results suggest that the intercalation of genistein and estradiol into DNA may alter the DNA structural integrity, interrupt the production of oxidizing species, and subsequently reduce the formation of 8-OHdG by UV radiation.