DNA Structural Integrity and Base Composition Affect Ultraviolet Light-Induced Oxidative DNA Damage

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• 作者：Huachen Wei ; Qiuyin Ca ; Ronald Rahn ; Xueshu Zhang ; Yan Wang ; and Mark Lebwohl
• 刊名：Biochemistry
• 出版年：1998
• 出版时间：May 5, 1998
• 年：1998
• 卷：37
• 期：18
• 页码：6485 - 6490
• 全文大小：113K
• 年卷期：v.37,no.18(May 5, 1998)
• ISSN：1520-4995

文摘

We previously demonstrated that ultraviolet (UV) light (254 nm)induced the formation of8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA via a singlet oxygenmechanism. In the present paper,we provide novel findings that DNA structure and base compositionsignificantly affect the yield of 8-OHdGby UV radiation. Unlike ionizing radiation that induces 8-OHdGboth in free 2'-deoxyguanosine (dG)and in DNA, UV light induced 8-OHdG formation in intact DNA andpolydG·dC, but not in dG. Whenthermally denatured DNA was irradiated with UV light, the yield of8-OHdG was reduced by more than80% compared to intact DNA. Oxygenation of the denatured DNAsolution did not restore the yield ofUV-induced 8-OHdG. Irradiation of DNA with different AT/GC ratiosshowed that the yield of UV-induced 8-OHdG varied in proportion to the AT content, suggesting thatAT base pairs in DNA enhancegeneration of the oxidizing species and subsequent oxidation of dG.The natural antioxidants genistein,estradiol, protocatechuic acid (PCA), and oleanolic acid (OA) wereinvestigated for their inhibition ofUV-induced 8-OHdG. Genistein and estradiol, that intercalate intoDNA as shown by a computer modeling,significantly quenched UV-induced 8-OHdG, whereas PCA and OA did notfit into DNA and exhibitedweak or no effect. These results suggest that the intercalation ofgenistein and estradiol into DNA mayalter the DNA structural integrity, interrupt the production ofoxidizing species, and subsequently reducethe formation of 8-OHdG by UV radiation.