Radiation-induced formation of 8-hydroxy-2'-deoxyguanosine and its prevention by scavengers.
Reactive oxygen species (ROS) induce 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, which has been proposed as a key biomarker relevant to carcinogenesis. 8-OHdG has been induced in a number of different ways, most often without knowledge of the specific type and amount of ROS generated. We have measured 8-OHdG formation in calf thymus DNA exposed to ionizing radiation under conditions generating either hydroxyl radicals (OH.), superoxide anions (O2-) or both. Additionally, we investigated the relationship between the scavenger effect of the drug 5-aminosalicylic acid (5-ASA) and increasing OH. exposure toward 8-OHdG formation. The effect of this drug was compared to those of the physiological scavengers ascorbate and reduced glutathione (GSH). We found that OH. generated 8-OHdG in a dose-dependent manner, whereas O2- did not cause 8-OHdG formation. 5-ASA, ascorbate and GSH all acted as hydroxyl radical scavengers, although with different concentration-effect curves, emphasizing the importance of using relevant pharmaco-/physiological concentrations in studies focusing on therapeutic applications of scavengers. The scavenger effect of 5-ASA at concentrations > or = 0.1 mM was similar at 30 and 100 Gy radiation, i.e. within a wide range of OH. exposure, which is useful information considering clinical applications where the exact amount of ROS formed is unknown. Both 5-ASA and ascorbate at low concentrations (< or = 0.1 mM) were less efficient in preventing 8-OHdG formation from X-ray generated OH. than was shown in a previous comparable study using light as the source of ROS. This differentiation probably reflects variations in both number and type of ROS formed in the two systems.
Fischer-Nielsen
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Department of Pharmacology, University of Copenhagen, Denmark.
Jeding
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Loft
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D000080242:8-Hydroxy-2'-Deoxyguanosine; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002417:Cattle; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D016166:Free Radical Scavengers; D005978:Glutathione / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D019804:Mesalamine
D000636:Aminosalicylic Acids; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D019804:Mesalamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione; D001205:Ascorbic Acid