RADIATION-INDUCED FORMATION OF 8-HYDROXY-2'-DEOXYGUANOSINE AND ITS PREVENTION BY SCAVENGERS

Reactive oxygen species (ROS) induce 8-hydroxy-2'-deoxyguanosine (8-OH dG) 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 g enerated. We have measured 8-OHdG formation in calf thymus DNA exposed to ionizing radiation under conditions generating either hydroxyl rad icals (OH), superoxide anions (O-2(-)) or both. Additionally, we inves tigated the relationship between the scavenger effect of the drug 5-am inosalicylic acid (5-ASA) and increasing OH exposure toward 8-OHdG for mation. The effect of this drug was compared to those of the physiolog ical scavengers ascorbate and reduced glutathione (GSH). We found that OH generated 8-OHdG in a dose-dependent manner, whereas O-2(-) did no t cause 8-OHdG formation. 5-ASA, ascorbate and GSH all acted as hydrox yl radical scavengers, although with different concentration-effect cu rves, emphasizing the importance of using relevant pharmaco-/physiolog ical concentrations in studies focusing on therapeutic applications of scavengers. The scavenger effect of 5-ASA at concentrations greater t han or equal to 0.1 mM was similar at 30 and 100 Gy radiation, i.e. wi thin a wide range of OH exposure, which is useful information consider ing clinical applications where the exact amount of ROS formed is unkn own. Both 5-ASA and ascorbate at low concentrations (less than or equa l to 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 var iations in both number and type of ROS formed in the two systems.