Effect of hydroxyl radical scavenging capacity on clustering of DNA damage.

We have shown previously that the thiol N-(2'-mercaptoethyl)-1,3-diaminopropane (WR-1065) can attenuate the formation of strand breaks associated with ionizing radiation. The mechanism of this protection is predominantly the reduction of DNA radical species which otherwise would attenuate the chemical repair of DNA radical species which are strand break precursors. We had observed that the presence of a hydroxyl radical scavenger during irradiation resulted in a decrease in the ability of WR-1065 to attenuate the formation of strand breaks. Since ionic compounds are known to affect the binding of the dicationic WR-1065 with the polyanion DNA, the effect of the scavenger was initially attributed to its polar nature having a similar effect on the interaction of WR-1065 with DNA, and not as a consequence of its ability to scavenge hydroxyl radicals. After examining additional scavengers, we now conclude that an increased hydroxyl radical scavenging capacity does attenuate the repair of strand break precursors to some extent. The probable explanation for this observation is that an increased scavenging capacity results in a greater degree of radical clustering on the DNA, and that these clusters of multiple radicals are repaired more slowly than are single radical species.